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Sample records for single painful bone

  1. Radiotherapy for bone pain.

    PubMed Central

    Needham, P R; Mithal, N P; Hoskin, P J

    1994-01-01

    Painful bone metastases are a common problem for cancer patients. Although current evidence supports the use of a single fraction of radiotherapy as the treatment of choice, many radiotherapists, for a variety of reasons, continue to use fractionated regimens. Over one six month period 105 patients received external beam irradiation for painful bone metastases at the Royal London Hospital (RLH). Thirty-one per cent of the patients were aged 70 or over. The treatment of 97 of these patients was assessed. They had a total of 280 sites treated over the course of their disease. Fifty-nine per cent of sites treated received a fractionated course of radiotherapy. Site significantly influenced fractionation. Overall response rates of 82% were achieved. Fractionation did not appear to influence this. Ten patients received large field irradiation. Fifteen patients had five or more sites irradiated, of whom only one received hemibody irradiation. PMID:7523672

  2. The effect of a single dose of bupivacaine on donor site pain after anterior iliac crest bone harvesting.

    PubMed

    Barkhuysen, R; Meijer, G J; Soehardi, A; Merkx, M A W; Borstlap, W A; Bergé, S J; Bronkhorst, E M; Hoppenreijs, T J M

    2010-03-01

    Transplants from the anterior iliac crest are used for most reconstructive procedures in cranio-maxillofacial surgery. The advantages are easy accessibility, the ability to work in two teams and the amount of corticocancellous bone available; disadvantages are postoperative pain and gait disturbances. To reduce donor-site pain, the effect of a single dose of bupivacaine (10 cc of 2.5mg/cc with 1:80.000 epinephrine) was studied. 200 consecutive patients, who underwent anterior iliac crest bone harvesting for reconstructive procedures, were randomly divided into those receiving bupivacaine and those not. They completed a standardized questionnaire. Patients scored the intensity of the pain and difficulties walking at different times with a visual analogue scale. They recorded analgesics used. 98 questionnaires were eligible for analysis. No differences between the bupivacaine and the control group were detected for postoperative pain and gait disturbance. There is no support for administration of a single dose of bupivacaine to reduce pain in the first postoperative days. The surface area of the removed bone had a significant influence on pain and walking; pain is related to the local osseous damage or periosteal stripping rather than to the length of incision or the operation time.

  3. [Radionuclides for metastatic bone pain palliation].

    PubMed

    Lass, Piotr

    2002-10-01

    The paper overviews the role of systemic radionuclide therapy in patients with disseminated bone metastases. Most patients with bone metastases experience painful symptoms. Systemic radioisotope therapy is an alternative to traditional hemibody radiation in cases of multiple, diffuse metastases. Usually given as a single i.v. slow infusion it provides a pain relief beginning in one to three weeks, with a mean duration up to several months, depending on the kind of radioisotope applied. The paper overviews the role of unsealed source therapy with these bone-seeking radiopharmaceuticals in palliating pain, improving quality of life, indications, contraindications and complications of this therapy are discussed, as well as cost-benefit aspects.

  4. Pain and nociception: mechanisms of cancer-induced bone pain.

    PubMed

    Falk, Sarah; Dickenson, Anthony H

    2014-06-01

    Cancer pain, especially pain caused by metastasis to bone, is a severe type of pain, and unless the cause and consequences can be resolved, the pain will become chronic. As detection and survival among patients with cancer have improved, pain has become an increasing challenge, because traditional therapies are often only partially effective. Until recently, knowledge of cancer pain mechanisms was poor compared with understanding of neuropathic and inflammatory pain states. We now view cancer-induced bone pain as a complex pain state involving components of both inflammatory and neuropathic pain but also exhibiting elements that seem unique to cancer pain. In addition, the pain state is often unpredictable, and the intensity of the pain is highly variable, making it difficult to manage. The establishment of translational animal models has started to reveal some of the molecular components involved in cancer pain. We present the essential pharmacologic and neurobiologic mechanisms involved in the generation and continuance of cancer-induced bone pain and discuss these in the context of understanding and treating patients. We discuss changes in peripheral signaling in the area of tumor growth, examine spinal cord mechanisms of sensitization, and finally address central processing. Our aim is to provide a mechanistic background for the sensory characteristics of cancer-induced bone pain as a basis for better understanding and treating this condition.

  5. Pain and Paget's Disease of Bone

    MedlinePlus

    ... Home Paget’s Disease of Bone Paget’s Disease Management Pain and Paget’s Disease of Bone Publication available in: ... focus(); */ } //--> Print-Friendly Page May 2015 Types of Pain Paget’s disease can cause several different kinds of ...

  6. Preventing painful age-related bone fractures

    PubMed Central

    Thompson, Michelle L; Chartier, Stephane R; Mitchell, Stefanie A

    2016-01-01

    Age-related bone fractures are usually painful and have highly negative effects on a geriatric patient’s functional status, quality of life, and survival. Currently, there are few analgesic therapies that fully control bone fracture pain in the elderly without significant unwanted side effects. However, another way of controlling age-related fracture pain would be to preemptively administer an osteo-anabolic agent to geriatric patients with high risk of fracture, so as to build new cortical bone and prevent the fracture from occurring. A major question, however, is whether an osteo-anabolic agent can stimulate the proliferation of osteogenic cells and build significant amounts of new cortical bone in light of the decreased number and responsiveness of osteogenic cells in aging bone. To explore this question, geriatric and young mice, 20 and 4 months old, respectively, received either vehicle or a monoclonal antibody that sequesters sclerostin (anti-sclerostin) for 28 days. From days 21 to 28, animals also received sustained administration of the thymidine analog, bromodeoxyuridine (BrdU), which labels the DNA of dividing cells. Animals were then euthanized at day 28 and the femurs were examined for cortical bone formation, bone mineral density, and newly borne BrdU+ cells in the periosteum which is a tissue that is pivotally involved in the formation of new cortical bone. In both the geriatric and young mice, anti-sclerostin induced a significant increase in the thickness of the cortical bone, bone mineral density, and the proliferation of newly borne BrdU+ cells in the periosteum. These results suggest that even in geriatric animals, anti-sclerostin therapy can build new cortical bone and increase the proliferation of osteogenic cells and thus reduce the likelihood of painful age-related bone fractures. PMID:27837171

  7. Bone scintigraphy in patients with pain

    PubMed Central

    Kim, Seong Jang

    2017-01-01

    Nuclear medicine imaging is widely used in pain medicine. Low back pain is commonly encountered by physicians, with its prevalence from 49% to 70%. Computed tomography (CT) or magnetic resonance imaging (MRI) are usually used to evaluate the cause of low back pain, however, these findings from these scans could also be observed in asymptomatic patients. Bone scintigraphy has an additional value in patients with low back pain. Complex regional pain syndrome (CRPS) is defined as a painful disorder of the extremities, which is characterized by sensory, autonomic, vasomotor, and trophic disturbances. To assist the diagnosis of CRPS, three-phase bone scintigraphy is thought to be superior compared to other modalities, and could be used to rule out CRPS due to its high specificity. Studies regarding the effect of bone scintigraphy in patients with extremity pain have not been widely conducted. Ultrasound, CT and MRI are widely used imaging modalities for evaluating extremity pain. However, SPECT/CT has an additional role in assessing pain in the extremities. PMID:28757916

  8. Acupuncture for Cancer-Induced Bone Pain?

    PubMed Central

    Paley, Carole A.; Bennett, Michael I.; Johnson, Mark I.

    2011-01-01

    Bone pain is the most common type of pain in cancer. Bony metastases are common in advanced cancers, particularly in multiple myeloma, breast, prostate or lung cancer. Current pain-relieving strategies include the use of opioid-based analgesia, bisphosphonates and radiotherapy. Although patients experience some pain relief, these interventions may produce unacceptable side-effects which inevitably affect the quality of life. Acupuncture may represent a potentially valuable adjunct to existing strategies for pain relief and it is known to be relatively free of harmful side-effects. Although acupuncture is used in palliative care settings for all types of cancer pain the evidence-base is sparse and inconclusive and there is very little evidence to show its effectiveness in relieving cancer-induced bone pain (CIBP). The aim of this critical review is to consider the known physiological effects of acupuncture and discuss these in the context of the pathophysiology of malignant bone pain. The aim of future research should be to produce an effective protocol for treating CIBP with acupuncture based on a sound, evidence-based rationale. The physiological mechanisms presented in this review suggest that this is a realistic objective. PMID:21799687

  9. The role of drugs in bone pain

    PubMed Central

    Marras, Francesco; Leali, Paolo Tranquilli

    2016-01-01

    Summary Painful symptomatology in the skeletal system can be found in various pathological conditions and can be either localised or diffused. Bone tenderness is common in those who are of an elderly age. Treatment strategy Patients should be informed of the possible causes of their pain and the different therapies that could alleviate it; furthermore they should be encouraged to have an active role in their therapy. It is necessary to prevent the onset of the pain (by the clock) by considering the biological half-life, the bioavailability and the duration of action of the therapy. According to the World Health Organization (WHO), pain treatment is based on a three-step ladder. Adjuvant therapies Adjuvant therapies are often associated with the drugs in the WHO three step ladder. This heterogeneous group of non-analgesic drugs is used in the treatment of bone pain by bettering the analgesia or reducing the side effects brought on by analgesics. Conclusion In the daily struggle that doctors face to treat their patients, pain management should not be disregarded. Among the various types of pain, bone pain, must not be underestimated but be fought against by using all means available. Patients need to be treated depending on the severity of their pain, NSAIDs should be the preferred choice of treatment for acute pain but not for that of chronic pain. In the case of chronic pain opioids should be used in their most recent fomulations as they can guarantee fewer side effects. Patients should also be prescribed adjuvant drugs as well as being given psychological support in order to ensure successful treatment. PMID:27920802

  10. Acidic microenvironment and bone pain in cancer-colonized bone

    PubMed Central

    Yoneda, Toshiyuki; Hiasa, Masahiro; Nagata, Yuki; Okui, Tatsuo; White, Fletcher A

    2015-01-01

    Solid cancers and hematologic cancers frequently colonize bone and induce skeletal-related complications. Bone pain is one of the most common complications associated with cancer colonization in bone and a major cause of increased morbidity and diminished quality of life, leading to poor survival in cancer patients. Although the mechanisms responsible for cancer-associated bone pain (CABP) are poorly understood, it is likely that complex interactions among cancer cells, bone cells and peripheral nerve cells contribute to the pathophysiology of CABP. Clinical observations that specific inhibitors of osteoclasts reduce CABP indicate a critical role of osteoclasts. Osteoclasts are proton-secreting cells and acidify extracellular bone microenvironment. Cancer cell-colonized bone also releases proton/lactate to avoid intracellular acidification resulting from increased aerobic glycolysis known as the Warburg effect. Thus, extracellular microenvironment of cancer-colonized bone is acidic. Acidosis is algogenic for nociceptive sensory neurons. The bone is densely innervated by the sensory neurons that express acid-sensing nociceptors. Collectively, CABP is evoked by the activation of these nociceptors on the sensory neurons innervating bone by the acidic extracellular microenvironment created by bone-resorbing osteoclasts and bone-colonizing cancer cells. As current treatments do not satisfactorily control CABP and can elicit serious side effects, new therapeutic interventions are needed to manage CABP. Understanding of the cellular and molecular mechanism by which the acidic extracellular microenvironment is created in cancer-colonized bone and by which the expression and function of the acid-sensing nociceptors on the sensory neurons are regulated would facilitate to develop novel therapeutic approaches for the management of CABP. PMID:25987988

  11. The Walker 256 Breast Cancer Cell- Induced Bone Pain Model in Rats.

    PubMed

    Shenoy, Priyank A; Kuo, Andy; Vetter, Irina; Smith, Maree T

    2016-01-01

    The majority of patients with terminal breast cancer show signs of bone metastasis, the most common cause of pain in cancer. Clinically available drug treatment options for the relief of cancer-associated bone pain are limited due to either inadequate pain relief and/or dose-limiting side-effects. One of the major hurdles in understanding the mechanism by which breast cancer causes pain after metastasis to the bones is the lack of suitable preclinical models. Until the late twentieth century, all animal models of cancer induced bone pain involved systemic injection of cancer cells into animals, which caused severe deterioration of animal health due to widespread metastasis. In this mini-review we have discussed details of a recently developed and highly efficient preclinical model of breast cancer induced bone pain: Walker 256 cancer cell- induced bone pain in rats. The model involves direct localized injection of cancer cells into a single tibia in rats, which avoids widespread metastasis of cancer cells and hence animals maintain good health throughout the experimental period. This model closely mimics the human pathophysiology of breast cancer induced bone pain and has great potential to aid in the process of drug discovery for treating this intractable pain condition.

  12. The Walker 256 Breast Cancer Cell- Induced Bone Pain Model in Rats

    PubMed Central

    Shenoy, Priyank A.; Kuo, Andy; Vetter, Irina; Smith, Maree T.

    2016-01-01

    The majority of patients with terminal breast cancer show signs of bone metastasis, the most common cause of pain in cancer. Clinically available drug treatment options for the relief of cancer-associated bone pain are limited due to either inadequate pain relief and/or dose-limiting side-effects. One of the major hurdles in understanding the mechanism by which breast cancer causes pain after metastasis to the bones is the lack of suitable preclinical models. Until the late twentieth century, all animal models of cancer induced bone pain involved systemic injection of cancer cells into animals, which caused severe deterioration of animal health due to widespread metastasis. In this mini-review we have discussed details of a recently developed and highly efficient preclinical model of breast cancer induced bone pain: Walker 256 cancer cell- induced bone pain in rats. The model involves direct localized injection of cancer cells into a single tibia in rats, which avoids widespread metastasis of cancer cells and hence animals maintain good health throughout the experimental period. This model closely mimics the human pathophysiology of breast cancer induced bone pain and has great potential to aid in the process of drug discovery for treating this intractable pain condition. PMID:27630567

  13. Molecular Mechanisms That Contribute to Bone Marrow Pain

    PubMed Central

    Ivanusic, Jason J.

    2017-01-01

    Pain associated a bony pathology puts a significant burden on individuals, society, and the health-care systems worldwide. Pathology that involves the bone marrow activates sensory nerve terminal endings of peripheral bone marrow nociceptors, and is the likely trigger for pain. This review presents our current understanding of how bone marrow nociceptors are influenced by noxious stimuli presented in pathology associated with bone marrow. A number of ion channels and receptors are emerging as important modulators of the activity of peripheral bone marrow nociceptors. Nerve growth factor (NGF) sequestration has been trialed for the management of inflammatory bone pain (osteoarthritis), and there is significant evidence for interaction of NGF with bone marrow nociceptors. Activation of transient receptor potential cation channel subfamily V member 1 sensitizes bone marrow nociceptors and could contribute to increased sensitivity of patients to noxious stimuli in various bony pathologies. Acid-sensing ion channels sense changes to tissue pH in the bone marrow microenvironment and could be targeted to treat pathology that involves acidosis of the bone marrow. Piezo2 is a mechanically gated ion channel that has recently been reported to be expressed by most myelinated bone marrow nociceptors and might be a target for treatments directed against mechanically induced bone pain. These ion channels and receptors could be useful targets for the development of peripherally acting drugs to treat pain of bony origin. PMID:28955292

  14. Molecular Mechanisms That Contribute to Bone Marrow Pain.

    PubMed

    Ivanusic, Jason J

    2017-01-01

    Pain associated a bony pathology puts a significant burden on individuals, society, and the health-care systems worldwide. Pathology that involves the bone marrow activates sensory nerve terminal endings of peripheral bone marrow nociceptors, and is the likely trigger for pain. This review presents our current understanding of how bone marrow nociceptors are influenced by noxious stimuli presented in pathology associated with bone marrow. A number of ion channels and receptors are emerging as important modulators of the activity of peripheral bone marrow nociceptors. Nerve growth factor (NGF) sequestration has been trialed for the management of inflammatory bone pain (osteoarthritis), and there is significant evidence for interaction of NGF with bone marrow nociceptors. Activation of transient receptor potential cation channel subfamily V member 1 sensitizes bone marrow nociceptors and could contribute to increased sensitivity of patients to noxious stimuli in various bony pathologies. Acid-sensing ion channels sense changes to tissue pH in the bone marrow microenvironment and could be targeted to treat pathology that involves acidosis of the bone marrow. Piezo2 is a mechanically gated ion channel that has recently been reported to be expressed by most myelinated bone marrow nociceptors and might be a target for treatments directed against mechanically induced bone pain. These ion channels and receptors could be useful targets for the development of peripherally acting drugs to treat pain of bony origin.

  15. The use of radioisotopes for palliation of metastatic bone pain.

    PubMed

    Gkialas, I; Iordanidou, L; Galanakis, I; Giannopoulos, S

    2008-01-01

    Bone pain associated with advanced prostate and other cancers is a frequent and significant complication. Pharmaceutical therapy of bone pain includes nonsteroidal analgesics and opiates. While external beam radiation therapy remains the mainstay of pain palliation of solitary lesions, bone-seeking radiopharmaceuticals have entered the armamentarium for the treatment of multiple osseous metastases. The 3 radioisotopes currently approved for treatment of pain (strontium-89/(89)Sr, samarium-153/(153)Sm and rhenium-186/(186)Re) are discussed in this review including the approved dose, method of administration and indications for use.

  16. Neuropathic Pain Features in Patients with Bone Metastases.

    PubMed

    Nakamura, N; Takahashi, O; Zenda, S; Kawamori, J; Ogita, M; Onozawa, M; Arahira, S; Toshima, M; Motegi, A; Hirano, Y; Hojo, H; Akimoto, T

    2016-03-01

    The results of previous randomised controlled trials suggest that radiation oncologists should consider the presence of neuropathic pain when they prescribe dose fractionations for painful bone metastases. Although validated screening tools for neuropathic pain features are currently available, the prevalence of such features among patients with painful bone metastases is still poorly understood. The purpose of this study was to estimate the prevalence of neuropathic pain features among patients who received palliative radiotherapy for painful bone metastases. We conducted a cohort survey of consecutive patients who received palliative radiotherapy for painful bone metastases at St Luke's International Hospital between 2013 and 2014. Patients were prospectively assessed before radiotherapy using the validated screening questionnaire to identify neuropathic pain components in Japanese patients. Pain with neuropathic features was prospectively defined using the total score of the seven-item questionnaire and a cut-off score ≥9. The pain response was assessed 2 months after the start of radiotherapy according to the criteria defined by the International Bone Metastases Consensus Working Party. Eighty-seven patients were assessed. Twenty-four per cent of patients (95% confidence interval: 16-35%) were diagnosed as having pain with neuropathic features. On multivariate analysis, no significant correlations were seen between neuropathic pain features and patient characteristics. Sixty-four patients (74%) were assessable 2 months after the start of radiotherapy. Overall response rates were 59% (95% confidence interval: 33-82%) in patients with neuropathic features and 55% (95% confidence interval: 40-70%) in those without such features. A considerable proportion of the patients were proven to have bone pain with neuropathic features. Further investigations are warranted to validate symptom assessment tools in cooperation with pain distribution and image findings, and to

  17. Local autogenous bone mixed with bone expander: an optimal option of bone graft in single-segment posterolateral lumbar fusion.

    PubMed

    Chang, Chia-Hao; Lin, Mou-Zen; Chen, Yen-Jen; Hsu, Horng-Chaung; Chen, Hsien-Te

    2008-12-01

    This was a retrospective study of clinical results for single-segment posterolateral lumbar fusion using local autograft bone with bone expander. Sixty-six patients underwent single-segment decompression with instrumented posterolateral fusion. Locally harvested morselized bone from the decompressive site mixed with 2 mL calcium sulfate (OSTEOSET, Wright Medical Technology, Arlington, TN, USA) was used for the fusion at the posterolateral aspect of the lumbar spine. The minimum follow-up period was 15 months. The status of the fusion was evaluated by plain film, flexion-extension view, and fine-cut computed tomography (CT) with coronal reconstruction. Radiographic fusion criteria included less than 5 degrees of angular motion, less than 2 mm of translation, and evidence of bridging bone in the posterolateral lumbar area on the CT scan. The clinical outcome was recorded using VAS score and the ODI. The results were then compared with the result of the other group who had received the same procedure except that a pure autogenous bone graft harvested from the PSIS was used. In the group using local bone and OSTEOSET, the fusion rate was 92.3% by the strict criteria. The VAS scores for leg pain and back pain were decreased in the 2 groups, but there was no significant difference between them. The improvement in the ODI was also similar between the 2 groups. Intraoperative blood loss and the time needed for the operation were significantly decreased in the group using local bone and OSTEOSET as the bone graft. In the group using autogenous bone graft, donor site morbidity was still encountered. Using local laminectomy bone with calcium sulfate as bone graft is a practical option in posterolateral lumbar fusion with the advantages of less operative time, less blood loss, and avoidance of donor site morbidity.

  18. Retained foetal bones: an intrauterine cause of chronic pelvic pain.

    PubMed

    Kalu, Emmanuel; Richardson, Robert

    2009-02-01

    Intrauterine retention of foetal bones is an uncommon but recognised complication of late termination of pregnancy. Secondary subfertility, abnormal uterine bleeding and vaginal discharge are the usual presenting complaints. We report a case of prolonged retention of foetal bones for 14 years in a woman who presented with chronic pelvic pain. Hysteroscopic examination was diagnostic and therapeutic. Retained foetal bones are an uncommon intrauterine cause of chronic pelvic pain that should be considered particularly when a woman with a history of late termination presents with pelvic pain. Hysteroscopic evacuation is curative.

  19. Urinary cytokines/chemokines pattern in patients with painful bone metastases undergoing external beam radiotherapy experiencing pain flare.

    PubMed

    Bushehri, Ahmad; Chow, Edward; Zhang, Liying; Azad, Azar; Vuong, Sherlyn; Pasetka, Mark; Zhou, Michelle; Hird, Amanda; Dennis, Kristopher; McDonald, Rachel; DeAngelis, Carlo

    2016-04-01

    External beam radiotherapy (EBRT) is a mainstay for treatment of painful bone metastases. Transient worsening of pain ("pain flare") occurs in 40% of patients. We investigated the pathophysiology of pain flare through assessment of changes in urinary cytokines/chemokines in patients receiving EBRT for painful bone metastases. Urine samples were collected from patients receiving a single 8 Gy fraction for painful bone metastases preparation, day 1 or 2 and on an additional day between days 3 to 5 post radiation. Patients completed a standardized pain and analgesic use diary daily for 10 days following radiation. Patients were deemed to have pain flare if they had a two-point increase from baseline worst pain on 0-10 scale and no decrease in analgesic intake or a 25% increase in analgesic intake with no decrease in worst pain. The Millipore Milliplex 42-Plex Cyto-kine/Chemokine Kit™ was used to measure urinary levels of a panel of cytokines/chemokines. Forty-six patients consented to the study of which 28 were evaluable (complete urine and diary data), and 83/84 urine samples were available for analysis. Pain flare was experienced by 11 patients (39%). The following cytokines/chemokines were detectable in at least 50% of the patients: EGF, fractalkine, GRO, IL-4, IL-8, interferon gamma induced protein 10 (IP-10), MCP-1, macrophage derived chemokine (MDC), PDGF-AA, sIL-2Ra, TGF-Alpha, VEGF. Comparing patients with or without pain flare EGF, fractalkine, GRO, IL-8, IP-10, MCP-1, MDC, sIL-2Ra, and TGF-alpha increased following radiation in both groups. Patients with pain flare have significant lower levels on IL-8, IP-10, and MDC over time. No specific time trend was noticed. Patients who experience pain flare appear to have a different pattern in urinary cytokine/chemokine levels than patients without pain flare. A larger study is required to confirm the possible role of cytokines/chemokines in predisposition to and/or the cause of pain flare following radiation to

  20. Samarium-153 treatment of bone pain in patients with metastatic prostate cancer.

    PubMed

    Petersen, Lars J; Lund, Lars; Jønler, Morten; Jakobsen, Mette; Abrahamsen, Jan

    2010-06-01

    Painful bone metastases are common in advanced prostate cancer. We report the clinical outcome after administration of Samarium-153 ((153)Sm), an emitter of beta-particles that concentrates in the areas of enhanced osteoblastic activity. Twenty-two patients (median age 73 years) with metastatic, hormone-refractory prostate cancer received a single bolus infusion of (153)Sm (37 MBq/kg). All patients had painful bone metastases to more than one anatomical region, and most had inadequate pain relief to narcotic analgesics. Bone specific pain, analgesic score according to WHO, ECOG performance status, and blood count were evaluated before and up to 28 weeks after treatment. Median follow-up was six weeks (mean 14 weeks). Eleven patients died within the 28 week observation period (ten from terminal disease), and four patients had their observation period truncated. Median pain score was 56.3%, 50.0%, and 50.0% of baseline values at week 4 (n = 20), 16 (n = 10), and 28 (n = 7), respectively. A reduction of baseline pain score by 50% or more was observed in 50%, 70% and 71% of patients at week 4, 16, and 28, respectively. Hematological toxicity was mild and reversible in most cases. Administration of (153)Sm to prostate cancer patients with painful bone metastases offered clinical relevant pain relief with tolerable hematological toxicity.

  1. Treatment of metastatic bone pain with strontium-89.

    PubMed

    Robinson, R G; Spicer, J A; Preston, D F; Wegst, A V; Martin, N L

    1987-01-01

    We have utilized 89Sr as palliative treatment for bone pain secondary to metastatic cancer in the skeleton of over 200 patients. The best results have been in patients with carcinoma of the prostate (80% response rate) and breast (89%). Results in a small number of patients with a variety of other cell types were not nearly as encouraging. Strontium-89 provides excellent palliation in the management of bone pain secondary to prostate and breast carcinoma.

  2. Incremental value of single photon emission tomography/computed tomography in 3-phase bone scintigraphy of an accessory navicular bone.

    PubMed

    Jain, Sachin; Karunanithi, Sellam; Agarwal, Krishan Kant; Kumar, Ganesh; Roy, Shambo Guha; Tripathi, Madhavi

    2014-07-01

    Accessory navicular bone is one of the supernumerary ossicles in the foot. Radiography is non diagnostic in symptomatic cases. Accessory navicular has been reported as a cause of foot pain and is usually associated with flat foot. Increased radio tracer uptake on bone scan is found to be more sensitive. We report a case highlighting the significance of single photon emission tomography/computed tomography in methylene diphosphonate bone scan in the evaluation of symptomatic accessory navicular bone where three phase bone scan is equivocal.

  3. Incremental value of single photon emission tomography/computed tomography in 3-phase bone scintigraphy of an accessory navicular bone

    PubMed Central

    Jain, Sachin; Karunanithi, Sellam; Agarwal, Krishan Kant; Kumar, Ganesh; Roy, Shambo Guha; Tripathi, Madhavi

    2014-01-01

    Accessory navicular bone is one of the supernumerary ossicles in the foot. Radiography is non diagnostic in symptomatic cases. Accessory navicular has been reported as a cause of foot pain and is usually associated with flat foot. Increased radio tracer uptake on bone scan is found to be more sensitive. We report a case highlighting the significance of single photon emission tomography/computed tomography in methylene diphosphonate bone scan in the evaluation of symptomatic accessory navicular bone where three phase bone scan is equivocal. PMID:25210293

  4. Single dose dihydrocodeine for acute postoperative pain.

    PubMed

    Edwards, J E; McQuay, H J; Moore, R A

    2000-01-01

    Dihydrocodeine is a synthetic opioid analgesic developed in the early 1900s. Its structure and pharmacokinetics are similar to that of codeine and it is used for the treatment of postoperative pain or as an antitussive. It is becoming increasingly important to assess the relative efficacy and harm caused by different treatments. Relative efficacy can be determined when an analgesic is compared with control under similar clinical circumstances. To quantitatively assess the analgesic efficacy and adverse effects of single-dose dihydrocodeine compared with placebo in randomised trials in moderate to severe postoperative pain. Published reports were identified from a variety of electronic databases including Medline, Biological Abstracts, Embase, the Cochrane Library and the Oxford Pain Relief Database. Additional studies were identified from the reference lists of retrieved reports. The following inclusion criteria were used: full journal publication, clinical trial, random allocation of patients to treatment groups, double blind design, adult patients, pain of moderate to severe intensity at baseline, postoperative administration of study drugs, treatment arms which included dihydrocodeine and placebo and either oral or injected (intramuscular or intravenous) administration of study drugs. Data collection and analysis: Summed pain intensity and pain relief data over 4-6 hours were extracted and converted into dichotomous information to yield the number of patients obtaining at least 50% pain relief. This was used to calculate relative benefit and number-needed-to-treat for one patient to obtain at least 50% pain relief. Single-dose adverse effect data were collected and used to calculate relative risk and number-needed-to-harm. Fifty-two reports were identified as possible randomised trials which assessed dihydrocodeine in postoperative pain. Four reports met the inclusion criteria; all assessed oral dihydrocodeine. Three reports (194 patients) compared

  5. Bone pain mechanism in osteoporosis: a narrative review

    PubMed Central

    Mattia, Consalvo; Coluzzi, Flaminia; Celidonio, Ludovica; Vellucci, Renato

    2016-01-01

    Summary Bone pain in elderly people dramatically affects their quality of life, with osteoporosis being the leading cause of skeletal related events. Peripheral and central mechanisms are involved in the pathogenesis of the nervous system sensitization. Osteoporosis in the elderly has been associated with increased density of bone sensory nerve fibers and their pathological modifications, together with an over-expression of nociceptors sensitized by the lowering pH due to the osteoclastic activity. The activation of N-methyl-D-aspartate (NMDA) receptors and the microglia, as a response to a range of pathological conditions, represent the leading cause of central sensitization. Unfortunately, osteoporosis is named the “silent thief” because it manifests with painful manifestation only when a fracture occurs. In the management of patients suffering from bone pain, both the nociceptive and the neuropathic component of chronic pain should be considered in the selection of the analgesic treatment. PMID:27920803

  6. The management of pain in metastatic bone disease.

    PubMed

    Buga, S; Sarria, J E

    2012-04-01

    Metastatic bone disease is a common cause of pain in cancer patients. A multidisciplinary approach to treatment is often necessary because simplified analgesic regimens may fail in the face of complex pain generators, especially those involved in the genesis of neuropathic pain. From the origins of formalized guidelines by the World Health Organization (WHO) to recent developments in implantable therapies, great strides have been made to meet the needs of these patients. The authors review the existing literature on the pathophysiology and treatment options for pain generated by metastatic bone disease and summarize classic and new approaches. Relatively recent animal models of malignant bone disease have allowed a better understanding of the intimate mechanisms involved in the genesis of pain, resulting in a mechanistic approach to its treatment. Analgesic strategies can be developed with specific targets in mind to complement the classic, opioid-centered WHO analgesic ladder obtaining improved outcomes and quality of life. Unfortunately, high-quality evidence is difficult to produce in pain medicine, and these concepts are evolving slowly. Treatment options are expanding for the challenging clinical problem of painful metastatic bone disease. Efforts are concentrated on developing alternative nonopioid approaches that appear to increase the success rate and improve patients' quality of life.

  7. Cancer-induced bone pain: Mechanisms and models.

    PubMed

    Lozano-Ondoua, A N; Symons-Liguori, A M; Vanderah, T W

    2013-12-17

    Cancerous cells can originate in a number of different tissues such as prostate, breast and lung, but often go undetected and are non-painful. Many types of cancers have a propensity to metastasize to the bone microenvironment first. Tumor burden within the bone causes excruciating breakthrough pain with properties of ongoing pain that is inadequately managed with current analgesics. Part of this failure is due to the poor understanding of the etiology of cancer pain. Animal models of cancer-induced bone pain (CIBP) have revealed that the neurochemistry of cancer has features distinctive from other chronic pain states. For example, preclinical models of metastatic cancer often result in the positive modulation of neurotrophins, such as NGF and BDNF, that can lead to nociceptive sensitization. Preclinical cancer models also demonstrate nociceptive neuronal expression of acid-sensing receptors, such as ASIC1 and TRPV1, which respond to cancer-induced acidity within the bone. CIBP is correlated with a significant increase in pro-inflammatory mediators acting peripherally and centrally, contributing to neuronal hypersensitive states. Finally, cancer cells generate high levels of oxidative molecules that are thought to increase extracellular glutamate concentrations, thus activating primary afferent neurons. Knowledge of the unique neuro-molecular profile of cancer pain will ultimately lead to the development of novel and superior therapeutics for CIBP.

  8. Angiotensin-(1-7)/Mas receptor as an antinociceptive agent in cancer-induced bone pain.

    PubMed

    Forte, Brittany L; Slosky, Lauren M; Zhang, Hong; Arnold, Moriah R; Staatz, William D; Hay, Meredith; Largent-Milnes, Tally M; Vanderah, Todd W

    2016-12-01

    Many cancerous solid tumors metastasize to the bone and induce pain (cancer-induced bone pain [CIBP]). Cancer-induced bone pain is often severe because of enhanced inflammation, rapid bone degradation, and disease progression. Opioids are prescribed to manage this pain, but they may enhance bone loss and increase tumor proliferation, further compromising patient quality of life. Angiotensin-(1-7) (Ang-(1-7)) binds and activates the Mas receptor (MasR). Angiotensin-(1-7)/MasR activation modulates inflammatory signaling after acute tissue insult, yet no studies have investigated whether Ang-(1-7)/MasR play a role in CIBP. We hypothesized that Ang-(1-7) inhibits CIBP by targeting MasR in a murine model of breast CIBP. 66.1 breast cancer cells were implanted into the femur of BALB/cAnNHsd mice as a model of CIBP. Spontaneous and evoked pain behaviors were assessed before and after acute and chronic administration of Ang-(1-7). Tissues were collected from animals for ex vivo analyses of MasR expression, tumor burden, and bone integrity. Cancer inoculation increased spontaneous pain behaviors by day 7 that were significantly reduced after a single injection of Ang-(1-7) and after sustained administration. Preadministration of A-779 a selective MasR antagonist prevented this reduction, whereas pretreatment with the AT2 antagonist had no effect; an AT1 antagonist enhanced the antinociceptive activity of Ang-(1-7) in CIBP. Repeated Ang-(1-7) administration did not significantly change tumor burden or bone remodeling. Data here suggest that Ang-(1-7)/MasR activation significantly attenuates CIBP, while lacking many side effects seen with opioids. Thus, Ang-(1-7) may be an alternative therapeutic strategy for the nearly 90% of patients with advanced-stage cancer who experience excruciating pain.

  9. Angiotensin-(1-7)/Mas receptor as an antinociceptive agent in cancer-induced bone pain

    PubMed Central

    Forte, Brittany L.; Slosky, Lauren M.; Zhang, Hong; Arnold, Moriah R.; Staatz, William D.; Hay, Meredith; Largent-Milnes, Tally M.; Vanderah, Todd W.

    2016-01-01

    Abstract Many cancerous solid tumors metastasize to the bone and induce pain (cancer-induced bone pain [CIBP]). Cancer-induced bone pain is often severe because of enhanced inflammation, rapid bone degradation, and disease progression. Opioids are prescribed to manage this pain, but they may enhance bone loss and increase tumor proliferation, further compromising patient quality of life. Angiotensin-(1-7) (Ang-(1-7)) binds and activates the Mas receptor (MasR). Angiotensin-(1-7)/MasR activation modulates inflammatory signaling after acute tissue insult, yet no studies have investigated whether Ang-(1-7)/MasR play a role in CIBP. We hypothesized that Ang-(1-7) inhibits CIBP by targeting MasR in a murine model of breast CIBP. 66.1 breast cancer cells were implanted into the femur of BALB/cAnNHsd mice as a model of CIBP. Spontaneous and evoked pain behaviors were assessed before and after acute and chronic administration of Ang-(1-7). Tissues were collected from animals for ex vivo analyses of MasR expression, tumor burden, and bone integrity. Cancer inoculation increased spontaneous pain behaviors by day 7 that were significantly reduced after a single injection of Ang-(1-7) and after sustained administration. Preadministration of A-779 a selective MasR antagonist prevented this reduction, whereas pretreatment with the AT2 antagonist had no effect; an AT1 antagonist enhanced the antinociceptive activity of Ang-(1-7) in CIBP. Repeated Ang-(1-7) administration did not significantly change tumor burden or bone remodeling. Data here suggest that Ang-(1-7)/MasR activation significantly attenuates CIBP, while lacking many side effects seen with opioids. Thus, Ang-(1-7) may be an alternative therapeutic strategy for the nearly 90% of patients with advanced-stage cancer who experience excruciating pain. PMID:27541850

  10. Single dose dipyrone for acute postoperative pain

    PubMed Central

    Derry, Sheena; Faura, Clara; Edwards, Jayne; McQuay, Henry J; Moore, R Andrew

    2014-01-01

    Background Dipyrone (metamizole) is a non-steroidal anti-inflammatory drug used in some countries to treat pain (postoperative, colic, cancer, and migraine); it is banned in others because of an association with life-threatening blood agranulocytosis. This review updates a 2001 Cochrane review, and no relevant new studies were identified, but additional outcomes were sought. Objectives To assess the efficacy and adverse events of single dose dipyrone in acute postoperative pain. Search methods The earlier review searched CENTRAL, MEDLINE, EMBASE, LILACS and the Oxford Pain Relief Database to December 1999. For the update we searched CENTRAL, MEDLINE,EMBASE and LILACS to February 2010. Selection criteria Single dose, randomised, double-blind, placebo or active controlled trials of dipyrone for relief of established moderate to severe postoperative pain in adults. We included oral, rectal, intramuscular or intravenous administration of study drugs. Data collection and analysis Studies were assessed for methodological quality and data extracted by two review authors independently. Summed total pain relief over six hours (TOTPAR) was used to calculate the number of participants achieving at least 50% pain relief. Derived results were used to calculate, with 95% confidence intervals, relative benefit compared to placebo, and the number needed to treat (NNT) for one participant to experience at least 50% pain relief over six hours. Use and time to use of rescue medication were additional measures of efficacy. Information on adverse events and withdrawals was collected. Main results Fifteen studies tested mainly 500 mg oral dipyrone (173 participants), 2.5 g intravenous dipyrone (101), 2.5 g intramuscular dipyrone (99); fewer than 60 participants received any other dose. All studies used active controls (ibuprofen, paracetamol, aspirin, flurbiprofen, ketoprofen, dexketoprofen, ketorolac, pethidine, tramadol, suprofen); eight used placebo controls. Over 70% of participants

  11. Single dose dipyrone for acute postoperative pain.

    PubMed

    Edwards, Jayne; Meseguer, Fuensanta; Faura, Clara; Moore, R Andrew; McQuay, Henry J; Derry, Sheena

    2010-09-08

    Dipyrone (metamizole) is a non-steroidal anti-inflammatory drug used in some countries to treat pain (postoperative, colic, cancer, and migraine); it is banned in others because of an association with life-threatening blood agranulocytosis. This review updates a 2001 Cochrane review, and no relevant new studies were identified, but additional outcomes were sought. To assess the efficacy and adverse events of single dose dipyrone in acute postoperative pain. The earlier review searched CENTRAL, MEDLINE, EMBASE, LILACS and the Oxford Pain Relief Database to December 1999. For the update we searched CENTRAL, MEDLINE,EMBASE and LILACS to February 2010. Single dose, randomised, double-blind, placebo or active controlled trials of dipyrone for relief of established moderate to severe postoperative pain in adults. We included oral, rectal, intramuscular or intravenous administration of study drugs. Studies were assessed for methodological quality and data extracted by two review authors independently. Summed total pain relief over six hours (TOTPAR) was used to calculate the number of participants achieving at least 50% pain relief. Derived results were used to calculate, with 95% confidence intervals, relative benefit compared to placebo, and the number needed to treat (NNT) for one participant to experience at least 50% pain relief over six hours. Use and time to use of rescue medication were additional measures of efficacy. Information on adverse events and withdrawals was collected. Fifteen studies tested mainly 500 mg oral dipyrone (173 participants), 2.5 g intravenous dipyrone (101), 2.5 g intramuscular dipyrone (99); fewer than 60 participants received any other dose. All studies used active controls (ibuprofen, paracetamol, aspirin, flurbiprofen, ketoprofen, dexketoprofen, ketorolac, pethidine, tramadol, suprofen); eight used placebo controls.Over 70% of participants experienced at least 50% pain relief over 4 to 6 hours with oral dipyrone 500 mg compared to 30

  12. Incidence of pain flare following palliative radiotherapy for symptomatic bone metastases: multicenter prospective observational study.

    PubMed

    Gomez-Iturriaga, Alfonso; Cacicedo, Jon; Navarro, Arturo; Morillo, Virginia; Willisch, Patricia; Carvajal, Claudia; Hortelano, Eduardo; Lopez-Guerra, Jose Luis; Illescas, Ana; Casquero, Francisco; Del Hoyo, Olga; Ciervide, Raquel; Irasarri, Ana; Pijoan, Jose Ignacio; Bilbao, Pedro

    2015-10-01

    Palliative radiotherapy (RT) is an effective treatment for symptomatic bone metastases. Pain flare, a transient worsening of the bone pain after RT, has been described in previous reports with different incidence rates. The aim of the study was to prospectively evaluate the incidence of pain flare following RT for painful bone metastases and evaluate its effects on pain control and functionality of the patients. Between June 2010 and June 2014, 204 patients were enrolled in this study and 135 patients with complete data were evaluable. Pain flare was defined as a 2- point increase in worst pain score as compared with baseline with no decrease in analgesic intake or a 25% increase in analgesic intake as compared with baseline with no decrease in worst pain score. All pain medications and worst pain scores were collected before, daily during, and for 10 days after RT. The Brief Pain Inventory (BPI) was filled out on the pretreatment and at the 4 weeks follow-up visit. There were 90 men (66.7%) and 45 women (33.3%). Mean age was 66 years (SD 9.8). The most common primary cancer site was lung in 42 patients (31.1%), followed by prostate in 27 patients (20.0%). Forty-two patients (31.1%) patients received a single fraction of 8 Gy and 83 (61.5%) received 20 Gy in five fractions. The overall pain flare incidence across all centers was 51/135 (37.7%). The majority of pain flares occurred on days 1-5 (88.2%). The mean duration of the pain flare was 3 days (SD: 3). There were no significant relationships between the occurrence of pain flare and collected variables. All BPI items measured four weeks after end of RT showed significant improvement as compared with pretreatment scores (p < 0.001). No significant differences in BPI time trends were found between patients with and without flare pain. Pain flare is a common event, occurring in nearly 40% of the patients that receive palliative RT for symptomatic bone metastases. This phenomenon is not a predictor for pain

  13. Bone density in chronic low back pain: a pilot study.

    PubMed

    Gaber, T A Z K; McGlashan, K A; Love, S; Jenner, J R; Crisp, A J

    2002-12-01

    Levels of physical activity in chronic low back pain patients are relatively low due to their fear of provoking pain. This may have a secondary impact on maintenance of bone mass. The objective of this study is to determine if patients with chronic low back pain are at a higher risk of bone demineralization. Bone mineral density (BMD) was measured in 25 chronic low back pain patients at the lumbar spine, hip and distal forearm. A university hospital. Twenty-five chronic low back pain patients (mean age 45 years) enrolled on a residential back pain rehabilitation programme. Thirteen patients (52%) were osteopenic or osteoporotic in one or more sites. BMD at the lumbar spine was generally lower than the mean BMD of age-matched subjects (p = 0.04). There was no significant relationship between BMD and duration of pain, disability, sex or previous surgical intervention. Chronic low back pain patients have an increased incidence of osteopenia and osteoporosis. This finding reinforces the importance of motivating patients to incorporate exercise into daily life. Given the limited set of subjects used in the present study, further studies are required.

  14. Effect of Bisphosphonates, Denosumab, and Radioisotopes on Bone Pain and Quality of Life in Patients with Non-Small Cell Lung Cancer and Bone Metastases: A Systematic Review.

    PubMed

    Hendriks, Lizza E L; Hermans, Bregtje C M; van den Beuken-van Everdingen, Marieke H J; Hochstenbag, Monique M H; Dingemans, Anne-Marie C

    2016-02-01

    Bone metastases are common in patients with non-small cell lung cancer (NSCLC), often causing pain and a decrease in quality of life (QoL). The effect of bone-targeted agents is evaluated by reduction in skeletal-related events in which neither pain nor QoL are included. Radioisotopes can be administered for more diffuse bone pain that is not eligible for palliative radiotherapy. The evidence that bone-targeted agents relieve pain or improve QoL is not solid. We performed a systematic review of the effect of bone-targeted agents on pain and QoL in patients with NSCLC. Our systematic literature search included original articles or abstracts reporting on bisphosphonates, denosumab, or radioisotopes or combinations thereof in patients with bone metastases (≥5 patients with NSCLC), with pain, QoL, or both serving as the primary or secondary end point. Of the twenty-five eligible studies, 13 examined bisphosphonates (one also examined denosumab) and 12 dealt with radioisotopes. None of the randomized studies on bisphosphonates or denosumab evaluated pain and QoL as the primary end point. In the single-arm studies of bisphosphonates a decrease in pain or analgesic consumption was found for 38% to 77% of patients. QoL was included in five of 13 studies, but improvement was found in only two. No high-level evidence that bisphosphonates or denosumab reduce pain or improve QoL was found. Although the data are limited, radioisotopes seem to reduce pain with a rapid onset of action and duration of response of 1 to 3 months. The evidence that bisphosphonates or denosumab reduce or prevent pain in patients with NSCLC and bone metastases or that they have an influence on QoL is very weak. Radioisotopes can be used to reduce diffuse pain, although there is no high-level evidence supporting such use.

  15. New Mechanism of Bone Cancer Pain: Tumor Tissue-Derived Endogenous Formaldehyde Induced Bone Cancer Pain via TRPV1 Activation.

    PubMed

    Wan, You

    2016-01-01

    In recent years, our serial investigations focused on the role of cancer cells-derived endogenous formaldehyde in bone cancer pain. We found that cancer cells produced formaldehyde through demethylation process by serine hydroxymethyltransferase (SHMT1 and SHMT2) and lysine-specific histone demethylase 1 (LSD1). When the cancer cells metastasized into bone marrow, the elevated endogenous formaldehyde induced bone cancer pain through activation on the transient receptor potential vanilloid subfamily member 1 (TRPV1) in the peripheral nerve fibers. More interestingly, TRPV1 expressions in the peripheral fibers were upregulated by the local insulin-like growth factor I (IGF-I) produced by the activated osteoblasts. In conclusion, tumor tissue-derived endogenous formaldehyde induced bone cancer pain via TRPV1 activation.

  16. Pathophysiology and medical treatment of pain in fibrous dysplasia of bone.

    PubMed

    Chapurlat, Roland D; Gensburger, Deborah; Jimenez-Andrade, Juan M; Ghilardi, Joseph R; Kelly, Marilyn; Mantyh, Patrick

    2012-05-24

    One of the most common complications of fibrous dysplasia of bone (FD) is bone pain. Usual pain killers are often of inadequate efficacy to control this bone pain. The mechanism of bone pain in FD remains uncertain, but by analogy with bone tumors one may consider that ectopic sprouting and formation of neuroma-like structures by sensory and sympathetic nerve fibers also occur in the dysplastic skeleton. Bone pain has been reported in up to 81% of adults and 49% of children. It affects predominantly the lower limbs and the spine. The degree of pain is highly variable and adults reports more pain than children. Bisphosphonates have been shown to reduce bone pain in uncontrolled studies. Their influence on bone strength remains unknown. In a randomized trial testing alendronate, bone pain was not significantly improved. Another trial assessing the effect of risedronate is ongoing. Possible future therapies include tocilizumab, denosumab and drugs targeting nerve growth factor and its receptor TrkA.

  17. Bone alterations are associated with ankle osteoarthritis joint pain

    PubMed Central

    Nakamura, Yukio; Uchiyama, Shigeharu; Kamimura, Mikio; Komatsu, Masatoshi; Ikegami, Shota; Kato, Hiroyuki

    2016-01-01

    The etiology of ankle osteoarthritis (OA) is largely unknown. We analyzed 24 ankle OA of 21 patients diagnosed by plain radiographs using magnetic resonance imaging (MRI). Ankle joint pain disappeared in 22 out of 24 joints by conservative treatment. MRI bone signal changes in and around the ankle joints were observed in 22 of 24 joints. Bone signal changes along the joint line were seen in 10 of 11 joints as a Kellgren-Lawrence (KL) grade of II to IV. Such signal changes were witnessed in only 4 of 13 joints with KL grade 0 or I. In the talocrural joint, bone alterations occurred in both tibia and talus bones through the joint line in cases of KL grade III or IV, while focal bone alterations were present in the talus only in KL grade I or II cases. Sixteen of 24 joints exhibited intraosseous bone signal changes, which tended to correspond to joint pain of any ankle OA stage. Our results suggest that bone alterations around the ankle joint might be one of the etiologies of OA and associated with ankle joint pain. PMID:26776564

  18. The Physiology of Bone Pain. How Much Do We Really Know?

    PubMed Central

    Nencini, Sara; Ivanusic, Jason J.

    2016-01-01

    Pain is associated with most bony pathologies. Clinical and experimental observations suggest that bone pain can be derived from noxious stimulation of the periosteum or bone marrow. Sensory neurons are known to innervate the periosteum and marrow cavity, and most of these have a morphology and molecular phenotype consistent with a role in nociception. However, little is known about the physiology of these neurons, and therefore information about mechanisms that generate and maintain bone pain is lacking. The periosteum has received greater attention relative to the bone marrow, reflecting the easier access of the periosteum for experimental assessment. With the electrophysiological preparations used, investigators have been able to record from single periosteal units in isolation, and there is a lot of information available about how they respond to different stimuli, including those that are noxious. In contrast, preparations used to study sensory neurons that innervate the bone marrow have been limited to recording multi-unit activity in whole nerves, and whilst they clearly report responses to noxious stimulation, it is not possible to define responses for single sensory neurons that innervate the bone marrow. There is only limited evidence that peripheral sensory neurons that innervate bone can be sensitized or that they can be activated by multiple stimulus types, and at present this only exists in part for periosteal units. In the central nervous system, it is clear that spinal dorsal horn neurons can be activated by noxious stimuli applied to bone. Some can be sensitized under pathological conditions and may contribute in part to secondary or referred pain associated with bony pathology. Activity related to stimulation of sensory nerves that innervate bone has also been reported in neurons of the spinoparabrachial pathway and the somatosensory cortices, both known for roles in coding information about pain. Whilst these provide some clues as to the way

  19. The child with bone pain: malignancies and mimickers

    PubMed Central

    2009-01-01

    Abstract Bone pain in children is common. The cause may be as benign as growing pains or as life-threatening as a malignancy. When a cause cannot be established by laboratory tests, physical examination or patient history, imaging of the affected body part is often obtained. Distinguishing benign from malignant processes involving the bones of children, based on imaging findings, can be challenging. The most common benign conditions that mimic pediatric bone tumors on imaging are Langerhan's cell histiocytosis and osteomyelitis. In this review, the current literature regarding the pathology and imaging of these conditions is reviewed. Benign conditions are compared with the most common pediatric bone tumors, Ewing sarcoma and osteosarcoma, with an emphasis on clinical and imaging features that may aid in diagnosis. PMID:19965301

  20. Painful scoliosis due to superposed giant cell bone tumor and aneurysmal bone cyst in a child.

    PubMed

    Togral, Guray; Arikan, Murat; Hasturk, Askin E; Gungor, Safak

    2014-07-01

    Giant cell bone tumors are the most common precursor lesions of aneurysmal bone cysts (ABCs) developing secondarily. In giant cell bone tumors containing an explicit ABC component, the observation of the solid component of the giant cell bone tumor plays a critical role in the separation of the primary ABC. In general, ABC cases together with giant cell tumors in the bone are diagnosed histopathologically. The combination of giant cell bone tumor with superposed ABC and that of painful scoliosis with backache is rarely seen in children. In this case study, we discussed the diagnosis and the treatment of a giant cell tumor and superposed an ABC present in the fifth lumbar spine in a pediatric patient admitted to our clinic with a complaint of acute scoliotic back pain.

  1. Re-evaluation of bone pain in patients with type 1 Gaucher disease suggests that bone crises occur in small bones as well as long bones.

    PubMed

    Baris, Hagit N; Weisz Hubshman, Monika; Bar-Sever, Zvi; Kornreich, Liora; Shkalim Zemer, Vered; Cohen, Ian J

    2016-09-01

    Bone crises in type 1 Gaucher disease are reported in long bones and occasionally in weight bearing bones and other bones, but rarely in small bones of the hands and feet. We retrospectively examined the incidence of bone pain in patients followed at the Rabin Medical Center, Israel, before and following the initiation of enzyme replacement therapy (ERT) and evaluated them for bone crises. Of 100 type I Gaucher disease patients, 30 (30%) experienced one or more bone crises. Small bone crises represented 31.5% of all bone crises and were always preceded by crises in other bones. While the incidence of long bone crises reduced after the initiation of ERT, small bone crises increased. Almost 60% of patients with bone crises were of the N370S/84GG genotype suggesting a greater susceptibility of N370S/84GG patients to severe bone complications. These patients also underwent the greatest number of splenectomies (70.6% of splenectomised patients). Splenectomised patients showed a trend towards increased long and small bone crises after surgery. Active investigation of acute pain in the hands and feet in patients in our cohort has revealed a high incidence of small bone crises. Physicians should consider imaging studies to investigate unexplained pain in these areas. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Patient-reported outcome instruments used to assess pain and functioning in studies of bisphosphonate treatment for bone metastases.

    PubMed

    Matza, Louis S; Fallowfield, Lesley J; Chung, Karen C; Currie, Brooke M; Van Brunt, Kate; Patrick, Donald L

    2012-04-01

    When treating metastatic bone disease, relief of bone pain is often a key outcome. Because pain cannot be quantified with objective clinical measures, patient-reported outcome (PRO) measures are required to assess patients' subjective experience. The goal of the current review was to examine measures used to assess pain, as well as the impact of pain on functional status and health-related quality of life (HRQL), in trials of bisphosphonates for the treatment of bone metastases. A literature search focused on articles published from January 1999 to April 2009. A total of 49 articles were located that used PROs to assess pain-related outcomes of bisphosphonate treatment for bone metastases. The Brief Pain Inventory was the most commonly used multi-item instrument. However, the most common approach for assessing pain was to administer a single-item scale such as a visual analog scale, numerical rating scale, or verbal rating scale. Of the 49 studies, 19 included a PRO assessing functional status or HRQL. Although pain is an important outcome of trials examining treatment for bone metastases, the current review suggests that there is little consistency in PRO measurement across studies. Furthermore, presentation of measures often lacked clear description, information on measurement properties, citations, clarity regarding method of administration, and consistent instrument names. Recommendations are provided for instrument validation within the target population, assessment of content validity, use of PRO instruments recently developed for patients with bone metastases, clear description of instruments, and implementation of measures consistent with recommendations from instrument developers.

  3. Determining the Incidence of Pain Flare Following Palliative Radiotherapy for Symptomatic Bone Metastases: Results From Three Canadian Cancer Centers

    SciTech Connect

    Hird, Amanda; Chow, Edward Zhang Liying; Wong, Rebecca; Wu, Jackson; Sinclair, Emily; Danjoux, Cyril; Tsao, May; Barnes, Elizabeth; Loblaw, Andrew

    2009-09-01

    Purpose: To determine the incidence of pain flare following radiotherapy (RT) for painful bone metastases. Materials and Methods: Patients with bone metastases treated with RT were eligible. Worst pain scores and analgesic consumption were collected before, daily during, and for 10 days after treatment. Pain flare was defined as a 2-point increase in the worst pain score (0-10) compared to baseline with no decrease in analgesic intake, or a 25% increase in analgesic intake with no decrease in worst pain score. Pain flare was distinguished from progression of pain by requiring the worst pain score and analgesic intake return to baseline levels after the increase/flare (within the 10-day follow-up period). Results: A total of 111 patients from three cancer centers were evaluable. There were 50 male and 61 female patients with a median age of 62 years (range, 40-89 years). The primary cancers were mainly breast, lung, and prostate. Most patients received a single 8 Gy (64%) or 20 Gy in five fractions (25%). The overall pain flare incidence was 44/111 (40%) during RT and within 10 days following the completion of RT. Patients treated with a single 8 Gy reported a pain flare incidence of 39% (27/70) and, with multiple fractions, 41% (17/41). Conclusion: More than one third of the enrolled patients experienced a pain flare. Identifying at-risk individuals and managing potential pain flares is crucial to achieve an optimal level of care.

  4. Hairy Cell Leukemia and Bone Pain.

    PubMed

    Streu, Erin

    2016-01-01

    Hairy cell leukemia is a relatively rare but distinct B-cell lympho-proliferative disorder of the blood, bone marrow, and spleen that accounts for only 2% of all adult leukemia cases. The median age at presentation is 50-55 years, with a 4:1 male to female predominance. Although considered uncommon, a number of unusual clinical presentations have been noted in the literature, including the presence of peripheral lymphadenopathy, lytic bone lesions, skin involvement, organ involvement, and central nervous system involvement. Unlike the clinical management of other hematologic malignancies, no current system is used to stage hairy cell leukemia.

  5. Bone pain as the presenting manifestation of secondary syphilis.

    PubMed

    Middleton, S; Rowntree, C; Rudge, S

    1990-08-01

    A 31 year old fireman presented with acute pain and tenderness in both shins and forearms. Radiographs were normal but bone scintigraphy showed widespread increased isotope uptake. Serology was consistent with a diagnosis of secondary syphilis, and the patient's symptoms resolved completely six weeks after a course of penicillin.

  6. Palliation of bone pain with Sn-117m(4+)DTPA

    SciTech Connect

    Atkins, L.F.; Mausner, L.F.; Meinken, G.E.

    1994-05-01

    Sn-117m(4+)DTPA prepared at Brookhaven National Laboratory has favorable physical and biological characteristics for use as a palliative agent to relieve pain from osseous metastases. The short range of the emitted conversion electrons permits large bone radiation doses without excessive radiation to the bone marrow. An accompanying 158.6 keV gamma is useful for monitoring the distribution. The T1/2 of 13.6 days provides an adequate shelf life. A previous study in humans has demonstrated favorable dosimetry with a bone surface dose of approximately 57.9 mGy/MBq and a bone surface to marrow ratio of 10:1. This study was instituted to find a dose level which was effective and to monitor effects on bone marrow. Sn-117m was administered to 14 patients. Administered activity ranged between 66 and 573 MBq or 1.2-5.8 MBq/kg body weight. At the lower dose levels (<3.1 MBq/kg, n=7), 1 obtained good relief of pain, 1 partial relief, and 1 no relief. The remaining 4 were not evaluated because of the need for further treatment of soft tissue disease or because of intervening death. The 7 patients treated at the higher dose level (4.8-5.8 MBq/kg) included patients with prostate (3), breast (3) and unknown (1) primary cancers. All patients experienced relief of pain, 5 excellent and 2 partial. No marrow suppression was observed as a result of Sn-117m therapy. Initial observations indicate that Sn-117m DTPA is effective in palliation of pain from osseous metastases without producing bone marrow suppression. Further studies at a higher dose level are planned.

  7. [Bone disease with Pain. Colles' fracture].

    PubMed

    Yajima, Hiroshi

    2008-11-01

    The distal radius is one of the most commonly fractured long bone. Colles' fracture results from a fall on the dorsiflexed and pronated hand. The dinner-fork deformity is the typical deformity of the Colles' fracture. For patients with no or a little displacement, conservative treatment is applied. The non-bridge type external fixator is applied for patients without an intra articular fracture. For patients with a comminuted fracture, the locking plate (volar approach) is recommended. During the healing period, shoulder, elbow and finger exercise should be insisted.

  8. Painful patellofemoral instability secondary to peroperative patellar fracture during bone-patellar tendon-bone autograft harvesting for anterior cruciate ligament reconstruction.

    PubMed

    Vidal, C; Guingand, O; de Thomasson, E; Conso, C; Terracher, R; Balabaud, L; Mazel, C

    2012-10-01

    Reconstructive surgery of the anterior cruciate ligament (ACL) of the knee in young active patients is a routine procedure, but with certain risks that need to be taken into account. Peroperative patellar fracture after bone-patellar tendon-bone autograft harvesting is a rare complication, which can significantly impair the functional outcome of ACL single-bundle reconstruction. We report the case of a patient presenting with disabling patellofemoral syndrome 3 years after arthroscopic ACL reconstruction by bone-tendon-bone autograft, revealing unnoticed mal-union of a iatrogenic sagittal patellar fracture. Patellar osteotomy corrected this painful iatrogenic patellar instability. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  9. Efficacy of Magnetic Resonance-guided Focused Ultrasound Surgery for Bone Metastases Pain Palliation

    NASA Astrophysics Data System (ADS)

    Kawasaki, Motohiro; Nanba, Hirofumi; Kato, Tomonari; Tani, Toshikazu; Ushida, Takahiro

    2011-09-01

    Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is a novel treatment method that achieves non-invasive thermal ablation by focusing many ultrasound waves on a target tissue with real-time monitoring of the location and temperature of the target during the procedure. We investigated the palliative effect on pain and safety of MRgFUS in painful bone metastases. Six patients (mean age, 65.8 years) who met eligibility criteria for the clinical study approved by our Institutional Ethics Committee based on the cooperative protocol were treated with MRgFUS. Targeted sites included the sacrum (n = 1), ilium (n = 2), scapula (n = 2), and femur (n = 1). The mean follow-up period was 9.2 months. All procedures were performed as a single-session treatment using the treatment system that is integrated into the patient table of a magnetic resonance image (MRI) scanner. Endpoints were change in the intensity of pain due to bone metastases from before to after the treatment, as measured on a numerical rating scale, pain interference with daily activities as determined by the Brief pain inventory (BPI), change in images, and safety. Pain relief was obtained in all patients early after treatment, with a reduction in the mean pain score from 6.0±1.3 at baseline to 1.2±1.0 at the end of follow-up as well as in pain interference with daily activities. The mean time required for a single-session treatment was 83.7±37.0 min, with a mean number of sonications required of 13.3±3.7 and mean energy applied of 846.4±273.5 J. No significant growth of tumors was observed, nor were there treatment-related adverse events. These results suggest that MRgFUS has a non-invasive palliative effect on the localized pain in patients with bone metastasis. MRgFUS could become an option in treatment strategies for painful bone metastases in the future.

  10. Subchondral bone changes and the impacts on joint pain and articular cartilage degeneration in osteoarthritis.

    PubMed

    Yu, Degang; Xu, Jiawei; Liu, Fengxiang; Wang, Xiaoqing; Mao, Yuanqing; Zhu, Zhenan

    2016-01-01

    Subchondral bone has received increasing attention in both basic and clinical research on osteoarthritis (OA). Subchondral bone in OA presents abnormalities in structure, biochemical composition, biomechanics and cellular function. Overall, subchondral bone mainly shows bone resorption in early OA and bone formation in late OA. More and more evidence suggests that abnormalities in subchondral bone of OA promote joint pain generation and articular cartilage degeneration. Inhibition or amelioration of subchondral bone abnormalities can reduce joint pain and can delay cartilage degeneration; thus, subchondral bone-targeted treatment promises to be a new treatment approach for OA. The pathological changes and the role of subchondral bone in OA still require further investigation.

  11. Differences in electrophysiological properties of functionally identified nociceptive sensory neurons in an animal model of cancer-induced bone pain

    PubMed Central

    Zhu, Yong Fang; Ungard, Robert; Seidlitz, Eric; Zacal, Natalie; Huizinga, Jan; Henry, James L

    2016-01-01

    Background Bone cancer pain is often severe, yet little is known about mechanisms generating this type of chronic pain. While previous studies have identified functional alterations in peripheral sensory neurons that correlate with bone tumours, none has provided direct evidence correlating behavioural nociceptive responses with properties of sensory neurons in an intact bone cancer model. Results In a rat model of prostate cancer-induced bone pain, we confirmed tactile hypersensitivity using the von Frey test. Subsequently, we recorded intracellularly from dorsal root ganglion neurons in vivo in anesthetized animals. Neurons remained connected to their peripheral receptive terminals and were classified on the basis of action potential properties, responses to dorsal root stimulation, and to mechanical stimulation of the respective peripheral receptive fields. Neurons included C-, Aδ-, and Aβ-fibre nociceptors, identified by their expression of substance P. We suggest that bone tumour may induce phenotypic changes in peripheral nociceptors and that these could contribute to bone cancer pain. Conclusions This work represents a significant technical and conceptual advance in the study of peripheral nociceptor functions in the development of cancer-induced bone pain. This is the first study to report that changes in sensitivity and excitability of dorsal root ganglion primary afferents directly correspond to mechanical allodynia and hyperalgesia behaviours following prostate cancer cell injection into the femur of rats. Furthermore, our unique combination of techniques has allowed us to follow, in a single neuron, mechanical pain-related behaviours, electrophysiological changes in action potential properties, and dorsal root substance P expression. These data provide a more complete understanding of this unique pain state at the cellular level that may allow for future development of mechanism-based treatments for cancer-induced bone pain. PMID:27030711

  12. Effect of music therapy on pain behaviors in rats with bone cancer pain.

    PubMed

    Gao, Ji; Chen, Shaoqin; Lin, Suyong; Han, Hongjing

    2016-01-01

    To investigate the effects of music therapy on the pain behaviors and survival of rats with bone cancer pain and analyze the mediating mechanism of mitogen activated protein kinase (MAPK) signal transduction pathway. Male Wistar rats aged 5-8 weeks and weighing 160-200 g were collected. The rat models of colorectal cancer bone cancer pain was successfully established. Animals were divided into experimental and control group, each with 10 rats. The animals in the observation group were given Mozart K448 sonata, sound intensity of 60 db, played the sonata once every 1 hr in the daytime, stopped playing during the night, and this cycle was kept for 2 weeks. On the other hand, rats in the control group were kept under the same environment without music. Animals in the experimental group consumed more feed and gained significant weight in comparison to the control group. The tumor volume of the experimental group was significantly smaller than that of the control group (p<0.05). After 1-2 weeks of treatment, spontaneous foot withdrawal reflection caused by pain in the experimental group was significantly lower than that in the control group, heat pain threshold and free walking pain scoring in the experimental group were also significantly higher as compared with the control group (p<0.05). The expression of p38á and p38β in animals' spinal cord and dorsal root ganglion was significantly lower in the experimental group than in the control group (p< 0.05). Music therapy may improve the pain behaviors in rats with bone cancer pain, which might be related with low expression of p38á and p38β in the MAPK signal transduction pathway.

  13. Intrathecal substance-p saporin in the dog: Efficacy in bone cancer pain

    PubMed Central

    Brown, Dorothy Cimino; Agnello, Kimberly

    2013-01-01

    Background Substance-p saporin (SP-SAP), a chemical conjugate of substance-p and a recombinant version of the ribosome-inactivating protein, saporin, when administered intrathecally, acts as a targeted neurotoxin producing selective destruction of superficial neurokinin 1 receptor bearing cells in the spinal dorsal horn. The goal of this project was to provide proof of concept data, that a single intrathecal injection of SP-SAP could safely provide effective pain relief in spontaneous bone cancer pain in companion (pet) dogs. Methods In a single blind, controlled study, 70 companion dogs with bone cancer pain were randomized to standard of care analgesic therapy alone (control, n=35) or intrathecal SP-SAP (20-60μg) in addition to standard of care analgesic therapy (n=35). Activity, pain scores, and videography data was collected at baseline, 2 weeks post randomization, and then monthly until death. Results While the efficacy results at the 2-week post randomization point were equivocal, the outcomes evaluated beyond two weeks revealed a positive effect of SP-SAP on chronic pain management. Significantly more dogs in the control group (74%) required unblinding and adjustment in analgesic protocol or euthanasia within 6 weeks of randomization, than dogs that were treated with SP-SAP (24%; p<0.001); and overall, dogs in the control group required unblinding significantly sooner than dogs that had been treated with SP-SAP (p<0.01). Conclusions Intrathecal SP-SAP administration in dogs with bone cancer produces a time dependent anti-nociceptive effect with no evidence of development of deafferentation pain syndrome that can be seen with neurolytic therapies. PMID:24195949

  14. Functional adaptation to loading of a single bone is neuronally regulated and involves multiple bones.

    PubMed

    Sample, Susannah J; Behan, Mary; Smith, Lesley; Oldenhoff, William E; Markel, Mark D; Kalscheur, Vicki L; Hao, Zhengling; Miletic, Vjekoslav; Muir, Peter

    2008-09-01

    Regulation of load-induced bone formation is considered a local phenomenon controlled by osteocytes, although it has also been hypothesized that functional adaptation may be neuronally regulated. The aim of this study was to examine bone formation in multiple bones, in response to loading of a single bone, and to determine whether adaptation may be neuronally regulated. Load-induced responses in the left and right ulnas and humeri were determined after loading of the right ulna in male Sprague-Dawley rats (69 +/- 16 days of age). After a single period of loading at -760-, -2000-, or -3750-microepsilon initial peak strain, rats were given calcein to label new bone formation. Bone formation and bone neuropeptide concentrations were determined at 10 days. In one group, temporary neuronal blocking was achieved by perineural anesthesia of the brachial plexus with bupivicaine during loading. We found right ulna loading induces adaptive responses in other bones in both thoracic limbs compared with Sham controls and that neuronal blocking during loading abrogated bone formation in the loaded ulna and other thoracic limb bones. Skeletal adaptation was more evident in distal long bones compared with proximal long bones. We also found that the single period of loading modulated bone neuropeptide concentrations persistently for 10 days. We conclude that functional adaptation to loading of a single bone in young rapidly growing rats is neuronally regulated and involves multiple bones. Persistent changes in bone neuropeptide concentrations after a single loading period suggest that plasticity exists in the innervation of bone.

  15. Radionuclide bone scanning in females with chronic low back pain.

    PubMed Central

    Rothwell, R S; Davis, P; Lentle, B C

    1981-01-01

    Sixty female patients with chronic low back pain have been studied clinically, radiographically, and by radionuclide bone scanning for evidence of sacroiliac disease. Twenty-four patients had quantitative sacroiliac scintigraphy (QSS) results suggesting sacroiliitis. In only one of these patients was the radiograph abnormal. Clinical and laboratory examinations failed to reveal any possible associated aetiological factors. Six-month follow-up of 18 patients showed that subjective improvement of pain is associated with a return to normal of QSS results, often secondary to anti-inflammatory medication. It is concluded that sacroiliac disease may be a common cause for chronic low back pain in women and that its presence may be missed if radiographs are relied upon to confirm the diagnosis. Its aetiology remains obscure. PMID:6451204

  16. Contribution of acidic extracellular microenvironment of cancer-colonized bone to bone pain.

    PubMed

    Yoneda, Toshiyuki; Hiasa, Masahiro; Nagata, Yuki; Okui, Tatsuo; White, Fletcher

    2015-10-01

    Solid and hematologic cancer colonized bone produces a number of pathologies. One of the most common complications is bone pain. Cancer-associated bone pain (CABP) is a major cause of increased morbidity and diminishes the quality of life and affects survival. Current treatments do not satisfactorily control CABP and can elicit adverse effects. Thus, new therapeutic interventions are needed to manage CABP. However, the mechanisms responsible for CABP are poorly understood. The observation that specific osteoclast inhibitors can reduce CABP in patients indicates a critical role of osteoclasts in the pathophysiology of CABP. Osteoclasts create an acidic extracellular microenvironment by secretion of protons via vacuolar proton pumps during bone resorption. In addition, bone-colonized cancer cells also release protons and lactate via plasma membrane pH regulators to avoid intracellular acidification resulting from increased aerobic glycolysis known as the Warburg effect. Since acidosis is algogenic for sensory neurons and bone is densely innervated by sensory neurons that express acid-sensing nociceptors, the acidic bone microenvironments can evoke CABP. Understanding of the mechanism by which the acidic extracellular microenvironment is created in cancer-colonized bone and the expression and function of the acid-sensing nociceptors are regulated should facilitate the development of novel approaches for management of CABP. Here, the contribution of the acidic microenvironment created in cancer-colonized bone to elicitation of CABP and potential therapeutic implications of blocking the development and recognition of acidic microenvironment will be described. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers.

  17. Painful spondylolysis or spondylolisthesis studied by radiography and single-photon emission computed tomography

    SciTech Connect

    Collier, B.D.; Johnson, R.P.; Carrera, G.F.; Meyer, G.A.; Schwab, J.P.; Flatley, T.J.; Isitman, A.T.; Hellman, R.S.; Zielonka, J.S.; Knobel, J.

    1985-01-01

    Planar bone scintigraphy (PBS) and single-photon emission computed tomography (SPECT) were compared in 19 adults with radiographic evidence of spondylolysis and/or spondylolisthesis. SPECT was more sensitive than PBS when used to identify symptomatic patients and sites of painful defects in the pars interarticularis. In addition, SPECT allowed more accurate localization than PBS. In 6 patients, spondylolysis or spondylolisthesis was unrealted to low back pain, and SPECT images of the posterior neural arch were normal. The authors conclude that when spondylolysis or spondylolisthesis is the cause of low back pain, pars defects are frequently heralded by increased scintigraphic activity which is best detected and localized by SPECT.

  18. Post-operative breast cancer patients diagnosed with skeletal metastasis without bone pain had fewer skeletal-related events and deaths than those with bone pain

    PubMed Central

    2010-01-01

    Background Skeletal metastases are often accompanied by bone pain. To investigate the clinical meaning of bone pain associated with skeletal metastasis in breast cancer patients after surgery, we explored whether the presence of bone pain was due to skeletal-related events (SREs) or survival (cause specific death, CSD), retrospectively. Methods Consecutive breast cancer patients undergoing surgery between 1988 and 1998 were examined for signs of skeletal metastasis until December 2006. Patients who were diagnosed as having skeletal metastasis were the subjects of this study. Bone scans were performed annually for 5, 7 or 10 years; they were also conducted if skeletal metastasis was suspected. Data concerning bone pain and tumor markers at the time of skeletal metastasis diagnosis, and data relating to various factors including tumors, lymph nodes and hormone receptors at the time of surgery, were investigated. The relationships between factors such as bone pain, SRE and CSD were analyzed using the Kaplan-Meier method and Cox's analysis. Results Skeletal metastasis occurred in 668 patients but the pain status of two patients was unknown, therefore 666 patients were included in the study. At the time of skeletal metastasis diagnosis 270 patients complained of pain; however, 396 patients did not. Analysis of data using Cox's and Kaplan-Meier methods demonstrated that patients without pain had fewer SREs and better survival rates than those with pain. Hazard ratios regarding SRE (base = patients without pain) were 2.331 in univariate analysis and 2.243 in multivariate analysis. Hazard ratios regarding CSD (base = patients without pain) were 1.441 in univariate analysis and 1.535 in multivariate analysis. Similar results were obtained when analyses were carried out using the date of surgery as the starting point. Conclusion Bone pain at diagnosis of skeletal metastasis was an indicator of increased SRE and CSD. However, these data did not support recommendations of

  19. Risk factors for bone pain among patients with cancer receiving myelosuppressive chemotherapy and pegfilgrastim.

    PubMed

    Xu, H; Gong, Q; Vogl, F D; Reiner, M; Page, J H

    2016-02-01

    The purpose of this study was to evaluate risk factors for bone pain in patients receiving myelosuppressive chemotherapy and pegfilgrastim. Individual patient data from 22 pegfilgrastim clinical trials were analyzed. Multivariable logistic regression models were used to evaluate risk factors associated with grade ≥2 bone pain and any grade bone pain in the first chemotherapy cycle and across cycles 1-6. Of the 1949 patients analyzed, 19 and 36 % had grade ≥2 and any grade bone pain, respectively, in cycle 1, and 28 and 51 % had grade ≥2 and any grade bone pain, respectively, across cycles 1-6. In cycle 1, history of bone pain (odds ratio (OR), 1.51; 95 % confidence interval (CI), 1.09-2.07) was associated with increased risk of grade ≥2 bone pain; age ≥65 years (versus <45 years; OR, 0.64; 95 % CI, 0.42-0.98), the European Union region (versus the USA region; OR, 0.32; 95 % CI, 0.20-0.52), colorectal cancer (versus breast cancer; OR, 0.14; 95 % CI, 0.05-0.41), and small-cell lung cancer (OR, 0.34; 95 % CI, 0.12-0.98) were associated with reduced risk of grade ≥2 bone pain. Potential risk factors for bone pain in patients receiving myelosuppressive chemotherapy and primary prophylactic pegfilgrastim identified in this study are younger age and history of bone pain. No other association with clinical factors and risk of bone pain was detected. Better understanding of risk factors for bone pain would be useful in identifying patients who may benefit from pain prevention strategies.

  20. Do Laying Hens with Keel Bone Fractures Experience Pain?

    PubMed Central

    Nasr, Mohammed A. F.; Nicol, Christine J.; Murrell, Joanna C.

    2012-01-01

    The European ban on battery cages has forced a change towards the use of non-cage or furnished cage systems, but unexpectedly this has been associated with an increased prevalence of keel bone fractures in laying hens. Bone fractures are acutely painful in mammals, but the effect of fractures on bird welfare is unclear. We recently reported that keel bone fractures have an effect on bird mobility. One possible explanation for this is that flying becomes mechanically impaired. However it is also possible that if birds have a capacity to feel pain, then ongoing pain resulting from the fracture could contribute to decreased mobility. The aim was to provide proof of concept that administration of appropriate analgesic drugs improves mobility in birds with keel fracture; thereby contributing to the debate about the capacity of birds to experience pain and whether fractures are associated with pain in laying hens. In hens with keel fractures, butorphanol decreased the latency to land from perches compared with latencies recorded for these hens following saline (mean (SEM) landing time (seconds) birds with keel fractures treated with butorphanol and saline from the 50, 100 and 150 cm perch heights respectively 1.7 (0.3), 2.2 (0.3), p = 0.05, 50 cm; 12.5 (6.6), 16.9 (6.7), p = 0.03, 100 cm; 20.6 (7.4), 26.3 (7.6), p = 0.02 150 cm). Mobility indices were largely unchanged in birds without keel fractures following butorphanol. Critically, butorphanol can be considered analgesic in our study because it improved the ability of birds to perform a complex behaviour that requires both motivation and higher cognitive processing. This is the first study to provide a solid evidential base that birds with keel fractures experience pain, a finding that has significant implications for the welfare of laying hens that are housed in non-cage or furnished caged systems. PMID:22927930

  1. A Simple and Effective Daily Pain Management Method for Patients Receiving Radiation Therapy for Painful Bone Metastases

    SciTech Connect

    Andrade, Regiane S.; Proctor, Julian W.; Slack, Robert; Marlowe, Ursula; Ashby, Karlotta R.; Schenken, Larry L.

    2010-11-01

    Purpose: The incidence of painful bone metastases increases with longer survival times. Although external beam radiation therapy (EBRT) is an effective palliative treatment, it often requires several days from the start of treatment to produce a measurable reduction in pain scores and a qualitative amelioration of patient pain levels. Meanwhile, the use of analgesics remains the best approach early on in the treatment course. We investigated the role of radiation therapists as key personnel for collecting daily pain scores to supplement assessments by physician and oncology nursing staff and manage pain more effectively during radiation treatment. Methods and Materials: Daily pain scores were obtained by the radiation therapists for 89 patients undertaking a total of 124 courses of EBRT for bone metastases and compared with pretreatment pain scores. The majority of patients (71%) were treated to 30 Gy (range, 20-37.5) in 10 fractions (range, 8-15 fractions). Results: One hundred nineteen treatment courses (96%) were completed. Pain scores declined rapidly to 37.5%, 50%, and 75% of the pretreatment levels by Days 2, 4, and 10, respectively. Pain was improved in 91% of patients with only 4% of worse pain at the end of treatment. Improved pain scores were maintained in 83% of patients at 1-month follow-up, but in 35% of them, the pain was worse than at the end of treatment. Conclusions: Collection of daily pain scores by radiation therapists was associated with an effective reduction in pain scores early on during EBRT of painful osseous metastases.

  2. Preoperative radiofrequency ablation in painful osteolytic long bone metastases.

    PubMed

    Di Francesco, Alexander; Flamini, Stefano; Zugaro, Luigi; Zoccali, Carmine

    2012-08-01

    This study aimed to determine whether Radiofrequency Ablation (RFA) followed by prophylactic internal fixation produces better palliation in terms of pain and reduces the need for blood transfusion more than radiotherapy and surgical stabilization (RT-SS). Patients with solitary long bone metastases and a pain score of 5 or more on the VAS scale were selected. Fifteen patients were treated with RFA and surgical stabilization (RFA-SS) and were compared with a matched group (15 subjects) treated by radiotherapy and surgical stabilization (RT-SS). A complete response in terms of pain relief at 12 weeks was documented in 20% (3/15) and 533% (8/15) of the subjects treated by RT-SS or RFA-SS, respectively (p = 0.027). The overall response rate at 12 weeks was 93.3% (14 patients) in the group treated by RFA-SS and 59.9% (9 patients) in the group treated by RT-SS (p = 0.048). Although recurrent pain was documented more frequently after RT-SS (26.6%) than after RFA-SS (6.7%) the difference did not reach statistical significance. The morbidity related to RT-SS did not significantly differ when the treatment was associated with RFA. We observed a reduction in blood transfusion, as 3 patients in the RT-SS group required a blood transfusion, versus none in the RFA-SS group. Our results suggest that RFA-SS is safe and is more effective than RT-SS; furthermore, RFA may become an option for patients with metastases of the long bones to prevent tumour dissemination and reduce intraoperative blood loss. The findings described here should serve as a framework around which to design future clinical trials.

  3. Radiopharmaceuticals for Palliation of Bone Pain in Patients with Castration-resistant Prostate Cancer Metastatic to Bone: A Systematic Review.

    PubMed

    Jong, Joyce M van Dodewaard-de; Oprea-Lager, Daniela E; Hooft, Lotty; de Klerk, John M H; Bloemendal, Haiko J; Verheul, Henk M W; Hoekstra, Otto S; van den Eertwegh, Alfons J M

    2016-09-01

    The majority of patients with castration-resistant prostate cancer develop bone metastatic disease. It is often challenging to optimally palliate malignant bone pain. In case of multifocal pain due to diffuse osteoblastic metastases, treatment with bone-seeking radiopharmaceuticals can be considered. This systematic review evaluates the efficacy of different bone-seeking radiopharmaceuticals for palliation of malignant bone pain from prostate cancer. The PubMed (Medline) and Embase databases were searched for publications on 89-strontium-chloride ((89)Sr), 153-samarium-EDTMP ((153)Sm), 186-rhenium-HEDP ((186)Re), 188-rhenium-HEDP ((188)Re), and 223-radium-chloride ((223)Ra). Randomised controlled trials and prospective cohort studies were included. Metastatic bone pain had to be registered as outcome measure for prostate cancer patients separately. This review included 36 articles of which 13 randomised trials and 23 prospective studies. Of all trials, 10 studies used (89)Sr, 7 (153)Sm, 12 (186)Re, 2 (188)Re, and 2 (223)Ra; three reported on a combination of different radionuclides. Only a few trials contained a blinding procedure and several studies contained incomplete follow-up or lack of intention-to-treat analysis. It was not possible to calculate a pooled estimate of pain response to treatment with any of the radionuclides because different definitions of pain response were used. Overall, pain response percentages greater than 50-60% were seen with each radionuclide. Haematological toxicity was reported in 26 of the 36 studies and more than half of these trials stated no grade 3/4 leukopenia or thrombocytopenia occurred. In this report we reviewed the efficacy of bone-seeking radionuclides for treating bone pain from metastatic prostate cancer. Overall, treatment with bone-seeking radionuclides resulted in pain responses greater than 50-60%. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  4. Patients with patellofemoral pain exhibit elevated bone metabolic activity at the patellofemoral joint

    PubMed Central

    Draper, Christine E.; Fredericson, Michael; Gold, Garry E.; Besier, Thor F.; Delp, Scott L.; Beaupre, Gary S.; Quon, Andrew

    2011-01-01

    Summary Patellofemoral pain is characterized by pain behind the kneecap and is often thought to be due to high stress at the patellofemoral joint. While we cannot measure bone stress in vivo, we can visualize bone metabolic activity using 18F NaF PET/CT, which may be related to bone stress. Our goals were to use 18F NaF PET/CT to evaluate whether subjects with patellofemoral pan exhibit elevated bone metabolic activity and to determine whether bone metabolic activity correlates with pain intensity. We examined 20 subjects diagnosed with patellofemoral pain. All subjects received an 18F NaF PET/CT scan of their knees. Uptake of 18F NaF in the patella and trochlea was quantified by computing the standardized uptake value and normalizing by the background tracer uptake in bone. We detected increased tracer uptake in 85% of the painful knees examined. We found that the painful knees exhibited increased tracer uptake compared to the pain-free knees of four subjects with unilateral pain (p=0.0006). We also found a correlation between increasing tracer uptake and increasing pain intensity (r2 = 0.55; p = 0.0005). The implication of these results is that patellofemoral pain may be related to bone metabolic activity at the patellofemoral joint. PMID:21812024

  5. Analgesic effects of loperamide in bone cancer pain in mice.

    PubMed

    Menéndez, Luis; Lastra, Ana; Meana, Alvaro; Hidalgo, Agustín; Baamonde, Ana

    2005-05-01

    The intratibial inoculation of NCTC 2472 cells induces an osteosarcoma in C3H/HeJ mice. These mice show thermal hyperalgesic responses which may be blocked by the local administration of opiates over the tibial tumoral mass (Menéndez L, Lastra A, Hidalgo A, Meana A, Garcia E, Baamonde A. Peripheral opioids act as analgesics in bone cancer pain in mice. NeuroReport 2003b; 14:867-9). The aim of this report was to characterize the analgesic responses obtained by activating peripheral opioid receptors in bone cancer pain. Here, we initially describe that this osteosarcoma induces mechanical as well as thermal hyperalgesia. Loperamide, an opioid agonist unable to cross the blood-brain barrier, inhibits both thermal and mechanical hyperalgesia when s.c. injected, locally over the tibial tumoral mass (7.5-75 microg) or distantly, under the fur of the neck (4 mg/kg). These analgesic effects seem peripherally mediated since they are reverted by the administration of naloxone methiodide (10 mg/kg) and because the withdrawal latencies of the contralateral, non-affected, paws remain unaltered. Furthermore, only cyprodime (1 mg/kg) but not naltrindole (0.1 mg/kg) or nor-binaltorphimine (10 mg/kg) blocked these effects, showing the involvement of gamma-opioid receptors in the peripheral analgesia induced by loperamide on thermal and mechanical hyperalgesia. The advantages of using peripheral acting opiates -- devoid of central colateral effects -- for the treatment of cancer related pain are suggested.

  6. [Bone mineral density in children. Association with musculoskeletal pain and/or joint hypermobility].

    PubMed

    Roberto, Adriana Madureira; Terreri, Maria Teresa R A; Szejnfeld, Vera; Hilário, Maria Odete E

    2002-01-01

    Joint hypermobility can be associated with benign musculoskeletal pain. The relation between hypermobility and low bone mineral density is still unknown. Osteoporosis can be observed in some genetic syndromes associated with joint hypermobility. The aim of our study was to detect the possible relation between joint hypermobility, benign musculoskeletal pain and bone mineral density in children. Ninety-three children from 5 to 10 years of age were evaluated concerning the presence of joint hypermobility and the presence of musculoskeletal pain based on a questionnaire directed to parents. We also performed densitometry to measure bone mineral density. All children underwent an L2-L4 lumbar bone densitometry. Children were distributed into four groups according to the presence or not of joint hypermobility associated or not with musculoskeletal pain: 29 (31.2%) with hypermobility and pain, 20 (21.5%) with hypermobility and without pain, 22 (23.6%) without hypermobility and with pain and 22 (23.6%) without hypermobility and without pain (control group). Twenty-four children (25.8%) presented reduction in bone mineral density over 10% related to the adequate bone mineral density for age and gender. Bone mineral density was significantly lower in relation to the controls in the following groups: with hypermobility (independently of the presence of pain), with pain (independently of the presence of hypermobility), with hypermobility and without pain and without hypermobility and with pain. Bone mineral density may be lower in children with joint hypermobility (independently of musculoskeletal pain) and in children with pain (independently of hypermobility) when compared to controls.

  7. Acute abdominal pain following fracture of a heterotopically formed bone incorporating a prolene mesh.

    PubMed

    Nageswaran, H; Dunkley, A

    2010-09-01

    A case is presented of severe abdominal pain around a healed scar following fracture of a heterotopically formed bone. This should be considered an unusual differential diagnosis in patients with acute pain of unknown origin who had open abdominal surgery in the past. To our knowledge, we have also reported the first case of hetertopic bone formation incorporating a prolene mesh.

  8. Urinary cytokines/chemokines after magnetic resonance-guided high intensity focused ultrasound for palliative treatment of painful bone metastases.

    PubMed

    Bushehri, Ahmad; Czarnota, Gregory; Zhang, Liying; Hynynen, Kullervo; Huang, Yuexi; Chan, Michael; Chu, William; Dennis, Kristopher; Mougenot, Charles; Coccagna, Jennifer; Sahgal, Arjun; Chow, Edward; DeAngelis, Carlo

    2017-01-01

    Pain is experienced by 50-75% of patients with bone metastases, representing a major source of morbidity amongst cancer patients. Magnetic resonance-guided high intensity focused ultrasound (MRgHIFU) is a new, non-invasive, outpatient treatment modality for painful bone metastases. The aim of this study was to analyze urinary cytokines/chemokines pattern after MRgHIFU for palliative treatment of painful bone metastases. The findings were compared to the cytokines/chemokines pattern post single 8 Gy fraction radiation from our previous study. Urine samples were collected from patients with painful bone metastases 3 days before and 2 days after treatment with MRgHIFU. Each urine sample was tested for pro-inflammatory cytokines and anti-inflammatory cytokines. Patients received teaching on how to collect urine samples on their own. The Millipore Milliplex 42-Plex Cytokine/Chemokine Kit™ was used to measure urinary levels of a panel of cytokines/chemokines. Ten patients were enrolled for the study. The following 15 cytokines were above the level of detection (LOD) in at least 50% of patients at both pre MRgHIFU and post MRgHIFU: EGF, eotaxin, Fit-3 ligand, fractalkine, G-CSF, GRO, IFNα2, IL-1ra, IL-8, IP-10, MCP-1, PDGF-AA, RANTES, sIL-2Rα, and VEGF. Nine urinary cytokines significantly decreased post MRgHIFU, namely, eotaxin, GRO, IL-8, IL-13, IP-10, MCP-1, MIP-1β, RANTES, and sIL-2Rα. In addition, there were significant differences between post MRgHIFU and post-8 Gy fraction radiation in most urinary cytokines. Nine urinary cytokines significantly reduced post-MRgHIFU in patients with painful bone metastases. The significance of cytokines/chemokines pattern for palliative treatment of painful bone metastases is still unknown.

  9. Pain, PSA flare, and bone scan response in a patient with metastatic castration-resistant prostate cancer treated with radium-223, a case report.

    PubMed

    McNamara, Megan A; George, Daniel J

    2015-05-07

    Radium-223 has been shown to improve overall survival in men with metastatic castration-resistant prostate cancer with symptomatic bone metastases. The bone scan response to radium-223 has only been described in one single center trial of 14 patients, none of whom achieved the outstanding bone scan response presented in the current case. In this case report, we describe a 75 year-old white man with extensively pre-treated metastatic castration-resistant prostate cancer and symptomatic bone metastases who experienced a flare in pain and prostate-specific antigen, followed by dramatic clinical (pain), biochemical (prostate-specific antigen), and imaging (bone scan) response. The flare phenomena and bone scan response we observed have not previously been described with radium-223. This case suggests that the degree and duration of bone scan response may be predictive of overall survival benefit.

  10. Pegfilgrastim-Induced Bone Pain: A Review on Incidence, Risk Factors, and Evidence-Based Management.

    PubMed

    Moore, Donald C; Pellegrino, Annie E

    2017-09-01

    To review the incidence, risk factors, and management of pegfilgrastim-induced bone pain (PIBP). PubMed was searched from 1980 to March 31, 2017, using the terms pegfilgrastim and bone pain. English-language, human studies and reviews assessing the incidence, risk factors, and management of PIBP were incorporated. A total of 3 randomized, prospective studies and 2 retrospective studies evaluated pharmacological management of PIBP. Naproxen compared with placebo demonstrated a reduction in the degree, incidence, and duration of bone pain secondary to pegfilgrastim. Loratadine was not effective in reducing the incidence of bone pain prophylactically, but a retrospective study evaluating dual antihistamine blockade with loratadine and famotidine demonstrated a decreased incidence in bone pain when administered before pegfilgrastim. Naproxen is effective at managing PIBP. Although commonly used, antihistamines have a paucity of data supporting their use. Dose reductions of pegfilgrastim and opioids may also be potential management options; however, data supporting these treatment modalities are scarce.

  11. [Role of bone-density-conserving agents in the treatment for pain in patients with bone metastases].

    PubMed

    Zhabina, A S; Semiglazova, T Yu

    2015-01-01

    Bones are the fourth area of metastases of malignant tumors that significantly burden the disease reducing the quality of life of a patient as cause pain, threat pathological fracture, deteriorate limb function, and develop hypercalcemia. Treatment of patients should be comprehensive and base on the rational use of systemic therapy and local impacts. The use of bisphosphonates inhibits bone resorption and progression of bone metastases, reduces the risk of complications due to metastatic bone disease including pain. Bisphosphonates significantly reduce the incidence of SRE in patients with bone metastases, diminish the need for analgesic radiotherapy, postpone terms of SRE occurrence, reduce pain syndrome as well as the need for analgetics. They also easily tolerated by patients.

  12. Targeting G-Protein Signaling for the Therapeutics of Prostate Tumor Bone Metastases and the Associated Chronic Bone Pain

    DTIC Science & Technology

    2013-07-01

    results in increased activity/expression of key pain-sensing receptor channels, such as TRPV1 , such that the channels are constitutively activated...Keywords: Prostate Cancer Bone Metastasis, Bone Cancer Pain, Heterotrimeric G protein betagamma subunits, G protein coupled receptors (GPCRs), TRPV1 ...cell growth, migration and invasion in vitro, as well as mediating GPCR-regulated TRPV1 channel function in cultured mouse sensory neurons (Aim 1

  13. Targeting G-Protein Signaling for the Therapeutics of Prostate Tumor Bone Metastases and the Associated Chronic Bone Pain

    DTIC Science & Technology

    2015-09-01

    results in increased activity/expression of key pain-sensing receptor channels, such as TRPV1 , such that the channels are constitutively activated...Keywords: Prostate Cancer Bone Metastasis, Bone Cancer Pain, Heterotrimeric G protein betagamma subunits, G protein coupled receptors (GPCRs), TRPV1 ...vitro, as well as mediating GPCR-regulated TRPV1 channel function in cultured mouse sensory neurons (Aim 1) Major Goal/Objective 1: Determine the

  14. Extracellular signal-regulated kinase activation in spinal astrocytes and microglia contributes to cancer-induced bone pain in rats.

    PubMed

    Wang, X-W; Li, T-T; Zhao, J; Mao-Ying, Q-L; Zhang, H; Hu, S; Li, Q; Mi, W-L; Wu, G-C; Zhang, Y-Q; Wang, Y-Q

    2012-08-16

    Cancer pain, especially cancer-induced bone pain, affects the quality of life of cancer patients, and current treatments for this pain are limited. The present study demonstrates that spinal extracellular signal-regulated kinase (ERK) activation in glial cells plays a crucial role in cancer-induced bone pain. From day 4 to day 21 after the intra-tibia inoculation with Walker 256 mammary gland carcinoma cells, significant mechanical allodynia was observed as indicated by the decrease of mechanical withdrawal thresholds in the von Frey hair test. Intra-tibia inoculation with carcinoma cells induced a vast and persistent (>21 D) activation of ERK in the bilateral L2-L3 and L4-L5 spinal dorsal horn. The increased pERK1/2-immunoreactivity was observed in both Iba-1-expressing microglia and GFAP-expressing astrocytes but not in NeuN-expressing neurons. A single intrathecal injection of the selective MEK (ERK kinase) inhibitors PD98059 (10 μg) on day 12 and U0126 (1.25 and 3 μg) on day 14, attenuated the bilateral mechanical allodynia in the von Frey hair test. Altogether, our results suggest that ERK activation in spinal microglia and astrocytes is correlated with the onset of allodynia and is important for allodynia maintenance in the cancer pain model. This study indicated that inhibition of the ERK pathway may provide a new therapy for cancer-induced bone pain.

  15. Mechanisms of nerve growth factor signaling in bone nociceptors and in an animal model of inflammatory bone pain.

    PubMed

    Nencini, Sara; Ringuet, Mitchell; Kim, Dong-Hyun; Chen, Yu-Jen; Greenhill, Claire; Ivanusic, Jason J

    2017-01-01

    Sequestration of nerve growth factor has been used successfully in the management of pain in animal models of bone disease and in human osteoarthritis. However, the mechanisms of nerve growth factor-induced bone pain and its role in modulating inflammatory bone pain remain to be determined. In this study, we show that nerve growth factor receptors (TrkA and p75) and some other nerve growth factor-signaling molecules (TRPV1 and Nav1.8, but not Nav1.9) are expressed in substantial proportions of rat bone nociceptors. We demonstrate that nerve growth factor injected directly into rat tibia rapidly activates and sensitizes bone nociceptors and produces acute behavioral responses with a similar time course. The nerve growth factor-induced changes in the activity and sensitivity of bone nociceptors we report are dependent on signaling through the TrkA receptor, but are not affected by mast cell stabilization. We failed to show evidence for longer term changes in expression of TrkA, TRPV1, Nav1.8 or Nav1.9 in the soma of bone nociceptors in a rat model of inflammatory bone pain. Thus, retrograde transport of NGF/TrkA and increased expression of some of the common nerve growth factor signaling molecules do not appear to be important for the maintenance of inflammatory bone pain. The findings are relevant to understand the basis of nerve growth factor sequestration and other therapies directed at nerve growth factor signaling, in managing pain in bone disease.

  16. Dissociation between the relief of skeletal pain behaviors and skin hypersensitivity in a model of bone cancer pain.

    PubMed

    Guedon, Jean-Marc G; Longo, Geraldine; Majuta, Lisa A; Thomspon, Michelle L; Fealk, Michelle N; Mantyh, Patrick W

    2016-06-01

    Recent studies have suggested that in humans and animals with significant skeletal pain, changes in the mechanical hypersensitivity of the skin can be detected. However, whether measuring changes in skin hypersensitivity can be a reliable surrogate for measuring skeletal pain itself remains unclear. To explore this question, we generated skeletal pain by injecting and confining GFP-transfected NCTC 2472 osteosarcoma cells unilaterally to the femur of C3H male mice. Beginning at day 7 post-tumor injection, animals were administered vehicle, an antibody to the P2X3 receptor (anti-P2X3) or anti-NGF antibody. Pain and analgesic efficacy were then measured on days 21, 28, and 35 post-tumor injection using a battery of skeletal pain-related behaviors and von Frey assessment of mechanical hypersensitivity on the plantar surface of the hind paw. Animals with bone cancer pain treated with anti-P2X3 showed a reduction in skin hypersensitivity but no attenuation of skeletal pain behaviors, whereas animals with bone cancer pain treated with anti-NGF showed a reduction in both skin hypersensitivity and skeletal pain behaviors. These results suggest that although bone cancer can induce significant skeletal pain-related behaviors and hypersensitivity of the skin, relief of hypersensitivity of the skin is not always accompanied by attenuation of skeletal pain. Understanding the relationship between skeletal and skin pain may provide insight into how pain is processed and integrated and help define the preclinical measures of skeletal pain that are predictive end points for clinical trials.

  17. Dissociation between the relief of skeletal pain behaviors and skin hypersensitivity in a model of bone cancer pain

    PubMed Central

    Guedon, Jean-Marc G.; Longo, Geraldine; Majuta, Lisa A.; Thomspon, Michelle L.; Fealk, Michelle N.; Mantyh, Patrick W.

    2016-01-01

    Recent studies have suggested that in humans and animals with significant skeletal pain, changes in the mechanical hypersensitivity of the skin can be detected. However, whether measuring changes in skin hypersensitivity can be a reliable surrogate for measuring skeletal pain itself remains unclear. To explore this question we generated skeletal pain by injecting and confining GFP-transfected NCTC 2472 osteosarcoma cells unilaterally to the femur of C3H male mice. Beginning at day 7 post-tumor injection, animals were administered vehicle, an antibody to the P2X3 receptor (anti-P2X3) or anti-NGF antibody. Pain and analgesic efficacy was then measured on days 21, 28 and 35 post-tumor injection using a battery of skeletal pain-related behaviors and von Frey assessment of mechanical hypersensitivity on the plantar surface of the hindpaw. Animals with bone cancer pain treated with anti-P2X3 showed a reduction in skin hypersensitivity but no attenuation of skeletal pain behaviors. Whereas animals with bone cancer pain treated with anti-NGF showed a reduction in both skin hypersensitivity and skeletal pain behaviors. These results suggest that while bone cancer can induce significant skeletal pain-related behaviors and hypersensitivity of the skin, relief of hypersensitivity of the skin is not always accompanied by attenuation of skeletal pain. Understanding the relationship between skeletal and skin pain may provide insight into how pain is processed and integrated and help define the preclinical measures of skeletal pain that are predictive endpoints for clinical trials. PMID:27186713

  18. TC99m MDP bone scan in evaluation of painful scoliosis

    PubMed Central

    Nilegaonkar, Sujit; Sonar, Sameer; Ranade, Ashish; Khadilkar, Madhav

    2010-01-01

    A 18-year-old male presented with low back ache. The patient was investigated and was diagnosed to have painful scoliosis. X-ray and other examinations could not reveal any diagnosis. The patient was referred to undergo bone scan on clinical suspicion of osteoid osteoma and to rule out stress fracture if any. Planar bone scan was performed, which showed a lesion in L3 vertebra and was further evaluated with SPECT (Single photon emission computed tomography) study to characterize the lesion. On SPECT examination, the classical features of osteoid osteoma, the double density sign (11), was noted in the pars interarticularis region. These findings were confirmed by a CT scan, which showed a sclerotic lesion in pars interarticularis of L3 vertebra. The patient was posted for operation and was relieved of symptoms in the postoperative follow-up. PMID:21188068

  19. Intrathecal resiniferatoxin in a dog model: efficacy in bone cancer pain.

    PubMed

    Brown, Dorothy C; Agnello, Kimberly; Iadarola, Michael J

    2015-06-01

    Resiniferatoxin (RTX) is the most potent among all known endogenous and synthetic agonists for the transient receptor potential vanilloid 1 (TRPV1) receptor, which is a calcium-permeable nonselective cation channel, expressed on the peripheral and central terminals of small-diameter sensory neurons. Prolonged calcium influx induced by RTX causes cytotoxicity and death of only those sensory neurons that express the TRPV1 ion channel leading to selective targeting and permanent deletion of the TRPV1-expressing C-fiber neuronal cell bodies in the dorsal root ganglia. The goal of this project was to provide preclinical efficacy data, that intrathecal RTX could provide effective pain relief and improve function in dogs with bone cancer without significant long-term side effects. In a single-blind, controlled study, 72 companion dogs with bone cancer pain were randomized to standard of care analgesic therapy alone (control, n = 36) or 1.2 μg/kg intrathecal RTX in addition to standard of care analgesic therapy (treated, n = 36). Significantly more dogs in the control group (78%) required unblinding and adjustment in analgesic protocol or euthanasia within 6 weeks of randomization, than dogs that were treated with RTX (50%; P < 0.03); and overall, dogs in the control group required unblinding significantly sooner than dogs that had been treated with RTX (P < 0.02). The analgesic effect was documented in these dogs without any evidence of development of deafferentation pain syndrome that can be seen with neurolytic therapies.

  20. Mechanisms of PDGF siRNA-mediated inhibition of bone cancer pain in the spinal cord

    PubMed Central

    Xu, Yang; Liu, Jia; He, Mu; Liu, Ran; Belegu, Visar; Dai, Ping; Liu, Wei; Wang, Wei; Xia, Qing-Jie; Shang, Fei-Fei; Luo, Chao-Zhi; Zhou, Xue; Liu, Su; McDonald, JohnW.; Liu, Jin; Zuo, Yun-Xia; Liu, Fei; Wang, Ting-Hua

    2016-01-01

    Patients with tumors that metastasize to bone frequently suffer from debilitating pain, and effective therapies for treating bone cancer are lacking. This study employed a novel strategy in which herpes simplex virus (HSV) carrying a small interfering RNA (siRNA) targeting platelet-derived growth factor (PDGF) was used to alleviate bone cancer pain. HSV carrying PDGF siRNA was established and intrathecally injected into the cavum subarachnoidale of animals suffering from bone cancer pain and animals in the negative group. Sensory function was assessed by measuring thermal and mechanical hyperalgesia. The mechanism by which PDGF regulates pain was also investigated by comparing the differential expression of pPDGFRα/β and phosphorylated ERK and AKT. Thermal and mechanical hyperalgesia developed in the rats with bone cancer pain, and these effects were accompanied by bone destruction in the tibia. Intrathecal injection of PDGF siRNA and morphine reversed thermal and mechanical hyperalgesia in rats with bone cancer pain. In addition, we observed attenuated astrocyte hypertrophy, down-regulated pPDGFRα/β levels, reduced levels of the neurochemical SP, a reduction in CGRP fibers and changes in pERK/ERK and pAKT/AKT ratios. These results demonstrate that PDGF siRNA can effectively treat pain induced by bone cancer by blocking the AKT-ERK signaling pathway. PMID:27282805

  1. Bone mineral density and perceived menopausal symptoms: factors influencing low back pain in postmenopausal women.

    PubMed

    Ahn, Sukhee; Song, Rhayun

    2009-06-01

    This paper is a report of a study of the relationships between the factors influencing low back pain in postmenopausal women (i.e. menopausal symptoms, bone mineral density, duration of menopause, hormonal therapy, obesity, inactivity during leisure time, parity, osteoarthritis and drinking coffee). Previous studies have shown that low back pain in postmenopausal women is associated with bone mineral density, menopausal symptoms and lifestyle factors, yet the factors influencing low back pain are not clear and vary with ethnicity. A survey was conducted with postmenopausal women (n = 134) in Korea in 2006. Bone mineral density in the lumbar spine, back pain status, menopausal symptoms and health habits were assessed. Participants' mean age was 59 years. About 70% experienced back pain on more than 1 day during the week prior to the survey and 35% suffered back pain daily. Women with back pain reported more severe menopausal symptoms than those without back pain. Based on bone mineral density scores, 26.9% of the women were considered to be at risk of osteoporosis. However, there was no association between back pain status and fracture risk status. Based on a multiple logistic regression model, menopausal symptoms, drinking coffee and inactivity during leisure time were statistically significant influencing factors for low back pain in this sample. The prevalence of low back pain in postmenopausal women should be recognized in association with menopausal symptoms and health habits. Further research is needed to develop interventions for the management of low back pain in postmenopausal women.

  2. Behavioral, Medical Imaging and Histopathological Features of a New Rat Model of Bone Cancer Pain

    PubMed Central

    Doré-Savard, Louis; Otis, Valérie; Belleville, Karine; Lemire, Myriam; Archambault, Mélanie; Tremblay, Luc; Beaudoin, Jean-François; Beaudet, Nicolas; Lecomte, Roger; Lepage, Martin; Gendron, Louis; Sarret, Philippe

    2010-01-01

    Pre-clinical bone cancer pain models mimicking the human condition are required to respond to clinical realities. Breast or prostate cancer patients coping with bone metastases experience intractable pain, which affects their quality of life. Advanced monitoring is thus required to clarify bone cancer pain mechanisms and refine treatments. In our model of rat femoral mammary carcinoma MRMT-1 cell implantation, pain onset and tumor growth were monitored for 21 days. The surgical procedure performed without arthrotomy allowed recording of incidental pain in free-moving rats. Along with the gradual development of mechanical allodynia and hyperalgesia, behavioral signs of ambulatory pain were detected at day 14 by using a dynamic weight-bearing apparatus. Osteopenia was revealed from day 14 concomitantly with disorganization of the trabecular architecture (µCT). Bone metastases were visualized as early as day 8 by MRI (T1-Gd-DTPA) before pain detection. PET (Na18F) co-registration revealed intra-osseous activity, as determined by anatomical superimposition over MRI in accordance with osteoclastic hyperactivity (TRAP staining). Pain and bone destruction were aggravated with time. Bone remodeling was accompanied by c-Fos (spinal) and ATF3 (DRG) neuronal activation, sustained by astrocyte (GFAP) and microglia (Iba1) reactivity in lumbar spinal cord. Our animal model demonstrates the importance of simultaneously recording pain and tumor progression and will allow us to better characterize therapeutic strategies in the future. PMID:21048940

  3. Palliation of bone cancer pain by antagonists of platelet-activating factor receptors.

    PubMed

    Morita, Katsuya; Shiraishi, Seiji; Motoyama, Naoyo; Kitayama, Tomoya; Kanematsu, Takashi; Uezono, Yasuhito; Dohi, Toshihiro

    2014-01-01

    Bone cancer pain is the most severe among cancer pain and is often resistant to current analgesics. Thus, the development of novel analgesics effective at treating bone cancer pain are desired. Platelet-activating factor (PAF) receptor antagonists were recently demonstrated to have effective pain relieving effects on neuropathic pain in several animal models. The present study examined the pain relieving effect of PAF receptor antagonists on bone cancer pain using the femur bone cancer (FBC) model in mice. Animals were injected with osteolytic NCTC2472 cells into the tibia, and subsequently the effects of PAF receptor antagonists on pain behaviors were evaluated. Chemical structurally different type of antagonists, TCV-309, BN 50739 and WEB 2086 ameliorated the allodynia and improved pain behaviors such as guarding behavior and limb-use abnormalities in FBC model mice. The pain relieving effects of these antagonists were achieved with low doses and were long lasting. Blockade of spinal PAF receptors by intrathecal injection of TCV-309 and WEB 2086 or knockdown of the expression of spinal PAF receptor protein by intrathecal transfer of PAF receptor siRNA also produced a pain relieving effect. The amount of an inducible PAF synthesis enzyme, lysophosphatidylcholine acyltransferase 2 (LPCAT2) protein significantly increased in the spinal cord after transplantation of NCTC 2472 tumor cells into mouse tibia. The combination of morphine with PAF receptor antagonists develops marked enhancement of the analgesic effect against bone cancer pain without affecting morphine-induced constipation. Repeated administration of TCV-309 suppressed the appearance of pain behaviors and prolonged survival of FBC mice. The present results suggest that PAF receptor antagonists in combination with, or without, opioids may represent a new strategy for the treatment of persistent bone cancer pain and improve the quality of life of patients.

  4. Palliative treatment of bone metastases with samarium-153 EDTMP at onset of pain.

    PubMed

    Gallicchio, Rosj; Giacomobono, Sabrina; Nardelli, Anna; Pellegrino, Teresa; Simeon, Vittorio; Gattozzi, Domenico; Maddalena, Francesca; Mainenti, Pierpaolo; Storto, Giovanni

    2014-07-01

    We evaluated the pain response and daily discomfort in patients suffering from a borderline degree of bone pain due to breast or lung cancer bone metastases, who had undergone early palliative radionuclide treatment. The results were compared with those from patients who had received standard analgesic therapy. Twenty-one patients (65.7 ± 3 years; 17 women) with metastatic bone cancer underwent samarium-153 (Sm-153) ethylene diamine tetramethylene phosphonate (EDTMP) administration (group A) and 18 patients (64.3 ± 8 years; 16 women)continued to receive standard analgesics (group B; control group). The patients kept a daily pain diary assessing both their discomfort and the pain at specific sites by means of a visual analog scale, rating from 0 (no discomfort–no pain)to 10 (worst discomfort–pain). These diaries were reviewed weekly for 2 months and three physicians rated the pain response on a scale from -2 (considerable deterioration) to +2 (considerable improvement). Baseline characteristics were similar in both groups. The reduction of total discomfort and of bone pain in group A was significantly greater compared to group B (p < 0.0001). A significant improvement of clinical conditions was observed in group A, where the physician rate changed from -1 to 1, compared to group B in which the rate changed from -1 to 0. Sm-153 EDTMP therapy can be considered for patients with bone pain from breast and lung cancer in advance, i.e.,before the establishment of severe pain syndrome.

  5. Lumbar bone mass predicts low back pain in males.

    PubMed

    Hoozemans, Marco J M; Koppes, Lando L J; Twisk, Jos W R; van Dieën, Jaap H

    2012-08-15

    Longitudinal study of lumbar bone mass as predictor of low back pain (LBP). To investigate whether low bone mineral content (BMC) and bone mineral density (BMD) values at the age of 36 years are associated with the prevalence of LBP at the age of 42 years among the study population of the Amsterdam Growth and Health Longitudinal Study. Results of epidemiological, clinical, and in vitro studies indicate that spinal injuries, caused by mechanical loading, might be a cause of LBP. BMC and BMD are determinants of spinal strength. We therefore hypothesized that BMC and BMD are associated with LBP. At the age of 36 years, the lumbar BMC and BMD were determined by dual-energy x-ray absorptiometry in 140 men and 152 women. At the age of 42 years, the participants were asked whether they had experienced LBP in the previous 12 months. Logistic regression analyses were performed to determine odds ratios (ORs)-adjusted for stature, body weight, physical activity, and smoking-for the relationship of BMC and BMD with LBP. BMC and BMD at the age of 36 years were significantly associated with the reported 12-month prevalence of LBP at the age of 42 years. This association, however, was observed only for men and not for women. Men within the quartile with the lowest BMC or BMD values had higher odds for LBP with ORs of 4.78 (95% confidence interval, 1.52-15.00) and 3.48 (95% confidence interval, 1.23-9.85), respectively. For a male population that is not characterized by osteoporosis or old age, lower lumbar BMC and BMD values at the age of 36 years are associated with an increased risk of reporting to have had LBP in the previous 12 months at the age of 42 years.

  6. Elderly Patients With Painful Bone Metastases Should be Offered Palliative Radiotherapy

    SciTech Connect

    Campos, Sarah; Presutti, Roseanna; Zhang Liying; Salvo, Nadia; Hird, Amanda; Tsao, May; Barnes, Elizabeth A.; Danjoux, Cyril; Sahgal, Arjun; Mitera, Gunita; Sinclair, Emily; DeAngelis, Carlo; Nguyen, Janet; Napolskikh, Julie; Chow, Edward

    2010-04-15

    Purpose: To investigate the efficacy of palliative radiotherapy (RT) in relieving metastatic bone pain in elderly patients. Methods and Materials: The response to RT for palliation of metastatic bone pain was evaluated from a prospective database of 558 patients between 1999 and 2008. The pain scores and analgesic intake were used to calculate the response according to the International Bone Metastases Consensus Working Party palliative RT endpoints. Subgroup analyses for age and other demographic information were performed. Results: No significant difference was found in the response rate in patients aged >=65, >=70, and >=75 years compared with younger patients at 1, 2, or 3 months after RT. The response was found to be significantly related to the performance status. Conclusion: Age alone did not affect the response to palliative RT for bone metastases. Elderly patients should be referred for palliative RT for their painful bone metastases, regardless of age, because they receive equal benefit from the treatment.

  7. Severe pegfilgrastim-induced bone pain completely alleviated with loratadine: A case report.

    PubMed

    Romeo, Cristina; Li, Quan; Copeland, Larry

    2015-08-01

    Febrile neutropenia is an oncologic emergency that can result in serious consequences. Granulocyte colony stimulating factors (G-CSFs) are often used as prophylaxis for febrile neutropenia. Bone pain is the most notorious adverse effect caused by G-CSFs. Specifically, with pegfilgrastim (Neulasta(®)), the incidence of bone pain is higher in practice than was observed during clinical trials. Traditional analgesics, such as non-steroidal anti-inflammatory drugs (NSAIDs) and opioids, can be ineffective in severe pegfilgrastim-induced bone pain. With the high frequency of this adverse effect, it is clear that health practitioners need additional treatment options for patients who experience severe pegfilgrastim-induced bone pain. The mechanisms of bone pain secondary to G-CSFs are not fully known, but research has shown that histamine release is involved in the inflammatory process. There is scant previous clinical data on antihistamine use in the management of G-CSF-induced pain. We present the first case report in which loratadine prophylaxis completely alleviated NSAID-resistant severe pain secondary to pegfilgrastim. The result showed that loratadine may be a promising option for severe, resistant pegfilgrastim-induced bone pain. Further clinical studies are warranted and ongoing.

  8. Single dose oral fenbufen for acute postoperative pain in adults

    PubMed Central

    Moore, R Andrew; Derry, Sheena; McQuay, Henry J

    2014-01-01

    Background Fenbufen is a non-selective non-steroidal anti-inflammatory drug (NSAID), used to treat acute and chronic painful conditions. There is no known systematic review of its use in acute postoperative pain. Objectives To assess efficacy, duration of action, and associated adverse events of single dose oral fenbufen in acute postoperative pain in adults. Search methods We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief database for studies to June 2009. Selection criteria Randomised, double blind, placebo-controlled trials of single dose orally administered fenbufen in adults with moderate to severe acute postoperative pain. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk and number needed to treat to benefit (NNT) were calculated. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals were collected. Main results Searches identified only one study with (90 participants in total, 31 taking fenbufen). The study compared oral fenbufen 800 mg, fenbufen 400 mg, and placebo in participants with established postoperative pain. Fenbufen at both doses had apparent analgesic efficacy, but the numbers of participants was too small to allow sensible analysis. Gastrointestinal adverse events were noted in 4 of 15 participants taking fenbufen 800 mg. Authors’ conclusions In the absence of evidence of efficacy for oral fenbufen in acute postoperative pain, its use in this indication is not justified at present. Because trials clearly demonstrating analgesic efficacy in the most basic of acute pain studies is lacking, use in other indications should be

  9. Involvement of acidic microenvironment in the pathophysiology of cancer-associated bone pain.

    PubMed

    Yoneda, Toshiyuki; Hata, Kenji; Nakanishi, Masako; Nagae, Maho; Nagayama, Tomotaka; Wakabayashi, Hiroki; Nishisho, Toshihiko; Sakurai, Teruhisa; Hiraga, Toru

    2011-01-01

    Bone pain is one of the most common complications in cancer patients with bone metastases. Although the mechanism of cancer-associated bone pain is poorly understood, clinical observations that inhibitors of osteoclasts such as bisphosphonates (BPs) efficiently reduce bone pain suggest a potential role of osteoclasts, which play a central role in the development and progression of bone metastasis. Osteoclasts dissolve bone minerals by releasing protons through the a3 isoform of the vacuolar-H(+)-ATPase, creating acidic microenvironments. In addition, cancer cells, inflammatory cells and immune cells that reside in bone metastases also produce acidic conditions by releasing protons. It has been well-known that acidic conditions due to proton release cause pain. Our study showed that the sensory nociceptive neurons innervate bone and these neurons express acid-sensing nociceptors such as the acid-sensing ion channels and transient receptor potential channel-vanilloid subfamily members. Acid signals received by these nociceptors subsequently activate intracellular signaling pathways and transcription factors in sensory neurons. The understanding of the nociceptive events following proton release and subsequent creation of acidic microenvironments leads us to design novel molecular-based approaches for reducing bone pain associated with cancer and inflammation.

  10. Patterns of Practice in Palliative Radiotherapy for Painful Bone Metastases: A Survey in Japan

    SciTech Connect

    Nakamura, Naoki; Shikama, Naoto; Wada, Hitoshi; Harada, Hideyuki; Nozaki, Miwako; Nagakura, Hisayasu; Tago, Masao; Oguchi, Masahiko; Uchida, Nobue

    2012-05-01

    Purpose: To determine the current patterns of practice in Japan and to investigate factors that may make clinicians reluctant to use single-fraction radiotherapy (SF-RT). Methods and Materials: Members of the Japanese Radiation Oncology Study Group (JROSG) completed an Internet-based survey and described the radiotherapy dose fractionation they would recommend for four hypothetical cases describing patients with painful bone metastasis (BM). Case 1 described a patient with an uncomplicated painful BM in a non-weight-bearing site from non-small-cell lung cancer. Case 2 investigated whether management for a case of uncomplicated spinal BM would be different from that in Case 1. Case 3 was identical with Case 2 except for the presence of neuropathic pain. Case 4 investigated the prescription for an uncomplicated painful BM secondary to oligometastatic breast cancer. Radiation oncologists who recommended multifraction radiotherapy (MF-RT) for Case 2 were asked to explain why they considered MF-RT superior to SF-RT. Results: A total of 52 radiation oncologists from 50 institutions (36% of JROSG institutions) responded. In all four cases, the most commonly prescribed regimen was 30 Gy in 10 fractions. SF-RT was recommended by 13% of respondents for Case 1, 6% for Case 2, 0% for Case 3, and 2% for Case 4. For Case 4, 29% of respondents prescribed a high-dose MF-RT regimen (e.g., 50 Gy in 25 fractions). The following factors were most often cited as reasons for preferring MF-RT: 'time until first increase in pain' (85%), 'incidence of spinal cord compression' (50%), and 'incidence of pathologic fractures' (29%). Conclusions: Japanese radiation oncologists prefer a schedule of 30 Gy in 10 fractions and are less likely to recommend SF-RT. Most Japanese radiation oncologists regard MF-RT as superior to SF-RT, based primarily on the time until first increase in pain.

  11. Evaluation of pain in single and multi rooted teeth treated in single visit endodontic therapy.

    PubMed

    Raju, T B V G; Seshadri, Abitha; Vamsipavani, B; Abhilash, K; Subhash, A V; Kumari, K V Halini

    2014-02-01

    The incidence of post-operative pain was compared following single-visit canal treatment in single- and multi-rooted teeth, with and without periapical radiolucency. The article also reviews the issues of postoperative pain and healing, following single-visit and multi-visit endodontic therapy. Single-visit endodontic therapy (SVE) was performed in 50 single-rooted teeth and 60 multiple-rooted teeth. Single-visit endodontic therapy (SVE) was performed in 50 single-rooted teeth and 60 multiple-rooted teeth. The subjects were divided as follows: Group I -Single-rooted teeth with periapical radiolucency (n=25); Group II-Single-rooted teeth without periapical radiolucency (n=25); Group III-Multiple-rooted teeth with periapical radiolucency (n=30); and Group IV-Multiple-rooted teeth without periapical radiolucency (n=30). Assessment of postoperative pain was done at 24hrs, 3 days and 1 week using a self report questionnaire. The data was analyzed using non-parametric Kruskal -Wallis test. No statistically significant difference was observed in postoperative pain following SVE between the single-rooted and multiple-rooted teeth groups at 24hrs, 3 days and 1 week. The presence or absence of periapical radiolucency had no significant influence on the incidence of reported postoperative pain following SVE. There was no difference in incidence of pain in single rooted teeth and multi-rooted teeth with and without periapical radiolucencies following SVE. Thus, incidence of post-operative pain does not seem to be a valid comparison criterion between single- and multiple-visit endodontic therapies. Also, the literature suggests similar success rates with single-visit and multiple-visit root canal treatment. How to cite the article: Raju TB, Seshadri A, Vamsipavani B, Abhilash K, Subhash AV, Kumari KV. Evaluation of Pain in Single and Multi Rooted Teeth Treated in Single Visit Endodontic Therapy. J Int Oral Health 2014;6(1):27-32.

  12. Ethnicity and reported pain scores among children with long-bone fractures requiring emergency care.

    PubMed

    Ortega, Henry W; Velden, Heidi Vander; Lin, Chia-Wei; Reid, Samuel

    2012-11-01

    Previous studies have shown that regular pain measurement improves pain management. As the diversity of patients seeking emergency care continues to grow, a better understanding of the potential differences in pain perception and analgesic needs among various cultural groups will be required. The purpose of this study was to describe the differences in pain scores reported among ethnic groups treated for a long-bone fracture. A retrospective review of patients with a long-bone fracture treated in an urban pediatric emergency department during a 12-month period was performed. Pain scores were assessed using previously validated pain scales. Eight hundred eighty patients met our inclusion criteria. Wrist fracture was the most common type of fracture in our study. There were significant differences noted in reported pain scores. Patients identified as Hmong had the highest pain scores, and patients identified as Somali had the lowest pain scores reported. Patients with wrist fractures had the highest average pain score when compared with other types of fractures. Children with fractures requiring reduction in the emergency department had higher pain scores than those who had a fracture that did not require reduction. To our knowledge, this is the first study to investigate the relationships between ethnicity and pain scores reported in children treated emergently for a long-bone fracture.

  13. Primary pain palliation and local tumor control in bone metastases treated with magnetic resonance-guided focused ultrasound.

    PubMed

    Napoli, Alessandro; Anzidei, Michele; Marincola, Beatrice Cavallo; Brachetti, Giulia; Ciolina, Federica; Cartocci, Gaia; Marsecano, Claudia; Zaccagna, Fulvio; Marchetti, Luca; Cortesi, Enrico; Catalano, Carlo

    2013-06-01

    The objectives of this study were to evaluate the efficacy in pain management of magnetic resonance (MR)-guided focused ultrasound for the primary treatment of painful bone metastases and to assess its potential for local control of bone metastases. This was a prospective, single-arm research study with approval from the institutional review board. Eighteen consecutive patients (female, 8; male, 10; mean [SD] age, 62.7 [11.5] years) with painful bone metastases were enrolled. The patients were examined clinically for pain severity and pain interference in accordance with the Brief Pain Inventory-Quality of Life criteria before and at each follow-up visit. Computed tomography and MR imaging were performed before and at 1 and 3 months after the magnetic resonance-guided focused ultrasound treatment. The nonperfused volume (NPV) was calculated to correlate the extension of the ablated pathological tissue in the responder and nonresponder patients. No treatment-related adverse events were recorded during the study. The evaluation of pain palliation revealed a statistically significant difference between baseline and follow-up values for pain severity and pain interference (P = 0.001, both evaluations). In the evaluation of local tumor control, we observed increased bone density with restoration of cortical borders in 5 of the 18 patients (27.7%). In accordance with the MD Anderson criteria, complete and partial responses were obtained in 2 of the 18 patients (11.1%) and 4 of the 18 patients (22.2%), respectively. Nonperfused volume values ranged between 20% and 93%. Mean NPV values remained substantially stable after the treatment (P = 0.08). There was no difference in the NPV values between the responder and nonresponder patients (46.7% [24.2%] [25%-90%] versus 45% [24.9%] [20%-93%]; P = 0.7). Magnetic resonance-guided focused ultrasound can be safely and effectively used as the primary treatment of pain palliation in patients with bone metastases and has a potential

  14. Role of nuclear medicine bone scans in evaluating pain in athletic injuries

    SciTech Connect

    Martire, J.R.

    1987-10-01

    The utilization of nuclear medicine bone scanning examinations early in the diagnostic process allows physicians to render prompt and correct treatment in urgent or difficult athletic cases. Bone scanning should be performed for athletic injuries whenever (1) x-rays are normal but bone or joint pain persists; (2) x-rays are positive but it cannot be determined if the findings are acute or chronic; (3) soft-tissue injuries present and x-rays are not useful; and (4) bone pain or joint impairment present without a history of trauma.89 references.

  15. Improving quality of life in patients with advanced cancer: Targeting metastatic bone pain.

    PubMed

    von Moos, Roger; Costa, Luis; Ripamonti, Carla Ida; Niepel, Daniela; Santini, Daniele

    2017-01-01

    Metastatic bone disease in patients with advanced cancer is frequently associated with skeletal complications. These can be debilitating, causing pain, impaired functioning and decreased quality of life, as well as reduced survival. This review considers how the management of metastatic bone pain might be optimised, to limit the considerable burden it can impose on affected patients. Cancer-related pain is notoriously under-reported and under-treated, despite the availability of many therapeutic options. Non-opioid and opioid analgesics can be used; the latter are typically administered with radiotherapy, which forms the current standard of care for patients with metastatic bone pain. Surgery is appropriate for certain complicated cases of metastatic bone disease, and other options such as radiopharmaceuticals may provide additional relief. Treatments collectively referred to as bone-targeted agents (BTAs; bisphosphonates and denosumab) can offer further pain reduction. Initiation of therapy with BTAs is recommended for all patients with metastatic bone disease because these agents delay not only the onset of skeletal-related events but also the onset of bone pain. With evidence also emerging for pain control properties of new anticancer agents, the potential to individualise care for these patients is increased further. Optimisation of care depends on physicians' thorough appreciation of the complementary benefits that might be achieved with the various agents, as well as their limitations. Appropriate anti-tumour treatment combined with early initiation of BTAs and adequate analgesia plays a key role in the holistic approach to cancer pain management and may minimise the debilitating effects of metastatic bone pain. Copyright © 2016 Amgen Inc. Published by Elsevier Ltd.. All rights reserved.

  16. International Patterns of Practice in Palliative Radiotherapy for Painful Bone Metastases: Evidence-Based Practice?

    SciTech Connect

    Fairchild, Alysa; Barnes, Elizabeth; Ghosh, Sunita; Ben-Josef, Edgar; Roos, Daniel; Hartsell, William; Holt, Tanya; Wu, Jackson; Janjan, Nora; Chow, Edward

    2009-12-01

    Purpose: Multiple randomized controlled trials have demonstrated the equivalence of multifraction and single-fraction (SF) radiotherapy for the palliation of painful bone metastases (BM). However, according to previous surveys, SF schedules remain underused. The objectives of this study were to determine the current patterns of practice internationally and to investigate the factors influencing this practice. Methods and Materials: The members of three global radiation oncology professional organizations (American Society for Radiology Oncology [ASTRO], Canadian Association of Radiation Oncology [CARO], Royal Australian and New Zealand College of Radiologists) completed an Internet-based survey. The respondents described what radiotherapy dose fractionation they would recommend for 5 hypothetical cases describing patients with single or multiple painful BMs from breast, lung, or prostate cancer. Radiation oncologists rated the importance of patient, tumor, institution, and treatment factors, and descriptive statistics were compiled. The chi-square test was used for categorical variables and the Student t test for continuous variables. Logistic regression analysis identified predictors of the use of SF radiotherapy. Results: A total of 962 respondents, three-quarters ASTRO members, described 101 different dose schedules in common use (range, 3 Gy/1 fraction to 60 Gy/20 fractions). The median dose overall was 30 Gy/10 fractions. SF schedules were used the least often by ASTRO members practicing in the United States and most often by CARO members. Case, membership affiliation, country of training, location of practice, and practice type were independently predictive of the use of SF. The principal factors considered when prescribing were prognosis, risk of spinal cord compression, and performance status. Conclusion: Despite abundant evidence, most radiation oncologists continue to prescribe multifraction schedules for patients who fit the eligibility criteria of

  17. Percutaneous cementoplasty for the treatment of extraspinal painful bone lesion, a prospective study.

    PubMed

    Iannessi, A; Amoretti, N; Marcy, P-Y; Sedat, J

    2012-11-01

    The current gold standard treatment of localized painful bone lesion is radiotherapy but this technique has limitations. Our study aims to demonstrate that cementoplasty is an efficient alternative for these palliatives indications when lesions involve extraspinal bones. We prospectively followed 20 patients who received a percutaneous cementoplasty on painful lytic bone lesions between May 2008 and May 2010. Seventeen patients also had difficulty walking in relation to the pain experienced. The clinical indication for treatment was severe pain (≥4 on the numeric scale) due to bone lesion on CT or MRI. All procedures (except one) were performed under local anesthesia. Feasibility was 100% without immediate complications. The patients experienced a significant and rapid decrease of their pain (4.1 points, P<000.1) and this effect was sustained over the long term (7.75 months of follow-up on average). Sixty-four percent of patients treated on the lower limbs and pelvis improved mobility. In our experience, percutaneous cementoplasty may be a safe and effective palliative treatment for localized painful lytic lesion. Combining CT and fluoroscopic guidance seems to be the safer option because of extravertebral localization. Smart fill of the bone and careful selection of patient determine the effectiveness of the procedure. Diffuse painful lesions and long bone diaphysis should not be good indications. Copyright © 2012 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

  18. Method for palliation of pain in human bone cancer using therapeutic tin-117m compositions

    DOEpatents

    Srivastava, Suresh C.; Meinken, George E.; Mausner, Leonard F.; Atkins, Harold L.

    1998-12-29

    The invention provides a method for the palliation of bone pain due to cancer by the administration of a unique dosage of a tin-117m (Sn-117m) stannic chelate complex in a pharmaceutically acceptable composition. In addition, the invention provides a method for simultaneous palliation of bone pain and radiotherapy in cancer patients using compositions containing Sn-117m chelates. The invention also provides a method for palliating bone pain in cancer patients using Sn-117m-containing compositions and monitoring patient status by imaging the distribution of the Sn-117m in the patients. Also provided are pharmaceutically acceptable compositions containing Sn-117m chelate complexes for the palliation of bone pain in cancer patients.

  19. Method for palliation of pain in human bone cancer using therapeutic tin-117m compositions

    DOEpatents

    Srivastava, S.C.; Meinken, G.E.; Mausner, L.F.; Atkins, H.L.

    1998-12-29

    The invention provides a method for the palliation of bone pain due to cancer by the administration of a unique dosage of a tin-117m (Sn-117m) stannic chelate complex in a pharmaceutically acceptable composition. In addition, the invention provides a method for simultaneous palliation of bone pain and radiotherapy in cancer patients using compositions containing Sn-117m chelates. The invention also provides a method for palliating bone pain in cancer patients using Sn-117m-containing compositions and monitoring patient status by imaging the distribution of the Sn-117m in the patients. Also provided are pharmaceutically acceptable compositions containing Sn-117m chelate complexes for the palliation of bone pain in cancer patients. 5 figs.

  20. Bone

    NASA Astrophysics Data System (ADS)

    Helmberger, Thomas K.; Hoffmann, Ralf-Thorsten

    The typical clinical signs in bone tumours are pain, destruction and destabilization, immobilization, neurologic deficits, and finally functional impairment. Primary malignant bone tumours are a rare entity, accounting for about 0.2% of all malignancies. Also benign primary bone tumours are in total rare and mostly asymptomatic. The most common symptomatic benign bone tumour is osteoid osteoma with an incidence of 1:2000.

  1. Decreased sensory nerve excitation and bone pain associated with mouse Lewis lung cancer in TRPV1-deficient mice.

    PubMed

    Wakabayashi, Hiroki; Wakisaka, Satoshi; Hiraga, Toru; Hata, Kenji; Nishimura, Riko; Tominaga, Makoto; Yoneda, Toshiyuki

    2017-05-17

    Bone pain is one of the most common and life-limiting complications of cancer metastasis to bone. Although the mechanism of bone pain still remains poorly understood, bone pain is evoked as a consequence of sensitization and excitation of sensory nerves (SNs) innervating bone by noxious stimuli produced in the microenvironment of bone metastases. We showed that bone is innervated by calcitonin gene-related protein (CGRP)(+) SNs extending from dorsal root ganglia (DRG), the cell body of SNs, in mice. Mice intratibially injected with Lewis lung cancer (LLC) cells showed progressive bone pain evaluated by mechanical allodynia and flinching with increased CGRP(+) SNs in bone and augmented SN excitation in DRG as indicated by elevated numbers of pERK- and pCREB-immunoreactive neurons. Immunohistochemical examination of LLC-injected bone revealed that the tumor microenvironment is acidic. Bafilomycin A1, a selective inhibitor of H(+) secretion from vacuolar proton pump, significantly alleviated bone pain, indicating that the acidic microenvironment contributes to bone pain. We then determined whether the transient receptor potential vanilloid 1 (TRPV1), a major acid-sensing nociceptor predominantly expressed on SNs, plays a role in bone pain by intratibially injecting LLC cells in TRPV1-deficient mice. Bone pain and SN excitation in the DRG and spinal dorsal horn were significantly decreased in TRPV1 (-/-) mice compared with wild-type mice. Our results suggest that TRPV1 activation on SNs innervating bone by the acidic cancer microenvironment in bone contributes to SN activation and bone pain. Targeting acid-activated TRPV1 is a potential therapeutic approach to cancer-induced bone pain.

  2. Single dose oral ibuprofen for acute postoperative pain in adults

    PubMed Central

    Derry, Christopher J; Derry, Sheena; Moore, R Andrew; McQuay, Henry J

    2014-01-01

    Background This review updates a 1999 Cochrane review showing that ibuprofen at various doses was effective in postoperative pain in single dose studies designed to demonstrate analgesic efficacy. New studies have since been published. Ibuprofen is one of the most widely used non-steroidal anti-inflammatory (NSAID) analgesics both by prescription and as an over-the-counter medicine. Ibuprofen is used for acute and chronic painful conditions. Objectives To assess analgesic efficacy of ibuprofen in single oral doses for moderate and severe postoperative pain in adults. Search methods We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to May 2009. Selection criteria Randomised, double blind, placebo-controlled trials of single dose orally administered ibuprofen (any formulation) in adults with moderate to severe acute postoperative pain. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk and number-needed-to-treat-to-benefit (NNT) were calculated. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals were collected. Main results Seventy-two studies compared ibuprofen and placebo (9186 participants). Studies were predominantly of high reporting quality, and the bulk of the information concerned ibuprofen 200 mg and 400 mg. For at least 50% pain relief compared with placebo the NNT for ibuprofen 200 mg (2690 participants) was 2.7 (2.5 to 3.0) and for ibuprofen 400 mg (6475 participants) it was 2.5 (2.4 to 2.6). The proportion with at least 50% pain relief was 46% with 200 mg and 54% with 400 mg. Remedication within 6 hours was less

  3. Single dose oral flurbiprofen for acute postoperative pain in adults

    PubMed Central

    Sultan, Asquad; McQuay, Henry J; Moore, R Andrew; Derry, Sheena

    2014-01-01

    Background Flurbiprofen is a non-selective non-steroidal anti-inflammatory drug (NSAID), related to ibuprofen and naproxen, used to treat acute and chronic painful conditions. There is no systematic review of its use in acute postoperative pain. Objectives To assess efficacy, duration of action, and associated adverse events of single dose oral flurbiprofen in acute postoperative pain in adults. Search methods We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to January 2009. Selection criteria Randomised, double blind, placebo-controlled trials of single dose orally administered flurbiprofen in adults with moderate to severe acute postoperative pain. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk (RR) and number needed to treat to benefit (NNT) were calculated. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals were collected. Main results Eleven studies compared flurbiprofen (699 participants) with placebo (362 participants) in studies lasting 6 to 12 hours. Studies were of adequate reporting quality, and most participants had pain following dental extractions. The dose of flurbiprofen used was 25 mg to 100 mg, with most information for 50 mg and 100 mg. The NNT for at least 50% pain relief over 4 to 6 hours for flurbiprofen 50 mg compared with placebo (692 participants) was 2.7 (2.3 to 3.3) and for 100 mg (416 participants) it was 2.5 (2.0 to 3.1). With flurbiprofen 50 mg and 100 mg 65% to 70% of participants experienced at least 50% pain relief, compared with 25% to 30% with placebo. Rescue medication was used by 25

  4. Pain and Mean Absorbed Dose to the Pubic Bone After Radiotherapy Among Gynecological Cancer Survivors

    SciTech Connect

    Waldenstroem, Ann-Charlotte; Olsson, Caroline; Wilderaeng, Ulrica; Dunberger, Gail; Lind, Helena; Al-Abany, Massoud; Palm, Asa; Avall-Lundqvist, Elisabeth; Johansson, Karl-Axel; Steineck, Gunnar

    2011-07-15

    Purpose: To analyze the relationship between mean absorbed dose to the pubic bone after pelvic radiotherapy for gynecological cancer and occurrence of pubic bone pain among long-term survivors. Methods and Materials: In an unselected, population-based study, we identified 823 long-term gynecological cancer survivors treated with pelvic radiotherapy during 1991-2003. For comparison, we used a non-radiation-treated control population of 478 matched women from the Swedish Population Register. Pain, intensity of pain, and functional impairment due to pain in the pubic bone were assessed with a study-specific postal questionnaire. Results: We analyzed data from 650 survivors (participation rate 79%) with median follow-up of 6.3 years (range, 2.3-15.0 years) along with 344 control women (participation rate, 72 %). Ten percent of the survivors were treated with radiotherapy; ninety percent with surgery plus radiotherapy. Brachytherapy was added in 81%. Complete treatment records were recovered for 538/650 survivors, with dose distribution data including dose-volume histograms over the pubic bone. Pubic bone pain was reported by 73 survivors (11%); 59/517 (11%) had been exposed to mean absorbed external beam doses <52.5 Gy to the pubic bone and 5/12 (42%) to mean absorbed external beam doses {>=}52.5 Gy. Thirty-three survivors reported pain affecting sleep, a 13-fold increased prevalence compared with control women. Forty-nine survivors reported functional impairment measured as pain walking indoors, a 10-fold increased prevalence. Conclusions: Mean absorbed external beam dose above 52.5 Gy to the pubic bone increases the occurrence of pain in the pubic bone and may affect daily life of long-term survivors treated with radiotherapy for gynecological cancer.

  5. Successful treatment of pain in melorheostosis with zoledronate, with improvement on bone scintigraphy.

    PubMed

    Slimani, Samy; Nezzar, Adlen; Makhloufi, Hachemi

    2013-06-21

    Melorheostosis is a very rare sclerosing bone disorder that involves frequently one limb. It may be asymptomatic, but pain and limb deformity may occur and can be very debilitating. Different reports have indicated efficacy of bisphosphonates (pamidronate and etidronate) on symptoms. We report an adult patient with a very painful melorheostosis, who  improved after treatment with zoledronate, either on symptoms or on bone scans.

  6. Successful treatment of pain in melorheostosis with zoledronate, with improvement on bone scintigraphy

    PubMed Central

    Slimani, Samy; Nezzar, Adlen; Makhloufi, Hachemi

    2013-01-01

    Melorheostosis is a very rare sclerosing bone disorder that involves frequently one limb. It may be asymptomatic, but pain and limb deformity may occur and can be very debilitating. Different reports have indicated efficacy of bisphosphonates (pamidronate and etidronate) on symptoms. We report an adult patient with a very painful melorheostosis, who  improved after treatment with zoledronate, either on symptoms or on bone scans. PMID:23813581

  7. Tumor Tissue-Derived Formaldehyde and Acidic Microenvironment Synergistically Induce Bone Cancer Pain

    PubMed Central

    Yang, Fei; Han, Ying; Li, Hui; Luo, Hongjun; Duan, Bo; Xu, Tianle; Maoying, Qiliang; Tan, Huangying; Wang, Jun; Zhao, Hongmei; Liu, Fengyu; Wan, You

    2010-01-01

    Background There is current interest in understanding the molecular mechanisms of tumor-induced bone pain. Accumulated evidence shows that endogenous formaldehyde concentrations are elevated in the blood or urine of patients with breast, prostate or bladder cancer. These cancers are frequently associated with cancer pain especially after bone metastasis. It is well known that transient receptor potential vanilloid receptor 1 (TRPV1) participates in cancer pain. The present study aims to demonstrate that the tumor tissue-derived endogenous formaldehyde induces bone cancer pain via TRPV1 activation under tumor acidic environment. Methodology/Principal Findings Endogenous formaldehyde concentration increased significantly in the cultured breast cancer cell lines in vitro, in the bone marrow of breast MRMT-1 bone cancer pain model in rats and in tissues from breast cancer and lung cancer patients in vivo. Low concentrations (1∼5 mM) of formaldehyde induced pain responses in rat via TRPV1 and this pain response could be significantly enhanced by pH 6.0 (mimicking the acidic tumor microenvironment). Formaldehyde at low concentrations (1 mM to 100 mM) induced a concentration-dependent increase of [Ca2+]i in the freshly isolated rat dorsal root ganglion neurons and TRPV1-transfected CHO cells. Furthermore, electrophysiological experiments showed that low concentration formaldehyde-elicited TRPV1 currents could be significantly potentiated by low pH (6.0). TRPV1 antagonists and formaldehyde scavengers attenuated bone cancer pain responses. Conclusions/Significance Our data suggest that cancer tissues directly secrete endogenous formaldehyde, and this formaldehyde at low concentration induces metastatic bone cancer pain through TRPV1 activation especially under tumor acidic environment. PMID:20422007

  8. [Effect of a single dose of zoledronic acid in a case of Paget bone disease].

    PubMed

    Saban, Melina; Fidalgo, Silvina; Díaz, Carlos A; Lutfi, Ruben J

    2010-01-01

    Paget's disease is a chronic disorder of bone remodeling characterized by increase of bone resorption by atypical osteoclasts, followed by rapid increase in bone formation resulting in a disorganized mosaic bone. The biochemical marker for early diagnosis and monitoring is serum alkaline phosphatase (ALP). We report the case of a 90 year old male, with diagnose of Paget's disease. Pamidronate treatment was started orally with partial response, so it was switched to intravenous pamidronate. Pain intensity and FAL levels diminished. The scyntigraphic scan, however, though improved, persisted abnormal. After several years of treatment, with adequate calcium and vitamin D support, the patient presents pain and increase of FAL. We administered intravenous zoledronic acid (4 mg) in a single dose. After this treatment we observed clinical and biochemical remission during four years and a significantly improvement in the scintigraphy. We report a case of Paget's disease, resistant to pamidronate treatment in whom a single dose of zoledronic acid produced clinical and biochemical remission during 4 years and a significant improvement in the scintigraphic scan.

  9. Single dose oral sulindac for acute postoperative pain in adults

    PubMed Central

    Moore, R Andrew; Derry, Sheena; McQuay, Henry J

    2014-01-01

    Background Sulindac is a non-steroidal anti-inflammatory drug (NSAID) licensed for use in rheumatic disease and other musculoskeletal disorders in the UK, and widely available in other countries worldwide. This review sought to evaluate the efficacy and safety of oral sulindac in acute postoperative pain, using clinical studies of patients with established pain, and with outcomes measured primarily over 6 hours using standard methods. This type of study has been used for many decades to establish that drugs have analgesic properties. Objectives To assess the efficacy of single dose oral sulindac in acute postoperative pain, and any associated adverse events. Search methods We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies up to June 2009. Selection criteria Randomised, double-blind, placebo-controlled clinical trials of oral sulindac for relief of acute postoperative pain in adults. Data collection and analysis Two review authors independently assessed trial quality and extracted data. We planned to use area under the “pain relief versus time” curve to derive the proportion of participants with meloxicam experiencing least 50% pain relief over 4 to 6 hours, using validated equations; to use number needed to treat to benefit (NNT); the proportion of participants using rescue analgesia over a specified time period; time to use of rescue analgesia; information on adverse events and withdrawals. Main results No studies were identified by the searches that examined oral sulindac in patients with established postoperative pain. Authors’ conclusions In the absence of evidence of efficacy, at present, for oral sulindac in acute postoperative pain, its use in this indication is not justified. Because trials clearly demonstrating analgesic efficacy in the most basic of acute pain studies is lacking, use in other indications should be evaluated carefully. Given the large number of available drugs of this and similar classes

  10. Reversible bone pain and symmetric bone scan uptake in a dialysis patient treated with cinacalcet: a case report

    PubMed Central

    2010-01-01

    Introduction The medical management of secondary hyperparathyroidism in patients with end-stage renal disease involves a combination of dietary restrictions, phosphate binders, active vitamin D analogs, and calcimimetics. Case presentation We report the case of a 36-year-old Hispanic dialysis patient, originally from Cuba and now residing in the USA, who developed severe bone pain and muscle twitching after starting low dose cinacalcet, despite normal pre-dialysis ionized calcium and elevated parathyroid hormone. The clinical symptoms correlated with increased symmetrical uptake on bone scan that resolved rapidly upon discontinuation of cinacalcet. Conclusion Cinacalcet may induce severe bone pain and a unique bone scan uptake pattern in hemodialysis patients. PMID:20576153

  11. Single dose oral fenoprofen for acute postoperative pain in adults

    PubMed Central

    Traa, Maria X; Derry, Sheena; Moore, R Andrew

    2014-01-01

    Background Fenoprofen is a non-steroidal anti-inflammatory drug (NSAID), available in several different countries, but not widely used. Objectives To assess the efficacy of single dose oral fenoprofen in acute postoperative pain, and associated adverse events. Search methods We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to December 2010. Selection criteria Single oral dose, randomised, double-blind, placebo-controlled trials of fenoprofen for relief of established moderate to severe postoperative pain in adults. Data collection and analysis Studies were assessed for methodological quality and data extracted by two review authors independently. Summed total pain relief (TOTPAR) or pain intensity difference (SPID) over 4 to 6 hours was used to calculate the number of participants achieving at least 50% pain relief. These derived results were used to calculate, with 95% confidence intervals, the relative benefit compared to placebo, and the number needed to treat (NNT) for one participant to experience at least 50% pain relief over 4 to 6 hours. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals was collected. Main results Five studies (696 participants) met the inclusion criteria; 24 participants were treated with fenoprofen 12.5 mg, 23 with fenoprofen 25 mg, 79 with fenoprofen 50 mg, 78 with fenoprofen 100 mg, 146 with fenoprofen 200 mg, 55 with fenoprofen 300 mg, 43 with zomepirac 100 mg, 30 with morphine 8 mg, 77 with codeine 60 mg, and 141 with placebo. Participants had pain following third molar extraction, laparoscopy, minor day surgery and episiotomy. The NNT for at least 50% pain relief over 4 to 6 hours with a single dose of fenoprofen 200 mg compared to placebo was 2.3 (1.9 to 3.0). There were insufficient data to analyse other doses or active comparators

  12. Single dose oral diflunisal for acute postoperative pain in adults

    PubMed Central

    Wasey, Jack O; Derry, Sheena; Moore, R Andrew; McQuay, Henry J

    2014-01-01

    Background Diflunisal is a long-acting non-steroidal anti-inflammatory drug (NSAID) most commonly used to treat acute postoperative pain or chronic joint pain from osteoarthritis and rheumatoid arthritis. This review analyses the effectiveness and harm of different doses of diflunisal in the context of moderate to severe postoperative pain. Objectives To assess efficacy, duration of action, and associated adverse events of single dose oral diflunisal in acute postoperative pain in adults. Search methods We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to January 2010. Selection criteria Randomised, double blind, placebo-controlled trials of single dose orally administered diflunisal in adults with moderate to severe acute postoperative pain. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk and number-needed-to-treat-to-benefit (NNT) were calculated. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals were collected. Main results Nine studies in dental, orthopedic and gynaecological surgery met the inclusion criteria, testing doses of diflunisal from 125 mg to 1000 mg. For diflunisal 1000 mg, the NNT for at least 50% pain relief over 4 to 6 hours was 2.1 (1.8 to 2.6) (6 studies, 391 participants); the NNT to prevent remedication within 6 hours was 1.9 (1.7 to 2.3), and within 12 hours was 2.2 (1.9 to 2.7) (6 studies, 409 participants). More participants experienced adverse events with diflunisal 100 mg than with placebo, but none were serious or led to withdrawal. For diflunisal 500 mg, the NNT for at least 50% pain relief

  13. Effectiveness of Reirradiation for Painful Bone Metastases: A Systematic Review and Meta-Analysis

    SciTech Connect

    Huisman, Merel; Bosch, Maurice A.A.J. van den; Wijlemans, Joost W.; Vulpen, Marco van; Linden, Yvette M. van der; Verkooijen, Helena M.

    2012-09-01

    Purpose: Reirradiation of painful bone metastases in nonresponders or patients with recurrent pain after initial response is performed in up to 42% of patients initially treated with radiotherapy. Literature on the effect of reirradiation for pain control in those patients is scarce. In this systematic review and meta-analysis, we quantify the effectiveness of reirradiation for achieving pain control in patients with painful bone metastases. Methods and Materials: A free text search was performed to identify eligible studies using the MEDLINE, EMBASE, and the Cochrane Collaboration library electronic databases. After study selection and quality assessment, a pooled estimate was calculated for overall pain response for reirradiation of metastatic bone pain. Results: Our literature search identified 707 titles, of which 10 articles were selected for systematic review and seven entered the meta-analysis. Overall study quality was mediocre. Of the 2,694 patients initially treated for metastatic bone pain, 527 (20%) patients underwent reirradiation. Overall, a pain response after reirradiation was achieved in 58% of patients (pooled overall response rate 0.58, 95% confidence interval = 0.49-0.67). There was a substantial between-study heterogeneity (I{sup 2} = 63.3%, p = 0.01) because of clinical and methodological differences between studies. Conclusions: Reirradiation of painful bone metastases is effective in terms of pain relief for a small majority of patients; approximately 40% of patients do not benefit from reirradiation. Although the validity of results is limited, this meta-analysis provides a comprehensive overview and the most quantitative estimate of reirradiation effectiveness to date.

  14. Debate: single-fraction treatment should be standard in the retreatment of uncomplicated bone metastases.

    PubMed

    Tsang, Derek S; Yau, Vivian; Raziee, Hamid; Niglas, Mark; Soliman, Hany; Chow, Edward; Tsao, May

    2015-10-01

    There is controversy surrounding the optimal radiotherapy dose-fractionation for retreatment of painful bone metastases. Two commonly used regimens are 8 Gy in a single-fraction or 20 Gy in five or eight fractions. Randomized evidence, including the NCIC SC.20 randomized clinical trial, has failed to standardize clinical practice. Practitioners who use single-fraction regimens cite patient convenience, fewer acute adverse effects, and better cost-effectiveness. Practitioners who prefer multiple fractions raise questions about the interpretation of data that justifies single-fraction treatment, and the possibility that single-fraction treatment may provide inferior pain relief. Given this clinical controversy, should single-fraction irradiation be standard in retreatment of uncomplicated bone metastases? In this article, two teams debate both sides of the argument with commentary to summarize the relevant issues. The conclusion from the debate is that the "standard" treatment should be individualized to the patient with shared-decision making between the oncologist, patient and family members. In a cancer patient with poor performance status and short life expectancy, single-fraction repeat radiotherapy may be preferred; in a patient with a prolonged disease course, perhaps multiple fraction retreatments would be preferred. The choice between different fractionation schemes depends on an assessment of individual patient factors, tumour factors and unique patient circumstances.

  15. ‘Who’, ‘when’ and ‘how’ in re-irradiation of recurrent painful bone metastases

    PubMed Central

    Mok, Florence; Li, Kenneth; Yeung, Rebecca; Wong, Kam-Hung; Yu, Brian; Wong, Erin; Bedard, Gillian; Chow, Edward

    2013-01-01

    Re-irradiation of painful bony metastases is increasingly performed since patients are receiving better systemic treatments and having longer life expectancy, and may also be due to the increase use of initial single fraction radiotherapy. However, randomized control trial on the efficacy of re-irradiation is lacking. A recent meta-analysis concluded with a 58% response rate for pain relief by re-irradiation of symptomatic bone metastases. In this review, the effectiveness of re-irradiation in terms of clinical and economical aspects, and clinical questions on who, when, and how to re-irradiate would be discussed. A brief review of other treatment options and comparison with re-irradiation of bone metastases would be performed. PMID:26909270

  16. Single dose oral piroxicam for acute postoperative pain

    PubMed Central

    Moore, R Andrew; Edwards, Jayne; Loke, Yoon; Derry, Sheena; McQuay, Henry J

    2014-01-01

    Background This is an updated version of the original Cochrane review published in Issue 2, 2000. Piroxicam is a non-steroidal anti-inflammatory drug (NSAID) with analgesic properties, and is used mainly for treating rheumatic disorders. Some drugs have been directly compared against each other within a trial setting to determine their relative efficacies, whereas other have not. It is possible, however, to compare analgesics indirectly by examining the effectiveness of each drug against placebo when used in similar clinical situations. Objectives To determine the analgesic efficacy and adverse effects of single-dose piroxicam compared with placebo in moderate to severe postoperative pain. To compare the effects of piroxicam with other analgesics. Search methods Published studies were identified from systematic searching of MEDLINE, Biological Abstracts, EMBASE, CENTRAL and the Oxford Pain Relief Database in December 2007. Additional studies were identified from the reference lists of retrieved reports. Selection criteria The following inclusion criteria were used: full journal publication, randomised placebo controlled trial, double-blind design, adult participants, postoperative pain of moderate to severe intensity at the baseline assessment, postoperative administration of oral or intramuscular piroxicam. Data collection and analysis Summed pain intensity and pain relief data were extracted and converted into dichotomous information to yield the number of participants obtaining at least 50% pain relief. This was used to calculate estimates of relative benefit and number-needed-to-treat-to-benefit (NNT) for one participant to obtain at least 50% pain relief. Information was collected on adverse effects and estimates of relative risk and number-needed-to-treat-to-harm (NNH) were calculated. Main results In this update no further studies were found. The original search identified three studies (141 participants) which compared oral piroxicam 20 mg with placebo and

  17. Analgesic effects of capsazepine and resiniferatoxin on bone cancer pain in mice.

    PubMed

    Menéndez, Luis; Juárez, Lucía; García, Eva; García-Suárez, Olivia; Hidalgo, Agustín; Baamonde, Ana

    2006-01-23

    In the present paper, we describe the analgesic effects induced by the transient receptor potential vanilloid type 1 (TRPV1) antagonist, capsazepine, and the TRPV1 agonist, resiniferatoxin, on the thermal hyperalgesia induced by the presence of a tibial osteosarcoma or an inflammatory process in mice. The administration of capsazepine abolished the osteosarcoma-induced hyperalgesia at a dose range (3-10 mg/kg; s.c.) ineffective to inhibit the hyperalgesia elicited by the intraplantar administration of complete Freund's adjuvant (CFA). In contrast, the administration of resiniferatoxin (0.01-0.1 mg/kg; s.c.) inhibited both the osteosarcoma- and the CFA-induced hyperalgesia. Remarkably, a single dose of resiniferatoxin abolished the osteosarcoma-induced hyperalgesia for several days and completely prevented the instauration of thermal hyperalgesia when administered at the initial stages of osteosarcoma development. The potential of drugs acting through TRPV1 for the management of some types of bone cancer pain is proposed.

  18. Bone Marrow Aspiration: A Randomized Controlled Trial Assessing the Quality of Bone Marrow Specimens Using Slow and Rapid Aspiration Techniques and Evaluating Pain Intensity.

    PubMed

    Grønkjær, Mette; Hasselgren, Connie F; Østergaard, Anne Sofie L; Johansen, Preben; Korup, June; Bøgsted, Martin; Bilgrau, Anders E; Jensen, Paw

    2016-01-01

    Bone marrow aspiration (BMA) is an essential procedure in the examination of hematological disorders, but there is limited evidence as to whether the aspiration rate affects specimen quality. We aimed to assess the specimen quality and pain intensity using slow (S-technique) or rapid (R-technique) aspiration. This was a single-center, prospective, randomized patient- and assessor-blinded study of 482 patients scheduled for BMA. Specimen quality was evaluated by grading bone marrow (BM) cellularity and counting the number of marrow particles. Pain was assessed using a visual analog scale (VAS). We found a significant difference between the 2 groups with regard to the quality of specimens. For cellularity, the odds ratio (OR) for having a poor quality aspirate using the S-technique versus the R-technique was 3.05 [confidence interval (CI) 1.79-5.31]. For BM particles, the quality of specimens with the S-technique proved to be poor compared with the R-technique (OR 2.52; CI 1.51-4.28). We found a statistically significant difference of 1 VAS point (p < 0.001) of the median pain intensity in favor of the S-technique. Even though the pain intensity is significantly higher with the R-technique, the median difference is relatively small. We propose that the R-technique is preferable to the S-technique due to better specimen quality. © 2015 S. Karger AG, Basel.

  19. The management of painful bone metastases with an emphasis on radionuclide therapy.

    PubMed Central

    Hillegonds, Darren J.; Franklin, Stephen; Shelton, David K.; Vijayakumar, Srinivasan; Vijayakumar, Vani

    2007-01-01

    OBJECTIVE: This review provides an update on the management of painful bone metastases, with an emphasis on radionuclide therapy, and introduces oligometastases and quantitative imaging evaluations for clinical trials. METHODS: The current use of radionuclides, alone and in combination with chemotherapy and radiation therapy for painful bone metastases, is discussed, including toxicity, cost and overall outcomes. RESULTS: Radionuclide therapy is shown to be a useful and cost-effective means of alleviating bone pain in metastatic disease and may be more effective when combined with chemotherapy, bisphosphonates and radiation therapy. Early use of radionuclides in pain therapy may limit cancer progression by inhibiting oligometastases development. Thus, radionuclides can significantly decrease patient morbidity, prolong patient survival, and may decrease the occurrence of new bone metastases. CONCLUSION: Palliative pain therapy is critical for effectively managing bone metastases, with treatment options including analgesics, external beam radiotherapy, chemotherapy and radionuclides. Radionuclide therapy is underutilized. Recent studies using radionuclides with chemotherapy and bisphosponates, or using newer radionuclides or combinations of radionuclides and treatment paradigms (e.g., higher activities, repetitive or cyclic administration, chemo sensitization, chemo supplementation), are encouraging. A comprehensive, inter-disciplinary clinical approach is needed. Clinical collaborations will optimize radionuclide therapy for pain palliation and increase awareness of its benefits. PMID:17668645

  20. Feasibility study of Transcutaneous Electrical Nerve Stimulation (TENS) for cancer bone pain.

    PubMed

    Bennett, Michael I; Johnson, Mark I; Brown, Sarah R; Radford, Helen; Brown, Julia M; Searle, Robert D

    2010-04-01

    This multicenter study assessed the feasibility of conducting a phase III trial of transcutaneous electrical nerve stimulation (TENS) in patients with cancer bone pain recruited from palliative care services. Eligible patients received active and placebo TENS for 1 hour at site of pain in a randomized crossover design; median interval between applications 3 days. Responses assessed at 30 and 60 minutes included numerical and verbal ratings of pain at rest and on movement, and pain relief. Recruitment, tolerability, adverse events, and effectiveness of blinding were also evaluated. Twenty-four patients were randomised and 19 completed both applications. The intervention was well tolerated. Five patients withdrew: 3 due to deteriorating performance status, and 2 due to increased pain (1 each following active and placebo TENS). Confidence interval estimation around the differences in outcomes between active and placebo TENS suggests that TENS has the potential to decrease pain on movement more than pain on rest. Nine patients did not consider that a placebo was used; the remaining 10 correctly identified placebo TENS. Feasibility studies are important in palliative care prior to undertaking clinical trials. Our findings suggest that further work is required on recruitment strategies and refining the control arm before evaluating TENS in cancer bone pain. Cancer bone pain is common and severe, and partly mediated by hyperexcitability. Animal studies suggest that Transcutaneous Electrical Nerve Stimulation can reduce hyperalgesia. This study examined the feasibility of evaluating TENS in patients with cancer bone pain in order to optimize methods before a phase III trial. Copyright 2010 American Pain Society. Published by Elsevier Inc. All rights reserved.

  1. Expedited Delivery of Pain Medication for Long-Bone Fractures Using an Intranasal Fentanyl Clinical Pathway.

    PubMed

    Schacherer, Nicole Marie; Erikson Ramirez, Dana; Frazier, Steven Barron; Perkins, Amy M

    2015-08-01

    This study aims to determine whether a pathway designed to facilitate the use of intranasal (IN) fentanyl for long-bone fractures will expedite the delivery of pain medication, decrease the total length of emergency department (ED) stay, and provide faster analgesia compared with intravenous (IV) morphine. A pain pathway for IN fentanyl in long-bone fractures was instituted in our ED in July 2011. We performed a retrospective and prospective chart review of patients aged 3 to 21 years who presented to the ED with a clinically suspected long-bone fracture and either received IV morphine or were placed on IN fentanyl pain pathway. A total of 94 patients met our inclusion criteria; 71 received IV morphine, and 23 received IN fentanyl, per pathway protocol. The mean length of time to pain medication administration was statistically significantly faster for IN fentanyl (37 minutes) than for IV morphine (62 minutes) (P = 0.002). The mean total length of stay for patients who received IN fentanyl versus patients who received IV morphine was not statistically significantly different after excluding patients who needed reduction or surgery. Effectiveness of pain control was not statistically significantly different between the IN fentanyl group and the IV morphine group. Use of the IN fentanyl pain pathway significantly decreases time to pain medication administration in pediatric patients with suspected long-bone fractures.

  2. Increased bone formation in a rabbit long-bone defect model after single local and single systemic application of erythropoietin.

    PubMed

    Omlor, Georg W; Kleinschmidt, Kerstin; Gantz, Simone; Speicher, Anja; Guehring, Thorsten; Richter, Wiltrud

    2016-08-01

    Background and purpose - Delayed bone healing with non-union is a common problem. Further options to increase bone healing together with surgery are needed. We therefore evaluated a 1-dose single application of erythropoietin (EPO), applied either locally to the defect or systemically during surgery, in a critical-size rabbit long-bone defect. Material and methods - 19 New Zealand White rabbits received a 15-mm defect in the radius diaphysis. An absorbable gelatin sponge was soaked with saline (control group and systemic treatment group) or EPO (local treatment group) and implanted into the gap. The systemic treatment group received EPO subcutaneously. In vivo micro-CT analysis was performed 4, 8, and 12 weeks postoperatively. Vascularization was evaluated histologically. Results - Semiquantitative histomorphometric and radiological evaluation showed increased bone formation (2.3- to 2.5-fold) in both treatment groups after 12 weeks compared to the controls. Quantitative determination of bone volume and tissue volume showed superior bone healing after EPO treatment at all follow-up time points, with the highest values after 12 weeks in locally treated animals (3.0- to 3.4-fold). More vascularization was found in both EPO treatment groups. Interpretation - Initial single dosing with EPO was sufficient to increase bone healing substantially after 12 weeks of follow-up. Local application inside the defect was most effective, and it can be administered directly during surgery. Apart from effects on ossification, systemic and local EPO treatment leads to increased callus vascularization.

  3. Increased bone formation in a rabbit long-bone defect model after single local and single systemic application of erythropoietin

    PubMed Central

    Omlor, Georg W; Kleinschmidt, Kerstin; Gantz, Simone; Speicher, Anja; Guehring, Thorsten; Richter, Wiltrud

    2016-01-01

    Background and purpose Delayed bone healing with non-union is a common problem. Further options to increase bone healing together with surgery are needed. We therefore evaluated a 1-dose single application of erythropoietin (EPO), applied either locally to the defect or systemically during surgery, in a critical-size rabbit long-bone defect. Material and methods 19 New Zealand White rabbits received a 15-mm defect in the radius diaphysis. An absorbable gelatin sponge was soaked with saline (control group and systemic treatment group) or EPO (local treatment group) and implanted into the gap. The systemic treatment group received EPO subcutaneously. In vivo micro-CT analysis was performed 4, 8, and 12 weeks postoperatively. Vascularization was evaluated histologically. Results Semiquantitative histomorphometric and radiological evaluation showed increased bone formation (2.3- to 2.5-fold) in both treatment groups after 12 weeks compared to the controls. Quantitative determination of bone volume and tissue volume showed superior bone healing after EPO treatment at all follow-up time points, with the highest values after 12 weeks in locally treated animals (3.0- to 3.4-fold). More vascularization was found in both EPO treatment groups. Interpretation Initial single dosing with EPO was sufficient to increase bone healing substantially after 12 weeks of follow-up. Local application inside the defect was most effective, and it can be administered directly during surgery. Apart from effects on ossification, systemic and local EPO treatment leads to increased callus vascularization. PMID:27348783

  4. Single dose oral dihydrocodeine for acute postoperative pain

    PubMed Central

    Moore, R Andrew; Edwards, Jayne; Derry, Sheena; McQuay, Henry J

    2014-01-01

    Background This is an updated version of the original Cochrane review published in Issue 2, 2000. Dihydrocodeine is a synthetic opioid analgesic developed in the early 1900s. Its structure and pharmacokinetics are similar to that of codeine and it is used for the treatment of postoperative pain or as an antitussive. It is becoming increasingly important to assess the relative efficacy and harm caused by different treatments. Relative efficacy can be determined when an analgesic is compared with control under similar clinical circumstances. Objectives To quantitatively assess the analgesic efficacy and adverse effects of single-dose dihydrocodeine compared with placebo in randomised trials in moderate to severe postoperative pain. Search methods Published reports were identified from electronic databases (MEDLINE, EMBASE, CENTRAL, the Oxford Pain Relief Database in December 2007, the original search was conducted in October 1999). Additional studies were identified from the reference lists of retrieved reports. Selection criteria Inclusion criteria: full journal publication, clinical trial, random allocation of participants to treatment groups, double blind design, adult participants, baseline pain of moderate to severe intensity, postoperative administration of study drugs, treatment arms which included dihydrocodeine and placebo and either oral or injected (intramuscular or intravenous) administration of study drugs. Data collection and analysis Data collection and analysis: summed pain intensity and pain relief data over four to six hours were extracted and converted into dichotomous information to yield the number of participants obtaining at least 50% pain relief. This was used to calculate relative benefit and number-needed-to-treat-to-benefit (NNT) for one participant to obtain at least 50% pain relief. Single-dose adverse effect data were collected and used to calculate relative risk and number-needed-to-treat-to-harm (NNH). Main results Fifty-two reports

  5. The incidence of neuropathic pain in bone metastases patients referred for palliative radiotherapy.

    PubMed

    Lechner, Breanne; Chow, Selina; Chow, Ronald; Zhang, Liying; Tsao, May; Danjoux, Cyril; Barnes, Elizabeth; DeAngelis, Carlo; Vuong, Sherlyn; Ganesh, Vithusha; Chow, Edward

    2016-03-01

    To estimate the prevalence of neuropathic pain in patients with symptomatic bone metastases referred for palliative radiotherapy. A prospective study of patients with symptomatic bone metastases was conducted. Patients referred for palliative radiotherapy completed the Self-Reported Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) questionnaire to assess for neuropathic pain. Patient demographics, medication use, and radiotherapy prescribed were collected. Statistical approaches to identify relationships between the presence of neuropathic and other patient factors were conducted. 62 patients completed the S-LANSS and 16 (25.8%) patients had a score suggesting neuropathic pain. Fifty-nine (95.2%) patients received radiotherapy with total of 81 sites treated, the most common sites were spine and pelvis. No statistically significant difference in fractionation was found between patients with and without neuropathic pain. Of the 16 patients with neuropathic pain, only 2 were receiving a neuropathic specific analgesic. No significant difference between demographic factors or radiation treatments between patients with and without neuropathic pain was found. There was no significant difference in worst pain score between these two groups. Pain with neuropathic features remains prevalent in a population of patients referred for palliative radiotherapy. More frequent prescription of pain medications targeting neuropathic pain may be warranted in this patient population. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Topical Treatment with Xiaozheng Zhitong Paste (XZP) Alleviates Bone Destruction and Bone Cancer Pain in a Rat Model of Prostate Cancer-Induced Bone Pain by Modulating the RANKL/RANK/OPG Signaling

    PubMed Central

    Bao, Yanju; Gao, Yebo; Du, Maobo; Hou, Wei; Yang, Liping; Kong, Xiangying; Zheng, Honggang; Li, Weidong; Hua, Baojin

    2015-01-01

    To explore the effects and mechanisms of Xiaozheng Zhitong Paste (XZP) on bone cancer pain, Wistar rats were inoculated with vehicle or prostate cancer PC-3 into the tibia bone and treated topically with inert paste, XZP at 15.75, 31.5, or 63 g/kg twice per day for 21 days. Their bone structural damage, nociceptive behaviors, bone osteoclast and osteoblast activity, and the levels of OPG, RANL, RNAK, PTHrP, IGF-1, M-CSF, IL-8, and TNF-α were examined. In comparison with that in the placebo group, significantly reduced numbers of invaded cancer cells, decreased levels of bone damage and mechanical threshold and paw withdrawal latency, lower levels of serum TRACP5b, ICTP, PINP, and BAP, and less levels of bone osteoblast and osteoclast activity were detected in the XZP-treated rats (P<0.05). Moreover, significantly increased levels of bone OPG but significantly decreased levels of RANL, RNAK, PTHrP, IGF-1, M-CSF, IL-8, and TNF-α were detected in the XZP-treated rats (P<0.05 for all). Together, XZP treatment significantly mitigated the cancer-induced bone damage and bone osteoclast and osteoblast activity and alleviated prostate cancer-induced bone pain by modulating the RANKL/RANK/OPG pathway and bone cancer-related inflammation in rats. PMID:25691907

  7. Impact of iliac crest bone graft harvesting on fusion rates and postoperative pain during instrumented posterolateral lumbar fusion

    PubMed Central

    Triantafyllopoulos, Dimitrios; Kosmopoulos, Victor; Stafylas, Kosmas

    2007-01-01

    This study aims to evaluate the influence of bone harvesting on postoperative pain and fusion rates. Group 1 patients received iliac crest bone graft (ICBG) either alone or augmented with local bone. Group 2 received only local bone. No statistical significance was found in radiological union or in the Oswestry Disability Index scores. Visual Analogue Scale scores showed less pain in group 2. Logistic regression showed no correlation between residual pain and occurrence of fusion. Harvesting ICBG did not appear to increase fusion rates and no relation was found between radiological non-union and pain. PMID:17724591

  8. Dual Therapeutic Action of a Neutralizing Anti-FGF2 Aptamer in Bone Disease and Bone Cancer Pain

    PubMed Central

    Jin, Ling; Nonaka, Yosuke; Miyakawa, Shin; Fujiwara, Masatoshi; Nakamura, Yoshikazu

    2016-01-01

    Fibroblast growth factor 2 (FGF2) plays a crucial role in bone remodeling and disease progression. However, the potential of FGF2 antagonists for treatment of patients with bone diseases has not yet been explored. Therefore, we generated a novel RNA aptamer, APT-F2, specific for human FGF2 and characterized its properties in vitro and in vivo. APT-F2 blocked binding of FGF2 to each of its four cellular receptors, inhibited FGF2-induced downstream signaling and cells proliferation, and restored osteoblast differentiation blocked by FGF2. APT-F2P, a PEGylated form of APT-F2, effectively blocked the bone disruption in mouse and rat models of arthritis and osteoporosis. Treatment with APT-F2P also exerted a strong analgesic effect, equivalent to morphine, in a mouse model of bone cancer pain. These findings demonstrated dual therapeutic action of APT-F2P in bone diseases and pain, providing a promising approach to the treatment of bone diseases. PMID:27506449

  9. Pain and analgesic use associated with skeletal-related events in patients with advanced cancer and bone metastases.

    PubMed

    von Moos, Roger; Body, Jean-Jacques; Egerdie, Blair; Stopeck, Alison; Brown, Janet; Fallowfield, Lesley; Patrick, Donald L; Cleeland, Charles; Damyanov, Danail; Palazzo, Felipe Salvador; Marx, Gavin; Zhou, Ying; Braun, Ada; Balakumaran, Arun; Qian, Yi

    2016-03-01

    Bone metastases secondary to solid tumors increase the risk of skeletal-related events (SREs), including the occurrence of pathological fracture (PF), radiation to bone (RB), surgery to bone (SB), and spinal cord compression (SCC). The aim of this study was to evaluate the impact of SREs on patients' pain, analgesic use, and pain interference with daily functioning. Data were combined from patients with solid tumors and bone metastases who received denosumab or zoledronic acid across three identically designed phase 3 trials (N = 5543). Pain severity (worst pain) and pain interference were assessed using the Brief Pain Inventory at baseline and each monthly visit. Analgesic use was quantified using the Analgesic Quantification Algorithm. The proportion of patients with moderate/severe pain and strong opioid use generally increased in the 6 months preceding an SRE and remained elevated, while they remained relatively consistent over time in patients without an SRE. Regression analysis indicated that all SRE types were significantly associated with an increased risk of progression to moderate/severe pain and strong opioid use. PF, RB, and SCC were associated with significantly greater risk of pain interference overall. Results were similar for pain interference with emotional well-being. All SRE types were associated with significantly greater risk of pain interference with physical function. SREs are associated with increased pain and analgesic use in patients with bone metastases. Treatments that prevent SREs may decrease pain and the need for opioid analgesics and reduce the impact of pain on daily functioning.

  10. Pegfilgrastim use and bone pain: a cohort study of community-based cancer patients.

    PubMed

    Pawloski, Pamala A; Larsen, Mitch; Thoresen, Assel; Giordana, Monique D

    2016-06-01

    Bone pain is a common adverse effect of the granulocyte colony-stimulating factors filgrastim and pegfilgrastim. However, the incidence of reported bone pain varies and therapies to mitigate this adverse effect are limited to case reports and one randomized controlled trial. The purpose of this study was to describe pegfilgrastim use, the incidence and treatment of bone pain, and rate of severe or febrile neutropenia among cancer patients receiving pegfilgrastim at a metropolitan, hospital-based, community cancer center. This retrospective chart review included the first 100 adult oncology patients who received at least one dose of pegfilgrastim from 1 January 2012 to 31 December 2012. Descriptive analyses were used to evaluate the primary and secondary outcomes. Of the identified cases, 69 cancer patients were evaluable. Most patients (74%) received pegfilgrastim for primary prophylaxis. Pegfilgrastim-associated bone pain occurred in 19% and loratadine was the most common medication used to treat it. Among the patients who received pegfilgrastim for primary prophylaxis, 8% were hospitalized for febrile neutropenia. Among those hospitalized for febrile neutropenia, 64% had not received pegfilgrastim for primary prophylaxis. Pegfilgrastim is commonly used for primary prophylaxis during the first cycle of chemotherapy. Hospitalizations for febrile neutropenia occurred most commonly among patients without primary prophylaxis. Pegfilgrastim-associated bone pain occurred in a similar percentage, as reported in randomized controlled trials but less than that reported by survey. Loratadine was the most commonly employed medication to mitigate this adverse effect. © The Author(s) 2015.

  11. Bone scan usefulness in patients with painful hip or knee prosthesis: 10 situations that can cause pain, other than loosening and infection.

    PubMed

    Vaz, Sofia; Ferreira, Teresa C; Salgado, Lucília; Paycha, Frédéric

    2017-02-01

    In recent years, with the higher median life expectancy, the number of hip and knee replacements has increased. Clinical examination and morphological studies are essential to evaluate patients with a painful arthroplasty. Nuclear medicine examinations also play an important role, their main usefulness being the exclusion of prosthesis complications. Nevertheless, conventional examinations, namely bone scan and white blood cell scintigraphy, can also identify complications, such as loosening and infection. This study describes the normal and pathologic patterns of a bone scan and exemplifies ten common situations that can cause pain in patients with hip or knee arthroplasty, other than loosening and infection, which can be disclosed on a bone scintigraphy. The ten situations that should be considered and looked for when analysing a bone scan are: referred pain, patellofemoral pain syndrome, fractures, fissures, abscess/haematoma, bone insert behaviour, heterotopic ossification, greater trochanter pseudarthrosis, osteoarthritis extension in a knee with an unicompartmental prosthesis, and systemic disease with bone involvement.

  12. Single dose oral tenoxicam for acute postoperative pain in adults

    PubMed Central

    Moore, Owen A; McIntyre, Mairead; Moore, R Andrew; Derry, Sheena; McQuay, Henry J

    2014-01-01

    Background Tenoxicam is a non-steroidal anti-inflammatory drug (NSAID) licensed for use in rheumatic disease and other musculoskeletal disorders in the UK, and is widely available in other countries worldwide. This review sought to evaluate the efficacy and safety of oral tenoxicam in acute postoperative pain, using clinical studies of patients with established pain, and with outcomes measured primarily over 6 hours using standard methods. This type of study has been used for many decades to establish that drugs have analgesic properties. Objectives To assess the efficacy of single dose oral tenoxicam in acute postoperative pain, and any associated adverse events. Search methods We searched The Cochrane Library (Issue 1, 2009), MEDLINE (March 2009); EMBASE via Ovid (March 2009); the Oxford Pain Relief Database. Selection criteria Randomised, double-blind, placebo-controlled clinical trials of oral tenoxicam for relief of acute postoperative pain in adults. Data collection and analysis Two review authors independently assessed trial quality and extracted data. The area under the “pain relief versus time” curve was used to derive the proportion of participants with tenoxicam experiencing least 50% pain relief over 4 to 6 hours, using validated equations. The number needed to treat to benefit (NNT) was calculated using 95% confidence intervals (CI). The proportion of participants using rescue analgesia over a specified time period, and time to use of rescue analgesia, were sought as additional measures of efficacy. Information on adverse events and withdrawals was also collected. Main results Not one of sixteen studies identified by the searches and examined in detail studied oral tenoxicam in patients with established postoperative pain and therefore no results are available. Authors’ conclusions In the absence of evidence of efficacy for oral tenoxicam in acute postoperative pain, its use in this indication is not justified at present. Because trials clearly

  13. Clinical utility of bone scintigraphy in patients with limb pain of suspected musculoskeletal origin

    PubMed Central

    Ferrari, Robert

    2015-01-01

    Objective To determine the clinical utility of bone scintigraphy in patients with limb pain of suspected musculoskeletal origin. Material and Methods All patients aged ≥18 years who were referred for diagnosis and management of limb pain were diagnosed on the basis of history, physical examination, and investigations excluding bone scintigraphy. After the presumptive diagnosis was made (the pre-test diagnosis), all subjects underwent bone scintigraphy, or if they had a previous bone scintigram for their pain condition, the results of that scintigram were reviewed. Then, the pre-test diagnosis was reviewed in light of the bone scintigraphy findings and repeat clinical assessment as needed. The post-test diagnosis was considered either as unchanged diagnosis or changed diagnosis for the region or regions of interest. Results There were 118 females (54.8%) and 97 males (45.2%). The mean age of the entire group was 36±8.1 years (range: 18–87 years). The mean duration of the symptoms was 17.4±11.2 months (range: 1–264 months). Of the 215 subjects, 212 had a bone scintigram. Of these 212 subjects, none had a changed diagnosis. Conclusion In the evaluation of limb pain of suspected musculoskeletal origin, scintigraphy is unlikely to alter the pre-test diagnosis or affect treatment decisions after history, physical examination, and non-scintigraphic investigations. The clinical utility of scinitigraphy in this setting is low. PMID:27708914

  14. Risedronate decreases bone resorption and improves low back pain in postmenopausal osteoporosis patients without vertebral fractures.

    PubMed

    Ohtori, Seiji; Akazawa, Tsutomu; Murata, Yasuaki; Kinoshita, Tomoaki; Yamashita, Masaomi; Nakagawa, Koichi; Inoue, Gen; Nakamura, Junichi; Orita, Sumihisa; Ochiai, Nobuyasu; Kishida, Shunji; Takaso, Masashi; Eguchi, Yawara; Yamauchi, Kazuyo; Suzuki, Munetaka; Aoki, Yasuchika; Takahashi, Kazuhisa

    2010-02-01

    Elderly postmenopausal women who have osteoporosis sometimes experience low back pain, however, the relationship between low back pain and osteoporosis in the absence of vertebral fractures remains unclear. We examined the relationship between bone mineral density (BMD), bone resorption and low back pain in elderly female patients who did not have osteoporotic vertebral fractures. The average BMD was 0.675 g/cm(2) when assessed by dual-energy X-ray absorptiometry (DEXA). Patients were excluded from the study if they had vertebral fractures revealed by radiography, CT scans or MRI. Bisphosphonate (risedronate) was administered for 4 months. The visual analogue scale (VAS) pain score, Roland Morris Disability Questionnaire (RDQ), Short Form-36 (SF-36) questionnaire, BMD and N-terminal telopeptide of type I collagen (NTx; a marker for bone resorption) were examined before and after treatment. DEXA did not increase significantly, but serum and urinary NTx were decreased (-51.4% and -62.0%, respectively) after 4 months of risedronate treatment (p<0.01). The assessment was repeated using the VAS score, RDQ and SF-36, which revealed an improvement after risedronate treatment (p<0.01). A decrease in serum and urinary NTx was associated with improvement of low back pain, suggesting that despite the absence of vertebral fractures, bone resorption due to osteoporosis may cause low back pain. Copyright 2009 Elsevier Ltd. All rights reserved.

  15. Bisphosphonates inhibit pain, bone loss, and inflammation in a rat tibia fracture model of complex regional pain syndrome

    PubMed Central

    Wang, Liping; Guo, Tian-Zhi; Wei, Tzuping; Li, Wen-wu; Shi, Xiaoyou; Clark, J David; Kingery, Wade S

    2016-01-01

    BACKGROUND Bisphosphonates are used to prevent the bone loss and fractures associated with osteoporosis, bone metastases, multiple myeloma, and osteogenis deformans. Distal limb fractures cause regional bone loss with cutaneous inflammation and pain in the injured limb that can develop into complex regional pain syndrome (CRPS). Clinical trials have reported that anti-resorptive bisphosphonates can prevent fracture-induced bone loss, inhibit serum inflammatory cytokine levels, and alleviate CRPS pain. Previously we observed that the inhibition of inflammatory cytokines or adaptive immune responses attenuated the development of pain behavior in a rat fracture model of CRPS and we hypothesized that bisphosphonates could prevent pain behavior, trabecular bone loss, post-fracture cutaneous cytokine up-regulation, and adaptive immune responses in this CRPS model. METHODS Rats underwent tibia fracture and cast immobilization for 4 weeks and were chronically administered either subcutaneously perfused alendronate or oral zoledronate. Behavioral measurements included hindpaw von Frey allodynia, unweighting, warmth, and edema. Bone microarchitecture was measured by uCT and bone cellular activity was evaluated by static and dynamic histomorphometry. Spinal cord Fos immunostaining was performed and skin cytokine (TNF, IL-1, IL-6) and nerve growth factor (NGF) levels were determined by EIA. Skin and sciatic nerve immunoglobulin levels were determined by EIA. RESULTS Tibia fracture rats developed hindpaw allodynia, unweighting, warmth, and edema, increased spinal Fos expression, trabecular bone loss in the lumbar vertebra and bilateral distal femurs as measured by uCT, increased trabecular bone resorption and osteoclast surface with decreased bone formation rates, increased cutaneous inflammatory cytokine and NGF expression and elevated immunocomplex deposition in skin and nerve. Alendronate (60 μg/kg/day s.c.) or zoledronate (3 mg/kg/day p.o.) treatment for 28 days, started

  16. Bisphosphonates Inhibit Pain, Bone Loss, and Inflammation in a Rat Tibia Fracture Model of Complex Regional Pain Syndrome.

    PubMed

    Wang, Liping; Guo, Tian-Zhi; Wei, Tzuping; Li, Wen-Wu; Shi, Xiaoyou; Clark, J David; Kingery, Wade S

    2016-10-01

    Bisphosphonates are used to prevent the bone loss and fractures associated with osteoporosis, bone metastases, multiple myeloma, and osteogenesis deformans. Distal limb fractures cause regional bone loss with cutaneous inflammation and pain in the injured limb that can develop into complex regional pain syndrome (CRPS). Clinical trials have reported that antiresorptive bisphosphonates can prevent fracture-induced bone loss, inhibit serum inflammatory cytokine levels, and alleviate CRPS pain. Previously, we observed that the inhibition of inflammatory cytokines or adaptive immune responses attenuated the development of pain behavior in a rat fracture model of CRPS, and we hypothesized that bisphosphonates could prevent pain behavior, trabecular bone loss, postfracture cutaneous cytokine upregulation, and adaptive immune responses in this CRPS model. Rats underwent tibia fracture and cast immobilization for 4 weeks and were chronically administered either subcutaneously perfused alendronate or oral zoledronate. Behavioral measurements included hindpaw von Frey allodynia, unweighting, warmth, and edema. Bone microarchitecture was measured by microcomputed tomography, and bone cellular activity was evaluated by static and dynamic histomorphometry. Spinal cord Fos immunostaining was performed, and skin cytokine (tumor necrosis factor, interleukin [IL]-1, IL-6) and nerve growth factor (NGF) levels were determined by enzyme immunoassay. Skin and sciatic nerve immunoglobulin levels were determined by enzyme immunoassay. Rats with tibia fractures developed hindpaw allodynia, unweighting, warmth, and edema, increased spinal Fos expression and trabecular bone loss in the lumbar vertebra and bilateral distal femurs as measured by microcomputed tomography, increased trabecular bone resorption and osteoclast surface with decreased bone formation rates, increased cutaneous inflammatory cytokine and NGF expression, and elevated immunocomplex deposition in skin and nerve

  17. Single dose oral paracetamol (acetaminophen) for postoperative pain in adults.

    PubMed

    Toms, Laurence; McQuay, Henry J; Derry, Sheena; Moore, R Andrew

    2008-10-08

    This is an updated version of the original Cochrane review published in Issue 1, 2004 - this original review had been split from a previous title on 'Single dose paracetamol (acetaminophen) with and without codeine for postoperative pain'. The last version of this review concluded that paracetamol is an effective analgesic for postoperative pain, but additional trials have since been published. This review sought to evaluate the efficacy and safety of paracetamol using current data, and to compare the findings with other analgesics evaluated in the same way. To assess the efficacy of single dose oral paracetamol for the treatment of acute postoperative pain. We searched The Cochrane Library, MEDLINE, EMBASE, the Oxford Pain Relief Database and reference lists of articles to update an existing version of the review in July 2008. Randomised, double-blind, placebo-controlled clinical trials of paracetamol for acute postoperative pain in adults. Two review authors independently assessed trial quality and extracted data. Area under the "pain relief versus time" curve was used to derive the proportion of participants with paracetamol or placebo experiencing at least 50% pain relief over four to six hours, using validated equations. Number-needed-to-treat-to-benefit (NNT) was calculated, with 95% confidence intervals (CI). The proportion of participants using rescue analgesia over a specified time period, and time to use, were sought as measures of duration of analgesia. Information on adverse events and withdrawals was also collected. Fifty-one studies, with 5762 participants, were included: 3277 participants were treated with a single oral dose of paracetamol and 2425 with placebo. About half of participants treated with paracetamol at standard doses achieved at least 50% pain relief over four to six hours, compared with about 20% treated with placebo. NNTs for at least 50% pain relief over four to six hours following a single dose of paracetamol were as follows: 500 mg

  18. Orthopedic surgery and bone fracture pain are both significantly attenuated by sustained blockade of nerve growth factor.

    PubMed

    Majuta, Lisa A; Longo, Geraldine; Fealk, Michelle N; McCaffrey, Gwen; Mantyh, Patrick W

    2015-01-01

    The number of patients suffering from postoperative pain due to orthopedic surgery and bone fracture is projected to dramatically increase because the human life span, weight, and involvement in high-activity sports continue to rise worldwide. Joint replacement or bone fracture frequently results in skeletal pain that needs to be adequately controlled for the patient to fully participate in needed physical rehabilitation. Currently, the 2 major therapies used to control skeletal pain are nonsteroidal anti-inflammatory drugs and opiates, both of which have significant unwanted side effects. To assess the efficacy of novel therapies, mouse models of orthopedic and fracture pain were developed and evaluated here. These models, orthopedic surgery pain and bone fracture pain, resulted in skeletal pain-related behaviors that lasted 3 weeks and 8 to 10 weeks, respectively. These skeletal pain behaviors included spontaneous and palpation-induced nocifensive behaviors, dynamic weight bearing, limb use, and voluntary mechanical loading of the injured hind limb. Administration of anti-nerve growth factor before orthopedic surgery or after bone fracture attenuated skeletal pain behaviors by 40% to 70% depending on the end point being assessed. These data suggest that nerve growth factor is involved in driving pain due to orthopedic surgery or bone fracture. These animal models may be useful in developing an understanding of the mechanisms that drive postoperative orthopedic and bone fracture pain and the development of novel therapies to treat these skeletal pains.

  19. Single dose intravenous propacetamol or intravenous paracetamol for postoperative pain.

    PubMed

    Tzortzopoulou, Aikaterini; McNicol, Ewan D; Cepeda, M Soledad; Francia, Marie Belle D; Farhat, Tamman; Schumann, Roman

    2011-10-05

    Paracetamol (acetaminophen) is the most commonly prescribed analgesic for the treatment of acute pain. It may be administered orally or intravenously. The efficacy and safety of intravenous (IV) formulations of paracetamol, IV paracetamol and IV propacetamol, compared with placebo and other analgesics, is unclear. To assess the efficacy and safety of IV formulations of paracetamol for treatment of postoperative pain in both adults and children. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 2), MEDLINE (1950 to May 2010), EMBASE (1980 to 2010, Week 18), LILACS (1992 to May 2010) and reference lists of retrieved articles. Randomized, double-blind, placebo- or active-controlled single dose clinical trials of IV propacetamol or IV paracetamol for acute postoperative pain in adults or children. Two review authors independently assessed the risk of bias and extracted data. We contacted study authors for additional information. We collected adverse event information from the studies. Thirty-six studies (3896 participants) were included. Thirty-seven percent of participants receiving IV propacetamol/paracetamol experienced at least 50% pain relief over four hours compared with 16% of those receiving placebo (number needed to treat to benefit (NNT = 4.0; 95% confidence interval 3.5 to 4.8). The proportion of participants in IV propacetamol/paracetamol groups experiencing at least 50% pain relief diminished over six hours, as reflected in a higher NNT of 5.3 (4.2 to 6.7). Participants receiving IV propacetamol/paracetamol required 30% less opioid over four hours than those receiving placebo. However, this did not translate to a reduction in opioid-induced adverse events.Meta-analysis of efficacy comparisons between IV propacetamol/paracetamol and active comparators (opioids or nonsteroidal anti-inflammatories (NSAIDs)) were either not statistically significant, not clinically significant, or both.Adverse events

  20. Single dose oral lumiracoxib for postoperative pain in adults

    PubMed Central

    Roy, Yvonne M; Derry, Sheena; Moore, R Andrew

    2014-01-01

    Background Lumiracoxib is a selective cyclooxygenase-2 (COX-2) inhibitor. COX-2 inhibitors were developed to avoid COX-1-related gastrointestinal (GI) problems while maintaining the analgesic and anti-inflammatory activity of traditional non-steriodal anti-inflammatory drugs (NSAIDs). Objectives To review the analgesic efficacy, duration of analgesia, and adverse effects of a single oral dose of lumiracoxib for moderate to severe postoperative pain in adults. Search methods We searched Cochrane CENTRAL, MEDLINE, and EMBASE to February 2010. Selection criteria Single oral dose, randomised, double-blind, placebo-controlled trials of lumiracoxib for relief of established moderate to severe postoperative pain in adults. Data collection and analysis Studies were assessed for methodological quality and the data extracted by two review authors independently. Summed total pain relief over six hours (TOTPAR 6) was used to calculate the number of participants achieving at least 50% pain relief. These derived results were used to calculate, with 95% confidence intervals, the relative benefit compared to placebo, and the number needed to treat (NNT) for one participant to experience at least 50% pain relief over six hours. Numbers of participants using rescue medication, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals was collected. Main results In this updated review four studies met the inclusion criteria. In total 366 participants were treated with lumiracoxib 400 mg, 51 with lumiracoxib 100 mg, and 212 with placebo. Active comparators were naproxen 500 mg, rofecoxib 50 mg, celecoxib 200 mg, celecoxib 400 mg, and ibuprofen 400 mg. With lumiracoxib 400 mg 50% of participants had at least 50% pain relief over six hours, compared with 8% given placebo; RB 6.9 (95% CI 4.1 to 12), NNT 2.4 (2.1 to 2.8). Median time to onset of analgesia was shorter for lumiracoxib 400 mg (0.6 to 1.5 hours) than

  1. Effects of Src-kinase inhibition in cancer-induced bone pain

    PubMed Central

    De Felice, Milena; Lambert, Daniel; Holen, Ingunn; Escott, K Jane

    2016-01-01

    Background Bone metastases occur frequently in advanced breast, lung, and prostate cancer, with approximately 70% of patients affected. Pain is a major symptom of bone metastases, and current treatments may be inadequate or have unacceptable side effects. The mechanisms that drive cancer-induced bone pain are not fully understood; however, it is known that there is sensitization of both peripheral bone afferents and central spinal circuits. It is well established that the N-methyl-D-aspartate receptor plays a major role in the pathophysiology of pain hypersensitivity. Inhibition of the non-receptor tyrosine kinase Src controls N-methyl-D-aspartate receptor activity and inhibiting Src reduces the hypersensitivity associated with neuropathic and inflammatory pains. As Src is also implicated in osteoclastic bone resorption, we have investigated if inhibiting Src ameliorates cancer-induced bone pain. We have tested this hypothesis using an orally bioavailable Src inhibitor (saracatinib) in a rat model of cancer-induced bone pain. Results Intra-tibial injection of rat mammary cancer cells (Mammary rat metastasis tumor cells -1), but not vehicle, in rats produced hindpaw hypersensitivity to thermal and mechanical stimuli that was maximal after six days and persisted for at least 13 days postinjection. Daily oral gavage with saracatinib (20 mg/kg) beginning seven days after intra-tibial injection reversed the thermal hyperalgesia but not the mechanical allodynia. The analgesic mechanisms of saracatinib appear to be due to an effect on the nervous system as immunoblotting of L2-5 spinal segments showed that mammary rat metastasis tumor cells-1 injection induced phosphorylation of the GluN1 subunit of the N-methyl-D-aspartate receptor, indicative of receptor activation, and this was reduced by saracatinib. Additionally, histology showed no anti-tumor effect of saracatinib at any dose and no significant effect on bone preservation. Conclusions This is the first

  2. Painful Osteophytes, Ectopic Bone, and Pain in the Malleolar Gutters Following Total Ankle Replacement: Management and Strategies.

    PubMed

    Overley, Benjamin D; Beideman, Thomas C

    2015-10-01

    The development of osteophytes, ectopic bone, or malleolar impingement following total ankle replacement represents common complications that will frequently lead to secondary procedures to relieve painful impingement. Many studies have been conducted to discover the cause of these postoperative impingement syndromes; however, there is a paucity of literature with regard to the prevention, diagnosis, and management of these conditions. The authors discuss the potential causes of formation of osteophytes and ectopic bone formation, as well as malleolar impingement syndromes following primary total ankle replacement with focus placed on diagnosis and management of these complications.

  3. Single dose dipyrone (metamizole) for acute postoperative pain in adults.

    PubMed

    Hearn, Leslie; Derry, Sheena; Moore, R Andrew

    2016-04-20

    Dipyrone (metamizole) is a nonsteroidal anti-inflammatory drug used in some countries to treat pain (postoperative, colic, cancer, and migraine); it is banned in other countries because of an association with life-threatening blood disorders. This review replaces a 2010 Cochrane review that has been withdrawn. To assess the analgesic efficacy and associated adverse events of single dose dipyrone for moderate to severe acute postoperative pain using methods that permit comparison with other analgesics evaluated in standardised trials using almost identical methods and outcomes. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and LILACS to 11 August 2015; the Oxford Pain Relief Database; two clinical trial registries; and the reference lists of articles. We included randomised, double-blind, placebo-controlled trials of single dose dipyrone for relief of established moderate to severe postoperative pain in adults. We accepted oral, rectal, intramuscular, and intravenous routes of administration. Two review authors independently considered studies for inclusion in the review, assessed risk of bias, and extracted data. We used summed total pain relief or pain intensity difference (TOTPAR or SPID) over four to six hours to calculate the number of participants achieving at least 50% pain relief. From derived results, we calculated the risk ratio and number needed to treat for an additional beneficial outcome (NNT), with 95% confidence intervals (CI), for one participant to experience at least 50% pain relief over four to six hours compared to placebo. We looked at use of rescue medication and time to use of rescue medication as additional measures of efficacy. We also looked for information on adverse events and withdrawals. We included eight studies, involving 809 participants, comparing oral dipyrone 500 mg (143 participants), oral dipyrone 1000 mg (57 participants), and intramuscular dipyrone 2000 mg (35 participants) with

  4. The relief of bone pain in primary biliary cirrhosis with calcium infusions

    PubMed Central

    Ajdukiewicz, A. B.; Agnew, J. E.; Byers, P. D.; Wills, M. R.; Sherlock, Sheila

    1974-01-01

    Intravenous calcium infusions produced subjective relief of bone pain in 14 patients with primary biliary cirrhosis. The bone pain had developed despite long-term parenteral vitamin D therapy. The pain returned after two to three months, but a subsequent course of infusions again brought relief. Before treatment satisfactory iliac crest bone biopsies were obtained in 11 of the patients and were normal in seven; two patients had biopsies indicating osteomalacia and two osteoporosis. After treatment a repeat biopsy in one of the patients with osteomalacia showed marked reduction in osteoid. The infusion treatment produced no change in plasma calcium concentration, serum phosphate, or serum alkaline phosphatase. Absorption of oral calcium was also unchanged. PMID:4279816

  5. Single dose oral paracetamol (acetaminophen) for postoperative pain in adults

    PubMed Central

    Toms, Laurence; McQuay, Henry J; Derry, Sheena; Moore, R Andrew

    2014-01-01

    Background This is an updated version of the original Cochrane review published in Issue 1, 2004 - this original review had been split from a previous title on ‘Single dose paracetamol (acetaminophen) with and without codeine for postoperative pain’. The last version of this review concluded that paracetamol is an effective analgesic for postoperative pain, but additional trials have since been published. This review sought to evaluate the efficacy and safety of paracetamol using current data, and to compare the findings with other analgesics evaluated in the same way. Objectives To assess the efficacy of single dose oral paracetamol for the treatment of acute postoperative pain. Search methods We searched The Cochrane Library, MEDLINE, EMBASE, the Oxford Pain Relief Database and reference lists of articles to update an existing version of the review in July 2008. Selection criteria Randomised, double-blind, placebo-controlled clinical trials of paracetamol for acute postoperative pain in adults. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Area under the “pain relief versus time” curve was used to derive the proportion of participants with paracetamol or placebo experiencing at least 50% pain relief over four to six hours, using validated equations. Number-needed-to-treat-to-benefit (NNT) was calculated, with 95% confidence intervals (CI). The proportion of participants using rescue analgesia over a specified time period, and time to use, were sought as measures of duration of analgesia. Information on adverse events and withdrawals was also collected. Main results Fifty-one studies, with 5762 participants, were included: 3277 participants were treated with a single oral dose of paracetamol and 2425 with placebo. About half of participants treated with paracetamol at standard doses achieved at least 50% pain relief over four to six hours, compared with about 20% treated with placebo. NNTs for at

  6. Radiofrequency ablation therapy combined with cementoplasty for painful bone metastases: initial experience.

    PubMed

    Toyota, Naoyuki; Naito, Akira; Kakizawa, Hideaki; Hieda, Masashi; Hirai, Nobuhiko; Tachikake, Toshihiro; Kimura, Tomoki; Fukuda, Hideki; Ito, Katsuhide

    2005-01-01

    The purpose of this study was to assess the efficacy and safety of percutaneous radiofrequency (RF) ablation therapy combined with cementoplasty under computed tomography and fluoroscopic guidance for painful bone metastases. Seventeen adult patients with 23 painful bone metastases underwent RF ablation therapy combined with cementoplasty during a 2-year period. The mean tumor size was 52 x 40 x 59 mm. Initial pain relief, reduction of analgesics, duration of pain relief, recurrence rate of pain, survival rate, and complications were analyzed. The technical success rate was 100%. Initial pain relief was achieved in 100% of patients (n=17). The mean VAS scores dropped from 63 to 24 (p<0.001) (n=8). Analgesic reduction was achieved in 41% (7 out of 17 patients). The mean duration of pain relief was 7.3 months (median: 6 months). Pain recurred in three patients (17.6%) from 2 weeks to 3 months. Eight patients died and 8 patients are still alive (a patient was lost to follow-up). The one-year survival rate was 40% (observation period: 1--30 months). No major complications occurred, but one patient treated with this combined therapy broke his right femur 2 days later. There was transient local pain in most cases, and a hematoma in the psoas muscle (n=1) and a hematoma at the puncture site (n=1) occurred as minor complications. Percutaneous RF ablation therapy combined with cementoplasty for painful bone metastases is effective and safe, in particular, for bulky tumors extending to extraosseous regions. A comparison with cementoplasty or RF ablation alone and their long-term efficacies is needed.

  7. Radiofrequency Ablation Therapy Combined with Cementoplasty for Painful Bone Metastases: Initial Experience

    SciTech Connect

    Toyota, Naoyuki Naito, Akira; Kakizawa, Hideaki; Hieda, Masashi; Hirai, Nobuhiko; Tachikake, Toshihiro; Kimura, Tomoki; Fukuda, Hideki; Ito, Katsuhide

    2005-06-15

    The purpose of this study was to assess the efficacy and safety of percutaneous radiofrequency (RF) ablation therapy combined with cementoplasty under computed tomography and fluoroscopic guidance for painful bone metastases. Seventeen adult patients with 23 painful bone metastases underwent RF ablation therapy combined with cementoplasty during a 2-year period. The mean tumor size was 52 x 40 x 59 mm. Initial pain relief, reduction of analgesics, duration of pain relief, recurrence rate of pain, survival rate, and complications were analyzed. The technical success rate was 100%. Initial pain relief was achieved in 100% of patients (n = 17). The mean VAS scores dropped from 63 to 24 (p < 0.001) (n = 8). Analgesic reduction was achieved in 41% (7 out of 17 patients). The mean duration of pain relief was 7.3 months (median: 6 months). Pain recurred in three patients (17.6%) from 2 weeks to 3 months. Eight patients died and 8 patients are still alive (a patient was lost to follow-up). The one-year survival rate was 40% (observation period: 1-30 months). No major complications occurred, but one patient treated with this combined therapy broke his right femur 2 days later. There was transient local pain in most cases, and a hematoma in the psoas muscle (n = 1) and a hematoma at the puncture site (n = 1) occurred as minor complications. Percutaneous RF ablation therapy combined with cementoplasty for painful bone metastases is effective and safe, in particular, for bulky tumors extending to extraosseous regions. A comparison with cementoplasty or RF ablation alone and their long-term efficacies is needed.

  8. Monocyte chemoattractant protein-1 contributes to morphine tolerance in rats with cancer-induced bone pain

    PubMed Central

    Liu, Lei; Gao, Xiu-Juan; Ren, Chun-Guang; Hu, Ji-Hua; Liu, Xian-Wen; Zhang, Ping; Zhang, Zong-Wang; Fu, Zhi-Jian

    2017-01-01

    Cancer-induced bone pain can severely compromise the life quality of patients, while tolerance limits the use of opioids in the treatment of cancer pain. Monocyte chemoattractant protein-1 (MCP-1) is known to contribute to neuropathic pain. However, the role of spinal MCP-1 in the development of morphine tolerance in patients with cancer-induced bone pain remains unclear. The aim of the present study was to investigate the role of spinal MCP-1 in morphine tolerance in bone cancer pain rats (MTBP rats). Bone cancer pain was induced by intramedullary injection of Walker 256 cells into the tibia of the rats, while morphine tolerance was induced by continuous intrathecal injection of morphine over a period of 9 days. In addition, anti-MCP-1 antibodies were intrathecally injected to rats in various groups in order to investigate the association of MCP-1 with mechanical and heat hyperalgesia using the paw withdrawal threshold (PWT) and thermal withdrawal latency (TWL) tests, respectively. Furthermore, MCP-1 and CCR2 expression levels were measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, and CCR2 expression levels were measured using RT-qPCR. The results indicated that MCP-1 and CCR2 expression levels were significantly increased in the spinal cord of MTBP rats. Intrathecal administration of anti-MCP-1 neutralizing antibodies was observed to attenuate the mechanical and thermal allodynia in MTBP rats. Therefore, the upregulation of spinal MCP-1 and CCR2 expression levels may contribute to the development of mechanical allodynia in MTBP rats. In conclusion, MCP-1/CCR2 signaling may serve a crucial role in morphine tolerance development in rats suffering from cancer-induced bone pain. PMID:28352316

  9. Monocyte chemoattractant protein-1 contributes to morphine tolerance in rats with cancer-induced bone pain.

    PubMed

    Liu, Lei; Gao, Xiu-Juan; Ren, Chun-Guang; Hu, Ji-Hua; Liu, Xian-Wen; Zhang, Ping; Zhang, Zong-Wang; Fu, Zhi-Jian

    2017-02-01

    Cancer-induced bone pain can severely compromise the life quality of patients, while tolerance limits the use of opioids in the treatment of cancer pain. Monocyte chemoattractant protein-1 (MCP-1) is known to contribute to neuropathic pain. However, the role of spinal MCP-1 in the development of morphine tolerance in patients with cancer-induced bone pain remains unclear. The aim of the present study was to investigate the role of spinal MCP-1 in morphine tolerance in bone cancer pain rats (MTBP rats). Bone cancer pain was induced by intramedullary injection of Walker 256 cells into the tibia of the rats, while morphine tolerance was induced by continuous intrathecal injection of morphine over a period of 9 days. In addition, anti-MCP-1 antibodies were intrathecally injected to rats in various groups in order to investigate the association of MCP-1 with mechanical and heat hyperalgesia using the paw withdrawal threshold (PWT) and thermal withdrawal latency (TWL) tests, respectively. Furthermore, MCP-1 and CCR2 expression levels were measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, and CCR2 expression levels were measured using RT-qPCR. The results indicated that MCP-1 and CCR2 expression levels were significantly increased in the spinal cord of MTBP rats. Intrathecal administration of anti-MCP-1 neutralizing antibodies was observed to attenuate the mechanical and thermal allodynia in MTBP rats. Therefore, the upregulation of spinal MCP-1 and CCR2 expression levels may contribute to the development of mechanical allodynia in MTBP rats. In conclusion, MCP-1/CCR2 signaling may serve a crucial role in morphine tolerance development in rats suffering from cancer-induced bone pain.

  10. Orthopedic surgery and bone fracture pain are both significantly attenuated by sustained blockade of nerve growth factor

    PubMed Central

    Majuta, Lisa A.; Longo, Geraldine; Fealk, Michelle N.; McCaffrey, Gwen; Mantyh, Patrick W.

    2015-01-01

    The number of patients suffering from postoperative pain due to orthopedic surgery and bone fracture is projected to dramatically increase because the human life span, weight, and involvement in high-activity sports continue to rise worldwide. Joint replacement or bone fracture frequently results in skeletal pain that needs to be adequately controlled for the patient to fully participate in needed physical rehabilitation. Currently, the 2 major therapies used to control skeletal pain are nonsteroidal anti-inflammatory drugs and opiates, both of which have significant unwanted side effects. To assess the efficacy of novel therapies, mouse models of orthopedic and fracture pain were developed and evaluated here. These models, orthopedic surgery pain and bone fracture pain, resulted in skeletal pain–related behaviors that lasted 3 weeks and 8 to 10 weeks, respectively. These skeletal pain behaviors included spontaneous and palpation-induced nocifensive behaviors, dynamic weight bearing, limb use, and voluntary mechanical loading of the injured hind limb. Administration of anti–nerve growth factor before orthopedic surgery or after bone fracture attenuated skeletal pain behaviors by 40% to 70% depending on the end point being assessed. These data suggest that nerve growth factor is involved in driving pain due to orthopedic surgery or bone fracture. These animal models may be useful in developing an understanding of the mechanisms that drive postoperative orthopedic and bone fracture pain and the development of novel therapies to treat these skeletal pains. PMID:25599311

  11. Analgesic effects of adenylyl cyclase inhibitor NB001 on bone cancer pain in a mouse model

    PubMed Central

    Kang, Wen-bo; Yang, Qi; Guo, Yan-yan; Wang, Lu; Wang, Dong-sheng; Cheng, Qiang; Li, Xiao-ming; Tang, Jun; Zhao, Jian-ning; Liu, Gang; Zhuo, Min

    2016-01-01

    Background Cancer pain, especially the one caused by metastasis in bones, is a severe type of pain. Pain becomes chronic unless its causes and consequences are resolved. With improvements in cancer detection and survival among patients, pain has been considered as a great challenge because traditional therapies are partially effective in terms of providing relief. Cancer pain mechanisms are more poorly understood than neuropathic and inflammatory pain states. Chronic inflammatory pain and neuropathic pain are influenced by NB001, an adenylyl cyclase 1 (AC1)-specific inhibitor with analgesic effects. In this study, the analgesic effects of NB001 on cancer pain were evaluated. Results Pain was induced by injecting osteolytic murine sarcoma cell NCTC 2472 into the intramedullary cavity of the femur of mice. The mice injected with sarcoma cells for four weeks exhibited significant spontaneous pain behavior and mechanical allodynia. The continuous systemic application of NB001 (30 mg/kg, intraperitoneally, twice daily for three days) markedly decreased the number of spontaneous lifting but increased the mechanical paw withdrawal threshold. NB001 decreased the concentrations of cAMP and the levels of GluN2A, GluN2B, p-GluA1 (831), and p-GluA1 (845) in the anterior cingulate cortex, and inhibited the frequency of presynaptic neurotransmitter release in the anterior cingulate cortex of the mouse models. Conclusions NB001 may serve as a novel analgesic to treat bone cancer pain. Its analgesic effect is at least partially due to the inhibition of AC1 in anterior cingulate cortex. PMID:27612915

  12. Effect of the single-leg, lateral oblique, decline squat exercise on sacroiliac joint pain with knee pain

    PubMed Central

    Yoo, Won-gyu

    2016-01-01

    [Purpose] This study investigated the effect of the single-leg, lateral oblique, decline squat exercise on sacroiliac joint pain with knee pain. [Subjects and Methods] A 39-year-old female had severe pain in the right medial buttock and right anterior knee. This study assessed the anterior pelvic tilt angle and pain provocation tests before and after single-leg, lateral oblique, decline squat exercise for 4 weeks. [Results] Following the course of exercise, the anterior pelvic tilt angles were increased, and the visual analog scale pain scores for both the right buttock and right knee were 2/10. [Conclusion] Single-leg, lateral oblique, decline squat exercise may be effective for treating SI joint pain with knee pain in females. PMID:27799721

  13. Bilateral Knee Pain Associated with Bone Infarction in a Patient with Behcet's Disease.

    PubMed

    Oktayoglu, Pelin; Cevik, Figen; Tahtasiz, Mehmet; Em, Serda; Bozkurt, Mehtap; Kapukaya, Ahmet; Nas, Kemal

    2012-01-01

    We describe a 31-years-old female patient with severe pain in both knees who had been diagnosed as Behcet's disease (BD) for 12 years. She had had a history of complications due to BD including superior vena cava thrombosis, pulmonary thromboembolism, uveitis, and erythema nodosum and has reported the administration of corticosteroid therapy irregularly. After radiologic evaluation, she has been diagnosed with bone infarction of both left and right knee with the existance of lupus anticoagulants (LA) positivity. Severe joint pain without the evidence of arthritis must alert the clinician to the possibility of bone necrosis of the extremity, although those may rarely occur bilateral in BD.

  14. Single dose intravenous paracetamol or intravenous propacetamol for postoperative pain.

    PubMed

    McNicol, Ewan D; Ferguson, McKenzie C; Haroutounian, Simon; Carr, Daniel B; Schumann, Roman

    2016-05-23

    This is an updated version of the original Cochrane review published in Issue 10, 2011. Paracetamol (acetaminophen) is the most commonly prescribed analgesic for the treatment of acute pain. It may be administered orally, rectally, or intravenously. The efficacy and safety of intravenous (IV) formulations of paracetamol, IV paracetamol, and IV propacetamol (a prodrug that is metabolized to paracetamol), compared with placebo and other analgesics, is unclear. To assess the efficacy and safety of IV formulations of paracetamol for the treatment of postoperative pain in both adults and children. We ran the search for the previous review in May 2010. For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 1), MEDLINE (May 2010 to 16 February 2016), EMBASE (May 2010 to 16 February 2016), LILACS (2010 to 2016), a clinical trials registry, and reference lists of reviews for randomized controlled trials (RCTs) in any language and we retrieved articles. Randomized, double-blind, placebo- or active-controlled single dose clinical trials of IV paracetamol or IV propacetamol for acute postoperative pain in adults or children. Two review authors independently extracted data, which included demographic variables, type of surgery, interventions, efficacy, and adverse events. We contacted study authors for additional information. We graded each included study for methodological quality by assessing risk of bias and employed the GRADE approach to assess the overall quality of the evidence. We included 75 studies (36 from the original review and 39 from our updated review) enrolling a total of 7200 participants.Among primary outcomes, 36% of participants receiving IV paracetamol/propacetamol experienced at least 50% pain relief over four hours compared with 16% of those receiving placebo (number needed to treat to benefit (NNT) = 5; 95% confidence interval (CI) 3.7 to 5.6, high quality evidence). The proportion of participants in IV

  15. Single dose oral celecoxib for acute postoperative pain in adults

    PubMed Central

    Derry, Sheena; Moore, R Andrew

    2014-01-01

    Background This is an update of a review published in The Cochrane Library 2008, Issue 4. Celecoxib is a selective cyclo-oxygenase-2 (COX-2) inhibitor usually prescribed for the relief of chronic pain in osteoarthritis and rheumatoid arthritis. Celecoxib is believed to be associated with fewer upper gastrointestinal adverse effects than conventional non-steroidal anti-inflammatory drugs (NSAIDs). Its effectiveness in acute pain was demonstrated in the earlier reviews. Objectives To assess analgesic efficacy and adverse effects of a single oral dose of celecoxib for moderate to severe postoperative pain. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Oxford Pain Database, and ClinicalTrials.gov. The most recent search was to 3 January 2012. Selection criteria We included randomised, double-blind, placebo-controlled trials (RCTs) of adults prescribed any dose of oral celecoxib or placebo for acute postoperative pain. Data collection and analysis Two review authors assessed studies for quality and extracted data. We converted summed pain relief (TOTPAR) or pain intensity difference (SPID) into dichotomous information, yielding the number of participants with at least 50% pain relief over four to six hours, and used this to calculate the relative benefit (RB) and number needed to treat to benefit (NNT) for one patient to achieve at least 50% of maximum pain relief with celecoxib who would not have done so with placebo. We used information on use of rescue medication to calculate the proportion of participants requiring rescue medication and the weighted mean of the median time to use. Main results Eight studies (1380 participants) met the inclusion criteria. We identified five potentially relevant unpublished studies in the most recent searches, but data were not available at this time. The number of included studies therefore remains unchanged. The NNT for celecoxib 200 mg and 400 mg compared with placebo

  16. Current studies of acupuncture in cancer-induced bone pain animal models.

    PubMed

    Ryu, Hee Kyoung; Baek, Yong-Hyeon; Park, Yeon-Cheol; Seo, Byung-Kwan

    2014-01-01

    Acupuncture is generally accepted as a safe and harmless treatment option for alleviating pain. To explore the pain mechanism, numerous animal models have been developed to simulate specific human pain conditions, including cancer-induced bone pain (CIBP). In this study, we analyzed the current research methodology of acupuncture for the treatment of CIBP. We electronically searched the PubMed database for animal studies published from 2000 onward using these search terms: (bone cancer OR cancer) AND (pain OR analgesia) AND (acupuncture OR pharmacopuncture OR bee venom). We selected articles that described cancer pain in animal models. We analyzed the methods used to induce cancer pain and the outcome measures used to assess the effects of acupuncture on CIBP in animal models. We reviewed articles that met our inclusion criteria. Injection of mammary cancer cells into the cavity of the tibia was the most frequently used method for inducing CIBP in the animal models. Among the eight selected studies, five studies demonstrated the effects of electroacupuncture on CIBP. The effects of acupuncture were assessed by measuring pain-related behavior. Future researches will be needed to ascertain the effectiveness of acupuncture for treating CIBP and to explore the specific mechanism of CIBP in animal models.

  17. Positive relationship between bone mineral density and low back pain in middle-aged women.

    PubMed

    Manabe, Takashi; Takasugi, Shin-ichiro; Iwamoto, Yukihide

    2003-12-01

    There have been a large number of epidemiological studies demonstrating various primary factors that cause musculoskeletal disorders in middle-aged and older women. However, the relationship between low back pain and bone mineral density is not well documented, and no evidence for any direct relationship between the two has been found. To investigate the relationship, we conducted a cross-sectional study, on a population of 2,244 Japanese women aged 25-85 years who were participating in a regional health screening program. Information on lifestyle, reproductive characteristics and the presence of current low back pain was collected by self-administered questionnaires, and bone mineral density at the distal radius was measured. We found increasing bone mineral density to be significantly associated with low back pain in middle-aged women using a logistic regression analysis. Exercise and smoking were also significantly associated with low back pain. This association remained even after entering other lifestyle and reproductive factors into the final model. Accordingly, high bone mineral density would seem to be as important a public health problem as low bone mineral density and osteoporosis when considering the musculoskeletal symptoms and disabilities that appear in middle-aged women.

  18. Radiopharmaceuticals for metastatic bone pain palliation: available options in the clinical domain and their comparisons.

    PubMed

    Das, Tapas; Banerjee, Sharmila

    2017-01-01

    Bone pain arising due to skeletal metastases is one of the common complications experienced by the majority of patients suffering from prostate, breast and lung cancer at the advanced stage of the disease. These patients are subjected to palliative care in order to improve the quality of their remaining life. With the gradually increasing number of cancer cases, palliation of metastatic bone pain is gaining importance. Bone-seeking radiopharmaceuticals play a pivotal role in the management of cancer pain, particularly in patients with multiple metastases, as these agents are proven to be effective in controlling the bone pain with minimum side effects. Although a plethora of such radiopharmaceuticals have been developed and evaluated in animal models, only a few are regularly used in clinics while some of these agents are at different stages of clinical evaluations. The present article describes only those bone-seeking radiopharmaceuticals, which have been reported to be clinically administered till date, along with their relative merits and drawbacks.

  19. Effects of music therapy on pain and anxiety in patients undergoing bone marrow biopsy and aspiration.

    PubMed

    Shabanloei, Reza; Golchin, Mehri; Esfahani, Ali; Dolatkhah, Roya; Rasoulian, Marzieh

    2010-06-01

    Bone marrow biopsy and aspiration are commonly used for diagnosing, treating, and following up after treatment for blood disorders and solid tumors. For adults, the infiltration of local anesthesia at the biopsy site has been used as the principal form of analgesia for bone marrow biopsy and aspiration. Pain relief during these procedures is often incomplete, especially during aspiration of the bone marrow, and pain is likely to contribute to patient anxiety. Researchers at the Tabriz Hematology and Oncology Center in Iran conducted a study to quantify and evaluate the effectiveness of music therapy interventions on pain and anxiety control for 100 patients undergoing bone marrow biopsy and aspiration. Participants in the study were randomly assigned to one of two groups: one group listened to music during the procedure, and the other did not. Patients completed the Spielberger State-Trait Anxiety Inventory both before and after the procedure and reported pain severity by using a visual analog scale. Results showed that participants who listened to music had lower state anxiety and pain levels than those who did not listen to music.

  20. Morin Suppresses Astrocyte Activation and Regulates Cytokine Release in Bone Cancer Pain Rat Models.

    PubMed

    Jiang, Wei; Wang, Ying; Sun, Wei; Zhang, Mengyuan

    2017-09-01

    As inflammatory and immune responses are involved in pathophysiology of debilitating neuropathic pain, reagents that can modulate these two responses may have therapeutic potential. Morin, derived from the moraceae family of plants, benefits inflammation-related diseases, but its antinociceptive effects on cancer pain remain elusive. In the present study, we investigated antinociceptive effects of morin on bone cancer pain using a rat model, where rats were subject to implantation of Walker 256 mammary gland carcinoma cells into the tibia. Morin (5-20 mg/kg) dose-dependently attenuated behavioral hypersensitivities, including mechanical allodynia and free movement pain, which was accompanied by downregulation of astrocyte marker glial fibrillary acidic protein in the spinal cord in cancer-bearing rats. Treatment with morin also induced reduction of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 and upregulation of an antiinflammatory cytokine IL-10. Furthermore, intrathecal injection of AM630 (an antagonist of cannabinoid receptor 2, CB2 ), but not naloxone (an antagonist of opioid receptors), significantly blocked morin attenuation of behavioral hypersensitivities. Taken together, these results suggest that morin suppresses astrocyte activation and neuro-inflammation induced by bone cancer pain and its antinociceptive effects on bone cancer pain may be associated with activation of CB2 receptors in the spinal cord. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  1. The Usefulness of Single-Photon Emission Computed Tomography in Defining Painful Upper Cervical Facet Arthropathy.

    PubMed

    Ravindra, Vijay M; Mazur, Marcus D; Bisson, Erica F; Barton, Craig; Shah, Lubdha M; Dailey, Andrew T

    2016-12-01

    Standard imaging techniques have low predictive value for identifying sources of neck pain. Single-photon emission computed tomography (SPECT) imaging in conjunction with computed tomography (CT) provides the sensitivity of bone scanning for areas of high metabolic activity with the sensitivity of CT for anatomic localization. We evaluated the usefulness of SPECT-CT imaging in identifying pain generators in upper cervical facet arthropathy. In a retrospective study, we reviewed 7 patients (mean age, 68.7 years) who underwent diagnostic SPECT-CT imaging for upper cervical neck pain at our institution from August 2011 to February 2015. We assessed SPECT-CT radiotracer uptake and postoperative neck disability index (NDI) and visual analog scale (VAS) scores. Mean preoperative NDI and VAS scores were 42% (range, 34%-72%) and 7/10 (range, 5-8), respectively. SPECT-CT showed increased radiotracer uptake and inflammation at the level of pain generation indicated by history and physical examination. Intraoperatively, all patients had corresponding facet hypertrophy with degeneration at the site of increased radiotracer uptake. The mean postoperative NDI and VAS scores at 9 months were 23% (0%-54%) and 2/10 (0-5), respectively, representing improvements of 20% (P = 0.025) and 4 (P = 0.0028), respectively. SPECT-CT imaging of the upper cervical spine is a potentially sensitive diagnostic test that can implicate pain generators with increased metabolic activity. We propose that SPECT-CT may be a useful adjunct in the workup for neck pain secondary to facet arthropathy that could obviate diagnostic injections. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Argon laser induced single cortical responses: a new method to quantify pre-pain and pain perceptions.

    PubMed

    Bjerring, P; Arendt-Nielsen, L

    1988-01-01

    The shape (amplitude and latency) of single cortical responses to argon laser stimulation was found to match six perceptual classes: three pre-pain and three pain. The amplitude of the pain related single cortical responses correlated with the perceived feeling of pain. Easy detectable responses were obtained because habituation to the stimuli was reduced and a high degree of attention was given to each stimulus. Single cortical responses to argon laser stimuli are suggested as a new quantitative technique with application in the assessment of function in the thermal and nociceptive pathways.

  3. Argon laser induced single cortical responses: a new method to quantify pre-pain and pain perceptions.

    PubMed Central

    Bjerring, P; Arendt-Nielsen, L

    1988-01-01

    The shape (amplitude and latency) of single cortical responses to argon laser stimulation was found to match six perceptual classes: three pre-pain and three pain. The amplitude of the pain related single cortical responses correlated with the perceived feeling of pain. Easy detectable responses were obtained because habituation to the stimuli was reduced and a high degree of attention was given to each stimulus. Single cortical responses to argon laser stimuli are suggested as a new quantitative technique with application in the assessment of function in the thermal and nociceptive pathways. PMID:3351530

  4. Effect of sex in the MRMT-1 model of cancer-induced bone pain

    PubMed Central

    Falk, Sarah; Al-Dihaissy, Tamara; Mezzanotte, Laura; Heegaard, Anne-Marie

    2015-01-01

    An overwhelming amount of evidence demonstrates sex-induced variation in pain processing, and has thus increased the focus on sex as an essential parameter for optimization of in vivo models in pain research. Mammary cancer cells are often used to model metastatic bone pain in vivo, and are commonly used in both males and females. Here we demonstrate that compared to male rats, female rats have an increased capacity for recovery following inoculation of MRMT-1 mammary cells, thus potentially causing a sex-dependent bias in interpretation of the data. PMID:26834983

  5. Treatment of Extraspinal Painful Bone Metastases with Percutaneous Cementoplasty: A Prospective Study of 50 Patients

    SciTech Connect

    Anselmetti, Giovanni Carlo Manca, Antonio; Ortega, Cinzia; Grignani, Giovanni; DeBernardi, Felicino; Regge, Daniele

    2008-11-15

    The aim of this study was to assess the efficacy of percutaneous cementoplasty (PC) with polymethylmethacrylate (PMMA) in painful extravertebral lytic bone metastases not responding to conventional therapy. Fifty patients (25 females), mean age 64.7 {+-} 11.2 years, underwent PC after giving informed consent. Procedures were performed under fluoroscopy (1/50) or combined fluoroscopy-CT (49/50) guidance in local anesthesia or under deep sedation in 7 patients with large metastases who underwent radiofrequency thermoablation (RFA) in the same session. Seventy lesions were treated (1-6 per patient; average, 1.4 {+-} 0.9), arranging in size from 1 to 10 cm (average, 3.6 {+-} 2.1 cm). Mean volume of PMMA per lesion was 5.9 {+-} 3.2 ml (range, 1.5-15.0 ml). Pain was prospectively evaluated on an 11-point visual analog scale (VAS) before and after the procedure (follow-up, 15 to 36 months). Mean VAS score dropped from 9.1 {+-} 1.2 (range: 6-10) to 2.1 {+-} 2.5 (range: 0-9). Mean VAS difference was 7.0 {+-} 2.3 (range, 1-10; p < 0.0001, Wilcoxon signed rank test). Forty-seven of the 50 patients (94%) suspended narcotic drugs, in 22 (44%) pain was controlled with a nonsteroidal anti-inflammatory drug, in 25 (50%) analgesic therapy was suspended, and 13 of 50 (26%) had complete pain regression. In 3 of the 50 patients (6%) pain was not improved. No statistical difference between osteoplasty and osteoplasty plus RFA was found (p = 0.8338, Mann-Whitney test). No complications arose during the procedure. Two patients with metastases in the femoral diaphysis reported a fracture 1 month after treatment. PC is effective to obtain pain regression in painful bone metastases not responding to conventional analgesic therapy; bone consolidation cannot be obtained in the diaphysis of long weight-bearing bones.

  6. Management of foot pain associated with accessory bones of the foot: two clinical case reports.

    PubMed

    Requejo, S M; Kulig, K; Thordarson, D B

    2000-10-01

    Case study. To discuss the differential diagnosis, the nonsurgical and postoperative management of common accessory bones of the foot. Accessory bones of the foot that are formed during abnormal ossification are commonly found in asymptomatic feet. Two of the most common accessory bones are the accessory navicular and the os peroneum. Their painful presence must be considered in the differential diagnosis of any acute or chronic foot pain. The optimal treatment for the conservative and postoperative management of painful os peroneum and accessory navicular bones remains undefined. Therapeutic management of the fractured os peroneum included bracing, taping, and foot orthotics to allow healing of involved tissues, and stretching. The focus of the postoperative management of the accessory navicular was joint mobilization and progressive strengthening. Dependent variables included level of pain with provocation and alleviation tests of joint and soft tissue; girth and sensory tests of the foot and ankle; goniometric measures of foot and ankle; strength of ankle and hip muscles; functional tests; and patient's self-reported pain status. The patient with the fractured os peroneum was treated in 13 visits for 10 weeks. At discharge from physical therapy, the patient had the following outcomes relative to the noninvolved side: 100% return of normal sensation tested by light touch and vibration; pain decreased from 6/10 to 1/10; 100% reduction of swelling with ankle girth to normal; 100% range of motion of ankle and subtalar joints. Strength in plantar flexion and eversion remained 20% impaired (80% return to normal) secondary to pain. Upon discharge, he still reported mild pain when walking but was able to return to previous leisure activities. The second patient with the accessory navicular was treated in 18 visits over 9 weeks. Relative to the uninvolved side, she was discharged with the following: 70% return of range of motion in the foot and ankle, 100% of strength in

  7. Single dose oral analgesics for acute postoperative pain in adults.

    PubMed

    Moore, R Andrew; Derry, Sheena; McQuay, Henry J; Wiffen, Philip J

    2011-09-07

    Thirty-five Cochrane Reviews of randomised trials testing the analgesic efficacy of individual drug interventions in acute postoperative pain have been published. This overview brings together the results of all those reviews and assesses the reliability of available data. To summarise data from all Cochrane Reviews that have assessed the effects of pharmaceutical interventions for acute pain in adults with at least moderate pain following surgery, who have been given a single dose of oral analgesic taken alone. We identified systematic reviews in The Cochrane Library through a simple search strategy. All reviews were overseen by a single Review Group, had a standard title, and had as their primary outcome numbers of participants with at least 50% pain relief over four to six hours compared with placebo. For individual reviews we extracted the number needed to treat (NNT) for this outcome for each drug/dose combination, and also the percentage of participants achieving at least 50% maximum pain relief, the mean of mean or median time to remedication, the percentage of participants remedicating by 6, 8, 12, or 24 hours, and results for participants experiencing at least one adverse event. The overview included 35 separate Cochrane Reviews with 38 analyses of single dose oral analgesics tested in acute postoperative pain models, with results from about 45,000 participants studied in approximately 350 individual studies. The individual reviews included only high-quality trials of standardised design and outcome reporting. The reviews used standardised methods and reporting for both efficacy and harm. Event rates with placebo were consistent in larger data sets. No statistical comparison was undertaken.There were reviews but no trial data were available for acemetacin, meloxicam, nabumetone, nefopam, sulindac, tenoxicam, and tiaprofenic acid. Inadequate amounts of data were available for dexibuprofen, dextropropoxyphene 130 mg, diflunisal 125 mg, etoricoxib 60 mg

  8. Single dose oral analgesics for acute postoperative pain in adults

    PubMed Central

    Moore, R Andrew; Derry, Sheena; McQuay, Henry J; Wiffen, Philip J

    2014-01-01

    Background Thirty-five Cochrane Reviews of randomised trials testing the analgesic efficacy of individual drug interventions in acute postoperative pain have been published. This overview brings together the results of all those reviews and assesses the reliability of available data. Objectives To summarise data from all Cochrane Reviews that have assessed the effects of pharmaceutical interventions for acute pain in adults with at least moderate pain following surgery, who have been given a single dose of oral analgesic taken alone. Methods We identified systematic reviews in The Cochrane Library through a simple search strategy. All reviews were overseen by a single Review Group, had a standard title, and had as their primary outcome numbers of participants with at least 50% pain relief over four to six hours compared with placebo. For individual reviews we extracted the number needed to treat (NNT) for this outcome for each drug/dose combination, and also the percentage of participants achieving at least 50% maximum pain relief, the mean of mean or median time to remedication, the percentage of participants remedicating by 6, 8, 12, or 24 hours, and results for participants experiencing at least one adverse event. Main results The overview included 35 separate Cochrane Reviews with 38 analyses of single dose oral analgesics tested in acute postoperative pain models, with results from about 45,000 participants studied in approximately 350 individual studies. The individual reviews included only high-quality trials of standardised design and outcome reporting. The reviews used standardised methods and reporting for both efficacy and harm. Event rates with placebo were consistent in larger data sets. No statistical comparison was undertaken. There were reviews but no trial data were available for acemetacin, meloxicam, nabumetone, nefopam, sulindac, tenoxicam, and tiaprofenic acid. Inadequate amounts of data were available for dexibuprofen, dextropropoxyphene 130

  9. Back Pain Caused by a Solitary Plasmacytoma of Bone

    PubMed Central

    Rattican, Debra; Kelly, Debra L.; Filler, Kristin A.; Lyon, Debra E.

    2015-01-01

    This article presents initial diagnostic workup and criteria for diagnosing solitary plasmacytoma of bone (SPB) versus multiple myeloma. The authors discuss the incorporation of current imaging technologies into the diagnosis and staging of SPB and multiple myeloma. In addition, the article addresses treatment modalities and discusses the importance of oncology nurses’ awareness of this rare condition. PMID:20350888

  10. Accessory navicular bone: when ankle pain does not originate from the ankle.

    PubMed

    Issever, Ahi Sema; Minden, Kirsten; Eshed, Iris; Hermann, Kay-Geert A

    2007-12-01

    A young girl suffering from ankle pain occurring after gymnastics classes was referred to the rheumatology department by an orthopedic surgeon because a rheumatological condition was suspected to cause her symptoms. MRI was useful in pointing to the correct diagnosis of accessory navicular bone (AN). The morphological classification of ANs is discussed and the imaging modalities for diagnosis are presented.

  11. Behavioral and neurochemical analysis of ongoing bone cancer pain in rats.

    PubMed

    Remeniuk, Bethany; Sukhtankar, Devki; Okun, Alec; Navratilova, Edita; Xie, Jennifer Y; King, Tamara; Porreca, Frank

    2015-10-01

    Cancer-induced bone pain is described as dull, aching ongoing pain. Ongoing bone cancer pain was characterized after intratibial injection of breast cancer cells in rats. Cancer produced time-dependent bone remodeling and tactile hypersensitivity but no spontaneous flinching. Conditioned place preference (CPP) and enhanced dopamine (DA) release in the nucleus accumbens (NAc) shell was observed after peripheral nerve block (PNB) selectively in tumor-bearing rats revealing nociceptive-driven ongoing pain. Oral diclofenac reversed tumor-induced tactile hypersensitivity but did not block PNB-induced CPP or NAc DA release. Tumor-induced tactile hypersensitivity, and PNB-induced CPP and NAc DA release, was blocked by prior subcutaneous implantation of a morphine pellet. In sham rats, morphine produced a modest but sustained increase in NAc DA release. In contrast, morphine produced a transient 5-fold higher NAc DA release in tumor bearing rats compared with sham morphine rats. The possibility that this increased NAc DA release reflected the reward of pain relief was tested by irreversible blockade of rostral anterior cingulate cortex (rACC) μ-opioid receptors (MORs). The rACC MOR blockade prevented the morphine-induced transient increased NAc DA release in tumor bearing rats but did not affect morphine-induced effects in sham-operated animals. Consistent with clinical experience, ongoing cancer pain was controlled by morphine but not by a dose of diclofenac that reversed evoked hypersensitivity. Additionally, the intrinsic reward of morphine can be dissociated from the reward of relief of cancer pain by blockade of rACC MOR. This approach allows mechanistic and therapeutic assessment of ongoing cancer pain with likely translation relevance.

  12. Behavioral and neurochemical analysis of ongoing bone cancer pain in rats

    PubMed Central

    Remeniuk, Bethany; Sukhtankar, Devki; Okun, Alec; Navratilova, Edita; Xie, Jennifer Y.; King, Tamara; Porreca, Frank

    2015-01-01

    Abstract Cancer-induced bone pain is described as dull, aching ongoing pain. Ongoing bone cancer pain was characterized after intratibial injection of breast cancer cells in rats. Cancer produced time-dependent bone remodeling and tactile hypersensitivity but no spontaneous flinching. Conditioned place preference (CPP) and enhanced dopamine (DA) release in the nucleus accumbens (NAc) shell was observed after peripheral nerve block (PNB) selectively in tumor-bearing rats revealing nociceptive-driven ongoing pain. Oral diclofenac reversed tumor-induced tactile hypersensitivity but did not block PNB-induced CPP or NAc DA release. Tumor-induced tactile hypersensitivity, and PNB-induced CPP and NAc DA release, was blocked by prior subcutaneous implantation of a morphine pellet. In sham rats, morphine produced a modest but sustained increase in NAc DA release. In contrast, morphine produced a transient 5-fold higher NAc DA release in tumor bearing rats compared with sham morphine rats. The possibility that this increased NAc DA release reflected the reward of pain relief was tested by irreversible blockade of rostral anterior cingulate cortex (rACC) μ-opioid receptors (MORs). The rACC MOR blockade prevented the morphine-induced transient increased NAc DA release in tumor bearing rats but did not affect morphine-induced effects in sham-operated animals. Consistent with clinical experience, ongoing cancer pain was controlled by morphine but not by a dose of diclofenac that reversed evoked hypersensitivity. Additionally, the intrinsic reward of morphine can be dissociated from the reward of relief of cancer pain by blockade of rACC MOR. This approach allows mechanistic and therapeutic assessment of ongoing cancer pain with likely translation relevance. PMID:25955964

  13. 21 CFR 888.3030 - Single/multiple component metallic bone fixation appliances and accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Single/multiple component metallic bone fixation....3030 Single/multiple component metallic bone fixation appliances and accessories. (a) Identification. Single/multiple component metallic bone fixation appliances and accessories are devices intended to be...

  14. 21 CFR 888.3030 - Single/multiple component metallic bone fixation appliances and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Single/multiple component metallic bone fixation....3030 Single/multiple component metallic bone fixation appliances and accessories. (a) Identification. Single/multiple component metallic bone fixation appliances and accessories are devices intended to be...

  15. 21 CFR 888.3030 - Single/multiple component metallic bone fixation appliances and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Single/multiple component metallic bone fixation....3030 Single/multiple component metallic bone fixation appliances and accessories. (a) Identification. Single/multiple component metallic bone fixation appliances and accessories are devices intended to be...

  16. Inducible Lentivirus-Mediated siRNA against TLR4 Reduces Nociception in a Rat Model of Bone Cancer Pain.

    PubMed

    Pan, Ruirui; Di, Huiting; Zhang, Jinming; Huang, Zhangxiang; Sun, Yuming; Yu, Weifeng; Wu, Feixiang

    2015-01-01

    Although bone cancer pain is still not fully understood by scientists and clinicians alike, studies suggest that toll like receptor 4 (TLR4) plays an important role in the initiation and/or maintenance of pathological pain state in bone cancer pain. A promising treatment for bone cancer pain is the downregulation of TLR4 by RNA interference; however, naked siRNA (small interference RNA) is not effective in long-term treatments. In order to concoct a viable prolonged treatment for bone cancer pain, an inducible lentivirus LvOn-siTLR4 (tetracycline inducible lentivirus carrying siRNA targeting TLR4) was prepared and the antinociception effects were observed in bone cancer pain rats induced by Walker 256 cells injection in left leg. Results showed that LvOn-siTLR4 intrathecal injection with doxycycline (Dox) oral administration effectively reduced the nociception induced by Walker 256 cells while inhibiting the mRNA and protein expression of TLR4. Proinflammatory cytokines as TNF-α and IL-1β in spinal cord were also decreased. These findings suggest that TLR4 could be a target for bone cancer pain treatment and tetracycline inducible lentivirus LvOn-siTLR4 represents a new potential option for long-term treatment of bone cancer pain.

  17. Modulation of Nav1.8 by Lysophosphatidic Acid in the Induction of Bone Cancer Pain.

    PubMed

    Pan, Hai-Li; Liu, Ben-Long; Lin, Wei; Zhang, Yu-Qiu

    2016-10-01

    Given that lysophosphatidic acid (LPA) and the tetrodotoxin-resistant sodium channel Nav1.8 are both involved in bone cancer pain, the present study was designed to investigate whether crosstalk between the LPA receptor LPA1 (also known as EDG2) and Nav1.8 in the dorsal root ganglion (DRG) contributes to the induction of bone cancer pain. We showed that the EDG2 antagonist Ki16198 blocked the mechanical allodynia induced by intrathecal LPA in naïve rats and attenuated mechanical allodynia in a rat model of bone cancer. EDG2 and Nav1.8 expression in L4-6 DRGs was upregulated following intrathecal or hindpaw injection of LPA. EDG2 and Nav1.8 expression in ipsilateral L4-6 DRGs increased with the development of bone cancer. Furthermore, we showed that EDG2 co-localized with Nav1.8 and LPA remarkably enhanced Nav1.8 currents in DRG neurons, and this was blocked by either a protein kinase C (PKC) inhibitor or a PKCε inhibitor. Overall, we demonstrated the modulation of Nav1.8 by LPA in DRG neurons, and that this probably underlies the peripheral mechanism by which bone cancer pain is induced.

  18. Initial thermal heat hypoalgesia and delayed hyperalgesia in a murine model of bone cancer pain.

    PubMed

    Menéndez, Luis; Lastra, Ana; Fresno, Manuel F; Llames, Sara; Meana, Alvaro; Hidalgo, Agustín; Baamonde, Ana

    2003-04-18

    The recent development of rodent models of bone cancer pain has started to provide the basis for demonstrating the particular neurochemical and behavioral entity of cancer pain. Behaviourally, both spontaneous pain and hyperalgesia related to mechanical, but not thermal, noxious stimuli have been described in cancer-bearing animals. We have carried out a histological and behavioural study focused on the reactivity to noxious heat in C3H/HeJ mice receiving an intratibial injection of 10(5) NCTC 2472 cells. These cells, able to induce an osteosarcoma, break through bone into soft tissues 2 weeks after cell inoculation, producing a macroscopical increase of the limb size from the fourth week. Thermal reactivity is diminished during the first 2 weeks after cell implantation, this hypoalgesia being reversed by the administration of naloxone (10 mg/kg). In contrast, during the fourth and fifth weeks after NCTC 2472 cell implantation, an increased nociceptive heat reactivity, instead of hypoalgesia, was obtained. This thermal hyperalgesia was prevented by the systemic administration of morphine (15 mg/kg). Throughout the whole period studied, mice showed signs of spontaneous pain behaviour that reached its maximum 3 weeks after inoculation. In conclusion, we show that the presence of thermal heat hyperalgesia is preceded by an initial opioid-mediated hypoalgesic state, in this murine model of bone cancer pain.

  19. Randomized phase II study of loratadine for the prevention of bone pain caused by pegfilgrastim.

    PubMed

    Moukharskaya, J; Abrams, D M; Ashikaga, T; Khan, F; Schwartz, J; Wilson, K; Verschraegen, C; Openshaw, T; Valentine, J; Eneman, J; Unger, P; Ades, S

    2016-07-01

    Bone pain is a common side effect of pegfilgrastim and can interfere with quality of life and treatment adherence. This study investigated the impact of antihistamine prophylaxis on pegfilgrastim-induced bone pain. This is a two-stage enrichment trial design. Patients receiving an initial dose of pegfilgrastim after chemotherapy were enrolled into the observation (OBS) stage. Those who developed significant back or leg bone pain (SP) were enrolled into the treatment (TRT) stage and randomized to daily loratadine 10 mg or placebo for 7 days. SP was defined by Brief Pain Inventory as back or leg pain score ≥5 and a 2-point increase after pegfilgrastim. The primary end point of TRT was reduction of worst back or leg bone pain with loratadine, defined as a 2-point decrease after treatment compared to OBS. Two hundred thirteen patients were included in the final analysis. Incidence of SP was 30.5 %. The SP subset had a worse overall Functional Assessment of Cancer Therapy-Bone Pain score (33.9 vs. 51.7, p < 0.001) and a higher mean white blood cell count (15.4 vs. 8.4 K/cm(3), p = 0.013) following pegfilgrastim than those without SP. Forty-six patients were randomized in the TRT. Benefit was 77.3 % with loratadine and 62.5 % with placebo (p = 0.35). Baseline NSAID use was documented in four patients (18.2 %) in loratadine arm and two patients (8.3 %) in placebo arm, with baseline non-NSAID use documented in five (22.7 %) and six (25 %) patients, respectively. Eight additional patients used NSAIDS by day 8 compared to day 1 (six in the loratadine and two in the placebo arm). A total of six additional patients used non-NSAIDS by day 8 compared to day 1 (four in the loratadine and two in the placebo arm). Administration of prophylactic loratadine does not decrease the incidence of severe bone pain or improve quality of life in a high-risk patient population. ClinicalTrials.gov identifier: NCT01311336.

  20. Osteoid osteoma of the cuboid bone: a rare cause of foot pain.

    PubMed

    Gürkan, Volkan; Orhun, Haldun; Bülbül, Murat; Kayahan, Sibel

    2011-01-01

    Osteoid osteoma, a common bone lesion of benign nature, is more rarely seen in feet. It most commonly involves the talus yet rarely the cuboid. The atypical symptoms of foot involvement may delay the diagnosis. Differential diagnosis most commonly includes ankle sprain, monoarticular arthritis, anterior impingement syndrome, tarsal spur, osteomyelitis, stress fracture, eosinophilic granuloma. The delay in diagnosis and treatment of osteoid osteoma in the foot may be a cause of chronic foot pain. In this study, we present a 17-year-old boy with osteoid osteoma in his right cuboid bone. The patient was undiagnosed during the first year of his symptoms. After surgical removal of the tumor, his complaints were resolved. The pathological examination confirmed the diagnosis of osteoid osteoma. Osteoid osteoma is an unusual bone tumor of the foot. It should be included in the differential diagnosis of patients exhibiting foot pain. In speculative cases with no obvious radiographic findings, further imaging studies, such as CT, should be considered.

  1. An unusual case of pelvic pain: retention of fetal bone after abortion.

    PubMed

    Samraj, S; Crawford, S; Singh, N; Patel, R; Rowen, D

    2008-05-01

    We present a 21-year-old woman with a short history of pelvic pain. The history was unremarkable apart from that of undergoing a surgical termination of pregnancy (TOP) some three-and-half years ago. Examination revealed a foreign body at the cervical os. Subsequent investigations revealed more foreign bodies within the cervical canal and uterine cavity, which were removed. Histologically these were found to be bones. Removal of the bone fragment initially discovered lead to an improvement of symptoms. Although the patient was treated for pelvic-inflammatory disease, no infective cause could be established. The condition of intrauterine retained fetal bones is recognized, but rare. Patients experiencing pelvic pain usually present sooner after TOP than did this patient. Although rare, it is an important condition to diagnose as it represents a treatable cause of infertility.

  2. Wideband Single-Crystal Transducer for Bone Characterization

    NASA Technical Reports Server (NTRS)

    Liang, Yu; Snook, Kevin

    2012-01-01

    The microgravity conditions of space travel result in unique physiological demands on the human body. In particular, the absence of the continual mechanical stresses on the skeletal system that are present on Earth cause the bones to decalcify. Trabecular structure decreases in thickness and increases in spacing, resulting in decreased bone strength and increased risk of injury. Thus, monitoring bone health is a high priority for long-term space travel. A single probe covering all frequency bands of interest would be ideal for such measurements, and this would also minimize storage space and eliminate the complexity of integrating multiple probes. This invention is an ultrasound transducer for the structural characterization of bone. Such characterization measures features of reflected and transmitted ultrasound signals, and correlates these signals with bone structure metrics such as bone mineral density, trabecular spacing, and thickness, etc. The techniques used to determine these various metrics require measurements over a broad range of ultrasound frequencies, and therefore, complete characterization requires the use of several narrowband transducers. This is a single transducer capable of making these measurements in all the required frequency bands. The device achieves this capability through a unique combination of a broadband piezoelectric material; a design incorporating multiple resonator sizes with distinct, overlapping frequency spectra; and a micromachining process for producing the multiple-resonator pattern with common electrode surfaces between the resonators. This device consists of a pattern of resonator bars with common electrodes that is wrapped around a central mandrel such that the radiating faces of the resonators are coplanar and can be simultaneously applied to the sample to be measured. The device operates as both a source and receiver of acoustic energy. It is operated by connection to an electronic system capable of both providing an

  3. Effectiveness of elcatonin for alleviating pain and inhibiting bone resorption in patients with osteoporotic vertebral fractures.

    PubMed

    Tanaka, Shinya; Yoshida, Akira; Kono, Shinjiro; Oguma, Tadanori; Hasegawa, Kyoichi; Ito, Manabu

    2016-11-09

    Elderly patients with osteoporotic vertebral fractures often experience severe pain that reduces their quality of life (QOL). Calcitonin, a bone resorption inhibitor, has been reported to alleviate pain in such patients; however, few clinical studies have demonstrated this effect. The objective of this study was to compare changes in pain scores, activities of daily living (ADL), QOL, bone resorption, bone mineral density (BMD), and fracture healing among patients with new vertebral fractures who received different treatment modalities. We conducted an open-label, multicenter, randomized, parallel control group study comprising 107 female patients ≥55 years old with acute back pain from vertebral fracture. All subjects received either intramuscular injections of elcatonin, a derivative of calcitonin, or an oral nonsteroidal antiinflammatory drug (NSAID) combined with an active vitamin D3 (VD3) analogue for 6 months. The pain was assessed using a visual analogue scale, and ADL and QOL were assessed using questionnaires. BMD was measured using dual-energy X-ray absorptiometry. A two-tailed significance level of 5% was used. The elcatonin IM group had significantly higher QOL score at 2 weeks and later, and significantly lower VAS and ADL scores than those in the NSAID + VD3 group at 1 month and later. The elcatonin IM group had significantly reduced TRACP-5b levels compared with those in the NSAID + VD3 group at 3 months and later and significantly higher percent changes in BMD than the NSAID + VD3 group. These results suggest that elcatonin significantly alleviated pain, inhibited bone resorption, and improved ADL, QOL, and BMD compared with NSAID + VD3.

  4. 125I Seed Implant Brachytherapy for Painful Bone Metastases After Failure of External Beam Radiation Therapy

    PubMed Central

    Feng, Shi; Wang, Li; Xiao, Zhang; Maharjan, Rakesh; Chuanxing, Li; Fujun, Zhang; Jinhua, Huang; Peihong, Wu

    2015-01-01

    Abstract The purpose of this study was to evaluate the safety and therapeutic efficacy of computed tomography (CT)-guided 125I seed implant brachytherapy in patients with painful metastatic bone lesions after failure of external beam radiation therapy (EBRT). From August 2012 to July 2014, 26 patients with painful bone metastases after failure of EBRT were treated with CT-guided 125I seed implant brachytherapy. Patient pain and analgesic use were measured using the Brief Pain Inventory before treatment, weekly for 4 weeks, and every 4 weeks thereafter for a total of 24 weeks. Opioid analgesic medications and complications were monitored at the same follow-up intervals. Before 125I seed implantation, the mean score for worst pain in a 24-hour period was 7.3 out of 10. Following treatment, at weeks 1, 4, 8, 12, and 24, worst pain decreased to 5.0 (P < 0.0001), 3.0 (P < 0.0001), 2.8 (P < 0.0001), 2.6 (P < 0.0001), and 2.0 (P = 0.0001), respectively. Opioid usage significantly decreased at weeks 4, 8, and 12. Overall response rates of osseous metastases after 125I seed implantation at 1, 4, 8, 12, and 24 weeks were 58%, 79%, 81%, 82%, and 80%, respectively. Adverse events were seen in 4 patients, including Grade 1 myelosuppression and Grade 1 late skin toxicity. 125I seed brachytherapy is a safe and effective treatment for patients with painful bone metastases after failure of EBRT. PMID:26252288

  5. Immediate post-operative pain in anterior cruciate ligament reconstruction surgery with bone patellar tendon bone graft versus hamstring graft.

    PubMed

    Gupta, Ravi; Kapoor, Dheeraj; Kapoor, Love; Malhotra, Anubhav; Masih, Gladson David; Kapoor, Anil; Joshi, Shweta

    2016-06-08

    Pain in the immediate post-operative period after anterior cruciate ligament (ACL) surgery, apart from an unpleasant experience for the patient, can act as a barrier for static quadriceps contractions and optimum execution of the initial rehabilitation protocol resulting in slow recovery and a later return to full function for a sportsperson. There is no report in the literature comparing pain in the immediate post-operative period after using the two most widely used autografts, bone patellar tendon bone (BPTB) graft and hamstring graft. The present study compared the visual analogue scale (VAS) pain score in the immediate post-operative period after arthroscopic ACL reconstruction with the BPTB and hamstring autografts. Both groups consisted of 50 patients each. The mean age of the BPTB and hamstring cohorts was 26.9 ± 7.3 years (age range 18-59 years) and 26.7 ± 9.0 years (age range 17-52 years), respectively. Unpaired t test was applied to compare pain scores between the BPTB and hamstring cohorts. In the present study, patients in the BPTB cohort showed higher mean pain scores across all the post-operative time intervals except at 6 h. However, the difference in the mean VAS pain score at post-operative 6, 12,18, 24, 36 and 48 h in the two groups was statistically not significant (p value of 1, 0.665, 0.798, 0.377, 0.651 and 0.215 at 6, 12, 18, 24, 36 and 48 h, respectively). Our study concludes that the arthroscopic ACL reconstruction with BPTB autograft and hamstring autograft is associated with similar pain in the immediate post-operative period. As a result, aggressive physiotherapy regime is not affected by the type of graft being used for ACL reconstruction, as the pain scores in the immediate post-operative period are similar for both techniques. Clinical Trials Registry-India, CTRI/2016/01/006502.

  6. A rat model of bone cancer pain induced by intra-tibia inoculation of Walker 256 mammary gland carcinoma cells

    SciTech Connect

    Mao-Ying, Q.-L.; Zhao Jun; Dong Zhiqiang; Wang Jun; Yu Jin; Yan Minfen; Zhang Yuqiu; Wu Gencheng; Wang Yanqing . E-mail: wangyanqing@shmu.edu.cn

    2006-07-14

    This study described a modified rat model of bone cancer pain. Syngeneic Walker 256 mammary gland carcinoma cells were injected into the tibia medullary cavity via intercondylar eminence. Series of tests were carried out including bone radiology, bone histology, ambulatory pain, thermal hyperalgesia, mechanical allodynia, weight bearing ability, and electrophysiological recording from primary afferent fibers. The rats inoculated with carcinoma cells showed significant ambulatory pain, mechanical allodynia, and reduction in weight bearing, as well as increased incidence of spontaneous activity in A{beta} fibers in affected limb, whereas PBS (vehicle) or heat-killed cells (sham) injected rats showed no significant difference in comparison to normal rats. The pain hypersensitive behaviors were aggravated with time and destruction of bone. Interestingly, mechanical allodynia was also observed in the contralateral limb, indicating the involvement of 'mirror image' pain in bone cancer pain. In summary, the present study provided a useful and easily established rat model of bone cancer pain which will contribute to further study of the mechanisms underlying cancer pain.

  7. Single incision laparoscopic cholecystectomy: Less scar, less pain

    PubMed Central

    Tyagi, Shantanu; Sinha, Rajeev; Tyagi, Aarti

    2017-01-01

    CONTEXT AND AIMS: Our study aims to evaluate the post-operative pain and cosmesis of single-incision laparoscopic cholecystectomy (SILC) in comparison with the standard, 3-port laparoscopic cholecystectomy (SLC) with respect to the length of incision, cosmetic scores, post-operative pain scores and duration of hospital stay. SETTINGS AND DESIGN: This comparative randomised study was conducted in a tertiary care centre teaching hospital between September 2012 and 2014. One hundred and fifty consecutive patients, who qualified as per inclusion criteria, were included in the study. SUBJECTS AND METHODS: Seventy-five patients were included in the SLC arm and 75 in the SILC arm. SILC procedure was carried out as transumbilical multiport technique and SLC as 3-port technique utilizing - 5, 5, 10 mm ports. STATISTICAL ANALYSIS USED: The data for the primary observations (post-operative pain scores, cosmetic score and incision length) and secondary observation (post-operative hospital stay) were noted. Weighted mean difference was used for calculation of quantitative variables, and odds ratios were used for pooling qualitative variables. RESULTS: Pain scores at 4 and 24 h were significantly better for SILC arm than SLC arm (at 4 h - 4.84 ± 0.95 vs. 6.17 ± 0.98, P < 0.05 and at 24 h - 3.84 ± 0.96 vs. 5.17 ± 0.09, P < 0.05). Length of incision was significantly smaller (SILC - 2.631 ± 0.44 cm vs. SLC - 5.11 ± 0.44 cm), P < 0.05 and cosmetic score was significantly better in SILC arm (6.25 ± 1.24) than SLC arm (4.71 ± 1.04), P < 0.05. Difference between the hospital stay is insignificant for two arms SILC (2.12 ± 0.34) and SLC (2.13 ± 0.35), P > 0.05. DISCUSSION: Significant difference was found in duration and intensity of pain between two procedures at 4 and 24 h. Cosmesis was significantly better in SILC than SLC group, the sample size in our study was small to arrive at a definite conclusion. The procedure can be selectively and judiciously performed by surgeons

  8. Single dose oral codeine, as a single agent, for acute postoperative pain in adults.

    PubMed

    Derry, Sheena; Moore, R Andrew; McQuay, Henry J

    2010-04-14

    Codeine is an opioid metabolised to active analgesic compounds, including morphine. It is widely available by prescription, and combination drugs including low doses of codeine are commonly available without prescription. To assess the efficacy, the time to onset of analgesia, the time to use of rescue medication and any associated adverse events of single dose oral codeine in acute postoperative pain. We searched CENTRAL, MEDLINE, EMBASE and PubMed to November 2009. Single oral dose, randomised, double-blind, placebo-controlled trials of codeine for relief of established moderate to severe postoperative pain in adults. Studies were assessed for methodological quality and data independently extracted by two review authors. Summed total pain relief (TOTPAR) or pain intensity difference (SPID) over 4 to 6 hours were used to calculate the number of participants achieving at least 50% pain relief, which were used to calculate, with 95% confidence intervals, the relative benefit compared to placebo, and the number needed to treat (NNT) for one participant to experience at least 50% pain relief over 4 to 6 hours. Numbers using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Data on adverse events and withdrawals were collected. Thirty-five studies were included (1223 participants received codeine 60 mg, 27 codeine 90 mg, and 1252 placebo). Combining all types of surgery (33 studies, 2411 participants), codeine 60 mg had an NNT of at least 50% pain relief over 4 to 6 hours of 12 (8.4 to 18) compared with placebo. At least 50% pain relief was achieved by 26% on codeine 60 mg and 17% on placebo.Following dental surgery the NNT was 21 (12 to 96) (15 studies, 1146 participants), and following other types of surgery the NNT was 6.8 (4.6 to 13) (18 studies, 1265 participants). The NNT to prevent use of rescue medication within 4 to 6 hours was 11 (6.3 to 50) (11 studies, 765 participants

  9. Single dose oral codeine, as a single agent, for acute postoperative pain in adults

    PubMed Central

    Derry, Sheena; Moore, R Andrew; McQuay, Henry J

    2014-01-01

    Background Codeine is an opioid metabolised to active analgesic compounds, including morphine. It is widely available by prescription, and combination drugs including low doses of codeine are commonly available without prescription. Objectives To assess the efficacy, the time to onset of analgesia, the time to use of rescue medication and any associated adverse events of single dose oral codeine in acute postoperative pain. Search methods We searched CENTRAL, MEDLINE, EMBASE and PubMed to November 2009. Selection criteria Single oral dose, randomised, double-blind, placebo-controlled trials of codeine for relief of established moderate to severe postoperative pain in adults. Data collection and analysis Studies were assessed for methodological quality and data independently extracted by two review authors. Summed total pain relief (TOTPAR) or pain intensity difference (SPID) over 4 to 6 hours were used to calculate the number of participants achieving at least 50% pain relief, which were used to calculate, with 95% confidence intervals, the relative benefit compared to placebo, and the number needed to treat (NNT) for one participant to experience at least 50% pain relief over 4 to 6 hours. Numbers using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Data on adverse events and withdrawals were collected. Main results Thirty-five studies were included (1223 participants received codeine 60 mg, 27 codeine 90 mg, and 1252 placebo). Combining all types of surgery (33 studies, 2411 participants), codeine 60 mg had an NNT of at least 50% pain relief over 4 to 6 hours of 12 (8.4 to 18) compared with placebo. At least 50% pain relief was achieved by 26% on codeine 60 mg and 17% on placebo. Following dental surgery the NNT was 21 (12 to 96) (15 studies, 1146 participants), and following other types of surgery the NNT was 6.8 (4.6 to 13) (18 studies, 1265 participants). The NNT to prevent

  10. MR Imaging Findings of Painful Type II Accessory Navicular Bone: Correlation with Surgical and Pathologic Studies

    PubMed Central

    Lee, Kyung Tai; Kang, Heung Sik; Kim, Eun Kyung

    2004-01-01

    Objective To evaluate the MR imaging findings of painful type II accessory navicular bone and to correlate these with the surgical and pathologic findings. Materials and Methods The MR images of 17 patients with medial foot pain and surgically proven type II accessory navicular abnormalities were reviewed. The changes of signal intensity in the accessory navicular, synchondrosis and adjacent soft tissue, the presence of synchondrosis widening, and posterior tibial tendon (PTT) pathology on the T1-weighted and fat-suppressed T2-weighted images were analyzed. The MR imaging findings were compared with the surgical and pathologic findings. Results The fat-suppressed T2-weighted images showed high signal intensity in the accessory navicular bones and synchondroses in all patients, and in the soft tissue in 11 (64.7%) of the 17 patients, as well as synchondrosis widening in 3 (17.6%) of the 17 patients. The MR images showed tendon pathology in 12 (75%) of the 16 patients with PTT dysfunction at surgery. The pathologic findings of 16 surgical specimens included areas of osteonecrosis with granulomatous inflammation, fibrosis and destruction of the cartilage cap. Conclusion The MR imaging findings of painful type II accessory navicular bone are a persistent edema pattern in the accessory navicular bone and within the synchondrosis, indicating osteonecrosis, inflammation and destruction of the cartilage cap. Posterior tibial tendon dysfunction was clinically evident in most patients. PMID:15637478

  11. MR imaging findings of painful type II accessory navicular bone: correlation with surgical and pathologic studies.

    PubMed

    Choi, Yun Sun; Lee, Kyung Tai; Kang, Heung Sik; Kim, Eun Kyung

    2004-01-01

    To evaluate the MR imaging findings of painful type II accessory navicular bone and to correlate these with the surgical and pathologic findings. The MR images of 17 patients with medial foot pain and surgically proven type II accessory navicular abnormalities were reviewed. The changes of signal intensity in the accessory navicular, synchondrosis and adjacent soft tissue, the presence of synchondrosis widening, and posterior tibial tendon (PTT) pathology on the T1-weighted and fat-suppressed T2-weighted images were analyzed. The MR imaging findings were compared with the surgical and pathologic findings. The fat-suppressed T2-weighted images showed high signal intensity in the accessory navicular bones and synchondroses in all patients, and in the soft tissue in 11 (64.7%) of the 17 patients, as well as synchondrosis widening in 3 (17.6%) of the 17 patients. The MR images showed tendon pathology in 12 (75%) of the 16 patients with PTT dysfunction at surgery. The pathologic findings of 16 surgical specimens included areas of osteonecrosis with granulomatous inflammation, fibrosis and destruction of the cartilage cap. The MR imaging findings of painful type II accessory navicular bone are a persistent edema pattern in the accessory navicular bone and within the synchondrosis, indicating osteonecrosis, inflammation and destruction of the cartilage cap. Posterior tibial tendon dysfunction was clinically evident in most patients.

  12. External beam radiotherapy for palliation of painful bone metastases: pooled data bioeffect dose response analysis of dose fractionation

    NASA Astrophysics Data System (ADS)

    Naveen, T.; Supe, Sanjay S.; Ganesh, K. M.; Samuel, Jacob

    2009-01-01

    Bone metastases develop in up to 70% of newly diagnosed cancer patients and result in immobility, anxiety, and depression, severely diminishing the patients quality of life. Radiotherapy is a frequently used modality for bone metastasis and has been shown to be effective in reducing metastatic bone pain and in some instances, causing tumor shrinkage or growth inhibition. There is controversy surrounding the optimal fractionation schedule and total dose of external beam radiotherapy, despite many randomized trials and overviews addressing the issue. This study was undertaken to apply BED to clinical fractionation data of radiotherapeutic management of bone metastases in order to arrive at optimum BED values for acceptable level of response rate. A computerised literature search was conducted to identify all prospective clinical studies that addressed the issue of fractionation for the treatment of bone metastasis. The results of these studies were pooled together to form the database for the analysis. A total of 4111 number of patients received radiation dose ranging from 4 to 40.5 Gy in 1 to 15 fractions with dose per fraction ranging from 2 to 10 Gy. Single fraction treatments were delivered in 2013 patients and the dose varied from 4 to 10 Gy. Multifraction treatments were delivered in 2098 patients and the dose varied from 15 to 40.5 Gy. The biological effective dose (BED) was evaluated for each fractionation schedule using the linear quadratic model and an α/β value of 10 Gy. Response rate increased significantly beyond a BED value of 14.4 Gy (p < 0.01). Based on our analysis and indications from the literature about higher retreatment and fracture rate of single fraction treatments, minimum BED value of 14.4 Gy is recommended.

  13. Topical treatment with Tong-Luo-San-Jie Gel alleviates bone cancer pain in rats

    PubMed Central

    Wang, Juyong; Zhang, Ruixin; Dong, Changsheng; Jiao, Liying; Xu, Ling; Liu, Jiyong; Wang, Zhengtao; Ying, Qi Liang Mao; Fong, Harry; Lao, Lixing

    2012-01-01

    Ethnopharmacological relevance The herbal analgesic gel Tong-Luo-San-Jie (TLSJ) and its modifications are used in traditional Chinese medicine to manage cancer pain. However, its mechanisms are still unknown. Aim of the study To investigate the effects and mechanisms of TLSJ gel on bone cancer pain in a rat model. Materials and Methods A bone cancer pain rat model was established by inoculating Walker 256 rat carcinoma cells directly into the right tibial medullary cavity of Sprague-Dawley rats (150–170 g); Phosphate buffered saline (PBS) tibial inoculation was used as control. Cancer-bearing rats were treated twice a day with external TLSJ gel (0.5 g/cm2/day) or inert gel control for 21 days (n=10/group). Behavioral tests such as mechanical threshold and paw withdrawal latency (PWL) were carried out. Osteoclastic activities were determined and carboxyterminal pyridinoline cross-linked type I collagen telopeptides (ICTP) and bone-specific alkaline phosphatase (BAP) concentrations were detected with ELISA after treatment. Adverse effects were monitored, and biochemical and histological tests were performed in naïve rats treated with local TLSJ gel for six weeks. Results TLSJ treatment significantly restored bone cancer-induced decrease of PWL and mechanical threshold compared to inert gel. It also decreased the level of blood serum ICTP and BAP and inhibited osteoclast activities. No adverse effects or abnormal biochemical and histological changes were detected after TLSJ treatment. Conclusion The present study shows that TLSJ significantly inhibits bone cancer-induced thermal and mechanical sensitization. It suggests that the gel may be useful in managing cancer pain and that it may act by inhibiting osteoclastic activity. PMID:22960543

  14. Pathobiology and management of prostate cancer-induced bone pain: recent insights and future treatments.

    PubMed

    Muralidharan, Arjun; Smith, Maree T

    2013-10-01

    Prostate cancer (PCa) has a high propensity for metastasis to bone. Despite the availability of multiple treatment options for relief of PCa-induced bone pain (PCIBP), satisfactory relief of intractable pain in patients with advanced bony metastases is challenging for the clinicians because currently available analgesic drugs are often limited by poor efficacy and/or dose-limiting side effects. Rodent models developed in the past decade show that the pathobiology of PCIBP comprises elements of inflammatory, neuropathic and ischemic pain arising from ectopic sprouting and sensitization of sensory nerve fibres within PCa-invaded bones. In addition, at the cellular level, PCIBP is underpinned by dynamic cross talk between metastatic PCa cells, cellular components of the bone matrix, factors associated with the bone microenvironment as well as peripheral components of the somatosensory system. These insights are aligned with the clinical management of PCIBP involving use of a multimodal treatment approach comprising analgesic agents (opioids, NSAIDs), radiotherapy, radioisotopes, cancer chemotherapy agents and bisphosphonates. However, a major drawback of most rodent models of PCIBP is their short-term applicability due to ethical concerns. Thus, it has been difficult to gain insight into the mal(adaptive) neuroplastic changes occurring at multiple levels of the somatosensory system that likely contribute to intractable pain at the advanced stages of metastatic disease. Specifically, the functional responsiveness of noxious circuitry as well as the neurochemical signature of a broad array of pro-hyperalgesic mediators in the dorsal root ganglia and spinal cord of rodent models of PCIBP is relatively poorly characterized. Hence, recent work from our laboratory to develop a protocol for an optimized rat model of PCIBP will enable these knowledge gaps to be addressed as well as identification of novel targets for drug discovery programs aimed at producing new analgesics

  15. Wideband Single-Crystal Transducer for Bone Characterization

    NASA Technical Reports Server (NTRS)

    Liang, Yu; Snook, Kevin

    2012-01-01

    The microgravity conditions of space travel result in unique physiological demands on the human body. In particular, the absence of the continual mechanical stresses on the skeletal system that are present on Earth cause the bones to decalcify. Trabecular structure decreases in thickness and increases in spacing, resulting in decreased bone strength and increased risk of injury. Thus, monitoring bone health is a high priority for long-term space travel. A single probe covering all frequency bands of interest would be ideal for such measurements, and this would also minimize storage space and eliminate the complexity of integrating multiple probes. This invention is an ultrasound transducer for the structural characterization of bone. Such characterization measures features of reflected and transmitted ultrasound signals, and correlates these signals with bone structure metrics such as bone mineral density, trabecular spacing, and thickness, etc. The techniques used to determine these various metrics require measurements over a broad range of ultrasound frequencies, and therefore, complete characterization requires the use of several narrowband transducers. This is a single transducer capable of making these measurements in all the required frequency bands. The device achieves this capability through a unique combination of a broadband piezoelectric material; a design incorporating multiple resonator sizes with distinct, overlapping frequency spectra; and a micromachining process for producing the multiple-resonator pattern with common electrode surfaces between the resonators. This device consists of a pattern of resonator bars with common electrodes that is wrapped around a central mandrel such that the radiating faces of the resonators are coplanar and can be simultaneously applied to the sample to be measured. The device operates as both a source and receiver of acoustic energy. It is operated by connection to an electronic system capable of both providing an

  16. Considerations in the selection of radiopharmaceuticals for palliation of bone pain from metastatic osseous lesions.

    PubMed

    Bouchet, L G; Bolch, W E; Goddu, S M; Howell, R W; Rao, D V

    2000-04-01

    Bone pain is a common complication for terminal patients with bone metastases from prostate, lung, breast, and other malignancies. A multidisciplinary approach in treating bone pain is generally required, 1 which includes a combination of analgesic drug therapy, radiation therapy, hormonal therapy, and chemotherapy. Over the years, treatment of bone pain using bone-seeking radiopharmaceuticals has been explored extensively. Pharmaceuticals labeled with energetic 1-particle emitters such as 32p, 89Sr, 153Sm, and 186Re, in addition to the low-energy electron emitter 117mSn, have been studied for this purpose. Bone-marrow toxicity as a consequence of chronic irradiation by the energetic , particles is a general problem associated with this form of treatment. It is therefore desirable to identify radiochemicals that minimize the dose to the bone marrow and at the same time deliver therapeutic doses to the bone. New S values (mean absorbed dose per unit cumulated activity) for target regions of human bone and marrow were used to ascertain the capacity of various radiochemicals to deliver a high bone dose while minimizing the marrow dose. The relative dosimetric advantage of a given radiopharmaceutical compared with a reference radiochemical was quantitated as a dosimetric relative advantage factor (RAF). Several radionuclides that emit energetic 1 particles (32p, 89Sr, 153Sm, 186Re, and 177Lu) and radionuclides that emit low-energy electrons or beta particles (169Er, 117mSn, and 33p) were evaluated. For these calculations, ratios of the cumulated activity in the bone relative to cumulated activity in the marrow alpha equal to 10 and 100 were used. When the radiopharmaceutical was assumed to be uniformly distributed in the endosteum and alpha was taken as 100 for both the reference and test radiochemicals, the RAF values compared with the reference radionuclide 32p were 1.0, 1.2, 1.4, 1.6, 1.7, 1.9, and 2.0 for 89Sr, 186Re, 153Sm, 177Lu, 169Er, 117mSn, and 33P

  17. Evaluation of Efficacy of Bone Scan With SPECT/CT in the Management of Low Back Pain: A Study Supported by Differential Diagnostic Local Anesthetic Blocks.

    PubMed

    Jain, Anuj; Jain, Suruchi; Agarwal, Anil; Gambhir, Sanjay; Shamshery, Chetna; Agarwal, Amita

    2015-12-01

    Conventional radiologic modalities provide details only about the anatomic aspect of the various structures of the spine. Frequently the structures that show abnormal morphology may not be the cause of low back pain (LBP). Functional imaging in the form of bone scan along with single photon emission computerized tomography (SPECT/CT) may be helpful in identifying structures causing pain, whether morphologically normal or not. The objective of this study is to evaluate the role of bone scan with SPECT/CT in management of patients with LBP. This is randomized double-blinded controlled study performed on 80 patients with LBP aged 20 to 80 years, ASA physical status I to III. Patients were randomized into bone scan and control groups consisting of 40 patients each. On the basis of the clinical features and radiologic findings a clinical diagnosis was made. After making a clinical diagnosis, the patients in bone scan group were subjected to bone scan with SPECT/CT. On the basis of the finding of the bone scan and SPECT/CT, a new working diagnosis was made and intervention was performed according to the new working diagnosis. Diagnostic blocks in the control group were given based on clinical diagnosis. Controlled comparative diagnostic blocks were performed with local anesthetic. The pain score just after the diagnostic block and at the time of discharge (approximately 4 h later) was recorded; the pain relief was recorded in percentage. In both the groups, sacroilitis was the most common diagnosis followed by facet joint arthropathy. The number of patients obtaining pain relief of >50% was significantly higher in the bone scan-positive group as compared with the control group. Three new clinical conditions were identified in the bone scan group. These conditions were multiple myeloma, avascular necrosis of the femoral head, and ankylosing spondylitis. Bone scan with SPECT/CT was found to complement the clinical workup of patients with LBP. Inclusion of bone scan with

  18. Clinical Assessment of Percutaneous Radiofrequency Ablation for Painful Metastatic Bone Tumors

    SciTech Connect

    Kojima, Hiroyuki Tanigawa, Noboru; Kariya, Shuji; Komemushi, Atsushi; Shomura, Yuzo; Sawada, Satoshi

    2006-12-15

    Purpose. To investigate the pain-alleviating effects of radiofrequency ablation (RFA) on metastatic bone tumors in relation to tumor size, combined therapy, and percent tumor necrosis rate following RFA. Methods. Subjects comprised 24 patients with 28 painful metastatic bone tumors. A 17G internally cooled electrode was inserted into the tumor for CT guidance and ablation was performed. Bone cement was injected following RFA for 4 tumors involving a weight-bearing bone, while 5 tumors were treated using combined RFA and external irradiation. Percent necrosis rate of the tumor was measured using contrast-enhanced computed tomography 1 week after RFA. Results. Improvement in the visual analog scale (VAS) score was 4.6 {+-} 2.2 for large tumors (>5 cm, n = 12), 3.7 {+-} 1.8 for medium-sized tumors (3.1-5.0 cm, n = 11), and 3.5 {+-} 1.7 for small tumors ({<=}3 cm, n = 4), with no significant differences noted among tumor sizes. Improvement in the VAS score was 3.5 {+-} 1.3 for the 4 tumors in the RFA + bone cement group, 3.2 {+-} 1.9 for the 5 tumors in the RFA + radiation therapy group, and 4.8 {+-} 2.2 for the 18 tumors in the RFA group. No significant differences were identified between groups. The improvement in the VAS score was 3.8 {+-} 2.3, 4.0 {+-} 1.9, and 4.7 {+-} 2.6 in patients with tumor necrosis rates of 0-49%, 50-74%, and 75-100%, respectively. No significant association was observed among these three groups. Conclusion. Percutaneous RFA therapy was effective in relieving pain due to metastatic bone tumors. No relationships appear to exist between initial response and tumor size, combined therapy, and percent tumor necrosis.

  19. Methods of reducing pain during bone marrow biopsy: a narrative review.

    PubMed

    Zahid, Mohammad Faizan

    2015-10-01

    Bone marrow examination plays a crucial role in the diagnosis and management of various hematological and systemic diseases. Even though the procedure has been carried out for decades, it remains an extremely painful and uncomfortable experience for a majority of patients. This paper reviews the different strategies used to provide analgesia and summarizes the advantages and drawbacks of one strategy over the other. A literature review was carried out addressing the different approaches to providing pain relief during bone marrow aspiration and biopsy. Several different methods, procedure modifications and protocols are employed at various centers but pain control and analgesia remain incomplete. Local infiltration with lidocaine or similar local analgesics is the standard at most centers. Although there is limited data, there are several studies in literature demonstrating the pain relieving effects of different methods and drugs when used with local anesthetics. Sedation, usually using benzodiazepines, reduces anticipatory anxiety, provides analgesia and also short term amnesia. Combinations of different agents not only yield potent effects but also reduce the required dose of each individual drug, minimizing adverse effects. Non-pharmacological factors also play key roles. Providing patients with complete and comprehensible information is vital to ensure the least amount of discomfort during the biopsy. Distraction techniques, such as cognitive behavioral therapy, hypnosis and music therapy, may also play a role in minimizing pain.

  20. [Pain control of bone and joint diseases in the elderly].

    PubMed

    Soen, Satoshi

    2014-10-01

    The decline of multiple physiological processes, even in the absence of disease, combined should logically influence treatment options. Decreased gastric secretions, intestinal motility, and vitamin D receptors lead to loss of appetite, malnutrition. Increased arterial thickening and rigidity elevate cardiac risk, while decreased elasticity in the lungs potentially exacerbates breathing disorders. Memory impairment and cognitive decline progress as neurons become less resilient to stress over time. Reduced hepatic and renal blood flow limit metabolism and filtration, increasing the risk for accumulation of toxic substances. Physiologic changes, drug-drug interactions resulting from polypharmacy, and drug-disease interactions combine to make elderly patients more sensitive to the AEs of medications. Effective pain management in the elderly is challenging. The purpose of this review is to highlight the use of several treatment options for elderly patients.

  1. Sports nuclear medicine. Bone imaging for lower extremity pain in athletes

    SciTech Connect

    Brill, D.R.

    1983-03-01

    Increased participation in sports by the general public has led to an increase in sports-induced injuries, including stress fractures, shin splints, arthritis, and a host of musculotendinous maladies. Bone scintigraphy with Tc-99m MDP has been used with increasing frequency in detecting stress fractures, but this study can miss certain important conditions and detect other lesions of lesser clinical significance. This paper demonstrates the spectrum of findings on bone scanning in nonacute sports trauma and offers suggestions for the optimal use of Tc-99m MDP for detecting the causes of lower extremity pain in athletes.

  2. CXCR3: latest evidence for the involvement of chemokine signaling in bone cancer pain.

    PubMed

    Guo, Genhua; Gao, Feng

    2015-03-01

    Growing evidence indicates that chemokines participate in the generation and maintenance of bone cancer pain (BCP). Recent work in Exp Neurol by Guan et al. (2015) demonstrated the involvement of spinal chemokine receptor CXCR3 and its downstream PI3K/Akt and Raf/MEK/ERK signaling pathways in BCP. This work provides new evidence to support that chemokines participate in central sensitization in BCP condition. Reviewed evidence suggests that few chemokines have been proved to be related to cancer pain. The underlying relationship between CXCR3 signaling and BCP condition requires further study.

  3. Bone Marrow Edema and Low Back Pain in Elderly Degenerative Lumbar Scoliosis: A Cross-Sectional Study.

    PubMed

    Nakamae, Toshio; Yamada, Kiyotaka; Shimbo, Takuro; Kanazawa, Toshikatsu; Okuda, Teruaki; Takata, Haruhiko; Hashimoto, Takashi; Hiramatsu, Takeshi; Tanaka, Nobuhiro; Ochi, Mitsuo; Olmarker, Kjell; Fujimoto, Yoshinori

    2016-05-01

    Cross-sectional study. To examine whether bone marrow edema is associated with low back pain in elderly patients with degenerative lumbar scoliosis. The cause of low back pain in degenerative lumbar scoliosis is unclear. A total of 120 degenerative lumbar scoliosis patients 65 years of age or older were evaluated. Radiography, computed tomography (CT), magnetic resonance imaging (MRI), and tender point examination in the lumbar spine were performed. On MRI, coronal gadolinium-contrasted T1- or T2-weighed fat-saturated images were used to score the size of bone marrow edema. The prevalence of bone marrow edema in patients with and without low back pain was compared; in patients with low back pain, we tested whether the locations of lumbar tender point were consistent with that of bone marrow edema. Bone marrow edema was found in 62 of 64 (96.9%) patients with low back pain compared with 21 of 56 (37.5%) patients without it (P < 0.001). Bone marrow edema located more frequently on the concave side than on the convex side of scoliosis (P < 0.001). Among patients with low back pain, bone marrow edema score was associated with low back pain severity (r = 0.724; P < 0.001), and the location of lumbar tender point were consistent with that of bone marrow edema (κ value = 0.745; P < 0.001). Bone marrow edema on MRI was closely associated with the presence of low back pain in elderly degenerative lumbar scoliosis. 4.

  4. Pain Palliation in Patients with Bone Metastases Using Magnetic Resonance-Guided Focused Ultrasound with Conformal Bone System: A Preliminary Report

    PubMed Central

    Joo, Bio; Lee, Soo Hyeon; Choi, Hye Jin; Lim, Seung Tack; Rha, Sun Young; Rachmilevitch, Itay; Lee, Young Han; Suh, Jin-Suck

    2015-01-01

    Purpose We evaluated the safety and effectiveness of the Magnetic Resonance-guided Focused Ultrasound (MRgFUS) with the ExAblate Conformal Bone System for the palliation of painful bone metastases. Materials and Methods Our Institutional Review Board approved this study, and all patients gave informed consent prior to enrollment. A total of six painful metastatic bone lesions in five patients were treated using MRgFUS with the ExAblate Conformal Bone System for pain palliation. The follow-up sessions were at 3 days, 2 weeks, 1, 2, and 3 months, and 1 year after treatment. Efficacy was evaluated by the changes in visual analog scale (VAS) scores. At 3-months and 1-year follow-ups, unenhanced computed tomography and contrast-enhanced MR imaging examinations were performed. All adverse events were assessed to evaluate treatment safety. Results All patients showed significant pain relief within 2 weeks. Two patients experienced complete pain reduction that lasted for 1 year. Two other patients showed pain relief measured as VAS scores of 2 and 4 on their last follow-up. Although the remaining patient had experienced significant pain relief in two lesions, the VAS score re-increased on his last follow-up. The size of the enhancing soft tissue mass in metastatic lesions decreased, and new bone formation was seen on follow-up images. Although adverse events were not serious, non-specific leg pain and second degree skin burn were noted. Conclusion MRgFUS was demonstrated to be effective palliative treatment within 2 weeks in selected patients with painful bone metastases. PMID:25684002

  5. Marrow toxicity of 33P-versus 32P-orthophosphate: implications for therapy of bone pain and bone metastases.

    PubMed

    Goddu, S M; Bishayee, A; Bouchet, L G; Bolch, W E; Rao, D V; Howell, R W

    2000-05-01

    Several bone-seeking radiopharmaceuticals, such as 32P-orthophosphate, 89Sr-chloride, 186Re-1,1 hydroxyethylidene diphosphonate (HEDP), and 153Sm-ethylene diamine tetramethylene phosphonic acid (EDTMP), have been used to treat bone pain. The major limiting factor with this modality is bone marrow toxicity, which arises from the penetrating nature of the high-energy beta particles emitted by the radionuclides. It has been hypothesized that marrow toxicity can be reduced while maintaining therapeutic efficacy by using radionuclides that emit short-range beta particles or conversion electrons. In view of the significant clinical experience with 32P-orthophosphate, and the similarity in pain relief afforded by 32P-orthophosphate and 89Sr-chloride, this hypothesis is examined in this study using 32P- and 33P-orthophosphate in a mouse femur model. Survival of granulocyte macrophage colony-forming cells (GM-CFCs) in femoral marrow was used as a biologic dosimeter for bone marrow. 32P- and 33P-orthophosphate were administered intravenously, and GM-CFC survival was determined as a function of time after injection and, at the nadir, as a function of injected activity. The kinetics of radioactivity in the marrow, muscle, and femoral bone were also determined. The biologic dosimeter was calibrated by assessing GM-CFC survival at its nadir after chronic irradiation of Swiss Webster mice with exponentially decreasing dose rates of gamma rays (relative biologic effectiveness equivalent to that of beta particles) from a low-dose rate 137Cs irradiator. Dose-rate decrease half-times (Td) (time required for 137Cs gamma ray dose rate to decrease by one half) of 62, 255, and 425 h and infinity were used to simulate the dose rate patterns delivered by the radiopharmaceuticals as dictated by their effective clearance half-times from the mouse femurs. These data were used to experimentally determine the mean absorbed dose to the femoral marrow per unit injected activity. Finally, a

  6. Determination of the painful level in osteoporotic vertebral fractures--Retrospective comparison between plain film, bone scan, and magnetic resonance imaging.

    PubMed

    Lin, Hsi-Hsien; Chou, Po-Hsin; Wang, Shih-Tien; Yu, Jung-Kuang; Chang, Ming-Chau; Liu, Chien-Lin

    2015-12-01

    Determining the actual painful vertebral level is difficult when evaluating osteoporotic vertebral fracture, especially when there are acute and chronic fractures simultaneously. In this study, we retrospectively evaluated and compared the findings between plain film, bone scan, and magnetic resonance imaging (MRI) in the diagnosis of new fracture in osteoporotic vertebral fractures. This is a retrospective clinical study of patients who were diagnosed with osteoporotic vertebral fractures using plain film, bone scan, and MRI within a 1-month interval between February 2008 and December 2012. The findings in plain film, the extent of increased uptake in bone scan, and signal change in MRI were compared to evaluate the actual level of pain. All patients received percutaneous vertebroplasty according to MR finding. Pain scores (visual analog scale) of the study patients were compared prior to and after the procedure. A total of 52 patients with a mean age of 79.1 years (range 59-92 years) were enrolled in this study, and were treated by vertebroplasty confirmed by MRI. It was observed that patient pain score (visual analog scale) improved from 7.6 to 2.8. Plain film examination revealed 79 vertebrae that were suspected to be compression fractures. Among the suspected vertebrae, 62 showed increased uptake in bone scan, and MRI showed bony edema change in 58 vertebrae. The consistency between bone scan and MRI was 96.9% in patients with single-level suspected fracture on plain film. There was moderate agreement (kappa was 0.56) in patients where multiple levels were noted. Fifteen vertebrae with vacuum cleft sign on plain film showed total concordance in both bone scan and MRI. For patients with single-level compression fracture, the painful level in osteoporotic vertebral fractures can be determined by plain film and bone scan testing. Vacuum cleft sign noted on plain film may be enough to localize the level of pain. However, MRI testing is further needed in multiple

  7. Chronic Osteoporotic Pain in Mice: Cutaneous and Deep Musculoskeletal Pain Are Partially Independent of Bone Resorption and Differentially Sensitive to Pharmacological Interventions

    PubMed Central

    Millecamps, Magali; Naso, Lina; Mori, Chisato

    2017-01-01

    Although the pathological changes in osteoporotic bones are well established, the characterization of the osteoporotic pain and its appropriate treatment are not fully elucidated. We investigated the behavioral signs of cutaneous and deep musculoskeletal pain and physical function; time-dependent changes in bone mineral density (BMD) and the emergence of the behavioral phenotype; and the effects of pharmacological interventions having different mechanisms of action (chronic intraperitoneal administration of pamidronate [0.25 mg/kg, 5x/week for 5 weeks] versus acute treatment with intraperitoneal morphine [10 mg/kg] and pregabalin [100 mg/kg]) in a mouse model of ovariectomized or sham-operated mice 6 months following surgery. We observed reduced BMD associated with weight gain, referred cutaneous hypersensitivity, and deep musculoskeletal pain that persisted for 6 months. Chronic bisphosphonate treatment, 6 months after ovariectomy, reversed bone loss and hypersensitivity to cold, but other behavioral indices of osteoporotic pain were unchanged. While the efficacy of acute morphine on cutaneous pain was weak, pregabalin was highly effective; deep musculoskeletal pain was intractable. In conclusion, the reversal of bone loss alone is insufficient to manage pain in chronic osteoporosis. Additional treatments, both pharmacological and nonpharmacological, should be implemented to improve quality of life for osteoporosis patients. PMID:28299231

  8. Comparison of patella bone strain between females with and without patellofemoral pain: a finite element analysis study.

    PubMed

    Ho, Kai-Yu; Keyak, Joyce H; Powers, Christopher M

    2014-01-03

    Elevated bone principal strain (an indicator of potential bone injury) resulting from reduced cartilage thickness has been suggested to contribute to patellofemoral symptoms. However, research linking patella bone strain, articular cartilage thickness, and patellofemoral pain (PFP) remains limited. The primary purpose was to determine whether females with PFP exhibit elevated patella bone strain when compared to pain-free controls. A secondary objective was to determine the influence of patella cartilage thickness on patella bone strain. Ten females with PFP and 10 gender, age, and activity-matched pain-free controls participated. Patella bone strain fields were quantified utilizing subject-specific finite element (FE) models of the patellofemoral joint (PFJ). Input parameters for the FE model included (1) PFJ geometry, (2) elastic moduli of the patella bone, (3) weight-bearing PFJ kinematics, and (4) quadriceps muscle forces. Using quasi-static simulations, peak and average minimum principal strains as well as peak and average maximum principal strains were quantified. Cartilage thickness was quantified by computing the perpendicular distance between opposing voxels defining the cartilage edges on axial plane magnetic resonance images. Compared to the pain-free controls, individuals with PFP exhibited increased peak and average minimum and maximum principal strain magnitudes in the patella. Additionally, patella cartilage thickness was negatively associated with peak minimum principal patella strain and peak maximum principal patella strain. The elevated bone strain magnitudes resulting from reduced cartilage thickness may contribute to patellofemoral symptoms and bone injury in persons with PFP.

  9. Effective and rapid treatment of painful localized transient osteoporosis (bone marrow edema) with intravenous ibandronate.

    PubMed

    Ringe, J D; Dorst, A; Faber, H

    2005-12-01

    Localized transient osteoporosis (LTO; bone marrow edema syndrome) is a rare disorder of generally unknown etiology that is characterized by acute onset of disabling bone pain. Treatment options are currently limited and largely ineffective. The locally increased bone turnover and low bone mineral density (BMD) typical of LTO indicate a potential role for bisphosphonate therapy. Ibandronate, a potent nitrogen-containing bisphosphonate, has proven efficacy in the management of postmenopausal osteoporosis and corticosteroid-induced osteoporosis when administered as a convenient intermittent intravenous (i.v.) injection with a between-dose interval of 2 or 3 months. In a study of 12 patients with LTO, ibandronate was administered as an initial 4-mg i.v. dose with a second, optional injection of 2 mg at 3 months. Daily calcium and vitamin D supplements were provided. Pain was measured at baseline and at 1, 2, 3, and 6 months using a visual analog scale (VAS) of 1-10, and BMD was measured at baseline and 6 months. I.v. ibandronate provided rapid and substantial pain relief. The mean (SD) VAS score decreased from 8.4 (1.3) at baseline to 0.5 (0.7) at 6 months, at which time seven patients had achieved complete pain relief. At 6 months, mean lumbar spine BMD had increased by 4.0% (range -0.8 to 7.7%) in the overall population. I.v. ibandronate injection affords advantages over currently available oral and i.v. bisphosphonates and thus offers a promising therapeutic advance in the treatment of LTO.

  10. The Bone Pain Crisis of Sickle Cell Disease and Malaria: Observations from Gujarat, India.

    PubMed

    Patel, Jyotish; Patel, Bharati; Serjeant, Graham R

    2017-01-01

    Sickle cell disease is a common problem across central India, but its clinical features may differ from that in African populations. There is a need to define the features of sickle cell disease in India, and the current study addresses some features of the bone pain crisis. The objective of the study was to describe the epidemiology of the bone pain crisis of sickle cell disease in Gujarat and explore the relationship with infection by Plasmodium vivax. This was a prospective review of all admissions in patients with sickle cell disease to a private pediatric institution in Bardoli, Gujarat, in the year 2015. Hemoglobin electrophoresis of all patients was consistent with homozygous sickle cell disease, but family studies indicated that at least seven cases had the severe sickle cell-beta + thalassemia presumed to be the common IVS1-5G>C mutation. Clinical, hematological, and parasitological features were recorded. There were 914 admissions among 654 patients who had between one and seven admissions. The bone pain crisis accounted for 763 (83%) of admissions and increased between July and October coinciding with the monsoon period. Blood smears were examined for malarial parasites in 811 admissions and were positive for P. vivax in 73% patients. There was no evidence that P. vivax infections varied with the cause of admission or increased during the monsoon period. There was a high prevalence of P. vivax infection in hospital admissions of sickle cell patients, but the data did not support an etiological role in the bone pain crisis. A trial of malarial prophylaxis might determine its effect on the clinical features and outcome of sickle cell disease.

  11. Groin pain in footballers: the association between preseason clinical and pubic bone magnetic resonance imaging findings and athlete outcome.

    PubMed

    Slavotinek, John Paul; Verrall, Geoffrey Mark; Fon, Gerald Tau; Sage, Michael Radford

    2005-06-01

    Groin pain and tenderness are common in athletes from a variety of codes of football, but little attention has been directed to the influence of magnetic resonance imaging and such clinical findings on athlete participation. Preseason groin pain, tenderness, and magnetic resonance imaging findings such as pubic bone marrow edema are associated with restricted training capacity and missed games. Cohort study; Level of evidence, 2. Fifty-two Australian footballers in the national competition were recruited. Preseason groin pain and focal tenderness were recorded, and magnetic resonance imaging of the groin was performed within 1 week of examination. Training restriction and games missed owing to groin pain were documented during the subsequent season. Magnetic resonance imaging showed pubic bone marrow edema in 19 of 52 (37%) footballers and linear parasymphyseal T2 hyperintensity in 16 of 52 (31%) footballers. Groin pain restricted training during the season in 22 of 52 (42%) footballers, and 9 of 52 (17%) footballers missed at least 1 game. Preseason pain (P = .0004), pubic bone tenderness (P = .02), and linear parasymphyseal T2 hyperintensity (P = .01) were associated with restricted training capacity during the subsequent season. Preseason groin pain (P = .03) was associated with missed games, but magnetic resonance imaging findings were not. Preseason pubic bone marrow edema, groin pain, and linear parasymphyseal T2 hyperintensity were associated with training restriction, but only preseason groin pain was associated with missed games.

  12. Dosimetry and toxicity of Samarium-153-EDTMP administered for bone pain due to skeletal metastases

    SciTech Connect

    Bayouth, J.E.; Macey, D.J.; Kasi, L.P.

    1994-01-01

    Palliation of bone pain in patients with cancer metastatic to bone is being evaluated in several cancer centers by the administration of the bone-seeking phosphonate ethylenediaminetetramethylenephosphonic acid (EDTMP) chelated with the beta particle-emitting radionuclide {sup 153}Sm. In this study {sup 153}Sm-EDTMP was intravenously injected into 19 patients over a 1-min period. Patients received up to four injections of 18.5 MBq (0.5 mCi) or 37 MBq (1.0mCi) per kilogram of body weight. Skeletal retention was calculated from urinary excretion. No uptake of {sup 153}Sm-EDTMP in nonskeletal tissues was observed in whole-body gamma camera images. The mean skeletal uptake for all patients was 54% {plus_minus} 16% of the injected dose (%ID). This resulted in the bone marrow receiving 89 cGy/GBq {plus_minus} 27 cGy/GBq (3.28 cGy/mCi {plus_minus} 0.99 cGy/mCi), with calculated marrow doses ranging from 27 cGy to 338 cGy. For each patient, the estimated radiation absorbed dose to the marrow was correlated to the percent decrease in platelet number, ranging from 7.4% to 78.9%. Since the deviation of uptake between the four injections for a given patient (7.6% ID) was less than the deviation for all patients (16% ID), the initial dose may be used to estimate the skeletal uptake for the remaining doses. These radiation dose estimates permit patients at risk to be identified prior to reaching myelotoxicity and develop dose-response models. Thirteen patients (68%) reported significant pain relief from this radionuclide therapy. Bone pain appears to be alleviated by {sup 153}Sm-EDTMP with limited red marrow doses and no toxic effects in other organs. 15 refs., 8 figs., 2 figs.

  13. A case report of disabling bone pain after long-term kidney transplantation.

    PubMed

    Myint, T M M; Vucak-Dzumhur, M; Ebeling, P R; Elder, G J

    2014-02-01

    A 77-year-old man, who received a renal transplant 13 years before for IgA glomerulonephritis, was referred after he developed bilateral mid-tibial aching pain that did not improve with simple analgesia. He had recently been changed from low-dose cyclosporine to tacrolimus, but the pain did not improve when this was reversed. He had a history of focal prostatic adenocarcinoma, cryptococcal lung infection, osteoporosis treated with alendronate for 2 years and multiple squamous cell carcinomas, including one requiring left neck dissection and radiotherapy. Upon physical examination, he had gouty tophi and marked bilateral tibial tenderness but had no other clinical findings. Laboratory investigations included an elevated intact parathyroid hormone value of 7.9 pmol/L (1.6 to 6.9), bone specific alkaline phosphatase of 22 µg/L (3.7 to 20.9), urinary deoxypyridinoline/creatinine ratio of 7.2 nmol/mmol (2.5 to 5.4) and C-reactive protein. Chest X-ray and tibial X-rays were normal, but there was marrow oedema and a prominent periosteal reaction on magnetic resonance imaging. A radionuclide bone scan showed increased symmetrical, linear uptake in both tibiae and the left femur, and uptake was also noted in both clinically asymptomatic humeri. Tibial bone biopsy disclosed small deposits of poorly differentiated metastatic cancer and a follow-up chest CT revealed a lung lesion. It was concluded that the bone pain and periostitis was caused by primary lung cancer with metastatic disease to bone, and an associated hypertrophic osteoarthropathy.

  14. Combined Microwave Ablation and Cementoplasty in Patients with Painful Bone Metastases at High Risk of Fracture

    SciTech Connect

    Pusceddu, Claudio; Sotgia, Barbara Fele, Rosa Maria; Ballicu, Nicola; Melis, Luca

    2016-01-15

    PurposeTo retrospectively evaluate the effectiveness of computed tomography-guided percutaneous microwave ablation (MWA) and cementoplasty in patients with painful bone metastases at high risk of fracture.Materials and MethodsThirty-five patients with 37 metastatic bone lesions underwent computed tomography-guided MWA combined with cementoplasty (polymethylmethacrylate injection). Vertebrae, femur, and acetabulum were the intervention sites and the primary end point was pain relief. Pain severity was estimated by visual analog scale (VAS) before treatment; 1 week post-treatment; and 1, 6, and 12 months post-treatment. Functional outcome was assessed by improved patient walking ability. Radiological evaluation was performed at baseline and 3 and 12 months post-procedure.ResultsIn all patients, pain reduction occurred from the first week after treatment. The mean reduction in the VAS score was 84, 90, 90 % at week 1, month 1, and month 6, respectively. Improved walking ability occurred in 100 and 98 % of cases at the 1- and 6-month functional outcome evaluations, respectively. At the 1-year evaluation, 25 patients were alive, and 10 patients (28 %) had died because of widespread disease. The mean reduction in the VAS score and improvement in surviving patients’ walking ability were 90 and 100 %, respectively. No patients showed evidence of local tumor recurrence or progression and pathological fracture in the treated sites.ConclusionOur results suggest that MWA combined with osteoplasty is safe and effective when treating painful bone metastases at high risk of fracture. The number of surviving patients at the 1-year evaluation confirms the need for an effective and long-lasting treatment.

  15. {sup 188}Rhenium-HEDP in the Treatment of Pain in Bone Metastases

    SciTech Connect

    Gaudiano, J.; Savio, E.; Robles, A.; Muniz, S.; Leon, A.; Verdera, S.; Martinez, G.; Hermida, J.C.; Knapp, F.F., Jr.

    1999-01-18

    Systemic use of radiopharmaceuticals is a recognized alternative method for the treatment of pain in patients with multiple bone metastasis. A new option, {sup 188}Re-HEDP is proposed, using generator-obtained {sup 188}Rhenium ({beta} energy = 2.1 MeV, {gamma} energy = 155 keV, half-life = 16.9 hours). After establishing parameters of biodistribution, dosimetry and image acquisition in mice, rats and rabbits, Phase I and II studies were conducted on 12 patients with multiple metastasis from carcinomas, with pain surpassing other analgesic options. More than 50% pain relief was found in 91% of the patients, with total relief during a variable period in 41% of them allowing opiate and other analgesic drugs to be decreased or withdrawn, and showing a lower bone marrow contribution to total absorbed dose than that reported for other similar radiopharmaceuticals. Further study of this option is recommended in order to determine higher dose protocols without toxic bone marrow reaction possibilities.

  16. Expectations and effects of a single yoga session on pain perception

    PubMed Central

    Ferrari, Marie-Louise Gander; Thuraisingam, Silvia; Känel, Roland v; Egloff, Niklaus

    2015-01-01

    Background: Several studies show yoga may benefit chronic pain management. We investigated the effect of a single yoga session on the perception of pain, measured by a standardized pain provocation test in healthy yoga participants while also comparing pain perception to participants’ own expectations. Materials and Methods: Ninety yoga participants were recruited at hatha yoga schools in Switzerland. Pain perception was measured with a standardized algometric pain provocation test; i.e., a calibrated peg was applied for 10 seconds after which the participant rated pain intensity on a 0–10 numerical rating scale. The test was applied to the middle finger, ear lobe, and second toe before and after a 60-minute yoga session. Results: Sixty out of 90 (66.7%) yoga participants expected a reduced pain perception after the yoga session. However, 36 (40%) participants actually experienced less pain after compared to before the yoga session. But overall, pain perception statistically did not significantly change from before to after the yoga session at any of the three body locations assessed. The expectations and also the previous yoga experience did not significantly influence the participants’ pain perception. Conclusions: Regardless of the high positive expectations on the influence of yoga on pain, a single yoga session does not significantly influence pain perception induced by a pain provocation test. Hypoalgesic effects of yoga should be explained otherwise. PMID:26170598

  17. Expectations and effects of a single yoga session on pain perception.

    PubMed

    Ferrari, Marie-Louise Gander; Thuraisingam, Silvia; von Känel, Roland; Egloff, Niklaus

    2015-01-01

    Several studies show yoga may benefit chronic pain management. We investigated the effect of a single yoga session on the perception of pain, measured by a standardized pain provocation test in healthy yoga participants while also comparing pain perception to participants' own expectations. Ninety yoga participants were recruited at hatha yoga schools in Switzerland. Pain perception was measured with a standardized algometric pain provocation test; i.e., a calibrated peg was applied for 10 seconds after which the participant rated pain intensity on a 0-10 numerical rating scale. The test was applied to the middle finger, ear lobe, and second toe before and after a 60-minute yoga session. Sixty out of 90 (66.7%) yoga participants expected a reduced pain perception after the yoga session. However, 36 (40%) participants actually experienced less pain after compared to before the yoga session. But overall, pain perception statistically did not significantly change from before to after the yoga session at any of the three body locations assessed. The expectations and also the previous yoga experience did not significantly influence the participants' pain perception. Regardless of the high positive expectations on the influence of yoga on pain, a single yoga session does not significantly influence pain perception induced by a pain provocation test. Hypoalgesic effects of yoga should be explained otherwise.

  18. The relationship between patient age and pain management of acute long-bone fracture in the ED.

    PubMed

    Boccio, Eric; Wie, Benjamin; Pasternak, Susan; Salvador-Kelly, Anabella; Ward, Mary Frances; D'Amore, Jason

    2014-12-01

    Certain patient populations may be unable to communicate their needs in the emergency department (ED) setting, and the ability to communicate varies between age groups. We aim to determine if there are differences in pain management of acute long-bone fracture (ALBF) among age groups presenting to the ED. This study was a retrospective chart review of a consecutive sample of subjects over 13 months. Fracture site, subject age, arrival time, whether pain medication was administered, and time to initial administration were recorded. Subjects were categorized into 3 groups based on age: pediatric (<18 years), adult (≥18 and <65 years), and geriatric (≥65 years). A total of 1255 patients were included in analysis. One hundred seventy-seven (78.0%) pediatric, 364 (86.5%) adult, and 486 (80.1%) geriatric patients received pain medication during their ED stay. Median and average times to initial pain medication administration with 95% confidence intervals were 44 and 52.0 minutes (45.9-58.1), 39 and 53.6 minutes (48.8-58.4), and 55 and 73.2 minutes (68.1-78.3) for pediatric, adult, and geriatric groups, respectively. A single-factor analysis of variance indicated a significant difference between the groups (P<.01). Student t tests revealed significant differences between pediatric and geriatric groups (P<.01) and adult and geriatric groups (P<.01). Although most patients presenting to the ED with ALBF were geriatric, these patients were the least likely to have their pain addressed in a timely fashion. Subgroup analysis of pediatric and geriatric populations indicates significant delay, especially for those ages younger than 3 and 85 years and older. We believe that patients within these groups experience the greatest difficulty communicating their needs effectively due to age-related issues. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Antinociceptive Effect of Intrathecal Microencapsulated Human Pheochromocytoma Cell in a Rat Model of Bone Cancer Pain

    PubMed Central

    Li, Xiao; Li, Guoqi; Wu, Shaoling; Zhang, Baiyu; Wan, Qing; Yu, Ding; Zhou, Ruijun; Ma, Chao

    2014-01-01

    Human pheochromocytoma cells, which are demonstrated to contain and release met-enkephalin and norepinephrine, may be a promising resource for cell therapy in cancer-induced intractable pain. Intrathecal injection of alginate-poly (l) lysine-alginate (APA) microencapsulated human pheochromocytoma cells leads to antinociceptive effect in a rat model of bone cancer pain, and this effect was blocked by opioid antagonist naloxone and alpha 2-adrenergic antagonist rauwolscine. Neurochemical changes of cerebrospinal fluid are in accordance with the analgesic responses. Taken together, these data support that human pheochromocytoma cell implant-induced antinociception was mediated by met-enkephalin and norepinephrine secreted from the cell implants and acting at spinal receptors. Spinal implantation of microencapsulated human pheochromocytoma cells may provide an alternative approach for the therapy of chronic intractable pain. PMID:25007069

  20. Spinal interleukin-33 and its receptor ST2 contribute to bone cancer-induced pain in mice.

    PubMed

    Zhao, J; Zhang, H; Liu, S-B; Han, P; Hu, S; Li, Q; Wang, Z-F; Mao-Ying, Q-L; Chen, H-M; Jiang, J-W; Wu, G-C; Mi, W-L; Wang, Y-Q

    2013-12-03

    Cancer pain, particularly bone cancer pain, affects the quality of life of cancer patients, and current treatments are limited. Interleukin (IL)-33, a new member of the IL-1 super family, has been reported to be involved in the modulation of inflammatory pain. However, studies focused on its role in the modulation of cancer pain have been rare. The present study was designed to investigate whether spinal IL-33/ST2 signaling was involved in bone cancer-induced pain in mice. Bone cancer was induced via intra-femoral inoculation of 4T1 mammary carcinoma cells. The mice inoculated with carcinoma cells showed mechanical allodynia, heat hyperalgesia and a reduction in limb use, whereas phosphate-buffered saline or heat-killed cells-injected mice showed no significant difference compared to non-treated mice. The pain hypersensitive behaviors worsened over time and with bone destruction. Both the mRNA and the protein levels of IL-33 and relative cytokines (IL-1β, IL-6, TNF-a) were significantly increased in the spinal cord after the inoculation of carcinoma cells. Intrathecal administration of ST2 antibody to block IL-33/ST2 signaling alleviated pain behaviors in a dose-dependent manner in bone cancer pain mice compared with vehicle-injected mice. Moreover, the ST2(-/-) mice showed a significant amelioration of limb use and heat hyperalgesia compared to wild-type mice. Meanwhile, concentrations of spinal IL-1β, IL-6 and TNF-a in the cancer-bearing ST2(-/-) mice had no significant changes. These data further suggested that IL-33/ST2 signaling played a vital role in cancer pain. Our results provided evidence that IL-33 and its receptor ST2 may be a potential therapeutic target for the treatment of pain in bone cancer patients.

  1. Radiofrequency ablation versus 125I-seed brachytherapy for painful metastases involving the bone

    PubMed Central

    Jiao, Dechao; Wu, Gang; Ren, Jianzhuang; Han, Xinwei

    2016-01-01

    This retrospective study aimed to demonstrate and compare the safety and effectiveness of computed tomography-guided radiofrequency ablation (RFA) and 125I-seed brachytherapy for painful bone metastases after failure of external beam radiotherapy (EBRT). From June 2013 to October 2015, 79 patients with moderate-to-severe pain caused by metastatic bone lesions who underwent either RFA (n = 41) or 125I-seed brachytherapy (n = 38) were enrolled. Pain in patients was measured using the brief pain inventory (BPI) before treatment, 1 week after treatment, and 3 months after treatment. Response rates were assessed by measuring the changes in pain and incorporation of changes in the analgesic requirements. At baseline, 1 week, and 3 months, the mean worst pain scores of BPI were 7.8, 5.4, and 2.7, respectively, for the RFA group and 7.7, 6.1, and 2.8, respectively, for the brachytherapy group. At 1 week, the complete and partial response rates were 12% and 59%, respectively, in the RFA group compared with 3% and 45%, respectively, in the brachytherapy group. At 3 months, the complete and partial response rates were 23% and 58%, respectively, in the RFA group compared with 24% and 52% in the brachytherapy group (p = 0.95). The response rates in the RFA group were significantly higher than those in the brachytherapy group at 1 week (p = 0.32), but comparable at 3 weeks (p = 0.95). Both groups had low rates of complications and no treatment-related mortality. In conclusion, the short-term curative efficiency of RFA was better than that of brachytherapy, but the log-term efficiency of both treatments was equal. PMID:27636995

  2. A Prospective, Single-Blind, Placebo-Controlled Trial of Bone Marrow Aspirate Concentrate for Knee Osteoarthritis.

    PubMed

    Shapiro, Shane A; Kazmerchak, Shari E; Heckman, Michael G; Zubair, Abba C; O'Connor, Mary I

    2017-01-01

    Bone marrow aspirate concentrate (BMAC) is increasingly used as a regenerative therapy for musculoskeletal pathological conditions despite limited evidence-based support. BMAC will prove feasible, safe, and efficacious for the treatment of pain due to mild to moderate degenerative joint disease of the knee. Randomized controlled trial; Level of evidence, 2. In this prospective, single-blind, placebo-controlled trial, 25 patients with bilateral knee pain from bilateral osteoarthritis were randomized to receive BMAC into one knee and saline placebo into the other. Fifty-two milliliters of bone marrow was aspirated from the iliac crests and concentrated in an automated centrifuge. The resulting BMAC was combined with platelet-poor plasma for an injection into the arthritic knee and was compared with a saline injection into the contralateral knee, thereby utilizing each patient as his or her own control. Safety outcomes, pain relief, and function as measured by Osteoarthritis Research Society International (OARSI) measures and the visual analog scale (VAS) score were tracked initially at 1 week, 3 months, and 6 months after the procedure. There were no serious adverse events from the BMAC procedure. OARSI Intermittent and Constant Osteoarthritis Pain and VAS pain scores in both knees decreased significantly from baseline at 1 week, 3 months, and 6 months ( P ≤ .019 for all). Pain relief, although dramatic, did not differ significantly between treated knees ( P > .09 for all). Early results show that BMAC is safe to use and is a reliable and viable cellular product. Study patients experienced a similar relief of pain in both BMAC- and saline-treated arthritic knees. Further study is required to determine the mechanisms of action, duration of efficacy, optimal frequency of treatments, and regenerative potential. Registration: ClinicalTrials.gov record 12-004459.

  3. An Easy Tool to Predict Survival in Patients Receiving Radiation Therapy for Painful Bone Metastases

    SciTech Connect

    Westhoff, Paulien G.; Graeff, Alexander de; Monninkhof, Evelyn M.; Bollen, Laurens; Dijkstra, Sander P.; Steen-Banasik, Elzbieta M. van der; Vulpen, Marco van; Leer, Jan Willem H.; Marijnen, Corrie A.; Linden, Yvette M. van der

    2014-11-15

    Purpose: Patients with bone metastases have a widely varying survival. A reliable estimation of survival is needed for appropriate treatment strategies. Our goal was to assess the value of simple prognostic factors, namely, patient and tumor characteristics, Karnofsky performance status (KPS), and patient-reported scores of pain and quality of life, to predict survival in patients with painful bone metastases. Methods and Materials: In the Dutch Bone Metastasis Study, 1157 patients were treated with radiation therapy for painful bone metastases. At randomization, physicians determined the KPS; patients rated general health on a visual analogue scale (VAS-gh), valuation of life on a verbal rating scale (VRS-vl) and pain intensity. To assess the predictive value of the variables, we used multivariate Cox proportional hazard analyses and C-statistics for discriminative value. Of the final model, calibration was assessed. External validation was performed on a dataset of 934 patients who were treated with radiation therapy for vertebral metastases. Results: Patients had mainly breast (39%), prostate (23%), or lung cancer (25%). After a maximum of 142 weeks' follow-up, 74% of patients had died. The best predictive model included sex, primary tumor, visceral metastases, KPS, VAS-gh, and VRS-vl (C-statistic = 0.72, 95% CI = 0.70-0.74). A reduced model, with only KPS and primary tumor, showed comparable discriminative capacity (C-statistic = 0.71, 95% CI = 0.69-0.72). External validation showed a C-statistic of 0.72 (95% CI = 0.70-0.73). Calibration of the derivation and the validation dataset showed underestimation of survival. Conclusion: In predicting survival in patients with painful bone metastases, KPS combined with primary tumor was comparable to a more complex model. Considering the amount of variables in complex models and the additional burden on patients, the simple model is preferred for daily use. In addition, a risk table for survival is provided.

  4. Single walled carbon nanotube composites for bone tissue engineering.

    PubMed

    Gupta, Ashim; Woods, Mia D; Illingworth, Kenneth David; Niemeier, Ryan; Schafer, Isaac; Cady, Craig; Filip, Peter; El-Amin, Saadiq F

    2013-09-01

    The purpose of this study was to develop single walled carbon nanotubes (SWCNT) and poly lactic-co-glycolic acid (PLAGA) composites for orthopedic applications and to evaluate the interaction of human stem cells (hBMSCs) and osteoblasts (MC3T3-E1 cells) via cell growth, proliferation, gene expression, extracellular matrix production and mineralization. PLAGA and SWCNT/PLAGA composites were fabricated with various amounts of SWCNT (5, 10, 20, 40, and 100 mg), characterized and degradation studies were performed. Cells were seeded and cell adhesion/morphology, growth/survival, proliferation and gene expression analysis were performed to evaluate biocompatibility. Imaging studies demonstrated uniform incorporation of SWCNT into the PLAGA matrix and addition of SWCNT did not affect the degradation rate. Imaging studies revealed that MC3T3-E1 and hBMSCs cells exhibited normal, non-stressed morphology on the composites and all were biocompatible. Composites with 10 mg SWCNT resulted in highest rate of cell proliferation (p < 0.05) among all composites. Gene expression of alkaline phosphatase, collagen I, osteocalcin, osteopontin, Runx-2, and Bone Sialoprotein was observed on all composites. In conclusion, SWCNT/PLAGA composites imparted beneficial cellular growth capabilities and gene expression, and mineralization abilities were well established. These results demonstrate the potential of SWCNT/PLAGA composites for musculoskeletal regeneration and bone tissue engineering (BTE) and are promising for orthopedic applications.

  5. A Traditional Chinese Medicine Xiao-Ai-Tong Suppresses Pain through Modulation of Cytokines and Prevents Adverse Reactions of Morphine Treatment in Bone Cancer Pain Patients

    PubMed Central

    Cong, Yan; Sun, Kefu; He, Xueming; Li, Jinxuan; Dong, Yanbin; Zheng, Bin; Tan, Xiao; Song, Xue-Jun

    2015-01-01

    Treating cancer pain continues to possess a major challenge. Here, we report that a traditional Chinese medicine Xiao-Ai-Tong (XAT) can effectively suppress pain and adverse reactions following morphine treatment in patients with bone cancer pain. Visual Analogue Scale (VAS) and Quality of Life Questionnaire (EORTC QLQ-C30) were used for patient's self-evaluation of pain intensity and evaluating changes of adverse reactions including constipation, nausea, fatigue, and anorexia, respectively, before and after treatment prescriptions. The clinical trials showed that repetitive oral administration of XAT (200 mL, bid, for 7 consecutive days) alone greatly reduced cancer pain. Repetitive treatment with a combination of XAT and morphine (20 mg and 30 mg, resp.) produced significant synergistic analgesic effects. Meanwhile, XAT greatly reduced the adverse reactions associated with cancer and/or morphine treatment. In addition, XAT treatment significantly reduced the proinflammatory cytokines interleukin-1β and tumor necrosis factor-α and increased the endogenous anti-inflammatory cytokine interleukin-10 in blood. These findings demonstrate that XAT can effectively reduce bone cancer pain probably mediated by the cytokine mechanisms, facilitate analgesic effect of morphine, and prevent or reduce the associated adverse reactions, supporting a use of XAT, alone or with morphine, in treating bone cancer pain in clinic. PMID:26617438

  6. A Traditional Chinese Medicine Xiao-Ai-Tong Suppresses Pain through Modulation of Cytokines and Prevents Adverse Reactions of Morphine Treatment in Bone Cancer Pain Patients.

    PubMed

    Cong, Yan; Sun, Kefu; He, Xueming; Li, Jinxuan; Dong, Yanbin; Zheng, Bin; Tan, Xiao; Song, Xue-Jun

    2015-01-01

    Treating cancer pain continues to possess a major challenge. Here, we report that a traditional Chinese medicine Xiao-Ai-Tong (XAT) can effectively suppress pain and adverse reactions following morphine treatment in patients with bone cancer pain. Visual Analogue Scale (VAS) and Quality of Life Questionnaire (EORTC QLQ-C30) were used for patient's self-evaluation of pain intensity and evaluating changes of adverse reactions including constipation, nausea, fatigue, and anorexia, respectively, before and after treatment prescriptions. The clinical trials showed that repetitive oral administration of XAT (200 mL, bid, for 7 consecutive days) alone greatly reduced cancer pain. Repetitive treatment with a combination of XAT and morphine (20 mg and 30 mg, resp.) produced significant synergistic analgesic effects. Meanwhile, XAT greatly reduced the adverse reactions associated with cancer and/or morphine treatment. In addition, XAT treatment significantly reduced the proinflammatory cytokines interleukin-1β and tumor necrosis factor-α and increased the endogenous anti-inflammatory cytokine interleukin-10 in blood. These findings demonstrate that XAT can effectively reduce bone cancer pain probably mediated by the cytokine mechanisms, facilitate analgesic effect of morphine, and prevent or reduce the associated adverse reactions, supporting a use of XAT, alone or with morphine, in treating bone cancer pain in clinic.

  7. JNK in spinal cord facilitates bone cancer pain in rats through modulation of CXCL1.

    PubMed

    Wang, Zhong-liang; Du, Ting-ting; Zhang, Rui-guang

    2016-02-01

    In patients with advanced cancer, cancer-induced bone pain (CIBP) is a severe and common problem that is difficult to manage and explain. As c-Jun N-terminal kinase (JNK) and chemokine (C-X-C motif) ligand 1 (CXCL1) have been shown to participate in several chronic pain processes, we investigated the role of JNK and CXCL1 in CIBP and the relationship between them. A rat bone cancer pain model was established by intramedullary injection of Walker 256 rat gland mammary carcinoma cells into the left tibia of Sprague-Dawley rats. As a result, intramedullary injection of Walker 256 carcinoma cells induced significant bone destruction and persistent pain. Both phosphorylated JNK1 (pJNK1) and pJNK2 showed time-dependent increases in the ipsilateral spinal cord from day 7 to day 18 after tumor injection. Inhibition of JNK activation by intrathecal administration of SP600125, a selective pJNK inhibitor, attenuated mechanical allodynia and heat hyperalgesia caused by tumor inoculation. Tumor cell inoculation also induced robust CXCL1 upregulation in the ipsilateral spinal cord on day 18 after tumor injection. Inhibition of CXCL1 by intrathecal administration of CXCL1 neutralizing antibody showed a stable analgesic effect. Intrathecal administration of SP600125 reduced CXCL1 increase in the spinal cord, whereas inhibition of CXCL1 in the spinal cord showed no influence on JNK activation. Taken together, these results suggested that JNK activation in spinal cord contributed to the maintenance of CIBP, which may act through modulation of CXCL1. Inhibition of the pJNK/CXCL1 pathway may provide a new choice for treatment of CIBP.

  8. Endoscopically and Fluoroscopically Assisted Curettage and Bone Grafting of the Navicular Bone Cyst.

    PubMed

    Lui, Tun Hing

    2016-12-01

    Simple bone cyst is a common tumorlike lesion of the bone and can involve the bones of the foot. It is usually asymptomatic but can also present with pain or pathologic fracture. The purpose of this technical note is to describe the uni-osseous portal approach of endoscopic curettage and bone grafting of simple bone cyst of the navicular bone. The single-portal approach reduces the risk of iatrogenic fracture of the navicular bone. This is indicated for painful bone cyst of the navicular bone resistant to conservative treatment. It is contraindicated in multiple septated cysts, the presence of pathologic fracture, or the presence of aggressive cystic lesions.

  9. CXCL12/CXCR4 chemokine signaling in spinal glia induces pain hypersensitivity through MAPKs-mediated neuroinflammation in bone cancer rats.

    PubMed

    Hu, Xue-Ming; Liu, Yan-Nan; Zhang, Hai-Long; Cao, Shou-Bin; Zhang, Ting; Chen, Li-Ping; Shen, Wen

    2015-02-01

    The activation of MAPK pathways in spinal cord and subsequent production of proinflammatory cytokines in glial cells contribute to the development of spinal central sensitization, the basic mechanism underlying bone cancer pain (BCP). Our previous study showed that spinal CXCL12 from astrocytes mediates BCP generation by binding to CXCR4 in both astrocyters and microglia. Here, we verified that CXCL12/CXCR4 signaling contributed to BCP through a MAPK-mediated mechanism. In naïve rats, a single intrathecal administration of CXCL12 considerably induced pain hyperalgesia and phosphorylation expression of spinal MAPK members (including extracellular signal-regulated kinase, p38, and c-Jun N-terminal kinase), which could be partially prevented by pre-treatment with CXCR4 inhibitor AMD3100. This CXCL12-induced hyperalgesia was also reduced by MAPK inhibitors. In bone cancer rats, tumor cell inoculation into the tibial cavity caused prominent and persistent pain hyperalgesia, and associated with up-regulation of CXCL12 and CXCR4, activation of glial cells, phosphorylation of MAPKs, and production of proinflammatory cytokines in the spinal cord. These tumor cell inoculation-induced behavioral and neurochemical alterations were all suppressed by blocking CXCL12/CXCR4 signaling or MAPK pathways. Taken together, these results demonstrate that spinal MAPK pathways mediated CXCL12/CXCR4-induced pain hypersensitivity in bone cancer rats, which could be druggable targets for alleviating BCP and glia-derived neuroinflammation. Following tumor cell inoculation, chemokine CXCL12 from astrocytes spreads around the spinal environment, resulting in functional activation of CXCR4-expressing astrocytes and microglia. Once glia are activated, they may initiate MAPK (mitogen-activated protein kinase) pathways, and subsequently produce proinflammatory cytokines and chemokines. Among them, CXCL12 could reinforce the astrocytic and microglial activation in autocrine and paracrine manners

  10. Joint pain undergoes a transition in accordance with signal changes of bones detected by MRI in hip osteoarthritis.

    PubMed

    Kamimura, Mikio; Nakamura, Yukio; Ikegami, Shota; Uchiyama, Shigeharu; Kato, Hiroyuki

    2013-01-01

    In this study, we aimed to investigate whether joint pain is derived from cartilage or bone alterations. We reviewed 23 hip joints of 21 patients with primary hip osteoarthritis (OA), which were classified into Kellgren-Laurence (KL) grading I to IV. Plain radiographs and magnetic resonance imaging (MRI) were obtained from all of the 23 joints. Two of the 21 patients had bilateral hip OA. Pain was assessed based on the pain scale of Denis. A Welch t test was performed for age, height, weight, body mass index, bone mineral density, and a Mann-Whitney U test was performed for KL grading. Four of 8 hip joints with pain and OA showed broad signal changes detected by MRI. Fourteen hip joints without pain, but with OA did not show broad signal changes by MRI. Collectively, MRI analyses showed that broad signal changes in OA cases without joint pain or with a slight degree of joint pain were not observed, while broad signal changes were observed in OA cases with deteriorated joint pain. Our findings suggest that hip joint pain might be associated with bone signal alterations in the hips of OA patients.

  11. Painful pathologic fracture of the humerus: percutaneous osteoplasty with bone marrow nails under hybrid computed tomography and fluoroscopic guidance.

    PubMed

    Anselmetti, Giovanni Carlo; Manca, Antonio; Chiara, Gabriele; Tutton, Sean; Iussich, Gabriella; Gino, Giancarlo; Grignani, Giovanni; Ortega, Cinzia; Moselli, Nora; Regge, Daniele

    2011-07-01

    A case of a 75-year-old patient with a painful pathologic humeral shaft fracture, with unacceptably high surgical risk and unsatisfactory analgesia is reported. In this case, impaired arm function and persistent pain with conservative management resulted in a poor quality of life. Palliation with image-guided percutaneous osteoplasty was considered. Because of potential cement leakage, inadequate fracture reduction, the site of the fracture, and the mobility of the joints in that area, image-guided percutaneous delivery of metallic bone marrow nails implanted together with polymethyl methacrylate (PMMA) osteoplasty was performed. This procedure achieved humeral shaft stabilization, bone fragment alignment, fracture reduction, and pain relief.

  12. Role of ATP-sensitive potassium channels in modulating nociception in rat model of bone cancer pain.

    PubMed

    Xia, Hui; Zhang, Dengwen; Yang, Shijie; Wang, Yu; Xu, Lin; Wu, Jinjing; Ren, Jing; Yao, Wenlong; Fan, Longchang; Zhang, Chuanhan; Tian, Yuke; Pan, Hui-Lin; Wang, Xueren

    2014-03-20

    Bone cancer pain is a major clinical problem and remains difficult to treat. ATP-sensitive potassium (KATP) channels may be involved in regulating nociceptive transmission at the spinal cord level. We determined the role of spinal KATP channels in the control of mechanical hypersensitivity in a rat model of bone cancer pain. The rat model of bone cancer pain was induced by implanting rat mammary gland carcinoma cells (Walker256) into the tibias. KATP modulators (pinacidil and glibenclamide) or the specific Kir6.2-siRNA were injected via an intrathecal catheter. The mechanical withdrawal threshold of rats was tested using von Frey filaments. The Kir6.2 mRNA and protein levels were measured by quantitative PCR and western blots, respectively. Intrathecal injection of pinacidil, a KATP channel opener, significantly increased the tactile withdrawal threshold of cancer cell-injected rats in a dose-dependent manner. In contrast, intrathecal delivery of glibenclamide, a KATP channel blocker, or the specific Kir6.2-siRNA significantly reduced the tactile withdrawal threshold of cancer cell-injected rats. The mRNA and protein levels of Kir6.2 in the spinal cord of cancer cell-injected rats were significantly lower than those in control rats. Our findings suggest that the KATP channel expression level in the spinal cord is reduced in bone cancer pain. Activation of KATP channels at the spinal level reduces pain hypersensitivity associated with bone cancer pain.

  13. Catestatin, vasostatin, cortisol, and pain assessments in dogs suffering from traumatic bone fractures.

    PubMed

    Srithunyarat, Thanikul; Hagman, Ragnvi; Höglund, Odd V; Stridsberg, Mats; Olsson, Ulf; Hanson, Jeanette; Nonthakotr, Chalermkwan; Lagerstedt, Anne-Sofie; Pettersson, Ann

    2017-03-21

    Traumatic bone fractures cause moderate to severe pain, which needs to be minimized for optimal recovery and animal welfare, illustrating the need for reliable objective pain biomarkers for use in a clinical setting. The objectives of this study were to investigate catestatin (CST) and vasostatin (VS) concentrations as two new potential biomarkers, and cortisol concentrations, scores of the short form of the Glasgow composite measure pain scale (CMPS-SF), and visual analog scale (VAS) in dogs suffering from traumatic bone fractures before and after morphine administration in comparison with healthy dogs. Fourteen dogs with hind limb or pelvic fractures and thirty healthy dogs were included. Dogs with fractures were divided into four groups according to analgesia received before participation. Physical examination, CMPS-SF, pain and stress behavior VAS scores were recorded in all dogs. Saliva and blood were collected once in healthy dogs and in dogs with fractures before and 35-70 min after morphine administration. Blood samples were analyzed for CST, VS, and cortisol. Saliva volumes, however, were insufficient for analysis. Catestatin and cortisol concentrations, and CMPS-SF, and VAS scores differed significantly between dogs with fractures prior to morphine administration and healthy dogs. After morphine administration, dogs with fractures had significantly decreased CMPS-SF and VAS scores and, compared to healthy dogs, CST concentrations, CMPS-SF, and VAS scores still differed significantly. However, CST concentrations remained largely within the normal range. Absolute delta values for CST significantly correlated with delta values for CMPS-SF. Catestatin and cortisol did not differ significantly before and after morphine administration. Vasostatin concentrations did not differ significantly between groups. Catestatin and cortisol concentrations, CMPS-SF, and VAS scores differed significantly in the dogs with traumatic bone fractures compared to the healthy dogs

  14. Involvement of RVM-expressed P2X7 receptor in bone cancer pain: mechanism of descending facilitation.

    PubMed

    Huang, Zhang Xiang; Lu, Zhi Jie; Ma, Wei Qing; Wu, Fei Xiang; Zhang, Yu Qiu; Yu, Wei-Feng; Zhao, Zhi Qi

    2014-04-01

    Patients with bone cancer commonly experience bone pain that is severe, intolerable, and difficult to manage. The rostral ventromedial medulla (RVM) plays an important role in the development of chronic pain via descending facilitation of spinal nociception. The compelling evidence shows that glial P2X7 receptor (P2X7R) is involved in the induction and maintenance of chronic pain syndromes. The present study explored the mechanism of glial activation and P2X7R expression underlying the induction of bone cancer pain. The results demonstrated that microglia and astrocytes in the RVM were markedly activated in bone cancer rats, and the expression of P2X7R was significantly upregulated. Injection of Brilliant Blue G (BBG), an inhibitor of P2X7R, into the RVM significantly alleviated pain behaviors of cancer rats, which was supported by intra-RVM injection of RNA interference targeting the P2X7R in the RVM. It is suggested that activation of microglia-expressed P2X7R in the RVM contributes to bone cancer pain. Given that 5-HT in the RVM is involved in modulating spinal nociception, changes in 5-HT and Fos expression were addressed in the spinal cord. Inhibition of P2X7R by BBG or small-interference RNA targeting P2X7 in the RVM markedly reduced 5-HT level and Fos expression in the spinal cord. The data clearly suggest that the activation of microglial P2X7R in the RVM contributes to the development of bone cancer pain via upregulation of spinal 5HT levels by the descending pain facilitatory system.

  15. Successful management of complex regional pain syndrome type 1 using single injection interscalene brachial plexus block

    PubMed Central

    Fallatah, Summayah M.A.

    2014-01-01

    Complex regional pain syndrome (CRPS) type 1 of the upper limb is a painful and debilitating condition. Interscalene brachial plexus block (ISB) in conjugation with other modalities was shown to be a feasible therapy with variable success. We reported a case of CRPS type 1 as diagnosed by International Association for the Study of Pain criteria in which pharmacological approaches failed to achieve adequate pain relief and even were associated with progressive dysfunction of the upper extremity. Single injection ISB, in combination with physical therapy and botulinum toxin injection, was successful to alleviate pain with functional restoration. PMID:25422619

  16. Optimal treatment of painful bone metastases with Samarium EDTMP in a haemodialysis patient: effectiveness and safety of internal radiotherapy.

    PubMed

    Skalli, Saadia; Desruet, Marie-Dominique; Bourre, Jean-Cyril; Caravel, Jean-Pierre; Vuillez, Jean-Philippe

    2009-08-01

    One of the current therapeutic approaches in the treatment of osteoblastic bone metastases uses the affinity of Samarium ((153)Sm) ethylene-diamine-tetramethylene phosphonic acid (EDTMP) for bone areas of bone turnover. As Samarium EDTMP is a beta-emitter, the radiotherapy contributes to osteoblastic bone lesion control over time. To date, the safety and effectiveness of Samarium therapy have not been established in patients with renal impairment. In this first report, we describe our experience of use of Samarium EDTMP in conjunction with biphosphonates in a haemodialysis patient for treatment of painful bone metastasis. Encouraging results were obtained in achieving pain control. The use of this radioisotope could be more widely applied to treat haemodialysis patients.

  17. Effects of massage therapy on pain and anxiety arising from intrathecal therapy or bone marrow aspiration in children with cancer.

    PubMed

    Çelebioğlu, Ayda; Gürol, Ayşe; Yildirim, Zuhal Keskin; Büyükavci, Mustafa

    2015-12-01

    Cancer and its treatment are stressful and reduce the quality of life in children. The aim of this study was to investigate the effect of massage therapy on pain and anxiety arising from intrathecal therapy or bone marrow aspiration in children with cancer. We conducted a controlled pretest/posttest quasi-experimental study at a paediatric oncology unit in Turkey. Twenty-five children were enrolled in this study. Their pain and anxiety were determined using a visual analogue scale. When the pretest and posttest pain and anxiety levels of the groups were compared, no statistically significant difference was found (P > 0.05). It was determined that pain and anxiety levels in the experimental group decreased significantly. This study provides preliminary evidence for the effectiveness in children of massage in reducing pain and anxiety arising from intrathecal therapy or bone marrow aspiration. © 2014 Wiley Publishing Asia Pty Ltd.

  18. Magnetic resonance guided focused ultrasound surgery (MRgFUS) of bone metastases: From primary pain palliation to local tumor control

    NASA Astrophysics Data System (ADS)

    Napoli, A.; Leonardi, A.; Andrani, F.; Boni, F.; Anzidei, M.; Catalano, C.

    2017-03-01

    Purpose: To evaluate the clinical performance of MRgFUS in primary pain palliation of painful bone metastases and in local tumor control. Materials and Methods: We enrolled 26 consecutive patients (female/male 12/14; age: 64.7±7.5yrs) with painful bone metastases. Before and 3 months after MRgFUS treatment pain severity and pain interference scores were assessed according to Brief Pain Inventory-Quality of Life (BPI-QoL) criteria and patients underwent both CT and MRI. Local tumor control was evaluated according to lesion size, density and perfusion at CT, dynamic contrast enhancement at MRI (Discovery 750HD, GE; Gd-Bopta, Bracco) and metabolic activity at PET or scintigraphy. Patients were classified as responders or non-responders. Results: No treatment-related adverse events were recorded during the study. As statistically significant difference between baseline and follow-up values for both pain severity and pain interference scores was observed (p<0.05). Increased bone density was observed in 9/26 (34.6%) patients. Non-Perfused Volume values ranged between 20% and 92%. There was no difference in NPV values between responders and non-responders (46.7±24.2% [25 - 90 %] vs. 45±24.9% [20 - 93 %]; p=0.7). In 6 patients (5 prostate and 1 breast primary cancer) there was nearly absence of metabolic activity after treatment (mean SUV=1.2). Conclusion: MRgFUS can be safely and effectively used as the primary treatment for pain palliation in patients with painful bone metastases; moreover our experience demonstrated also a potential role for the MRgFUS in local tumor control.

  19. (153)Sm-EDTMP for pain relief of bone metastases from prostate and breast cancer and other malignancies.

    PubMed

    Correa-González, Luis; Arteaga de Murphy, Consuelo; Pichardo-Romero, Pablo; Pedraza-López, Martha; Moreno-García, Claudia; Correa-Hernández, Luis

    2014-05-01

    Approximately 85% of patients with cancer suffer severe metastatic bone pain for which radionuclide therapy has been employed for pain palliation. We undertook this study to evaluate the pain relief effect of (153)Sm-EDTMP in Mexican patients with severe and painful bone metastases from mainly prostate, breast, and renal cancer and other malignancies. Patients (277) with intense sustained pain caused by bone metastases were referred to the Nuclear Medicine Department of the Oncology Hospital of the Mexican Social Security Institute. The patients had to have acceptable physical conditions, a previous positive (99m)Tc-MDP scan and blood values within normal range. (153)Sm-EDTMP was prepared at the Instituto Nacional de Investigaciones Nucleares (ININ) and 37 MBq/kg of body weight was injected intravenously. Pain palliation was evaluated with a visual analogue scale (VAS) and a verbal rating scale (VRS) before treatment and 3 and 12 weeks after treatment was started. The age interval of the patients was 24-92 years with a mean age of 64 ± 12 years. Mean values for hemoglobin, leukocyte and platelet counts did not statistically differ at zero time, 3 and 12 weeks after treatment. Pain intensity and relief assessment were statistically different: 9.1 ± 0.61 units initially; 4.2 ± 1.3 units 3 weeks later (54%) and after 12 weeks the pain diminished to 2.4 ± 1.4 units (74%) in the pain relief score scales. (153)Sm-EDTMP was readily available, safe and well tolerated. We conclude that (153)Sm-EDTMP was an adequate palliative agent and was the best option for our Mexican patients to relieve their severe metastatic bone pain. Copyright © 2014 IMSS. Published by Elsevier Inc. All rights reserved.

  20. Gorham-Stout disease presenting with dyspnea and bone pain in a 9-year-old girl.

    PubMed

    Davalos, Eric A; Gandhi, Nishant M; Barank, David; Varma, Rajeev K

    2015-01-01

    Gorham-Stout (GS) disease is a rare bone disorder of unknown etiology that is characterized by local proliferation of small vascular or lymphatic channels, resulting in progressive osteolysis and bone resorption. The diagnosis of GS disease is one of exclusion, with radiography and histopathology playing key roles. We describe a 9-year-old girl who presented to us with dyspnea and bone pain. She was found to have a cystic mass of the upper extremity, multiple cystic bone lesions, multiple fractures of different ages, and pleural effusions. We review the radiologic images that helped establish the diagnosis of GS disease.

  1. The use of dynamic bone scanning in the evaluation of wrist and hand pain

    SciTech Connect

    Gandsman, E.J.; Deutsch, S.D.; Catalozzi, K.; Herndon, J.

    1984-01-01

    Twenty-seven patients with complaints of wrist and/or hand pain were evaluated using a quantitative technique of dynamic (blood flow analysis) and static bone scan. The patients were divided in two groups according to their clinical history. Group A included 13 patients with a history of trauma. Seven patients had scaphoid fracture and 6 of them were scanned to determine non-union and/or avascular necrosis of the joint. One patient was scanned to determine the viability of a graft for non-union fracture. In all cases the scan gave a correct diagnosis as confirmed by later x-ray changes. Six patients in this group had negative x-rays. The scan demonstrated 4 cases of occult fractures, 4 had early Kienbock's Disease (KD) and 1 a soft tissue tumor. Group B included 14 patients with no known history of trauma. Nine had positive x-rays including 3 with KD that were scanned to determine their viability for surgical replacement of the lunate. The scan could distinguish between isolated involvement of the lunate and secondary degenerative changes of the surrounding carpal bones and radiocarpal joint. Two patients with tumor were correctly diagnosed by the scan, one as benign and one malignant. Four other patients with nonspecific changes on x-ray showed early arthritis (3 cases) and a cyst of the triquetrum ( 1 case) on the bone scan. Four patients in Group B had negative x-rays and the scan showed degenerative changes (3 cases) and an occult fracture of the hamate (1 case). The use of dynamic and static bone scanning appears to be a very valuable technique in the evaluation of patients with wrist and hand pain.

  2. A study of bone densitometry in patients with complex regional pain syndrome after stroke

    PubMed Central

    Kumar, V; Kalita, J; Gujral, R; Sharma, V; Misra, U

    2001-01-01

    INTRODUCTION—This study was undertaken to evaluate the bone mineral density (BMD) in patients with complex regional pain syndrome type-I (CRPS-I) after stroke, and to correlate it with various clinical and neurophysiological parameters.
PATIENTS AND METHODS—Twenty patients with CRPS-I after stroke were included and a detailed neurological evaluation was carried out. The severity of CRPS-I was graded on the basis of shoulder hand syndrome score. All the patients underwent bone mineral densitometry of paralysed and non-paralysed forearm by dual energy x ray absorptiometry. The BMD of paralysed forearm was also compared with that of age matched healthy controls. Neurophysiological tests included sympathetic skin response in both upper and lower limbs and median somatosensory evoked potentials.
RESULTS—The mean age of patients was 57.2 (45-75) years and eight were females. Eight patients had severe weakness and 12 had moderate weakness of grade 2 on the hemiplegic side. There was significant reduction in BMD in the patients compared with controls (p<0.01). The bone density reduction correlated well with duration of illness (r = −0.673, p<0.01), shoulder hand syndrome score (r = −0.804, p<0.01), and Canadian neurological scale score (r = −0.738 p<0.01). Sympathetic skin response was not recordable bilaterally in all patients. Median somatosensory evoked potentials were not recordable in seven out of 20 patients who also had higher grade of CRPS-I.
CONCLUSION—Our results show significant reduction of BMD in patients with CRPS-I after stroke. The reduction in BMD correlates with the severity of shoulder hand syndrome score, degree of weakness, duration of hemiplegia, and the severity of stroke.


Keywords: stroke; complex regional pain syndrome type I; bone mineral density PMID:11470933

  3. Mechanical Properties of a Single Cancellous Bone Trabeculae Taken from Bovine Femur

    NASA Astrophysics Data System (ADS)

    Enoki, Shinichi; Sato, Mitsuhiro; Tanaka, Kazuto; Katayama, Tsutao

    The increase of patients with osteoporosis is becoming a social problem, thus it is an urgent issue to find its prevention and treatment methods. Since cancellous bone is metabolically more active than cortical bone, cancellous bone is often used for diagnosis of osteoporosis and has received much attention within the study of bone. Bone is a hierarchically structured material and its mechanical properties vary at different structural levels, therefore it is important to break down the mechanical testing of bone according to the various levels within bone material. Mechanical properties of cancellous bone is said to be depended on quantities and orientation of trabecular bone. It is supposed that mechanical properties of trabecular bone are constant without depending on any structural arrangement and parts. However, such assumption has not been established in studies of trabecular bone. Furthermore test results have a large margin of error caused by insufficient shape assessment. In this study, three point bending tests of single cancellous bone trabeculae extracted from bovine femur were conducted to evaluate the effects of directions to the femur major axis direction on the mechanical properties. X-ray μCT was used to obtain shape of trabecular bone specimens. Furthermore compression tests of cancellous bone specimens, which were extracted in 10mm cubic geometry, were conducted for evaluation of directional properties.There were small difference in the elastic modulus of the trabecular bones which were extracted in parallel and in perpendicular to the major axis of femur. Considering from the results that the cancellous bone specimens, which were extracted in 10mm cubic geometry, have different elastic properties depending on the tested directions; the bone structure has larger influence than bone material property on the mechanical properties of cancellous bone.

  4. Single-level instrumented posterolateral fusion of the lumbar spine with a local bone graft versus an iliac crest bone graft: a prospective, randomized study with a 2-year follow-up.

    PubMed

    Ohtori, Seiji; Suzuki, Miyako; Koshi, Takana; Takaso, Masashi; Yamashita, Masaomi; Yamauchi, Kazuyo; Inoue, Gen; Suzuki, Munetaka; Orita, Sumihisa; Eguchi, Yawara; Ochiai, Nobuyasu; Kishida, Shunji; Kuniyoshi, Kazuki; Nakamura, Junichi; Aoki, Yasuchika; Ishikawa, Tetsuhiro; Arai, Gen; Miyagi, Masayuki; Kamoda, Hiroto; Toyone, Tomoaki; Takahashi, Kazuhisa

    2011-04-01

    The iliac crest bone grafting (ICBG) technique for lumbar posterolateral fusion surgery is widely used; however, donor site problems such as pain and sensory disturbance have been reported. Local bone is available for fusion surgery, but its reliability as a graft has not been fully reported. In the current study, we examined single-level instrumented posterolateral fusion with a local bone graft versus an ICBG in a prospective randomized study. Eighty-two patients diagnosed with L4 degenerated spondylolisthesis were divided into two groups at random. Forty-two patients underwent instrumented posterolateral fusion with a local bone graft (L4-L5 level), and 40 patients underwent instrumented posterolateral fusion with an ICBG (L4-L5 level). Rate and duration of bone union, visual analog scale (VAS) score, Japanese orthopedic association score (JOAS), Oswestry Disability Index (ODI), and complications were evaluated before and 2 years after therapy. VAS score, JOAS, and ODI were not significantly different between the two groups before and after surgery (P > 0.05). Rate and average duration of bone union were 90% and 8.5 months in the local bone graft group, and 85% and 7.7 months in the ICBG group, but without significant difference (P > 0.05). Prolonged surgical time and complications such as donor site pain (8 patients) and sensory disturbance (6 patients) were observed in the ICBG group. If single-level posterolateral fusion was performed, local bone graft technique has the same bone union rate compared with ICBG, requires less surgical time, and has fewer complications.

  5. Effects of massage on pain, mood status, relaxation, and sleep in Taiwanese patients with metastatic bone pain: a randomized clinical trial.

    PubMed

    Jane, Sui-Whi; Chen, Shu-Ling; Wilkie, Diana J; Lin, Yung-Chang; Foreman, Shuyuann Wang; Beaton, Randal D; Fan, Jun-Yu; Lu, Mei-Ying; Wang, Yi-Ya; Lin, Yi-Hsin; Liao, Mei-Nan

    2011-10-01

    To date, patients with bony metastases were only a small fraction of the samples studied, or they were entirely excluded. Patients with metastatic cancers, such as bone metastases, are more likely to report pain, compared to patients without metastatic cancer (50-74% and 15%, respectively). Their cancer pain results in substantial morbidity and disrupted quality of life in 34-45% of cancer patients. Massage therapy (MT) appears to have positive effects in patients with cancer; however, the benefits of MT, specifically in patients with metastatic bone pain, remains unknown. The purpose of this randomized clinical trial was to compare the efficacy of MT to a social attention control condition on pain intensity, mood status, muscle relaxation, and sleep quality in a sample (n=72) of Taiwanese cancer patients with bone metastases. In this investigation, MT was shown to have beneficial within- or between-subjects effects on pain, mood, muscle relaxation, and sleep quality. Results from repeated-measures analysis of covariance demonstrated that massage resulted in a linear trend of improvements in mood and relaxation over time. More importantly, the reduction in pain with massage was both statistically and clinically significant, and the massage-related effects on relaxation were sustained for at least 16-18 hours postintervention. Furthermore, massage-related effects on sleep were associated with within-subjects effects. Future studies are suggested with increased sample sizes, a longer interventional period duration, and an objective and sensitive measure of sleep. Overall, results from this study support employing MT as an adjuvant to other therapies in improving bone pain management.

  6. Dexamethasone in the prophylaxis of radiation-induced pain flare after palliative radiotherapy for bone metastases: a double-blind, randomised placebo-controlled, phase 3 trial.

    PubMed

    Chow, Edward; Meyer, Ralph M; Ding, Keyue; Nabid, Abdenour; Chabot, Pierre; Wong, Philip; Ahmed, Shahida; Kuk, Joda; Dar, A Rashid; Mahmud, Aamer; Fairchild, Alysa; Wilson, Carolyn F; Wu, Jackson S Y; Dennis, Kristopher; Brundage, Michael; DeAngelis, Carlo; Wong, Rebecca K S

    2015-11-01

    Pain flare occurs after palliative radiotherapy, and dexamethasone has shown potential for prevention of such flare. We aimed to compare the efficacy of dexamethasone with that of placebo in terms of reduction of incidence of pain flare. In this double-blind, randomised, placebo-controlled phase 3 trial, patients from 23 Canadian centres were randomly allocated (1:1) with a web-based system and minimisation algorithm to receive either two 4 mg dexamethasone tablets or two placebo tablets taken orally at least 1 h before the start of radiation treatment (a single 8 Gy dose to bone metastases; day 0) and then every day for 4 days after radiotherapy (days 1-4). Patients were eligible if they had a non-haematological malignancy and bone metastasis (or metastases) corresponding to the clinically painful area or areas. Patients reported their worst pain scores and opioid analgesic intake before treatment and daily for 10 days after radiation treatment. They completed the European Organisation for Research and Treatment of Cancer (EORTC) quality of life QLQ-C15-PAL, the bone metastases module (EORTC QLQ-BM22), and the Dexamethasone Symptom Questionnaire at baseline, and at days 10 and 42 after radiation treatment. Pain flare was defined as at least a two-point increase on a scale of 0-10 in the worst pain score with no decrease in analgesic intake, or a 25% or greater increase in analgesic intake with no decrease in the worst pain score from days 0-10, followed by a return to baseline levels or below. Primary analysis of incidence of pain flare was by intention-to-treat (patients with missing primary data were classified as having pain flare). This study is registered with ClinicalTrials.gov, number NCT01248585, and is completed. Between May 30, 2011, and Dec 11, 2014, 298 patients were enrolled. 39 (26%) of 148 patients randomly allocated to the dexamethasone group and 53 (35%) of 150 patients in the placebo group had a pain flare (difference 8·9%, lower 95% confidence

  7. Mas-related G-protein-coupled receptor c agonist bovine adrenal medulla 8-22 attenuates bone cancer pain in mice

    PubMed Central

    Sun, Yu-E; Lu, Cui-E; Lei, Yishan; Liu, Yue; Ma, Zhengliang; Gu, Xiaoping

    2015-01-01

    Objectives: The aim of this study is to investigate the effects of Mas-related G-protein-coupled receptor C (MrgC) agonist bovine adrenal medulla 8-22 (BAM8-22) on bone cancer pain and mirror-image pain. Methods: Bone cancer pain was induced by intramedullary injection of NC2472 fibrosarcoma cells in the mice. BAM8-22 and/or anti-MrgC antibody were injected intrathecally at day 14 after bone cancer induction and their effects on pain behaviors were detected. The pain behaviours were assessed by the number of spontaneous foot lifts and paw withdrawal mechanical threshold (PWMT) tests. MrgC expression was detected using western blot analysis and immunofluorescence assay. Results: There were increased bone cancer pain and mirror-image pain in the tumor-bearing mice while not in the sham-treated mice. BAM8-22 attenuated bone cancer pain in mice dose dependently with the highest effects at 2 hr after BAM8-22 administration, and anti-MrgC antibody reversed the effects of BAM8-22. However, intrathecal administration of BAM8-22 did not affect the mirror-image pain. Furthermore, BAM8-22 stimulated the expression of MrgC in the spinal dorsal horn. Conclusions: MrgC agonist BAM8-22 could attenuate bone cancer pain in mice. This study may provide a novel strategy for the treatment of bone cancer pain. PMID:26884930

  8. A systematic review of the relationship between subchondral bone features, pain and structural pathology in peripheral joint osteoarthritis.

    PubMed

    Barr, Andrew J; Campbell, T Mark; Hopkinson, Devan; Kingsbury, Sarah R; Bowes, Mike A; Conaghan, Philip G

    2015-08-25

    Bone is an integral part of the osteoarthritis (OA) process. We conducted a systematic literature review in order to understand the relationship between non-conventional radiographic imaging of subchondral bone, pain, structural pathology and joint replacement in peripheral joint OA. A search of the Medline, EMBASE and Cochrane library databases was performed for original articles reporting association between non-conventional radiographic imaging-assessed subchondral bone pathologies and joint replacement, pain or structural progression in knee, hip, hand, ankle and foot OA. Each association was qualitatively characterised by a synthesis of the data from each analysis based upon study design, adequacy of covariate adjustment and quality scoring. In total 2456 abstracts were screened and 139 papers were included (70 cross-sectional, 71 longitudinal analyses; 116 knee, 15 hip, six hand, two ankle and involved 113 MRI, eight DXA, four CT, eight scintigraphic and eight 2D shape analyses). BMLs, osteophytes and bone shape were independently associated with structural progression or joint replacement. BMLs and bone shape were independently associated with longitudinal change in pain and incident frequent knee pain respectively. Subchondral bone features have independent associations with structural progression, pain and joint replacement in peripheral OA in the hip and hand but especially in the knee. For peripheral OA sites other than the knee, there are fewer associations and independent associations of bone pathologies with these important OA outcomes which may reflect fewer studies; for example the foot and ankle were poorly studied. Subchondral OA bone appears to be a relevant therapeutic target. PROSPERO registration number: CRD 42013005009.

  9. Inhibition of spinal UCHL1 attenuates pain facilitation in a cancer-induced bone pain model by inhibiting ubiquitin and glial activation

    PubMed Central

    Cheng, Wei; Chen, Yuan-Li; Wu, Liang; Miao, Bei; Yin, Qin; Wang, Jin-Feng; Fu, Zhi-Jian

    2016-01-01

    The present study examined alterations of spinal ubiquitin C-terminal hydrolase L1 (UCHL1), ubiquitin expression and glial activation in the cancer-induced bone pain rats. Furthermore, whether inhibition of spinal UCHL1 could alleviate cancer-induced bone pain was observed. The CIBP model was established by intrathecal Walker 256 mammary gland carcinoma cells in SD rats. The rats of CIBP developed significant pain facilitation in the Von Frey test. Double immunofluorescence analyses revealed that in the spines of CIBP rats, ubiquitin co-localized with NeuN, Iba-1 or GFAP; UCHL1 and NeuN were co-expressed and UCHL1 also co-localized with ubiquitin. The CIBP model induced up-regulation of ubiquitin and UCHL1 in the spines, as well as glial activation. Inhibition of spinal UCHL1 attenuated pain facilitation by down-regulation of ubiquitin expression and glial activation. in the CIBP rats. Our data suggests that UCHL1/ubiquitin distributed and increased in the spines of CIBP rats, that glial activation also increased in the CIBP model and that inhibition of spinal UCHL1 may be an effective method to alleviate cancer-induced bone pain. PMID:27508024

  10. Single walled carbon nanotube networks as substrates for bone cells

    NASA Astrophysics Data System (ADS)

    Tutak, Wojtek

    A central effort in biomedical research concerns the development of materials for sustaining and controlling cell growth. Carbon nanotube based substrates have been shown to support the growth of different kinds of cells. However the underlying molecular mechanisms remain poorly defined. To address the fundamental question of mechanisms by which nanotubes promote bone mitosis and histogenesis, primary calvariae osteoblastic cells were grown on single walled carbon nanotube (SWNT) network substrates. Using a combination of biochemical and optical techniques, we demonstrate here that SWNT networks promote cell development through two distinct steps. Initially, SWNTs are absorbed in a process that resembles endocytosis, inducing acute toxicity. Nanotube mediated cell destruction, however, induces a release of endogenous factors that act to boost the activity of the surviving cells by stimulating the synthesis of extracellular matrix. In the second part of the research, minimally invasive SWNT matrices were used to further investigate network properties for biomedical applications without extensive presence of cytotoxicity. In the literature, carbon nanotube based substrates have been shown to support the growth of different cell types and, as such, have raised considerable interest in their possible use in biomedical applications. Nanotube matrices that are embedded in polymers cause inherent changes in nanotube chemical and physical film properties. Thus, it is critical to understand how the physical properties of the pristine networks affect the biology of the host tissue. Here, we investigated how the physical and chemical properties of SWNT networks impact the response of MC3T3-E1 bone osteoblasts. We found that two fundamental steps in cell growth: initial attachment to the substrate and proliferation, are strongly dependent on the energy and roughness of the surface, respectively. Thus, fine-tuning the properties of the film may represent a strategy to optimize

  11. Onset of analgesia and analgesic efficacy of tramadol/acetaminophen and codeine/acetaminophen/ibuprofen in acute postoperative pain: a single-center, single-dose, randomized, active-controlled, parallel-group study in a dental surgery pain model.

    PubMed

    Jung, Young-Soo; Kim, Dong Kee; Kim, Moon-Key; Kim, Hyung-Jun; Cha, In-Ho; Lee, Eui-Wung

    2004-07-01

    The combination of tramadol and acetaminophen has demonstrated good efficacy in various clinical pain models. However, there is a need for comparisons of the onset of analgesia and other measures of analgesic efficacy with this combination and other strong combination analgesics for the management of acute pain. The goal of this study was to compare the time to onset of analgesia and other measures of analgesic efficacy with tramadol/acetaminophen 75/650 mg (Tr/Ac) and codeine/acetaminophen/ibuprofen 20/500/400 mg (Co/Ac/Ib) in the management of acute pain after oral surgery. This was a single-center, single-dose, randomized, active-controlled, parallel-group study in healthy subjects who had undergone surgical extraction of > or =1 impacted third molar requiring bone removal. When patients reported at least moderate pain after dental surgery (score > or =5 on a 10-point scale), they were randomized to 1 of 2 treatment groups. The time to onset of analgesia was measured using a 2-stopwatch technique. The time to the onset of perceptible and meaningful pain relief, pain intensity, pain relief, patient's overall assessment, and adverse events were recorded for 6 hours after dosing. One hundred twenty-eight subjects participated in the study, 64 in each treatment group. The 2 groups were similar in terms of baseline pain severity and demographic characteristics (mean age, 23.7 and 23.4 years in the Tr/Ac and Co/Ac/Ib groups, respectively; mean body weight, 58.5 and 60.3 kg). The median times to the onset of perceptible pain relief were a respective 21.0 and 24.4 minutes, and the median times to the onset of meaningful pain relief were 56.4 and 57.3 minutes. Mean total pain relief and the sum of pain intensity difference were also similar in the early period after dosing (0-4 hours). However, between 4 and 6 hours, Co/Ac/Ib was associated with significant differences in both variables compared with Tr/Ac (P < 0.05). Although similar through the 4-hour assessment, mean

  12. Effect of Radiotherapy on Painful Bone Metastases: A Secondary Analysis of the NCIC Clinical Trials Group Symptom Control Trial SC.23.

    PubMed

    McDonald, Rachel; Ding, Keyue; Brundage, Michael; Meyer, Ralph M; Nabid, Abdenour; Chabot, Pierre; Coulombe, Genevieve; Ahmed, Shahida; Kuk, Joda; Dar, A Rashid; Mahmud, Aamer; Fairchild, Alysa; Wilson, Carolyn F; Wu, Jackson S Y; Dennis, Kristopher; DeAngelis, Carlo; Wong, Rebecca K S; Zhu, Liting; Chan, Stephanie; Chow, Edward

    2017-07-01

    Many studies that found improved quality of life (QOL) after radiotherapy of bone metastases have small sample sizes and do not use specific questionnaires. How soon after radiotherapy one can expect an improvement in QOL is unknown. To investigate QOL at days 10 and 42 after radiotherapy with a bone metastases-specific QOL tool. In this secondary analysis of the NCIC Clinical Trials Group Symptom Control Trial SC.23, a double-blind randomized clinical trial that investigated dexamethasone for the prophylaxis of pain flare after radiotherapy, patients were accrued from 23 Canadian centers from May 30, 2011, to December 11, 2014, and were followed up for 42 days after treatment. Participants referred for radiotherapy for bone metastases were required to have a pain score at the site(s) of treatment of at least 2 (range, 0-10). Patients were treated with a single 8-Gy radiotherapy dose for 1 or 2 bone metastases. Patients reported their worst pain score and analgesic intake at baseline and days 10 and 42 after treatment. Pain response was assessed with International Bone Metastases Consensus Endpoint Definitions. Self-reported QOL was completed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Bone Metastases Module (QLQ-BM22) and the European Organisation for Research and Treatment of Cancer Quality of Life Core 15 Palliative (QLQ-C15-PAL) at the same time points. A total of 298 patients were accrued (median age, 68.8 [range, 32-94] years at day 10 and 68.0 [range, 34-90] years at day 42). A total of 122 patients (40.9%) responded to radiotherapy at day 10 and 116 patients (38.9%) at day 42. At day 10, compared with nonresponders, patients with a pain response had a greater reduction in pain (mean reduction, 17.0 vs 1.8; P = .002) and pain characteristics (mean reduction, 12.8 vs 1.1; P = .002), as well as greater improvements in functional interference (mean increase, 11.6 vs 3.6; P = .01) and

  13. Lysine-Specific Demethylase 1 in Breast Cancer Cells Contributes to the Production of Endogenous Formaldehyde in the Metastatic Bone Cancer Pain Model of Rats

    PubMed Central

    Tong, Zhi-Qian; Li, Zhi-Hua; Chen, Wen; Luo, Wen-Hong; Li, Hui; Luo, Hong-Jun; Tang, Yan; Tang, Jun-Min; Cai, Jie; Liao, Fei-Fei; Wan, You

    2013-01-01

    Background Bone cancer pain seriously affects the quality of life of cancer patients. Our previous study found that endogenous formaldehyde was produced by cancer cells metastasized into bone marrows and played an important role in bone cancer pain. However, the mechanism of production of this endogenous formaldehyde by metastatic cancer cells was unknown in bone cancer pain rats. Lysine-specific demethylase 1 (LSD1) is one of the major enzymes catalyzing the production of formaldehyde. The expression of LSD1 and the concentration of formaldehyde were up-regulated in many high-risk tumors. Objective This study aimed to investigate whether LSD1 in metastasized MRMT-1 breast cancer cells in bone marrows participated in the production of endogenous formaldehyde in bone cancer pain rats. Methodology/Principal Findings Concentration of the endogenous formaldehyde was measured by high performance liquid chromatography (HPLC). Endogenous formaldehyde dramatically increased in cultured MRMT-1 breast cancer cells in vitro, in bone marrows and sera of bone cancer pain rats, in tumor tissues and sera of MRMT-1 subcutaneous vaccination model rats in vivo. Formaldehyde at a concentration as low as the above measured (3 mM) induced pain behaviors in normal rats. The expression of LSD1 which mainly located in nuclei of cancer cells significantly increased in bone marrows of bone cancer pain rats from 14 d to 21 d after inoculation. Furthermore, inhibition of LSD1 decreased the production of formaldehyde in MRMT-1 cells in vitro. Intraperitoneal injection of LSD1 inhibitor pargyline from 3 d to 14 d after inoculation of MRMT-1 cancer cells reduced bone cancer pain behaviors. Conclusion Our data in the present study, combing our previous report, suggested that in the endogenous formaldehyde-induced pain in bone cancer pain rats, LSD1 in metastasized cancer cells contributed to the production of the endogenous formaldehyde. PMID:23516587

  14. Role of nitric oxide synthase in the development of bone cancer pain and effect of L-NMMA

    PubMed Central

    YANG, YAN; ZHANG, JUAN; LIU, YUE; ZHENG, YAGUO; BO, JINHUA; ZHOU, XIAOFANG; WANG, JUNHUA; MA, ZHENGLIANG

    2016-01-01

    Spinal nitric oxide is involved in the mechanisms of pain generation and transmission during inflammatory and neuropathic pain. The aim of the present study was to explore the role of spinal nitric oxide in the development of bone cancer pain. 2×105 osteosarcoma cells were implanted into the intramedullary space of right femurs of C3H/HeJ mice to induce a model of ongoing bone cancer. Polymerase chain reaction and immunohistochemical analyses were performed to assess the expression of neuronal nitric oxide synthase (nNOS) and inducible (i)NOS in the spinal cord following inoculation. The results showed that inoculation of osteosarcoma cells induced progressive bone cancer, accompanied with pain-associated behavior. The levels of nNOS mRNA in the spinal cord of tumor mice began to increase at day 10 and then decreased to the level in sham mice at day 14, while iNOS mRNA markedly increased in the tumor group at days 10 and 14. Immunohistochemical analysis showed that nNOS- and iNOS-positive neurons were mainly located in the superficial dorsal horn and around the central canal of the L3-L5 spinal cord. Intrathecal injection of 50 µg NOS inhibitor NG-monomethyl-l-arginine (L-NMMA) attenuated cancer-evoked pain behaviors at day 14. These findings indicated that an upregulation of nNOS and iNOS in the spinal cord is associated with bone cancer pain and suggests that exogenously administered L-NMMA may have beneficial effects to alleviate bone cancer pain. PMID:26648027

  15. Bone mineral density is not associated with musculoskeletal pain in postmenopausal Korean women aged ≥50 years.

    PubMed

    Lee, Kyoung Min; Chung, Chin Youb; Kwon, Soon-Sun; Kim, Tae Gyun; Lee, In Hyeok; Jung, Ki Jin; Park, Jin Woo; Moon, Sang Young; Park, Moon Seok

    2015-02-01

    Although many studies reported improvement of back pain after osteoporosis treatment, there is insufficient evidence to determine whether osteoporosis is painful. We investigated whether bone mineral density correlated with musculoskeletal pain in postmenopausal Korean women aged ≥50 years. Data for postmenopausal women aged ≥50 years were obtained from the fifth Korea National Health and Nutrition Examination Survey database. Demographics, Kellgren-Lawrence grade, and numeric rating scale for pain in the hip and knee joints, presence of back pain, and activity level were analyzed. Only subjects with dual-energy X-ray absorptiometry scans and hip and knee radiographs were included. Those with malignancy, pain medication use, or a history of fragility fractures were excluded. After univariate analysis, multiple linear regression analysis was performed to examine the significant factors correlated with the degree of hip and knee pain. Binary logistic regression analysis was performed to identify factors significantly associated with the presence of back pain. In total, 387 women were included in the data analysis. Age (p = 0.005) was the only significant factor correlated with the intensity of hip pain, while Kellgren-Lawrence grade (p < 0.001) was the only significant factor correlated with knee pain intensity in multiple regression analysis. Binary logistic regression analysis showed that age (p = 0.002) was the only significant factor associated with the presence of back pain. Musculoskeletal pain was not affected by or associated with the bone mineral density (BMD) of the affected body part in postmenopausal Korean women aged ≥50 years after adjusting for the degree of osteoarthritis.

  16. [Use of zoledronic acid in patients with prostate cancer bone metastases: control of pain and musculoskeletal complications].

    PubMed

    Paparella, Stefano; Finkelberg, Elisabetta; Varisco, Daniela; Tondelli, Elena; Rocco, Francesco

    2011-01-01

    Background. Patients suffering from prostatic carcinoma are at high risk of having bone complications because of the metastatic progression of the disease to the skeleton and the consequences of androgenic deprivation. Zoledronic acid is a potent inhibitor of the bone resorption mediated by the osteoclasts, and is the only bisphosphonate whose capacity of reducing significantly the skeleton morbidity in patients with bone metastases is statistically proved. Methods. To attest tolerability and efficacy of zoledronic acid in preventing unfavorable skeletal events and in reducing osteomuscular pain, 25 patients - aged 75 years, suffering from hormone-responsive prostatic carcinoma under hormonal therapy with bone metastases, have been followed and subjected to IV monthly infusion of 4 mg zoledronic acid for 12 consecutive months, associated to daily intake of calcium and multivitamin supplementations. Results. At the end of the study, a sensible improvement in their clinical conditions and in their perception of the pain has been recorded in 23 patients and valued through a set of questions (Brief Pain Inventory). Conclusions. Zoledronic acid is therefore confirmed to be an effective medicine in preventing the skeleton complications and in controlling the painful symptoms in patients suffering from prostatic carcinoma with bone metastases.

  17. A randomised trial of a brace for patellofemoral osteoarthritis targeting knee pain and bone marrow lesions.

    PubMed

    Callaghan, Michael J; Parkes, Matthew J; Hutchinson, Charles E; Gait, Andrew D; Forsythe, Laura M; Marjanovic, Elizabeth J; Lunt, Mark; Felson, David T

    2015-06-01

    Braces used to treat (PF) osteoarthritis (OA) may reduce contact stress across the PF joint. We hypothesised that in PF OA, braces would decrease knee pain and shrink PF bone marrow lesions (BMLs). Eligible subjects had painful PF OA. Subjects were randomly allocated to brace or no brace for 6 weeks. Knee MRIs were acquired at baseline and 6 weeks. We measured BMLs on post-contrast fat suppressed sagittal and proton density weighted axial images. The primary symptom outcome was change in pain at 6 weeks during a preselected painful activity, and the primary structural outcome was BML volume change in the PF joint. Analyses used multiple linear regression. We randomised 126 subjects aged 40-70 years (mean age 55.5  years; 72 females (57.1%)). Mean nominated visual analogue scale (0-10 cm) pain score at baseline was 6.5 cm. 94 knees (75%) had PF BMLs at baseline. Subjects wore the brace for a mean of 7.4 h/day. 6 subjects withdrew during the trial. After accounting for baseline values, the brace group had lower knee pain than the control group at 6 weeks (difference between groups -1.3 cm, 95% CI -2.0 to -0.7; p<0.001) and reduced PF BML volume (difference -490.6 mm(3), 95% CI -929.5 to -51.7; p=0.03) but not tibiofemoral volume (difference -53.9 mm(3), 95% CI -625.9 to 518.2; p=0.85). A PF brace reduces BML volume in the targeted compartment of the knee, and relieves knee pain. UK. ISRCTN50380458. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  18. Single-dose fentanyl sublingual spray for breakthrough cancer pain.

    PubMed

    Taylor, Donald R

    2013-01-01

    Breakthrough cancer pain (BTCP) is defined as a transient exacerbation of pain that arises in patients with otherwise controlled persistent pain. BTCP typically has a rapid onset and relatively short duration, but it causes a significant amount of physical and psychological distress for patients. Several rapid-onset fentanyl formulations have been introduced in the USA to replace traditional oral opioids for the treatment of BTCP: a transmucosal lozenge, a sublingual orally disintegrating tablet, a buccal tablet, a buccal soluble film, a pectin nasal spray and, the newest formulation to enter the market, a sublingual spray. This article reviews the six rapid-onset formulations of fentanyl approved in the USA for the management of BTCP with emphasis on describing the published literature on fentanyl sublingual spray. The different fentanyl formulations vary in pharmacokinetic properties and ease of use, but all have a rapid onset and a relatively short duration of analgesia. Fentanyl sublingual spray has demonstrated absorption within 5 minutes of administration, with fentanyl plasma concentrations increasing over the first 30 minutes and remaining elevated for 60-90 minutes in pharmacokinetic studies in healthy subjects. Fentanyl sublingual spray shows linear dose proportionality, and changes in the temperature or acidity of the oral cavity do not alter its pharmacokinetic properties. In patients with BTCP, statistically significant pain relief is measurable at 5 minutes after administration of fentanyl sublingual spray, when compared with placebo, with significant pain relief lasting at least 60 minutes after administration. Adverse events are typical of opioid treatment and are considered mild to moderate in intensity. In summary, fentanyl sublingual spray provides rapid onset of analgesia and is a tolerable and effective treatment for BTCP.

  19. Comparison of single- and dual-photon absorptiometry in postmenopausal bone mineral loss

    SciTech Connect

    Nilas, L.; Borg, J.; Gotfredsen, A.; Christiansen, C.

    1985-11-01

    The authors describe a single photon absorptiometric (SPA) technique, which enables differential estimation of the rates of loss from trabecular and cortical bone. Ten scans are obtained in the forearm: six in an area with about 7% trabecular bone and four scans in the adjacent distal area with a trabecular bone content of 25%. By comparing bone masses of these two sites in 19 postmenopausal and 53 premenopausal women, the postmenopausal trabecular bone loss was estimated to be approximately seven times greater than cortical loss within the first years of cessation of regular vaginal bleeding. On a group basis the bone loss at the distal forearm scan site (by SPA) corresponded closely to the spinal bone loss (by dual-photon absorptiometry). The reproducibility of the two scan sites in the forearm was 1-1.5% (CV%), which makes the method suitable for longitudinal studies. Corrections for variations in fatty tissue covering can be made without deterioration of the reproducibility.

  20. Would Larger Radiation Fields Lead to a Faster Onset of Pain Relief in the Palliation of Bone Metastases?

    SciTech Connect

    Chow, Edward Makhani, Leila; Culleton, Shaelyn; Makhani, Nadiya; Davis, Lori; Campos, Sarah; Sinclair, Emily

    2009-08-01

    Purpose: Hemibody irradiation has been shown to relieve bony metastatic pain within 24-48 hours of treatment, whereas for local external beam radiation, onset of pain relief is 1-4 weeks after radiation. The primary objective of this study is to examine whether there is a relationship between the areas of radiation treatment and onset of pain relief. Methods and Materials: From Jan 1999 to Jan 2002, a total of 653 patients with symptomatic bone metastases were treated with external beam radiation. Pain scores and analgesic consumption were recorded at baseline and Weeks 1, 2, 4, 8, and 12. The areas of radiation treatment for all patients were calculated, then correlated with the response and analyzed in various ways. We first compared pain score alone with mean radiation field size. Second, we combined pain score and analgesic consumption. Last, we implemented the International Consensus end points for pain score and analgesic intake. Results: Assessment of 653 patients showed no significant correlation comparing pain scores alone with radiation field area, with the exception of Week 4 for partial responders. Again, no significant correlation was found when combining both analgesic intake and pain score against radiation field size. Even when implementing the International Consensus end point definitions for radiation response, the only significant correlation between radiation field size and response was observed in Week 2 for partial response. Conclusion: There was no statistical significance between mean areas of radiation treatment with the onset of pain relief.

  1. Up-regulation of brain-derived neurotrophic factor in the dorsal root ganglion of the rat bone cancer pain model

    PubMed Central

    Tomotsuka, Naoto; Kaku, Ryuji; Obata, Norihiko; Matsuoka, Yoshikazu; Kanzaki, Hirotaka; Taniguchi, Arata; Muto, Noriko; Omiya, Hiroki; Itano, Yoshitaro; Sato, Tadasu; Ichikawa, Hiroyuki; Mizobuchi, Satoshi; Morimatsu, Hiroshi

    2014-01-01

    Metastatic bone cancer causes severe pain, but current treatments often provide insufficient pain relief. One of the reasons is that mechanisms underlying bone cancer pain are not solved completely. Our previous studies have shown that brain-derived neurotrophic factor (BDNF), known as a member of the neurotrophic family, is an important molecule in the pathological pain state in some pain models. We hypothesized that expression changes of BDNF may be one of the factors related to bone cancer pain; in this study, we investigated changes of BDNF expression in dorsal root ganglia in a rat bone cancer pain model. As we expected, BDNF mRNA (messenger ribonucleic acid) and protein were significantly increased in L3 dorsal root ganglia after intra-tibial inoculation of MRMT-1 rat breast cancer cells. Among the eleven splice-variants of BDNF mRNA, exon 1–9 variant increased predominantly. Interestingly, the up-regulation of BDNF is localized in small neurons (mostly nociceptive neurons) but not in medium or large neurons (non-nociceptive neurons). Further, expression of nerve growth factor (NGF), which is known as a specific promoter of BDNF exon 1–9 variant, was significantly increased in tibial bone marrow. Our findings suggest that BDNF is a key molecule in bone cancer pain, and NGF-BDNF cascade possibly develops bone cancer pain. PMID:25050075

  2. Dissociation between back pain and bone stress reaction as measured by CT scan in young cricket fast bowlers

    PubMed Central

    Millson, H; Gray, J; Stretch, R; Lambert, M

    2004-01-01

    Background: Bone stress reaction is prevalent among cricket fast bowlers. Few studies have addressed the sensitivity and specificity of imaging for diagnosis, and follow up assessment has been poorly investigated. Objective: To determine whether there was an association between back pain and bone stress reaction as measured by computed tomography (CT) scan in young cricket fast bowlers. Methods: Ten young cricket fast bowlers were included in the study. Nine bowlers presented to a physiotherapy practice with low back pain and were later diagnosed with lumbar stress fractures, while one was an experienced bowler with no pain. All players had a CT scan after presenting to the physiotherapy practice. Pain was assessed according to a subjective scale (0–10) where 10 represented the player's subjective, maximum pain score. Recovery and rehabilitation of all players was monitored until they returned to full participation. Results: There was no consistency in the relationship between pain and CT scan results. For example, one subject had evidence of un-united stress fractures after 15 months of rest but had experienced moderate pain for only 2 weeks after the onset of symptoms, in contrast to another subject who had intermittent pain for 11 months even though CT scan showed multiple stress fractures ranging from partially healed to fully healed status at 3 months. Conclusion: There is dissociation between back pain and bone stress reaction as measured by CT scan. Therefore, CT scan does not provide objective evidence for ongoing management or decision concerning return to sport in cricket fast bowlers. PMID:15388545

  3. Langerhans cell histiocytosis with multifocal bone lesions: comparative clinical features between single and multi-systems.

    PubMed

    Imashuku, Shinsaku; Kinugawa, Naoko; Matsuzaki, Akinobu; Kitoh, Toshiyuki; Ohki, Kentaro; Shioda, Yoko; Tsunematsu, Yukiko; Imamura, Toshihiko; Morimoto, Akira

    2009-11-01

    Langerhans cell histiocytosis (LCH) can be a single system or multi-system disease. Both disease types can be associated with multi-focal bone lesions, but their bone involvement patterns have not been compared systematically. Of the new pediatric LCH cases enrolled into the JLSG-02 study during 2002-2007, 67 cases of single system multifocal bone (SMFB) LCH and 97 cases of multi-system bone (MSB) LCH were analyzed to determine if the bone involvement patterns differ in these two types, and whether these differences correlate with outcome. Statistical analysis was performed with Mann-Whitney U test, Fisher's exact test, and other measures. Onset ages were higher for SMFB (P < 0.001), but the two types did not differ in the number of bone lesions per patient. The skull was most frequently affected in both types, followed by the spine. Lesions in the temporal bone (P = 0.002), ear-petrous bone (P < 0.001), orbita (P = 0.003), and zygomatic bone (P = 0.016) were significantly more common in MSB. The two types did not differ in response to treatment, but MSB was associated with a significantly higher incidence of diabetes insipidus (DI) (P < 0.001). Novel measures are required in preventing the development of DI in MSB-type LCH patients with "risk" bone lesions.

  4. Effect of systemic injection of heterogenous and homogenous opioids on peripheral cellular immune response in rats with bone cancer pain: A comparative study

    PubMed Central

    Du, Jun-Ying; Liang, Yi; Fang, Jun-Fan; Jiang, Yong-Liang; Shao, Xiao-Mei; He, Xiao-Fen; Fang, Jian-Qiao

    2016-01-01

    Exogenous and endogenous opioids have been shown to modulate the immune system. Morphine-induced immunosuppression has been investigated extensively. However, the immune-regulating function of endogenous opioid peptides is unclear. The present study aimed to evaluate the difference in effects on cellular immune function between recombinant rat β-endorphin (β-EP; 50 µg/kg) and plant source morphine (10 mg/kg) via intraperitoneal injection treatment in a rat model of bone cancer pain. Walker 256 cells were injected into a tibial cavity injection to establish the bone cancer pain model. The paw withdrawal thresholds and body weights were measured prior to surgery, at 6 days after surgery, and following 1, 3,6 and 8 treatments. The spleen cells were harvested for detection of T cell proliferation, natural killer (NK) cell cytotoxicity, and the relative quantities of T cell subtypes (CD3+, CD4+ and CD8+ cells). Plasma levels of interleukin-2 (IL-2) were also determined. It was found that single or multiple treatments with β-EP (a homogenous opioid peptide) and morphine (a heterogenous opioid) had good analgesic effects on bone cancer pain, while the analgesia provided by morphine was stronger than that of β-EP. Treatment with β-EP 3, 6 and 8 times increased the body weight gain in the rat model of bone cancer pain, while morphine treatment had on effect on it. With regard to immunomodulatory functions, β-EP treatment increased T cell proliferation and NK cell cytotoxicity, and increased the relative quantities of T cell subtypes, but no effect on T cell secretion. However, morphine treatment decreased T cell proliferation and the levels of T cell subtypes. These data indicate that opioids from different sources have different effects on cellular immune function in vivo. A small dose of homogenous opioid peptide exhibited positive effects (analgesia and immune enhancement) on cancer pain. These results provide experimental evidence supporting the exploitation of

  5. Targeting cells of the myeloid lineage attenuates pain and disease progression in a prostate model of bone cancer.

    PubMed

    Thompson, Michelle L; Jimenez-Andrade, Juan M; Chartier, Stephane; Tsai, James; Burton, Elizabeth A; Habets, Gaston; Lin, Paul S; West, Brian L; Mantyh, Patrick W

    2015-09-01

    Tumor cells frequently metastasize to bone where they can generate cancer-induced bone pain (CIBP) that can be difficult to fully control using available therapies. Here, we explored whether PLX3397, a high-affinity small molecular antagonist that binds to and inhibits phosphorylation of colony-stimulating factor-1 receptor, the tyrosine-protein kinase c-Kit, and the FMS-like tyrosine kinase 3, can reduce CIBP. These 3 targets all regulate the proliferation and function of a subset of the myeloid cells including macrophages, osteoclasts, and mast cells. Preliminary experiments show that PLX3397 attenuated inflammatory pain after formalin injection into the hind paw of the rat. As there is an inflammatory component in CIBP, involving macrophages and osteoclasts, the effect of PLX3397 was explored in a prostate model of CIBP where skeletal pain, cancer cell proliferation, tumor metastasis, and bone remodeling could be monitored in the same animal. Administration of PLX3397 was initiated on day 14 after prostate cancer cell injection when the tumor was well established, and tumor-induced bone remodeling was first evident. Over the next 6 weeks, sustained administration of PLX3397 attenuated CIBP behaviors by approximately 50% and was equally efficacious in reducing tumor cell growth, formation of new tumor colonies in bone, and pathological tumor-induced bone remodeling. Developing a better understanding of potential effects that analgesic therapies have on the tumor itself may allow the development of therapies that not only better control the pain but also positively impact disease progression and overall survival in patients with bone cancer.

  6. Patients' impression of change following treatment for chronic pain: global, specific, a single dimension, or many?

    PubMed

    Scott, Whitney; McCracken, Lance M

    2015-06-01

    The Patient Global Impression of Change (PGIC) measure has frequently been used as an indicator of meaningful change in treatments for chronic pain. However, limited research has examined the validity of PGIC items despite their wide adoption in clinical trials for pain. Additionally, research has not yet examined predictors of PGIC ratings following psychologically based treatment for pain. The purpose of the present study was to examine the validity, factor structure, and predictors of PGIC ratings following an interdisciplinary psychologically based treatment for chronic pain. Patients with chronic pain (N = 476) completed standard assessments of pain, daily functioning, and depression before and after a 4-week treatment program based on the principles of acceptance and commitment therapy. Following the program, patients rated 1 item assessing their impression of change overall and several items assessing their impression of more specific changes: physical and social functioning, work-related activities, mood, and pain. Results indicated that the global and specific impression of change items represent a single component. In the context of the acceptance and commitment therapy-based treatment studied here, overall PGIC ratings appeared to be influenced to a greater degree by patients' experienced improvements in physical activities and mood than by improvements in pain. The findings suggest that in addition to a single overall PGIC rating, domain-specific items may be relevant for some treatment trials. This article reports on the validity and predictors of patients' impression of change ratings following interdisciplinary psychologically based treatment for pain. In addition to a single overall PGIC rating, domain-specific items may be important for clinicians and researchers to consider depending on the focus of treatment. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

  7. Modulation of pain-induced neuromuscular trunk responses by pain expectations: a single group study.

    PubMed

    Tétreau, Charles; Dubois, Jean-Daniel; Piché, Mathieu; Descarreaux, Martin

    2012-10-01

    The purpose of this study was to investigate the alteration of pain-induced neuromuscular trunk responses by expectations in healthy volunteers. Twenty-three asymptomatic participants performed series of flexion-extension movements in 3 different experimental conditions: innocuous heat stimulation (control) and noxious heat stimulation associated with expectations of low or high pain intensity. These stimuli were administered by a contact thermode placed over the lumbar region (L4 and L5) to assess the modulation of neuromuscular responses and kinematics during the flexion-extension task. Surface electromyography (EMG) of lumbar erector spinae at L2 and L3 and L4 and L5 as well as lumbopelvic kinematic variables were compared across conditions. Noxious stimulation significantly altered EMG responses but only in full trunk flexion. Interestingly, this alteration was significant only for muscles where noxious stimulation was applied (L4 and L5) and not for the other segment (L2 and L3). Conversely, expectations significantly altered EMG activity at L2 and L3 but not at the segment where noxious stimulation was applied. These results confirm previous findings and indicate that experimental pain can alter neuromuscular responses during a trunk flexion-extension task. Furthermore, this study suggests that expectations can alter some of these alterations. Future studies should determine whether neuromuscular changes induced by expectations may contribute to the transition from acute to chronic low-back pain. Copyright © 2012 National University of Health Sciences. Published by Mosby, Inc. All rights reserved.

  8. Randomized Double-Blind Trial of Pregabalin Versus Placebo in Conjunction With Palliative Radiotherapy for Cancer-Induced Bone Pain

    PubMed Central

    Hoskin, Peter J.; Colvin, Lesley A.; Fleetwood-Walker, Susan M.; Adamson, Douglas; Byrne, Anthony; Murray, Gordon D.; Laird, Barry J.A.

    2016-01-01

    Purpose Cancer-induced bone pain (CIBP) affects one third of patients with cancer. Radiotherapy remains the gold-standard treatment; however, laboratory and clinical work suggest that pregabalin may be useful in treating CIBP. The aim of this study was to examine pregabalin in patients with CIBP receiving radiotherapy. Patients and Methods A multicenter, double-blind randomized trial of pregabalin versus placebo was conducted. Eligible patients were age ≥ 18 years, had radiologically proven bone metastases, were scheduled to receive radiotherapy, and had pain scores ≥ 4 of 10 (on 0-to-10 numeric rating scale). Before radiotherapy, baseline assessments were completed, followed by random assignment. Doses of pregabalin and placebo were increased over 4 weeks. The primary end point was treatment response, defined as a reduction of ≥ 2 points in worst pain by week 4, accompanied by a stable or reduced opioid dose, compared with baseline. Secondary end points assessed average pain, interference of pain with activity, breakthrough pain, mood, quality of life, and adverse events. Results A total of 233 patients were randomly assigned: 117 to placebo and 116 to pregabalin. The most common cancers were prostate (n = 88; 38%), breast (n = 77; 33%), and lung (n = 42; 18%). In the pregabalin arm, 45 patients (38.8%) achieved the primary end point, compared with 47 (40.2%) in the placebo arm (adjusted odds ratio, 1.07; 95% CI, 0.63 to 1.81; P = .816). There were no statistically significant differences in average pain, pain interference, or quality of life between arms. There were differences in mood (P = .031) and breakthrough pain duration (P = .037) between arms. Outcomes were compared at 4 weeks. Conclusion Our findings do not support the role of pregabalin in patients with CIBP receiving radiotherapy. The role of pregabalin in CIBP with a clinical neuropathic pain component is unknown. PMID:26644535

  9. Patella bone density is lower in knee osteoarthritis patients experiencing moderate-to-severe pain at rest.

    PubMed

    Burnett, W; Kontulainen, S; McLennan, C; Hazel, D; Talmo, C; Hunter, D; Wilson, D; Johnston, J

    2016-03-01

    To determine differences in patellar subchondral bone mineral density (BMD) between knee osteoarthritis (OA) patients with differing levels of pain at rest. The preoperative knee of 41 total knee replacement (TKR) patients was scanned using QCT and scored for pain using Western Ontario McMasters Osteoarthritis Index (WOMAC). 'Pain at rest' was defined as average pain while lying//sitting and nocturnal pain. Participants were divided into groups: 'mild-to-no pain at rest' and 'moderate-to-severe pain at rest'. We used a depth-specific CT-based mapping technique to measure patellar subchondral BMD at depths of 0-2.5 mm, 2.5-5 mm, and 5-7.5 mm from the subchondral surface. Mean lateral and medial facet BMD were compared between groups using MANCOVA. Mean adjusted BMD was lower in participants with 'moderate-to-severe pain at rest' over the total lateral facet at depths of 0-2.5 mm (10% lower, p=0.041), 2.5-5 mm (20% lower, p=0.017), and 5-7.5 mm (25% lower, p=0.004), and over the total medial facet at 2.5-5 mm (22% lower, p=0.033) and 5-7.5 mm (28% lower, p=0.016). In OA patients with 'moderate-to-severe pain at rest', depth-specific density measures demonstrated up to 28% lower lateral and medial subchondral BMD. Patients with high levels of pain at rest may have reduced amounts of native bone prior to TKR.

  10. Randomized Double-Blind Trial of Pregabalin Versus Placebo in Conjunction With Palliative Radiotherapy for Cancer-Induced Bone Pain.

    PubMed

    Fallon, Marie; Hoskin, Peter J; Colvin, Lesley A; Fleetwood-Walker, Susan M; Adamson, Douglas; Byrne, Anthony; Murray, Gordon D; Laird, Barry J A

    2016-02-20

    Cancer-induced bone pain (CIBP) affects one third of patients with cancer. Radiotherapy remains the gold-standard treatment; however, laboratory and clinical work suggest that pregabalin may be useful in treating CIBP. The aim of this study was to examine pregabalin in patients with CIBP receiving radiotherapy. A multicenter, double-blind randomized trial of pregabalin versus placebo was conducted. Eligible patients were age ≥ 18 years, had radiologically proven bone metastases, were scheduled to receive radiotherapy, and had pain scores ≥ 4 of 10 (on 0-to-10 numeric rating scale). Before radiotherapy, baseline assessments were completed, followed by random assignment. Doses of pregabalin and placebo were increased over 4 weeks. The primary end point was treatment response, defined as a reduction of ≥ 2 points in worst pain by week 4, accompanied by a stable or reduced opioid dose, compared with baseline. Secondary end points assessed average pain, interference of pain with activity, breakthrough pain, mood, quality of life, and adverse events. A total of 233 patients were randomly assigned: 117 to placebo and 116 to pregabalin. The most common cancers were prostate (n = 88; 38%), breast (n = 77; 33%), and lung (n = 42; 18%). In the pregabalin arm, 45 patients (38.8%) achieved the primary end point, compared with 47 (40.2%) in the placebo arm (adjusted odds ratio, 1.07; 95% CI, 0.63 to 1.81; P = .816). There were no statistically significant differences in average pain, pain interference, or quality of life between arms. There were differences in mood (P = .031) and breakthrough pain duration (P = .037) between arms. Outcomes were compared at 4 weeks. Our findings do not support the role of pregabalin in patients with CIBP receiving radiotherapy. The role of pregabalin in CIBP with a clinical neuropathic pain component is unknown. © 2015 by American Society of Clinical Oncology.

  11. A Papillary Thyroid Microcarcinoma Revealed by a Single Bone Lesion with No Poor Prognostic Factors

    PubMed Central

    Godbert, Yann; Henriques-Figueiredo, Benedicte; Cazeau, Anne-Laure; Carrat, Xavier; Stegen, Marc; Soubeyran, Isabelle; Bonichon, Francoise

    2013-01-01

    Objectives. Thyroid carcinomas incidence, in particular papillary variants, is increasing. These cancers are generally considered to have excellent prognosis, and papillary microcarcinomas are usually noninvasive. Many prognostic histopathology factors have been described to guide therapeutic decisions. Most patients are treated with total thyroidectomy without radioiodine treatment or partial surgery. Case Summary. A 65-year-old man with no significant medical history presented with pain in the left chest wall that had been present for several months. A computed tomography (CT) found a large tissue mass of 4 cm responsible for lysis of the middle arch of the 4th rib on the left. It was a single lesion, highly hypermetabolic on the 18-FDG PET/CT. The histology analysis of the biopsy and surgical specimen favored an adenocarcinoma with immunostaining positive for TTF1 and thyroglobulin (Tg). The total thyroidectomy carried out subsequently revealed a 4 mm papillary microcarcinoma with vesicular architecture of the right lobe, well delimited and distant from the capsule without vascular embolisms. After two radioiodine treatments, the patient is in complete clinical, biological, and radiological remission. Conclusion. This extremely rare case of a singular bone metastasis revealing a papillary thyroid microcarcinoma illustrates the necessity of further research to better characterize the forms of papillary thyroid microcarcinomas with potentially poor prognosis. PMID:23509641

  12. Minocycline attenuates bone cancer pain in rats by inhibiting NF-κB in spinal astrocytes

    PubMed Central

    Song, Zhen-peng; Xiong, Bing-rui; Guan, Xue-hai; Cao, Fei; Manyande, Anne; Zhou, Ya-qun; Zheng, Hua; Tian, Yu-ke

    2016-01-01

    Aim: To investigate the mechanisms underlying the anti-nociceptive effect of minocycline on bone cancer pain (BCP) in rats. Methods: A rat model of BCP was established by inoculating Walker 256 mammary carcinoma cells into tibial medullary canal. Two weeks later, the rats were injected with minocycline (50, 100 μg, intrathecally; or 40, 80 mg/kg, ip) twice daily for 3 consecutive days. Mechanical paw withdrawal threshold (PWT) was used to assess pain behavior. After the rats were euthanized, spinal cords were harvested for immunoblotting analyses. The effects of minocycline on NF-κB activation were also examined in primary rat astrocytes stimulated with IL-1β in vitro. Results: BCP rats had marked bone destruction, and showed mechanical tactile allodynia on d 7 and d 14 after the operation. Intrathecal injection of minocycline (100 μg) or intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced mechanical tactile allodynia. Furthermore, intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced upregulation of GFAP (astrocyte marker) and PSD95 in spinal cord. Moreover, intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced upregulation of NF-κB, p-IKKα and IκBα in spinal cord. In IL-1β-stimulated primary rat astrocytes, pretreatment with minocycline (75, 100 μmol/L) significantly inhibited the translocation of NF-κB to nucleus. Conclusion: Minocycline effectively alleviates BCP by inhibiting the NF-κB signaling pathway in spinal astrocytes. PMID:27157092

  13. An acceptance-based intervention for children and adolescents with cancer experiencing acute pain - a single-subject study.

    PubMed

    Thorsell Cederberg, Jenny; Dahl, JoAnne; von Essen, Louise; Ljungman, Gustaf

    2017-01-01

    Children and adolescents with cancer report pain as one of their most recurrent and troublesome symptoms throughout the cancer trajectory. Pain evokes psychological distress, which in turn has an amplifying effect on the pain experience. Acceptance-based interventions for experimentally induced acute pain predict increased pain tolerance, decreased pain intensity and decreased discomfort of pain. The aim of this study was to preliminarily evaluate an acceptance-based intervention for children and adolescents with cancer experiencing acute pain, with regard to feasibility and effect on pain intensity and discomfort of pain. This is a single-subject study with an AB design with a nonconcurrent multiple baseline. Children and adolescents aged four to 18 years undergoing cancer treatment at the Children's University Hospital, Uppsala, Sweden, reporting sustained acute pain were offered participation. Pain intensity and discomfort of pain were measured during baseline and at post-intervention. The intervention consisted of a pain exposure exercise lasting approximately 15 minutes. Five children participated in the study. All participants completed the intervention and reported that it had helped them to cope with the pain in the moment. All participants reported decreased discomfort of pain at post-measurement, three of whom also reported decreased pain intensity. The results suggest that an acceptance-based intervention may help children and adolescents with cancer to cope with the pain that is often associated with cancer treatment in spite of pharmacological pain management. The results are tentative but promising and warrant further investigation.

  14. Single dose oral mefenamic acid for acute postoperative pain in adults

    PubMed Central

    Moll, Rachel; Derry, Sheena; Moore, R Andrew; McQuay, Henry J

    2014-01-01

    Background Mefenamic acid is a non-steroidal anti-inflammatory drug (NSAID). It is most often used for treating pain of dysmenorrhoea in the short term (seven days or less), as well as mild to moderate pain including headache, dental pain, postoperative and postpartum pain. It is widely available in many countries worldwide. Objectives To assess the efficacy of single dose oral mefenamic acid in acute postoperative pain, and any associated adverse events. Search methods We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to December 2010. Selection criteria Single oral dose, randomised, double-blind, placebo-controlled trials of mefenamic acid for relief of established moderate to severe postoperative pain in adults. Data collection and analysis Studies were assessed for methodological quality and the data extracted by two review authors independently. Summed total pain relief (TOTPAR) or pain intensity difference (SPID) over 4 to 6 hours was used to calculate the number of participants achieving at least 50% pain relief. These derived results were used to calculate, with 95% confidence intervals, the relative benefit compared to placebo, and the number needed to treat (NNT) for one participant to experience at least 50% pain relief over 4 to 6 hours. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals was collected. Main results Four studies with 842 participants met the inclusion criteria; 126 participants were treated with mefenamic acid 500 mg, 67 with mefenamic acid 250 mg, 197 with placebo, and 452 with lignocaine, aspirin, zomepirac or nimesulide. Participants had pain following third molar extraction, episiotomy and orthopaedic surgery. The NNT for at least 50% pain relief over 6 hours with a single dose of mefenamic acid 500 mg compared to placebo was 4.0 (2

  15. Strontium-89: treatment results and kinetics in patients with painful metastatic prostate and breast cancer in bone

    SciTech Connect

    Robinson, R.G.; Blake, G.M.; Preston, D.F.; McEwan, A.J.; Spicer, J.A.; Martin, N.L.; Wegst, A.V.; Ackery, D.M.

    1989-03-01

    Two hundred and two patients with bone pain from metastatic cancer were treated with 40 microCi/kg of Sr-89. Patients were followed with pain diaries, records of medication taken, sleep patterns, serial bone scans and a Karnofsky Index. One hundred and thirty-seven patients with adequate followup survived at least 3 months, including 100 with prostate and 28 with breast carcinoma. Eighty of the 100 patients with prostate cancer responded, and 25 of the 28 breast cancer patients improved. Ten patients with prostate cancer and five with breast cancer became pain free. Little hematologic depression was noted. Sr-89 kinetic studies showed that strontium taken up in osteoblastic areas remained for 100 days. The tumor-to-marrow absorbed dose ratio was 10:1.

  16. Strontium-89: treatment results and kinetics in patients with painful metastatic prostate and breast cancer in bone.

    PubMed

    Robinson, R G; Blake, G M; Preston, D F; McEwan, A J; Spicer, J A; Martin, N L; Wegst, A V; Ackery, D M

    1989-03-01

    Two hundred and two patients with bone pain from metastatic cancer were treated with 40 microCi/kg of Sr-89. Patients were followed with pain diaries, records of medication taken, sleep patterns, serial bone scans and a Karnofsky Index. One hundred and thirty-seven patients with adequate followup survived at least 3 months, including 100 with prostate and 28 with breast carcinoma. Eighty of the 100 patients with prostate cancer responded, and 25 of the 28 breast cancer patients improved. Ten patients with prostate cancer and five with breast cancer became pain free. Little hematologic depression was noted. Sr-89 kinetic studies showed that strontium taken up in osteoblastic areas remained for 100 days. The tumor-to-marrow absorbed dose ratio was 10:1.

  17. Infrared laser therapy after surgically assisted rapid palatal expansion to diminish pain and accelerate bone healing.

    PubMed

    Abreu, Marcelo Emir Requia; Viegas, Vinicius Nery; Pagnoncelli, Rogerio Miranda; de Lima, Eduardo Martinelli Santayama; Farret, Alessandro Marchiori; Kulczynski, Fernando Zugno; Farret, Marcel Marchiori

    2010-01-01

    The aim of this study was to illustrate how gallium arsenite aluminum diode laser (824 nm) irradiation can reduce postsurgical edema and discomfort and accelerate sutural osseous regeneration after surgically assisted rapid palatal expansion (SARPE). An adult patient with an 8-mm transverse maxillary discrepancy was treated with SARPE. Infrared laser therapy was started on the 7th postoperative day, with a total of eight sessions at intervals of 48 hours. The laser probe spot had a size of 0.2827 cm2 and was positioned in contact with the following (bilateral) points: infraorbital foramen, nasal alar, nasopalatine foramen, median palatal suture at the height of the molars, and transverse palatine suture distal to the second molars. The laser was run in continuous mode with a power of 100 mW and a fluency of 1.5 J/cm2 for 20 seconds at each point. Subsequently, an absence of edema and pain was observed. Further, fast bone regeneration in the median palatal suture could be demonstrated by occlusal radiographs. These findings suggest that laser therapy can accelerate bone regeneration of the median palatal suture in patients who have undergone SARPE.

  18. Spinal high-mobility group box 1 contributes to mechanical allodynia in a rat model of bone cancer pain

    SciTech Connect

    Tong, Wei; Wang, Wei; Huang, Jing; Ren, Ning; Wu, Sheng-Xi; Li, Yong-Qi

    2010-05-14

    Mechanisms underlying bone cancer-induced pain are largely unknown. Previous studies indicate that neuroinflammation in the spinal dorsal horn is especially involved. Being first reported as a nonhistone chromosomal protein, high-mobility group box 1 (HMGB1) is now implicated as a mediator of inflammation. We hypothesized that HMGB1 could trigger the release of cytokines in the spinal dorsal horn and contribute to bone cancer pain. To test this hypothesis, we first built a bone cancer pain model induced by intratibal injection of Walker 256 mammary gland carcinoma cells. The structural damage to the tibia was monitored by radiological analysis. The mechanical allodynia was measured and the expression of spinal HMGB1 and IL-1{beta} was evaluated. We observed that inoculation of cancer cells, but not heat-killed cells, induced progressive bone destruction from 9 d to 21 d post inoculation. Behavioral tests demonstrated that the significant nociceptive response in the cancer cells-injected rats emerged on day 9 and this kind of mechanical allodynia lasted at least 21 d following inoculation. Tumor cells inoculation significantly increased HMGB1 expression in the spinal dorsal horn, while intrathecal injecting a neutralizing antibody against HMGB1 showed an effective and reliable anti-allodynia effect with a dose-dependent manner. IL-1{beta} was significantly increased in caner pain rats while intrathecally administration of anti-HMGB1 could decrease IL-1{beta}. Together with previous reports, we predict that bone cancer induces HMGB1 production, enhancing spinal IL-1{beta} expression and thus modulating spinal excitatory synaptic transmission and pain response.

  19. Effects of Electroacupuncture Treatment on Bone Cancer Pain Model with Morphine Tolerance.

    PubMed

    Sima, Lei; Fan, Bifa; Yan, Longtao; Shui, Yuan

    2016-01-01

    Objective. To explore the efficacy of electroacupuncture treatment in cancer induced bone pain (CIBP) rat model with morphine tolerance and explore changes of calcitonin-gene related peptide (CGRP) expression in dorsal root ganglion (DRG). Methods. Forty SD rats were divided into five groups: sham, CIBP (B), CIBP + morphine (BM), CIBP + electroacupuncture (BE), and CIBP + morphine + electroacupuncture (BME). B, BM, BE, and BME groups were prepared CIBP model. The latter three groups then accepted morphine, electroacupuncture, and morphine combined electroacupuncture, separately, nine days consecutively (M1 to M9). Mechanical withdraw threshold (MWT) was evaluated. Results. BE group only had differences in M1, M2, and M3 compared to B group (P < 0.01). From M5, BM group showed significantly decreased MWT. Electroacupuncture could obtain analgesic effects only at early stage (M1 to M5). From M5 to M9, BME had the differences with BM group (P < 0.01). IOD value of CGRP in BM and BME was substantially less than in B group. CGRP in BME was significantly lower than that in BM group (P < 0.01). Conclusion. When used in combination with electroacupuncture, morphine could result in improving analgesic effects and reducing tolerance. CGRP may be associated with pain behaviors.

  20. Effects of Electroacupuncture Treatment on Bone Cancer Pain Model with Morphine Tolerance

    PubMed Central

    Fan, Bifa; Yan, Longtao; Shui, Yuan

    2016-01-01

    Objective. To explore the efficacy of electroacupuncture treatment in cancer induced bone pain (CIBP) rat model with morphine tolerance and explore changes of calcitonin-gene related peptide (CGRP) expression in dorsal root ganglion (DRG). Methods. Forty SD rats were divided into five groups: sham, CIBP (B), CIBP + morphine (BM), CIBP + electroacupuncture (BE), and CIBP + morphine + electroacupuncture (BME). B, BM, BE, and BME groups were prepared CIBP model. The latter three groups then accepted morphine, electroacupuncture, and morphine combined electroacupuncture, separately, nine days consecutively (M1 to M9). Mechanical withdraw threshold (MWT) was evaluated. Results. BE group only had differences in M1, M2, and M3 compared to B group (P < 0.01). From M5, BM group showed significantly decreased MWT. Electroacupuncture could obtain analgesic effects only at early stage (M1 to M5). From M5 to M9, BME had the differences with BM group (P < 0.01). IOD value of CGRP in BM and BME was substantially less than in B group. CGRP in BME was significantly lower than that in BM group (P < 0.01). Conclusion. When used in combination with electroacupuncture, morphine could result in improving analgesic effects and reducing tolerance. CGRP may be associated with pain behaviors. PMID:27672401

  1. Interdigitated craniotomy: a simple technique to fix a bone flap with only a single plate.

    PubMed

    Takahashi, Noboru; Fujiwara, Kazunori; Saito, Keiichi; Tominaga, Teiji

    2015-10-01

    In pterional craniotomy, fixation plates cause artifacts on postoperative radiological images; furthermore, they often disfigure the scalp in hairless areas. The authors describe a simple technique to fix a cranial bone flap with only a single plate underneath the temporalis muscle in an area with hair, rather than using a plate in a hairless area. The key to this technique is to cut the anterior site of the bone flap at alternate angles on the cut surface. Interdigitation between the bone flap and skull enables single-plate fixation in the area with hair, which reduces artifacts on postoperative radiological images and provides excellent postoperative cosmetic results.

  2. Research design considerations for single-dose analgesic clinical trials in acute pain: IMMPACT recommendations.

    PubMed

    Cooper, Stephen A; Desjardins, Paul J; Turk, Dennis C; Dworkin, Robert H; Katz, Nathaniel P; Kehlet, Henrik; Ballantyne, Jane C; Burke, Laurie B; Carragee, Eugene; Cowan, Penney; Croll, Scott; Dionne, Raymond A; Farrar, John T; Gilron, Ian; Gordon, Debra B; Iyengar, Smriti; Jay, Gary W; Kalso, Eija A; Kerns, Robert D; McDermott, Michael P; Raja, Srinivasa N; Rappaport, Bob A; Rauschkolb, Christine; Royal, Mike A; Segerdahl, Märta; Stauffer, Joseph W; Todd, Knox H; Vanhove, Geertrui F; Wallace, Mark S; West, Christine; White, Richard E; Wu, Christopher

    2016-02-01

    This article summarizes the results of a meeting convened by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) on key considerations and best practices governing the design of acute pain clinical trials. We discuss the role of early phase clinical trials, including pharmacokinetic-pharmacodynamic (PK-PD) trials, and the value of including both placebo and active standards of comparison in acute pain trials. This article focuses on single-dose and short-duration trials with emphasis on the perioperative and study design factors that influence assay sensitivity. Recommendations are presented on assessment measures, study designs, and operational factors. Although most of the methodological advances have come from studies of postoperative pain after dental impaction, bunionectomy, and other surgeries, the design considerations discussed are applicable to many other acute pain studies conducted in different settings.

  3. Frequency of bone marrow lesions and association with pain severity: results from a population-based symptomatic knee cohort.

    PubMed

    Ip, Stephen; Sayre, Eric C; Guermazi, Ali; Nicolaou, Savvakis; Wong, Hubert; Thorne, Anona; Singer, Joel; Kopec, Jacek A; Esdaile, John M; Cibere, Jolanda

    2011-06-01

    To evaluate the prevalence of bone marrow lesions (BML) and their association with pain severity in a population-based cohort of symptomatic early knee osteoarthritis (OA). Subjects with knee pain (n = 255), age 40-79 years, were evaluated by radiograph and magnetic resonance imaging (MRI) and classified into OA stages: no OA (NOA), preradiographic OA (PROA), and radiographic OA (ROA). BML were graded 0-3 (none, mild, moderate, severe) in 6 regions and defined as (1) BMLsum = the sum of 6 scores; and (2) BMLmax = the worst score at any region. Pain was assessed by the Western Ontario and McMaster Universities OA Index (WOMAC). Linear regression analysis was completed to assess the association of Total WOMAC Pain (primary outcome) versus BMLsum or BMLmax. Secondary outcomes were WOMAC Pain on Walking and WOMAC Pain on Climbing Stairs. All analyses were adjusted for age, sex, body mass index, OA stage, joint effusion, and meniscal damage. BML were present in 11% of NOA, 38% of PROA, and 71% of ROA subjects (p < 0.001). No association was seen for BMLsum or BMLmax versus Total WOMAC Pain or Pain on Walking. However, BMLsum was associated with Pain on Climbing Stairs [regression coefficients (RC) = 0.09, 95% CI 0.00-0.18]. BMLmax was associated with Pain on Climbing Stairs, with the strongest association for severe BML (RC 0.60, 95% CI 0.04-1.17). BML were present in 38% of PROA and 71% of ROA subjects in this symptomatic knee cohort. BML were significantly associated with Pain on Climbing Stairs but not Total WOMAC or Pain on Walking.

  4. Role of serum lipoprotein at the site of iloprost therapy in the treatment of painful bone marrow edema.

    PubMed

    Anagnostakos, Konstantinos; Orth, Patrick

    2013-10-01

    The authors hypothesized that the emergence of painful bone marrow edema occurs through microembolisms in the bone marrow that may be reflected in elevated plasma parameters of hypofibrinolysis or a disturbance of the lipid metabolism and that treatment with iloprost may lead to a decrease in or normalization of the elevated serum parameters and, therefore, to pain reduction. Twenty-one patients (12 men and 9 women; mean age, 50 years [range, 22-70 years]) with painful bone marrow edema and elevated lipoprotein(a) (Lp[a]) serum values were treated with intravenous iloprost. Before and 6 weeks after iloprost therapy, the serum concentrations of Lp(a), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB) were determined. At 6-week follow-up, 17 patients reported complete resolution of their symptoms. For these patients, complete bone marrow edema resolution was observed on magnetic resonance imaging. Four patients reported that their symptoms were either the same or had worsened but had partial bone marrow edema resolution on magnetic resonance imaging. In these patients, Lp(a) values either increased or remained the same. Hence, the total success rate of iloprost treatment was 86% at a mean follow-up of 17 months (range, 3-45 months). Before iloprost therapy, mean ApoA1, ApoB, and Lp(a) values were 159.8, 108.3, and 69.1 mg/dL, respectively. Six weeks after iloprost therapy, mean ApoA1, ApoB, and Lp(a) values decreased to 147.6 (P=.011), 98.4 (P=.042), and 38.3 (P<.001) mg/dL, respectively. The results of this study indicate a possible role of hypofibrinolysis or a disturbance in the lipid metabolism in the emergence of painful bone marrow edema.

  5. The cystine/glutamate antiporter system xc− drives breast tumor cell glutamate release and cancer-induced bone pain

    PubMed Central

    Slosky, Lauren M.; BassiriRad, Neemah M.; Symons, Ashley M.; Thompson, Michelle; Doyle, Timothy; Forte, Brittany L.; Staatz, William D.; Bui, Lynn; Neumann, William L.; Mantyh, Patrick W.; Salvemini, Daniela; Largent-Milnes, Tally M.; Vanderah, Todd W.

    2016-01-01

    Abstract Bone is one of the leading sites of metastasis for frequently diagnosed malignancies, including those arising in the breast, prostate and lung. Although these cancers develop unnoticed and are painless in their primary sites, bone metastases result in debilitating pain. Deeper investigation of this pain may reveal etiology and lead to early cancer detection. Cancer-induced bone pain (CIBP) is inadequately managed with current standard-of-care analgesics and dramatically diminishes patient quality of life. While CIBP etiology is multifaceted, elevated levels of glutamate, an excitatory neurotransmitter, in the bone-tumor microenvironment may drive maladaptive nociceptive signaling. Here, we establish a relationship between the reactive nitrogen species peroxynitrite, tumor-derived glutamate, and CIBP. In vitro and in a syngeneic in vivo model of breast CIBP, murine mammary adenocarcinoma cells significantly elevated glutamate via the cystine/glutamate antiporter system xc−. The well-known system xc− inhibitor sulfasalazine significantly reduced levels of glutamate and attenuated CIBP-associated flinching and guarding behaviors. Peroxynitrite, a highly reactive species produced in tumors, significantly increased system xc− functional expression and tumor cell glutamate release. Scavenging peroxynitrite with the iron and mangano-based porphyrins, FeTMPyP and SRI10, significantly diminished tumor cell system xc− functional expression, reduced femur glutamate levels and mitigated CIBP. In sum, we demonstrate how breast cancer bone metastases upregulate a cystine/glutamate co-transporter to elevate extracellular glutamate. Pharmacological manipulation of peroxynitrite or system xc− attenuates CIBP, supporting a role for tumor-derived glutamate in CIBP and validating the targeting of system xc− as a novel therapeutic strategy for the management of metastatic bone pain. PMID:27482630

  6. Phase II Study of Concurrent Capecitabine and External Beam Radiotherapy for Pain Control of Bone Metastases of Breast Cancer Origin

    PubMed Central

    Kundel, Yulia; Nasser, Nicola J.; Purim, Ofer; Yerushalmi, Rinat; Fenig, Eyal; Pfeffer, Raphael M.; Stemmer, Salomon M.; Rizel, Shulamith; Symon, Zvi; Kaufman, Bella; Sulkes, Aaron; Brenner, Baruch

    2013-01-01

    Background Pain from bone metastases of breast cancer origin is treated with localized radiation. Modulating doses and schedules has shown little efficacy in improving results. Given the synergistic therapeutic effect reported for combined systemic chemotherapy with local radiation in anal, rectal, and head and neck malignancies, we sought to evaluate the tolerability and efficacy of combined capecitabine and radiation for palliation of pain due to bone metastases from breast cancer. Methodology/Principal Findings Twenty-nine women with painful bone metastases from breast cancer were treated with external beam radiation in 10 fractions of 3 Gy, 5 fractions a week for 2 consecutive weeks. Oral capecitabine 700 mg/m2 twice daily was administered throughout radiation therapy. Rates of complete response, defined as a score of 0 on a 10-point pain scale and no increase in analgesic consumption, were 14% at 1 week, 38% at 2 weeks, 52% at 4 weeks, 52% at 8 weeks, and 48% at 12 weeks. Corresponding rates of partial response, defined as a reduction of at least 2 points in pain score without an increase in analgesics consumption, were 31%, 38%, 28%, 34% and 38%. The overall response rate (complete and partial) at 12 weeks was 86%. Side effects were of mild intensity (grade I or II) and included nausea (38% of patients), weakness (24%), diarrhea (24%), mucositis (10%), and hand and foot syndrome (7%). Conclusions/Significance External beam radiation with concurrent capecitabine is safe and tolerable for the treatment of pain from bone metastases of breast cancer origin. The overall and complete response rates in our study are unusually high compared to those reported for radiation alone. Further evaluation of this approach, in a randomized study, is warranted. Trial Registration ClinicalTrials.gov NCT01784393NCT01784393 PMID:23874586

  7. Large volume inside the cage leading incomplete interbody bone fusion and residual back pain after posterior lumbar interbody fusion.

    PubMed

    Takeuchi, Mikinobu; Kamiya, Mitsuhiro; Wakao, Norimitsu; Hirasawa, Atsuhiko; Kawanami, Katsuhisa; Osuka, Koji; Takayasu, Masakazu

    2015-07-01

    The purpose of this study is to compare intervertebral bone fusion and clinical outcomes in L4-5 posterior lumbar interbody fusion (PLIF) using the same posterior instrumentation with four combinations of one of three types of interbody cage with one of two bone grafts, iliac and local or only local. In 67 patients who underwent L4-5 PLIF, 19 patients had the Brantigan cage and iliac and local bone graft, 18 with the TELAMON C cage and iliac and local bone graft, 16 with the TELAMON C cage and local bone graft (TL), and 14 with the OIC PEEK cage and local bone graft. Clinical assessments were based on Japanese Orthopaedic Association (JOA) scores and on the visual analogue scale (VAS). The bone fusion assessments were based on radiography and CT scans according to the Brantigan, Steffee, and Fraser criteria. More than 2 years after surgery, these assessments were made. In the results, the fusion outcome for the group receiving TL was significantly less than those for the other three groups. In TL, multivariate logistic regression analysis showed that the inside volume of the cage of ≥2.0 mL was the only significant factor for incomplete fusion. Moreover, the VAS (low back pain) score was significantly higher for TL than for the other three groups. In conclusions, we believe that the large volume inside the cage (≥2.0 mL) with local bone graft may lead incomplete interbody bone fusion and residual postsurgical low back pain after PLIF.

  8. Repeated administration of mazindol reduces spontaneous pain-related behaviors without modifying bone density and microarchitecture in a mouse model of complete Freund's adjuvant-induced knee arthritis.

    PubMed

    Robledo-González, L E; Martínez-Martínez, A; Vargas-Muñoz, V M; Acosta-González, R I; Plancarte-Sánchez, R; Anaya-Reyes, M; Fernández Del Valle-Laisequilla, C; Reyes-García, J G; Jiménez-Andrade, J M

    2017-01-01

    The role of dopaminergic system in the development of rheumatoid arthritis-related pain, a major symptom in this disease, has not been explored. Therefore, the anti-nociceptive effect of mazindol, a dopamine uptake inhibitor, was evaluated in a model of complete Freund's adjuvant (CFA)-induced arthritis. Furthermore, as studies have shown that the dopaminergic system regulates bone metabolism, the effect of mazindol on bone mass and microarchitecture was determined. Adult ICR male mice received intra-articular injections of either CFA or saline into the right knee joint every week. Spontaneous pain-like behaviors (flinching and guarding) and locomotor activity were assessed at day 26 post-first CFA, following which, a single intraperitoneally (i.p.) administered dose of mazindol was given (1, 3 and 10 mg/kg). Then, the antinociceptive effect of a repeated administration of 3 mg/kg mazindol (daily, i.p.; day 15-day 26) was evaluated. Additionally, at day 26, the participation of D1-like, D2-like or opioid receptors in the antinociceptive effect of mazindol was evaluated. The effect of mazindol on bone density and microarchitecture was evaluated by micro-computed tomography. Acute administration of mazindol decreased the spontaneous pain-like behaviors in a dose-dependent manner without reducing the knee edema. However, mazindol at 10 mg/kg significantly increased the locomotor activity; therefore, 3 mg/kg mazindol was used for further studies. Repeated administration of 3 mg/kg mazindol significantly decreased the pain-like behaviors without modifying locomotor activity. The antinociceptive effect of mazindol was blocked by administration of a D2-like receptor antagonist (haloperidol), but not by administration of D1-like receptor antagonist (SCH 23390) or an opioid receptor antagonist (naloxone). Repeated administration of mazindol did not significantly modify the density and microarchitecture of periarticular bone of the arthritic and nonarthritic knee joints

  9. Quality assurance experience with the randomized neuropathic bone pain trial (Trans-Tasman Radiation Oncology Group, 96.05).

    PubMed

    Roos, Daniel E; Davis, Sidney R; Turner, Sandra L; O'Brien, Peter C; Spry, Nigel A; Burmeister, Bryan H; Hoskin, Peter J; Ball, David L

    2003-05-01

    Trans-Tasman Radiation Oncology Group 96.05 is a prospective randomized controlled trial comparing a single 8 Gy with 20 Gy in five fractions of radiotherapy (RT) for neuropathic pain due to bone metastases. This paper summarizes the quality assurance (QA) activities for the first 234 patients (accrual target 270). Independent audits to assess compliance with eligibility/exclusion criteria and appropriateness of treatment of the index site were conducted after each cohort of approximately 45 consecutive patients. Reported serious adverse events (SAEs) in the form of cord/cauda equina compression or pathological fracture developing at the index site were investigated and presented in batches to the Independent Data Monitoring Committee. Finally, source data verification of the RT prescription page and treatment records was undertaken for each of the first 234 patients to assess compliance with the protocol. Only one patient was found conclusively not to have genuine neuropathic pain, and there were no detected 'geographical misses' with RT fields. The overall rate of detected infringements for other eligibility criteria over five audits (225 patients) was 8% with a dramatic improvement after the first audit. There has at no stage been a statistically significant difference in SAEs by randomization arm. There was a 22% rate of RT protocol variations involving ten of the 14 contributing centres, although the rate of major dose violations (more than +/-10% from protocol dose) was only 6% with no statistically significant difference by randomization arm (P=0.44). QA auditing is an essential but time-consuming component of RT trials, including those assessing palliative endpoints. Our experience confirms that all aspects should commence soon after study activation.

  10. Single dose oral gabapentin for established acute postoperative pain in adults

    PubMed Central

    Straube, Sebastian; Derry, Sheena; Moore, R Andrew; Wiffen, Philip J; McQuay, Henry J

    2014-01-01

    Background Gabapentin is an antiepileptic drug, also used in the treatment of neuropathic pain, which is the subject of a Cochrane review, currently under revision. Its efficacy in treating established acute postoperative pain has not been demonstrated. Objectives To assess the efficacy and safety of single dose oral gabapentin compared with placebo in established acute postoperative pain using methods that permit comparison with other analgesics. Search methods We searched Cochrane CENTRAL, MEDLINE, EMBASE, and the Oxford Pain Relief Database. Additional studies were sought from reference lists of retrieved articles and reviews. Clinical trials databases were searched for unpublished studies; clinical trial reports of several unpublished studies have been made public following litigation in the US. Selection criteria Single oral dose, randomised, double-blind, placebo-controlled trials of gabapentin for relief of established moderate to severe postoperative pain in adults. Data collection and analysis Studies were assessed for methodological quality and data extracted by two review authors independently. Numbers of participants with at least 50% of maximum possible total pain relief (TOTPAR) or summed pain intensity difference (SPID) with gabapentin or placebo were calculated and used to derive relative benefit (RB) or risk (RR), and number-needed-to-treat-to-benefit (NNT). Numbers of participants using rescue medication, and time to its use, were sought as additional measures of efficacy. Information on adverse events and withdrawals was collected. Main results Four unpublished studies met inclusion criteria; in three, participants had pain following dental surgery, and one followed major orthopaedic surgery; 177 participants were treated with a single dose of gabapentin 250 mg, 21 with gabapentin 500 mg, and 172 with placebo. At least 50% pain relief over 6 hours was achieved by 15% with gabapentin 250 mg and 5% with placebo; giving a RB of 2.5 (95% CI 1.2 to 5

  11. Registration of CT to pre-treatment MRI for planning of MR-HIFU ablation treatment of painful bone metastases

    NASA Astrophysics Data System (ADS)

    Noorda, Yolanda H.; Bartels, Lambertus W.; Huisman, Merel; Nijenhuis, Robbert J.; AAJ van den Bosch, Maurice; Pluim, Josien PW

    2014-08-01

    MR-HIFU is a new non-invasive treatment modality that can be used for palliation in patients with painful bone metastases. Since treatment strategies are mainly focused on the ablation of periosteal nerves, information on the presence and geometry of cortical bone influences the treatment strategy, both in determining the acoustic power and in avoiding safety issues related to far-field heating. Although MRI is available for imaging during treatment, CT is best used for examining the cortical bone. We present a registration method for registering CT and MR images of patients with bone metastases prior to therapy. CT and MRI data were obtained from nine patients with metastatic bone lesions at varying locations. A two-step registration approach was used, performing simultaneous rigid registration of all available MR images in the first step and an affine and deformable registration with an additional bone metric in the second step. The performance was evaluated using landmark annotation by clinical observers. An average registration error of 4.5 mm was obtained, which was comparable to the slice thickness of the data. The performance of the registration algorithm was satisfactory, even with differences in MRI acquisition parameters and for various anatomical sites. The obtained CT overlay is useful for treatment planning, as it allows an assessment of the integrity of the cortical bone. CT-MR registration is therefore recommended for HIFU treatment planning of patients with bone metastases.

  12. Accessory navicular bone incidence in Chinese patients: a retrospective analysis of X-rays following trauma or progressive pain onset.

    PubMed

    Huang, Jiazhang; Zhang, Yijun; Ma, Xin; Wang, Xu; Zhang, Chao; Chen, Li

    2014-03-01

    Optimal treatment of symptomatic accessory navicular bones, generally asymptomatic 'extra' ossicles in the front interior ankle, remains debated. Incidence and type of accessory navicular bones in Chinese patients were examined as a basis for improving diagnostic and treatment standards. Accessory navicular bones were retrospectively examined in 1,625 (790 men and 835 women) patients with trauma-induced or progressive symptomatic ankle pain grouped by gender and age from August 2011 to May 2012. Anterior-posterior/oblique X-ray images; presence; type; affected side; modified Coughlin's classification types 1, 2A, 2B, and 3; and subgroups a-c were recorded. Accessory navicular bones were found in 329 (20.2%) patients (143 men and 186 women; mean age, 47.24 ± 18.34, ranging 14-96 years). Patients aged 51-60 exhibited most accessory navicular bones (29.7%), with risk slightly higher in women and generally increasing from minimal 10.9% at ages 11-20 to age 51 and thereafter declining to 0.4% by age 90. The incidence was 41.6% for Type 1 (Type 1a: 9.1%, Type 1b: 15.5%, and Type 1c: 19.4%), 36.8% for Type 2 (Type 2Aa: 2.1%, Type 2Ab: 13.7%, Type 2Ac: 5.1%, Type 2Ba: 2.1%, 2Bb: 2.1%, and 2Bc: 11.6%), and 21.6% for Type 3 (Type 3a: 4.5%, Type 3b: 14%, and Type 3c: 3.0%). Approximately one-fifth (20.3%) of ankle pain patients exhibited accessory navicular bones, with Type 2 most common and middle-aged patients most commonly affected. Thus, accessory navicular bones may be less rare than previously thought, underlying treatable symptomatic conditions of foot pain and deformity.

  13. Single dose oral indometacin for the treatment of acute postoperative pain

    PubMed Central

    Moore, R Andrew; Derry, Sheena; Mason, Lorna; McQuay, Henry J; Edwards, Jayne

    2014-01-01

    Background This is an updated version of the original Cochrane review published in Issue 4, 2004. Indometacin is a non-steroidal anti-inflammatory drug (NSAID) used most commonly for the treatment of inflammation and pain resulting from rheumatic disease (arthritis), and less commonly in postoperative pain management. When taken for chronic pain conditions, indometacin has been associated with a high incidence of adverse events. The benefits and harms of orally-administered indometacin for postoperative pain are not clear. Objectives To determine the efficacy of a single dose of oral indometacin compared with placebo in treating acute postoperative pain in adults, and to analyse information relating to adverse events. Search methods We searched the Cochrane CENTRAL Register of Controlled Trials in The Cochrane Library, MEDLINE, EMBASE and the Oxford Pain Relief Database for relevant studies in January 2002 and for the updated search in December 2007. Additional studies were sought from the reference lists of retrieved studies. Selection criteria Studies were included in the review if they were randomised, double blind, placebo-controlled clinical trials using a single oral dose of indometacin in adults with acute postoperative pain. Data collection and analysis Studies were assessed independently by two review authors. Pain relief or pain intensity data were extracted and converted into dichotomous information to give the number of participants with at least 50% pain relief over four to six hours. The relative benefit for at least 50% pain relief was calculated. Main results In the original review one study of 59 women with post-episiotomy pain met the inclusion criteria. The dose of indometacin assessed against placebo was 50 mg, and the results concluded that indometacin was not significantly better than placebo for relieving postoperative pain at four to six hours. There was insufficient information to conduct further efficacy analyses or assess adverse events

  14. Perineal pain secondary to tethered cord syndrome: retrospective review of single institution experience.

    PubMed

    Robbins, J Will; Lundy, Paige A; Gard, Andrew P; Puccioni, Mark J

    2015-11-01

    Tethered cord syndrome (TCS) encompasses a spectrum of neurological dysfunction related to excessive tension on the distal spinal cord resulting in anatomic deformation and metabolic disturbance. Symptoms typically manifest as back/leg pain, neurogenic bladder dysfunction, constipation, sphincter abnormalities, and scoliosis. To date, among the least well-described symptoms of TCS is pain or hypersensitivity in the perineal region. The authors reviewed their experience with spinal cord detethering to identify and further characterize those who present with perineal pain or hypersensitivity. Cases of spinal cord detethering at a single institution were retrospectively reviewed. Patients were initially identified by procedural codes. Cases were reviewed for presenting symptoms, specifically perineal pain or hypersensitivity. Magnetic resonance image (MRI) findings, clinical outcome, and length of follow-up were also noted. Of the 491 patients identified, seven patients (1.4%) were identified as having preoperative perineal pain or hypersensitivity. All of these patients had complete resolution of perineal pain/hypersensitivity at the time of last follow-up. Furthermore, five (71%) of these patients experienced resolution of all initial symptoms. Perineal pain or hypersensitivity can be an important symptom of spinal cord tethering. Spinal cord detethering may result in a good outcome and relief of perineal pain or hypersensitivity.

  15. Intrathecal injection of selected peptide Myr-RC-13 attenuates bone cancer pain by inhibiting KIF17 and NR2B expression.

    PubMed

    Ni, Kun; Zhou, Yu; Sun, Yu-e; Liu, Yue; Gu, Xiao-ping; Ma, Zheng-liang

    2014-07-01

    Although bone cancer pain is a common intractable clinical symptom, its underlying mechanisms are still elusive. Accumulating evidence reveals that the N-methyl-D-aspartate (NMDA) receptor containing a 2B subunit (NR2B) in the spinal cord contributes to bone cancer pain. Our preliminary study demonstrated that intrathecal injection of fusion peptide Myr-RC-13 could disrupt spinal KIF17/mLin10 interaction, which is an essential component of KIF17-mediated NR2B transport. Here we report a means by infusion of the selected peptide Myr-RC-13 intrathecally to attenuate bone cancer pain. The results showed that inoculation of fibrosarcoma NCTC 2472 cells into the femur cavity of C3H/HeJ mice induced progressive bone cancer pain and resulted in up-regulation of KIF17 and NR2B in the spinal cord. In addition, repetitive spinal delivery of Myr-RC-13 relieved bone cancer-related mechanical allodynia and spontaneous pain behaviors, and down-regulated expression of spinal KIF17 and NR2B. Finally, our results demonstrated that selected peptide Myr-RC-13 was able to attenuate bone cancer pain via decreasing spinal KIF17 and NR2B expressions. Therefore, selected peptide Myr-RC-13 might be a potential analgesic strategy for bone cancer pain.

  16. Antinociceptive Effect of Intrathecal Injection of Genetically Engineered Human Bone Marrow Stem Cells Expressing the Human Proenkephalin Gene in a Rat Model of Bone Cancer Pain

    PubMed Central

    Tian, Yuke; Li, Haifeng; Zhang, Dengwen; Sun, Qiang

    2017-01-01

    Background. This study aimed to investigate the use of human bone marrow mesenchymal stem cells (hBMSCs) genetically engineered with the human proenkephalin (hPPE) gene to treat bone cancer pain (BCP) in a rat model. Methods. Primary cultured hBMSCs were passaged and modified with hPPE, and the cell suspensions (6 × 106) were then intrathecally injected into a rat model of BCP. Paw mechanical withdrawal threshold (PMWT) was measured before and after BCP. The effects of hPPE gene transfer on hBMSC bioactivity were analyzed in vitro and in vivo. Results. No changes were observed in the surface phenotypes and differentiation of hBMSCs after gene transfer. The hPPE-hBMSC group showed improved PMWT values on the ipsilateral side of rats with BCP from day 12 postoperatively, and the analgesic effect was reversed by naloxone. The levels of proinflammatory cytokines such as IL-1β and IL-6 were ameliorated, and leucine-enkephalin (L-EK) secretion was augmented, in the hPPE-engineered hBMSC group. Conclusion. The intrathecal administration of BMSCs modified with the hPPE gene can effectively relieve pain caused by bone cancer in rats and might be a potentially therapeutic tool for cancer-related pain in humans. PMID:28286408

  17. The effect of aging on the density of the sensory nerve fiber innervation of bone and acute skeletal pain

    PubMed Central

    Jimenez-Andrade, Juan M.; Mantyh, William G.; Bloom, Aaron P.; Freeman, Katie T.; Ghilardi, Joseph R.; Kuskowski, Michael A.; Mantyh, Patrick W.

    2010-01-01

    As humans age there is a decline in most sensory systems including vision, hearing, taste, smell, and tactile acuity. In contrast, the frequency and severity of musculoskeletal pain generally increases with age. To determine whether the density of sensory nerve fibers that transduce skeletal pain changes with age, calcitonin gene related peptide (CGRP) and neurofilament 200 kDa (NF200) sensory nerve fibers that innervate the femur were examined in the femurs of young (4 month old), middle-aged (13 month) and old (36 month) male F344/BNF1 rats. Whereas the bone quality showed a significant age-related decline, the density of CGRP+ and NF200+ nerve fibers that innervate the bone remained remarkably unchanged as well as the severity of acute skeletal fracture pain. Thus, while bone mass, quality and strength undergo a significant decline with age, the density of sensory nerve fibers that transduce noxious stimuli remain largely intact. These data may in part explain why musculoskeletal pain increases with age. PMID:20947214

  18. Bone augmentation for single tooth implants: A review of the literature.

    PubMed

    Friberg, Bertil

    2016-01-01

    To analyse data on bone augmentation at single-tooth implants with regard to the type of graft materials, the stability of grafts over time, reported time span towards implant placement, implant survival rates, implant marginal bone maintenance and possible complications. A literature review resulted in 585 titles after exclusion of duplicates. Analyses of article titles and abstracts reduced the number to 93 studies, which were subsequently full-text analysed. After the final selection, a total of 24 studies were included, of which 13 reported on single implants and horizontal/vertical augmentation (onlay), 10 focused on single implants and sinus augmentation (inlay), and one study presented the outcome of single implants and distraction osteogenesis. All bone materials, i.e. autografts, allografts, xenografts, and alloplasts, were used with comparable satisfactory results, allowing for placement of 7 to 10 mm-long implants. Stability of bone graft volume over time was sparsely documented. Some onlay autografts tended to resorb early i.e. prior to implant placement, but minor bone resorption was also seen for other grafts over time. A continuous but small bone resorption of inlay autografts and alloplasts was seen over time for the few sites recorded. A staged approach predominated for the onlay grafts, with implants placed 3 to 6 months post-grafting, and overall a majority of these implants (347/363) were submerged. For the inlay graft procedures almost all implants were immediately inserted at the time of grafting, and the majority of these implants (253/256) were submerged. A total of five and two implant failures were registered during the various study periods for the onlays and inlays, respectively. Marginal bone conditions, around implants in grafted sites, were comparable to what has generally been reported for non-grafted sites. Bone augmentation for the single-tooth implant is a viable treatment option with predictable graft and implant outcomes.

  19. Differential activation of the μ-opioid receptor by oxycodone and morphine in pain-related brain regions in a bone cancer pain model

    PubMed Central

    Nakamura, Atsushi; Hasegawa, Minoru; Minami, Kazuhisa; Kanbara, Tomoe; Tomii, Takako; Nishiyori, Atsushi; Narita, Minoru; Suzuki, Tsutomu; Kato, Akira

    2013-01-01

    Background and Purpose Bone cancer pain is chronic and often difficult to control with opioids. However, recent studies have shown that several opioids have distinct analgesic profiles in chronic pain. Experimental Approach To clarify the mechanisms underlying these distinct analgesic profiles, functional changes in the μ-opioid receptor were examined using a mouse femur bone cancer (FBC) model. Key Results In the FBC model, the Bmax of [3H]-DAMGO binding was reduced by 15–45% in the periaqueductal grey matter (PAG), region ventral to the PAG (vPAG), mediodorsal thalamus (mTH), ventral thalamus and spinal cord. Oxycodone (10−8–10−5 M) and morphine (10−8–10−5 M) activated [35S]-GTPγS binding, but the activation was significantly attenuated in the PAG, vPAG, mTH and spinal cord in the FBC model. Interestingly, the attenuation of oxycodone-induced [35S]-GTPγS binding was quite limited (9–26%) in comparison with that of morphine (46–65%) in the PAG, vPAG and mTH, but not in the spinal cord. Furthermore, i.c.v. oxycodone at doses of 0.02–1.0 μg per mouse clearly inhibited pain-related behaviours, such as guarding, limb-use abnormalities and allodynia-like behaviour in the FBC model mice, while i.c.v. morphine (0.05–2.0 μg per mouse) had only partial or little analgesic effect on limb-use abnormalities and allodynia-like behaviour. Conclusion and Implications These results show that μ-opioid receptor functions are attenuated in several pain-related regions in bone cancer in an agonist-dependent manner, and suggest that modification of the μ-opioid receptor is responsible for the distinct analgesic effect of oxycodone and morphine. PMID:22889192

  20. Safety and efficacy of repeat administration of samarium Sm-153 lexidronam to patients with metastatic bone pain.

    PubMed

    Sartor, Oliver; Reid, Robert H; Bushnell, David L; Quick, Donald P; Ell, Peter J

    2007-02-01

    Samarium Sm 153 lexidronam (Sm-153) is an effective and well-tolerated treatment for painful bone metastases. The purpose of the analysis was to assess the safety and efficacy of repeated doses of Sm-153 in patients with metastatic bone pain. Data were collected prospectively for 202 patients administered 1.0 mCi/kg of Sm-153. Particular emphasis was placed on analysis of data from 55 patients receiving > or = 2 doses. Pain scores, adverse events, and hematologic parameters were assessed after each dose. Mild, transient suppression of platelets and white blood cell counts was the most common adverse event after treatment. Nadirs were approximately half of baseline at 4 weeks after dosing with recovery by Week 8 in 90% of patients. Temporary grade 3 thrombocytopenia occurred in 11%, 12%, and 17% of patients after the first, second, and third drug administration, respectively. Grade 3 leukopenia occurred in less than 7% of patients independent of the number of administrations. Significant decreases in pain scores (P < .001) were observed at Week 4 after each of the first 3 doses and maintained at Week 8 after the first 2 doses (P < .003) but not the third. Decreases in pain scores were observed in 70%, 63%, and 80% of patients, respectively, at Week 4 after the first 3 administrations. Repeated dosing of 1.0 mCi/kg of Sm-153 was both safe and effective and is a reasonable treatment option in patients whose bone pain responds and then recurs after an initial dose provided that adequate hematologic function is present at the time of drug administration. (c) 2007 American Cancer Society.

  1. Single x-ray transmission system for bone mineral density determination

    SciTech Connect

    Jimenez-Mendoza, Daniel; Vargas-Vazquez, Damian; Giraldo-Betancur, Astrid L.; Hernandez-Urbiola, Margarita I.; Rodriguez-Garcia, Mario E.

    2011-12-15

    Bones are the support of the body. They are composed of many inorganic compounds and other organic materials that all together can be used to determine the mineral density of the bones. The bone mineral density is a measure index that is widely used as an indicator of the health of the bone. A typical manner to evaluate the quality of the bone is a densitometry study; a dual x-ray absorptiometry system based study that has been widely used to assess the mineral density of some animals' bones. However, despite the success stories of utilizing these systems in many different applications, it is a very expensive method that requires frequent calibration processes to work properly. Moreover, its usage in small species applications (e.g., rodents) has not been quite demonstrated yet. Following this argument, it is suggested that there is a need for an instrument that would perform such a task in a more reliable and economical manner. Therefore, in this paper we explore the possibility to develop a new, affordable, and reliable single x-ray absorptiometry system. The method consists of utilizing a single x-ray source, an x-ray image sensor, and a computer platform that all together, as a whole, will allow us to calculate the mineral density of the bone. Utilizing an x-ray transmission theory modified through a version of the Lambert-Beer law equation, a law that expresses the relationship among the energy absorbed, the thickness, and the absorption coefficient of the sample at the x-rays wavelength to calculate the mineral density of the bone can be advantageous. Having determined the parameter equation that defines the ratio of the pixels in radiographies and the bone mineral density [measured in mass per unit of area (g/cm{sup 2})], we demonstrated the utility of our novel methodology by calculating the mineral density of Wistar rats' femur bones.

  2. Single x-ray transmission system for bone mineral density determination.

    PubMed

    Jimenez-Mendoza, Daniel; Espinosa-Arbelaez, Diego G; Giraldo-Betancur, Astrid L; Hernandez-Urbiola, Margarita I; Vargas-Vazquez, Damian; Rodriguez-Garcia, Mario E

    2011-12-01

    Bones are the support of the body. They are composed of many inorganic compounds and other organic materials that all together can be used to determine the mineral density of the bones. The bone mineral density is a measure index that is widely used as an indicator of the health of the bone. A typical manner to evaluate the quality of the bone is a densitometry study; a dual x-ray absorptiometry system based study that has been widely used to assess the mineral density of some animals' bones. However, despite the success stories of utilizing these systems in many different applications, it is a very expensive method that requires frequent calibration processes to work properly. Moreover, its usage in small species applications (e.g., rodents) has not been quite demonstrated yet. Following this argument, it is suggested that there is a need for an instrument that would perform such a task in a more reliable and economical manner. Therefore, in this paper we explore the possibility to develop a new, affordable, and reliable single x-ray absorptiometry system. The method consists of utilizing a single x-ray source, an x-ray image sensor, and a computer platform that all together, as a whole, will allow us to calculate the mineral density of the bone. Utilizing an x-ray transmission theory modified through a version of the Lambert-Beer law equation, a law that expresses the relationship among the energy absorbed, the thickness, and the absorption coefficient of the sample at the x-rays wavelength to calculate the mineral density of the bone can be advantageous. Having determined the parameter equation that defines the ratio of the pixels in radiographies and the bone mineral density [measured in mass per unit of area (g/cm(2))], we demonstrated the utility of our novel methodology by calculating the mineral density of Wistar rats' femur bones.

  3. Single x-ray transmission system for bone mineral density determination

    NASA Astrophysics Data System (ADS)

    Jimenez-Mendoza, Daniel; Espinosa-Arbelaez, Diego G.; Giraldo-Betancur, Astrid L.; Hernandez-Urbiola, Margarita I.; Vargas-Vazquez, Damian; Rodriguez-Garcia, Mario E.

    2011-12-01

    Bones are the support of the body. They are composed of many inorganic compounds and other organic materials that all together can be used to determine the mineral density of the bones. The bone mineral density is a measure index that is widely used as an indicator of the health of the bone. A typical manner to evaluate the quality of the bone is a densitometry study; a dual x-ray absorptiometry system based study that has been widely used to assess the mineral density of some animals' bones. However, despite the success stories of utilizing these systems in many different applications, it is a very expensive method that requires frequent calibration processes to work properly. Moreover, its usage in small species applications (e.g., rodents) has not been quite demonstrated yet. Following this argument, it is suggested that there is a need for an instrument that would perform such a task in a more reliable and economical manner. Therefore, in this paper we explore the possibility to develop a new, affordable, and reliable single x-ray absorptiometry system. The method consists of utilizing a single x-ray source, an x-ray image sensor, and a computer platform that all together, as a whole, will allow us to calculate the mineral density of the bone. Utilizing an x-ray transmission theory modified through a version of the Lambert-Beer law equation, a law that expresses the relationship among the energy absorbed, the thickness, and the absorption coefficient of the sample at the x-rays wavelength to calculate the mineral density of the bone can be advantageous. Having determined the parameter equation that defines the ratio of the pixels in radiographies and the bone mineral density [measured in mass per unit of area (g/cm2)], we demonstrated the utility of our novel methodology by calculating the mineral density of Wistar rats' femur bones.

  4. Effect of intracanal cryotherapy on pain after single-visit root canal treatment.

    PubMed

    Keskin, Cangül; Özdemir, Özgür; Uzun, İsmail; Güler, Buğra

    2016-10-04

    The purpose of this study was to evaluate the effect of 2.5°C cold saline irrigation as final irrigant on postoperative pain after single-visit root canal treatment of teeth with vital pulps. One-hundred and seventy patients were assessed as eligible and included to the study. The teeth were randomly divided into two groups (n = 85) (i.e. the control group and the cryotherapy group). In the cryotherapy group, final irrigation with 2.5°C 0.9% physiological saline solution for 5 min was performed following completion of biomechanical preparation, whereas in control group same solution stored at the root temperature was used. Treatments were performed in a single visit. Participants were asked to rate the intensity of their postoperative pain using visual analogue scale at 24 and 48 h. Data were analysed by Mann-Whitney U test and Student's t test. In the cryotherapy group level of reported postoperative pain was significantly lower than the control group (P < 0.05, Mann-Whitney U test). The outcome of this investigation indicates that 2.5°C cold saline irrigation as final irrigant can result a significant reduction in postoperative pain levels in comparison to the control group. Cryotherapy is a simple, cost-effective, and non-toxic option for postoperative pain control in single visit root canal treatment.

  5. Single strip lesions radiofrequency denervation for treatment of sacroiliac joint pain: two years' results.

    PubMed

    Bellini, Martina; Barbieri, Massimo

    2016-01-01

    Sacroiliac joint pain can be managed by intra-articular injections or radiofrequency of its innervation. Single strip lesions radiofrequency denervation is a new system. The objective of this study was to present one of the first utilizations of this innovative technique. 60 patients who met the diagnostic criteria for sacroiliac joint syndrome were enrolled in the study. In total, 102 single strip lesions radiofrequency denervations were performed. Pain intensity was measured with the Oswestry low back pain disability questionnaire and the Oswestry Disability Index whose scores were assessed at 1, 3, 6 and 12 months after the procedure. 91.8 % of the 102 radiofrequency treatments resulted in a reduction of more than 50% pain intensity relief at 1 month, 81.6% at 3 months and 59.16% at 6 months. In 35.7% of cases, the relief was continuative up to 1 year. No relief was observed in 12.24% of cases. The ODI scores improved significantly 1 month after the procedure, compared with the baseline scores. The ODI scores after 6 months improved very clearly compared with the baseline scores and with the 3-month scores. Single strip lesions radiofrequency denervation using the Simplicity III probe is a potential modality for intermediate term relief for patients with sacroiliac pain.

  6. Kinesin superfamily protein 17 contributes to the development of bone cancer pain by participating in NR2B transport in the spinal cord of mice.

    PubMed

    Liu, Ming; Liu, Yue; Hou, Bailing; Bu, Dan; Shi, Linyu; Gu, Xiaoping; Ma, Zhengliang

    2015-03-01

    Τreatment of bone cancer pain remains a challenge, while the mechanisms causing the pain remain elusive. We demonstrated that the expression of the N‑methyl‑D‑aspartate (NMDA) receptor NR2B subunit was upregulated in mice with bone cancer pain. Kinesin superfamily protein 17 (KIF17), a recently characterized member of the kinesin superfamily proteins, has been demonstrated to transport and deliver the NR2B subunit to dendrites in mammalian neurons. In the present study, we induced bone cancer pain via femur bone cavity osteosarcoma NCTC 2472 tumor cell implantation (TCI) in mice. The results showed that TCI in mice increased the number of spontaneous flinches, mechanical allodynia events, expression of spinal KIF17 and NR2B subunits. Intrathecal administration of KIF17 antisense oligodeoxynucleotide (ODN) attenuated the behavioral signs of bone cancer pain and suppressed the increased expression of NR2B induced by TCI. In addition, KIF17 binds to a protein complex that contains mLin‑10 to transport NR2B, and we determined that the increase of mLin‑10 was suppressed following admini-stration. Thus, these findings suggested that KIF17 contributed to the development of bone cancer pain in the spinal cord through NR2B transport and that mLin‑10 may also play a role in pain development.

  7. Monoaxial distraction of ulna to second metacarpal followed by single bone forearm in massive post infective radial bone loss

    PubMed Central

    Pal, Jitendra N; Banik, Rajeeb

    2012-01-01

    Introduction: Radial bone loss associated with gross manus valgus deformity can be managed by open reduction internal fixation using intervening strut bone graft, callus distraction using ring or monoaxial fixator, and achieving union by distraction histogenesis. These methods are particularly suitable when bone loss is small. Single or staged procedure is described for congenital as well as in acquired extensive bone loss of radius. Distraction through radial proximal to distal segments, to achieve reduction of distal radio-ulnar joint (DRUJ), is also described in acquired cases. In the present series, functional results of distraction through ulna to 2nd metacarpal is studied alongwith, functional status of hand, stability of wrist, level of patient's satisfaction are also studied. Materials and Methods: 7 unilateral cases of radial loss (M = 5, F = 2) affecting 4 right hands of mean age 17 years (range 9 to 24 years) were included in this study. They were treated by distracting through ulna to 2nd metacarpal to achieve DRUJ alignment in first stage. Subsequently ulna was osteotomised and translated to distal stump of radius. It was then fixed to the distal radial remnant in 30° pronation in dominant and 30° supination non dominant hands. Results: Union was achieved in all cases associated with beneficial cross union of distal ulna. Hand functions improved near to normal, with fully corrected stable wrist joint, hypertrophied ulna and without recurrence. All of them had practically complete loss of forearm rotations, however patients were fully satisfied. Conclusion: This method is particularly suitable when associated with 6 cm or more radial bone loss. But when loss is small, sacrifice of one bone may not be justifiable. PMID:23325973

  8. A novel single pulsed electromagnetic field stimulates osteogenesis of bone marrow mesenchymal stem cells and bone repair.

    PubMed

    Fu, Yin-Chih; Lin, Chih-Chun; Chang, Je-Ken; Chen, Chung-Hwan; Tai, I-Chun; Wang, Gwo-Jaw; Ho, Mei-Ling

    2014-01-01

    Pulsed electromagnetic field (PEMF) has been successfully applied to accelerate fracture repair since 1979. Recent studies suggest that PEMF might be used as a nonoperative treatment for the early stages of osteonecrosis. However, PEMF treatment requires a minimum of ten hours per day for the duration of the treatment. In this study, we modified the protocol of the single-pulsed electromagnetic field (SPEMF) that only requires a 3-minute daily treatment. In the in vitro study, cell proliferation and osteogenic differentiation was evaluated in the hBMSCs. In the in vivo study, new bone formation and revascularization were evaluated in the necrotic bone graft. Results from the in vitro study showed no significant cytotoxic effects on the hBMSCs after 5 days of SPEMF treatment (1 Tesla, 30 pulses per day). hBMSC proliferation was enhanced in the SPEMF-treated groups after 2 and 4 days of treatment. The osteogenic differentiation of hBMSCs was significantly increased in the SPEMF-treated groups after 3-7 days of treatment. Mineralization also increased after 10, 15, 20, and 25 days of treatment in SPEMF-treated groups compared to the control group. The 7-day short-course treatment achieved similar effects on proliferation and osteogenesis as the 25-day treatment. Results from the in vivo study also demonstrated that both the 7-day and 25-day treatments of SPEMF increased callus formation around the necrotic bone and also increased new vessel formation and osteocyte numbers in the grafted necrotic bone at the 2nd and 4th weeks after surgery. In conclusion, the newly developed SPEMF accelerates osteogenic differentiation of cultured hBMSCs and enhances bone repair, neo-vascularization, and cell growth in necrotic bone in mice. The potential clinical advantage of the SPEMF is the short daily application and the shorter treatment course. We suggest that SPEMF may be used to treat fractures and the early stages of osteonecrosis.

  9. Effects of cyclical etidronate with alfacalcidol on lumbar bone mineral density, bone resorption, and back pain in postmenopausal women with osteoporosis.

    PubMed

    Iwamoto, Jun; Takeda, Tsuyoshi; Ichimura, Shoichi; Matsu, Kenjiro; Uzawa, Mitsuyoshi

    2003-01-01

    The purpose of the present open-labeled, randomized, prospective study was to compare the effects of cyclical etidronate combined with alfacalcidol with those of cyclical etidronate alone on lumbar bone mineral density (BMD), bone resorption, and back pain in postmenopausal women with osteoporosis. Forty postmenopausal women with osteoporosis, 60-86 years of age, without any vertebral fractures in the lumbar spine, were randomly divided into two groups with 20 patients in each group. One group was treated with cyclical etidronate (oral etidronate 200 mg daily for 2 weeks every 3 months) and the other was given cyclical etidronate combined with alfacalcidol (cyclical etidronate plus alfacalcidol 1 Ig daily continuously). The BMD of the lumbar spine (L1-L4) measured by dual-energy X-ray absorptiometry, urinary crosslinked N-terminal telopeptides of type I collagen (NTX) measured by an enzyme-linked immunosorbent assay, and back pain evaluated by the face scale score were assessed at baseline, 6 months, and 12 months. There were no significant differences in baseline characteristics including age, body mass index, years since menopause, lumbar BMD, urinary NTX level, and face scale score between the two treatment groups. Both treatments significantly reduced the urinary NTX level and back pain. Cyclical etidronate combined with alfacalcidol significantly increased the lumbar BMD with a more significant reduction in the urinary NTX level than cyclical etidronate alone, but cyclical etidronate alone did not significantly increase the lumbar BMD. Alleviation of back pain was similar in the two groups. These results suggest that cyclical etidronate combined with alfacalcidol appears to be more useful than cyclical etidronate alone for increasing the lumbar BMD by more markedly suppressing bone resorption in postmenopausal women with osteoporosis.

  10. No effect of a single session of transcranial direct current stimulation on experimentally induced pain in patients with chronic low back pain--an exploratory study.

    PubMed

    Luedtke, Kerstin; May, Arne; Jürgens, Tim P

    2012-01-01

    Transcranial direct current stimulation (tDCS) has been shown to modulate cortical excitability. A small number of studies suggested that tDCS modulates the response to experimental pain paradigms. No trials have been conducted to evaluate the response of patients already suffering from pain, to an additional experimental pain before and after tDCS. The present study investigated the effect of a single session of anodal, cathodal and sham stimulation (15 mins/1 mA) over the primary motor cortex on the perceived intensity of repeated noxious thermal and electrical stimuli and on elements of quantitative sensory testing (thermal pain and perception thresholds) applied to the right hand in 15 patients with chronic low back pain. The study was conducted in a double-blind sham-controlled and cross-over design. No significant alterations of pain ratings were found. Modalities of quantitative sensory testing remained equally unchanged. It is therefore hypothesized that a single 15 mins session of tDCS at 1 mA may not be sufficient to alter the perception of experimental pain and in patients with chronic pain. Further studies applying repetitive tDCS to patients with chronic pain are required to fully answer the question whether experimental pain perception may be influenced by tDCS over the motor cortex.

  11. No Effect of a Single Session of Transcranial Direct Current Stimulation on Experimentally Induced Pain in Patients with Chronic Low Back Pain – An Exploratory Study

    PubMed Central

    Luedtke, Kerstin; May, Arne; Jürgens, Tim P.

    2012-01-01

    Transcranial direct current stimulation (tDCS) has been shown to modulate cortical excitability. A small number of studies suggested that tDCS modulates the response to experimental pain paradigms. No trials have been conducted to evaluate the response of patients already suffering from pain, to an additional experimental pain before and after tDCS. The present study investigated the effect of a single session of anodal, cathodal and sham stimulation (15 mins/1 mA) over the primary motor cortex on the perceived intensity of repeated noxious thermal and electrical stimuli and on elements of quantitative sensory testing (thermal pain and perception thresholds) applied to the right hand in 15 patients with chronic low back pain. The study was conducted in a double-blind sham-controlled and cross-over design. No significant alterations of pain ratings were found. Modalities of quantitative sensory testing remained equally unchanged. It is therefore hypothesized that a single 15 mins session of tDCS at 1 mA may not be sufficient to alter the perception of experimental pain and in patients with chronic pain. Further studies applying repetitive tDCS to patients with chronic pain are required to fully answer the question whether experimental pain perception may be influenced by tDCS over the motor cortex. PMID:23189136

  12. Evaluation of the pain and local tenderness in bone metastasis treated with magnetic resonance-guided focused ultrasound surgery (MRgFUS)

    NASA Astrophysics Data System (ADS)

    Namba, Hirofumi; Kawasaki, Motohiro; Kato, Tomonari; Tani, Toshikazu; Ushida, Takahiro; Koizumi, Norihiro

    2017-03-01

    It has been reported that MRgFUS has pain palliative effects on the local pain in patients with bone metastasis. In general, a severity of pain has been evaluated using only subjective method with numerical rating scale (NRS) or visual analogue scale (VAS). It is important to evaluate local pain-palliative effects of MRgFUS treatment with objective and quantitative method. The aim of this study is to investigate changes in the severity of local pain of bone metastasis before and after MRgFUS treatments, measuring pressure pain threshold (PPT) using pressure algometer, and pain intensity using electrical stimulation device (the Pain Vision system) at most painful site of bone metastasis. We have conducted MRgFUS for pain palliation of bone metastasis for 8 patients, and evaluated the local tenderness quantitatively for 8 patients, and evaluated local pain intensity for 7 patients. Before the treatments, PPTs were 106.3kPa [40.0-431.5] at metastatic site and 344.8 kPa [206.0-667.0] at normal control site, which showed a significant difference. The PPTs at metastatic site shows a significant increase from 106.3 kPa [40.0-431.5] at the baseline to 270.5 kPa [93.5-533.5] at 3 months after the treatment. The NRS score shows a significant decrease from 6.0 [4-8] at baseline to 1 [0-3] at 3 months after the treatment. Similarly, the pain intensity shows a significant decrease 245 [96.3-888.7] at baseline to 55.9 [2.8-292] at 3 months after the treatment. The results of our study illustrate the pain-relieving effects of MRgFUS for the treatment of painful bone metastasis. PPT might be a useful parameter not only for assessing a treatment's effect, but also for the decision of the painful area to treat with MRgFUS. Pain Vision seems to be useful for quantitative and objective evaluation of local pain of painful bone metastasis.

  13. [Outcome of accessory navicular fusion for the treatment of the painful accessory navicular bone of type II in adults].

    PubMed

    Xie, Bing; Tian, Jing; Liu, Xin-wei; Zhou, Da-peng; Xiang, Liang-bi

    2014-10-01

    To evaluate the clinical outcome of accessory navicular fusion for treatment of the painful accessory navicular bone of type II in adults. From June 2006 to June 2012, a total of 38 feet (in 35 adult patients) with painful accessory navicular with type I underwent an fusion operation of the primary and accessory navicular bones,including 26 males and 9 females with a mean age of (32.4±7.3) years old ranging from 18 to 44 years old. The course of disease ranged from 3 to 10 months. The perioperative complications and radiological outcomes were observed and recorded. The foot function before and after operation were assessed by the American Orthopedic Foot and Ankle Society (AOFAS) midfoot score, and the easement of the pain was evaluated by visual analog score (VAS). Two patients had transient superficial inflammation of the incision, no obvious perioperative complications occurred. All patients were follow-up for (53.5±14.7) months (12 to 84 months). Bone union was confirmed on plain radiography in 32 cases (35 feet). The mean time from the operation to union was (13.7±2.3) weeks (9 to 18 weeks). Postoperative pain VAS score was improved obviosly than preoperative (V=12.14,P< 0.01). The talar-to-first metatarsal angle [(9.4±3.5)° vs (8.3±2.7)°, t=0.736, P>0.05)], calcaneal tilt angle [(17.7±2.2)° vs (18.9±3.4)°, t=0.794, P>0.05],talonavicular uncoverage angle [(14.3±3.4)° vs(12.5?4.6)°,t=0.947, P>0.05) ],and height of the first tarsometatarsal joint [(14.8±3.1) mm vs (15.9±2.8) mm,t=0.814,P>0.05)] before and after operations had no statistic difference. The AOFAS midfoot score was improced from preoperative 45.6±5.3 to postoperative 82.5±7.4 (t=3.214,P< 0.01). For the painful accessory navicular bone of type II in adults, if the patient has a large navicular bone and not complicated with rigid flatfoot, once the conservative treatment fails, fusion of the primary and accessory naviculars may be a successful intervention. Overall, the procedure

  14. Single dose oral dexibuprofen [S(+)-ibuprofen] for acute postoperative pain in adults

    PubMed Central

    Moore, R Andrew; Derry, Sheena; McQuay, Henry J

    2014-01-01

    Background Dexibuprofen (S(+)-ibuprofen) is a non-steroidal anti-inflammatory drug (NSAID) licensed for use in rheumatic disease and other musculoskeletal disorders in the UK, and widely available in other countries worldwide. It is an active isomer of ibuprofen. This review sought to evaluate the efficacy and safety of oral dexibuprofen in acute postoperative pain, using clinical studies of patients with established pain, and with outcomes measured primarily over 6 hours using standard methods. This type of study has been used for many decades to establish that drugs have analgesic properties. Objectives To assess efficacy, duration of action, and associated adverse events of single dose oral dexibuprofen in acute postoperative pain in adults. Search methods We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to May 2009. Selection criteria Randomised, double blind, placebo-controlled clinical trials of oral dexibuprofen for relief of acute postoperative pain in adults. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk and number needed to treat to benefit (NNT) were calculated. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals were collected. Main results In the single included study, both S(+)-ibuprofen (dexibuprofen, an active isomer of ibuprofen) 200 mg and 400 mg gave high levels of response, with 31/51 (61%) and 35/50 (70%) respectively having at least 50% pain relief over 4 to 6 hours, compared with 2/25 (8%) with placebo. The median time to additional analgesic use was 5.8 hours, 6.1 hours, and 1.8 hours

  15. Therapeutic Targeting of TRPV1 for the Treatment of Chronic Pain Associated with Prostate Cancer Bone Metastasis

    DTIC Science & Technology

    2013-07-30

    1 AD_________________ Award Number: W81XWH-11-1-0333 TITLE: Therapeutic Targeting of TRPV1 for the...TITLE AND SUBTITLE Therapeutic Targeting of TRPV1 for the Treatment of Chronic Pain 5a. CONTRACT NUMBER Associated with Prostate Cancer Bone...specific inflammatory factors, IL-6 and TNF-α, PTHrP and ET-1 on upregulation of TRPV1 channel function/expression, and nociceptor sensitization

  16. Use of the On-Q Pain Pump in Alveolar Bone Grafting: Effect on Hospital Length of Stay.

    PubMed

    Muzaffar, Arshad R; Warren, Abby; Baker, C Lynette

    2016-03-01

    Alveolar bone grafting (ABG) with iliac crest bone graft can be associated with significant pain at the donor site. The On-Q pain pump has been shown to be efficacious in treating postsurgical pain. The aim of this study was to compare the length of postoperative hospital stay in patients undergoing ABG who received the On-Q pain pump at the iliac crest donor site (On-Q+) with that of patients who did not receive the On-Q pain pump (On-Q-). A retrospective, cohort study, approved by institutional review board, was performed. Thirty-one consecutive patients in the On-Q- group were compared with 38 consecutive patients in the On-Q+ group. The two cohorts were assessed for length of stay. Statistical analysis was performed using the Fisher exact probability test. Tertiary care academic medical center. Sixty-nine patients with cleft lip and/or cleft palate (CL/P) undergoing secondary ABG with iliac crest bone graft were operated on between May 1993 and January 2014. Length of postoperative hospital stay. Mean length of stay in the On-Q- patients was 0.52 days versus 0.37 days for the On-Q+ patients. This difference between the two cohorts was not statistically significant (P = .234). Although there is a trend toward a shorter length of stay in our patients who received the On-Q pump, this finding was not statistically significant. Given the expense and additional burden of care associated with the device, we have become more selective in its utilization.

  17. Conditional TNF-α Overexpression in the Tooth and Alveolar Bone Results in Painful Pulpitis and Osteitis

    PubMed Central

    Hall, B.E.; Zhang, L.; Sun, Z.J.; Utreras, E.; Prochazkova, M.; Cho, A.; Terse, A.; Arany, P.; Dolan, J.C.; Schmidt, B.L.; Kulkarni, A.B.

    2016-01-01

    Tumor necrosis factor–α (TNF-α) is a proalgesic cytokine that is commonly expressed following tissue injury. TNF-α expression not only promotes inflammation but can also lead to pain hypersensitivity in nociceptors. With the established link between TNF-α and inflammatory pain, we identified its increased expression in the teeth of patients affected with caries and pulpitis. We generated a transgenic mouse model (TNF-αglo) that could be used to conditionally overexpress TNF-α. These mice were bred with a dentin matrix protein 1 (DMP1)–Cre line for overexpression of TNF-α in both the tooth pulp and bone to study oral pain that would result from subsequent development of pulpitis and bone loss. The resulting DMP1/TNF-αglo mice show inflammation in the tooth pulp that resembles pulpitis while also displaying periodontal bone loss. Inflammatory infiltrates and enlarged blood vessels were observed in the tooth pulp. Pulpitis and osteitis affected the nociceptive neurons innervating the orofacial region by causing increased expression of inflammatory cytokines within the trigeminal ganglia. With this new mouse model morphologically mimicking pulpitis and osteitis, we tested it for signs of oral pain with an oral function assay (dolognawmeter). This assay/device records the time required by a mouse to complete a discrete gnawing task. The duration of gnawing required by the DMP1/TNF-αglo mice to complete the task was greater than that for the controls; extended gnaw time in a dolognawmeter indicates reduced orofacial function. With the DMP1/TNF-αglo mice, we have shown that TNF-α expression alone can produce inflammation similar to pulpitis and osteitis and that this mouse model can be used to study dental inflammatory pain. PMID:26503912

  18. Conditional TNF-α Overexpression in the Tooth and Alveolar Bone Results in Painful Pulpitis and Osteitis.

    PubMed

    Hall, B E; Zhang, L; Sun, Z J; Utreras, E; Prochazkova, M; Cho, A; Terse, A; Arany, P; Dolan, J C; Schmidt, B L; Kulkarni, A B

    2016-02-01

    Tumor necrosis factor-α (TNF-α) is a proalgesic cytokine that is commonly expressed following tissue injury. TNF-α expression not only promotes inflammation but can also lead to pain hypersensitivity in nociceptors. With the established link between TNF-α and inflammatory pain, we identified its increased expression in the teeth of patients affected with caries and pulpitis. We generated a transgenic mouse model (TNF-α(glo)) that could be used to conditionally overexpress TNF-α. These mice were bred with a dentin matrix protein 1 (DMP1)-Cre line for overexpression of TNF-α in both the tooth pulp and bone to study oral pain that would result from subsequent development of pulpitis and bone loss. The resulting DMP1/TNF-α(glo) mice show inflammation in the tooth pulp that resembles pulpitis while also displaying periodontal bone loss. Inflammatory infiltrates and enlarged blood vessels were observed in the tooth pulp. Pulpitis and osteitis affected the nociceptive neurons innervating the orofacial region by causing increased expression of inflammatory cytokines within the trigeminal ganglia. With this new mouse model morphologically mimicking pulpitis and osteitis, we tested it for signs of oral pain with an oral function assay (dolognawmeter). This assay/device records the time required by a mouse to complete a discrete gnawing task. The duration of gnawing required by the DMP1/TNF-α(glo) mice to complete the task was greater than that for the controls; extended gnaw time in a dolognawmeter indicates reduced orofacial function. With the DMP1/TNF-α(glo) mice, we have shown that TNF-α expression alone can produce inflammation similar to pulpitis and osteitis and that this mouse model can be used to study dental inflammatory pain. © International & American Associations for Dental Research 2015.

  19. [Comparison of anxiety and pain in two procedures of hematopoietic stem cell collection: cytapheresis and bone marrow collection].

    PubMed

    Macquart-Moulin, G; Auquier, P; Le Corroller, A G; Blache, J L; Novakovitch, G; Blaise, D; Faucher, C; Viens, P; Maraninchi, D; Moatti, J P

    1995-07-01

    The aim of this study was to compare anxiety, pain and discomfort of cancer patients submitted to two procedures of hematopoietic stem cells collection: peripheral blood stem cells collection (PBSCC) or bone marrow collection (BMC). Patients, randomized (July 1993-February 1994), in view of autograft, to receive the first procedure or the second one, completed self-administered questionnaires before, during and after the procedure. Anxiety was evaluated by State-Trait Anxiety Inventory. Pain was assessed using visual analogical scale (VAS) and McGill Pain questionnaire. Before the procedure, in comparison with PBSCC patients (n = 40), BMC patients (n = 25) experienced more State-anxiety due to the procedure approach (p < 0.01) and more trouble or inconvenience for having to come and stay at the hospital (p < 0.0001). During the procedure, pain related to BMC, as assessed by VAS, is significatively higher than pain induced by PBSCC, whichever the access used (p < 0.001). The McGill total score is twice as high for BMC patients than for patients submitted to PBSCC with femoral catheter (n = 19). The latter patients significatively reported more pain than patients without femoral catheter (n = 21). At the discharge from hospital, 32% of BMC patients judged the procedure quite difficult vs 5% of PBSCC patients (p < 0.05). These results explain a higher acceptability of the peripheral blood stem cells collection.

  20. Optimal control of reaching is disturbed in complex regional pain syndrome: a single-case study

    PubMed Central

    Osumi, Michihiro; Sumitani, Masahiko; Kumagaya, Shin-ichiro; Morioka, Shu

    2017-01-01

    Objective Disturbance of goal-directed motor control may cause or exacerbate pathological pain in patients with complex regional pain syndrome (CRPS). We conducted a single-case study about motor control involved in reaching with a patient with CRPS in an upper limb. Methods Using a three-dimensional measurement system, we recorded reaching movement trajectories of the intact and affected hand before and after pain alleviation by therapeutic nerve blockade. We assessed degrees of tremor in the acceleration phase (from start until maximum peak velocity) and the deceleration phase (from maximum peak velocity until goal). To quantify the smoothness of reaching movements, we analyzed the curves of the trajectories during the initial movement phase (from start and maximum peak acceleration). Results The results showed that the tremor of the affected hand was greater than that of the intact hand during the deceleration phase, both before and after pain alleviation. Reaching trajectories of the intact hand smoothly traced curves convexed toward the intact side, while those of the affected hand represented unnaturally rectilinear functions associated with the loss of smooth movements. Further, these unnatural trajectories partially recovered after pain alleviation. Conclusion Disturbance of sensorimotor integration and pain-related fear might affect goal-directed motor control in CRPS patients. PMID:28138265

  1. Optimal control of reaching is disturbed in complex regional pain syndrome: a single-case study.

    PubMed

    Osumi, Michihiro; Sumitani, Masahiko; Kumagaya, Shin-Ichiro; Morioka, Shu

    2017-01-01

    Disturbance of goal-directed motor control may cause or exacerbate pathological pain in patients with complex regional pain syndrome (CRPS). We conducted a single-case study about motor control involved in reaching with a patient with CRPS in an upper limb. Using a three-dimensional measurement system, we recorded reaching movement trajectories of the intact and affected hand before and after pain alleviation by therapeutic nerve blockade. We assessed degrees of tremor in the acceleration phase (from start until maximum peak velocity) and the deceleration phase (from maximum peak velocity until goal). To quantify the smoothness of reaching movements, we analyzed the curves of the trajectories during the initial movement phase (from start and maximum peak acceleration). The results showed that the tremor of the affected hand was greater than that of the intact hand during the deceleration phase, both before and after pain alleviation. Reaching trajectories of the intact hand smoothly traced curves convexed toward the intact side, while those of the affected hand represented unnaturally rectilinear functions associated with the loss of smooth movements. Further, these unnatural trajectories partially recovered after pain alleviation. Disturbance of sensorimotor integration and pain-related fear might affect goal-directed motor control in CRPS patients.

  2. Single-cortex is better than double-cortex in fibula grafts for large tibia bone defect in a 2-year-old child

    PubMed Central

    Li, Jianbin; Pan, Zhijun; Yan, Shigui; Zhao, Xiang

    2017-01-01

    Abstract Background: Large bone defect in infant or small patients has been little reported and the management of such a patient is difficult. Considering the little knowledge of this area, we present this special case of a successful single-cortex fibula graft for the treatment of a large tibia bone defect in a 2-year-old patient to share our experience. Case summary: A 2-year-old male patient presented to our hospital with history of leg pain for 4 months. According to his medical records, he was involved in a traffic accident and diagnosed with open tibia fracture. A previous surgery of emergent debridement and external fixation was performed in our institution, leaving a 6-cm tibia bone defect. After that this patient received several times of vacuum sealing drainage (VSD), skin grafting, and changed external fixation to cast because of pin tract infection. The physical examination of the patient showed a healed skin wound and a good dorsal arterial pulse. X-ray indicated a large bone defect at the tibia fracture site with osteosclerosis at the fracture sections. This patient received ipsilateral single-cortex vascularized single-cortex fibula graft, other than double-cortex fibula graft. X-ray and CT scan 4 months after the operation confined bone healing. The patient returned to normal activities with an inconspicuous limb. Conclusion: Ipsilateral single-cortex fibula graft is effective for the treatment of large tibia bone defect in infant or small aged patients. It exhibited better potential benefits than double-cortex graft in such cases. PMID:28151885

  3. Fractionated Wide-Field Radiation Therapy Followed by Fractionated Local-Field Irradiation for Treating Widespread Painful Bone Metastasis

    SciTech Connect

    Ki, Yongkan; Kim, Wontaek; Nam, Jiho; Kim, Donghyun; Jeon, Hosang; Park, Dahl; Kim, Dongwon

    2011-01-01

    Purpose: Wide-field radiation therapy (WFRT) is an effective treatment for widespread bone metastasis. We evaluated local-field irradiation (LFI) after fractionated WFRT (f-WFRT) for treating the patients with multiple painful bone lesions. Methods and Materials: From 1998 to 2007, 32 patients with multiple bone metastases were treated with fractionated LFI (f-LFI) after f-WFRT. All patients initially received 15 Gy in 5 fractions to a wide field, followed by LFI (9-15 Gy in 3 Gy fractions). Response was assessed by evaluating the degree of pain relief using a visual analog scale before radiotherapy, after f-WFRT, and after f-LFI. Results: Fractionated LFI following f-WFRT yielded an overall relief rate of 93.8% and a complete relief rate of 43.8%. The rate of the appearance of new disease was 6.3% for the patients with complete relief, 20.5% for the patients with a partial relief, and 50% for the patients with no relief. Conclusion: Fractionated LFI after f-WFRT is a well-tolerated and effective treatment for multiple metastatic bone disease.

  4. [Minor bcr/abl positive acute lymphoblastic leukemia preceded by knee joint pain due to bone marrow necrosis].

    PubMed

    Sato, Kazuya; Mori, Masaki; Meguro, Akiko; Miyoshi, Takuji; Nagai, Tadashi; Muroi, Kazuo; Komatsu, Norio; Ozawa, Keiya

    2004-11-01

    A 16-year-old male was referred to our hospital in April 2003 due to severe knee joint pain from five months previously. Lymphoblasts were identified in his peripheral blood, resulting in a diagnosis of acute lymphoblastic leukemia (ALL). Bone marrow examination revealed massive necrosis with clusters of lymphoblasts and the bcr/abl fusion gene. Magnetic resonance imaging (MRI) of the knee joint showed low signal intensity on T1-weighted images, and peripheral rim enhancement on Gd-DTPA enhanced fat suppression images, which was compatible with bone marrow necrosis. After the patient achieved complete remission (CR), the knee joint pain has disappeared. He was treated with an allogeneic bone marrow transplantation (BMT) from an HLA-identical unrelated donor and has been in CR for 26 months after the diagnosis of ALL. In the knee joint, the replacement of fatty marrow after BMT has been confirmed with MRI. Hematological malignancies including ALL should be considered in the cases of bone marrow necrosis and adequate treatment may improve necrosis.

  5. Involvement of chemokine CXCL11 in the development of morphine tolerance in rats with cancer-induced bone pain.

    PubMed

    Guo, Genhua; Peng, Yawen; Xiong, Bingrui; Liu, Daiqiang; Bu, Huilian; Tian, Xuebi; Yang, Hui; Wu, Zhen; Cao, Fei; Gao, Feng

    2017-05-01

    Morphine is viewed as one of the classical treatments for intractable pain, but its role is limited by side effects, including analgesic tolerance. A few chemokines have been reported to be engaged in the mechanisms of morphine tolerance. However, the exact roles of CXC chemokine 11 (CXCL11) in chronic morphine tolerance remain unknown. In this study, Walker 256 mammary gland carcinoma cells were inoculated into the tibia of rats to provoke cancer-induced bone pain. Then, morphine was intrathecally administered twice daily for seven consecutive days to induce drug tolerance. We found that the level of CXCL11 in lumbar spinal cord was increased during the development of morphine tolerance in cancer-induced bone pain rats. Meanwhile, CXCL11 was co-localized with markers of astrocytes and neurons in the spinal cord. Inhibition of CXCL11 by neutralizing antibodies could remarkably attenuate the degree of morphine tolerance and decrease the activation of astrocytes. Moreover, blocking astrocyte activation by d, l-Fluorocitric acid could distinctly alleviate morphine tolerance and reduce the expression of CXCL11. Finally, morphine stimulation could induce the release of CXCL11 by cultured astrocytes and neurons in vitro. In summary, our results provide evidence that spinal CXCL11 plays a powerful modulatory role in the development of morphine tolerance through cross-talking between astrocytes and neurons. Read the Review series "Pain". © 2016 International Society for Neurochemistry.

  6. Relationship between bone mineral density and the frequent administration of epidural steroid injections in postmenopausal women with low back pain.

    PubMed

    Kim, Sungyun; Hwang, Byeongmun

    2014-01-01

    Epidural steroid injection (ESI) is one of the most common nonsurgical treatments for low back pain. In general, corticosteroid therapy often results in bone loss and osteoporosis. In previous studies, bone mineral density (BMD) was evaluated after epidural injections of relatively small numbers and relatively low total doses of corticosteroids. However, the relationship between BMD and multiple ESIs remains to be elucidated. To explore the relationship between BMD and multiple ESIs in postmenopausal women with low back pain. Medical records of postmenopausal women with low back pain treated with or without ESIs were reviewed. BMD was measured in the lumbar spine, femoral neck and total femur after the treatments. A total of 71 patients were divided into two groups: group 1 included patients who had received non-ESI medications; and group 2 included those who had received ESIs >10 times, with a cumulative administered triamcinolone dose >200 mg. Patients in group 2 showed lower BMD in the femoral neck and total femur. However, no significant intergroup differences in the BMD of the lumbar spine were observed. The prevalences of osteoporosis and osteopenia in the lumbar spine and femoral neck were significantly higher in group 2; these patients also had lower femoral neck BMD Z-scores. Multiple ESIs (approximately 14 injections with a cumulative triamcinolone dose of approximately 400 mg) can reduce BMD in postmenopausal women with low back pain.

  7. Relationship between bone mineral density and the frequent administration of epidural steroid injections in postmenopausal women with low back pain

    PubMed Central

    Kim, Sungyun; Hwang, Byeongmun

    2014-01-01

    BACKGROUND: Epidural steroid injection (ESI) is one of the most common nonsurgical treatments for low back pain. In general, corticosteroid therapy often results in bone loss and osteoporosis. In previous studies, bone mineral density (BMD) was evaluated after epidural injections of relatively small numbers and relatively low total doses of corticosteroids. However, the relationship between BMD and multiple ESIs remains to be elucidated. OBJECTIVE: To explore the relationship between BMD and multiple ESIs in postmenopausal women with low back pain. METHODS: Medical records of postmenopausal women with low back pain treated with or without ESIs were reviewed. BMD was measured in the lumbar spine, femoral neck and total femur after the treatments. A total of 71 patients were divided into two groups: group 1 included patients who had received non-ESI medications; and group 2 included those who had received ESIs >10 times, with a cumulative administered triamcinolone dose >200 mg. RESULTS: Patients in group 2 showed lower BMD in the femoral neck and total femur. However, no significant intergroup differences in the BMD of the lumbar spine were observed. The prevalences of osteoporosis and osteopenia in the lumbar spine and femoral neck were significantly higher in group 2; these patients also had lower femoral neck BMD Z-scores. CONCLUSIONS: Multiple ESIs (approximately 14 injections with a cumulative triamcinolone dose of approximately 400 mg) can reduce BMD in postmenopausal women with low back pain. PMID:24404559

  8. Modulation of an inhibitory reflex in single motor units in human masseter by tonic painful stimulation.

    PubMed

    Svensson, P; McMillan, A S; Graven-Nielsen, T; Wang, K; Arendt-Nielsen, L

    1999-12-01

    Perioral electrical stimuli cause inhibitory reflex responses in single motor-units (SMU) and surface electromyographic (EMG) recordings from voluntary contracted human jaw-closing muscles. Tonic experimental masseter pain has recently been shown to reduce the inhibitory reflex response in surface EMG recordings but the effect on SMU activity has not been described. In this study, motor-unit action potentials were recorded with wire electrodes inserted into the left masseter in eleven subjects. The subjects kept the SMU firing rate around 10 Hz by feedback. Ninety-nine electrical stimuli were applied sequentially to the left mental nerve with increasing stimulus delays in steps of 1 ms after the preceding motor unit action potential. The inhibitory reflex in SMU was recorded before, during and after infusion of hypertonic saline (5%) into the ipsilateral masseter muscle. Spike train data were used to calculate (1) the mean pre- and post-stimulus inter-spike-intervals (ISI) in all of the 99 trials, (2) cumulative changes in firing probability, and (3) estimation of the compound inhibitory post-synaptic potential (IPSP) in the masseter motoneuron. Tonic masseter pain did not change pre-stimulus SMU firing characteristics but the mean ISI for the first post-stimulus discharge (158.2+/-9.2 ms) was significantly decreased compared to the pre-pain (175.8+/-11.3 ms, P<0.05) and post-pain conditions (172. 6+/-11.6 ms, P<0.05). The post-stimulus firing probability was significantly increased and the relative amplitude of the estimated IPSP significantly decreased during tonic masseter pain compared to pre-pain and post-pain conditions. In conclusion, this study indicates that tonic masseter pain has a net excitatory effect on the inhibitory jaw-reflexes, which could be mediated by presynaptic mechanisms on the involved motoneurons.

  9. Single dose oral tiaprofenic acid for acute postoperative pain in adults

    PubMed Central

    Moore, R Andrew; Derry, Sheena; Moore, Maura; McQuay, Henry J

    2014-01-01

    Background Tiaprofenic acid is a a non-steroidal anti-inflammatory drug (NSAID). It is widely available around the world, with indications for osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, periarticular disorders, and strains and sprains. This review sought to evaluate the efficacy and safety of oral tiaprofenic acid in acute postoperative pain, using clinical studies of patients with established pain, and with outcomes measured primarily over 6 hours using standard methods. This type of study has been used for many decades to establish that drugs have analgesic properties. Objectives To assess the efficacy of single dose oral tiaprofenic acid in acute postoperative pain, and any associated adverse events. Search methods We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to June 2009. Selection criteria Randomised, double blind, placebo-controlled trials of single dose orally administered tiaprofenic acid in adults with moderate to severe acute postoperative pain. Data collection and analysis Two review authors independently assessed trial quality and extracted data. We planned to use area under the “pain relief versus time” curve to derive the proportion of participants with tiaprofenic acid experiencing at least 50% pain relief over 4 to 6 hours, using validated equations; to use number needed to treat to benefit (NNT); the proportion of participants using rescue analgesia over a specified time period; time to use of rescue analgesia; information on adverse events and withdrawals. Main results Not one of eleven studies identified by the searches and examined in detail studied oral tiaprofenic acid against placebo in patients with established postoperative pain and therefore no results are available. Authors’ conclusions In the absence of evidence of efficacy for oral tiaprofenic acid in acute postoperative pain, its use in this indication is not justified at present. Because trials clearly

  10. Single dose oral ibuprofen plus caffeine for acute postoperative pain in adults.

    PubMed

    Derry, Sheena; Wiffen, Philip J; Moore, R Andrew

    2015-07-14

    There is good evidence that combining two different analgesics in fixed doses in a single tablet can provide better pain relief in acute pain and headache than either drug alone, and that the drug-specific benefits are essentially additive. This appears to be broadly true in postoperative pain and migraine headache across a range of different drug combinations, and when tested in the same and different trials. Adding caffeine to analgesics also increases the number of people obtaining good pain relief. Combinations of ibuprofen and caffeine are available without prescription in some parts of the world. To assess the analgesic efficacy and adverse effects of a single oral dose of ibuprofen plus caffeine for moderate to severe postoperative pain, using methods that permit comparison with other analgesics evaluated in standardised trials using almost identical methods and outcomes. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Oxford Pain Relief Database, two clinical trial registries, and the reference lists of articles. The date of the most recent search was 1 February 2015. Randomised, double-blind, placebo- or active-controlled clinical trials of single dose oral ibuprofen plus caffeine for acute postoperative pain in adults. Two review authors independently considered trials for inclusion in the review, assessed risk of bias, and extracted data. We used the area under the pain relief versus time curve to derive the proportion of participants with at least 50% pain relief over six hours prescribed either ibuprofen plus caffeine or placebo. We calculated the risk ratio (RR) and number needed to treat to benefit (NNT). We used information on the use of rescue medication to calculate the proportion of participants requiring rescue medication and the weighted mean of the median time to use. We also collected information on adverse effects. We identified five randomised, double-blind studies with 1501 participants, but

  11. Targeting G-Protein Signaling for the Therapeutics of Prostate Tumor Bone Metastases and the Associated Chronic Bone Pain

    DTIC Science & Technology

    2014-07-01

    sensing receptor channels, such as TRPV1 , such that the channels are constitutively activated, leading to the sensation of chronic pain without any...Cancer Pain, Heterotrimeric G protein betagamma subunits, G protein coupled receptors (GPCRs), TRPV1 , Nociceptor Sensitization 3. Overall project...well as mediating GPCR-regulated TRPV1 channel function in cultured mouse sensory neurons (Aim 1). Major Goal/Objective 1: Determine the role of G

  12. Evaluation of a single miniplate use in treatment of zygomatic bone fracture.

    PubMed

    Mohammadinezhad, Cyrus

    2009-09-01

    Different methods of internal fixation of simple displaced zygomatic fracture, such as wiring, miniplate, and screw fixation, were compared for postreduction rotational stability caused by muscular forces. This study was performed to evaluate the minimally invasive therapy in cases of zygomatic bone fracture. Seventeen patients were treated by percutaneous hook reduction and miniplate fixation along the frontozygomatic suture. Postoperatively, repositioning of aesthetic and stability and also bone ends approximation were assessed clinically and radiologically. The patients were followed up for 6 to 49 months. Preoperative symptoms were subsided except the infraorbital sensitivity disturbances in one of the patients. Postoperative complications such as diplopia and hematoma were minimal and subsided by time. In this study, orbitozygomatic, commuted, and zygomatic bone fractures simultaneously with diplopia were excluded. We showed that treatment of an isolated zygomatic bone fracture according to aesthetic and functional requirements may be achieved by insertion of a single miniplate at the lateral rim of the orbit.

  13. Preventing painful age-related bone fractures: Anti-sclerostin therapy builds cortical bone and increases the proliferation of osteogenic cells in the periosteum of the geriatric mouse femur.

    PubMed

    Thompson, Michelle L; Chartier, Stephane R; Mitchell, Stefanie A; Mantyh, Patrick W

    2016-01-01

    Age-related bone fractures are usually painful and have highly negative effects on a geriatric patient's functional status, quality of life, and survival. Currently, there are few analgesic therapies that fully control bone fracture pain in the elderly without significant unwanted side effects. However, another way of controlling age-related fracture pain would be to preemptively administer an osteo-anabolic agent to geriatric patients with high risk of fracture, so as to build new cortical bone and prevent the fracture from occurring. A major question, however, is whether an osteo-anabolic agent can stimulate the proliferation of osteogenic cells and build significant amounts of new cortical bone in light of the decreased number and responsiveness of osteogenic cells in aging bone. To explore this question, geriatric and young mice, 20 and 4 months old, respectively, received either vehicle or a monoclonal antibody that sequesters sclerostin (anti-sclerostin) for 28 days. From days 21 to 28, animals also received sustained administration of the thymidine analog, bromodeoxyuridine (BrdU), which labels the DNA of dividing cells. Animals were then euthanized at day 28 and the femurs were examined for cortical bone formation, bone mineral density, and newly borne BrdU+ cells in the periosteum which is a tissue that is pivotally involved in the formation of new cortical bone. In both the geriatric and young mice, anti-sclerostin induced a significant increase in the thickness of the cortical bone, bone mineral density, and the proliferation of newly borne BrdU+ cells in the periosteum. These results suggest that even in geriatric animals, anti-sclerostin therapy can build new cortical bone and increase the proliferation of osteogenic cells and thus reduce the likelihood of painful age-related bone fractures.

  14. Intrathecal injection of lentivirus-mediated glial cell line-derived neurotrophic factor RNA interference relieves bone cancer-induced pain in rats.

    PubMed

    Meng, Fu-Fen; Xu, Yang; Dan, Qi-Qin; Wei, La; Deng, Ying-Jie; Liu, Jia; He, Mu; Liu, Wei; Xia, Qing-Jie; Zhou, Fiona H; Wang, Ting-Hua; Wang, Xi-Yan

    2015-04-01

    Bone cancer pain is a common symptom in cancer patients with bone metastases and the underlying mechanisms are largely unknown. The aim of this study is to explore the endogenous analgesic mechanisms to develop new therapeutic strategies for bone-cancer induced pain (BCIP) as a result of metastases. MRMT-1 tumor cells were injected into bilateral tibia of rats and X-rays showed that the area suffered from bone destruction, accompanied by an increase in osteoclast numbers. In addition, rats with bone cancer showed apparent mechanical and thermal hyperalgesia at day 28 after intratibial MRMT-1 inoculation. However, intrathecal injection of morphine or lentivirus-mediated glial cell line-derived neurotrophic factor RNAi (Lvs-siGDNF) significantly attenuated mechanical and thermal hyperalgesia, as shown by increases in paw withdrawal thresholds and tail-flick latencies, respectively. Furthermore, Lvs-siGDNF interference not only substantially downregulated GDNF protein levels, but also reduced substance P immunoreactivity and downregulated the ratio of pERK/ERK, where its activation is crucial for pain signaling, in the spinal dorsal horn of this model of bone-cancer induced pain. In this study, Lvs-siGDNF gene therapy appeared to be a beneficial method for the treatment of bone cancer pain. As the effect of Lvs-siGDNF to relieve pain was similar to morphine, but it is not a narcotic, the use of GDNF RNA interference may be considered as a new therapeutic strategy for the treatment of bone cancer pain in the future.

  15. Delayed activation of spinal microglia contributes to the maintenance of bone cancer pain in female Wistar rats via P2X7 receptor and IL-18.

    PubMed

    Yang, Yan; Li, Hui; Li, Ting-Ting; Luo, Hao; Gu, Xi-Yao; Lü, Ning; Ji, Ru-Rong; Zhang, Yu-Qiu

    2015-05-20

    Accumulating evidence suggests that activation of spinal microglia contributes to the development of inflammatory and neuropathic pain. However, the role of spinal microglia in the maintenance of chronic pain remains controversial. Bone cancer pain shares features of inflammatory and neuropathic pain, but the temporal activation of microglia and astrocytes in this model is not well defined. Here, we report an unconventional role of spinal microglia in the maintenance of advanced-phase bone cancer pain in a female rat model. Bone cancer elicited delayed and persistent microglial activation in the spinal dorsal horn on days 14 and 21, but not on day 7. In contrast, bone cancer induced rapid and persistent astrocytic activation on days 7-21. Spinal inhibition of microglia by minocycline at 14 d effectively reduced bone cancer-induced allodynia and hyperalgesia. However, pretreatment of minocycline in the first week did not affect the development of cancer pain. Bone cancer increased ATP levels in CSF, and upregulated P2X7 receptor, phosphorylated p38, and IL-18 in spinal microglia. Spinal inhibition of P2X7/p-38/IL-18 pathway reduced advanced-phase bone cancer pain and suppressed hyperactivity of spinal wide dynamic range (WDR) neurons. IL-18 induced allodynia and hyperalgesia after intrathecal injection, elicited mechanical hyperactivity of WDR neurons in vivo, and increased the frequency of mEPSCs in spinal lamina IIo nociceptive synapses in spinal cord slices. Together, our findings demonstrate a novel role of microglia in maintaining advanced phase cancer pain in females via producing the proinflammatory cytokine IL-18 to enhance synaptic transmission of spinal cord nociceptive neurons.

  16. Bio imaging of intracellular NO production in single bone cells after mechanical stimulation.

    PubMed

    Vatsa, Aviral; Mizuno, Daisuke; Smit, Theo H; Schmidt, Christoph F; MacKintosh, Fred C; Klein-Nulend, Jenneke

    2006-11-01

    We show the intracellular upregulation of NO production after mechanical stimulation, an essential chemical signal in bone remodeling. This is done in real time using the fluorescent chromophore DAR-4M AM. Differences in cellular response to mechanical stimulation of different regions of a single cell were observed. Osteocytes are the most abundant bone cells that are believed to be the mechanosensors of bone, responding to mechanical stresses in interstitial fluid flow through the canaliculi. Under mechanical load, chemical signals such as NO play a key role in the activity of osteoblasts/osteoclasts that regulate bone remodeling. Despite the importance of NO in signaling, its real-time detection has proved challenging. This is largely because of the short NO half-life (typically approximately 0.1-5 s). Here, we show the upregulation of intracellular NO production in single osteocytes under localized mechanical stimulation. We used the chromophore DAR-4M AM for NO detection. This is loaded into surface-attached MLO-Y4 osteocyte-like and MC3T3-E1 osteoblast-like cells that are subjected to a localized mechanical stimulation using optical tweezers or a microneedle tip. DAR-4M AM is membrane-permeable and chelates NO, forming a stable, fluorescent compound, which is visible with a rhodamine filter. Nonstimulated MLO-Y4 and MC3T3-E1 cells showed basal NO production levels, as indicated by a gradual increase in their fluorescence intensity. Localized mechanical stimulation of single MC3T3-E1 cells and MLO-Y4 cells by optical tweezers (150-550 pN, 0.5-3 Hz, 1 minute) showed a nearly 15-30% increase, whereas MLO-Y4 cells stimulated by a microneedle (10-20 nN, 1 minute) showed nearly 15-16% increase relative to their nonstimulated state. Furthermore, stimulation of a single cell process by a microneedle resulted in a 2-10% increase in the fluorescence intensity. NO is essential for mechanically induced bone remodeling and is a meaningful parameter for measuring bone cell

  17. Image-guided transplantation of single cells in the bone marrow of live animals.

    PubMed

    Turcotte, Raphaël; Alt, Clemens; Runnels, Judith M; Ito, Kyoko; Wu, Juwell W; Zaher, Walid; Mortensen, Luke J; Silberstein, Lev; Côté, Daniel C; Kung, Andrew L; Ito, Keisuke; Lin, Charles P

    2017-06-20

    Transplantation of a single hematopoietic stem cell is an important method for its functional characterization, but the standard transplantation protocol relies on cell homing to the bone marrow after intravenous injection. Here, we present a method to transplant single cells directly into the bone marrow of live mice. We developed an optical platform that integrates a multiphoton microscope with a laser ablation unit for microsurgery and an optical tweezer for cell micromanipulation. These tools allow image-guided single cell transplantation with high spatial control. The platform was used to deliver single hematopoietic stem cells. The engraftment of transplants was tracked over time, illustrating that the technique can be useful for studying both normal and malignant stem cells in vivo.

  18. Tibial stress reaction presenting as bilateral shin pain in a man taking denosumab for giant cell tumor of the bone.

    PubMed

    Lim, Sian Yik; Rastalsky, Naina; Choy, Edwin; Bolster, Marcy B

    2015-12-01

    Prolonged bisphosphonate use has been associated with increased risk of atypical femoral fractures. Very few cases of atypical femoral fractures have been reported with denosumab. We report a case of bilateral tibial stress reactions in a 60-year-old man with no history of osteoporosis who was on prolonged high-dose denosumab for the treatment of giant cell tumor of bone. He presented with a 3-month history of pain in his bilateral shins worsening with activity and improving with rest. Although initial radiographs were unremarkable, he was found to have changes consistent with a stress reaction on magnetic resonance imaging of the distal tibia. To our knowledge, bilateral tibial stress reactions have not been previously reported with anti-resorptive therapies (neither bisphosphonates nor denosumab). Our case is intriguing in terms of the development of stress reactions as a precursor to stress fractures which may also relate to atypical fractures. Our case suggests a possible association between denosumab use and stress reactions. Of note the indication for denosumab in our case was for the treatment of giant cell tumor of bone where the Food and Drug Administration (FDA) approved dose is substantially higher than the FDA approved dose for osteoporosis treatment. Although rare, clinicians should consider the possibility of stress fractures in patients on anti-resorptive medications such as denosumab, especially when a patient presents with new onset thigh pain, hip pain or pain over an area affecting the long bones. Evaluation by imaging of affected areas should be pursued to enable early detection and intervention, as well as prevention of morbidity and associated ongoing risk to the patient. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Single dose oral naproxen and naproxen sodium for acute postoperative pain (Review)

    PubMed Central

    Mason, L; Edwards, JE; Moore, RA; McQuay, HJ

    2014-01-01

    Background Postoperative pain is often poorly managed. Treatment options include a range of drug therapies such as non-steroidal anti-inflammatory drugs (NSAIDs) of which naproxen is one. Naproxen is used to treat a variety of painful conditions including acute postoperative pain, and is often combined with sodium to improve its solubility for oral administration. Naproxen sodium 550 mg (equivalent to 500 mg of naproxen) is considered to be an effective dose for treating postoperative pain but to date no systematic review of the effectiveness of naproxen/naproxen sodium at different doses has been published. Objectives To assess the efficacy, safety and duration of action of a single oral dose of naproxen or naproxen sodium for acute postoperative pain in adults. Search strategy We searched The Cochrane Library, MEDLINE, EMBASE and the Oxford Pain Relief Database for relevant studies. Additional studies were identified from the reference list of retrieved reports. The most recent search was undertaken in July 2004. Selection criteria Included studies were randomised, double blind, placebo-controlled trials of a single dose of orally administered naproxen or naproxen sodium in adults with moderate to severe acute postoperative pain. Data collection and analysis Pain relief or pain intensity data were extracted and converted into dichotomous information to give the number of patients with at least 50% pain relief over four to six hours. Relative risk estimates (RR) and the number-needed-to-treat (NNT) for at least 50% pain relief were then calculated. Information was sought on the percentage of patients experiencing any adverse event, and the number-needed-to-harm was derived. Time to remedication was also estimated. Main results Ten trials (996 patients) met the inclusion criteria: nine assessed naproxen sodium; one combined the results from two small trials of naproxen alone. Included studies scored well for methodological quality. Meta-analysis of six trials (500

  20. From Catastrophizing to Recovery: a pilot study of a single-session treatment for pain catastrophizing

    PubMed Central

    Darnall, Beth D; Sturgeon, John A; Kao, Ming-Chih; Hah, Jennifer M; Mackey, Sean C

    2014-01-01

    Background Pain catastrophizing (PC) – a pattern of negative cognitive-emotional responses to real or anticipated pain – maintains chronic pain and undermines medical treatments. Standard PC treatment involves multiple sessions of cognitive behavioral therapy. To provide efficient treatment, we developed a single-session, 2-hour class that solely treats PC entitled “From Catastrophizing to Recovery” [FCR]. Objectives To determine 1) feasibility of FCR; 2) participant ratings for acceptability, understandability, satisfaction, and likelihood to use the information learned; and 3) preliminary efficacy of FCR for reducing PC. Design and methods Uncontrolled prospective pilot trial with a retrospective chart and database review component. Seventy-six patients receiving care at an outpatient pain clinic (the Stanford Pain Management Center) attended the class as free treatment and 70 attendees completed and returned an anonymous survey immediately post-class. The Pain Catastrophizing Scale (PCS) was administered at class check-in (baseline) and at 2, and 4 weeks post-treatment. Within subjects repeated measures analysis of variance (ANOVA) with Student’s t-test contrasts were used to compare scores across time points. Results All attendees who completed a baseline PCS were included as study participants (N=57; F=82%; mean age =50.2 years); PCS was completed by 46 participants at week 2 and 35 participants at week 4. Participants had significantly reduced PC at both time points (P<0001) and large effect sizes were found (Cohen’s d=0.85 and d=1.15). Conclusion Preliminary data suggest that FCR is an acceptable and effective treatment for PC. Larger, controlled studies of longer duration are needed to determine durability of response, factors contributing to response, and the impact on pain, function and quality of life. PMID:24851056

  1. Randomized Trial of Immediate Postoperative Pain Following Single-incision Versus Traditional Laparoscopic Cholecystectomy

    PubMed Central

    Guo, Wei; Liu, Yang; Han, Wei; Liu, Jun; Jin, Lan; Li, Jian-She; Zhang, Zhong-Tao

    2015-01-01

    Background: We undertook a randomized controlled trial to ascertain if single-incision laparoscopic cholecystectomy (SILC) was more beneficial for reducing postoperative pain than traditional laparoscopic cholecystectomy (TLC). Moreover, the influencing factors of SILC were analyzed. Methods: A total of 552 patients with symptomatic gallstones or polyps were allocated randomly to undergo SILC (n = 138) or TLC (n = 414). Data on postoperative pain score, operative time, complications, procedure conversion, and hospital costs were collected. After a 6-month follow-up, all data were analyzed using the intention-to-treat principle. Results: Among SILC group, 4 (2.9%) cases required conversion to TLC. Mean operative time of SILC was significantly longer than that of TLC (58.97 ± 21.56 vs. 43.38 ± 19.02 min, P < 0.001). The two groups showed no significant differences in analgesic dose, duration of hospital stay, or cost. Median pain scores were similar between the two groups 7 days after surgery, but SILC-treated patients had a significantly lower median pain score 6 h after surgery (10-point scale: 3 [2, 4] vs. 4 [3, 5], P = 0.009). Importantly, subgroup analyses of operative time for SILC showed that a longer operative time was associated with greater prevalence of pain score >5 (≥100 min: 5/7 patients vs. <40 min, 3/16 patients, P = 0.015). Conclusions: The primary benefit of SILC appears to be slightly less pain immediately after surgery. Surgeon training seems to be important because the shorter operative time for SILC may elicit less pain immediately after surgery. PMID:26668145

  2. Aspirin (single dose) for perineal pain in the early postpartum period.

    PubMed

    Molakatalla, Sujana; Shepherd, Emily; Grivell, Rosalie M

    2017-02-09

    Perineal trauma (due to spontaneous tears, surgical incision (episiotomy) or in association with operative vaginal birth) is common after vaginal birth, and is often associated with postpartum perineal pain. Birth over an intact perineum may also lead to perineal pain. There are adverse health consequences associated with perineal pain for the women and their babies in the short- and long-term, and the pain may interfere with newborn care and the establishment of breastfeeding. Aspirin has been used in the management of postpartum perineal pain and its effectiveness and safety should be assessed. To determine the efficacy of a single dose of aspirin (acetylsalicylic acid), including at different doses, in the relief of acute postpartum perineal pain. We searched Cochrane Pregnancy and Childbirth's Trials Register (30 August 2016), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (31 May 2016) and reference lists of retrieved studies. Randomised controlled trials (RCTs) assessing single dose aspirin compared with placebo, no treatment, a different dose of aspirin, or single dose paracetamol/acetaminophen for women with perineal pain in the early postpartum period. We planned to include cluster-RCTs but none were identified. Quasi-RCTs and cross-over studies were not eligible for inclusion in this review. Two review authors independently assessed study eligibility, extracted data and assessed the risk of bias of the included RCTs. Data were checked for accuracy. The quality of the evidence for the main comparison (aspirin versus placebo) was assessed using the GRADE approach. We included 17 RCTs, with 16 involving 1132 women randomised to aspirin or placebo (one RCT did not report numbers of women). Two RCTs (of 16) did not contribute data to review meta-analyses. All women had perineal pain post-episiotomy, and were not breastfeeding. Studies were published between 1967 and 1997, and the risk of bias was often unclear due to poor

  3. Effect of estrogen on morphine- and oxycodone-induced antinociception in a female femur bone cancer pain model.

    PubMed

    Ono, Hiroko; Nakamura, Atsushi; Kanemasa, Toshiyuki; Sakaguchi, Gaku; Shinohara, Shunji

    2016-02-15

    Although estrous cycle has been reported to influence antiociceptive effect of morphine in several pain conditions, its effect on cancer pain is not well established. We investigated the effect of estrogen on morphine antinociception using a bone cancer pain model and compared its potency with that of oxycodone. Female mice were ovariectomized (OVX) for preparation of a femur bone cancer pain (FBC) model. β-estradiol was subcutaneously (s.c.) administered and antinociceptive effects of opioids was assessed using the von Frey monofilament test. Although morphine (5-20mg/kg, s.c.) did have significant antinociceptive effects in the FBC-OVX group, its effects in the FBC-OVX+β-estradiol (OVX+E) group was limited. Oxycodone (1-5mg/kg, s.c.) exhibited significant effects in both groups. Expression changes in opioid-related genes (μ-, κ-, δ-opioid receptors, prodynorphin, proenkephalin, proopiomelanocortin) in the spinal and supraspinal sites were examined among the sham-OVX, sham-OVX+E, FBC-OVX, and FBC-OVX+E groups by in situ hybridization. These studies detected a significant increase in prodynorphin in the spinal dorsal horn of the FBC-OVX+E group. Spinal injection of a dynorphin-A antibody to FBC-OVX+E mice restored antinociception of morphine. In conclusion, we detected a differential effect of estrogen on morphine- and oxycodone-induced antinociception in a female FBC model. The effect of morphine was limited with estrogen exposure, which may be due to estrogen- and pain-mediated spinal expression of dynorphin-A.

  4. Sigma-1 Receptor Antagonist BD1047 Reduces Mechanical Allodynia in a Rat Model of Bone Cancer Pain through the Inhibition of Spinal NR1 Phosphorylation and Microglia Activation

    PubMed Central

    Zhu, Shanshan; Wang, Chenchen; Han, Yuan; Song, Chao; Hu, Xueming; Liu, Yannan

    2015-01-01

    Previous studies have demonstrated that sigma-1 receptor plays important roles in the induction phase of rodent neuropathic pain; however, whether it is involved in bone cancer pain (BCP) and the underlying mechanisms remain elusive. The aim of this study was to examine the potential role of the spinal sigma-1 receptor in the development of bone cancer pain. Walker 256 mammary gland carcinoma cells were implanted into the intramedullary space of the right tibia of Sprague-Dawley rats to induce ongoing bone cancer-related pain behaviors; our findings indicated that, on days 7, 10, 14, and 21 after operation, the expression of sigma-1 receptor in the spinal cord was higher in BCP rats compared to the sham rats. Furthermore, intrathecal injection of 120 nmol of sigma-1 receptor antagonist BD1047 on days 5, 6, and 7 after operation attenuated mechanical allodynia as well as the associated induction of c-Fos and activation of microglial cells, NR1, and the subsequent Ca2+-dependent signals of BCP rats. These results suggest that sigma-1 receptor is involved in the development of bone cancer pain and that targeting sigma-1 receptor may be a new strategy for the treatment of bone cancer pain. PMID:26696751

  5. Sigma-1 Receptor Antagonist BD1047 Reduces Mechanical Allodynia in a Rat Model of Bone Cancer Pain through the Inhibition of Spinal NR1 Phosphorylation and Microglia Activation.

    PubMed

    Zhu, Shanshan; Wang, Chenchen; Han, Yuan; Song, Chao; Hu, Xueming; Liu, Yannan

    2015-01-01

    Previous studies have demonstrated that sigma-1 receptor plays important roles in the induction phase of rodent neuropathic pain; however, whether it is involved in bone cancer pain (BCP) and the underlying mechanisms remain elusive. The aim of this study was to examine the potential role of the spinal sigma-1 receptor in the development of bone cancer pain. Walker 256 mammary gland carcinoma cells were implanted into the intramedullary space of the right tibia of Sprague-Dawley rats to induce ongoing bone cancer-related pain behaviors; our findings indicated that, on days 7, 10, 14, and 21 after operation, the expression of sigma-1 receptor in the spinal cord was higher in BCP rats compared to the sham rats. Furthermore, intrathecal injection of 120 nmol of sigma-1 receptor antagonist BD1047 on days 5, 6, and 7 after operation attenuated mechanical allodynia as well as the associated induction of c-Fos and activation of microglial cells, NR1, and the subsequent Ca(2+)-dependent signals of BCP rats. These results suggest that sigma-1 receptor is involved in the development of bone cancer pain and that targeting sigma-1 receptor may be a new strategy for the treatment of bone cancer pain.

  6. Periprosthetic bone turnover after primary total hip arthroplasty measured by single-photon emission computed tomography.

    PubMed

    Venesmaa, P; Vanninen, E; Miettinen, H; Kröger, H

    2012-01-01

    Alterations in periprosthetic bone are common sequlae of prosthetic implants.This prospective 3-year study was performed to follow regional periprosthetic bone turnover after uncomplicated total hip arthroplasty (THA) using single-photon emission computed tomography (SPECT). Eighteen patients (nine men, nine women: mean age 61 years, range from 50 to 73 years) with primary hip osteoarthritis underwent either uncemented or cemented THA. The SPECT measurements were taken 6, 12, and 36 months after THA. Bone mineral density (BMD) measurements were performed on the patients during follow-up. The mean SPECT uptake ratios decreased significantly in the regions of interest (ROIs) during follow-up compared to baseline value, in the trochanter major (p = 0.006), the trochanter minor (p = 0.009) and the total area (p = 0.018). Despite these decreases the uptake ratios in the medial cortex (p = 0.014), tip (p = 0.002) and total area (p = 0.016) remained significantly higher in the operated side than in the contralateral side (non-operated) 3 years after THA. Changes in bone turnover in the vicinity of the implant did not correlate with changes in periprosthetic BMD. Local periprosthetic bone turnover decreased slowly after THA and did not recover to the level typical of non-operated hips. This led us to suggest that bone turnover around the femoral implants remains increased more than 3 years after THA even if there are no signs of failure of the prosthesis.

  7. Single-walled carbon nanotubes functionalized with sodium hyaluronate enhance bone mineralization

    PubMed Central

    Sá, M.A.; Ribeiro, H.J.; Valverde, T.M.; Sousa, B.R.; Martins-Júnior, P.A.; Mendes, R.M.; Ladeira, L.O.; Resende, R.R.; Kitten, G.T.; Ferreira, A.J.

    2015-01-01

    The aim of this study was to evaluate the effects of sodium hyaluronate (HY), single-walled carbon nanotubes (SWCNTs) and HY-functionalized SWCNTs (HY-SWCNTs) on the behavior of primary osteoblasts, as well as to investigate the deposition of inorganic crystals on titanium surfaces coated with these biocomposites. Primary osteoblasts were obtained from the calvarial bones of male newborn Wistar rats (5 rats for each cell extraction). We assessed cell viability using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay and by double-staining with propidium iodide and Hoechst. We also assessed the formation of mineralized bone nodules by von Kossa staining, the mRNA expression of bone repair proteins, and the deposition of inorganic crystals on titanium surfaces coated with HY, SWCNTs, or HY-SWCNTs. The results showed that treatment with these biocomposites did not alter the viability of primary osteoblasts. Furthermore, deposition of mineralized bone nodules was significantly increased by cells treated with HY and HY-SWCNTs. This can be partly explained by an increase in the mRNA expression of type I and III collagen, osteocalcin, and bone morphogenetic proteins 2 and 4. Additionally, the titanium surface treated with HY-SWCNTs showed a significant increase in the deposition of inorganic crystals. Thus, our data indicate that HY, SWCNTs, and HY-SWCNTs are potentially useful for the development of new strategies for bone tissue engineering. PMID:26648087

  8. Postoperative Pain and Flare-Ups: Comparison of Incidence Between Single and Multiple Visit Pulpectomy in Primary Molars.

    PubMed

    Sevekar, Shrirang Anand; Gowda, Subhadra Halemane Nagaraj

    2017-03-01

    Endodontic treatment performed in either single- or multiple visit can be followed by numerous short- and long term complications. One of the short term complications include postoperative pain and flare-ups. The ability to predict its prevalence and forewarn the patient may go some way towards enabling coping strategies and help dentist in pain management treatment decisions. To compare the incidence and intensity of postoperative pain and flare-ups between single- and multiple visit pulpectomy in primary molars. Also, to correlate the preoperative status of the pulp to postoperative pain and flare-ups. Eighty primary molars indicated for pulpectomy were included in the study and divided into two groups. Tooth treated and preoperative status of the pulp vitality was recorded. All the conventional steps in pulpectomy were followed. Teeth in Group 1 (single visit pulpectomy) were obturated on the same visit. Teeth in Group 2 (multiple visit pulpectomy) were obturated in the subsequent appointment. The recording of postoperative pain, flare-ups, use of medication were done after 24 hours, seven days and one month. Four cases in both the groups reported postoperative pain (10%) at 24 hour recall, p=0.74. One flare-up (2.5%) was recorded in each group p=0.67. None of the patients reported pain at seventh day and one month recall. Postoperative pain was recorded in five non-vital teeth (13.5%) and three vital teeth (6.9%). However, it was statistically not significant p=0.53. From the perspective of our study there was a low incidence of postoperative pain. The majority of patients in both groups reported no pain or only minimal pain within 24 hours of treatment. There were no differences between single- and multi visit treatment protocols with respect to the incidence of postoperative pain. No significant correlation could be found between pulp vitality and the incidence of postoperative pain.

  9. Postoperative Pain and Flare-Ups: Comparison of Incidence Between Single and Multiple Visit Pulpectomy in Primary Molars

    PubMed Central

    Gowda, Subhadra Halemane Nagaraj

    2017-01-01

    Introduction Endodontic treatment performed in either single- or multiple visit can be followed by numerous short- and long term complications. One of the short term complications include postoperative pain and flare–ups. The ability to predict its prevalence and forewarn the patient may go some way towards enabling coping strategies and help dentist in pain management treatment decisions Aim To compare the incidence and intensity of postoperative pain and flare-ups between single- and multiple visit pulpectomy in primary molars. Also, to correlate the preoperative status of the pulp to postoperative pain and flare-ups. Materials and Methods Eighty primary molars indicated for pulpectomy were included in the study and divided into two groups. Tooth treated and preoperative status of the pulp vitality was recorded. All the conventional steps in pulpectomy were followed. Teeth in Group 1 (single visit pulpectomy) were obturated on the same visit. Teeth in Group 2 (multiple visit pulpectomy) were obturated in the subsequent appointment. The recording of postoperative pain, flare-ups, use of medication were done after 24 hours, seven days and one month. Results Four cases in both the groups reported postoperative pain (10%) at 24 hour recall, p=0.74. One flare-up (2.5%) was recorded in each group p=0.67. None of the patients reported pain at seventh day and one month recall. Postoperative pain was recorded in five non-vital teeth (13.5%) and three vital teeth (6.9%). However, it was statistically not significant p=0.53. Conclusion From the perspective of our study there was a low incidence of postoperative pain. The majority of patients in both groups reported no pain or only minimal pain within 24 hours of treatment. There were no differences between single- and multi visit treatment protocols with respect to the incidence of postoperative pain. No significant correlation could be found between pulp vitality and the incidence of postoperative pain. PMID:28511499

  10. Pain.

    PubMed

    Melzack, Ronald; Katz, Joel

    2013-01-01

    Pain has many valuable functions. It often signals injury or disease, generates a wide range of adaptive behaviors, and promotes healing through rest. Despite these beneficial aspects of pain, there are negative features that challenge our understanding of the puzzle of pain, including persistent phantom limb pain after amputation or total spinal cord transection. Pain is a personal, subjective experience influenced by cultural learning, the meaning of the situation, attention, and other psychological variables. Pain processes do not begin with the stimulation of receptors. Rather, injury or disease produces neural signals that enter an active nervous system that (in the adult organism) is the substrate of past experience, culture, and a host of other environmental and personal factors. These brain processes actively participate in the selection, abstraction, and synthesis of information from the total sensory input. Pain is not simply the end product of a linear sensory transmission system; it is a dynamic process that involves continuous interactions among complex ascending and descending systems. The neuromatrix theory guides us away from the Cartesian concept of pain as a sensation produced by injury, inflammation, or other tissue pathology and toward the concept of pain as a multidimensional experience produced by multiple influences. These influences range from the existing synaptic architecture of the neuromatrix-which is determined by genetic and sensory factors-to influences from within the body and from other areas in the brain. Genetic influences on synaptic architecture may determine-or predispose toward-the development of chronic pain syndromes. WIREs Cogn Sci 2013, 4:1-15. doi: 10.1002/wcs.1201 For further resources related to this article, please visit the WIREs website.

  11. Production, quality control, and bio-distribution studies of (159)Gd-EDTMP as a palliative agent for bone pain.

    PubMed

    Arani, Simindokht Shirvani; Ghasemi, Somaye; Samani, Ali Bahrami; Zafarghandi, Mojtaba Shamsaei

    2015-01-01

    Particle-emitting, bone-seeking radiopharmaceuticals have attracted the attention of the nuclear medicine community over the last three decades for the treatment of the pain of osteoblastic metastases. The objectives of this research were to produce quality-controlled (159)Gd-EDTMP in order to provide a new therapeutic radiopharmaceutical for use in clinical applications. The investigation was an experimental study in which (159)Gd (T1/2=18.479 h, Eβ (max)=970.60 keV, Eγ=363.55 (11.4%) keV] was produced by thermal neutron bombardment of natural Gd2O3 at the Tehran Research Reactor (TRR) for a period of 7 d at a flux of 3-4×10(13) neutrons/cm(2).s. It was then quality-controlled and used to radio-label the in-house prepared ethylene diamine tetra acetic acid (EDTM). Complexation parameters were optimized to achieve maximum yields (>99%). The radiochemical purity of (159)Gd-EDTMP was checked by radio thin layer chromatography RTLC. It was found to retain its stability at room temperature (>95%). Bio-distribution studies of the complexes conducted in wild rats showed significant bone uptake with rapid clearance from blood. The properties of the (159)Gd-EDTMP that was produced suggest then use of a new, efficient, palliative therapeutic agent for metastatic bone pain instead of some other current radiopharmaceuticals.

  12. Protocol of plain radiographs, hip ultrasound, and triple phase bone scans in the evaluation of the painful pediatric hip

    SciTech Connect

    Alexander, J.E.; Seibert, J.J.; Aronson, J.; Williamson, S.L.; Glasier, C.M.; Rodgers, A.B.; Corbitt, S.L.

    1988-04-01

    A useful protocol for the evaluation of hip pain in the pediatric patient, using a combination of plain radiographs, hip ultrasound (US), and triple phase radionuclide bone scans is presented. Patients with hip pain were initially evaluated by plain radiographs of the pelvis and hips. If no diagnosis was reached, the hips were studied for effusions by real-time hip ultrasonography. If an effusion was present, the joint was aspirated for diagnosis. If no effusion was present by US or if no diagnosis was reached by aspiration, triple phase radionuclide bone scans were performed. Fifty patients were evaluated by this prospective protocol, and the diagnosis was reached in 48 of the 50 cases (10 by plain radiographs, 16 by US, and aspiration of the joint, and 22 by triple phase bone scans). Hip effusions were found in 20 patients by US, with no false positives or false negatives. Previous studies for detecting effusions by US have emphasized absolute measurements of the capsular width, but we report a typical appearance of the hip capsule when fluid is present (a bulging convex capsule). When no effusion is present, the capsule is concave and parallels the long axis of the femoral neck.

  13. Evaluation of extremity pain in children using technetium-99m MDP bone scan: A general hospital experience

    SciTech Connect

    Park, H.M.; Rothschild, P.A.; Kernek, C.B.

    1984-01-01

    This study was undertaken to evaluate the efficacy of three-phase bone scan in detection of significant pathology i.e., osteomyelitis (OM), septic joint, cellulitis, etc., in children with symptoms of extremity pain. A total of 100 consecutive patients (age 9 days - 16 yrs, 63 boys and 37 girls) were studied. The authors reviewed their scans, x-rays and hospital records. The final diagnoses were based on the findings of needle aspiration, surgical drainage, biopsy, culture, and on the therapeutic response. In 87%, sufficiently long clinical follow-up was available to confirm the final diagnoses. In the remaining 13%, the symptoms resolved quickly and follow-up was not felt necessary. The scan was essential in pinpointing the lesions in pts with referred or nonlocalizing extremity pain. The +ve and -ve predictive values of the scan and OM were 89% and 96% respectively. One spiral fracture was misinterpreted as diffuse OM. One ''Subacute epiphyseal OM'' was not detected. In two cases, cellulitis and septic joint obscured underlying OM. Prior antibotic therapy resulted in one equivocal scan. Although less sensitive (29%) in early OM, radiographs play an important complimentary role. Bone scans detected underlying pathology for extremity pain in 61% of all pts studied.

  14. Study on correlation between bone marrow edema, stage of necrosis and area ratio of necrosis with the hip pain grading in nontraumatic osteonecrosis of the femoral head

    PubMed Central

    Jianchuan, Wang; Lei, Yang; Benjie, Wang; Dewei, Zhao

    2015-01-01

    The objective of this study was to explore the correlation between bone marrow edema, stage of necrosis, and area ratio of necrosis with the hip pain grading in non-traumatic osteonecrosis of the femoral head. Bone marrow edema grading at all levels and the hip pain grade differences were statistically significant (P < 0.001). Bone marrow edema grading increased by levels of 0, 1, and 2, whereas average pain rating increased as well to 40.73, 104.66 and 143.49. I ~ III period stage of necrosis and the hip pain grade difference was statistically significant (P < 0.001), with the average grade progress pain stage by the death of a rank gradually increased, I period, II period, III period was 57.00, 88.58 and 120.62, respectively. Area ratio of necrosis between 0 ~ 3 were positively correlated with pain, compared the two was statistically significant (P < 0.001), and with the degree of pathological changes is aggravating, increase the average rank of levels of pain. 0, 1, 2 and 3 are 36.88, 98.03, 123.87 and 151.93 respectively. We can choose the treatment method and evaluate treatment effect by considering a patients’ degree of bone marrow edema, stage of necrosis and area ratio of necrosis.

  15. Improvements in kinematics, muscle activity and pain during functional tasks in females with patellofemoral pain following a single patterned electrical stimulation treatment.

    PubMed

    Glaviano, Neal R; Huntsman, Stephanie; Dembeck, Ashley; Hart, Joseph M; Saliba, Susan

    2016-02-01

    Individuals with patellofemoral pain present with altered hip muscle activation, faulty movement patterns, and pain during functional tasks. Examining new treatment options to address these impairments may better treat those with patellofemoral pain. The purpose of this study was to determine if patterned electrical stimulation to the lower extremity affects muscle activity, movement patterns, and pain following a single treatment. Fifteen females with patellofemoral pain were randomized to receive a single 15-minute treatment of either a patterned electrical neuromuscular stimulation or a sham. Peak kinematics of the knee, hip, and trunk, electromyography and pain were examined pre and post-intervention during a single leg squat and lateral step-down task. Group means and pre/post reduced kinematic values were also plotted during the entire task with 90% confidence intervals to identify differences in movement strategies. No baseline differences were found in peak kinematics between groups. No pre to post-intervention differences in peak knee, hip and trunk kinematics were found, however differences were seen when the quality of movement across the entire tasks was assessed. The electrical stimulation group had improved knee flexion and hip abduction during the lateral step-down. A significant improvement in gluteus medius activation following patterned electrical neuromuscular stimulation occurred during the step-down (P=0.039). Significant pain improvements were also seen in both the single leg squat (P=0.025) and lateral step-down (P=0.006). A single treatment of patterned electrical neuromuscular stimulation improved muscle activation, lower extremity kinematics during functional tasks, and pain. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Classification of painful bone metastases as mild, moderate, or severe using both EORTC QLQ-C15-PAL and EORTC QLQ-BM22.

    PubMed

    McDonald, Rachel; Ding, Keyue; Chow, Edward; Meyer, Ralph M; Nabid, Abdenour; Chabot, Pierre; Coulombe, Genevieve; Ahmed, Shahida; Kuk, Joda; Dar, Rashid; Mahmud, Aamer; Fairchild, Alysa; Wilson, Carolyn F; Wu, Jackson S Y; Dennis, Kristopher; DeAngelis, Carlo; Wong, Rebecca K S; Zhu, Liting; Brundage, Michael

    2016-12-01

    Previous studies have determined optimal cut points (CPs) for the classification of pain severity as mild, moderate, or severe using only the Brief Pain Inventory (BPI) or the BPI in conjunction with a quality of life (QOL) tool. The purpose of our study was to determine the optimal CPs based on correlation with only QOL outcomes. We conducted an analysis of 298 patients treated with radiation therapy for painful bone metastases on a phase III randomized trial. Prior to treatment, patients provided their worst pain score on a scale of 0 (no pain) to 10 (worst possible pain), as well as completed the European Organization of Cancer Research and Treatment (EORTC) QOL Questionnaire Bone Metastases module (QLQ-BM22) and the EORTC QOL Questionnaire Core-15 Palliative (QLQ-C15-PAL). Optimal CPs were determined to be those that yielded the largest F ratio for the between category effect on each subscale of the QLQ-BM22 and QLQ-C15-PAL using the multivariate analysis of variance (MANOVA). The two largest F ratios for Wilk's λ, Pillai's Trace, and Hotelling's Trace were for CPs 5,6 and 5,7. Combining both, the optimal CPs to differentiate between mild, moderate, and severe pain were 5 and 7. Pain scores of 1-5, 6, and 7-10 were classified as mild, moderate, and severe, respectively. Patients with severe pain experienced greater functional interference and poorer QOL when compared to those with mild pain. Our results suggest that, based on the impact of pain on QOL measures, pain scores should be classified as follows: 1-5 as mild pain, 6 as moderate pain, and 7-10 as severe pain. Optimal CPs vary depending on the type of outcome measurement used.

  17. Enhanced function of TRPV1 via up-regulation by insulin-like growth factor-1 in a rat model of bone cancer pain.

    PubMed

    Li, Y; Cai, J; Han, Y; Xiao, X; Meng, X L; Su, L; Liu, F Y; Xing, G G; Wan, Y

    2014-07-01

    Up-regulation of transient receptor potential vanilloid subfamily, member 1 (TRPV1) is associated with the development and maintenance of cancer pain. The present study aimed to investigate the electrophysiological function of the up-regulated TRPV1 and the potential regulatory effects of insulin-like growth factor-1 (IGF-1) on TRPV1 expression in peripheral nerves in a rat model of bone cancer pain. A bone cancer pain model of rats was established by injecting MRMT-1 (rat mammary gland carcinoma cells) breast cancer cells into the tibia bone cavity. Thermal hyperalgesia was assessed by paw-withdrawal latency to a thermal stimulus, and mechanical allodynia was measured with von Frey monofilaments. TRPV1 and IGF-1 expression were examined with immunohistochemical staining and Western blot. TRPV1 current density of dorsal root ganglion (DRG) neurons was measured with whole-cell patch clamping recording technique. Rats showed thermal hyperalgesia and mechanical allodynia 14-21 days after MRMT-1 inoculation into the tibia bone marrow. TRPV1 protein expression and its current density increased in DRG neurons. At the same time, IGF-1 expression increased in tibia bone cavity, and IGF-1 incubation increased total or membrane TRPV1 protein expression and TRPV1 current in primary cultured DRG neurons. Inhibition of IGF-1 receptors in vivo reversed mechanical allodynia and thermal hyperalgesia in rats with bone cancer pain. Our results provide novel evidence for the increase of IGF-1 in tibia bone marrow, which is responsible for the up-regulation of TRPV1 expression and function in the peripheral nerves of bone cancer pain rats. © 2013 European Pain Federation ‐ EFIC®

  18. [A single metastasis in the carpal bones as the first clinical manifestation of a hepatocellular carcinoma].

    PubMed

    Corrales Pinzón, R; Alonso Sánchez, J M; de la Mano González, S; El Karzazi Tarazona, K

    2014-01-01

    Hepatocellular carcinoma is the most common primary tumor of the liver. Spreading outside the liver usually takes place in advanced stages of the disease, and bone is the third most common site of metastases. We present a case of hepatocellular carcinoma in which the first clinical manifestation was a single metastasis to the carpal bones. The interest of this case lies in the way this hepatocellular carcinoma manifested as well as in the unusual site of the metastasis. Copyright © 2012 SERAM. Published by Elsevier Espana. All rights reserved.

  19. Quality of Life After Palliative Radiation Therapy for Patients With Painful Bone Metastases: Results of an International Study Validating the EORTC QLQ-BM22

    SciTech Connect

    Zeng Liang; Chow, Edward; Bedard, Gillian; Zhang, Liying; Fairchild, Alysa; Vassiliou, Vassilios; Alm El-Din, Mohamed A.; Jesus-Garcia, Reynaldo; Kumar, Aswin; Forges, Fabien; Tseng, Ling-Ming; Hou, Ming-Feng; Chie, Wei-Chu; Bottomley, Andrew

    2012-11-01

    Purpose: Radiation therapy (RT) is an effective method of palliating painful bone metastases and can improve function and reduce analgesic requirements. In advanced cancer patients, quality of life (QOL) is the primary outcome of interest over traditional endpoints such as survival. The purpose of our study was to compare bone metastasis-specific QOL scores among patients who responded differently to palliative RT. Methods and Materials: Patients receiving RT for bone metastases across 6 countries were prospectively enrolled from March 2010-January 2011 in a trial validating the QLQ-BM22 and completed the QLQ-BM22 and the core measure (QLQ-C30) at baseline and after 1 month. Pain scores and analgesic intake were recorded, and response to RT was determined according to the latest published guidelines. The Kruskal-Wallis nonparametric and Wilcoxon rank sum tests compared changes in QOL among response groups. A Bonferroni-adjusted P<.003 indicated statistical significance. Results: Of 79 patients who received palliative RT, 59 were assessable. Partial response, pain progression, and indeterminate response were observed in 22, 8, and 29 patients, respectively; there were no patients with a complete response. Patients across all groups had similar baseline QOL scores apart from physical functioning (patients who progressed had better initial functioning). One month after RT, patients who responded had significant improvements in 3 of 4 QLQ-BM22 domains (painful site, P<.0001; painful characteristic, P<.0001; and functional interference, P<.0001) and 3 QLQ-C30 domains (physical functioning, P=.0006; role functioning, P=.0026; and pain, P<.0001). Patients with progression in pain had significantly worse functional interference (P=.0007) and pain (P=.0019). Conclusions: Patients who report pain relief after palliative RT also have better QOL with respect to bone metastasis-specific issues. The QLQ-BM22 and QLQ-C30 are able to discriminate among patients with varying

  20. Evaluation of bone remodeling around single dental implants of different lengths: a mechanobiological numerical simulation and validation using clinical data.

    PubMed

    Sotto-Maior, Bruno Salles; Mercuri, Emílio Graciliano Ferreira; Senna, Plinio Mendes; Assis, Neuza Maria Souza Picorelli; Francischone, Carlos Eduardo; Del Bel Cury, Altair Antoninha

    2016-01-01

    Algorithmic models have been proposed to explain adaptive behavior of bone to loading; however, these models have not been applied to explain the biomechanics of short dental implants. Purpose of present study was to simulate bone remodeling around single implants of different lengths using mechanoregulatory tissue differentiation model derived from the Stanford theory, using finite elements analysis (FEA) and to validate the theoretical prediction with the clinical findings of crestal bone loss. Loading cycles were applied on 7-, 10-, or 13-mm-long dental implants to simulate daily mastication and bone remodeling was assessed by changes in the strain energy density of bone after a 3, 6, and 12 months of function. Moreover, clinical findings of marginal bone loss in 45 patients rehabilitated with same implant designs used in the simulation (n = 15) were computed to validate the theoretical results. FEA analysis showed that although the bone density values reduced over time in the cortical bone for all groups, bone remodeling was independent of implant length. Clinical data showed a similar pattern of bone resorption compared with the data generated from mathematical analyses, independent of implant length. The results of this study showed that the mechanoregulatory tissue model could be employed in monitoring the morphological changes in bone that is subjected to biomechanical loads. In addition, the implant length did not influence the bone remodeling around single dental implants during the first year of loading.

  1. Single-unit analysis of the spinal dorsal horn in patients with neuropathic pain.

    PubMed

    Guenot, Marc; Bullier, Jean; Rospars, Jean-Pierre; Lansky, Petr; Mertens, Patrick; Sindou, Marc

    2003-04-01

    Despite the key role played by the dorsal horn of the spinal cord in pain modulation, single-unit recordings have only been performed very rarely in this structure in humans. The authors report the results of a statistical analysis of 64 unit recordings from the human dorsal horn. The recordings were done in three groups of patients: patients with deafferentation pain resulting from brachial plexus avulsion, patients with neuropathic pain resulting from peripheral nerve injury, and patients with pain resulting from disabling spasticity. The patterns of neuronal activities were compared among these three groups. Nineteen neurons were recorded in the dorsal horns of five patients undergoing DREZotomy for a persistent pain syndrome resulting from peripheral nerve injury (i.e., nondeafferented dorsal horns), 31 dorsal horn neurons were recorded in nine patients undergoing DREZotomy for a persistent pain syndrome resulting from brachial plexus avulsion (i.e., deafferented dorsal horns), and 14 neurons were recorded in eight patients undergoing DREZotomy for disabling spasticity. These groups were compared in terms of mean frequency, coefficient of variation of the discharge, other properties of the neuronal discharge studied by the nonparametric test of Wald-Wolfowitz, and the possible presence of bursts. The coefficient of variation tended to be higher in the deafferented dorsal horn group than in the other two groups. Two neurons displaying burst activity could be recorded, both of which belonged to the deafferented dorsal horn group. A significant difference was found in term of neuronal behavior between the peripheral nerve trauma group and the other groups: The brachial plexus avulsion and disabling spasticity groups were very similar, including various types of neuronal behavior, whereas the peripheral nerve lesion group included mostly neurons with "nonrandom" patterns of discharge (i.e., with serial dependency of interspike intervals).

  2. Incidence and characteristics of acute referred orofacial pain caused by a posterior single tooth pulpitis in an Iranian population.

    PubMed

    Hashemipour, Maryam Alsadat; Borna, Roya

    2014-02-01

    This study was designed to evaluate incidence and characteristics of acute referred orofacial pain caused by a posterior single tooth pulpitis in an Iranian population. In this cross-sectional study, 3,150 patients (1,400 males and 1,750 females) with pain in the orofacial region were evaluated via clinical and radiographic examination to determine their pain source. Patients completed a standardized clinical questionnaire consisting of a numerical rating scale for pain intensity and chose verbal descriptors from short form McGill questionnaire to describe the quality of their pain. Visual analog scale (VAS) was used to score pain intensity. In addition, patients indicated sites to which pain referred by drawing on an illustration of the head and neck. Data were analyzed using chi-square, fisher exact, and Mann-Whitney tests. Two thousand and hundred twenty patients (67/3%) reported pain in sites that diagnostically differed from the pain source. According to statistical analysis, sex (P = 0.02), intensity of pain (0.04), and quality (P = 0.001) of pain influenced its referral nature, while age of patients and kind of stimulus had no considerable effect on pain referral (P > 0.05). The results of the present study show the prevalence of referred pain in the head, face, and neck region is moderately high. Therefore, in patients with orofacial pain, it is essential to carefully examination before carrying out treatment that could be inappropriate. © 2013 The Authors Pain Practice © 2013 World Institute of Pain.

  3. Involvement of spinal monocyte chemoattractant protein-1 (MCP-1) in cancer-induced bone pain in rats.

    PubMed

    Hu, Ji-Hua; Zheng, Xiao-Yan; Yang, Jian-Ping; Wang, Li-Na; Ji, Fu-Hai

    2012-05-23

    In this study, we examined the involvement of chemokine monocyte chemoattractant protein-1 (MCP-1) in the spinal cord of a rat model of cancer-induced bone pain (CIBP). In this model, CIBP was established by an intramedullary injection of Walker 256 cells into the tibia of rats. We observed a significant increase in expression levels of MCP-1 and its receptor CCR2 in the spinal cord of CIBP rats. Furthermore, the intrathecal administration of an anti-MCP-1 neutralizing antibody attenuated the mechanical allodynia established in CIBP rats. Likewise, an intrathecal injection of exogenous recombinant MCP-1 induced a striking mechanical allodynia in naïve rats. These results suggest that increases in spinal MCP-1 and CCR2 expression are involved in the development of mechanical allodynia associated with bone cancer rats.

  4. Further observations on the behavioral and neural effects of bone marrow stromal cells in rodent pain models

    PubMed Central

    Guo, Wei; Chu, Yu-Xia; Imai, Satoshi; Yang, Jia-Le; Zou, Shiping; Mohammad, Zaid; Wei, Feng; Dubner, Ronald

    2016-01-01

    Background Bone marrow stromal cells (BMSCs) have shown potential to treat chronic pain, although much still needs to be learned about their efficacy and mechanisms of action under different pain conditions. Here, we provide further convergent evidence on the effects of BMSCs in rodent pain models. Results In an orofacial pain model involving injury of a tendon of the masseter muscle, BMSCs attenuated behavioral pain conditions assessed by von Frey filaments and a conditioned place avoidance test in female Sprague-Dawley rats. The antihyperalgesia of BMSCs in females lasted for <8 weeks, which is shorter than that seen in males. To relate preclinical findings to human clinical conditions, we used human BMSCs. Human BMSCs (1.5 M cells, i.v.) attenuated mechanical and thermal hyperalgesia induced by spinal nerve ligation and suppressed spinal nerve ligation-induced aversive behavior, and the effect persisted through the 8-week observation period. In a trigeminal slice preparation, BMSC-treated and nerve-injured C57B/L mice showed reduced amplitude and frequency of spontaneous excitatory postsynaptic currents, as well as excitatory synaptic currents evoked by electrical stimulation of the trigeminal nerve root, suggesting inhibition of trigeminal neuronal hyperexcitability and primary afferent input by BMSCs. Finally, we observed that GluN2A (N-methyl-D-aspartate receptor subunit 2A) tyrosine phosphorylation and protein kinase Cgamma (PKCγ) immunoreactivity in rostral ventromedial medulla was suppressed at 8 weeks after BMSC in tendon-injured rats. Conclusions Collectively, the present work adds convergent evidence supporting the use of BMSCs in pain control. As PKCγ activity related to N-methyl-D-aspartate receptor activation is critical in opioid tolerance, these results help to understand the mechanisms of BMSC-produced long-term antihyperalgesia, which requires opioid receptors in rostral ventromedial medulla and apparently lacks the development of tolerance

  5. Subchondral Bone Marrow Edema Had Greater Effect on Postoperative Pain After Medial Unicompartmental Knee Arthroplasty Than Total Knee Arthroplasty.

    PubMed

    Jacobs, Cale A; Christensen, Christian P; Karthikeyan, Tharun

    2016-02-01

    Although the relationship between pain and bone marrow edema (BME) in the osteoarthritic knee has been established, little is known about the effect of preoperative BME on postoperative outcomes after knee arthroplasty or if the influence of BME on postoperative outcomes differs between medial unicompartmental knee arthroplasty (UKA) and total knee arthroplasty (TKA). The purpose of this study was to compare pain, patient satisfaction, and revision rates between medial UKA and TKA patients with and without magnetic resonance imaging evidence of BME in the proximal tibia. We identified 71 patients (72 knees) from our prospective outcomes database with magnetic resonance images taken before undergoing either medial UKA or TKA and recorded the absence or presence of tibial BME. We then compared preoperative and postoperative Knee Society pain scores, patient satisfaction, and revisions between groups of UKA and TKA patients with or without preoperative tibial BME. Pain scores for UKA patients with BME were worse both before and after surgery, whereas TKA patients with BME demonstrated greater postoperative improvements in pain scores when compared to TKA patients without BME. Similarly, significantly fewer UKA patients with BME were satisfied with their procedure than those without BME (8/11, 73% vs 17/17, 100%; P = .05), but BME did not affect patient satisfaction after TKA. Preoperative BME did not influence TKA outcomes; however, pain scores for UKA patients with BME were worse both before and after surgery and fewer UKA patients with preoperative tibial BME were satisfied with their surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Spinal cord stimulation for Raynaud's syndrome: long-term alleviation of bilateral pain with a single cervical lead.

    PubMed

    Wolter, Tilman; Kieselbach, Kristin

    2011-01-01

      Spinal cord stimulation (SCS) has been described in a variety of neuropathic and vasospastic pain conditions including Raynaud's syndrome.   We report here the outcome of single lead SCS in the case of a 49-year-old woman with severe Raynaud's syndrome, which had failed to respond to medical therapy.   With a single quadripolar cervical lead in midline position at the C2/C3 level sustained pain relief of the bilateral pain was accomplished. Pain scores sank from 7/10 to 2-3/10 on the nominal analog scale and remained stable more than nearly four years by now.   Treatment of bilateral pain in Raynaud's syndrome with SCS in a single technique is feasible. Advantages and disadvantages as compared with stimulation with bilateral leads are discussed. © 2011 International Neuromodulation Society.

  7. Does single cortical spreading depression elicit pain behaviour in freely moving rats?

    PubMed

    Akcali, Didem; Sayin, Aslihan; Sara, Yildirim; Bolay, Hayrunnisa

    2010-10-01

    Behavioural animal studies are critical, particularly to translate results to human beings. Cortical spreading depression (CSD) has been implicated in migraine pathogenesis. We aimed to investigate the effects of CSD on the behaviour of freely moving rats, since available CSD models do not include awake animals. We developed a new model to induce single CSD by applying topical N-methyl-D-aspartate (NMDA) and employed a combination of an automated behavioural analysis system, video camera and ultrasonic vocalisation (USV) calls for the first time. Electrocorticograms were also studied during CSD in freely moving rats. Behaviour associated with cephalic pain was assessed in a group of rats that received sumatriptan. Cortical c-fos immunoreactivity was performed in order to confirm CSD. NMDA induced single CSD in ipsilateral cortex, evoked freezing behaviour (P < 0.01) and increased the number of wet dog shakes (WDS; P < 0.01). Grooming, locomotion, eating, drinking, and circling were not significantly altered among groups. Ultrasonic vocalisations compatible with pain calls (22-27 kHz) were only detected in 3 out of 25 rats. Sumatriptan did not significantly reduce the freezing behaviour. CSD induced significant c-fos expression in ipsilateral cerebral cortex and amygdala (P < 0.01). CSD induces freezing behaviour by invoking anxiety/fear via amygdala activation in freely-moving rats. Single CSD is unlikely to lead to severe pain in freely-moving rats, though the development of mild or vague pain cannot be excluded. The relevance of rat behavioural responses triggered by CSD to migraine symptoms in humans needs further evaluation.

  8. Detection of melorheostosis in a young lady with upper limb pain on Three Phase Bone Scintigram/SPECT-CT

    PubMed Central

    Hassan, Aamna; Khalid, Madeeha; Khawar, Saquib

    2016-01-01

    Summary Melorheostosis is a benign, noninheritable bone dysplasia characterized by its classic radiographic features of dense, flowing hyperostosis. It frequently affects one limb, usually the lower extremity and rarely the axial skeleton. A 26-year-old lady with obesity, polycystic ovarian syndrome and scalp dandruff presented with a long standing history of upper extremity pain and inability to adduct the arm completely. A Tc-99m MDP whole body and SPECT/CT scan performed for suspected fibrous dysplasia showed increased radiotracer uptake in densely sclerotic humeral and radial melorheostosis. This case highlighted the role of SPECT/CT imaging in this rare condition. PMID:27252746

  9. Detection of melorheostosis in a young lady with upper limb pain on Three Phase Bone Scintigram/SPECT-CT.

    PubMed

    Hassan, Aamna; Khalid, Madeeha; Khawar, Saquib

    2016-01-01

    Melorheostosis is a benign, noninheritable bone dysplasia characterized by its classic radiographic features of dense, flowing hyperostosis. It frequently affects one limb, usually the lower extremity and rarely the axial skeleton. A 26-year-old lady with obesity, polycystic ovarian syndrome and scalp dandruff presented with a long standing history of upper extremity pain and inability to adduct the arm completely. A Tc-99m MDP whole body and SPECT/CT scan performed for suspected fibrous dysplasia showed increased radiotracer uptake in densely sclerotic humeral and radial melorheostosis. This case highlighted the role of SPECT/CT imaging in this rare condition.

  10. Low bone mineral density, but not epidural steroid injection, is associated with fracture in postmenopausal women with low back pain.

    PubMed

    Yi, Yuri; Hwang, Byeongmun; Son, Heejeong; Cheong, Ilyoung

    2012-01-01

    Therapy with glucocorticoids often results in bone loss and glucocorticoid-induced osteoporosis. However, the relationship between epidural steroid injection (ESI), bone mineral density (BMD), and vertebral fracture remains to be determined. To establish a relationship between ESI, BMD, and vertebral fracture in postmenopausal women with low back pain. This study was a retrospective, nonblinded, cross-sectional clinical study. University-based pain management center. We reviewed the medical records of postmenopausal women with low back pain who were treated with ESI. A total of 352 postmenopausal women were divided into 2 groups. Group 1 consisted of patients without fracture and Group 2 consisted of those with fractures. The results of BMD measurements, as well as any fragility fractures, the anatomical site involved, and the treatment administered, were also recorded. BMD was measured in the lumbar spine, femoral neck, and total femur after the treatment. Of the 352 patients, 218 (62%) had no fractures while 134 (38%) sustained a fracture. The age was significantly higher among patients who sustained fractures, and BMD at the lumbar spine, total femur, and femoral neck regions was significantly lower among patients who sustained fractures. In each region, the prevalence of osteoporosis was significantly higher in patients with fracture than in patients without fracture (all P < 0.05). Age, height, and weight were associated with low BMD. However, our study showed no consistent correlation between BMD and the mean number of ESIs, mean total dose of glucocorticoids, or mean duration of ESIs. First, this study is limited by the fact that it was retrospective. Second, the number of cases receiving very frequent, high-dose glucocorticoid injections was very small. Older age and lower BMD were associated with osteoporotic fracture in postmenopausal women treated for low back pain with ESI. The ESIs were not associated with low BMD or fracture.

  11. Cost-Effectiveness Analysis of Single Fraction of Stereotactic Body Radiation Therapy Compared With Single Fraction of External Beam Radiation Therapy for Palliation of Vertebral Bone Metastases

    SciTech Connect

    Kim, Hayeon; Rajagopalan, Malolan S.; Beriwal, Sushil; Huq, M. Saiful; Smith, Kenneth J.

    2015-03-01

    Purpose: Stereotactic body radiation therapy (SBRT) has been proposed for the palliation of painful vertebral bone metastases because higher radiation doses may result in superior and more durable pain control. A phase III clinical trial (Radiation Therapy Oncology Group 0631) comparing single fraction SBRT with single fraction external beam radiation therapy (EBRT) in palliative treatment of painful vertebral bone metastases is now ongoing. We performed a cost-effectiveness analysis to compare these strategies. Methods and Materials: A Markov model, using a 1-month cycle over a lifetime horizon, was developed to compare the cost-effectiveness of SBRT (16 or 18 Gy in 1 fraction) with that of 8 Gy in 1 fraction of EBRT. Transition probabilities, quality of life utilities, and costs associated with SBRT and EBRT were captured in the model. Costs were based on Medicare reimbursement in 2014. Strategies were compared using the incremental cost-effectiveness ratio (ICER), and effectiveness was measured in quality-adjusted life years (QALYs). To account for uncertainty, 1-way, 2-way and probabilistic sensitivity analyses were performed. Strategies were evaluated with a willingness-to-pay (WTP) threshold of $100,000 per QALY gained. Results: Base case pain relief after the treatment was assumed as 20% higher in SBRT. Base case treatment costs for SBRT and EBRT were $9000 and $1087, respectively. In the base case analysis, SBRT resulted in an ICER of $124,552 per QALY gained. In 1-way sensitivity analyses, results were most sensitive to variation of the utility of unrelieved pain; the utility of relieved pain after initial treatment and median survival were also sensitive to variation. If median survival is ≥11 months, SBRT cost <$100,000 per QALY gained. Conclusion: SBRT for palliation of vertebral bone metastases is not cost-effective compared with EBRT at a $100,000 per QALY gained WTP threshold. However, if median survival is ≥11 months, SBRT costs ≤$100

  12. Evaluation of a Single Dose Intravenous Paracetamol for Pain Relief After Maxillofacial Surgery: A Randomized Clinical Trial Study.

    PubMed

    Eftekharian, Hamidreza; Tabrizi, Reza; Kazemi, Hamidreza; Nili, Mahsa

    2014-12-01

    The aim of this study was to evaluate, using a single dose of intravenous paracetamol, pain relief after maxillofacial surgery. This is a controlled, randomized, uni- blind, clinical trial study to evaluate using a single dose of IV paracetamol for pain relief after maxillofacial surgery. The subjects were randomly divided into two groups with 40 subjects in each: group I received paracetamol (Apotel)* as a single dose and group II received placebo. Subjects were randomly allocated according to randomization lists. Paracetamol was used as a single dose (20 mg/kg in 100 cc of normal saline which was infused for 10 min after surgery in recovery room just before discharging). We used a visual analogue scale to investigate pain relief at various times. Analysis of the data, did not show any significant difference for age, sex and weight between the treatment group and the control group. Pain decreased 6 h after paracetamol infusion; then it increased mildly. In the control group, pain severity increased after operation, then it decreased mildly. Results showed a correlation between duration of surgery and pain severity in both the groups. Paracetamol is effective on pain relief after maxillofacial surgeries. Operation time may be an important factor for induction of pain after the surgeries.

  13. The inhibitor of calcium/calmodulin-dependent protein kinase II KN93 attenuates bone cancer pain via inhibition of KIF17/NR2B trafficking in mice.

    PubMed

    Liu, Yue; Liang, Ying; Hou, Bailing; Liu, Ming; Yang, Xuli; Liu, Chenglong; Zhang, Juan; Zhang, Wei; Ma, Zhengliang; Gu, Xiaoping

    2014-09-01

    The N-methyl-d-aspartate receptor (NMDAR) containing subunit 2B (NR2B) is critical for the regulation of nociception in bone cancer pain, although the precise molecular mechanisms remain unclear. KIF17, a kinesin motor, plays a key role in the dendritic transport of NR2B. The up-regulation of NR2B and KIF17 transcription results from an increase in phosphorylated cAMP-response element-binding protein (CREB), which is activated by calcium/calmodulin-dependent protein kinase II (CaMKII). In this study, we hypothesized that CaMKII-mediated KIF17/NR2B trafficking may contribute to bone cancer pain. Osteosarcoma cells were implanted into the intramedullary space of the right femurs of C3H/HeJ mice to induce progressive bone cancer-related pain behaviors. The expression of spinal t-CaMKII, p-CaMKII, NR2B and KIF17 after inoculation was also evaluated. These results showed that inoculation of osteosarcoma cells induced progressive bone cancer pain and resulted in a significant up-regulation of p-CaMKII, NR2B and KIF17 expression after inoculation. Intrathecal administration of KN93, a CaMKII inhibitor, down-regulated these three proteins and attenuated bone cancer pain in a dose- and time-dependent manner. These findings indicated that CaMKII-mediated KIF17/NR2B trafficking may contribute to bone cancer pain, and inhibition of CaMKII may be a useful alternative or adjunct therapy for relieving cancer pain.

  14. Single dose oral paracetamol (acetaminophen) with codeine for postoperative pain in adults

    PubMed Central

    Toms, Laurence; Derry, Sheena; Moore, R Andrew; McQuay, Henry J

    2014-01-01

    Background This is an updated version of the Cochrane review published in Issue 4, 1998. Combining drugs from different classes with different modes of action may offer opportunity to optimise efficacy and tolerability, using lower doses of each drug to achieve the same degree of pain relief. Previously we concluded that addition of codeine to paracetamol provided additional pain relief, but at expense of additional adverse events. New studies have been published since. This review sought to evaluate efficacy and safety of paracetamol plus codeine using current data, and compare findings with other analgesics evaluated similarly. Objectives Assess efficacy of single dose oral paracetamol plus codeine in acute postoperative pain, increase in efficacy due to the codeine component, and associated adverse events. Search methods We searched CENTRAL, MEDLINE, EMBASE, the Oxford Pain Relief Database in October 2008 for this update. Selection criteria Randomised, double-blind, placebo-controlled trials of paracetamol plus codeine, compared with placebo or the same dose of paracetamol alone, for relief of acute postoperative pain in adults. Data collection and analysis Two authors assessed trial quality and extracted data. The area under the “pain relief versus time” curve was used to derive proportion of participants with paracetamol plus codeine and placebo or paracetamol alone experiencing least 50% pain relief over four-to-six hours, using validated equations. Number-needed-to-treat-to-benefit (NNT) was calculated using 95% confidence intervals (CIs). Proportion of participants using rescue analgesia over a specified time period, and time to use of rescue analgesia, were sought as additional measures of efficacy. Information on adverse events and withdrawals were collected. Main results Twenty-six studies, with 2295 participants, were included comparing paracetamol plus codeine with placebo. Significant dose response was seen for the outcome of at least 50% pain

  15. Single dose oral paracetamol (acetaminophen) with codeine for postoperative pain in adults.

    PubMed

    Toms, Laurence; Derry, Sheena; Moore, R Andrew; McQuay, Henry J

    2009-01-21

    This is an updated version of the Cochrane review published in Issue 4, 1998. Combining drugs from different classes with different modes of action may offer opportunity to optimise efficacy and tolerability, using lower doses of each drug to achieve the same degree of pain relief. Previously we concluded that addition of codeine to paracetamol provided additional pain relief, but at expense of additional adverse events. New studies have been published since. This review sought to evaluate efficacy and safety of paracetamol plus codeine using current data, and compare findings with other analgesics evaluated similarly. Assess efficacy of single dose oral paracetamol plus codeine in acute postoperative pain, increase in efficacy due to the codeine component, and associated adverse events. We searched CENTRAL, MEDLINE, EMBASE, the Oxford Pain Relief Database in October 2008 for this update. Randomised, double-blind, placebo-controlled trials of paracetamol plus codeine, compared with placebo or the same dose of paracetamol alone, for relief of acute postoperative pain in adults. Two authors assessed trial quality and extracted data. The area under the "pain relief versus time" curve was used to derive proportion of participants with paracetamol plus codeine and placebo or paracetamol alone experiencing least 50% pain relief over four-to-six hours, using validated equations. Number-needed-to-treat-to-benefit (NNT) was calculated using 95% confidence intervals (CIs). Proportion of participants using rescue analgesia over a specified time period, and time to use of rescue analgesia, were sought as additional measures of efficacy. Information on adverse events and withdrawals were collected. Twenty-six studies, with 2295 participants, were included comparing paracetamol plus codeine with placebo. Significant dose response was seen for the outcome of at least 50% pain relief over four-to-six hours, with NNTs of 2.2 (95% CI 1.8 to 2.9) for 800 to 1000 mg paracetamol plus

  16. Neural Correlates of Maladaptive Pain Behavior in Chronic Neck Pain - A Single Case Control fMRI Study.

    PubMed

    Beinert, Konstantin; Mouthon, Audrey; Keller, Martin; Mouthon, Michael; Annoni, Jean-Marie; Taube, Wolfgang

    2017-01-01

    Chronic neck pain patients display functional impairments like decreased range of motion, decreased strength, and reduced sensorimotor function. In patients without structural damage, the reason for the persistence of pain is not well understood. Therefore, it is assumed that in chronic pain states, memory processes play an important role. We have now detected and tested a patient that might help us to better understand the neural correlates of maladaptive pain expectation/memory. This patient displays chronic neck pain and restricted unilateral motion of the cervical spine to the left. However, when the patient is distracted, she can perform head rotations without experiencing pain and without restricting her range of movement. Based on this observation, we asked her to imagine movements shown in a video: conscious, non-distracted head rotations (pain-provoking) versus distracted head rotations (pain-free) and compared these results with an age and gender matched control volunteer. Functional magnetic resonance imaging (fMRI) showed distinct brain activation patterns that depended on the side of rotation (pain-free versus painful side) and the kind of movement (distracted versus non-distracted head rotation). Interestingly, brain areas related to the processing of pain such as primary somatosensory cortex, thalamus, insula, anterior cingulate cortex, primary motor cortex, supplementary motor area, prefrontal cortex, and posterior cingulate cortex were always more strongly activated in the non-distracted condition and when turning to the left. The age and gender matched control volunteer displayed no comparable activation of pain centers. In the patient, maladaptive pain behavior and the activity of pain-related brain areas during imagined head rotations were task-specific, indicating that the activation and/or recall of pain memories were context-dependent. These findings are important not only to improve the understanding of the neural organization of maladaptive

  17. Randomised study of single dose (8 Gy vs. 6 Gy) of analgesic radiotherapy plus zoledronic acid in patients with bone metastases.

    PubMed

    Mañas, A; Casas, F; Ciria, J P; López, C; Sáez, J; Palacios, A; de las Heras, M; Porto, C; Sánchez, E; Martín, C; Esco, R; Veiras, C; Martínez, J C; Márquez, M; Ramos, A; Calvo, F; Fuertes, J; Andreu, F J; Contreras, J; Pérez, L; Romero, J; Vayreda, J; Victoria, C

    2008-05-01

    To assess the effectiveness of a single dose of radio therapy (8 Gy vs. 6 Gy) plus zoledronic acid in cancer patients with bone metastases in treating pain; quality of life, time to onset of skeletal events and functional status. A total of 139 patients from 22 Spanish hospitals were randomly assigned to: Group A, administered a single dose of 8 Gy+zoledronic acid (4 mg iv, in 15-min infusions), and Group B, administered a single dose of 6 Gy+zoledronic acid (4 mg iv, in 15-min infusions). The main variable was pain, which was assessed with the Visual Analogue Pain Scale (VAS) in supine, seated and standing positions. There was a total of 118 patients for intention to treat (n=67 in Group A and n=51 in Group B). The most frequent primary neoplasms were the lung (29.66%), prostate (22.03%) and breast (21.19%). Sixty patients were analysed per protocol, n=34 in group A and n=26 in group B. Improvements were observed in the VAS scores for pain in all three positions. The mean time to onset of the event was greater (p=0.0211) in Group A than in Group B (122 vs. 81.62 days). Functional status improved in Group A, and quality of life improved in both groups. The two groups achieved similar levels of pain control in supine, seated and standing positions. Quality of life also improved in both groups. However, the higher dose (8 Gy dose) in combination with zoledronic acid is associated with a longer period without skeletal events.

  18. Involvement of lysophosphatidic acid in bone cancer pain by potentiation of TRPV1 via PKCε pathway in dorsal root ganglion neurons.

    PubMed

    Pan, Hai-Li; Zhang, Yu-Qiu; Zhao, Zhi-Qi

    2010-12-01

    It has been demonstrated that lysophosphatidic acid (LPA) released from injury tissue and transient receptor potential vanilloid 1 (TRPV1) receptor are implicated in the induction of chronic pain. In the present study we examined whether an interaction between LPA receptor LPA(1) and TRPV1 in dorsal root ganglion (DRG) neurons contributes to the development of bone cancer pain. Bone cancer was established by injection of mammary gland carcinoma cells into the rat tibia. Following the development of bone cancer pain, the TRPV1 expression and capsaicin-evoked currents were up-regulated in rat DRG neurons at L(4-6) segments. Immunohistochemistry staining revealed a high co-localization of LPA(1) with TRPV1 in DRG neurons. In isolated DRG neurons, whole-cell patch recording showed that capsaicin-induced currents were potentiated by LPA in a dose-dependent manner. The potentiation was blocked by either LPA(1) antagonist, protein kinase C (PKC) inhibitor or PKCε inhibitor, but not by protein kinase A (PKA) inhibitor or Rho inhibitor. In the behavioral tests, both mechanical allodynia and thermal hyperalgesia in bone cancer rats were attenuated by LPA(1) antagonist. LPA potentiates TRPV1 current via a PKCε-dependent pathway in DRG neurons of rats with bone cancer, which may be a novel peripheral mechanism underlying the induction of bone cancer pain.

  19. Process of Change in Pain-Related Fear: Clinical Insights From a Single Case Report of Persistent Back Pain Managed With Cognitive Functional Therapy.

    PubMed

    Caneiro, J P; Smith, Anne; Rabey, Martin; Moseley, G Lorimer; O'Sullivan, Peter

    2017-09-01

    Study Design Single case report with repeated measures over 18 months. Background Management of persistent low back pain (PLBP) associated with high pain-related fear is complex. This case report aims to provide clinicians with insight into the process of change in a person with PLBP and high bending-related fear, who was managed with an individualized behavioral approach of cognitive functional therapy. Case Description A retired manual worker with PLBP believed that his spine was degenerating, that bending would hurt him, and that avoidance was the only form of pain control. At baseline, he presented high levels of pain-related fear on the Tampa Scale of Kinesiophobia (score, 47/68) and a high-risk profile on the Örebro Musculoskeletal Pain Questionnaire (score, 61/100). Unhelpful beliefs and behaviors led to a vicious cycle of fear and disengagement from valued life activities. Guided behavioral experiments were used to challenge his thoughts and protective responses, indicating that his behavior was modifiable and the pain controllable. Using a multidimensional clinical-reasoning framework, cognitive functional therapy management was tailored to target key drivers of PLBP and delivered over 6 sessions in a 3-month period. Outcomes Over an 18-month clinical journey, he demonstrated improvements in bending-related fear, pain expectancy, and pain experience, and substantial changes in pain-related fear (Tampa Scale of Kinesiophobia: 33/68; change, -14 points) and risk profile (Örebro Musculoskeletal Pain Questionnaire: 36/100; change, -25 points). Clinical interviews at 6 and 18 months revealed positive changes in mindset, understanding of pain, perceived pain control, and behavioral responses to pain. Discussion This case report provides clinicians with an insight to using a multidimensional clinical-reasoning framework to identify and target the key drivers of the disorder, and to using cognitive functional therapy to address unhelpful psychological and

  20. Single dose oral ibuprofen plus codeine for acute postoperative pain in adults.

    PubMed

    Derry, Sheena; Karlin, Samuel M; Moore, R Andrew

    2015-02-05

    This is an update of the original Cochrane review published in Issue 3, 2013. There is good evidence that combining two different analgesics in fixed doses in a single tablet can provide better pain relief in acute pain and headache than either drug alone, and that the drug-specific effects are essentially additive. This appears to be broadly true in postoperative pain and migraine headache across a range of different drug combinations and when tested in the same and different trials. Some combinations of ibuprofen and codeine are available without prescription (but usually only from a pharmacy) where the dose of codeine is lower, and with a prescription when the dose of codeine is higher.Use of combination analgesics that contain codeine has been a source of some concern because of misuse from over-the-counter preparations. To assess the analgesic efficacy and adverse effects of a single oral dose of ibuprofen plus codeine for acute moderate-to-severe postoperative pain using methods that permit comparison with other analgesics evaluated in standardised trials using almost identical methods and outcomes. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Oxford Pain Relief Database, ClinicalTrials.gov, and the reference lists of articles. The date of the most recent search was 1 December 2014. Randomised, double-blind, placebo- or active-controlled clinical trials of single dose oral ibuprofen plus codeine for acute postoperative pain in adults. Two review authors independently considered trials for inclusion in the review, assessed risk of bias, and extracted data. We used the area under the pain relief versus time curve to derive the proportion of participants prescribed ibuprofen plus codeine, placebo, or the same dose of ibuprofen alone with at least 50% pain relief over six hours, using validated equations. We calculated the risk ratio (RR) and number needed to treat to benefit (NNT). We used information on the use

  1. Single dose oral ibuprofen plus codeine for acute postoperative pain in adults.

    PubMed

    Derry, Sheena; Karlin, Samuel M; Moore, R Andrew

    2013-03-28

    There is good evidence that combining two different analgesics in fixed doses in a single tablet can provide better pain relief in acute pain and headache than either drug alone, and that the drug-specific effects are essentially additive. This appears to be broadly true in postoperative pain and migraine headache across a range of different drug combinations and when tested in the same and different trials. Some combinations of ibuprofen and codeine are available without prescription (but usually only from a pharmacy) where the dose of codeine is lower, and with a prescription when the dose of codeine is higher. To assess the analgesic efficacy and adverse effects of a single oral dose of ibuprofen plus codeine for moderate to severe postoperative pain. We compared ibuprofen plus codeine with placebo and with the same dose of ibuprofen alone. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Oxford Pain Database, ClinicalTrials.gov, and reference lists of articles. The date of the most recent search was 30 September 2012. Randomised, double-blind, placebo- or active-controlled clinical trials of single dose oral ibuprofen plus codeine for acute postoperative pain in adults. Two review authors independently considered trials for inclusion in the review, assessed quality, and extracted data. We used the area under the pain relief versus time curve to derive the proportion of participants prescribed ibuprofen plus codeine, placebo, or the same dose of ibuprofen alone with at least 50% pain relief over six hours, using validated equations. We calculated the relative risk (RR) and number needed to treat to benefit (NNT). We used information on the use of rescue medication to calculate the proportion of participants requiring rescue medication and the weighted mean of the median time to use. We also collected information on adverse effects. Analyses were planned for different doses of ibuprofen and codeine, but especially for

  2. Comparison of Intravenous Ketamine with Morphine in Pain Relief of Long Bones Fractures: a Double Blind Randomized Clinical Trial

    PubMed Central

    Majidinejad, Saeed; Esmailian, Mehrdad; Emadi, Mehrdad

    2014-01-01

    Introduction: The selective medication for pain control in many clinical situations is morphine but its complications prevent its widespread use. Ketamine has been introduced as an alternative for morphine in some studies. However, the efficacy of its solitary use has not yet been evaluated. Therefore, the present study was undertaken to evaluate the effect of ketamine alone in relieving pain in trauma patients referring to an emergency unit. Methods: In this double-blind clinical trial, patients with long bone fractures were randomly divided into two groups of treatment with intravenous (IV) morphine at a dose of 0.1 mg/kg and treatment with IV ketamine at a dose of 0.5 mg/kg. Pain severity of the patients was recorded before and 10 minutes after injection based on numeric rating scale. The means in the two groups were compared using independent t-test. Then the Kaplan-Meier curve and log rank analysis were used to evaluate the success of treatment. Results: 126 patients were included in this study. The mean ages of the patients in the morphine and ketamine groups were 33.6±14.3 and 35.1±13.5 years, respectively (P=0.54). After therapeutic intervention, the pain severity significantly decreased in ketamine (2.7±1.8; P<0.0001) and morphine (2.4±1.5; P<0.0001) groups, with a similar effect of both medications on alleviating pain (P=0.28). The success rate of the treatment at 10-minute interval in groups receiving ketamine and morphine were 59 (93.65%) and 61 (96.8%) patients, respectively (P=0.62). Conclusion: The results of the present study showed that administration of ketamine at a low dose (0.5 mg/kg) results in a significant decrease in the severity of acute pain in patients with fractures of long bones. This palliative effect is very similar to that of morphine. PMID:26495351

  3. Tramadol-Paracetamol Combination for Postoperative Pain Relief in Elective Single-level Microdisectomy Surgery.

    PubMed

    Dogar, Samie A; Khan, Fauzia A

    2017-04-01

    The tramadol and paracetamol combination is used frequently for postoperative pain management. The literature on the use of this combination for vertebral surgery is limited. Our objective was to compare a combination of paracetamol 1 g and a lower dose of tramadol (1 mg/kg: group 1T) with a combination of paracetamol 1 g and a higher dose of tramadol (1.5 mg/kg: group 1.5T) for postoperative pain after microdisectomy surgery. Our main outcome measure was Visual Analogue Scale pain scores for 4 hours postoperatively. This prospective randomized triple-blind clinical trial was conducted at Aga Khan University Hospital, Karachi. Ninety-four patients aged between 18 and 50 years scheduled for elective single-level microdisectomy were allocated randomly into 1 of 2 groups. Twenty minutes before the end of the surgery, patients received the study drugs. There was no significant demographic difference between groups. None of the patients experienced severe pain (VAS>6). There was no significant difference in the mean pain score between groups. The mean score at 4 hours was 2.17 (1.38) in group 1.5T and 1.74 (1.37) in group 1T. The difference was not statistically significant (P=0.14). In group 1.5T, 13 patients reported having nausea and vomiting compared with 2 patients in group 1T. This was a statistically significant difference (P=0.004). The sedation score was similar between groups. The combination of low-dose tramadol (1 mg/kg) and paracetamol has comparable analgesia and a decreased incidence of nausea and vomiting compared with the higher dose of tramadol (1.5 mg/kg) and paracetamol combination.

  4. Bone mineral density, rib pain and other features of the female athlete triad in elite lightweight rowers.

    PubMed

    Dimitriou, Lygeri; Weiler, Richard; Lloyd-Smith, Rebecca; Turner, Antony; Heath, Luke; James, Nic; Reid, Anna

    2014-02-12

    To determine bone mineral density (BMD) and the associations among BMD, menstrual history, disordered eating (DE), training history, intentional weight loss (IWL) and rib pain for the first time in female lightweight rowers. 9 lightweight rowing clubs, UK. 29 Caucasian female lightweight rowers volunteered. 21 (12 active, 9 retired) completed the study. female lightweight rowers aged over 18 years. participants with a history of bone disease, used medications known to influence BMD or if they were pregnant, lactating or postmenopausal. Dual-energy X-ray absorptiometry measured total body (TB) composition and BMD at the spine, femoral neck (FN), radius and TB. DE, oligomenorrhoea/amenorrhoea years; rib pain and training history. DE was reported in six of the rowers. The active with DE started rowing younger (p<0.05) than those without, and their amount of IWL was associated with Eating Attitudes Test-26 score (p<0.05). Some participants reported a history of oligomenorrhoea/amenorrhoea 17 (76%) and/or rib pain 7 (32%) with those with rib pain having lower spine and TB Z-scores (p<0.05) than those without. Those with oligomenorrhoea/amenorrhoea had lower spine Z-scores (p<0.01) than those without. Twelve participants had low BMD; three at spine; one at FN; and eight at radius. Thirteen per cent of mean total training hours (18.6±9.1 h/week) were spent strength training (2.4±2.2 h/week). Upper body exercises incorporating multidimensional high peak bone strain were not reported and may need to be considered in their strength training to improve radial BMD. Results suggest IWL and high-level training at a young age increases the likelihood of DE and there may be a lack of quality nutritional support for these athletes. Thus, multidisciplinary sport science support should be offered at a young age and perhaps also to consider changing the weight rules to prevent the development of the Triad.

  5. Bone mineral density, rib pain and other features of the female athlete triad in elite lightweight rowers

    PubMed Central

    Dimitriou, Lygeri; Weiler, Richard; Lloyd-Smith, Rebecca; Turner, Antony; Heath, Luke; James, Nic; Reid, Anna

    2014-01-01

    Objective To determine bone mineral density (BMD) and the associations among BMD, menstrual history, disordered eating (DE), training history, intentional weight loss (IWL) and rib pain for the first time in female lightweight rowers. Setting 9 lightweight rowing clubs, UK. Participants 29 Caucasian female lightweight rowers volunteered. 21 (12 active, 9 retired) completed the study. Inclusion criteria: female lightweight rowers aged over 18 years. Exclusion criteria: participants with a history of bone disease, used medications known to influence BMD or if they were pregnant, lactating or postmenopausal. Main outcome measures Dual-energy X-ray absorptiometry measured total body (TB) composition and BMD at the spine, femoral neck (FN), radius and TB. DE, oligomenorrhoea/amenorrhoea years; rib pain and training history. Results DE was reported in six of the rowers. The active with DE started rowing younger (p<0.05) than those without, and their amount of IWL was associated with Eating Attitudes Test-26 score (p<0.05). Some participants reported a history of oligomenorrhoea/amenorrhoea 17 (76%) and/or rib pain 7 (32%) with those with rib pain having lower spine and TB Z-scores (p<0.05) than those without. Those with oligomenorrhoea/amenorrhoea had lower spine Z-scores (p<0.01) than those without. Twelve participants had low BMD; three at spine; one at FN; and eight at radius. Thirteen per cent of mean total training hours (18.6±9.1 h/week) were spent strength training (2.4±2.2 h/week). Conclusions Upper body exercises incorporating multidimensional high peak bone strain were not reported and may need to be considered in their strength training to improve radial BMD. Results suggest IWL and high-level training at a young age increases the likelihood of DE and there may be a lack of quality nutritional support for these athletes. Thus, multidisciplinary sport science support should be offered at a young age and perhaps also to consider changing the weight rules

  6. Formaldehyde up-regulates TRPV1 through MAPK and PI3K signaling pathways in a rat model of bone cancer pain.

    PubMed

    Han, Ying; Li, Yan; Xiao, Xing; Liu, Jia; Meng, Xiang-Ling; Liu, Feng-Yu; Xing, Guo-Gang; Wan, You

    2012-04-01

    Our previous study showed that tumor tissue-derived formaldehyde at low concentrations plays an important role in bone cancer pain through activating transient receptor potential vanilloid subfamily member 1 (TRPV1). The present study further explored whether this tumor tissue-derived endogenous formaldehyde regulates TRPV1 expression in a rat model of bone cancer pain, and if so, what the possible signal pathways are during the development of this type of pain. A rat model of bone cancer pain was established by injecting living MRMT-1 tumor cells into the tibia. The formaldehyde levels were determined by high performance liquid chromatography, and the expression of TRPV1 was examined with Western blot and RT-PCR. In primary cultured dorsal root ganglion (DRG) neurons, the expression of TRPV1 was assessed after treatment with 100 µmol/L formaldehyde with or without pre-addition of PD98059 [an inhibitor for extracellular signal-regulated kinase], SB203580 (a p38 inhibitor), SP600125 [an inhibitor for c-Jun N-terminal kinase], BIM [a protein kinase C (PKC) inhibitor] or LY294002 [a phosphatidylinositol 3-kinase (PI3K) inhibitor]. In the rat model of bone cancer pain, formaldehyde concentration increased in blood plasma, bone marrow and the spinal cord. TRPV1 protein expression was also increased in the DRG. In primary cultured DRG neurons, 100 μmol/L formaldehyde significantly increased the TRPV1 expression level. Pre-incubation with PD98059, SB203580, SP600125 or LY294002, but not BIM, inhibited the formaldehyde-induced increase of TRPV1 expression. Formaldehyde at a very low concentration up-regulates TRPV1 expression through mitogen-activated protein kinase and PI3K, but not PKC, signaling pathways. These results further support our previous finding that TRPV1 in peripheral afferents plays a role in bone cancer pain.

  7. Idiopathic juvenile osteoporosis: a cross-sectional single-centre experience with bone histomorphometry and quantitative computed tomography

    PubMed Central

    2013-01-01

    Background Idiopathic juvenile osteoporosis (IJO) is a rare condition of poorly understood etiology and pathophysiology that affects otherwise healthy children. This condition is characterized clinically by bone pain and vertebral fractures; spontaneous recovery is observed after puberty in the majority of cases. Although decreased trabecular bone turnover has been noted previously, cortical and trabecular bone characteristics as determined by quantitative computed tomography (QCT) and their relationship to bone histomorphometry are unknown. Methods All children with a clinical diagnosis of IJO who were followed in our center since 1995 and who had undergone at least one diagnostic bone biopsy were included in this cross-sectional analysis. Results Fifteen patients (11 males/4 females) with median ages of 5.8 and 10.2 years at first symptoms and at referral, respectively, were included in the analysis. Histomorphometric analysis demonstrated decreased trabecular bone turnover (BFR/BS) in the majority of patients with heterogeneous parameters of trabecular mineralization and volume. QCTresults demonstrated that bone mineral density (BMD) was reduced in both trabecular/lumbar and cortical/femoral bone: Z score: -2.1 (−3.6;–1.0) and −0.9 (−8.2;1.4)in the two compartments, respectively. In the eight patients who underwent both bone biopsy and QCT, cortical BMD was associated with trabecular separation and with trabecular bone formation rate (r = 0.898 and −0.881, respectively, both p < 0.05). Conclusions This series confirms that IJO is characterized by impaired trabecular architecture that can be detected by both bone biopsy and QCT. The association between bone biopsy and QCT results may have implications for diagnosis, treatment, and follow-up of these children. PMID:23418950

  8. Engagement of signaling pathways of protease-activated receptor 2 and μ-opioid receptor in bone cancer pain and morphine tolerance.

    PubMed

    Bao, Yanju; Gao, Yebo; Hou, Wei; Yang, Liping; Kong, Xiangying; Zheng, Honggang; Li, Conghuang; Hua, Baojin

    2015-09-15

    Pain is one of the most common and distressing symptoms suffered by patients with progression of cancer. Using a rat model of bone cancer, recent findings suggest that proteinase-activated receptor 2 (PAR2) signaling pathways contribute to neuropathic pain and blocking PAR2 amplifies antinociceptive effects of systemic morphine. The purpose of our study was to examine the underlying mechanisms responsible for the role of PAR2 in regulating bone cancer-evoked pain and the tolerance of systemic morphine. Breast sarcocarcinoma Walker 256 cells were implanted into the tibia bone cavity of rats and this evoked significant mechanical and thermal hyperalgesia. Our results showed that the protein expression of PAR2 and its downstream pathways (protein kinases namely, PKCε and PKA) and transient receptor potential vanilloid 1 (TRPV1) were amplified in the dorsal horn of the spinal cord of bone cancer rats compared to control rats. Blocking spinal PAR2 by using FSLLRY-NH2 significantly attenuated the activities of PKCε/PKA signaling pathways and TRPV1 expression as well as mechanical and thermal hyperalgesia. Also, inhibition of PKCε/PKA and TRPV1 significantly diminished the hyperalgesia observed in bone cancer rats. Additionally, blocking PAR2 enhanced the attenuations of PKCε/PKA and cyclic adenosine monophosphate induced by morphine and further extended analgesia of morphine via μ-opioid receptor (MOR). Our data revealed specific signaling pathways, leading to bone cancer pain, including the activation of PAR2, downstream PKCε/PKA, TRPV1 and resultant sensitization of MOR. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of bone cancer pain often observed in clinics.

  9. Colocalization of aromatase in spinal cord astrocytes: Differences in expression and relationship to mechanical and thermal hyperalgesia in murine models of a painful and a non-painful bone tumor

    PubMed Central

    O’Brien, Elaine E; Smeester, Branden A; Michlitsch, Kyle S; Lee, Jang-Hern; Beitz, Alvin J

    2015-01-01

    While spinal cord astrocytes play a key role in the generation of cancer pain, there have been no studies that have examined the relationship of tumor-induced astrocyte activation and aromatase expression during the development of cancer pain. Here, we examined tumor-induced mechanical hyperalgesia and cold allodynia, and changes in GFAP and aromatase expression in murine models of painful and non-painful bone cancer. We demonstrate that implantation of fibrosarcoma cells, but not melanoma cells, produces robust mechanical hyperalgesia and cold allodynia in tumor-bearing mice compared to saline-injected controls. Secondly, this increase in mechanical hyperalgesia and cold allodynia is mirrored by significant increases in both spinal astrocyte activity and aromatase expression in the dorsal horn of fibrosarcoma-bearing mice. Importantly, we show that aromatase is only found within a subset of astrocytes and not in neurons in the lumbar spinal cord. Finally, administration of an aromatase inhibitor reduced tumor-induced hyperalgesia in fibrosarcoma-bearing animals. We conclude that a painful fibrosarcoma tumor induces a significant increase in spinal astrocyte activation and aromatase expression and that the up-regulation of aromatase plays a role in the development of bone tumor-induced hyperalgesia. Since spinal aromatase is also upregulated, but to a lesser extent, in non-painful melanoma bone tumors, it may also be neuroprotective and responsive to the changing tumor environment. PMID:26071956

  10. Changes in bone mineral density in postmenopausal women treated with epidural steroid injections for lower back pain.

    PubMed

    Kang, Seong-Sik; Hwang, Byeong-Mun; Son, Heejeong; Cheong, Il-Young; Lee, Sang-Jin; Chung, Tae-Yoon

    2012-01-01

    Therapy with corticosteroids often results in bone loss and corticosteroid-induced osteoporosis. In previous studies, bone mineral density (BMD) has been examined after administration of relatively high oral doses of corticosteroids. However, practitioners use comparatively lower doses of corticosteroids for epidural steroid injections (ESI). The interactions and relationships between BMD and ESI remain to be determined. The aim of this study was to explore the relationship between BMD and ESI in postmenopausal women treated for lower back pain. This study was a retrospective evaluation. We reviewed the medical records of postmenopausal women with lower back pain who were treated with or without ESI. BMD was measured before treatment and one year after treatment in the lumbar spine, femoral neck, and total femur. A total of 90 postmenopausal women were divided into 2 groups. Group 1 patients received medications without ESI; Group 2 patients received ESI more than 4 times, with a cumulative administered triamcinolone dose of > 120 mg. Decreased BMD was observed in patients treated with ESI. However, no significant difference was observed between or within the groups in terms of mean percentage change from baseline BMD. First, this study is limited by the fact that it was retrospective. Second, our study did not consider the use of ESI with high-dose corticosteroids. Third, our study did not include any long-term assessments of the effects of ESI on BMD. These data suggest that ESI using triamcinolone (over 200 mg) for a period of one year will have a negative effect on BMD in postmenopausal women treated for lower back pain. However, ESI therapy using a maximum cumulative triamcinolone dose of 200 mg in one year would be a safe treatment method with no significant impact on BMD.

  11. Magnetic Acupressure in Reducing Pain in Cancer Patients Undergoing Bone Marrow Aspiration and Biopsy

    ClinicalTrials.gov

    2010-04-09

    Brain and Central Nervous System Tumors; Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Pain; Precancerous Condition; Unspecified Adult Solid Tumor, Protocol Specific

  12. Screening for psychological distress before radiotherapy for painful bone metastases may be useful to identify patients with high levels of distress.

    PubMed

    Westhoff, Paulien G; de Graeff, Alexander; Monninkhof, Evelyn M; Berveling, Maaike J; van Vulpen, Marco; Leer, Jan Willem H; Marijnen, Corrie A M; Reyners, Anna K L; van der Linden, Yvette M

    2017-09-12

    Psychological distress (PD) has a major impact on quality of life. We studied the incidence of PD before and after radiotherapy for painful bone metastases. Furthermore, we aimed to identify factors predictive for PD. Between 1996 and 1998, the Dutch Bone Metastasis Study included 1157 patients with painful bone metastases. Patients were randomized between two fractionation schedules. The study showed a pain response of 74% in both groups. Patients filled out weekly questionnaires for 13 weeks, then monthly for two years. The questionnaires included a subscale for PD on the Rotterdam Symptom Checklist. We used generalized estimating equations and multivariable logistic regression analyses. At baseline, 290 patients (27%) had a high level of PD. For the entire group, the level of PD remained constant over time. The majority of patients with a low level of PD at baseline remained at a low level during follow-up. In patients with a high level of PD at baseline, the mean level of PD decreased after treatment and stabilized around the cutoff level. Female patients, higher age, worse performance, lower pain score and worse self-reported QoL were associated with an increased chance of PD, although the model showed moderate discriminative power. A substantial proportion of patients had a high level of PD before and after radiotherapy for painful bone metastases. Most patients who reported high levels of PD when referred for palliative radiotherapy remained at high levels thereafter. Therefore, screening of PD prior to treatment seems appropriate, in order to select patients requiring intervention.

  13. Preparation, Biological Evaluation and Dosimetry Studies of 175Yb-Bis-Phosphonates for Palliative Treatment of Bone Pain

    PubMed Central

    Fakhari, Ashraf; Jalilian, Amir R.; Yousefnia, Hassan; Shanehsazzadeh, Saeed; Samani, Ali Bahrami; Daha, Fariba Johari; Ardestani, Mehdi Shafiee; Khalaj, Ali

    2015-01-01

    Objective: Optimized production and quality control of ytterbium-175 (Yb-175) labeled pamidronate and alendronate complexes as efficient agents for bone pain palliation has been presented. Methods: Yb-175 labeled pamidronate and alendronate (175Yb-PMD and 175Yb-ALN) complexes were prepared successfully at optimized conditions with acceptable radiochemical purity, stability and significant hydroxyapatite absorption. The biodistribution of complexes were evaluated up to 48 h, which demonstrated significant bone uptake ratios for 175Yb-PAM at all-time intervals. It was also detected that 175Yb-PAM mostly washed out and excreted through the kidneys. Results: The performance of 175Yb-PAM in an animal model was better or comparable to other 175Yb-bone seeking complexes previously reported. Conclusion: Based on calculations, the total body dose for 175Yb-ALN is 40% higher as compared to 175Yb-PAM (especially kidneys) indicating that 175Yb-PAM is probably a safer agent than 175Yb-ALN. PMID:27529886

  14. Optimization and In Vivo Profiling of a Refined Rat Model of Walker 256 Breast Cancer Cell-Induced Bone Pain Using Behavioral, Radiological, Histological, Immunohistochemical and Pharmacological Methods

    PubMed Central

    Shenoy, Priyank; Kuo, Andy; Vetter, Irina; Smith, Maree T.

    2017-01-01

    In the majority of patients with advanced breast cancer, there is metastatic spread to bones resulting in pain. Clinically available drug treatments for alleviation of breast cancer-induced bone pain (BCIBP) often produce inadequate pain relief due to dose-limiting side-effects. A major impediment to the discovery of novel well-tolerated analgesic agents for the relief of pain due to bony metastases is the fact that most cancer-induced bone pain models in rodents relied on the systemic injection of cancer cells, causing widespread formation of cancer metastases and poor general animal health. Herein, we have established an optimized, clinically relevant Wistar Han female rat model of breast cancer induced bone pain which was characterized using behavioral assessments, radiology, histology, immunohistochemistry and pharmacological methods. In this model that is based on unilateral intra-tibial injection (ITI) of Walker 256 carcinoma cells, animals maintained good health for at least 66 days post-ITI. The temporal development of hindpaw hypersensitivity depended on the initial number of Walker 256 cells inoculated in the tibiae. Hindpaw hypersensitivity resolved after approximately 25 days, in the continued presence of bone tumors as evidenced by ex vivo histology, micro-computed tomography scans and immunohistochemical assessments of tibiae. A possible role for the endogenous opioid system as an internal factor mediating the self-resolving nature of BCIBP was identified based upon the observation that naloxone, a non-selective opioid antagonist, caused the re-emergence of hindpaw hypersensitivity. Bolus dose injections of morphine, gabapentin, amitriptyline and meloxicam all alleviated hindpaw hypersensitivity in a dose-dependent manner. This is a first systematic pharmacological profiling of this model by testing standard analgesic drugs from four important diverse classes, which are used to treat cancer induced bone pain in the clinical setting. Our refined rat

  15. Rho/ROCK acts downstream of lysophosphatidic acid receptor 1 in modulating P2X3 receptor-mediated bone cancer pain in rats.

    PubMed

    Wu, Jing-Xiang; Yuan, Xiao-Min; Wang, Qiong; Wei, Wang; Xu, Mei-Ying

    2016-01-01

    Lysophosphatidic acid receptor 1 and Rho/ROCK signaling is implicated in bone cancer pain development. However, it remains unknown whether the two signaling pathways function together in P2X3 receptor-mediated bone cancer pain. In this study, using a rat model of bone cancer, we examined the expression of P2X3 and lysophosphatidic acid receptor 1 in rat dorsal root ganglion neurons and further dissected whether lysophosphatidic acid receptor 1 and Rho/ROCK-mediated pathways interacted in modulating rat pain behavior. Bone cancer was established by inoculating Walker 256 cells into the left tibia of female Wistar rats. We observed a gradual and yet significant decline in mean paw withdrawal threshold in rats with bone cancer, but not in control rats. Our immunohistochemical staining revealed that the number of P2X3- and lysophosphatidic acid receptor 1-positive dorsal root ganglion neurons was significantly greater in rats with bone cancer than control rats. Lysophosphatidic acid receptor 1 blockade with VPC32183 significantly attenuated decline in mean paw withdrawal threshold. Flinching behavior test further showed that lysophosphatidic acid receptor 1 inhibition with VPC32183 transiently but significantly attenuated α,β-meATP-induced increase in paw lift time per minute. Rho inhibition by intrathecal BoTXC3 caused a rapid reversal in decline in mean paw withdrawal threshold of rats with bone cancer. Flinching behavior test showed that BoTXC3 transiently and significantly attenuated α,β-meATP-induced increase in paw lift time per minute. Similar findings were observed with ROCK inhibition by intrathecal Y27632. Furthermore, VPC32183 and BoTXC3 effectively aborted the appearance of lysophosphatidic acid-induced calcium influx peak. Lysophosphatidic acid and its receptor LPAR1, acting through the Rho-ROCK pathway, regulate P2X3 receptor in the development of both mechanical and spontaneous pain in bone cancer. © The Author(s) 2016.

  16. Rho/ROCK acts downstream of lysophosphatidic acid receptor 1 in modulating P2X3 receptor-mediated bone cancer pain in rats

    PubMed Central

    Wu, Jing-xiang; Yuan, Xiao-min; Wang, Qiong; Wei, Wang

    2016-01-01

    Background Lysophosphatidic acid receptor 1 and Rho/ROCK signaling is implicated in bone cancer pain development. However, it remains unknown whether the two signaling pathways function together in P2X3 receptor-mediated bone cancer pain. Results In this study, using a rat model of bone cancer, we examined the expression of P2X3 and lysophosphatidic acid receptor 1 in rat dorsal root ganglion neurons and further dissected whether lysophosphatidic acid receptor 1 and Rho/ROCK-mediated pathways interacted in modulating rat pain behavior. Bone cancer was established by inoculating Walker 256 cells into the left tibia of female Wistar rats. We observed a gradual and yet significant decline in mean paw withdrawal threshold in rats with bone cancer, but not in control rats. Our immunohistochemical staining revealed that the number of P2X3- and lysophosphatidic acid receptor 1-positive dorsal root ganglion neurons was significantly greater in rats with bone cancer than control rats. Lysophosphatidic acid receptor 1 blockade with VPC32183 significantly attenuated decline in mean paw withdrawal threshold. Flinching behavior test further showed that lysophosphatidic acid receptor 1 inhibition with VPC32183 transiently but significantly attenuated α,β-meATP-induced increase in paw lift time per minute. Rho inhibition by intrathecal BoTXC3 caused a rapid reversal in decline in mean paw withdrawal threshold of rats with bone cancer. Flinching behavior test showed that BoTXC3 transiently and significantly attenuated α,β-meATP-induced increase in paw lift time per minute. Similar findings were observed with ROCK inhibition by intrathecal Y27632. Furthermore, VPC32183 and BoTXC3 effectively aborted the appearance of lysophosphatidic acid-induced calcium influx peak. Conclusions Lysophosphatidic acid and its receptor LPAR1, acting through the Rho-ROCK pathway, regulate P2X3 receptor in the development of both mechanical and spontaneous pain in bone cancer. PMID:27094551

  17. Bone oedema on MRI is highly associated with low bone mineral density in patients with early inflammatory back pain: results from the DESIR cohort.

    PubMed

    Briot, Karine; Durnez, Anne; Paternotte, Simon; Miceli-Richard, Corinne; Dougados, Maxime; Roux, Christian

    2013-12-01

    To assess bone mineral density (BMD) at lumbar spine and hip in a large cohort of patients with early inflammatory back pain (IBP) suggestive of axial spondyloarthritis (SpA), and to assess systemic and bone inflammation (according to MRI) as risk factors of low BMD. 332 (52.4% male) patients with IBP suggestive of axial SpA defined by Calin or Berlin criteria were recruited; they had lumbar spine and hip BMD and body composition measurements. Low BMD was defined by Z≤-2 (at least one site). Clinical, biological (erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)) and imaging (x-rays, spine and sacroiliac joint MRI) parameters were compared in patients with and without low BMD (Z≤-2). Significant parameters in univariate analysis were tested in multivariate models. Patients (mean age 33.8 years) had a short duration of axial symptoms (mean 1.6 years); 71.4% fulfilled the Assessment of Spondyloarthritis International Society criteria for axial SpA and HLA-B27 was present in 62.1%. 43 (13.0%) had low BMD (88% male). Multivariate logistic regression showed that parameters significantly associated with low BMD (any site) were the presence of bone marrow oedema (inflammatory lesions) on MRI (OR 4.63, p=0.001), either ESR or CRP (OR 2.60, p=0.037) and male gender (OR 9.60, p=0.0004). This study conducted in a large cohort of young adults with early IBP suggestive of SpA shows that 13.0% of patients have a low BMD and that the main risk factor associated with low BMD was inflammation on MRI.

  18. Accuracy and Early Clinical Outcome of 3-Dimensional Planned and Guided Single-Cut Osteotomies of Malunited Forearm Bones.

    PubMed

    Roner, Simon; Vlachopoulos, Lazaros; Nagy, Ladislav; Schweizer, Andreas; Fürnstahl, Philipp

    2017-09-06

    To investigate the reduction accuracy of 3-dimensional planned single-cut osteotomies (SCOTs) of the forearm that were performed using patient-specific guides. A retrospective analysis of SCOTs performed between 2012 and 2014 was performed. Ten patients (age, 15-59 years) with 6 malunions of the ulna and 6 malunions of the radius were identified. The reduction accuracy was assessed by comparing the 3-dimensional preoperative plan of each osteotomy with the superimposed bone model extracted from postoperative computed tomography data. The difference was assessed by 3-dimensional angle and in all 6 degrees of freedom (3 translations, 3 rotations) with respect to an anatomical coordinate system. Wrist range of motion and grip strength was assessed after a mean of 16.7 months and compared with the preoperative measurements. On average, the 12 SCOTs demonstrated excellent accuracy of the reduction with respect to rotation (ie, pronation/supination, 4.9°; flexion/extension, 1.7°; ulnar/radial angulation, 2.0°) and translation (ie, proximal/distal, 0.8 mm; radial/ulnar, 0.8 mm; dorsal/palmar, 0.8 mm). A mean residual 3-dimensional angle of 5.8° (SD, 3.6°) was measured after surgery. All 6 patients operated on for reasons of a reduced range of motion demonstrated improved symptoms and increased movement (from 20° to 80°). In the patients with unstable/painful distal radioulnar joint, 3 were totally free of complaints and 1 patient showed residual pain during sports. A SCOT combined with patient-specific guides is an accurate and reliable technique to restore normal anatomy in multiplanar deformities of the forearm. Therapeutic IV. Copyright © 2017 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

  19. Effect of a single session of ear acupuncture on pain intensity and postural control in individuals with chronic low back pain: a randomized controlled trial

    PubMed Central

    Ushinohama, Andrea; Cunha, Bianca P.; Costa, Leonardo O. P.; Barela, Ana M. F.; de Freitas, Paulo B.

    2016-01-01

    ABSTRACT Background Ear Acupuncture (EA) is a form of acupuncture in which needles are applied to the external ear and has been used in multiple painful conditions. Low back pain (LBP) is highly prevalent in active individuals and causes high economic burden to health systems worldwide. LBP affects the person’s ability to keep balance, especially in challenging conditions. Objective The aim of the study was to examine the effects of a single session of EA on pain intensity and body sway during postural tasks. Method Eighty adults with LBP and pain intensity equal to or greater than 4 (0-10 scale) were randomly allocated (1:1) to EA group (EAG) or placebo group (PG). Initially, the level of pain intensity was assessed. Next, participants stood still on a force plate either with feet in parallel or in semi-tandem and with eyes open or closed. Then, the EAG was treated with EA for 20 min and the PG was treated with detuned ultrasound. After the treatment, pain intensity was assessed again and the postural test was repeated. Pain intensity was the primary outcome and center of pressure sway area and speed were the secondary outcomes measured. Results Results revealed that pain intensity decreased in both groups after treatment, but decreased more in the EAG. For postural control, no effect of treatment and no interaction between treatment and postural condition on body sway were found. Conclusion Those findings indicate that EA is better than placebo to reduce pain, but neither treatment has any effect on postural control. PMID:27556389

  20. Modified Iliac Crest Reconstruction with Bone Cement for Reduction of Donor Site Pain and Morbidity after Open Wedge High Tibial Osteotomy: A Prospective Study

    PubMed Central

    Lee, Jong Seong; Park, Yong Jee; Wang, Lih; Chang, Yong Suk; Shetty, Gautam M.; Nha, Kyung Wook

    2016-01-01

    Purpose This study was to determine the efficacy of iliac crest reconstruction using bone cement in reducing pain and morbidity at the donor site in patients undergoing open wedge high tibial osteotomy (OWHTO) with tricortical iliac crest autologous graft. Materials and Methods Thirty-three patients who underwent iliac crest reconstruction using polymethyl methacrylate (PMMA) bone cement (group A) and thirty patients who had no iliac crest reconstruction (group B) were enrolled in this study. All patients were evaluated for pain and functional disability related to graft harvesting using the pain and functional visual analogue scale (VAS) score during hospital stay and at 6 weeks, 3 months, and 6 months postoperatively. Results There was significant difference between the two groups in terms of pain and function. The pain VAS score was significantly lower in group A than group B during the first 2 weeks postoperatively (p=0.04) and the functional VAS score was also significantly lower in group A during the first 2 weeks postoperatively (p<0.001) in terms of breathing, sitting up from the supine position, and standing up with crutches from the sitting position. Conclusions Iliac crest donor site reconstruction using PMMA bone cement in patients undergoing OWHTO significantly decreased pain and improved function during the first 2 weeks postoperatively when compared to patients who underwent OWHTO without iliac crest reconstruction. PMID:27894174

  1. Exuberant sprouting of sensory and sympathetic nerve fibers in nonhealed bone fractures and the generation and maintenance of chronic skeletal pain.

    PubMed

    Chartier, Stephane R; Thompson, Michelle L; Longo, Geraldine; Fealk, Michelle N; Majuta, Lisa A; Mantyh, Patrick W

    2014-11-01

    Skeletal injury is a leading cause of chronic pain and long-term disability worldwide. While most acute skeletal pain can be effectively managed with nonsteroidal anti-inflammatory drugs and opiates, chronic skeletal pain is more difficult to control using these same therapy regimens. One possibility as to why chronic skeletal pain is more difficult to manage over time is that there may be nerve sprouting in nonhealed areas of the skeleton that normally receive little (mineralized bone) to no (articular cartilage) innervation. If such ectopic sprouting did occur, it could result in normally nonnoxious loading of the skeleton being perceived as noxious and/or the generation of a neuropathic pain state. To explore this possibility, a mouse model of skeletal pain was generated by inducing a closed fracture of the femur. Examined animals had comminuted fractures and did not fully heal even at 90+days post fracture. In all mice with nonhealed fractures, exuberant sensory and sympathetic nerve sprouting, an increase in the density of nerve fibers, and the formation of neuroma-like structures near the fracture site were observed. Additionally, all of these animals exhibited significant pain behaviors upon palpation of the nonhealed fracture site. In contrast, sprouting of sensory and sympathetic nerve fibers or significant palpation-induced pain behaviors was never observed in naïve animals. Understanding what drives this ectopic nerve sprouting and the role it plays in skeletal pain may allow a better understanding and treatment of this currently difficult-to-control pain state.

  2. ¹⁷⁷Lu-Labeled Agents for Neuroendocrine Tumor Therapy and Bone Pain Palliation in Uruguay.

    PubMed

    Balter, Henia; Victoria, Trindade; Mariella, Terán; Javier, Gaudiano; Rodolfo, Ferrando; Andrea, Paolino; Graciela, Rodriguez; Juan, Hermida; Eugenia, De Marco; Patricia, Oliver

    2016-01-01

    Lutetium-177 is an emerging radionuclide due its convenient chemical and nuclear properties. In this paper we describe the development and evaluation in Uruguay of the targeted 177Lu labelled radiopharmaceuticals EDTMP (for bone pain palliation) and DOTA-TATE (neuroendocrine tumors). We optimized the preparation of these 177Lu radiopharmaceuticals including radiolabelling, quality control methods, in vitro and in vivo stability and their therapeutic application in patients. Radiation dosimetry aspects of 177Lu are also included. Nine male patients with prostate cancer and four female patients with breast carcinoma with multiple bone metastatic lesions were treated with 177Lu-EDTMP. Four patients with gastroentheropancreatic neuroendocrine tumors (GEP-NET) and one patient with bronchial NET were treated with 1- 3 cycles with a cumulative dose of 4.44-22.2 GBq of 177Lu-DOTA-TATE. Scintigraphic images of the patients treated with 177Lu-EDTMP evidenced high and rapid uptake in bone metastasis, remaining after 7 days post administration. Images allow skeletal visualization with high definition and demonstrate increased uptake in bone metastases. For 177Lu-DOTA-TATE, partial remissions were obtained in 4 patients and the remaining patient did not show significant progression 3 months after the second cycle. No serious adverse effects were registered, even in two patients with confirmed renal disease and high risk for renal disease Dosimetry assessments confirm the predictive value of the personalized therapy with radiolabelled peptides. We found it is possible to accumulate high therapeutic doses in tumours in sequential administrations of 177Lu-DOTA-TATE, increasing the probability of biological response without significant impairment of the renal function in patients with risk factors. These results demonstrate the attractive therapeutic properties of these two 177Lu labelled agents and the feasibility of this metabolic therapy in regions far away from 177Lu producing

  3. Diagnosis of partial and total physeal arrest by bone single-photon emission computed tomography.

    PubMed