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Sample records for intractable visceral pain

  1. Intractable pain with breast cancer.

    PubMed Central

    Watson, C. P.; Evans, R. J.

    1982-01-01

    This study examines retrospectively the cause, clinical features, natural history and results of treatment of intractable pain associated with breast cancer in 210 patients. The three chief types of pain were that due to skeletal metastases or brachial plexus neuropathy and pain of psychogenic origin. Onset at the time of cancer diagnosis characterized the psychogenic pain, whereas pain from metastases first occurred after a median latency of 3.7 years. Treatment was custom-tailored to the specific patient and pain problem, with several factors taken into account. The onset of intractable pain due to metastatic disease indicated a short survival (median, 9 months). PMID:6277445

  2. [Psychophysiology of visceral pain syndromes].

    PubMed

    Häuser, W; Grandt, D

    2002-12-01

    Psychosomatics of visceral pain syndromes. From a psychosomatic point of view visceral pain syndromes can be classified into nociceptive (somatic and visceral) pain syndromes without and with maladaptive pain coping resp.psychic comorbidity, functional pain syndromes (typical symptom clusters without biochemical or structural abnormalities in clinical routine diagnostics) and psychic disorders with pain as main symptom. With regard to the etiology and the course of chronic inflammatory bowel diseases (IBD) as representatives of somatic pain syndromes and of irritable bowel syndrome/chronic pelvic pain as representatives of functional pain syndromes empirically validated psychosocial aspects are summarized: Personality traits, illness behavior, daily hassles, life events and psychic comorbidity and effects of psychotherapy. Psychosocial factors are decisive in the etiology and the course of functional pain syndromes as determinants of their severity (psychosomatic disease in a narrow sense). Psychosocial factors are not decisive for the etiology, but for the course of IBD (psychosomatic disease in a broader sense). Within general pain therapy of visceral pain syndromes a biopsychosocial approach should be applied right from the beginning (psychosomatic basic care). Within special pain therapy of visceral pain syndromes a qualified psychiatric - psychotherapeutic diagnostics and co-therapy should be mandatory.

  3. Visceral Pain and Gastrointestinal Microbiome

    PubMed Central

    Chichlowski, Maciej; Rudolph, Colin

    2015-01-01

    A complex set of interactions between the microbiome, gut and brain modulate responses to visceral pain. These interactions occur at the level of the gastrointestinal mucosa, and via local neural, endocrine or immune activity; as well as by the production of factors transported through the circulatory system, like bacterial metabolites or hormones. Various psychological, infectious and other stressors can disrupt this harmonious relationship and alter both the microbiome and visceral pain responses. There are critical sensitive periods that can impact visceral pain responses in adulthood. In this review we provide a brief background of the intestinal microbiome and emerging concepts of the bidirectional interactions between the microbiome, gut and brain. We also discuss recent work in animal models, and human clinical trials using prebiotics and probiotics that alter the microbiome with resultant alterations in visceral pain responses. PMID:25829337

  4. Visceral Pain: The Neurophysiological Mechanism

    PubMed Central

    Sengupta, Jyoti N.

    2011-01-01

    The mechanism of visceral pain is still less understood compared with that of somatic pain. This is primarily due to the diverse nature of visceral pain compounded by multiple factors such as sexual dimorphism, psychological stress, genetic trait, and the nature of predisposed disease. Due to multiple contributing factors there is an enormous challenge to develop animal models that ideally mimic the exact disease condition. In spite of that, it is well recognized that visceral hypersensitivity can occur due to (1) sensitization of primary sensory afferents innervating the viscera, (2) hyperexcitability of spinal ascending neurons (central sensitization) receiving synaptic input from the viscera, and (3) dysregulation of descending pathways that modulate spinal nociceptive transmission. Depending on the type of stimulus condition, different neural pathways are involved in chronic pain. In early-life psychological stress such as maternal separation, chronic pain occurs later in life due to dysregulation of the hypothalamic–pituitary–adrenal axis and significant increase in corticotrophin releasing factor (CRF) secretion. In contrast, in early-life inflammatory conditions such as colitis and cystitis, there is dysregulation of the descending opioidergic system that results excessive pain perception (i.e., visceral hyperalgesia). Functional bowel disorders and chronic pelvic pain represent unexplained pain that is not associated with identifiable organic diseases. Often pain overlaps between two organs and approximately 35% of patients with chronic pelvic pain showed significant improvement when treated for functional bowel disorders. Animal studies have documented that two main components such as (1) dichotomy of primary afferent fibers innervating two pelvic organs and (2) common convergence of two afferent fibers onto a spinal dorsal horn are contributing factors for organ-to-organ pain overlap. With reports emerging about the varieties of peptide molecules

  5. Management of chronic visceral pain.

    PubMed

    Olesen, Anne E; Farmer, Adam D; Olesen, Søren S; Aziz, Qasim; Drewes, Asbjørn M

    2016-10-01

    Despite marked differences in underlying pathophysiology, the current management of visceral pain largely follows the guidelines derived from the somatic pain literature. The effective management of patients with chronic visceral pain should be multifaceted, including both pharmacological and psychological interventions, thereby providing a mechanism-orientated approach to treatment. Patients can frequently become disenfranchised, and subsequently disengaged, with healthcare providers leading to repeated consultations. Thus, a key aspect of management is to break this cycle by validating patients' symptoms, adopting an empathic approach and taking time to educate patients. To optimize treatment and outcomes in chronic visceral pain we need to move away from approaches exclusively based on dealing with peripheral nociceptive input toward more holistic strategies, taking into account alterations in central pain processing.

  6. Intracerebroventricular opioids for intractable pain

    PubMed Central

    Raffa, Robert B; Pergolizzi, Joseph V

    2012-01-01

    When pain is refractory to systemic opioid and non-opioid analgesic therapy and palliative chemoradiation or ablative or stimulant neurosurgical procedures are not possible, palliative treatment becomes limited, particularly if the patient wishes to be at home at the end of life. Intracerebroventricular (ICV) infusion of morphine in the home setting might be presented as an option. The present article reviews the basic and clinical evidence of the efficacy and safety of ICV administration of opioids. Information was gathered from various bibliographic sources, including PubMed and others, and summarized and evaluated to assess the efficacy and safety of ICV opioids for pain relief. Results from ICV infusion of morphine into terminally ill patients refractory to other pain treatments have been reported since the early 1980s. Good efficacy has been achieved for the vast majority of patients, without serious development of analgesic tolerance. There have also been a low incidence of adverse effects, such as constipation and respiratory depression, and a significant retention of alertness associated with this route of administration. Intracerebroventricular infusion of opioid analgesics thus appears to be a safe and effective therapy for the palliative treatment of refractory pain. PMID:22295988

  7. Visceral versus somatic pain: similarities and differences.

    PubMed

    Cervero, Fernando

    2009-01-01

    Inflammatory bowel disease and the irritable bowel syndrome are conditions characterized by chronic pain that generates persistent, hyperalgesic states in many regions of the body. It is difficult to explain the pain of conditions such as inflammatory bowel disease and irritable bowel syndrome by extrapolating directly from what is known about the mechanisms of somatic pain. Visceral and somatic pain show many differences not only in the psychophysics of the sensation, but also in the neurobiological mechanisms that mediate the sensory process. The activation and sensitization of visceral nociceptors are heavily influenced by the secretory and motor properties of the microenvironment where the sensory receptors are located. In some cases, epithelial cells can play a direct role in the activation of primary sensory neurons. Subclinical alterations of the epithelium can contribute to enhanced visceral sensitivity. Central hypersensitivity induced by visceral activation also shows differences with its somatic counterpart. Mobilization of AMPA receptors from the cytosol to the membrane of nociceptive neurons has been identified as a mechanism of sensitization of visceral pain pathways. Finally, functional pain syndromes, such as irritable bowel syndrome could be triggered or maintained by hormonal alterations, particularly those involving sex hormones such as estrogen.

  8. Early visceral pain predicts chronic pain after laparoscopic cholecystectomy.

    PubMed

    Blichfeldt-Eckhardt, Morten Rune; Ording, Helle; Andersen, Claus; Licht, Peter B; Toft, Palle

    2014-11-01

    Chronic pain after laparoscopic cholecystectomy is related to postoperative pain during the first postoperative week, but it is unknown which components of the early pain response is important. In this prospective study, 100 consecutive patients were examined preoperatively, 1 week postoperatively, and 3, 6, and 12 months postoperatively for pain, psychological factors, and signs of hypersensitivity. Overall pain, incisional pain (somatic pain component), deep abdominal pain (visceral pain component), and shoulder pain (referred pain component) were registered on a 100-mm visual analogue scale during the first postoperative week. Nine patients developed chronic unexplained pain 12 months postoperatively. In a multivariate analysis model, cumulated visceral pain during the first week and number of preoperative biliary pain attacks were identified as independent risk factors for unexplained chronic pain 12 months postoperatively. There were no consistent signs of hypersensitivity in the referred pain area either pre- or postoperatively. There were no significant associations to any other variables examined. The risk of chronic pain after laparoscopic cholecystectomy is relatively low, but significantly related to the visceral pain response during the first postoperative week.

  9. Purinergic mechanosensory transduction and visceral pain

    PubMed Central

    2009-01-01

    In this review, evidence is presented to support the hypothesis that mechanosensory transduction occurs in tubes and sacs and can initiate visceral pain. Experimental evidence for this mechanism in urinary bladder, ureter, gut, lung, uterus, tooth-pulp and tongue is reviewed. Potential therapeutic strategies are considered for the treatment of visceral pain in such conditions as renal colic, interstitial cystitis and inflammatory bowel disease by agents that interfere with mechanosensory transduction in the organs considered, including P2X3 and P2X2/3 receptor antagonists that are orally bioavailable and stable in vivo and agents that inhibit or enhance ATP release and breakdown. PMID:19948030

  10. Purinergic mechanosensory transduction and visceral pain.

    PubMed

    Burnstock, Geoffrey

    2009-11-30

    In this review, evidence is presented to support the hypothesis that mechanosensory transduction occurs in tubes and sacs and can initiate visceral pain. Experimental evidence for this mechanism in urinary bladder, ureter, gut, lung, uterus, tooth-pulp and tongue is reviewed. Potential therapeutic strategies are considered for the treatment of visceral pain in such conditions as renal colic, interstitial cystitis and inflammatory bowel disease by agents that interfere with mechanosensory transduction in the organs considered, including P2X3 and P2X2/3 receptor antagonists that are orally bioavailable and stable in vivo and agents that inhibit or enhance ATP release and breakdown.

  11. Drug Management of Visceral Pain: Concepts from Basic Research

    PubMed Central

    Davis, Mellar P.

    2012-01-01

    Visceral pain is experienced by 40% of the population, and 28% of cancer patients suffer from pain arising from intra- abdominal metastasis or from treatment. Neuroanatomy of visceral nociception and neurotransmitters, receptors, and ion channels that modulate visceral pain are qualitatively or quantitatively different from those that modulate somatic and neuropathic pain. Visceral pain should be recognized as distinct pain phenotype. TRPV1, Na 1.8, and ASIC3 ion channels and peripheral kappa opioid receptors are important mediators of visceral pain. Mu agonists, gabapentinoids, and GABAB agonists reduce pain by binding to central receptors and channels. Combinations of analgesics and adjuvants in animal models have supra-additive antinociception and should be considered in clinical trials. This paper will discuss the neuroanatomy, receptors, ion channels, and neurotransmitters important to visceral pain and provide a basic science rationale for analgesic trials and management. PMID:22619712

  12. Intractable sacroiliac joint pain treated with peripheral nerve field stimulation

    PubMed Central

    Chakrabortty, Shushovan; Kumar, Sanjeev; Gupta, Deepak; Rudraraju, Sruthi

    2016-01-01

    As many as 62% low back pain patients can have sacroiliac joint (SIJ) pain. There is limited (to poor) evidence in regards to long-term pain relief with therapeutic intra-articular injections and/or conventional (heat or pulsed) radiofrequency ablations (RFAs) for SIJ pain. We report our pain-clinic experience with peripheral nerve field stimulation (PNFS) for two patients of intractable SIJ pain. They had reported absence of long-term pain relief (pain relief >50% for at least 2 weeks postinjection and at least 3 months post-RFA) with SIJ injections and SIJ RFAs. Two parallel permanent 8-contact subcutaneous stimulating leads were implanted under the skin overlying their painful SIJ. Adequate stimulation in the entire painful area was confirmed. For implantable pulse generator placement, a separate subcutaneous pocket was made in the upper buttock below the iliac crest level ipsilaterally. During the pain-clinic follow-up period, the patients had reduced their pain medications requirements by half with an additional report of more than 50% improvement in their functional status. The first patient passed away 2 years after the PNFS procedure due to medical causes unrelated to his chronic pain. The second patient has been comfortable with PNFS-induced analgesic regimen during her pain-clinic follow-up during last 5 years. In summary, PNFS can be an effective last resort option for SIJ pain wherein conventional interventional pain techniques have failed, and analgesic medication requirements are escalating or causing unwarranted side-effects. PMID:27625495

  13. Treating Intractable Post-Amputation Phantom Limb Pain with Ambulatory Continuous Peripheral Nerve Blocks

    DTIC Science & Technology

    2016-01-01

    AD_________________ Award Number: W81XWH-13-2-0009 TITLE: Treating Intractable Post-Amputation Phantom Limb Pain with Ambulatory Continuous...Annual 3. DATES COVERED 26 Dec 2014- 25 Dec 2015 4. TITLE AND SUBTITLE Treating Intractable Post-Amputation Phantom Limb Pain with Ambulatory...effective treatment for intractable phantom limb pain following a traumatic limb amputation. There is currently no reliable treatment for phantom limb pain

  14. Intractable pain due to rectus abdominis intramuscular haemangioma.

    PubMed

    Scozzari, G; Reddavid, R; Conti, L; Trombetta, F; Toppino, M; Sandrucci, S

    2014-08-01

    Haemangiomas are tumours of vascular origin accounting for approximately 7 % of all benign tumours. Three types of haemangioma have been described according to the vessel type involved: capillary, cavernous and mixed. Intramuscular haemangiomas (IMHs) are infrequent, accounting for less than 1 % of all haemangiomas and are mostly located in the extremities and the trunk. Intramuscular haemangiomas of the rectus abdominis muscle are extremely rare, with only one previous case reported in the literature to the best of our knowledge. In this report, we present the case of a patient with intractable pain related to IMHs of the rectus abdominis and we analyse diagnostic assessment and surgical management of the condition.

  15. Trigeminal branch stimulation for the treatment of intractable craniofacial pain.

    PubMed

    Ellis, Jason A; Mejia Munne, Juan C; Winfree, Christopher J

    2015-07-01

    OBJECT Trigeminal branch stimulation has been used in the treatment of craniofacial pain syndromes. The risks and benefits of such an approach have not been clearly delineated in large studies, however. The authors report their experience in treating craniofacial pain with trigeminal branch stimulation and share the lessons they have learned after 93 consecutive electrode placements. METHODS A retrospective review of all patients who underwent trigeminal branch electrode placement by the senior author (C.J.W.) for the treatment of craniofacial pain was performed. RESULTS Thirty-five patients underwent implantation of a total of 93 trial and permanent electrodes between 2006 and 2013. Fifteen patients who experienced improved pain control after trial stimulation underwent implantation of permanent stimulators and were followed for an average of 15 months. At last follow-up 73% of patients had improvement in pain control, whereas only 27% of patients had no pain improvement. No serious complications were seen during the course of this study. CONCLUSIONS Trigeminal branch stimulation is a safe and effective treatment for a subset of patients with intractable craniofacial pain.

  16. Epidemiological Investigation of Asymptomatic Dogs with Leishmania Infection in Southwestern China Where Visceral Leishmaniasis is Intractable

    PubMed Central

    Zhao, Gui-Hua; Yin, Kun; Zhong, Wei-Xia; Xiao, Ting; Wei, Qing-Kuan; Cui, Yong; Liu, Gong-Zhen; Xu, Chao; Wang, Hong-Fa

    2016-01-01

    Heishui county, located in northwest Sichuan province, southwestern China, is an endemic area of zoonotic visceral leishmaniasis (VL) and is the most intractable area. VL is never destroyed in it. Asymptomatic dogs (Leishmania parasites have been diagnosed but clinically healthy) are considered to be a potential reservoir host in zoonotic VL area, and most can lead to infection of individuals, that is a new challenge for controlling VL in humans. The present study aimed to assess the Leishmania infection rate of asymptomatic dogs in Heishui county. Total 105 asymptomatic domestic dogs were gathered from 4 districts in Heishui county to investigate the infection rate with serological and molecular methods based on ELISA and kinetoplast minicircle DNA(kDNA) PCR, respectively. Out of 105 dogs, 44 (41.9%) were positive by more than 1 method; 21 (20.0%) were positive by ELISA, and 30 (28.6%) were positive by kDNA-PCR. Our study showed that Leishmania infection of domestic dogs which is clinically healthy is prevalent in the studied district, and the asymptomatic dogs infected by Leishmania may be the primary reason for the prevalence of visceral leishmaniasis in the area. PMID:28095666

  17. Briquet syndrome in a man with chronic intractable pain.

    PubMed

    de Figueiredo, J M; Baiardi, J J; Long, D M

    1980-09-01

    A 51-year-old man was admitted for evaluation and treatment of scrotal pain of 20 years' duration following unilateral orchiectomy for right testicular injury. Past attempts had failed to provide definitive or persistent relief. Physical examination and investigations were unremarkable. Psychiatric assessment revealed an angry, depressed man with a drasmatic, hypermasculine manner and hysterical and obsessive personality traits. Review of systems with a structured interview indicated that the patient had numerous medically unexplained symptoms and that he fulfilled both the Feighner and the Diagnostic and Statistical Manual of Mental Disorders 3rd edition (DSM-III) diagnostic criteria for Briquet syndrome. The case is important because it demonstrates the usefulness of recognizing Briquet syndrome in patients with the single presenting complaint of chronic, intractable pain, and the fact that Briquet syndrome, commonly considered a female disorder, can occur in men regardless of sexual orientation and in the absence of expected compensation. In addition, the case confirms the utility of a structured interview and defined criteria for making the diagnosis of Briquet syndrome.

  18. Treating Intractable Post-Amputation Phantom Limb Pain With Ambulatory Continuous Peripheral Nerve Blocks

    DTIC Science & Technology

    2015-01-01

    AD_________________ Award Number: W81XWH-13-2-0009 TITLE: Treating Intractable Post-Amputation Phantom Limb Pain With Ambulatory Continuous...TYPE Annual 3. DATES COVERED 26 Dec 2013 – 25 Dec 2014 4. TITLE AND SUBTITLE Treating Intractable Post-Amputation Phantom Limb Pain With Ambulatory...AKAs, and phantom pain in multiple locations • Approval received by National Amputee Coalition research committee to advertise in their website, e

  19. Assessment of visceral pain associated with metritis in dairy cows

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Metritis is a common disease in dairy cattle but to our knowledge no work has assessed pain associated with this disease. Tissue palpation is commonly used to assess pain in human and veterinary medicine. The objective of this study was to evaluate visceral pain responses during rectal and uterine p...

  20. Intracerebroventricular Pain Treatment with Analgesic Mixtures including Ziconotide for Intractable Pain.

    PubMed

    Staquet, Héléne; Dupoiron, Denis; Nader, Edmond; Menei, Philippe

    2016-07-01

    Intracerebroventricular (ICV) administration of opioids for control of intractable cancer pain has been used since 1982. We present here our experience of intracerebroventricular administration of pain treatments including ziconotide associated with morphine and ropivacaine for patients resistant to a conventional approach, with nociceptive, neuropathic, or mixed pain. These clinical cases were conducted with patients suffering from refractory pain, more than 6/10 on a numerical pain rating scale (NPRS) while on high-dose medical treatment and/or intolerance with significant side effects from oral medication. The baseline study visit included a physical examination and an assessment of pain intensity on a NPRS. Under general anesthesia, a neuronavigation device was used to place the catheter on the floor of the third ventricle, supported by an endoscope. Then, drugs were injected in the cerebroventricular system, through a pump (external or subcutaneous). The primary objective was to measure pain evaluation with ICV treatment after a complete withdrawal of other medications.Four patients were enrolled: 3 with intractable cancer pain and one with central neuropathic pain. The median NPRS at baseline was 9.5 [8.5; 19]. The mean NPRS after one month was 3.5 [3; 4.5]. Ziconotide was initiated at 0.48 µg/d and up to a median of 1.2 µg/d [1.0; 1.56]. The median dose of morphine and ropivacaine used initially was respectively 0.36 mg/d [0.24; 0.66] up to 0.6 mg/d [0.45; 4.63] and 1.2 mg/d [0; 2.4] up to 2.23 mg/d [1.2; 3.35]. Minor side effects were initially observed but transiently. One psychiatric agitation required discontinuation of ziconotide infusion. For intractable pain, using ziconotide by intracerebroventricular infusion seems safe and efficient, specifically for chronic neoplastic pain of cervicocephalic, thoracic, or diffuse origin and also for pain arising from a central neuropathic mechanism.

  1. Renal Artery Embolization Controls Intractable Pain in a Patient with Polycystic Kidney Disease

    SciTech Connect

    Hahn, Seong Tai; Park, Seog Hee; Lee, Jae Mun; Kim, Choon-Yul; Chang, Yoon Sik

    1999-09-15

    A 65-year-old man with adult polycystic kidney disease (APKD) and chronic renal failure suffered from intractable abdominal pain and distension for 2 weeks. Meperidine infusion did not alleviate his pain. However, pain and abdominal distension were successfully controlled by embolization of both renal arteries.

  2. Models of visceral pain: colorectal distension (CRD).

    PubMed

    Jones, R Carter W; Gebhart, G F

    2004-09-01

    The visceromotor response to balloon distension of the colon is a robust behavioral model of visceral nociception in rodents and is ideally suited for studying the visceral antinociceptive activity of drugs. This unit describes, in detail, quantification of this response with the use of electromyography in both rats and mice.

  3. Stress and visceral pain: from animal models to clinical therapies

    PubMed Central

    Larauche, Muriel; Mulak, Agata; Taché, Yvette

    2011-01-01

    Epidemiological studies have implicated stress (psychosocial and physical) as a trigger of first onset or exacerbation of irritable bowel syndrome (IBS) symptoms of which visceral pain is an integrant landmark. A number of experimental acute or chronic exteroceptive or interoceptive stressors induce visceral hyperalgesia in rodents although recent evidence also points to stress-related visceral analgesia as established in the somatic pain field. Underlying mechanisms of stress-related visceral hypersensitivity may involve a combination of sensitization of primary afferents, central sensitization in response to input from the viscera and dysregulation of descending pathways that modulate spinal nociceptive transmission or analgesic response. Biochemical coding of stress involves the recruitment of corticotropin releasing factor (CRF) signaling pathways. Experimental studies established that activation of brain and peripheral CRF receptor subtype 1 plays a primary role in the development of stress-related delayed visceral hyperalgesia while subtype 2 activation induces analgesic response. In line with stress pathways playing a role in IBS, non-pharmacologic and pharmacologic treatment modalities aimed at reducing stress perception using a broad range of evidence-based mind-body interventions and centrally-targeted medications to reduce anxiety impact on brain patterns activated by visceral stimuli and dampen visceral pain. PMID:21575632

  4. Botulinum Toxin A Injection into the Subscapularis Muscle to Treat Intractable Hemiplegic Shoulder Pain

    PubMed Central

    2016-01-01

    Objective To evaluate the beneficial effect of botulinum toxin A (Botox) injection into the subscapularis muscle on intractable hemiplegic shoulder pain. Methods Six stroke patients with intractable hemiplegic shoulder pain were included. Botulinum toxin A was injected into the subscapularis muscle. Intractable hemiplegic shoulder pain was evaluated using an 11-point numerical rating scale. Pain-free range of motion was assessed for shoulder abduction and external rotation. The spasticity of the shoulder internal rotator was measured using the modified Ashworth scale. Assessments were carried out at baseline and at 1, 2, 4, and, if possible, 8 weeks. Results Intractable hemiplegic shoulder pain was improved (p=0.004) after botulinum toxin injection into the subscapularis muscle. Restricted shoulder abduction (p=0.003), external rotation (p=0.005), and spasticity of the shoulder internal rotator (p=0.005) were also improved. Improved hemiplegic shoulder pain was correlated with improved shoulder abduction (r=–1.0, p<0.001), external rotation (r=–1.0, p<0.001), and spasticity of the internal rotator (r=1.0, p<0.001). Conclusion Botulinum toxin A injection into the subscapularis muscle appears to be valuable in the management of intractable hemiplegic shoulder pain. PMID:27606265

  5. Sacral Nerve Stimulation for Treatment of Chronic Intractable Anorectal Pain -A Case Report-

    PubMed Central

    Yang, Kyung Seung; Kim, Young Hoon; Park, Hue Jung; Lee, Min Hye; Kim, Dong Hee

    2010-01-01

    Despite recent methodological advancement of the practical pain medicine, many cases of the chronic anorectal pain have been intractable. A 54-year-old female patient who had a month history of a constant severe anorectal pain was referred to our clinic for further management. No organic or functional pathology was found. In spite of several modalities of management, such as medications and nerve blocks had been applied, the efficacy of such treatments was not long-lasting. Eventually, she underwent temporary then subsequent permanent sacral nerve stimulation. Her sequential numerical rating scale for pain and pain disability index were markedly improved. We report a successful management of the chronic intractable anorectal pain via permanent sacral nerve stimulation. But further controlled studies may be needed. PMID:20552076

  6. The role of TRPA1 in visceral inflammation and pain.

    PubMed

    Lapointe, Tamia K; Altier, Christophe

    2011-01-01

    Despite significant progress in our understanding of the cellular and molecular mechanisms underlying sensory transduction and nociception, clinical pain management remains a considerable challenge in health care and basic research. The identification of the superfamily of transient receptor potential (TRP) cation channels, particularly TRPV1 and TRPA1, has shed light on the molecular basis of pain signaling during inflammatory conditions. TRPV1 and TRPA1 are considered as potential targets in the treatment of inflammatory pain because of their ability to be activated by nociceptive signals and sensitized by pro-inflammatory mediators. Notably, TRPA1 is expressed in visceral afferent neurons and is known to participate in inflammatory responses and the establishment of hypersensitivity. This review summarizes the current knowledge of the role of TRPA1 in sensory transduction, particularly in the context of visceral inflammation and pain in the gastrointestinal and urinary tracts.

  7. The role of TRPA1 in visceral inflammation and pain

    PubMed Central

    Lapointe, Tamia K

    2011-01-01

    Despite significant progress in our understanding of the cellular and molecular mechanisms underlying sensory transduction and nociception, clinical pain management remains a considerable challenge in health care and basic research. The identification of the superfamily of transient receptor potential (TRP) cation channels, particularly TRPV1 and TRPA1, has shed light on the molecular basis of pain signaling during inflammatory conditions. TRPV1 and TRPA1 are considered as potential targets in the treatment of inflammatory pain because of their ability to be activated by nociceptive signals and sensitized by pro-inflammatory mediators. Notably, TRPA1 is expressed in visceral afferent neurons and is known to participate in inflammatory responses and the establishment of hypersensitivity. This review summarizes the current knowledge of the role of TRPA1 in sensory transduction, particularly in the context of visceral inflammation and pain in the gastrointestinal and urinary tracts. PMID:21993194

  8. [Controlled release hydromorphone for visceral, somatic and neuropathic pain].

    PubMed

    Alon, E; Cachin, C

    2010-03-03

    The aim of this multicentre, longitudinal investigation was to document the efficacy and tolerability profiles of controlled release hydromorphone in patients with heavy visceral, somatic or neuropathic pain under practical conditions. To this end, a prospective observational study was conducted in 57 centres in Switzerland, on a total of 196 patients. After an average of 43 days of treatment with controlled release hydromorphone, the intensity of momentary pain dropped by 46.5% and that of maximum pain dropped by 41.3%, with the efficacy of the treatment being most pronounced with visceral and somatic pain. At the same time, the prevalence of sleep disorders as a result of pain decreased from initially 86.7% to 21.0%. Controlled release hydromorphone was excellently tolerated in this group of elderly (average age 70.6 years), multimorbid pain patients receiving various medical treatments (average of 2.4 drugs in addition to pain medication), even in the voluntary long-term extension study of up to 96 days. No medical interactions were reported. Six and thirteen weeks after introducing the treatment, 89.8% and 85.2%, respectively, were still taking controlled release hydromorphone. Controlled release hydromorphone is a recommendable option for practical treatment of heavy and extremely heavy pain of various genesis.

  9. Visceral and somatic pain modalities reveal NaV 1.7-independent visceral nociceptive pathways.

    PubMed

    Hockley, James R F; González-Cano, Rafael; McMurray, Sheridan; Tejada-Giraldez, Miguel A; McGuire, Cian; Torres, Antonio; Wilbrey, Anna L; Cibert-Goton, Vincent; Nieto, Francisco R; Pitcher, Thomas; Knowles, Charles H; Baeyens, José Manuel; Wood, John N; Winchester, Wendy J; Bulmer, David C; Cendán, Cruz Miguel; McMurray, Gordon

    2017-01-20

    Voltage-gated sodium channel NaV 1.7 is required for acute and inflammatory pain in mice and humans but its significance for visceral pain is unknown. Here we examine the role of NaV 1.7 in visceral pain processing and the development of referred hyperalgesia using a conditional nociceptor-specific NaV 1.7 knockout mouse (NaV 1.7(Nav1.8) ) and selective small-molecule NaV 1.7 antagonist PF-5198007. NaV 1.7(Nav1.8) mice showed normal nociceptive behaviours to intracolonic application of either capsaicin or mustard oil, stimuli known to evoke sustained nociceptor activity and sensitization following tissue damage, respectively. Normal responses following induction of cystitis by cyclophosphamide were also observed in both NaV 1.7(Nav1.8) and littermate controls. Loss, or blockade, of NaV 1.7 did not affect afferent responses to noxious mechanical and chemical stimuli in nerve-gut preparations in mouse, or following antagonism of NaV 1.7 in resected human appendix stimulated by noxious distending pressures. However, expression analysis of voltage-gated sodium channel α subunits revealed NaV 1.7 mRNA transcripts in nearly all retrogradely-labelled colonic neurons suggesting redundancy in function. By contrast, using comparative somatic behavioral models we identify that genetic deletion of NaV 1.7 (in NaV 1.8-expressing neurons) regulates noxious heat pain threshold and that this can be recapitulated by the selective NaV 1.7 antagonist PF-5198007. Our data demonstrates that NaV 1.7 (in NaV 1.8-expressing neurons) contributes to defined pain pathways in a modality-dependent manner, modulating somatic noxious heat pain but is not required for visceral pain processing, and advocates that pharmacological block of NaV 1.7 alone in the viscera may be insufficient in targeting chronic visceral pain. This article is protected by copyright. All rights reserved.

  10. Evaluation of intrathecal drug delivery system for intractable pain in advanced malignancies

    PubMed Central

    Zheng, Shuyue; He, Liangliang; Yang, Xiaohui; Li, Xiuhua; Yang, Zhanmin

    2017-01-01

    Abstract Pain is prevalent in advanced malignancies; however, some patients cannot get adequate pain relief by conservative routes of analgesic administration or experience serious side effects related to high dose of opioids. For those who have exhausted multimodal conservative analgesic, intrathecal drug delivery is an alternative intervention for truly effective pain management. The objective of this study was to evaluate the clinical efficacy and safety of intrathecal drug delivery system (IDDS) for the treatment of intractable pain in advanced cancer patients. A prospective cohort study was performed between July 2015 and October 2016. Fifty-three patients undergoing intractable cancer-related pain or intolerable drug-related adverse effects were recruited and received IDDS therapy with a patient-controlled intrathecal analgesia pump. The assessment was conducted during admission, in titration period, and followed up monthly to death by scheduled refill visits. Pain numeric rating scale scores, comprehensive toxicity scores, quality of life scores, systemic opioid use (basal and breakthrough dose), intrathecal morphine use (basal and patient-controlled intrathecal analgesia dose), and complications were recorded to evaluate the curative effect and safety. Between baseline and all subsequent follow-ups, statistically significant decreases in pain numeric rating scale scores and comprehensive toxicity scores were verified. A statistical improvement in quality of life scores was found after starting IDDS therapy. Both basal and breakthrough doses of systemic opioid showed a significant decrease during the follow-up period. And there was a modest escalation in the intrathecal morphine dose throughout the duration of study. No infective, device-related, and catheter-related complications were observed. The findings showed that IDDS therapy allowed for rapid and highly effective pain relief with less toxicity in comparison to conservative medications. Patients with

  11. [Management of intractable cancer pain: from intrathecal morphine to cell allograft].

    PubMed

    Lazorthes, Y; Sallerin, B; Verdie, J C; Sol, J C; Duplan, H; Tkaczuk, J; Tafani, M; Bastide, R; Bes, J C

    2000-11-01

    The durable effectiveness of intrathecal morphine administration is well established for the management of intractable cancer pain, after failure of systemic opioids, secondary to the persistence of non-reversible undesirable side effects. Many patients are referred to late in the disease course. This conservative method to control pain of malignant origin must not be reserved for last resort treatment for terminal patients. Intra-cerebro-ventricular morphine administration is a very effective and generally safe method for controlling intractable cancer pain. Because of the chronic implantation of an intra-ventricular catheter this method is somewhat invasive. Its indications remain a simple and effective alternative when the topography of nociceptive pain is diffuse or cephalic. In clinical practice, intrathecal and/or intra-cerebro-ventricular administration of opioids is limited by cost, the need for specialized maintenance and mechanical malfunctions if implantable drug delivery systems, or by the risk of bacterial contamination and ambulatory constraints when repeated daily injections via an intrathecal access port are used. To answer these limitations, cell therapy using intrathecal chromaffin cell allograft is a promising approach for the management of cancer pain refractory to traditional drug therapy and pain lesion surgery. The basic rationale and preclinical studies on experimental pain models have enabled starting prospective clinical trials. Prior to transplantation, handling and preparation of the chromaffin tissue is critical for allograft viability. The initial results of clinical trials with human chromaffin cell grafts from intractable cancer pain have reported long-lasting pain relief, in correlation with met-enkephalin release into the CSF. Convincing evidence will require controlled studies. The limitations of this innovative cell therapy and especially the lack of human adrenal gland availability point to the need for new sources of cells

  12. Intractable Acute Pain Related to Fluoroquinolone-Induced Peripheral Neuropathy.

    PubMed

    Danesh, Arash; Onyima, Chiemeka; Dukewich, Matthew; Gupta, Anita

    2017-03-30

    Fluoroquinolones are widely prescribed antibiotics, used for various infectious etiologies. These antibiotics carry the possibility of the serious adverse effect of peripheral neuropathy, with a true incidence not known owing to its rare existence. Recently, the Food and Drug Administration (FDA) has required alterations to drug labels to highlight this adverse effect of fluoroquinolones. This is a case report of a single patient at an inpatient neurology service at an urban academic medical center in the United States. The patient is a 20-year-old male, with well-controlled type 1 diabetes mellitus, presenting with a short duration of bilateral lower extremity pain following a 10-day course of levofloxacin for suspected epididymitis. The patient was initially diagnosed with complex regional pain syndrome and treated with a variety of pain medications, including lidocaine infusions, hydromorphone, methadone, and ketamine infusions. After review of the patient's history and limited response to medical management, the patient's condition was reclassified as an adverse effect from fluoroquinolone treatment. Pain of unknown etiology can be perplexing, both for the physician and the patient. Reporting of similar incidents attributed to medication adverse effects will increase the awareness of this type of neuropathy, avoid future cases of misdiagnosis, and enable early detection and treatment.

  13. Transforaminal 5% phenol neurolysis for the treatment of intractable cancer pain.

    PubMed

    Candido, Kenneth D; Philip, Cyril N; Ghaly, Ramsis F; Knezevic, Nebojsa Nick

    2010-01-01

    This is the first case report of using a transforaminal approach for phenol administration. A 76-yr-old patient with a history of leiomyosarcoma and multiple metastatic lesions had unremitting pain in the right thoracic and lumbar regions and had prohibitive opioid-induced side effects. The patient underwent phenol neurolysis using a transforaminal approach in 2 stages at 3 levels (L3-4, L1-2, and T12-L1). The patient had complete resolution of pain, without any complications, and opioid treatment was nearly discontinued. Transforaminal phenol neurolysis is a reasonable treatment option for patients suffering from intractable pain for whom conventional therapies have proven ineffective.

  14. Stress-Induced Visceral Pain: Toward Animal Models of Irritable-Bowel Syndrome and Associated Comorbidities

    PubMed Central

    Moloney, Rachel D.; O’Mahony, Siobhain M.; Dinan, Timothy G.; Cryan, John F.

    2015-01-01

    Visceral pain is a global term used to describe pain originating from the internal organs, which is distinct from somatic pain. It is a hallmark of functional gastrointestinal disorders such as irritable-bowel syndrome (IBS). Currently, the treatment strategies targeting visceral pain are unsatisfactory, with development of novel therapeutics hindered by a lack of detailed knowledge of the underlying mechanisms. Stress has long been implicated in the pathophysiology of visceral pain in both preclinical and clinical studies. Here, we discuss the complex etiology of visceral pain reviewing our current understanding in the context of the role of stress, gender, gut microbiota alterations, and immune functioning. Furthermore, we review the role of glutamate, GABA, and epigenetic mechanisms as possible therapeutic strategies for the treatment of visceral pain for which there is an unmet medical need. Moreover, we discuss the most widely described rodent models used to model visceral pain in the preclinical setting. The theory behind, and application of, animal models is key for both the understanding of underlying mechanisms and design of future therapeutic interventions. Taken together, it is apparent that stress-induced visceral pain and its psychiatric comorbidities, as typified by IBS, has a multifaceted etiology. Moreover, treatment strategies still lag far behind when compared to other pain modalities. The development of novel, effective, and specific therapeutics for the treatment of visceral pain has never been more pertinent. PMID:25762939

  15. Effects of Kamishoyosan, a Traditional Japanese Kampo Medicine, on Pain Conditions in Patients with Intractable Persistent Dentoalveolar Pain Disorder

    PubMed Central

    Arai, Young-Chang P.; Makino, Izumi; Aono, Shuichi; Yasui, Hiromichi; Isai, Hideya; Nishihara, Makoto; Hatakeyama, Noboru; Kawai, Takashi; Ikemoto, Tatsunori; Inoue, Shinsuke; Ushida, Takahiro

    2015-01-01

    There are patients who suffer from persistent dentoalveolar pain disorder (PDAP) which is a pain of the teeth, either dentoalveolar pain or nonodontogenic toothache, and its cause has not yet been identified. An effective intervention for PDAP has not yet been established. Interventions for patients with PDAP are generally pharmacological treatments such as antidepressants, anticonvulsants, and pregabalin. However, these medicines are not always effective for patients. The pain disorder in the orofacial region including temporomandibular disorder (TMD) and PDAP was effectively treated with our original exercise therapy. However, we did observe some intractable cases of PDAP even when our original exercise therapy was used. This paper presents our findings in which Kamishoyosan improved the pain intensity in 14 out of 15 PDAP patients refractory to our original exercise therapy. PMID:26495024

  16. Bupivacaine administered intrathecally versus rectally in the management of intractable rectal cancer pain in palliative care

    PubMed Central

    Zaporowska-Stachowiak, Iwona; Kowalski, Grzegorz; Łuczak, Jacek; Kosicka, Katarzyna; Kotlinska-Lemieszek, Aleksandra; Sopata, Maciej; Główka, Franciszek

    2014-01-01

    Background Unacceptable adverse effects, contraindications to and/or ineffectiveness of World Health Organization step III “pain ladder” drugs causes needless suffering among a population of cancer patients. Successful management of severe cancer pain may require invasive treatment. However, a patient’s refusal of an invasive procedure necessitates that clinicians consider alternative options. Objective Intrathecal bupivacaine delivery as a viable treatment of intractable pain is well documented. There are no data on rectal bupivacaine use in cancer patients or in the treatment of cancer tenesmoid pain. This study aims to demonstrate that bupivacaine administered rectally could be a step in between the current treatment options for intractable cancer pain (conventional/conservative analgesia or invasive procedures), and to evaluate the effect of the mode of administration (intrathecal versus rectal) on the bupivacaine plasma concentration. Cases We present two Caucasian, elderly inpatients admitted to hospice due to intractable rectal/tenesmoid pain. The first case is a female with vulvar cancer, and malignant infiltration of the rectum/vagina. Bupivacaine was used intrathecally (0.25–0.5%, 1–2 mL every 6 hours). The second case is a female with ovarian cancer and malignant rectal infiltration. Bupivacaine was adminstered rectally (0.05–0.1%, 100 mL every 4.5–11 hours). Methods Total bupivacaine plasma concentrations were determined using the high-performance liquid chromatography-ultraviolet method. Results Effective pain control was achieved with intrathecal bupivacaine (0.077–0.154 mg·kg−1) and bupivacaine in enema (1.820 mg·kg−1). Intrathecal bupivacaine (0.5%, 2 mL) caused a drop in blood pressure; other side effects were absent in both cases. Total plasma bupivacaine concentrations following intrathecal and rectal bupivacaine application did not exceed 317.2 ng·mL−1 and 235.7 ng·mL−1, respectively. Bupivacaine elimination was

  17. Chronic Visceral Right Upper Quadrant Pain Without Gallstones.

    PubMed

    Shrestha, Sanjeeb; Pasricha, Pankaj J.

    2001-04-01

    Patients with chronic visceral right upper quadrant pain without gallstones can be broadly categorized into two groups: patients with gallbladder dyskinesia, and patients with sphincter of Oddi dysfunction (SOD). Treating patients with these disorders is often challenging to clinicians due to the difficulty at arriving at a definite diagnosis, and the lack of efficacy of various treatment modalities. The only real treatment option for patients with gallbladder dyskinesia is cholecystectomy; however, the results are difficult to predict in an individual patient. Patients with SOD can be approached according to a classification that at least partially reflects the underlying pathophysiology. Patients with type I SOD have underlying papillary stenosis, and benefit from empiric sphincterotomy. Patients with type II SOD may have muscle spasm as predominant pathophysiology; this group of patients benefit from sphincterotomy only if increased sphincter pressure is demonstrated by sphincter of Oddi manometry. Patients with type III SOD may have visceral hyperalgesia; a trial of antidepressants or a therapeutic trial with botulinum toxin injection into the ampulla should be considered prior to more invasive endoscopic therapy.

  18. Involvement of metabotropic glutamate 5 receptor in visceral pain.

    PubMed

    Lindström, Erik; Brusberg, Mikael; Hughes, Patrick A; Martin, Christopher M; Brierley, Stuart M; Phillis, Benjamin D; Martinsson, Rakel; Abrahamsson, Christina; Larsson, Håkan; Martinez, Vicente; Blackshaw, L Ashley

    2008-07-15

    Metabotropic glutamate 5 receptor (mGluR5) antagonists are effective in animal models of inflammatory and neuropathic pain. The involvement of mGluR5 in visceral pain pathways from the gastrointestinal tract is as yet unknown. We evaluated effects of mGluR5 antagonists on the colorectal distension (CRD)-evoked visceromotor (VMR) and cardiovascular responses in conscious rats, and on mechanosensory responses of mouse colorectal afferents in vitro. Sprague-Dawley rats were subjected to repeated, isobaric CRD (12 x 80 mmHg, for 30s with 5 min intervals). The VMR and cardiovascular responses to CRD were monitored. The mGluR5 antagonists MPEP (1-10 micromol/kg, i.v.) and MTEP (1-3 micromol/kg, i.v.) reduced the VMR to CRD dose-dependently with maximal inhibition of 52+/-8% (p<0.01) and 25+/-11% (p<0.05), respectively, without affecting colonic compliance. MPEP (10 micromol/kg, i.v.) reduced CRD-evoked increases in blood pressure and heart rate by 33+/-9% (p<0.01) and 35+/-8% (p<0.05), respectively. Single afferent recordings were made from mouse pelvic and splanchnic nerves of colorectal mechanoreceptors. Circumferential stretch (0-5 g force) elicited slowly-adapting excitation of action potentials in pelvic distension-sensitive afferents. This response was reduced 55-78% by 10 microM MTEP (p<0.05). Colonic probing (2g von Frey hair) activated serosal splanchnic afferents; their responses were reduced 50% by 10 microM MTEP (p<0.01). We conclude that mGluR5 antagonists inhibit CRD-evoked VMR and cardiovascular changes in conscious rats, through an effect, at least in part, at peripheral afferent endings. Thus, mGluR5 participates in mediating mechanically evoked visceral nociception in the gastrointestinal tract.

  19. [Selection of drugs suitable for the treatment of intractable chronic pain patients by using drug challenge tests].

    PubMed

    Hanaoka, Kazuo; Arita, Hideko; Nagase, Masaki; Ide, Yasuo; Tagami, Megumi; Hayashida, Masakazu

    2008-05-01

    Intractable chronic pain is very difficult to treat. Nowadays, small amounts of drugs, that have different actions on the mechanism of pain relief are administered intravenously, and the effects of the test drugs on individual chronic pain patients are investigated by using the evaluation method of the visual analogue scale (VAS). This will enable elucidation of the mechanisms of pain in each chronic pain patient. Based on this information, drugs that are effective for the treatment of individual chronic pain patients can be prescribed. Drugs that are used for the drug challenge tests are phentolamine, barbiturate, morphine, lidocaine, ketamine, benzodiazepine, adenosine-3-phosphate (ATP), neurotropine, and prostaglandine E1. Phentolamine is effective for the management of sympathetically maintained pain. Barbiturate and morphine are effective for the treatment of deafferentation pain and nociceptive pain, respectively. Lidocaine is effective for the treatment of neuropathic pain; ketamine, for allodynia; and benzodiazepine, for anxiety-related pain. ATP exerts a positive effect in total pain management. Neurotropine and prostaglandine E1 are effective for the management of neuropathic pain and ischemic pain, respectively. These tests aid in the selection of drugs that maybe useful for the treatment of intractable chronic pain in patients.

  20. Long term follow-up results of dorsal root entry zone lesions for intractable pain after brachial plexus avulsion injuries.

    PubMed

    Chen, H J; Tu, Y K

    2006-01-01

    Brachial plexus avulsion injury is one of the major complications after traffic, especially motorcycle accidents and machine injuries. Intractable pain and paralysis of the affected limbs are the major neurological deficits. During the past 18 years, we have encountered and treated more than 500 cases with brachial plexus avulsion injuries. Dorsal root entry zone lesions (DREZ) made by thermocoagulation were performed for intractable pain in 60 cases. Forty cases were under regular follow-up for 5-18 years. In early postoperative stage, the pain relief rate was excellent or good in 32 cases (80%). The pain relief rate dropped to 60% in 5 year follow-up period and only 9 cases (50%) had excellent or good result in 10 year follow-up. Reconstructive procedures were performed in almost all patients in the last 10 years. Dorsal root entry zone lesion is an effective procedure for pain control after brachial plexus avulsion injuries.

  1. Clinical approach to visceral pain in irritable bowel syndrome - pathophysiology, symptoms, and treatment.

    PubMed

    Prystupa, Andrzej; Mróz, Tomasz; Wojciechowska, Katarzyna; Mróz, Katarzyna; Prystupa, Tomasz; Nowicki, Grzegorz; Załuska, Wojciech; Filip, Rafał

    2013-01-01

    Visceral pain has been defined as a pain resulting from activation of pain receptors localized in mucous membrane, serous membrane, and smooth muscles of hollow organs. The great majority of these organs are innervated by parasympathetic and sympathetic outflows. Afferent nerve fibres are involved in conduction of both acute and persistent pain and hyperalgesia. Visceral pain differs significantly from other types of pain in the way it originates and in clinical presentation. It can be misleading as a symptom, producing several problems in the diagnostic process. Sometimes, severe visceral pain is observed in the course of non-lifethreatening functional gastrointestinal disorders, while slight abdominal discomfort may be a first symptom of malignant tumours. For many years, the treatment of visceral pain has been considered as not satisfactory enough and covered a wide variety of pharmacological substances. For example, the complex therapy of pain and other manifestations associated with irritable bowel syndrome include psychotherapy/behavioural therapy, bulk-forming agents, probiotics, laxatives, antidiarrheals, antibacterial agents, antispasmodics, and antidepressants. The current knowledge about the pathogenesis of visceral pain gives a rationale for the development of new, more efficacious drugs with a positive benefit/risk ratio. Unfortunately, experience gained so far with the use of some agents affecting serotoninergic transmission in the gastrointestinal tract have shown a serious danger associated with their administration for patients with irritable bowel syndrome.

  2. Spinal Cauda Equina Stimulation for Alternative Location of Spinal Cord Stimulation in Intractable Phantom Limb Pain Syndrome: A Case Report.

    PubMed

    Lee, Pil Moo; So, Yun; Park, Jung Min; Park, Chul Min; Kim, Hae Kyoung; Kim, Jae Hun

    2016-04-01

    Phantom limb pain is a phenomenon in which patients experience pain in a part of the body that no longer exists. In several treatment modalities, spinal cord stimulation (SCS) has been introduced for the management of intractable post-amputation pain. A 46-year-old male patient complained of severe ankle and foot pain, following above-the-knee amputation surgery on the right side amputation surgery three years earlier. Despite undergoing treatment with multiple modalities for pain management involving numerous oral and intravenous medications, nerve blocks, and pulsed radiofrequency (RF) treatment, the effect duration was temporary and the decreases in the patient's pain score were not acceptable. Even the use of SCS did not provide completely satisfactory pain management. However, the trial lead positioning in the cauda equina was able to stimulate the site of the severe pain, and the patient's pain score was dramatically decreased. We report a case of successful pain management with spinal cauda equina stimulation following the failure of SCS in the treatment of intractable phantom limb pain.

  3. Glial contributions to visceral pain: implications for disease etiology and the female predominance of persistent pain

    PubMed Central

    Dodds, K N; Beckett, E A H; Evans, S F; Grace, P M; Watkins, L R; Hutchinson, M R

    2016-01-01

    In the central nervous system, bidirectional signaling between glial cells and neurons (‘neuroimmune communication') facilitates the development of persistent pain. Spinal glia can contribute to heightened pain states by a prolonged release of neurokine signals that sensitize adjacent centrally projecting neurons. Although many persistent pain conditions are disproportionately common in females, whether specific neuroimmune mechanisms lead to this increased susceptibility remains unclear. This review summarizes the major known contributions of glia and neuroimmune interactions in pain, which has been determined principally in male rodents and in the context of somatic pain conditions. It is then postulated that studying neuroimmune interactions involved in pain attributed to visceral diseases common to females may offer a more suitable avenue for investigating unique mechanisms involved in female pain. Further, we discuss the potential for primed spinal glia and subsequent neurogenic inflammation as a contributing factor in the development of peripheral inflammation, therefore, representing a predisposing factor for females in developing a high percentage of such persistent pain conditions. PMID:27622932

  4. Phenytoin (Dilantin) and acupuncture therapy in the treatment of intractable oral and facial pain.

    PubMed

    Lu, Dominic P; Lu, Winston I; Lu, Gabriel P

    2011-01-01

    Phenytoin is an anti-convulsant and anti-arrhythmic medication. Manufactured by various pharmaceutical companies with various brand names, phenytoin (PHT) is also known as Dilantain, Hydantoin or Phenytek in the United States; Dilantain or Remytoine in Canada; Epamin, Hidantoina in Mexico; and Fenidatoin or Fenitron or other names elsewhere in the world. Phenytoin (PHT) is especially useful for patients suffering from intractable oral and facial pain especially those who exhibit anger, stress, depression and irrational emotions commonly seen in the patients with oral and facial pain. When used properly, Phenytoin is also an effective anxiolysis drug in addition to its theraputic effects on pain and can be used alone or, even better, if combined with other compatible sedatives. Phenytoin is particularly valuable when combined with acupuncture for patients with trigeminal neuralgia, glossopharyneal neuralgia, Bell's palsy, and some other facial paralysis and pain. It also has an advantage of keeping the patient relatively lucid after treatment. Either PHT or acupuncture alone can benefit patients but the success of treatment outcome may be limited. We found by combining both acupuncture and PHT with Selective Drug Uptake Enhancement by stimulating middle finger at the first segment of ventral (palmar) and lateral surfaces, as well as prescribing PHT with the dosage predetermined for each patient by Bi-Digital O-Ring Test (BDORT), the treatment outcome was much better resulted with less recurrence and intensity of pain during episodes of attack. Patients with Bell's palsy were most benefited by acupuncture therapy that could completely get rid of the illness.

  5. Spinal cord stimulation for intractable chronic upper abdominal pain: a case report of the first patient in New Zealand.

    PubMed

    Al-Mahrouqi, Haitham; Munro, Zea; Acland, Richard H; MacFarlane, Martin R

    2012-12-14

    We present the first patient in New Zealand to undergo Spinal Cord Stimulation (SCS) for intractable upper abdominal pain. The patient was a 53-year-old man with a 20-year history of debilitating upper abdominal pain associated with chronic pancreatitis secondary to pancreatic divisum. Prior to the SCS, he was prescribed 680 mg of morphine sulphate equi-analgesia a day. Despite the intense analgesia, he still suffered monthly attacks of upper abdominal pain requiring hospitalisation. Nine months after implanting a Spinal Cord Stimulator, the monthly attacks ceased, his background pain was effectively controlled and the need for opioids decreased to 510 mg of morphine sulphate equi-analgesia a day.

  6. Neurobiological Mechanism of Acupuncture for Relieving Visceral Pain of Gastrointestinal Origin

    PubMed Central

    Zhao, Jimeng

    2017-01-01

    It is currently accepted that the neural transduction pathways of gastrointestinal (GI) visceral pain include the peripheral and central pathways. Existing research on the neurological mechanism of electroacupuncture (EA) in the treatment of GI visceral pain has primarily been concerned with the regulation of relevant transduction pathways. The generation of pain involves a series of processes, including energy transduction of stimulatory signals in the sensory nerve endings (signal transduction), subsequent conduction in primary afferent nerve fibers of dorsal root ganglia, and transmission to spinal dorsal horn neurons, the ascending transmission of sensory signals in the central nervous system, and the processing of sensory signals in the cerebral cortex. Numerous peripheral neurotransmitters, neuropeptides, and cytokines participate in the analgesic process of EA in visceral pain. Although EA has excellent efficacy in the treatment of GI visceral pain, the pathogenesis of the disease and the analgesic mechanism of the treatment have not been elucidated. In recent years, research has examined the pathogenesis of GI visceral pain and its influencing factors and has explored the neural transduction pathways of this disease. PMID:28243252

  7. High-Level Cervical Spinal Cord Stimulation Used to Treat Intractable Pain Arising from Transverse Myelitis Caused by Schistosomiasis

    PubMed Central

    Kim, Jin Kyung; Hong, Seok Ho

    2010-01-01

    The efficacy of spinal cord stimulation (SCS) for treatment of various chronic painful conditions is well established. Very few reports have documented the use of SCS for treatment of chronic pain after spinal cord injury. We present a case showing a good outcome after such treatment, and suggest that high cervical stimulation may be efficacious. A 53-year-old male underwent SCS on the C1-3 level for treatment of intractable neuropathic pain below the T3 level, and in the upper extremities, arising from spinal cord injury resulting from transverse myelitis caused by schistosomiasis. High cervical SCS significantly improved the pain in the upper extremities and at the T3-T10 dermatome level. The patient continues to report excellent pain relief 9 months later. The present case suggests that high cervical stimulation may improve chronic pain in the upper extremities and the T3-T10 dermatome level arising from spinal cord injury. PMID:20224718

  8. Stress and the Microbiota-Gut-Brain Axis in Visceral Pain: Relevance to Irritable Bowel Syndrome.

    PubMed

    Moloney, Rachel D; Johnson, Anthony C; O'Mahony, Siobhain M; Dinan, Timothy G; Greenwood-Van Meerveld, Beverley; Cryan, John F

    2016-02-01

    Visceral pain is a global term used to describe pain originating from the internal organs of the body, which affects a significant proportion of the population and is a common feature of functional gastrointestinal disorders (FGIDs) such as irritable bowel syndrome (IBS). While IBS is multifactorial, with no single etiology to completely explain the disorder, many patients also experience comorbid behavioral disorders, such as anxiety or depression; thus, IBS is described as a disorder of the gut-brain axis. Stress is implicated in the development and exacerbation of visceral pain disorders. Chronic stress can modify central pain circuitry, as well as change motility and permeability throughout the gastrointestinal (GI) tract. More recently, the role of the gut microbiota in the bidirectional communication along the gut-brain axis, and subsequent changes in behavior, has emerged. Thus, stress and the gut microbiota can interact through complementary or opposing factors to influence visceral nociceptive behaviors. This review will highlight the evidence by which stress and the gut microbiota interact in the regulation of visceral nociception. We will focus on the influence of stress on the microbiota and the mechanisms by which microbiota can affect the stress response and behavioral outcomes with an emphasis on visceral pain.

  9. Glutamatergic activation of anterior cingulate cortex mediates the affective component of visceral pain memory in rats.

    PubMed

    Yan, Ni; Cao, Bing; Xu, Jiahe; Hao, Chun; Zhang, Xu; Li, Ying

    2012-01-01

    Studies of both humans and animals suggest that anterior cingulate cortex (ACC) is important for processing pain perception. We identified that perigenul ACC (pACC) sensitization and enhanced visceral pain in a visceral hypersensitive rat in previous studies. Pain contains both sensory and affective dimensions. Teasing apart the mechanisms that control the neural pathways mediating pain affect and sensation in nociceptive behavioral response is a challenge. In this study, using a rodent visceral pain assay that combines the colorectal distension (CRD)-induced visceromotor response (VMR) with the conditioning place avoidance (CPA), we measured a learned behavior that directly reflects the affective component of visceral pain. When CRD was paired with a distinct environment context, the rats spent significantly less time in this compartment on the post-conditioning test days as compared with the pre-conditioning day. Effects were lasted for 14 days. Bilateral pACC lesion significantly reduced CPA scores without reducing acute visceral pain behaviors (CRD-induced VMR). Bilateral administration of non-NMDA receptor antagonist CNQX or NMDA receptor antagonist AP5 into the pACC decreased the CPA scores. AP5 or CNQX at dose of 400 mM produced about 70% inhibition of CRD-CPA in the day 1, 4 and 7, and completely abolished the CPA in the day 14 after conditioning. We concluded that neurons in the pACC are necessary for the "aversiveness" of visceral nociceptor stimulation. pACC activation is critical for the memory processing involved in long-term negative affective state and prediction of aversive stimuli by contextual cue.

  10. Exploring relationships for visceral and somatic pain with autonomic control and personality.

    PubMed

    Paine, Peter; Kishor, Jessin; Worthen, Sian F; Gregory, Lloyd J; Aziz, Qasim

    2009-08-01

    The autonomic nervous system (ANS) integrates afferent and motor activity for homeostatic processes including pain. The aim of the study was to compare hitherto poorly characterised relations between brainstem autonomic control and personality in response to visceral and somatic pain. Eighteen healthy subjects (16 females, mean age 34) had recordings during rest and pain of heart rate (HR), cardiac vagal tone (CVT), cardiac sensitivity to baroreflex (CSB), skin conductance level (SC), cardiac sympathetic index (CSI) and mean blood pressure (MBP). Visceral pain was induced by balloon distension in proximal (PB) and distal (DB) oesophagus and somatic pain by nail-bed pressure (NBP). Eight painful stimuli were delivered at each site and unpleasantness and intensity measured. Personality was profiled with the Big Five inventory. (1) Oesophageal intubation evoked "fight-flight" responses: HR and sympathetic (CSI, SC, MBP) elevation with parasympathetic (CVT) withdrawal (p<0.05). (2) Pain at all sites evoked novel parasympathetic/sympathetic co-activation with elevated HR but vasodepression (all p<0.05). (3) Personality traits correlated with slope of distal oesophageal pain-related CVT changes wherein more neurotic-introvert subjects had greater positive pain-related CVT slope change (neuroticism r 0.8, p<0.05; extroversion r -0.5, p<0.05). Pain-evoked heart rate increases were mediated by parasympathetic and sympathetic co-activation - a novel finding in humans but recently described in mammals too. Visceral pain-related parasympathetic change correlated with personality. ANS defence responses are nuanced and may relate to personality type for visceral pain. Clinical relevance of these findings warrants further exploration.

  11. Effective management of intractable neuropathic pain using an intrathecal morphine pump in a patient with acute transverse myelitis.

    PubMed

    Wu, Wei-Ting; Huang, Yu-Hui; Chen, Der-Cherng; Huang, Yu-Hsuan; Chou, Li-Wei

    2013-01-01

    Transverse myelitis is a rare inflammatory myelopathy characterized by loss of motor and sensory function below the affected level of the spinal cord, and causes neurogenic bowel and bladder. Occasionally, it also causes neuropathic pain with spasticity. Traditional therapies for neuropathic pain are multiple, including multimodal analgesic regimens, antiepileptic or antidepressant medications, opioids, sympathetic blocks, and spinal cord stimulation. Persistent neuropathic pain can cause emotional distress by affecting sleep, work, recreation, and emotional well-being. Here we report the case of a patient suffering from intractable neuropathic pain following acute transverse myelitis that was not relieved by combinations of nonsteroidal anti-inflammatory, anti-epileptic, antidepressant, and opioid medications, or by acupuncture. Implantation of an intrathecal morphine pump controlled the pain successfully without side effects, and enabled the patient to embark on intensive rehabilitation. The patient's muscle strength has improved significantly and the patient may soon be able to use a walker with minimal assistance.

  12. Effective management of intractable neuropathic pain using an intrathecal morphine pump in a patient with acute transverse myelitis

    PubMed Central

    Wu, Wei-Ting; Huang, Yu-Hui; Chen, Der-Cherng; Huang, Yu-Hsuan; Chou, Li-Wei

    2013-01-01

    Transverse myelitis is a rare inflammatory myelopathy characterized by loss of motor and sensory function below the affected level of the spinal cord, and causes neurogenic bowel and bladder. Occasionally, it also causes neuropathic pain with spasticity. Traditional therapies for neuropathic pain are multiple, including multimodal analgesic regimens, antiepileptic or antidepressant medications, opioids, sympathetic blocks, and spinal cord stimulation. Persistent neuropathic pain can cause emotional distress by affecting sleep, work, recreation, and emotional well-being. Here we report the case of a patient suffering from intractable neuropathic pain following acute transverse myelitis that was not relieved by combinations of nonsteroidal anti-inflammatory, anti-epileptic, antidepressant, and opioid medications, or by acupuncture. Implantation of an intrathecal morphine pump controlled the pain successfully without side effects, and enabled the patient to embark on intensive rehabilitation. The patient’s muscle strength has improved significantly and the patient may soon be able to use a walker with minimal assistance. PMID:23935366

  13. Amygdala activation by corticosterone alters visceral and somatic pain in cycling female rats.

    PubMed

    Gustafsson, Jenny K; Greenwood-Van Meerveld, Beverley

    2011-06-01

    Irritable bowel syndrome (IBS) is often seen in women, and symptom severity is known to vary over the menstrual cycle. In addition, activation of the hypothalamic-pituitary-adrenal (HPA) axis enhances symptomology and patients with IBS have increased activation of the amygdala, a brain region known to facilitate HPA output. However, little is known about the effects of amygdala activation during different stages of the menstrual cycle. We therefore investigated the effects of amygdala activation on somatic and visceral pain perception over the rat estrous cycle. Female Wistar rats were implanted with either corticosterone (Cort) or cholesterol as a control onto the dorsal margin of the central amygdala. Visceral sensitivity was quantified by recording the visceromotor response (VMR) to colorectal distension (CRD) and somatic sensitivity was assessed via the Von Frey test. In cholesterol controls, both visceral and somatic sensitivity varied over the estrous cycle. Rats in proestrus/estrus responded to CRD with an increased VMR compared with rats in metestrus/diestrus. Somatic sensitivity followed a similar pattern with enhanced sensitivity during proestrus/estrus compared with metestrus/diestrus. Elevated amygdala Cort induced visceral hypersensitivity during metestrus/diestrus but had no effect during proestrus/estrus. In contrast, elevated amygdala Cort increased somatic sensitivity during both metestrus/diestrus and proestrus/estrous. These results suggests that amygdala activation by Cort eliminates spontaneously occurring differences in visceral and somatic pain perception, which could explain the lowered pain thresholds and higher incidence of somatic pain observed in women with IBS.

  14. Chronic Stress and Peripheral Pain: Evidence for Distinct, Region-specific Changes in Visceral and Somatosensory Pain Regulatory Pathways

    PubMed Central

    Zheng, Gen; Hong, Shuangsong; Hayes, John M; Wiley, John W

    2015-01-01

    Chronic stress alters the hypothalamic-pituitary-adrenal (HPA) axis and enhances visceral and somatosensory pain perception. It is unresolved whether chronic stress has distinct effects on visceral and somatosensory pain regulatory pathways. Previous studies reported that stress-induced visceral hyperalgesia is associated with reciprocal alterations of endovanilloid and endocannabinoid pain pathways in DRG neurons innervating the pelvic viscera. In this study, we compared somatosensory and visceral hyperalgesia with respect to differential responses of peripheral pain regulatory pathways in a rat model of chronic, intermittent stress. We found that chronic stress induced reciprocal changes in the endocannabinoid 2-AG (increased) and endocannabinoid degradation enzymes COX-2 and FAAH (decreased), associated with down-regulation of CB1 and up-regulation of TRPV1 receptors in L6-S2 DRG but not L4-L5 DRG neurons. In contrast, sodium channels Nav1.7 and Nav1.8 were up-regulated in L4-L5 but not L6-S2 DRGs in stressed rats, which was reproduced in control L4-L5 DRGs treated with corticosterone in vitro. The reciprocal changes of CB1, TRPV1 and sodium channels were cell-specific and observed in the sub-population of nociceptive neurons. Behavioral assessment showed that visceral hyperalgesia persisted, whereas somatosensory hyperalgesia and enhanced expression of Nav1.7 and Nav1.8 sodium channels in L4-L5 DRGs normalized 3 days after completion of the stress phase. These data indicate that chronic stress induces visceral and somatosensory hyperalgesia that involves differential changes in endovanilloid and endocannabinoid pathways, and sodium channels in DRGs innervating the pelvic viscera and lower extremities. These results suggest that chronic stress-induced visceral and lower extremity somatosensory hyperalgesia can be treated selectively at different levels of the spinal cord. PMID:26408049

  15. Mild social stress in mice produces opioid-mediated analgesia in visceral but not somatic pain states.

    PubMed

    Pitcher, M H; Gonzalez-Cano, R; Vincent, K; Lehmann, M; Cobos, E J; Coderre, T J; Baeyens, J M; Cervero, F

    2017-02-17

    Visceral pain has a greater emotional component than somatic pain. To determine if the stress-induced analgesic response is differentially expressed in visceral versus somatic pain states, we studied the effects of a mild social stressor in either acute visceral or somatic pain states in mice. We show that the presence of an unfamiliar conspecific (stranger) in an adjacent cubicle of a standard transparent observation box produced elevated plasma corticosterone levels compared to mice tested alone, suggesting that the mere presence of a stranger is stressful. We then observed noxious visceral or somatic stimulation-induced nociceptive behavior in mice tested alone or under mildly stressful conditions (i.e. beside an unfamiliar stranger). Compared to mice tested alone, the presence of a stranger produced a dramatic opioid-dependent reduction in pain behavior associated with visceral but not somatic pain. This social stress-induced reduction of visceral pain behavior relied on visual but not auditory/olfactory cues. These findings suggest that visceral pain states may provoke heightened responsiveness to mild stressors, an effect that could interfere with testing outcomes during simultaneous behavioral testing of multiple rodents.

  16. Intradural approach to selective stimulation in the spinal cord for treatment of intractable pain: design principles and wireless protocol

    NASA Astrophysics Data System (ADS)

    Howard, M. A.; Utz, M.; Brennan, T. J.; Dalm, B. D.; Viljoen, S.; Jeffery, N. D.; Gillies, G. T.

    2011-08-01

    We introduce an intradural approach to spinal cord stimulation for the relief of intractable pain, and describe the biophysical rationale that underlies its design and performance requirements. The proposed device relies on wireless, inductive coupling between a pial surface implant and its epidural controller, and we present the results of benchtop experiments that demonstrate the ability to transmit and receive a frequency-modulated 1.6 MHz carrier signal between micro-coil antennae scaled to the ≈ 1 cm dimensions of the implant, at power levels of about 5 mW. Plans for materials selection, microfabrication, and other aspects of future development are presented and discussed.

  17. A New Perspective of Neuromyopathy to Explain Intractable Pancreatic Cancer Pains; Dry Needling as an Effective Adjunct to Neurolytic Blocks

    PubMed Central

    Vas, Lakshmi; Phanse, Sushama; Pai, Renuka

    2016-01-01

    We present a new perspective of neuromyopathy in pancreatic cancer pain (PCP) referral to bodywall; proposal of new rationale to include ultrasound guided dry needling (USGDN) of body wall muscles as an effective adjunct to neurolytic coeliac plexus block (NCPB) or splanchnic nerve radiofrequency ablation (SRF) for comprehensive interventional management. Methods: PCP response to SRF in 2 patients and NCPB in 3 patients was documented on numerical rating scale (NRS) on post procedure days 3 and 15. If the residual pain was >5 NRS on day 15, USGDN of abdominal and back muscles was started on a thrice weekly basis. The response to USGDN documented on day 30 after approximately 6 sessions of DN, showed a significant pain reduction (0-2 NRS) with 50% reduction of pre-treatment opioid consumption. This was sustained at 6 months or till their demise. Convergence of visceral and somatic nerves at the dorsal horn (viscerosomatic neurons) causes referral of visceral pain to the back and abdominal muscles. This leads to formation of myofascial trigger points (MTrPs) in the muscles which sets up a parallel network of sensitized peripheral and central motor nociceptive processing (neuromyopathy). USGDN specifically addressed the MTrPs that develop as an epiphenomenon of self-perpetuating neuromyopathy while SRF/NCPB, analgesics and neuromodulators could address only visceral nociceptive afferents (pain mediated through celiac plexus) which forms a meagre 10% of the total spinal cord afferent input. Thus, we conclude that combination of neuromyopathy and viscerosomatic convergence in PCP indicate a specific role for DN as an adjunct to SRF/NCPB in our patients PMID:26962286

  18. Trigeminal nerve block with alcohol for medically intractable classic trigeminal neuralgia: long-term clinical effectiveness on pain

    PubMed Central

    Han, Kyung Ream; Chae, Yun Jeong; Lee, Jung Dong; Kim, Chan

    2017-01-01

    Background: Trigeminal nerve block (Tnb) with alcohol for trigeminal neuralgia (TN) may not be used widely as a percutaneous procedure for medically intractable TN in recent clinical work, because it has been considered having a limited duration of pain relief, a decrease in success rate and increase in complications on repeated blocks. Objectives: To evaluate the clinical outcome of the Tnb with alcohol in the treatment of medically intractable TN. Methods: Six hundred thirty-two patients were diagnosed with TN between March 2000 and February 2010. Four hundred sixty-five out of 632 underwent Tnb with alcohol under a fluoroscope. Pain relief duration were analyzed and compared in the individual branch blocks. Outcomes were compared between patients with and without a previous Tnb with alcohol. Results: Tnb with alcohol were performed in a total 710 (1st-465, 2nd-155, 3rd-55, 4th-23, 5th-8, 6th-4) cases for a series of consecutive 465 patients during the study period. Forty hundred sixty two out of the 465 patients experienced immediate complete pain relief (99%) at the first Tnb. Of the 465 patients, 218 patients (46.9%) did not require any further treatment after the first Tnb with alcohol during an entire study period. One hundred fifty nine (34.2 %) out of the 465 patients experienced recurring pain after the first block, among whom 155 patients received subsequent blocks, and the remaining 4 patients decided to take medication. According to the Kaplan-Meier analysis, the probabilities of remaining pain relief for 1, 2, 3, and 5 years after the procedures were 86.2%, 65.5%, 52.5%, and 33.4%, respectively. There was no significant difference in the probability of pain relief duration between patients with and without previous Tnb with alcohol. Median (95% CI) pain relief durations of the first and repeated blocks were 39 (36-51) and 37 (28-54) months, respectively. There was no significant difference in occurrence of complications between patients with and

  19. Cross-sectional study of alteration of phantom limb pain with visceral stimulation in military personnel with amputation.

    PubMed

    Rafferty, Michael; Bennett Britton, Thomas M; Drew, Benjamin T; Phillip, Rhodri D

    2015-01-01

    While phantom limb pain is a well-recognized phenomenon, clinical experience has suggested that the augmentation of phantom limb pain with visceral stimulation is an issue for many military personnel with amputation (visceral stimulation being the sensation of the bowel or bladder either filling or evacuating). However, the prevalence of this phenomenon is not known. The aim of this study was to investigate the prevalence of the alteration in phantom limb pain and the effect that visceral stimulation has on phantom limb pain intensity. A cross-sectional study of 75 military personnel who have lost one or both lower limbs completed a questionnaire to assess the prevalence of the alteration of phantom limb pain with visceral stimulation. Included in the questionnaire was a pain visual analog scale (VAS) graded from 0 to 10. Patients recorded the presence and intensity of phantom limb pain. They also recorded whether and how this pain altered with a need to micturate or micturition, and/or a need to defecate or defecation, again using a pain VAS. Time since amputation, level of amputation, and medications were also recorded. Patients reported a phantom limb pain prevalence of 85% with a mean VAS of 3.6. In all, 56% of patients reported a change in the severity of phantom limb pain with visceral stimuli. The mean increase in VAS for visceral stimulation was 2.5 +/- 1.6 for bladder stimulation and 2.9 +/- 2.0 for bowel stimulation. Of the patients questioned, 65% reported an improvement in symptoms over time. VAS scores were highest in the subgroup less than 6 mo postamputation. An increase in phantom limb pain with visceral stimulation is a common problem for military personnel with amputation.

  20. Transient receptor potential ankyrin-1 has a major role in mediating visceral pain in mice.

    PubMed

    Cattaruzza, Fiore; Spreadbury, Ian; Miranda-Morales, Marcela; Grady, Eileen F; Vanner, Stephen; Bunnett, Nigel W

    2010-01-01

    The excitatory ion channel transient receptor potential ankyrin-1 (TRPA1) is prominently expressed by primary afferent neurons and is a mediator of inflammatory pain. Inflammatory agents can directly activate [e.g., hydroxynonenal (HNE), prostaglandin metabolites] or indirectly sensitize [e.g., agonists of protease-activated receptor (PAR(2))] TRPA1 to induce somatic pain and hyperalgesia. However, the contribution of TRPA1 to visceral pain is unknown. We investigated the role of TRPA1 in visceral hyperalgesia by measuring abdominal visceromotor responses (VMR) to colorectal distention (CRD) after intracolonic administration of TRPA1 agonists [mustard oil (MO), HNE], sensitizing agents [PAR(2) activating peptide (PAR(2)-AP)], and the inflammatory agent trinitrobenzene sulfonic acid (TNBS) in trpa1(+/+) and trpa1(-/-) mice. Sensory neurons innervating the colon, identified by retrograde tracing, coexpressed immunoreactive TRPA1, calcitonin gene-related peptide, and substance P, expressed TRPA1 mRNA and responded to MO with depolarizing currents. Intracolonic MO and HNE increased VMR to CRD and induced immunoreactive c-fos in spinal neurons in trpa1+/+ but not in trpa1(-/-) mice. Intracolonic PAR(2)-AP induced mechanical hyperalgesia in trpa1+/+ but not in trpa1(-/-) mice. TNBS-induced colitis increased in VMR to CRD and induced c-fos in spinal neurons in trpa1(+/+) but not in trpa1(-/-) mice. Thus TRPA1 is expressed by colonic primary afferent neurons. Direct activation of TRPA1 causes visceral hyperalgesia, and TRPA1 mediates PAR(2)-induced hyperalgesia. TRPA1 deletion markedly reduces colitis-induced mechanical hyperalgesia in the colon. Our results suggest that TRPA1 has a major role in visceral nociception and may be a therapeutic target for colonic inflammatory pain.

  1. Divergent effects of amygdala glucocorticoid and mineralocorticoid receptors in the regulation of visceral and somatic pain.

    PubMed

    Myers, Brent; Greenwood-Van Meerveld, Beverley

    2010-02-01

    Elevated amygdala activity and increased responsiveness of the hypothalamic-pituitary-adrenal axis have been observed in irritable bowel syndrome (IBS) patients. Recently, we demonstrated that corticosterone (Cort) placed on the amygdala induced anxiety-like behavior coupled with decreased thresholds for visceral and somatic pain in rats. Moreover, these studies suggested that the effects of Cort were dependent on both the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR); however, the specific contributions of these receptors to the interaction between corticosteroids and the amygdala are still unclear. In the present study, we sought to define the distinct roles of amygdaloid GR and MR in anxiety-like behavior, visceral sensitivity, and somatic sensitivity through selective pharmacological activation. Male Fischer 344 rats received bilateral implants on the dorsal margin of the central amygdala containing the GR agonist dexamethasone (Dex), the MR agonist aldosterone (Aldo), or cholesterol as a control. Our results showed that GR or MR activation significantly reduced open arm exploration on the elevated plus maze, a measure of anxiety-like behavior. Aldo increased the number of abdominal muscle contractions in response to all levels of colorectal distension (CRD). In contrast, Dex only increased visceral sensitivity at noxious levels of CRD. Furthermore, GR but not MR activation reduced somatic pain thresholds measured by the mechanical force required to elicit hindlimb withdrawal. In summary, GR and MR mediated-mechanisms induce anxiety and visceral hypersensitivity, whereas somatic sensitivity involves only GR, suggesting that corticosteroids may enhance visceral and somatic sensation via divergent processes originating in the amygdala and involving specific steroid receptor mechanisms.

  2. The management of intractable pain with adjuvant pulsed electromagnetic field therapy.

    PubMed

    Niezgoda, Jeffrey A; Hardin, Scott T; Kubat, Nicole; Acompanado, Jocelyn

    2014-05-01

    This case describes a 51-year-old woman who reported experiencing severe, constant pain, diffusely located in the region of her right mandible neck (primarily involving the mandible, lower right molars, the neck, the upper back, and the shoulder) during the course of several years. Surgical interventions (root canal, spinal fusion) were performed to address potential sources of pain. Despite these interventions, the patient reported severe pain after both surgeries, which persisted beyond the acute postoperative period. Additional pharmacological interventions and physical therapy were also attempted; nonetheless, the patient reported that pain remained severe and constant for approximately 2 years. On the basis of the patient's poor response to conventional treatments, a novel approach of botulinum toxin (BTX) injections was initiated. When pulsed electromagnetic field therapy was added, the need for BTX injections decreased, with the patient reporting a noticeable decrease in pain intensity and an improvement in quality of life measures. Currently, the patient continues to use pulsed electromagnetic field therapy regularly for pain management, which has allowed her to reduce the use of other interventions and avoid continued use of narcotic medications. Considering the need for multifaceted pain management approaches in the treatment of chronic pain, this case is relevant for wound care practitioners attending to patients with chronic postincisional wound pain because the outcome highlights the utility of a nonpharmacological, complementary pain management intervention for closed, yet persistently painful, postoperative wounds.

  3. Visceral pain triggered by traction on the ileocecal ligament with ileitis

    PubMed Central

    Janyaro, Habibullah; Wan, Juan; Tahir, Adnan H; Shah, Manoj K; Li, Xiao-Jing; Ding, Ming-Xing

    2016-01-01

    Background Visceral pain is a common symptom of several gastrointestinal disorders. Despite tremendous progress in understanding its basic mechanisms, it remains a significant health challenge for clinicians. The present study quantified the intensity of visceral pain using ileocecal ligament traction on an inflamed ileum in goats. Materials and methods A total of 36 male goats weighing 20.05±2.1 kg were randomly allocated equally into a 2,4,6-trinitrobenzenesulfonic acid (TNBS) group (n=18) and a saline group (n=18). Ileitis was induced via the injection of 30 mg TNBS dissolved in 30% ethanol into the ileal wall through a laparotomy. An equal volume of normal saline was injected into the ileal wall of the saline goats. Behavioral responses to traction (2, 4, and 6 N) on the ileocecal ligament were observed on days 3, 7, and 14. Six goats from each group received a laparotomy and partial intestinal resection for ileal sample collection immediately after behavioral testing on days 3, 7, and 14. Ileal histopathological changes were assessed and concentrations of myeloperoxidase, IL-1β, IL-6, and TNFα investigated using enzyme-linked immunosorbent assay. Results The TNBS-treated goats exhibited remarkably increased macroscopic scores, mast-cell counts, myeloperoxidase, and TNFα concentrations on days 3 and 7 compared to the saline group, and increased microscopic scores and IL-1β and IL-6 concentrations on days 3–14. The TNBS-treated goats exhibited behavioral changes in response to traction in the same pattern as their microscopic changes and cytokine levels. The traction force correlated positively with pain-behavior responses. Conclusion Traction on the ileocecal ligament of goats with ileitis provoked an apparent, stable, and reproducible ileum-derived pain. The current model may be helpful in evaluating the efficacy of new drugs for the management of visceral pain and in investigating its underlying mechanisms. PMID:27757049

  4. CGRP and Visceral Pain: The Role of Sex Hormones in In Vitro Experiment.

    PubMed

    Pota, Vincenzo; Quagliariello, Vincenzo; Armenia, Emilia; Aurilio, Caterina; Passavanti, Maria Beatrice; Sansone, Pasquale; Iannotti, Mario; Catauro, Michelina; Coaccioli, Stefano; Barbarisi, Manlio; Pace, Maria Caterina

    2017-03-01

    A large number of studies have showed that women reported feeling pain more acutely than men. In support of this hypothesis, many research groups proved that in different animals model of pain the sex hormones regulate the somatic and visceral sensitivity to different noxious stimuli. Therefore, in this study, we went to evaluate if estrogen hormones by regulating the CGRP levels are implicated during the visceral pain transmission. Toward this aim, we have investigated the effect of 17β-estradiol in regulating the synthesis and release of CGRP, as well as the expression levels of the opioid receptor of type K. In order to gain information about the potential effects of 17β-estradiol on K-opioid receptor expression and activity, we have cultured F11 cells. Our results revealed that, when F11 cells were short-term exposed (30 min) to 17β-estradiol, the expression of the opioid K receptor was not significantly modified. We carried out enzyme immunoassay analysis to evaluate the potential effects of short-term exposure to 17-estradiol (30 min) on the release of CGRP in F11 cells. The results obtained showed that 17β-estradiol at the dose of 100 nM is able to induce the release of CGRP from F11 cells; whereas, a higher dose of 17β-estradiol (200 nM) did not produce significant effects when compared to control. In conclusion, all these findings suggest that the 17β-estradiol-regulated release of CGRP could at least in part provide a rational explanation for the difference of gender in the visceral pain sensitivity. J. Cell. Biochem. 118: 510-517, 2017. © 2016 Wiley Periodicals, Inc.

  5. Milnacipran is active in models of irritable bowel syndrome and abdominal visceral pain in rodents.

    PubMed

    Depoortère, Ronan; Meleine, Mathieu; Bardin, Laurent; Aliaga, Monique; Muller, Emilie; Ardid, Denis; Newman-Tancredi, Adrian

    2011-12-15

    The role of antidepressants in the treatment of visceral pain has not been extensively examined. Milnacipran, a serotonin/noradrenalin reuptake inhibitor, has recently been approved in the USA for fibromyalgia, a chronic pathology characterized by diffused/chronic musculoskeletal pain, and a high prevalence of irritable bowel syndrome. Here, we determined its antinociceptive efficacy in two visceral pain tests in rodents: the acetic acid-induced writhing model in mice and the butyrate/colonic distension assay in rats, a model of irritable bowel syndrome. Acute milnacipran (5-40 mg/kgi.p.) significantly and dose-dependently reduced writhing (72.2 ± 3.2 versus 17.0 ± 4.1 writhes at 40 mg/kg). Following repeated administration (40 m/kgi.p. for 5 days), milnacipran preserved its ability to significantly reduce writhing (76 ± 8.3 versus 21.1 ± 6.7 writhes). Similarly, in the butyrate model, acute milnacipran (17.5 and 35 mg/kg, i.p.) significantly and dose-dependently increased cramps induction thresholds (from 45.7 ± 5.7 to 66.3 ± 4.8 and 75.6 ± 2.9 mm Hg, for 17.5 and 35 mg/kg, respectively) and reduced the number of cramps (from 3.0 ± 0.8 to 1.2 ± 0.8 and 0.3 ± 0.3 following inflation of an intra-rectal balloon. To summarise, milnacipran was efficacious in the writhing test, after acute and semi-chronic administration. This effect was confirmed after acute administration in a more specific model of colonic hypersensitivity induced by butyrate. This suggests that milnacipran has potential clinical application in the treatment of visceral pain, such as in irritable bowel syndrome, highly co-morbid with fibromyalgia.

  6. Visceral pain and public speaking stress: neuroendocrine and immune cell responses in healthy subjects.

    PubMed

    Lucas, A; Holtmann, G; Gerken, G; Pietsch, A; Braun-Lang, U; Gilani, K; Strassburger, K; Gesing, S; Janssen, O E; Kavelaars, A; Heijnen, C J; Schedlowski, M; Elsenbruch, S

    2006-01-01

    Whereas responses to psychological stressors are well-characterized, little is known regarding responses to painful visceral stimuli. We analyzed the emotional, cardiovascular, neuroendocrine, and cellular immune responses to painful rectal stimulation and psychological stress in healthy individuals. Eleven healthy subjects were studied in three conditions on separate days: painful rectal distension, public speaking stress, and rest. Blood was drawn for endocrinological and immunological analyses; heart rate and blood pressure were measured continuously; state anxiety was assessed with a questionnaire (STAI-S). Anxiety scores were highest in the rectal distension condition. This was evident following rectal distension (mean STAI-S scores: 44.2+/-3.5 post-distension vs. 36.6+/-3.8 post-speech, p<.05), but anxiety was also elevated at baseline (41.6+/-3.9 vs. 32+/-3.2 recovery, p<.01). This anticipatory effect was reflected by elevated baseline cortisol (p<.05) and baseline ACTH (p<.01) levels, as well as circulating lymphocytes and lymphocyte subsets, including decreased basal CD3+CD4+ cells (p<.05) and increased CD16+CD56+ cells (p=.06) compared to rest. Both public speech and rectal distension induced cardiovascular activation, but the effect was more pronounced following rectal distension (+63.8+/-9.4 mmHg in response to distension vs. +36.4+/-6.2 mmHg in response to speech for systolic BP, p<.05). Different response patterns were also observed in the distribution of circulating leukocytes and lymphocyte subsets, including CD16+CD56+ cells (p<.05). An acute visceral pain stimulus causes profound emotional, neuroendocrine, and immune cell responses, which are markedly affected by anticipatory anxiety. These findings may have implications for conditions associated with visceral hyperalgesia.

  7. Mechanisms of referred visceral pain: uterine inflammation in the adult virgin rat results in neurogenic plasma extravasation in the skin.

    PubMed

    Wesselmann, U; Lai, J

    1997-12-01

    The purpose of this study was to investigate the mechanisms of referred pain observed in female patients with pain from the reproductive organs. We developed a model of inflammatory uterine pain in the rat. Inflammation of the uterus in rats pretreated with Evans Blue Dye resulted in dye extravasation in the skin over the abdomen, groin, lower back, thighs, perineal area and proximal tail, thus providing for the first time evidence for the trophic changes observed in the area of referred visceral pain in an animal model of uterine pain. The neuronal pathways mediating the observed dye extravasation in the skin after uterine inflammation may include dichotomizing afferent fibers, afferent-afferent interactions via a spinal cord pathway or a sympathetic reflex. This model will allow to gain further insight into the mechanisms of referred pain and the trophic changes observed in the area of referred pain in visceral disease.

  8. Decreased miR-199 augments visceral pain in patients with IBS through translational upregulation of TRPV1

    PubMed Central

    Zhou, QiQi; Yang, Liuqing; Larson, Scott; Basra, Sapreet; Merwat, Shehzad; Tan, Alai; Croce, Carlo; Verne, G Nicholas

    2016-01-01

    Objective Many patients with irritable bowel syndrome IBS not only have abdominal pain but also may suffer from visceral hypersensitivity and heighted visceral nociception. Moreover, IBS has few effective therapeutic agents and mechanisms of disease are unclear. Our goals were to (i) identify microRNA (miRNA) expression, signalling and targets in human colon (controls; patients with IBS); (ii) verify in vitro, IBS-associated changes in miRNAs, especially miR-199, which is complementary to the transient receptor potential vanilloid type 1 (TRPV1) gene; and (iii) determine whether modulating the expression of miRNAs in vivo, especially miR-199, reverses associated changes and pathological hallmarks of visceral hypersensitivity via TRPV1 signalling. Design We evaluated 45 patients with diarrhoea-predominant IBS (IBS-D) and 40 controls with (1) visceral pain severity score and (2) colonoscopy with biopsies. miRNA expression was evaluated in human colon following miRNA array analysis. Luciferase assays were done to confirm relationships between miR-199 and TRPV1 expression. A rat model of visceral hypersensitivity was used to study miR-199 and its target gene (TRPV1) expression in dorsal root ganglion (DRG) and colon in vivo. Results Gut miR-199a/b expression in IBS-D was significantly decreased, which correlated directly with both increased visceral pain scores and TRPV1 expression. In vivo upregulation of miR-199a by intraperitoneal injection of lenti-miR-199a precursors decreased visceral hypersensitivity via diminished TRPV1 signalling. Conclusions Decreased colonic miR-199a/b correlates with visceral pain in patients with IBS-D. Similarly, reduced miR-199a expression in rat DRG and colon tissue is associated with heightened visceral hypersensitivity. In vivo upregulation of miR-199a decreases visceral pain via inhibition of TRPV1 signalling. Thus, miR-199 precursors may be promising therapeutic candidates for the treatment in patients with visceral pain. PMID

  9. Influence of exercise on visceral pain: an explorative study in healthy volunteers

    PubMed Central

    van Weerdenburg, Laura JGM; Brock, Christina; Drewes, Asbjørn Mohr; van Goor, Harry; de Vries, Marjan; Wilder-Smith, Oliver HG

    2017-01-01

    Background and objectives Contradictory results have been found about the effect of different exercise modalities on pain. The aim of this study was to investigate the early effects of aerobic and isometric exercise on different types of experimental pain, including visceral pain, compared to an active control condition. Methods Fifteen healthy subjects (6 women, mean [standard deviation] age 25 [6.5] years) completed 3 interventions consisting of 20 minutes of aerobic cycling, 12 minutes of isometric knee extension and a deep breathing procedure as active control. At baseline and after each intervention, psychophysical tests were performed, including electrical stimulation of the esophagus, pressure pain thresholds and the cold pressor test as a measure for conditioned pain modulation. Participants completed the Medical Outcome Study Short-Form 36 and State-Trait Anxiety Inventory prior to the experiments. Data were analyzed using two-way repeated measures analysis of variance. Results No significant differences were found for the psychophysical tests after the interventions, compared to baseline pain tests and the control condition. Conclusion No hypoalgesic effect of aerobic and isometric exercise was found. The evidence for exercise-induced hypoalgesia appears to be not as consistent as initially thought, and caution is recommended when interpreting the effects of exercise on pain. PMID:28096689

  10. Phosphorylated CaMKII post-synaptic binding to NR2B subunits in the anterior cingulate cortex mediates visceral pain in visceral hypersensitive rats.

    PubMed

    Li, Ying; Zhang, Xu; Liu, Haiyan; Cao, Zhijun; Chen, Shengliang; Cao, Bing; Liu, Jin

    2012-05-01

    The NR2B subunit of NMDA receptor in the anterior cingulate cortex (ACC) is up-regulated in viscerally hypersensitive (VH) rats induced by colonic anaphylaxis. It plays a critical role in modulation of ACC sensitization and visceral pain responses. Given the key role of calcium/calmodulin-dependent protein kinase II (CaMKII) in synaptic plasticity and behavior learning and memory, we hypothesize that phosphorylation of CaMKII binding to NR2B mediates visceral pain in VH states. We performed in vivo electroporation of CaMKII siRNA produced inhibition of colorectal distension-induced visceromotor response in the VH rats. The NR2B, CaMKII and P-CaMKII-Thr²⁸⁶ protein levels were increased in 180%, 220% and 304% fold in the post-synaptic density (PSD) fraction in VH rats separately. Western blotting following co-immunoprecipitation showed that P-CaMKII-Thr²⁸⁶ bound to NR2B in the PSD, which was increased to 267% of control in VH rats. Administration of CaMKII antagonist Antennapedia-CaMKIINtide suppressed visceromotor response in VH rats in parallel with decrease of NR2B levels and reduction of the NR2B-P-CaMKII-Thr²⁸⁶ protein complex in PSD. In conclusion, CaMKII is a critical signaling molecule in the ACC glutamatergic synaptic transmission and phosphorylation of CaMKII at Thr286, which binds to NR2B subunit at post-synaptic site, modulates visceral pain in viscerally hypersensitive state.

  11. H2S and Pain: A Novel Aspect for Processing of Somatic, Visceral and Neuropathic Pain Signals.

    PubMed

    Terada, Yuka; Kawabata, Atsufumi

    2015-01-01

    Hydrogen sulfide (H2S) formed by multiple enzymes including cystathionine-γ-lyase (CSE) targets Cav3.2 T-type Ca2+ channels (T-channels) and transient receptor potential ankyrin-1 (TRPA1). Intraplantar and intracolonic administration of H2S donors promotes somatic and visceral pain, respectively, via activation of Cav3.2 and TRPA1 in rats and/or mice. Injection of H2S donors into the plantar tissues, pancreatic duct, colonic lumen, or bladder causes T-channel-dependent excitation of nociceptors, determined as phosphorylation of ERK or expression of Fos in the spinal dorsal horn. Electrophysiological studies demonstrate that exogenous and/or endogenous H2S facilitates membrane currents through T-channels in NG108-15 cells and isolated mouse dorsal root ganglion (DRG) neurons that abundantly express Cav3.2 and also in Cav3.2-transfected HEK293 cells. In mice with cerulein-induced pancreatitis and cyclophosphamide-induced cystitis, visceral pain and/or referred hyperalgesia are inhibited by CSE inhibitors and by pharmacological blockade or genetic silencing of Cav3.2, and CSE protein is upregulated in the pancreas and bladder. In rats with neuropathy induced by L5 spinal nerve cutting or by repeated administration of paclitaxel, an anticancer drug, the neuropathic hyperalgesia is reversed by inhibitors of CSE or T-channels and by silencing of Cav3.2. Upregulation of Cav3.2 protein in DRG is detectable in the former, but not in the latter, neuropathic pain models. Thus, H2S appears to function as a nociceptive messenger by facilitating functions of Cav3.2 and TRPA1, and the enhanced function of the CSE/H2S/Cav3.2 pathway is considered to be involved in the pancreatitis- and cystitis-related pain and in neuropathic pain.

  12. Effect of commensals and probiotics on visceral sensitivity and pain in irritable bowel syndrome.

    PubMed

    Theodorou, Vassilia; Ait Belgnaoui, Afifa; Agostini, Simona; Eutamene, Helene

    2014-01-01

    The last ten years' wide progress in the gut microbiota phylogenetic and functional characterization has been made evidencing dysbiosis in several gastrointestinal diseases including inflammatory bowel diseases and irritable bowel syndrome (IBS). IBS is a functional gut disease with high prevalence and negative impact on patient's quality of life characterized mainly by visceral pain and/or discomfort, representing a good paradigm of chronic gut hypersensitivity. The IBS features are strongly regulated by bidirectional gut-brain interactions and there is increasing evidence for the involvement of gut bacteria and/or their metabolites in these features, including visceral pain. Further, gut microbiota modulation by antibiotics or probiotics has been promising in IBS. Mechanistic data provided mainly by animal studies highlight that commensals or probiotics may exert a direct action through bacterial metabolites on sensitive nerve endings in the gut mucosa, or indirect pathways targeting the intestinal epithelial barrier, the mucosal and/or systemic immune activation, and subsequent neuronal sensitization and/or activation.

  13. Lumbar paravertebral blockade as intractable pain management method in palliative care.

    PubMed

    Zaporowska-Stachowiak, Iwona; Kotlinska-Lemieszek, Aleksandra; Kowalski, Grzegorz; Kosicka, Katarzyna; Hoffmann, Karolina; Główka, Franciszek; Luczak, Jacek

    2013-01-01

    Optimal symptoms control in advanced cancer disease, with refractory to conventional pain treatment, needs an interventional procedure. This paper presents coadministration of local anesthetic (LA) via paravertebral blockade (PVB) as the alternative to an unsuccessful subcutaneous fentanyl pain control in a 71-year old cancer patient with pathological fracture of femoral neck, bone metastases, and contraindications to morphine. Bupivacaine in continuous infusion (0.25%, 5 mL · hour(-1)) or in boluses (10 mL of 0.125%-0.5% solution), used for lumbar PVB, resulted in pain relief, decreased demand for opioids, and led to better social interactions. The factors contributing to an increased risk of systemic toxicity from LA in the patient were: renal impairment; heart failure; hypoalbuminemia; hypocalcemia; and a complex therapy with possible drug-drug interactions. These factors were taken into consideration during treatment. Bupivacaine's side effects were absent. Coadministered drugs could mask LA's toxicity. Elevated plasma α1-acid glycoprotein levels were a protective factor. To evaluate the benefit-risk ratio of the PVB treatment in boluses and in constant infusion, bupivacaine serum levels were determined and the drug plasma half-lives were calculated. Bupivacaine's elimination was slower when administered in constant infusion than in boluses (t½ = 7.80 hours versus 2.64 hours). Total drug serum concentrations remained within the safe ranges during the whole treatment course (22.9-927.4 ng mL(-1)). In the case presented, lumbar PVB with bupivacaine in boluses (≤ 137.5 mg · 24 hours(-1)) was an easy to perform, safe, effective method for pain control. Bupivacaine in continuous infusion (≤150 mg · 12 hours(-1)) had an acceptable risk-benefits ratio, but was ineffective.

  14. The effect of chemically induced colitis, psychological stress and their combination on visceral pain in female Wistar rats.

    PubMed

    Deiteren, Annemie; Vermeulen, Wim; Moreels, Tom G; Pelckmans, Paul A; De Man, Joris G; De Winter, Benedicte Y

    2014-09-01

    Visceral sensitivity is of pathophysiological importance in abdominal pain disorders and can be modulated by inflammation and stress. However, it is unclear whether inflammation and stress alter visceral perception independently of each other or in conjunction through neuroendocrine interactions. Therefore, we compared the short- and long-term effects of experimental colitis and water avoidance stress (WAS), alone or in combination, on visceral sensitivity in female Wistar rats. Colitis was induced by trinitrobenzene sulfonic acid (TNBS) and colonoscopically confirmed. During WAS, rats were placed on a platform surrounded by water for 1 h. Visceral sensitivity was assessed by quantifying the visceromotor responses (VMRs) to colorectal distension. Activation of the hypothalamic-pituitary-adrenal axis was determined by measuring serum corticosterone in a separate protocol. TNBS instillation resulted in overt colitis, associated with significant visceral hypersensitivity during the acute inflammatory phase (3 days post-TNBS; n = 8/group); after colitis had subsided (28 days post-TNBS), hypersensitivity was resolved (n = 4-8/group). Single WAS was associated with increased VMRs of a magnitude comparable to acute TNBS-induced hypersensitivity (n = 8/group). However, after repetitive WAS no significant hypersensitivity was present (n = 8/group). No additive effect of colitis and stress was seen on visceral pain perception (n = 6-8/group). Corticosterone levels were only increased in acute TNBS-colitis, acute WAS and their combination. To conclude, both colitis and stress successfully induced short-term visceral hypersensitivity and activated the hypothalamic-pituitary-adrenal axis, but long-term effects were absent. In addition, our current findings do not support an additive effect of colitis and stress on visceral sensitivity in female Wistar rats.

  15. Difficult Cases of Pain and Nonpain Symptoms in Intractable Spinal Infections: A Case Series

    PubMed Central

    Olsen, Molly L.; Havyer, Rachel D. A.; Smith, Thomas J.; Swetz, Keith M.

    2014-01-01

    In the modern age of advanced surgical techniques and pharmacologic management, bacterial spinal infections (SIs) can be managed (either eradicated or suppressed) in many hosts. However, the optimal management of SIs may be limited by patient comorbidities, which do not allow for surgical management, or limited by antimicrobial options due to side effects, toxicities, or emerging drug resistance. In these settings, frank and honest discussion regarding risks and benefits of treatment should be pursued, including that the SI may be a terminal illness. In this case series, we present 3 patients who had bacterial SIs whose treatments were limited by the above-mentioned factors. Furthermore, each case presented challenges regarding optimal medical management of somatic and neuropathic pain associated with the SI. PMID:22144661

  16. Identification of the visceral pain pathway activated by noxious colorectal distension in mice.

    PubMed

    Kyloh, Melinda; Nicholas, Sarah; Zagorodnyuk, Vladimir P; Brookes, Simon J; Spencer, Nick J

    2011-01-01

    In patients with irritable bowel syndrome, visceral pain is evoked more readily following distension of the colorectum. However, the identity of extrinsic afferent nerve pathway that detects and transmits visceral pain from the colorectum to the spinal cord is unclear. In this study, we identified which extrinsic nerve pathway(s) underlies nociception from the colorectum to the spinal cord of rodents. Electromyogram recordings were made from the transverse oblique abdominal muscles in anesthetized wild type (C57BL/6) mice and acute noxious intraluminal distension stimuli (100-120 mmHg) were applied to the terminal 15 mm of colorectum to activate visceromotor responses (VMRs). Lesioning the lumbar colonic nerves in vivo had no detectable effect on the VMRs evoked by colorectal distension. Also, lesions applied to the right or left hypogastric nerves failed to reduce VMRs. However, lesions applied to both left and right branches of the rectal nerves abolished VMRs, regardless of whether the lumbar colonic or hypogastric nerves were severed. Electrical stimulation applied to either the lumbar colonic or hypogastric nerves in vivo, failed to elicit a VMR. In contrast, electrical stimulation (2-5 Hz, 0.4 ms, 60 V) applied to the rectum reliably elicited VMRs, which were abolished by selective lesioning of the rectal nerves. DiI retrograde labeling from the colorectum (injection sites 9-15 mm from the anus, measured in unstretched preparations) labeled sensory neurons primarily in dorsal root ganglia (DRG) of the lumbosacral region of the spinal cord (L6-S1). In contrast, injection of DiI into the mid to proximal colon (injection sites 30-75 mm from the anus, measured in unstretched preparations) labeled sensory neurons in DRG primarily of the lower thoracic level (T6-L2) of the spinal cord. The visceral pain pathway activated by acute noxious distension of the terminal 15 mm of mouse colorectum is transmitted predominantly, if not solely, through rectal

  17. The role of cannabinoids in regulation of nausea and vomiting, and visceral pain.

    PubMed

    Malik, Zubair; Baik, Daniel; Schey, Ron

    2015-02-01

    Marijuana derived from the plant Cannabis sativa has been used for the treatment of many gastrointestinal (GI) disorders, including anorexia, emesis, abdominal pain, diarrhea, and others. However, its psychotropic side effects have often limited its use. Several cannabinoid receptors, which include the cannabinoid receptor 1 (CB1), CB2, and possibly GPR55, have been identified throughout the GI tract. These receptors may play a role in the regulation of food intake, nausea and emesis, gastric secretion and gastroprotection, GI motility, ion transport, visceral sensation, intestinal inflammation, and cell proliferation in the gut. However, the regulation of nausea and vomiting by cannabinoids and the endocannabinoid system has shed new knowledge in this field. Thus far, despite evidence of visceral sensitivity inhibition in animal models, data in irritable bowel syndrome (IBS) patients is scarce and not supportive. Furthermore, many compounds that either act directly at the receptor or increase (or reduce) ligand availability have the potential to affect other brain functions and cause side effects. Novel drug targets such as FAAH and monoacylglycerol lipase (MAGL) inhibitors appear to be promising in animal models, but more studies are necessary to prove their efficiency. The promise of emerging drugs that are more selective and peripherally acting suggest that, in the near future, cannabinoids will play a major role in managing an array of GI diseases.

  18. Vinpocetine and piracetam exert antinociceptive effect in visceral pain model in mice.

    PubMed

    Abdel Salam, Omar M E

    2006-01-01

    The effect of vinpocetine or piracetam on thermal and visceral pain was studied in mice. In the hot plate test, vinpocetine (0.9 and 1.8 mg/kg), but not piracetam, produced a reduction in nociceptive response. Vinpocetine (0.45-1.8 mg/kg, ip) or piracetam (75-300 mg/kg, ip) caused dose-dependent inhibition of the abdominal constrictions evoked by ip injection of acetic acid. The effect of vinpocetine or piracetam was markedly potentiated by co-administration of propranolol, guanethidine, atropine, naloxone, yohimbine or prazosin. The marked potentiation of antinociception occurred upon a co-administration of vinpocetine and baclofen (5 or 10 mg/kg). In contrast, piracetam antagonized antinociception caused by the low (5 mg/kg), but not the high (10 mg/kg) dose of baclofen. The antinociception caused by vinpocetine was reduced by sulpiride; while that of piracetam was enhanced by haloperidol or sulpiride. Either vinpocetine or piracetam enhanced antinociception caused by imipramine. The antinociceptive effects of vinpocetine or piracetam were blocked by prior administration of theophylline. Low doses of either vinpocetine or piracetam reduced immobility time in the Porsolt's forced-swimming test. This study indicates that vinpocetine and piracetam possess visceral antinociceptive properties. This effect depends on activation of adenosine receptors. Piracetam in addition inhibits GABA-mediated antinociception.

  19. Gap junctions in dorsal root ganglia: possible contribution to visceral pain.

    PubMed

    Huang, Tian-Ying; Belzer, Vitali; Hanani, Menachem

    2010-01-01

    Peripheral injuries can lead to sensitization of neurons in dorsal root ganglia (DRGs), which can contribute to chronic pain. The neurons are sensitized by a combination of physiological and biochemical changes, whose full details are still obscure. Another cellular element in DRGs are satellite glial cells (SGCs), which surround the neurons, but little is known about their role in nociception. We investigated the contribution of SGCs to neuronal sensitization in isolated S1 DRGs from a mouse model of colonic inflammation induced by local application of dinitrosulfonate benzoate (DNBS). Retrograde labeling was used to identify DRG neurons projecting to the colon. Cell-to-cell coupling was determined by intracellular dye injection, and the electrical properties of the neurons were studied with intracellular electrodes. Pain behavior was assessed with von-Frey hairs. The dye injections showed that 10-12 days after DNBS application there was a 6.6-fold increase in gap junction-mediated coupling between SGCs surrounding adjacent neurons, and this occurred preferentially (another 2-fold increase) near neurons that project to the colon. Neuron-neuron coupling incidence increased from 0.7% to 12.1% by colonic inflammation. Inflammation led to an augmented neuronal excitability, and to a reduced pain threshold. Gap junction blockers abolished the inflammation-induced changes in SGCs and neurons, and significantly reversed the pain behavior. We propose that inflammation induces augmented cell coupling in DRGs that contributes to neuronal hyperexcitability, which in turn leads to visceral pain. Gap junction blockers may have potential as analgesic drugs.

  20. Necrotic arachnidism and intractable pain from recluse spider bites treated with lumbar sympathetic block: a case report and review of literature.

    PubMed

    Yi, Xiaobin; AuBuchon, Jacob; Zeltwanger, Shawn; Kirby, John P

    2011-06-01

    Brown recluse (Loxosceles reclusa) spider bites mainly occur in the southern and Midwestern United States. The clinical manifestation of brown recluse spider bites varies from skin irritation, a small area of tissue damage to neuropathic pain, necrotic arachnidism and severe systemic reactions such as acute renal failure and even death. Treatment is controversial and nonspecific. We describe a case of extensive right lower extremity tissue necrosis and intractable neuropathic pain treated with lumbar sympathetic block in a patient with a documented brown recluse spider bite. Both his pain and tissue necrosis improved significantly with lumbar sympathetic block with local anesthetic. After a series of lumbar sympathetic blocks, his symptoms resolved and lower extremity wound healed rapidly. We discuss the benefit of sympathetic blockade not only for neuropathic pain but also possibly as a treatment for necrotic arachnidism from a brown recluse spider bite.

  1. Hippocampal NR2B-containing NMDA receptors enhance long-term potentiation in rats with chronic visceral pain.

    PubMed

    Chen, Yu; Chen, Ai-qin; Luo, Xiao-qing; Guo, Li-xia; Tang, Ying; Bao, Cheng-jia; Lin, Ling; Lin, Chun

    2014-06-27

    Pain and learning memory have striking similarities in synaptic plasticity. Activation of the N-methyl-D-aspartic acid receptors 2B subunits (NR2B-NMDAs) is responsible for the hippocampal LTP in memory formation. In our previous studies, we found the significant enhancement of CA1 hippocampal long-term potentiation (LTP) induced by high-frequency stimulation (HFS) in rats with chronic visceral pain. However, it is unclear whether the NR2B-NMDAs are required for the LTP in chronic visceral pain. In this study, a rat model with irritable bowel syndrome (IBS) was established by colorectal distention (CRD). The sensitivity of visceral pain and HFS-induced LTP at SC-CA1 synapses were significantly enhanced in IBS-like rats (p<0.05). In addition, hippocampal NR2B protein levels significantly increased in IBS-like rats (p<0.05). To test whether NR2B-NMDAs are responsible for the LTP, effects of Ro 25-6981, a selective antagonist of NR2B-NMDAs, on field potential in CA1 region were investigated in vitro. Our results demonstrated that Ro 25-6981 dose-dependently inhibited the facilitation of CA1 LTP in IBS-like rats. The plausible activation mechanism of hippocampal NR2B-NMDAs in the LTP enhancement was further explored. Western blot data indicated that expression of tyrosine phosphorylated NR2B protein in hippocampus significantly enhanced in IBS-like rats. Accordingly, genistein, a specific inhibitor of tyrosine kinases, dose-dependently blocked the facilitation of hippocampal LTP in IBS-like rats. Furthermore, EMG data revealed that intra-hippocampal injection of Ro 25-6981 dose-dependently attenuated the visceral hypersensitivity. In conclusion, hippocampal NR2B-NMDAs are responsible for the facilitation of CA1 LTP via tyrosine phosphorylation, which leads to visceral hypersensitivity.

  2. Pain and Interoception Imaging Network (PAIN): A multimodal, multisite, brain-imaging repository for chronic somatic and visceral pain disorders.

    PubMed

    Labus, Jennifer S; Naliboff, Bruce; Kilpatrick, Lisa; Liu, Cathy; Ashe-McNalley, Cody; dos Santos, Ivani R; Alaverdyan, Mher; Woodworth, Davis; Gupta, Arpana; Ellingson, Benjamin M; Tillisch, Kirsten; Mayer, Emeran A

    2016-01-01

    The Pain and Interoception Imaging Network (PAIN) repository (painrepository.org) is a newly created NIH (NIDA/NCCAM) funded neuroimaging data repository that aims to accelerate scientific discovery regarding brain mechanisms in pain and to provide more rapid benefits to pain patients through the harmonization of efforts and data sharing. The PAIN Repository consists of two components, an Archived Repository and a Standardized Repository. Similar to other 'open' imaging repositories, neuroimaging researchers can deposit any dataset of chronic pain patients and healthy controls into the Archived Repository. Scans in the Archived Repository can be very diverse in terms of scanning procedures and clinical metadata, complicating the merging of datasets for analyses. The Standardized Repository overcomes these limitations through the use of standardized scanning protocols along with a standardized set of clinical metadata, allowing an unprecedented ability to perform pooled analyses. The Archived Repository currently includes 741 scans and is rapidly growing. The Standardized Repository currently includes 433 scans. Pain conditions currently represented in the PAIN repository include: irritable bowel syndrome, vulvodynia, migraine, chronic back pain, and inflammatory bowel disease. Both the PAIN Archived and Standardized Repositories promise to be important resources in the field of chronic pain research. The enhanced ability of the Standardized Repository to combine imaging, clinical and other biological datasets from multiple sites in particular make it a unique resource for significant scientific discoveries.

  3. NMDA receptor mediates chronic visceral pain induced by neonatal noxious somatic stimulation

    PubMed Central

    Miranda, Adrian; Mickle, Aaron; Bruckert, Mitchell; Kannampalli, Pradeep; Banerjee, Banani; Sengupta, Jyoti N.

    2014-01-01

    NMDA receptors (NMDAR) are important in the development and maintenance of central sensitization. Our objective was to investigate the role of spinal neurons and NMDAR in the maintenance of chronic visceral pain. Neonatal rats were injected with acidic saline adjusted to pH4.0 in the gastrocnemius muscle every other day for 12 days. In adult rats, NR1 and NR2B subunits were examined in the lumbo-sacral (LS) spinal cord. A baseline, visceromotor response (VMR) to graded colorectal distension (CRD) was recorded before and after administration of the NMDA antagonist, CGS-19755. Extracellular recordings were performed from CRD-sensitive LS spinal neurons and pelvic nerve afferents (PNA) before and after CGS-19755. Rats that received pH 4.0 saline injections demonstrated a significant increase in the expression NR2B subunits and VMR response to CRD >20mmHg. CGS-19755 (i.v. or i.t.) had no effect in naïve rats, but significantly decreased the response to CRD in pH4.0 saline injected rats. CGS-19755 had no effect on the spontaneous firing of SL-A, but decreased that of SL-S. Similarly, CGS-19755 attenuates the responses of SL-S neurons to CRD, but had no effect on SL-A neurons or on the response characteristics of PNA fibers. Neonatal noxious somatic stimulation results in chronic visceral hyperalgesia and sensitizes a specific subpopulation of CRD-sensitive spinal neurons. The sensitization of these SL-S spinal neurons is attenuated by the NMDAR antagonist. The results of this study suggest that spinal NMDARs play an important role in the development of hyperalgesia early in life. PMID:25281204

  4. NMDA receptor mediates chronic visceral pain induced by neonatal noxious somatic stimulation.

    PubMed

    Miranda, Adrian; Mickle, Aaron; Bruckert, Mitchell; Kannampalli, Pradeep; Banerjee, Banani; Sengupta, Jyoti N

    2014-12-05

    NMDA receptors (NMDAR) are important in the development and maintenance of central sensitization. Our objective was to investigate the role of spinal neurons and NMDAR in the maintenance of chronic visceral pain. Neonatal rats were injected with acidic saline adjusted to pH 4.0 in the gastrocnemius muscle every other day for 12 days. In adult rats, NR1 and NR2B subunits were examined in the lumbo-sacral (LS) spinal cord. A baseline, visceromotor response (VMR) to graded colorectal distension (CRD) was recorded before and after administration of the NMDA antagonist, CGS-19755. Extracellular recordings were performed from CRD-sensitive LS spinal neurons and pelvic nerve afferents (PNA) before and after CGS-19755. Rats that received pH 4.0 saline injections demonstrated a significant increase in the expression NR2B subunits and VMR response to CRD>20 mmHg. CGS-19755 (i.v. or i.t.) had no effect in naïve rats, but significantly decreased the response to CRD in pH 4.0 saline injected rats. CGS-19755 had no effect on the spontaneous firing of SL-A, but decreased that of SL-S. Similarly, CGS-19755 attenuates the responses of SL-S neurons to CRD, but had no effect on SL-A neurons or on the response characteristics of PNA fibers. Neonatal noxious somatic stimulation results in chronic visceral hyperalgesia and sensitizes a specific subpopulation of CRD-sensitive spinal neurons. The sensitization of these SL-S spinal neurons is attenuated by the NMDAR antagonist. The results of this study suggest that spinal NMDARs play an important role in the development of hyperalgesia early in life.

  5. Towards understanding sex differences in visceral pain: enhanced reactivation of classically-conditioned fear in healthy women.

    PubMed

    Benson, Sven; Kattoor, Joswin; Kullmann, Jennifer S; Hofmann, Sarah; Engler, Harald; Forsting, Michael; Gizewski, Elke R; Elsenbruch, Sigrid

    2014-03-01

    Sex differences in learned fear regarding aversive gastrointestinal stimuli could play a role in the female preponderance of chronic abdominal pain. In a fear conditioning model with rectal pain as unconditioned stimulus (US), we compared healthy males and females with respect to neural responses during aversive visceral learning, extinction and re-activation of fear memory (i.e., reinstatement). To do so, conditioned visual stimuli (CS(+)) were consistently paired with painful rectal distensions as US, while different visual stimuli (CS(-)) were presented without US. During extinction, both CSs were presented without US, whereas during reinstatement, a single, unpaired US was presented. In region-of-interest analyses, sexes were compared with respect to conditioned anticipatory neural activation (CS(+)>CS(-)). The results revealed that in late acquisition, CS+ presentation induced significantly greater anticipatory activation of the insula in women. During extinction, women demonstrated reduced activation of the posterior cingulate cortex. During reinstatement, the CS(+) led to greater activation of the hippocampus, thalamus and cerebellum in women. These group effects in neural activation during learning and memory processes were not accounted for by sex differences in pain thresholds, pain ratings, or stress parameters. In conclusion, this is the first study to support sex differences in neural processes mediating aversive visceral learning. Our finding of enhanced neural responses during reinstatement in key brain areas relevant for memory suggests enhanced reactivation of old fear memory trace in women. Sex differences in "gut memories" could play a role in the female preponderance of chronic abdominal pain.

  6. Tyrosine phosphorylation of the NR2B subunit of the NMDA receptor in the spinal cord contributes to chronic visceral pain in rats.

    PubMed

    Luo, Xiao-Qing; Cai, Qin-Yan; Chen, Yu; Guo, Li-Xia; Chen, Ai-Qin; Wu, Zhen-Quan; Lin, Chun

    2014-01-13

    The roles of spinal N-methyl-d-aspartic acid receptor 2B (NR2B) subunit in central sensitization of chronic visceral pain were investigated. A rat model with irritable bowel syndrome (IBS) was established by colorectal distention (CRD) on post-natal days 8-14. Responses of the external oblique muscle of the abdomen to CRD were measured to evaluate the sensitivity of visceral pain in rats. The sensitivity of visceral pain significantly increased in IBS-like rats. Expressions of spinal NR2B subunit and phosphorylated NR2B subunit significantly increased by 50-55% in IBS-like rats when compared with those in control rats. Ro 25-6981, a selective antagonist of NR2B subunit, has a dose-dependent anti-allodynic and anti-hyperalgesic effect without causing motor dysfunction in IBS-like rats. Furthermore, the activation mechanism of the spinal NR2B subunit in chronic visceral pain was also investigated. Spinal administration of genistein, a specific inhibitor of tyrosine kinases, also decreased the visceral pain hypersensitivity of IBS-like rats in a dose-dependent manner. In addition, the expression of phosphorylated NR2B subunit was decreased after spinal administration of Ro 25-6981 or genistein in IBS-like rats. In conclusion, tyrosine kinase activation-induced phosphorylation of NR2B subunit may play a crucial role in central sensitization of chronic visceral pain.

  7. Fentanyl-trazodone-paracetamol triple drug combination: multimodal analgesia in a mouse model of visceral pain.

    PubMed

    Fernández-Dueñas, Víctor; Poveda, Raquel; Fernández, Alejandro; Sánchez, Sílvia; Planas, Eulàlia; Ciruela, Francisco

    2011-05-01

    Multimodal or balanced analgesia is commonly used in the management of acute and chronic pain in humans, in order to achieve the best analgesic/safety profile. Here, by using a model of visceral acute tonic pain, the acetic acid-induced writhing test of mice, we show a synergistic interaction between fentanyl, trazodone and paracetamol on the inhibition of nociception. First of all, once assessed that all drugs induced dose-related antinociceptive effects, they were mixed in fixed ratio (1:1) combinations and a synergistic drug-drug interaction was obtained in all circumstances. Thereafter, we assayed the effects of the triple combination of fentanyl-trazodone-paracetamol and it was demonstrated that they displayed a potent synergistic interaction on the inhibition of acetic acid-mediated nociception. Interestingly, drug dosage reduction permitted to reduce the incidence of possible adverse effects, namely exploratory activity and motor coordination, thus it was demonstrated that it improved the benefit/risk profile of such treatment. Afterwards, we attempted to elucidate the mechanism of action of such interaction, by means of the non-selective opioid receptor antagonist naloxone. Interestingly, naloxone completely antagonized the antinociceptive effects of fentanyl, and it also partially reversed paracetamol and trazodone mediated analgesia. Furthermore, when naloxone was co-administered with the triple-drug treatment it blocked the previously observed enhanced antinociceptive effects of the combination. Thus, these results indicated that the endogenous opioid system played a main role in the present drug-drug interaction. Overall, the triple combination of fentanyl-trazodone-paracetamol induced a potent synergistic antinociceptive effect, which could be of interest for optimal multimodal clinical analgesia.

  8. Profound reduction of somatic and visceral pain in mice by intrathecal administration of the anti-migraine drug, sumatriptan.

    PubMed

    Nikai, Tetsuro; Basbaum, Allan I; Ahn, Andrew H

    2008-10-31

    Sumatriptan and the other triptan drugs target the serotonin receptor subtypes1B, 1D, and 1F (5-HT(1B/D/F)), and are prescribed widely in the treatment of migraine. An anti-migraine action of triptans has been postulated at multiple targets, within the brain and at both the central and peripheral terminals of trigeminal "pain-sensory" fibers. However, as triptan receptors are also located on "pain-sensory" afferents throughout the body, it is surprising that triptans only reduce migraine pain in humans, and experimental cranial pain in animals. Here we tested the hypothesis that sumatriptan can indeed reduce non-cranial, somatic and visceral pain in behavioral models in mice. Because sumatriptan must cross the blood brain barrier to reach somatic afferent terminals in the spinal cord, we compared systemic to direct spinal (intrathecal) sumatriptan. Acute nociceptive thresholds were not altered by sumatriptan pre-treatment, regardless of route. However, in behavioral models of persistent inflammatory pain, we found a profound anti-hyperalgesic action of intrathecal, but not systemic, sumatriptan. By contrast, sumatriptan was completely ineffective in an experimental model of neuropathic pain. The pronounced activity of intrathecal sumatriptan against inflammatory pain in mice raises the possibility that there is a wider spectrum of therapeutic indications for triptans beyond headache.

  9. Monosynaptic convergence of somatic and visceral C-fiber afferents on projection and local circuit neurons in lamina I: a substrate for referred pain.

    PubMed

    Luz, Liliana L; Fernandes, Elisabete C; Sivado, Miklos; Kokai, Eva; Szucs, Peter; Safronov, Boris V

    2015-10-01

    Referred pain is a phenomenon of feeling pain at a site other than the site of the painful stimulus origin. It arises from a pathological mixing of nociceptive processing pathways for visceral and somatic inputs. Despite numerous studies based on unit recordings from spinal and supraspinal neurons, the exact mechanism and site of this mixing within the central nervous system are not known. Here, we selectively recorded from lamina I neurons, using a visually guided patch-clamp technique, in thoracic spinal cord preparation with preserved intercostal (somatic) and splanchnic (visceral) nerves. We show that somatic and visceral C fibers converge monosynaptically onto a group of lamina I neurons, which includes both projection and local circuit neurons. Other groups of lamina I neurons received inputs from either somatic or visceral afferents. We have also identified a population of lamina I local circuit neurons showing overall inhibitory responses upon stimulation of both nerves. Thus, the present data allow us to draw two major conclusions. First, lamina I of the spinal cord is the first site in the central nervous system where somatic and visceral pathways directly converge onto individual projection and local circuit neurons. Second, the mechanism of somatovisceral convergence is complex and based on functional integration of monosynaptic and polysynaptic excitatory as well as inhibitory inputs in specific groups of neurons. This complex pattern of convergence provides a substrate for alterations in the balance between visceral and somatic inputs causing referred pain.

  10. Echo-Guided Differential Popliteal Block in an Obese Patient With Intractable Painful Leg Ulcer for Early Discharge in Day Surgery.

    PubMed

    Zampi, Maddalena; Iacovazzo, Carmine; Pagano, Tommaso; Buonanno, Pasquale; Carlomagno, Mariella; Cianciulli, Flavia; Servillo, Giuseppe

    2016-06-01

    Pain management is extremely important in day surgery, and it is one of the limiting factors for this type of procedures. Locoregional anesthesia is strongly recommended for day surgery; nevertheless, it could be very difficult to localize nerve position especially in obese patients. Furthermore, a complete nerve blockade could result in a delayed discharge. We present a case of analgesic ultrasound-guided block of tibial and common peroneal nerves in the popliteal fossa without any motor function involvement in an obese patient undergoing debridement of an infected lower limb ulcer; all previous attempts of surgical debridement in day surgery with topical anesthetics had failed because of discomfort due to pain. Our aim was to ensure an optimal degree of analgesia and, at the same time, to save motor function in order to make early discharge possible. We used 15 mL ropivacaine 0.375% to obtain a differential block, taking advantage of sensitive fibers selectivity of ropivacaine. Surgical debridement was performed successfully. Our peripheral blockade was able to provide significantly prolonged analgesia without motor block that guaranteed a safe and early discharge according to the Post Anesthetic Discharge Scoring System. The satisfaction expressed by the patient and her comfort during the procedure support the choice of this approach for intractable painful ulcers of lower limb.

  11. A cross-cultural adaptation and validation of the short-form McGill Pain Questionnaire-2: Chinese version in patients with chronic visceral pain

    PubMed Central

    Wang, Jiang-Lin; Zhang, Wei-Jun; Gao, Min; Zhang, Shengfa; Tian, Dong-Hua; Chen, Jun

    2017-01-01

    Objective The present study aimed to develop a culturally appropriate and functional Standard Mandarin Chinese translation of the short-form McGill Pain Questionnaire-2 (SF-MPQ-2) and to assess its reliability and validity for characterizing chronic visceral pain in Chinese patients. Background The SF-MPQ-2 has been widely used in studies of pain epidemiology, diagnosis and treatment, and even pathophysiologic mechanisms to assess the major symptoms of clinical pain. Previous reports have shown favorable reliability, validity, and responsiveness of the SF-MPQ-2 in diverse samples of patients with chronic and acute pain. However, a culturally appropriate, functional Chinese version of the scale has never been developed. Methods Beaton’s guidelines were used for the translation and back-translation procedures. Patients (n=145) with chronic visceral pain were recruited to complete the Standard Mandarin Chinese version of the SF-MPQ-2 (SF-MPQ-2-CN), of which 41 were asked to complete the SF-MPQ-2-CN a second time, 3 days after the initial visit. The test–retest reliability was quantified using the intraclass correlation coefficient (ICC), and Cronbach’s alpha was calculated to assess internal consistency. Possible components were determined by exploratory factor analysis with varimax rotation, and a value of 0.4 was considered requisite for the loading of each factor. Results The ICC for subscales ranged from 0.909 to 0.952, and that of the total scale was 0.927, suggesting excellent reliability and validity of the SF-MPQ-2-CN. Cronbach’s alpha for subscales ranged from 0.896 to 0.916, and that of the total scale was 0.836 and 0.831 for primary and secondary visits, respectively. The factor loading matrix of the SF-MPQ-2-CN ranged from 0.734 to 0.901 for each of the following subscales: continuous, intermittent, neuropathic, and affective, revealing four components similar to the original scale. Conclusion The reliability and validity of the SF-MPQ-2-CN scale

  12. Synergistic effect of 5-hydroxytryptamine 3 and neurokinin 1 receptor antagonism in rodent models of somatic and visceral pain.

    PubMed

    Greenwood-Van Meerveld, Beverley; Mohammadi, Ehsan; Tyler, Karl; Pietra, Claudio; Bee, Lucy A; Dickenson, Anthony

    2014-10-01

    Synergistic activity has been observed between serotonergic 5-hydroxytryptamine 3 (5-HT3) and tachykinergic neurokinin 1 (NK1) receptor-mediated responses. This study investigated the efficacy of a 5-HT3 antagonist, palonosetron, and a NK1 antagonist, netupitant, alone or in combination in rodent models of somatic and visceral colonic hypersensitivity. In a rat model of experimental neuropathic pain, somatic hypersensitivity was quantified by the number of ipsilateral paw withdrawals to a von Frey filament (6g). Electrophysiologic responses were recorded in the dorsal horn neurons after mechanical or thermal stimuli. Acute colonic hypersensitivity was induced experimentally in rats by infusing dilute acetic acid (0.6%) directly into the colon. Colonic sensitivity was assessed by a visceromotor behavioral response quantified as the number of abdominal contractions in response to graded isobaric pressures (0-60 mm Hg) of colorectal distension. Palonosetron or netupitant was administered alone or in combination via oral gavage. When dosed alone, both significantly reduced somatic sensitivity, decreased the evoked response of spinal dorsal horn neurons to mechanical or thermal stimulation, and caused significant (P < 0.05) inhibition of colonic hypersensitivity in a dose-dependent manner. The combined administration of palonosetron and netupitant at doses that were ineffective alone significantly reduced both somatic and visceral sensitivity and decreased the evoked response of spinal dorsal horn neurons to mechanical or thermal stimulation. In summary, the combination of palonosetron with a NK1 receptor antagonist showed synergistic analgesic activity in rodent models of somatic and visceral hypersensitivity, and may prove to be a useful therapeutic approach to treat pain associated with irritable bowel syndrome.

  13. Tageted bipolar radiofrequency decompression with vertebroplasty for intractable radicular pain due to spinal metastasis: a case report

    PubMed Central

    Baek, Seong Jin; Lee, Eun Young

    2016-01-01

    Metastatic spinal tumors are usually quite difficult to treat. In patients with metastatic spinal tumors, conventional radiotherapy fails to relieve pain in 20–30% of cases and open surgery often causes considerable trauma and complications, which delays treatment of the primary disease. Percutaneous vertebroplasty (PVP) is considered to be useful in achieving rapid pain control and preventing further vertebral collapse due to spinal metastasis. However, symptoms of intraspinal neural compression can be contraindications to PVP. To overcome this problem, we performed PVP following targeted bipolar radiofrequency decompression, and examined the effect of the combined treatment in relieving severe radicular pain related to spinal cord compression caused by malignant metastatic tumors. PMID:27482319

  14. Application of the Harms Technique to Treat Undiagnosed Intractable C1-C2 Unilateral Neck Pain: A Case Report

    PubMed Central

    Kim, Sunny

    2016-01-01

    A 79-year-old female presented with incapacitating chronic neck pain. The patient's pain which was greatest on the left side persisted for 18 months and was described as stabbing in nature (10/10 intensity). In addition to her neck pain, the patient described having frequent headaches. After six weeks of physical therapy and undergoing a rhizotomy procedure, she showed no prolonged improvement. An epidural steroid injection provided only temporary pain relief and was followed by a successful posterior fusion using the Harms technique with iliac crest autogenous bone grafting and placement of polyaxial screws in the C1 lateral masses and C2 pedicles. At the one-year follow-up the patient reported no pain or complaints. In general, C1-C2 arthrodesis is a surgical challenge due to the proximity of neurovascular structures (vertebral arteries and spinal cord) and wide range of the joint motion. The Harms technique is one of many techniques developed to reduce anatomical risk and improve results related to biomechanical stability and fusion rates. PMID:27774361

  15. Antinociceptive effects of systemic tanshinone IIA on visceral and somatic persistent nociception and pain hypersensitivity in rats.

    PubMed

    Cao, Fa-Le; Su, Xue-Jia; Wang, Yan; Xu, Min; Shan, Liang

    2014-09-01

    Previous studies showed that tanshinone IIA (TIIA), an important lipophilic component of Danshen, has been well-established to exhibit various neuroprotective actions in the nervous system. Although we previously reported that TIIA had a significant anti-nociceptive effect in complete Freund's adjuvant (CFA)-induced pain, it is surprisingly noted that few pharmacological studies have been carried out to explore the possible analgesic action of TIIA in animals and the appropriate indications for treatment of clinical pain remain unclear. Therefore, in the present study, by using both somatic and visceral pain models, the antinociceptive and antihyperalgesic effects of TIIA were evaluated by intraperitoneal administration in rats. In the bee venom (BV) test, when compared with saline controls, systemic pre- and post-treatment with TIIA resulted in an apparent antinociception against persistent spontaneous nociception (PSN) and primary heat and mechanical hypersensitivity, while for the mirror-image heat hypersensitivity, only pre-treatment was effective. Moreover, in the formalin test, the antinociception of TIIA was significant for both phases 1 and 2 in the pretreatment groups, but only effective for phase 2 in the post-treatment group. In the acetic acid writhing test, the number of writhes was effectively blocked by both pre- and post-treatment of TIIA. Taken together, these results provide a new line of evidence showing that TIIA is also able to produce analgesia against various 'phenotypes' of nociception and hypersensitivity.

  16. Intravenous phentolamine infusion alleviates the pain of abdominal visceral cancer, including pancreatic carcinoma.

    PubMed

    Yasukawa, Masako; Yasukawa, Ken'ichi; Kamiizumi, You; Yokoyama, Ryouji

    2007-01-01

    This case report series describes eight patients (four patients with pancreatic carcinoma, one patient with hepatocellular carcinoma, one patient with gastric and rectal carcinoma, one with sigmoid colon cancer, and one with rectal cancer), whose abdominal cancer pain was treated with intravenous phentolamine infusion at 80 mg x day(-1) for 2 days. All but one of the patients had already been treated with opioids. All eight patients complained of severe abdominal pain; in five patients the pain radiated to the back, and there was associated anal pain in two patients. Analgesia was achieved in three patients; pain alleviation was obtained in four patients, but was not sustained in two of these four patients; and the treatment in one patient could not be judged for efficacy because epidural morphine was used together with the phentolamine. Adverse effects of phentolamine were tachycardia and/or hypotension.

  17. Benefits of Preventive Administration of Chlorella sp. on Visceral Pain and Cystitis Induced by a Single Administration of Cyclophosphamide in Female Wistar Rat.

    PubMed

    Hidalgo-Lucas, Sophie; Rozan, Pascale; Guérin-Deremaux, Laetitia; Baert, Blandine; Violle, Nicolas; Saniez-Degrave, Marie-Hélène; Bisson, Jean-François

    2016-05-01

    Chlorella sp. is a green microalgae containing nutrients, vitamins, minerals, and chlorophyll. In some communities, Chlorella sp. is a traditional medicinal plant used for the management of inflammation-related diseases. In a rat model, ROQUETTE Chlorella sp. (RCs) benefits were investigated on visceral pain and associated inflammatory parameters related to cystitis both induced by cyclophosphamide (CYP). RCs was orally administered every day from day 1-16 (250 and 500 mg/kg body weight). Six hours after an intraperitoneal injection of 200 mg/kg body weight of CYP, body temperature, general behavior, food intake, and body weight were recorded. Twenty-four hours after CYP injection, rats were tested in two behavioral tests, an open field and the aversive light stimulus avoidance conditioning test, to evaluate the influence of pain on general activity and learning ability of rats. After euthanasia, bladders were weighed, their thickness was scored, and the urinary hemoglobin was measured. RCs orally administered at the two dosages significantly reduced visceral pain and associated inflammatory parameters related to cystitis both induced by CYP injection, and improved rat behavior. To conclude, RCs demonstrated beneficial effects against visceral pain and cystitis.

  18. Peripheral antinociceptive effects of the cyclic endomorphin-1 analog c[YpwFG] in a mouse visceral pain model.

    PubMed

    Bedini, Andrea; Baiula, Monica; Gentilucci, Luca; Tolomelli, Alessandra; De Marco, Rossella; Spampinato, Santi

    2010-11-01

    We previously described a novel cyclic endomorphin-1 analog c[Tyr-D-Pro-D-Trp-Phe-Gly] (c[YpwFG]), acting as a mu-opioid receptor (MOR) agonist. This study reports that c[YpwFG] is more lipophilic and resistant to enzymatic hydrolysis than endomorphin-1 and produces preemptive antinociception in a mouse visceral pain model when injected intraperitoneally (i.p.) or subcutaneously (s.c.) before 0.6% acetic acid, employed to evoke abdominal writhing (i.p. ED(50)=1.24 mg/kg; s.c. ED(50)=2.13 mg/kg). This effect is reversed by the selective MOR antagonist β-funaltrexamine and by a high dose of the mu(1)-opioid receptor-selective antagonist naloxonazine. Conversely, the kappa-opioid receptor antagonist nor-binaltorphimine and the delta-opioid receptor antagonist naltrindole are ineffective. c[YpwFG] produces antinociception when injected i.p. after acetic acid (ED(50)=4.80 mg/kg), and only at a dose of 20mg/kg did it elicit a moderate antinociceptive response in the mouse, evaluated by the tail flick assay. Administration of a lower dose of c[YpwFG] (10mg/kg i.p.) apparently produces a considerable part of antinociception on acetic acid-induced writhes through peripheral opioid receptors as this action is fully prevented by i.p. naloxone methiodide, which does not readily cross the blood-brain barrier; whereas this opioid antagonist injected intracerebroventricularly (i.c.v.) is not effective. Antinociception produced by a higher dose of c[YpwFG] (20mg/kg i.p.) is partially reversed by naloxone methiodide i.c.v. administered. Thus, only at the dose of 20mg/kg c[YpwFG] can produce antinociception through both peripheral and central opioid receptors. In conclusion, c[YpwFG] displays sufficient metabolic stability to be effective after peripheral administration and demonstrates the therapeutic potential of endomorphin derivatives as novel analgesic agents to control visceral pain.

  19. Selective corticotropin-releasing factor 1 receptor antagonist E2508 reduces restraint stress-induced defecation and visceral pain in rat models.

    PubMed

    Taguchi, Ryota; Shikata, Kodo; Furuya, Yoshiaki; Hirakawa, Tetsuya; Ino, Mitsuhiro; Shin, Kogyoku; Shibata, Hisashi

    2017-01-01

    N-Cyclopropylmethyl-7-(2,6-dimethoxy-4-methoxymethylphenyl)-2-ethyl-N-(tetrahydro-2H-pyran-4-ylmethyl)pyrazolo[1,5-a]pyridin-3-amine tosylate (E2508) is a newly discovered selective corticotropin-releasing factor 1 receptor antagonist. Here, we investigated the effects of E2508 on wrap restraint stress-induced defecation and visceral pain in rats. Oral pretreatment with E2508 dose-dependently decreased stool weights after 20min wrap restraint stress and significant effects were observed at doses of 30 and 100mg/kg. However, E2508 did not affect basal defecation at doses up to 100mg/kg. In contrast, alosetron, a 5-HT3 receptor antagonist, decreased both wrap restraint stress-induced and basal stool output at a dose of 0.1mg/kg. In a rat visceral pain model, subcutaneous injections of both E2508 (0.01 and 0.1mg/kg) and alosetron (0.001 and 0.01mg/kg) significantly decreased the number of abdominal muscle contractions induced by colonic distention, suggesting these drugs reduced visceral pain. Together, these results demonstrate E2508 has the potential to be an effective therapy for the treatment of irritable bowel syndrome with a lower risk of adverse events such as constipation compared with the current clinically used 5-HT3 receptor antagonist.

  20. Disturbance of the gut microbiota in early-life selectively affects visceral pain in adulthood without impacting cognitive or anxiety-related behaviors in male rats.

    PubMed

    O'Mahony, S M; Felice, V D; Nally, K; Savignac, H M; Claesson, M J; Scully, P; Woznicki, J; Hyland, N P; Shanahan, F; Quigley, E M; Marchesi, J R; O'Toole, P W; Dinan, T G; Cryan, J F

    2014-09-26

    Disruption of bacterial colonization during the early postnatal period is increasingly being linked to adverse health outcomes. Indeed, there is a growing appreciation that the gut microbiota plays a role in neurodevelopment. However, there is a paucity of information on the consequences of early-life manipulations of the gut microbiota on behavior. To this end we administered an antibiotic (vancomycin) from postnatal days 4-13 to male rat pups and assessed behavioral and physiological measures across all aspects of the brain-gut axis. In addition, we sought to confirm and expand the effects of early-life antibiotic treatment using a different antibiotic strategy (a cocktail of pimaricin, bacitracin, neomycin; orally) during the same time period in both female and male rat pups. Vancomycin significantly altered the microbiota, which was restored to control levels by 8 weeks of age. Notably, vancomycin-treated animals displayed visceral hypersensitivity in adulthood without any significant effect on anxiety responses as assessed in the elevated plus maze or open field tests. Moreover, cognitive performance in the Morris water maze was not affected by early-life dysbiosis. Immune and stress-related physiological responses were equally unaffected. The early-life antibiotic-induced visceral hypersensitivity was also observed in male rats given the antibiotic cocktail. Both treatments did not alter visceral pain perception in female rats. Changes in visceral pain perception in males were paralleled by distinct decreases in the transient receptor potential cation channel subfamily V member 1, the α-2A adrenergic receptor and cholecystokinin B receptor. In conclusion, a temporary disruption of the gut microbiota in early-life results in very specific and long-lasting changes in visceral sensitivity in male rats, a hallmark of stress-related functional disorders of the brain-gut axis such as irritable bowel disorder.

  1. The antinociceptive effect of intravenous imipramine in colorectal distension-induced visceral pain in rats: the role of serotonergic and noradrenergic receptors.

    PubMed

    İlkaya, Fatih; Bilge, S Sırrı; Bozkurt, Ayhan; Baş, Duygu B; Erdal, Arzu; Çiftçioğlu, Engin; Kesim, Yüksel

    2014-07-01

    It has been shown that imipramine, a tricyclic antidepressant (TCA), is a potent analgesic agent. However, the effect of imipramine on visceral pain has not been extensively investigated. In the current study, our aim was to characterise the putative analgesic effect of intravenous imipramine on visceral pain in rats. Our second aim was to assess the involvement of serotonergic (5-HT₂,₃,₄) and noradrenergic (α(2A, 2B, 2C)) receptor subtypes in this putative antinociceptive effect of imipramine. Male Sprague Dawley rats (250-300 g) were implanted with venous catheters for drug administration and implanted with enamelled nichrome electrodes for electromyography of the external oblique muscles. Noxious visceral stimulation was applied via by colorectal distension (CRD). The visceromotor responses (VMRs) to CRD were quantified electromyographically before and after imipramine administration at 5, 15, 30, 60, 90 and 120 min. In the antagonist groups, the agents were administered 10 min before imipramine. The administration of imipramine (5-40 mg/kg) produced a dose-dependent reduction in VMR. The administration of yohimbine (a nonselective α₂-adrenoceptor antagonist, 1 mg/kg), BRL-44408 (an α(2A)-adrenoceptor antagonist, 1 mg/kg) or MK-912 (an α2C-adrenoceptor antagonist, 300 μg/kg) but not imiloxan (an α(2B)-adrenoceptor antagonist, 1 mg/kg) inhibited the antinociceptive effect of imipramine (20 mg/kg). Additionally, ketanserin (a 5-HT₂ receptor antagonist, 0.5, 1, and 2 mg/kg) and GR113808 (a 5-HT₄ receptor antagonist, 1 mg/kg) enhanced, and ondansetron (a 5-HT₃ receptor antagonist, 0.5, 1, and 2 mg/kg) failed to alter the imipramine-induced antinociceptive effect. Our data demonstrated that, in the CDR-induced rat visceral pain model, intravenous imipramine appeared to have antinociceptive potential and that α(2A)-/α(2C)-adrenoceptors and 5-HT₂/5-HT₄ receptors may be responsible for the antinociceptive effect of imipramine on visceral pain

  2. Intractable paroxysmal sneezing.

    PubMed

    Gopalan, Pushkas; Browning, Simon T

    2002-11-01

    Intractable paroxysmal sneezing is a rare disease primarily affecting teenage girls. We present the case of a 12-year-old girl who demonstrated the classical features of intractable paroxysmal sneezing of psychogenic origin. Most of the reported cases are psychogenic in origin, but a number of other conditions may cause intractable paraoxysmal sneeze. Apart from a detailed history, clinical examination and relevant investigations, topical nasal anaesthesia should be tried for control of symptoms--that will help to differentiate psychogenic sneezing from organic sneezing. A timely diagnosis can avoid unnecessary medical trials, parental anxiety and poor school performance, as most of the patients are very young.

  3. The antinociceptive effects of intravenous tianeptine in colorectal distension-induced visceral pain in rats: the role of 5-HT₃ receptors.

    PubMed

    Bilge, S Sırrı; Bozkurt, Ayhan; Ilkaya, Fatih; Ciftcioğlu, Engin; Kesim, Yüksel; Uzbay, Tayfun I

    2012-04-15

    Tianeptine is an unusual tricyclic antidepressant drug. In this study, we aimed to investigate the antinociceptive effect of tianeptine on visceral pain in rats and to determine whether possible antinociceptive effect of tianeptine is mediated by serotonergic (5-HT(2,3)) and noradrenergic (α(1,2)) receptor subtypes. Male Sprague Dawley rats (250-300 g) were supplied with a venous catheter, for drug administrations, and enameled nichrome electrodes, for electromyography, at external oblique musculature. Colorectal distension (CRD) was employed as the noxious visceral stimulus and the visceromotor response (VMR) to CRD was quantified electromyographically before and 5, 15, 30, 60, 90 and 120 min after tianeptine administration. Antagonists were administered 10 min before tianeptine for their ability to change tianeptine antinociception. Intravenous administration of tianeptine (2.5-20 mg/kg) produced a dose-dependent reduction in VMR. Administration of 5-HT(3) receptor antagonist ondansetron (0.5, 1 and 2 mg/kg), but not 5-HT(2) receptor antagonist ketanserine (0.5, 1 and 2 mg/kg), reduced the antinociceptive effect of tianeptine (10mg/kg). In addition, administration of α(1)-adrenoceptor antagonist prazosin (1 mg/kg) or α(2)-adrenoceptor antagonist yohimbine (1 mg/kg) did not cause any significant effect on the tianeptine-induced antinociception. Our data indicate that intravenous tianeptine exerts a pronounced antinociception against CRD-induced visceral pain in rats, and suggests that the antinociceptive effect of tianeptine appears to be mediated in part by 5-HT(3) receptors, but does not involve 5-HT(2) receptors or α-adrenoceptors.

  4. Neuromodulation of the cervical spinal cord in the treatment of chronic intractable neck and upper extremity pain: a case series and review of the literature.

    PubMed

    Vallejo, Ricardo; Kramer, Jeffery; Benyamin, Ramsin

    2007-03-01

    Electrical spinal neuromodulation in the form of spinal cord stimulation is currently used for treating chronic painful conditions such as complex regional pain syndrome, diabetic neuropathy, postherpetic neuralgia, peripheral ischemia, low back pain, and other conditions refractory to more conservative treatments. To date, there are very few published reports documenting the use of spinal cord stimulation in the treatment of head/neck and upper limb pain. This paper reports a case series of 5 consecutive patients outlining the use of spinal cord stimulation to treat upper extremity pain. All subjects had previously undergone cervical fusion surgery to treat chronic neck and upper limb pain. Patients were referred following failure of the surgery to manage their painful conditions. Spinal cord stimulators were placed in the cervical epidural space through a thoracic needle placement. Stimulation parameters were adjusted to capture as much of the painful area(s) as possible. In total, 4 out of 5 patients moved to implantation. In all cases, patients reported significant (70-90%) reductions in pain, including axial neck pain and upper extremity pain. Interestingly, 2 patients with associated headache and lower extremity pain obtained relief after paresthesia-steering reportedly covered those areas. Moreover, 2 patients reported that cervical spinal cord stimulation significantly improved axial low back pain. Patients continue to report excellent pain relief up to 9 months following implantation. This case series documents the successful treatment of neck and upper extremity pain following unsuccessful cervical spine fusion surgery. Given this initial success, prospective, controlled studies are warranted to more adequately assess the long term utility and cost effectiveness of electrical neuromodulation treatment of chronic neck and upper extremity pain.

  5. The GABA(B) receptor agonist, baclofen, and the positive allosteric modulator, CGP7930, inhibit visceral pain-related responses to colorectal distension in rats.

    PubMed

    Brusberg, Mikael; Ravnefjord, Anna; Martinsson, Rakel; Larsson, Håkan; Martinez, Vicente; Lindström, Erik

    2009-02-01

    Activation of GABA(B) receptors by the selective agonist baclofen produces anti-nociceptive effects in animal models of somatic pain. The aim of the present study was to evaluate the effect of baclofen and the GABA(B) receptor positive allosteric modulator CGP7930 on pseudo-affective responses to colorectal distension in rats. Female Sprague-Dawley rats were subjected to repeated, noxious colorectal distension (CRD) (12 distensions at 80 mmHg, for 30 s with 5 min intervals). The visceromotor response (VMR) and cardiovascular responses (mean arterial blood pressure (ABP) and heart rate (HR)) to CRD were monitored in conscious, telemetrized animals. Baclofen (0.3-3 micromol/kg, i.v.) reduced the VMR to CRD dose-dependently, reaching a 61% maximal inhibition (p < 0.001). The highest doses of baclofen attenuated CRD-evoked increases in ABP by 17% (p > 0.05) and reduced the change in HR by 48% (p < 0.01). CGP7930 (3-30 micromol/kg, i.v.) reduced the VMR to CRD in a dose-dependent fashion with a maximal inhibition of 31% (p < 0.05). The highest dose of CGP7930 also attenuated the increase in ABP by 18% (p > 0.05) and inhibited the increase in HR by 24% (p < 0.05) associated with CRD. Neither baclofen nor CGP7930 affected colorectal compliance. The results suggest that activation of GABA(B) receptors produces anti-nociceptive effects in a rat model of mechanically induced visceral pain. While CGP7930 was less efficacious than baclofen overall, positive allosteric modulation of GABA(B) receptors may represent a valid approach in the treatment of visceral pain conditions, with the possibility of an improved safety profile compared to full agonism.

  6. The Glt1 glutamate receptor mediates the establishment and perpetuation of chronic visceral pain in an animal model of stress-induced bladder hyperalgesia.

    PubMed

    Ackerman, A Lenore; Jellison, Forrest C; Lee, Una J; Bradesi, Sylvie; Rodríguez, Larissa V

    2016-04-01

    Psychological stress exacerbates interstitial cystitis/bladder pain syndrome (IC/BPS), a lower urinary tract pain disorder characterized by increased urinary frequency and bladder pain. Glutamate (Glu) is the primary excitatory neurotransmitter modulating nociceptive networks. Glt1, an astrocytic transporter responsible for Glu clearance, is critical in pain signaling termination. We sought to examine the role of Glt1 in stress-induced bladder hyperalgesia and urinary frequency. In a model of stress-induced bladder hyperalgesia with high construct validity to human IC/BPS, female Wistar-Kyoto (WKY) rats were subjected to 10-day water avoidance stress (WAS). Referred hyperalgesia and tactile allodynia were assessed after WAS with von Frey filaments. After behavioral testing, we assessed Glt1 expression in the spinal cord by immunoblotting. We also examined the influence of dihydrokainate (DHK) and ceftriaxone (CTX), which downregulate and upregulate Glt1, respectively, on pain development. Rats exposed to WAS demonstrated increased voiding frequency, increased colonic motility, anxiety-like behaviors, and enhanced visceral hyperalgesia and tactile allodynia. This behavioral phenotype correlated with decreases in spinal Glt1 expression. Exogenous Glt1 downregulation by DHK resulted in hyperalgesia similar to that following WAS. Exogenous Glt1 upregulation via intraperitoneal CTX injection inhibited the development of and reversed preexisting pain and voiding dysfunction induced by WAS. Repeated psychological stress results in voiding dysfunction and hyperalgesia that correlate with altered central nervous system glutamate processing. Manipulation of Glu handling altered the allodynia developing after psychological stress, implicating Glu neurotransmission in the pathophysiology of bladder hyperalgesia in the WAS model of IC/BPS.

  7. Intractable Pruritus After Traumatic Spinal Cord Injury

    PubMed Central

    Crane, Deborah A; Jaffee, Kenneth M; Kundu, Anjana

    2009-01-01

    Background: This report describes a young woman with incomplete traumatic cervical spinal cord injury and intractable pruritus involving her dorsal forearm. Method: Case report. Findings: Anatomic distribution of the pruritus corresponded to the dermatomal distribution of her level of spinal cord injury and vertebral fusion. Symptoms were attributed to the spinal cord injury and possible cervical root injury. Pruritus was refractory to all treatments, including topical lidocaine, gabapentin, transcutaneous electrical nerve stimulation, intravenous Bier block, stellate ganglion block, and acupuncture. Conclusions: Further understanding of neuropathic pruritus is needed. Diagnostic workup of intractable pruritus should include advanced imaging to detect ongoing nerve root compression. If diagnostic studies suggest radiculopathy, epidural steroid injection should be considered. Because the autonomic nervous system may be involved in complex chronic pain or pruritic syndromes, sympatholysis via such techniques as stellate ganglion block might be effective. PMID:19777867

  8. Changes in saccharin preference behavior as a primary outcome to evaluate pain and analgesia in acetic acid-induced visceral pain in mice

    PubMed Central

    de la Puente, Beatriz; Romero-Alejo, Elizabeth; Vela, José Miguel; Merlos, Manuel; Zamanillo, Daniel; Portillo-Salido, Enrique

    2015-01-01

    Reflex-based procedures are important measures in preclinical pain studies that evaluate stimulated behaviors. These procedures, however, are insufficient to capture the complexity of the pain experience, which is often associated with the depression of several innate behaviors. While recent studies have made efforts to evidence the suppression of some positively motivated behaviors in certain pain models, they are still far from being routinely used as readouts for analgesic screening. Here, we characterized and compared the effect of the analgesic ibuprofen (Ibu) and the stimulant, caffeine, in assays of acute pain-stimulated and pain-depressed behavior. Intraperitoneal injection of acetic acid (AA) served as a noxious stimulus to stimulate a writhing response or depress saccharin preference and locomotor activity (LMA) in mice. AA injection caused the maximum number of writhes between 5 and 20 minutes after administration, and writhing almost disappeared 1 hour later. AA-treated mice showed signs of depression-like behaviors after writhing resolution, as evidenced by reduced locomotion and saccharin preference for at least 4 and 6 hours, respectively. Depression-like behaviors resolved within 24 hours after AA administration. A dose of Ibu (40 mg/kg) – inactive to reduce AA-induced abdominal writhing – administered before or after AA injection significantly reverted pain-induced saccharin preference deficit. The same dose of Ibu also significantly reverted the AA-depressed LMA, but only when it was administered after AA injection. Caffeine restored locomotion – but not saccharin preference – in AA-treated mice, thus suggesting that the reduction in saccharin preference – but not in locomotion – was specifically sensitive to analgesics. In conclusion, AA-induced acute pain attenuated saccharin preference and LMA beyond the resolution of writhing behavior, and the changes in the expression of hedonic behavior, such as sweet taste preference, can be

  9. Changes in saccharin preference behavior as a primary outcome to evaluate pain and analgesia in acetic acid-induced visceral pain in mice.

    PubMed

    de la Puente, Beatriz; Romero-Alejo, Elizabeth; Vela, José Miguel; Merlos, Manuel; Zamanillo, Daniel; Portillo-Salido, Enrique

    2015-01-01

    Reflex-based procedures are important measures in preclinical pain studies that evaluate stimulated behaviors. These procedures, however, are insufficient to capture the complexity of the pain experience, which is often associated with the depression of several innate behaviors. While recent studies have made efforts to evidence the suppression of some positively motivated behaviors in certain pain models, they are still far from being routinely used as readouts for analgesic screening. Here, we characterized and compared the effect of the analgesic ibuprofen (Ibu) and the stimulant, caffeine, in assays of acute pain-stimulated and pain-depressed behavior. Intraperitoneal injection of acetic acid (AA) served as a noxious stimulus to stimulate a writhing response or depress saccharin preference and locomotor activity (LMA) in mice. AA injection caused the maximum number of writhes between 5 and 20 minutes after administration, and writhing almost disappeared 1 hour later. AA-treated mice showed signs of depression-like behaviors after writhing resolution, as evidenced by reduced locomotion and saccharin preference for at least 4 and 6 hours, respectively. Depression-like behaviors resolved within 24 hours after AA administration. A dose of Ibu (40 mg/kg) - inactive to reduce AA-induced abdominal writhing - administered before or after AA injection significantly reverted pain-induced saccharin preference deficit. The same dose of Ibu also significantly reverted the AA-depressed LMA, but only when it was administered after AA injection. Caffeine restored locomotion - but not saccharin preference - in AA-treated mice, thus suggesting that the reduction in saccharin preference - but not in locomotion - was specifically sensitive to analgesics. In conclusion, AA-induced acute pain attenuated saccharin preference and LMA beyond the resolution of writhing behavior, and the changes in the expression of hedonic behavior, such as sweet taste preference, can be used as a more

  10. Renal infarction due to spontaneous dissection of the renal artery: an unusual cause of non-visceral type abdominal pain

    PubMed Central

    Kang, James H-E; Kang, Jin-Yong; Morgan, Robert

    2013-01-01

    A 44-year-old man presented with very severe right upper quadrant pain of sudden onset. This was exacerbated by movement but unaffected by food or defaecation. It was continuous—day and night —but resolved over a 1-week period. The physical examination was normal at presentation, by which time the pain had resolved. His white cell count, alanine transaminase and C reactive protein were elevated but normalised after 10 days. An abdominal CT showed low density lesions in the right kidney consistent with segmental infarcts. CT angiogram showed a dissection of the right renal artery. The patient remained asymptomatic and normotensive when reviewed 1 month later. PMID:24049091

  11. Effects of novel TRPA1 receptor agonist ASP7663 in models of drug-induced constipation and visceral pain.

    PubMed

    Kojima, Ryosuke; Nozawa, Katsura; Doihara, Hitoshi; Keto, Yoshihiro; Kaku, Hidetaka; Yokoyama, Toshihide; Itou, Hiroyuki

    2014-01-15

    Constipation is a major gastrointestinal motility disorder with clinical need for effective drugs. We previously reported that transient receptor potential ankyrin 1 (TRPA1) is highly expressed in enterochromaffin (EC) cells, which are 5-hydroxytryptamine (5-HT)-releasing cells, and might therefore be a novel target for constipation. Here, we examined the effects of ASP7663, a novel and selective TRPA1 agonist, in constipation models as well as an abdominal pain model. ASP7663 activated human, rat, and mouse TRPA1 and released 5-HT from QGP-1 cells, and oral but not intravenous administration of ASP7663 significantly improved the loperamide-induced delay in colonic transit in mice. While pretreatment with the TRPA1 antagonist HC-030031 and vagotomy both inhibited the ameliorating effect of oral ASP7663 on the colonic transit, both orally and intravenously administered ASP7663 significantly inhibited colorectal distension (CRD)-induced abdominal pain response in rats. Taken together, these results demonstrate that ASP7663 exerts both anti-constipation and anti-abdominal pain actions, the former is likely triggered from the mucosal side of the gut wall via activation of vagus nerves while the latter is assumed to be provoked through systemic blood flow. We conclude that ASP7663 can be an effective anti-constipation drug with abdominal analgesic effect.

  12. Cortical deactivations during gastric fundus distension in health: visceral pain-specific response or attenuation of 'default mode' brain function? A H2 15O-PET study.

    PubMed

    van Oudenhove, L; Vandenberghe, J; Dupont, P; Geeraerts, B; Vos, R; Bormans, G; van Laere, K; Fischler, B; Demyttenaere, K; Janssens, J; Tack, J

    2009-03-01

    Gastric distension activates a cerebral network including brainstem, thalamus, insula, perigenual anterior cingulate, cerebellum, ventrolateral prefrontal cortex and potentially somatosensory regions. Cortical deactivations during gastric distension have hardly been reported. To describe brain areas of decreased activity during gastric fundus distension compared to baseline, using data from our previously published study (Gastroenterology, 128, 2005 and 564). H(2) (15)O-brain positron emission tomography was performed in 11 healthy volunteers during five conditions (random order): (C(1)) no distension (baseline); isobaric distension to individual thresholds for (C(2)) first, (C(3)) marked, (C(4)) unpleasant sensation and (C(5)) sham distension. Subtraction analyses were performed (in SPM2) to determine deactivated areas during distension compared to baseline, with a threshold of P(uncorrected_voxel_level) < 0.001 and P(corrected_cluster_level) < 0.05. Baseline-maximal distension (C(1)-C(4)) yielded significant deactivations in: (i) bilateral occipital, lateral parietal and temporal cortex as well as medial parietal lobe (posterior cingulate and precuneus) and medial temporal lobe (hippocampus and amygdala), (ii) right dorsolateral and dorso- and ventromedial PFC, (iii) left subgenual ACC and bilateral caudate head. Intragastric pressure and epigastric sensation score correlated negatively with brain activity in similar regions. The right hippocampus/amygdala deactivation was specific to sham. Gastric fundus distension in health is associated with extensive cortical deactivations, besides the activations described before. Whether this represents task-independent suspension of 'default mode' activity (as described in various cognitive tasks) or an visceral pain/interoception-specific process remains to be elucidated.

  13. Development, plasticity and modulation of visceral afferents

    PubMed Central

    Christianson, Julie A.; Bielefeldt, Klaus; Altier, Christophe; Cenac, Nicolas; Davis, Brian M.; Gebhart, Gerald F.; High, Karin W.; Kollarik, Marian; Randich, Alan; Undem, Brad; Vergnolle, Nathalie

    2010-01-01

    Visceral pain is the most common reason for doctor visits in the US. Like somatic pain, virtually all visceral pain sensations begin with the activation of primary sensory neurons innervating the viscera and/or the blood vessels associated with these structures. Visceral afferents also play a central role in tissue homeostasis. Recent studies show that in addition to monitoring the state of the viscera, they perform efferent functions through the release of small molecules (e.g. peptides like CGRP) that can drive inflammation, thereby contributing to the development of visceral pathologies (e.g. diabetes Razavi, R., Chan, Y., Afifiyan, F.N., Liu, X.J., Wan, X., Yantha, J., Tsui, H., Tang, L., Tsai, S., Santamaria, P., Driver, J.P., Serreze, D., Salter, M.W., Dosch, H.M., 2006. TRPV1+ sensory neurons control beta cell stress and islet inflammation in autoimmune diabetes, Cell 127 1123–1135). Visceral afferents are heterogeneous with respect to their anatomy, neurochemistry and function. They are also highly plastic in that their cellular environment continuously influences their response properties. This plasticity makes them susceptible to long-term changes that may contribute significantly to the development of persistent pain states such as those associated with irritable bowel syndrome, pancreatitis, and visceral cancers. This review examines recent insights into visceral afferent anatomy and neurochemistry and how neonatal insults can affect the function of these neurons in the adult. New approaches to the treatment of visceral pain, which focus on primary afferents, will also be discussed. PMID:19150371

  14. Update in cancer pain syndromes.

    PubMed

    Chang, Victor T; Janjan, Nora; Jain, Subash; Chau, Chi

    2006-12-01

    Cancer pain assessment and management are integral to palliative medicine. This paper reviews recent publications in the period 1999-2004 in the broad categories of epidemiology, pain assessment, nonpharmacologic approaches to cancer pain (radiation therapy, anesthetic blocks, palliative surgery and chemotherapy, complementary and alternative medicine), and in nociceptive pain, neuropathic pain, visceral pain, and bone pain.

  15. Metabolic treatments for intractable epilepsy.

    PubMed

    Kelley, Sarah A; Hartman, Adam L

    2011-09-01

    When a child on anticonvulsant medications continues to have seizures, what other options should be considered? Over the past 100 years, dietary therapies for the treatment of intractable epilepsy have become more widely recognized, and their use has continued to expand throughout the world. An increasing number of studies has shown efficacy of these metabolic treatments in improving seizure control. Currently, 4 types of dietary therapy are available in the clinic: the classic long chain fatty acid "ketogenic" diet, the medium chain triglyceride diet, the modified Atkins diet, and the low glycemic index treatment. These therapies should be considered earlier in the treatment of intractable epilepsy because they offer a different approach to treatment that has proven efficacious, tolerable, and cost-effective.

  16. Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain.

    PubMed

    Johnson, Jeremy R; Burnell-Nugent, Mary; Lossignol, Dominique; Ganae-Motan, Elena Doina; Potts, Richard; Fallon, Marie T

    2010-02-01

    This study compared the efficacy of a tetrahydrocannabinol:cannabidiol (THC:CBD) extract, a nonopioid analgesic endocannabinoid system modulator, and a THC extract, with placebo, in relieving pain in patients with advanced cancer. In total, 177 patients with cancer pain, who experienced inadequate analgesia despite chronic opioid dosing, entered a two-week, multicenter, double-blind, randomized, placebo-controlled, parallel-group trial. Patients were randomized to THC:CBD extract (n = 60), THC extract (n = 58), or placebo (n = 59). The primary analysis of change from baseline in mean pain Numerical Rating Scale (NRS) score was statistically significantly in favor of THC:CBD compared with placebo (improvement of -1.37 vs. -0.69), whereas the THC group showed a nonsignificant change (-1.01 vs. -0.69). Twice as many patients taking THC:CBD showed a reduction of more than 30% from baseline pain NRS score when compared with placebo (23 [43%] vs. 12 [21%]). The associated odds ratio was statistically significant, whereas the number of THC group responders was similar to placebo (12 [23%] vs. 12 [21%]) and did not reach statistical significance. There was no change from baseline in median dose of opioid background medication or mean number of doses of breakthrough medication across treatment groups. No significant group differences were found in the NRS sleep quality or nausea scores or the pain control assessment. However, the results from the European Organisation for Research and Treatment of Cancer Quality of Life Cancer Questionnaire showed a worsening in nausea and vomiting with THC:CBD compared with placebo (P = 0.02), whereas THC had no difference (P = 1.0). Most drug-related adverse events were mild/moderate in severity. This study shows that THC:CBD extract is efficacious for relief of pain in patients with advanced cancer pain not fully relieved by strong opioids.

  17. The ERK 1 and 2 Pathway in the Nervous System: From Basic Aspects to Possible Clinical Applications in Pain and Visceral Dysfunction

    PubMed Central

    Cruz, Célia D; Cruz, Francisco

    2007-01-01

    The extracellular signal-regulated kinases 1 and 2 (ERK) cascade, member of the mitogen-activated protein kinases superfamily of signalling pathways, is one of the best characterized pathways as many protein interactions and phosphorylation events have been systematically studied. Traditionally, ERK are associated with the regulation of proliferation and differentiation as well as survival of various cell types. Their activity is controlled by phosphorylation on specific aminoacidic residues, which is induced by a variety of external cues, including growth-promoting factors. In the nervous system, ERK phosphorylation is induced by binding of neurotrophins to their specific tyrosine kinase receptors or by neuronal activity leading to glutamate release and binding to its ionotropic and metabotropic receptors. Some studies have provided evidence of its importance in neuroplastic events. In particular, ERK phosphorylation in the spinal cord was shown to be nociceptive-specific and its upregulation, occurring in cases of chronic inflammatory and neuropathic pain, seems to be of the utmost importance to behavioural changes observed in those conditions. In fact, experiments using specific inhibitors of ERK phosphorylation have proved that ERK directly contributes to allodynia and hyperalgesia caused by spinal cord injury or chronic pain. Additionally, spinal ERK phosphorylation regulates the micturition reflex in experimental models of bladder inflammation and chronic spinal cord transection. In this review we will address the main findings that suggest that ERK might be a future therapeutic target to treat pain and other complications arising from chronic pain or neuronal injury. PMID:19305741

  18. Therapeutic mechanisms of a mindfulness-based treatment for IBS: Effects on visceral sensitivity, catastrophizing, and affective processing of pain sensations

    PubMed Central

    Garland, Eric L.; Gaylord, Susan A.; Palsson, Olafur; Faurot, Keturah; Mann, J. Douglas; Whitehead, William E.

    2013-01-01

    Irritable bowel syndrome (IBS) is a prevalent functional disorder characterized by abdominal pain and hypervigilance to gastrointestinal sensations. We hypothesized that mindfulness training (MT), which promotes nonreactive awareness of emotional and sensory experience, may target underlying mechanisms of IBS including affective pain processing and catastrophic appraisals of gastrointestinal sensations. Seventy five female IBS patients were randomly assigned to participate in either 8 weeks of MT or a social support group. A theoretically grounded, multivariate path model tested therapeutic mediators of the effect of MT on IBS severity and quality of life. Results suggest that MT exerts significant therapeutic effects on IBS symptoms by promoting nonreactivity to gut-focused anxiety and catastrophic appraisals of the significance of abdominal sensations coupled with a refocusing of attention onto interoceptive data with less emotional interference. Hence, MT appears to target and ameliorate the underlying pathogenic mechanisms of IBS. PMID:22161025

  19. Attenuation of capsaicin-induced acute and visceral nociceptive pain by alpha- and beta-amyrin, a triterpene mixture isolated from Protium heptaphyllum resin in mice.

    PubMed

    Oliveira, Francisco A; Costa, Charllynton L S; Chaves, Mariana H; Almeida, Fernanda R C; Cavalcante, Italo J M; Lima, Alana F; Lima, Roberto C P; Silva, Regilane M; Campos, Adriana Rolim; Santos, Flavia A; Rao, Vietla S N

    2005-10-21

    The triterpene mixture, alpha- and beta-amyrin, isolated from Protium heptaphyllum resin was evaluated on capsaicin-evoked nociception in mice. Orally administered alpha- and beta-amyrin (3 to 100 mg/kg) significantly suppressed the nociceptive behaviors--evoked by either subplantar (1.6 microg) or intracolonic (149 microg) application of capsaicin. The antinociception produced by alpha- and beta-amyrin against subplantar capsaicin-induced paw-licking behavior was neither potentiated nor attenuated by ruthenium red (1.5 mg/kg, s.c.), a non-specific antagonist of vanilloid receptor (TRPV1), but was greatly abolished in animals pretreated with naloxone (2 mg/kg, s.c.), suggesting an opioid mechanism. However, participation of alpha2-adrenoceptor involvement was unlikely since yohimbine (2 mg/kg, i.p.) pretreatment failed to block the antinociceptive effect of alpha- and beta-amyrin in the experimental model of visceral nociception evoked by intracolonic capsaicin. The triterpene mixture (3 to 30 mg/kg, p.o.) neither altered significantly the pentobarbital sleeping time, nor impaired the ambulation or motor coordination in open-field and rota-rod tests, respectively, indicating the absence of sedative or motor abnormality that could account for its antinociception. Nevertheless, alpha- and beta-amyrin could significantly block the capsaicin (10 mg/kg, s.c.)-induced hyperthermic response but not the initial hypothermia. These results suggest that the triterpene mixture, alpha- and beta-amyrin has an analgesia inducing effect, possibly involving vanilloid receptor (TRPV1) and an opioid mechanism.

  20. Berberine Improves Intestinal Motility and Visceral Pain in the Mouse Models Mimicking Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D) Symptoms in an Opioid-Receptor Dependent Manner

    PubMed Central

    Pan, Qiuhui; Fichna, Jakub; Zheng, Lijun; Wang, Kesheng; Yu, Zhen; Li, Yongyu; Li, Kun; Song, Aihong; Liu, Zhongchen; Song, Zhenshun; Kreis, Martin

    2015-01-01

    Background and Aims Berberine and its derivatives display potent analgesic, anti-inflammatory and anticancer activity. Here we aimed at characterizing the mechanism of action of berberine in the gastrointestinal (GI) tract and cortical neurons using animal models and in vitro tests. Methods The effect of berberine was characterized in murine models mimicking diarrhea-predominant irritable bowel syndrome (IBS-D) symptoms. Then the opioidantagonists were used to identify the receptors involved. Furthermore, the effect of berberineon opioid receptors expression was established in the mouse intestine and rat fetal cortical neurons. Results In mouse models, berberine prolonged GI transit and time to diarrhea in a dose-dependent manner, and significantly reduced visceral pain. In physiological conditions the effects of berberine were mediated by mu- (MOR) and delta- (DOR) opioidreceptors; hypermotility, excessive secretion and nociception were reversed by berberine through MOR and DOR-dependent action. We also found that berberine increased the expression of MOR and DOR in the mouse bowel and rat fetal cortical neurons. Conclusion Berberine significantly improved IBS-D symptoms in animal models, possibly through mu- and delta- opioid receptors. Berberine may become a new drug candidate for the successful treatment of IBS-D in clinical conditions. PMID:26700862

  1. Delivery systems of opioid analgesics for pain relief: a review.

    PubMed

    Leppert, Wojciech; Krajnik, Malgorzata; Wordliczek, Jerzy

    2013-01-01

    Chronic pain is usually treated with pharmacological measures using opioids alone or in combination with adjuvant analgesics that play an important role in the treatment of pain not fully responsive to opioids administered alone, especially in neuropathic, bone and visceral colicky pain. The important part of the chronic pain treatment is the appropriate use of non-pharmacological measures along with psychosocial and spiritual support. Opioids may be administered by different routes; the most common and most convenient for majority of treated patients are oral and transdermal. However, in certain circumstances such as inability to swallow, lack of analgesic efficacy and intractable opioid-induced adverse effects parenteral routes (subcutaneous, intravenous) might be more useful. When these routes fail, in some patients intrathecal administration of opioids is required. Recently, more patients have been treated with short-acting opioids for breakthrough pain with sublingual, buccal and intranasal routes of opioid administration that may provide efficacy superior to oral and comparable to intravenous routes. Alternative routes comprise rectal, inhaled and topical administration of opioids. This article discusses various routes of opioid administration.

  2. Rejection of deeply implanted foreign body induced by acupuncture treatment in patient suffering intractable pains lasting ten years following traumatic injury to the left scapular region during a road accident.

    PubMed

    Sternfeld, M; Hod, I

    1986-01-01

    Upper back pains lasting ten years were promptly improved in a 63 year old woman following the rejection of a forgotten foreign glass body, through a scar located over the left scapula, and treated by acupuncture. The patient insisted on having this treatment after unsuccessful prolonged and multi-disciplinary formal medical interventions culminating in preparations for exploratory surgery. The acupuncture directed to the scar induced an inflammatory reaction characterized by a sterile granulomatous reaction which surrounded a large piece of glass, apparently implanted in the soft tissue of the suprascapular area during a severe road accident which occurred ten years previously. The surgical intervention was avoided.

  3. Visceral larva migrans

    MedlinePlus

    ... with certain parasites found in the intestines of dogs and cats. Causes Visceral larva migrans (VLM) is ... parasites) that are found in the intestines of dogs and cats. Eggs produced by these worms are ...

  4. New insights into visceral hypersensitivity--clinical implications in IBS.

    PubMed

    Zhou, QiQi; Verne, G Nicholas

    2011-06-01

    A subset of patients with IBS have visceral hypersensitivity and/or somatic hypersensitivity. Visceral hypersensitivity might have use as a clinical marker of IBS and could account for symptoms of urgency for bowel movements, bloating and abdominal pain. The mechanisms that lead to chronic visceral hypersensitivity in patients who have IBS are unclear. However, several working models may be considered, including: nociceptive input from the colon that leads to hypersensitivity; increased intestinal permeability that induces a visceral nociceptive drive; and alterations in the expression of microRNAs in gastrointestinal tissue that might be delivered via blood microvesicles to other target organs, such as the peripheral and/or central nervous system. As such, the chronic visceral hypersensitivity that is present in a subset of patients with IBS might be maintained by both peripheral and central phenomena. The theories underlying the development of chronic visceral hypersensitivity in patients with IBS are supported by findings from new animal models in which hypersensitivity follows transient inflammation of the colon. The presence of somatic hypersensitivity and an alteration in the neuroendocrine system in some patients who have IBS suggests that multisystemic factors are involved in the overall disorder. Thus, IBS is similar to other chronic pain disorders, such as fibromyalgia, chronic regional pain disorder and temporomandibular joint disorder, as chronic nociceptive mechanisms are activated in all of these disorders.

  5. Iohexol and diatrizoate: comparison in visceral arteriography

    SciTech Connect

    Adam, A.; Hemingway, A.P.; Allison, D.J.

    1985-05-01

    Iohexol, a low osmolality, nonionic contrast medium, and diatrizoate, a conventional ionic contrast medium, were evaluated for patient tolerance during visceral arteriography. Almost all the procedures performed with iohexol were painless: most patients given this agent reported only a mild feeling of warmth. Diatrizoate produced some pain and a feeling of intense heat in most patients. Both media produced excellent radiographic results and no serious adverse reactions occurred.

  6. Zeta Inhibitory Peptide as a Novel Therapy to Control Chronic Visceral Hypersensitivity in a Rat Model

    PubMed Central

    Chen, Yu; Guo, Lixia; Dai, Hengfen; Huang, Yang; Chen, Qianqian; Lin, Chun

    2016-01-01

    Background The pathogenesis of multiple chronic visceral pain syndromes, such as irritable bowel syndrome (IBS), is not well known, and as a result current therapies are ineffective. The objective of this study was to investigate the effect of spinal protein kinase M zeta (PKMζ) on visceral pain sensitivity in rats with IBS to better understand the pathogenesis and investigate the effect of zeta inhibitory peptide (ZIP) as a therapy for chronic visceral pain. Methods Visceral hypersensitivity rats were produced by neonatal maternal separation (NMS). Visceral pain sensitivity was assessed by electromyographic (EMG) responses of abdominal muscles to colorectal distention (CRD). Spinal PKMζ and phosphorylated PKMζ (p-PKMζ) were detected by western blot. Varying doses of ZIP were intrathecally administered to investigate the role of spinal PKMζ in chronic visceral hypersensitivity. The open field test was used to determine if ZIP therapy causes spontaneous motor activity side effects. Results Graded CRD pressure significantly increased EMG responses in NMS rats compared to control rats (p < 0.05). p-PKMζ expression increased in the thoracolumbar and lumbosacral spinal cord in the IBS-like rats with notable concomitant chronic visceral pain compared to control rats (p < 0.05). EMG data revealed that intrathecal ZIP injection (1, 5, and 10 μg) dose-dependently attenuated visceral pain hypersensitivity in IBS-like rats. Conclusions Phosphorylated PKMζ may be involved in the spinal central sensitization of chronic visceral hypersensitivity in IBS, and administration of ZIP could effectively treat chronic visceral pain with good outcomes in rat models. PMID:27776136

  7. Sequencing Intractable DNA to Close Microbial Genomes

    SciTech Connect

    Hurt, Jr., Richard Ashley; Brown, Steven D; Podar, Mircea; Palumbo, Anthony Vito; Elias, Dwayne A

    2012-01-01

    Advancement in high throughput DNA sequencing technologies has supported a rapid proliferation of microbial genome sequencing projects, providing the genetic blueprint for for in-depth studies. Oftentimes, difficult to sequence regions in microbial genomes are ruled intractable resulting in a growing number of genomes with sequence gaps deposited in databases. A procedure was developed to sequence such difficult regions in the non-contiguous finished Desulfovibrio desulfuricans ND132 genome (6 intractable gaps) and the Desulfovibrio africanus genome (1 intractable gap). The polynucleotides surrounding each gap formed GC rich secondary structures making the regions refractory to amplification and sequencing. Strand-displacing DNA polymerases used in concert with a novel ramped PCR extension cycle supported amplification and closure of all gap regions in both genomes. These developed procedures support accurate gene annotation, and provide a step-wise method that reduces the effort required for genome finishing.

  8. Intractable diarrhoea of infancy and latent otomastoiditis.

    PubMed Central

    Salazar de Sousa, J; da Silva, A; da Costa Ribeiro, V

    1980-01-01

    In 16 infants with intractable diarrhoea, latent otomastoiditis was found in 9 (3 at necropsy and 6 at myringotomy-antrotomy). In 5 of the 6 operated group, surgery was followed by a striking cessation of the diarrhoea and with weight gain. It is concluded that (1) latent otomastoiditis may be a perpetuating factor in intractable diarrhoea; (2) myringotomy-antrotomy should be considered if other forms of treatment have failed, and especially if there is leucocytosis; (3) mastoiditis with diffuse osteitis seems to be associated with a poor prognosis. PMID:7458392

  9. Roles of prefrontal cortex and paraventricular thalamus in affective and mechanical components of visceral nociception.

    PubMed

    Jurik, Angela; Auffenberg, Eva; Klein, Sabine; Deussing, Jan M; Schmid, Roland M; Wotjak, Carsten T; Thoeringer, Christoph K

    2015-12-01

    Visceral pain represents a major clinical challenge in the management of many gastrointestinal disorders, eg, pancreatitis. However, cerebral neurobiological mechanisms underlying visceral nociception are poorly understood. As a representative model of visceral nociception, we applied cerulein hyperstimulation in C57BL6 mice to induce acute pancreatitis and performed a behavioral test battery and c-Fos staining of brains. We observed a specific pain phenotype and a significant increase in c-Fos immunoreactivity in the paraventricular nucleus of the thalamus (PVT), the periaqueductal gray, and the medial prefrontal cortex (mPFC). Using neuronal tracing, we observed projections of the PVT to cortical layers of the mPFC with contacts to inhibitory GABAergic neurons. These inhibitory neurons showed more activation after cerulein treatment suggesting thalamocortical "feedforward inhibition" in visceral nociception. The activity of neurons in pancreatitis-related pain centers was pharmacogenetically modulated by designer receptors exclusively activated by designer drugs, selectively and cell type specifically expressed in target neurons using adeno-associated virus-mediated gene transfer. Pharmacogenetic inhibition of PVT but not periaqueductal gray neurons attenuated visceral pain and induced an activation of the descending inhibitory pain pathway. Activation of glutamatergic principle neurons in the mPFC, but not inhibitory neurons, also reversed visceral nociception. These data reveal novel insights into central pain processing that underlies visceral nociception and may trigger the development of novel, potent centrally acting analgesic drugs.

  10. Ultrasound-guided Pulsed Radiofrequency Lesioning of the Phrenic Nerve in a Patient with Intractable Hiccup

    PubMed Central

    Kang, Keum Nae; Park, In Kyung; Suh, Jeong Hun; Leem, Jeong Gill

    2010-01-01

    Persistent and intractable hiccups (with respective durations of more than 48 hours and 1 month) can result in depression, fatigue, impaired sleep, dehydration, weight loss, malnutrition, and aspiration syndromes. The conventional treatments for hiccups are either non-pharmacological, pharmacological or a nerve block treatment. Pulsed radiofrequency lesioning (PRFL) has been proposed for the modulation of the excited nervous system pathway of pain as a safe and nondestructive treatment method. As placement of the electrode in close proximity to the targeted nerve is very important for the success of PRFL, ultrasound appears to be well suited for this technique. A 74-year-old man suffering from intractable hiccups that had developed after a coronary artery bypass graft and had continued for 7 years was referred to our pain clinic. He had not been treated with conventional methods or medications. We performed PRFL of the phrenic nerve guided by ultrasound and the hiccups disappeared. PMID:20830266

  11. Advanced Innovations for Pain.

    PubMed

    Lamer, Tim J; Deer, Timothy R; Hayek, Salim M

    2016-02-01

    Chronic pain represents one of the most important public health problems in terms of both the number of patients afflicted and health care costs. Most patients with chronic pain are treated with medications as the mainstay of therapy, and yet most medically treated patients continue to report ongoing pain. Additionally, adverse effects from pain medications represent a major challenge for clinicians and patients. Spinal cord stimulation and intrathecal drug delivery systems are well-established techniques that have been utilized for over 25 years. Intrathecal drug delivery systems have proven efficacy for a wide variety of intractable pain conditions and fewer adverse effects than systemic medical therapy in patients with refractory cancer-related pain. Spinal cord stimulation is cost-effective and provides improved pain control compared with medical therapy in patients with a variety of refractory pain conditions including complex regional pain syndrome, painful diabetic neuropathy, and chronic radiculopathy. Patients who have intractable pain that has not responded to reasonable attempts at conservative pain care measures should be referred to a qualified interventional pain specialist to determine candidacy for the procedures discussed in this article.

  12. Irritable bowel syndrome: methods, mechanisms, and pathophysiology. Methods to assess visceral hypersensitivity in irritable bowel syndrome.

    PubMed

    Keszthelyi, D; Troost, F J; Masclee, A A

    2012-07-15

    Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder, characterized by recurrent abdominal pain or discomfort in combination with disturbed bowel habits in the absence of identifiable organic cause. Visceral hypersensitivity has emerged as a key hypothesis in explaining the painful symptoms in IBS and has been proposed as a "biological hallmark" for the condition. Current techniques of assessing visceral perception include the computerized barostat using rectal distensions, registering responses induced by sensory stimuli including the flexor reflex and cerebral evoked potentials, as well as brain imaging modalities such as functional magnetic resonance imaging and positron emission tomography. These methods have provided further insight into alterations in pain processing in IBS, although the most optimal method and condition remain to be established. In an attempt to give an overview of these methods, a literature search in the electronic databases PubMed and MEDLINE was executed using the search terms "assessment of visceral pain/visceral nociception/visceral hypersensitivity" and "irritable bowel syndrome." Both original articles and review articles were considered for data extraction. This review aims to discuss currently used modalities in assessing visceral perception, along with advantages and limitations, and aims also to define future directions for methodological aspects in visceral pain research. Although novel paradigms such as brain imaging and neurophysiological recordings have been introduced in the study of visceral pain, confirmative studies are warranted to establish their robustness and clinical relevance. Therefore, subjective verbal reporting following rectal distension currently remains the best-validated technique in assessing visceral perception in IBS.

  13. The selective 5-hydroxytryptamine 1A antagonist, AZD7371 [3(R)-(N,N-dicyclobutylamino)-8-fluoro-3,4-dihydro-2H-1-benzopyran-5-carboxamide (R,R)-tartrate monohydrate] (robalzotan tartrate monohydrate), inhibits visceral pain-related visceromotor, but not autonomic cardiovascular, responses to colorectal distension in rats.

    PubMed

    Lindström, E; Ravnefjord, A; Brusberg, M; Hjorth, S; Larsson, H; Martinez, V

    2009-06-01

    5-Hydroxytryptamine 1A (5-HT(1A)) receptors have been suggested as a target for the treatment of irritable bowel syndrome (IBS). A recent clinical trial investigating the efficacy of the selective 5-HT(1A) antagonist AZD7371 [3(R)-(N,N-dicyclobutylamino)-8-fluoro-3,4-dihydro-2H-1-benzopyran-5-carboxamide (R,R)-tartrate monohydrate] showed no symptomatic improvement in IBS patients. We characterized the mechanisms mediating potential analgesic effects of AZD7371 in a model of colorectal distension (CRD)-induced visceral pain in rats to understand its mechanism of action and the lack of clinical efficacy. Visceromotor and cardiovascular responses (telemetry) were assessed in conscious rats during noxious CRD (80 mm Hg). Effects of AZD7371 (3-300 nmol/kg i.v.; 1-30 micromol/kg p.o.) and a reference 5-HT(1A) antagonist, WAY-100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridyl)cyclohexanecarboxamide maleate salt; 3-300 nmol/kg i.v.), were assessed. Effects of intracerebroventricular AZD7371 were also evaluated. Intravenous AZD7371 or WAY-100635 and oral AZD7371 dose-dependently inhibited visceromotor responses to CRD (ED(50), 203, 231, and 14 micromol/kg, respectively). In telemetrized rats, oral AZD7371 inhibited visceromotor responses to CRD without affecting the concomitant hypertensive and tachycardic responses. Intracerebroventricular AZD7371 did not affect visceromotor responses, whereas it inhibited micturition. None of the doses tested induced visible gross side effects. AZD7371, likely acting at a spinal site, inhibited the visceromotor but not the cardiovascular responses to visceral pain in the CRD model in rats. Although agents effective on multiple pain-related readouts in the CRD model (e.g., pregabalin or clonidine) alleviate IBS symptoms, AZD7371, which is effective on only one pain-related pseudoaffective readout, does not. Data from preclinical CRD models of visceral pain need to be interpreted cautiously as it relates to their clinical

  14. SNF5 Mutation Leads to Intractable Pain in Schwannomatosis Patients

    DTIC Science & Technology

    2013-07-01

    increase in the number and type of sensory neurons that express the capsaicin receptor, TRPV1 . Using a culture system, we have determined that...soluble factor is released by snf5-/- Schwann cells that acts on sensory neurons to induce the expression of TRPV1 . This factor is greater than 10K...molecular weight and does not affect neuron survival. The increase in the immunoreactivity of TRPV1 is correlated with an increase in the expression of

  15. SNF5 Mutation Leads to Intractable Pain in Schwannomatosis Patients

    DTIC Science & Technology

    2012-07-01

    the capsaicin receptor, TRPV1 . Using a culture system, we have determined that soluble factor is released by snf5-/- Schwann cells that acts on...sensory neurons to induce the expression of TRPV1 . This factor is greater than 10K molecular weight and does not affect neuron survival. The increase in...the immunoreactivity of TRPV1 is correlated with an increase in the expression of functional capsaicin-sensitive ion fluxes. 15. SUBJECT TERMS

  16. [Global strategy for rare and intractable diseases].

    PubMed

    Kawashima Kodama, Tomoko

    2013-01-01

    The progress has been made in research on rare and intractable diseases, for which new drug development has long been limited due to rarity, by establishing a global network in recent years. In Japan, the countermeasure of rare and intractable diseases has been implemented under national policy outline as an integrated strategy since 1972, including surveys and research, construction of medical facilities, reducing burden of medical expenses for patients, and enhancement of welfare and improving QOL of patients. Along with legislation or regulation of orphan drugs development, treatment and care for rare diseases have been emphasized in each national healthcare system globally. In the US, the Office of Rare Diseases was established under NIH in 1989 and European countries also started collaboration for rare disease projects with their own national plans in 1999. As a platform of rare diseases patients, healthcare professionals, researchers, pharmaceutical industry, and policy makers, Orphanet has a well-designed website which networks them. In Japan, there are urgent needs for global standard patient registration system and strengthening global collaboration for developing treatment and care for the patients of rare and intractable diseases, which needs more cooperative relations with patient organizations and pharmaceutical industry within country.

  17. Subcutaneous tunneled intrapleural catheters in the long-term relief of right upper quadrant pain of malignant origin.

    PubMed

    Waldman, S D; Allen, M L; Cronen, M C

    1989-06-01

    A 33-yr-old, 42-kg female, with extensive hepatic metastatic disease with intractable pain unresponsive to narcotic analgesics, nonsteroidal antiinflammatory drugs, and tricyclic antidepressants, is presented. Management of this patient's intractable pain with local anesthetics administered via a tunneled intrapleural catheter is discussed. Tunneling techniques are described. The patient continued to experience excellent pain relief at 6 wk follow-up.

  18. Microglia: a newly discovered role in visceral hypersensitivity?

    PubMed Central

    Saab, Carl Y.; Wang, Jing; Gu, Chunping; Garner, Kirsten N.; Al-Chaer, Elie D.

    2007-01-01

    Given the growing body of evidence for a role of glia in pain modulation, it is plausible that the exaggerated visceral pain in chronic conditions might be regulated by glial activation. In this study, we have investigated a possible role for microglia in rats with chronic visceral hypersensitivity and previously documented altered neuronal function. Experiments were performed on adult male Sprague-Dawley rats pre-treated with neonatal colon irritation (CI) and on control rats. Effects of fractalkine (FKN, a chemokine involved in neuron-to-microglia signaling) and of minocycline (an inhibitor of microglia) on visceral sensitivity were examined. Visceral sensitivity was assessed by recording the electromyographic (EMG) responses to graded colorectal distension (CRD) in mildly sedated rats. Responses to CRD were recorded before and after injection of FKN, minocycline or vehicle. Somatic thermal hyperalgesia was measured by latency of paw withdrawal to radiant heat. The pattern and intensity of microglial distribution at L6–S2 in the spinal cord was also compared in rats with CI and controls by fluorescence microscopy using OX-42. Results show that: (1) FKN significantly facilitated EMG responses to noxious CRD by >52% in control rats. FKN also induced thermal hyperalgesia in control rats, consistent with previous reports; (2) minocycline significantly inhibited EMG responses to noxious CRD by >70% in rats with CI compared to controls 60 min after injection. The anti-nociceptive effect of minocycline lasted for 180 min in rats with CI, reaching peak values 60 min after injection. Our results show that FKN enhances visceral and somatic nociception, whereas minocycline inhibits visceral hypersensitivity in chronically sensitized rats, which indicates a role for microglia in visceral hypersensitivity. PMID:18496611

  19. Visceral adiposity syndrome.

    PubMed

    Lopes, Heno F; Corrêa-Giannella, Maria Lúcia; Consolim-Colombo, Fernanda M; Egan, Brent M

    2016-01-01

    The association of anthropometric (waist circumference) and hemodynamic (blood pressure) changes with abnormalities in glucose and lipid metabolism has been motivation for a lot of discussions in the last 30 years. Nowadays, blood pressure, body mass index/abdominal circumference, glycemia, triglyceridemia, and HDL-cholesterol concentrations are considered in the definition of Metabolic syndrome, referred as Visceral adiposity syndrome (VAS) in the present review. However, more than 250 years ago an association between visceral and mediastinal obesity with hypertension, gout, and obstructive apnea had already been recognized. Expansion of visceral adipose tissue secondary to chronic over-consumption of calories stimulates the recruitment of macrophages, which assume an inflammatory phenotype and produce cytokines that directly interfere with insulin signaling, resulting in insulin resistance. In turn, insulin resistance (IR) manifests itself in various tissues, contributing to the overall phenotype of VAS. For example, in white adipose tissue, IR results in lipolysis, increased free fatty acids release and worsening of inflammation, since fatty acids can bind to Toll-like receptors. In the liver, IR results in increased hepatic glucose production, contributing to hyperglycemia; in the vascular endothelium and kidney, IR results in vasoconstriction, sodium retention and, consequently, arterial hypertension. Other players have been recognized in the development of VAS, such as genetic predisposition, epigenetic factors associated with exposure to an unfavourable intrauterine environment and the gut microbiota. More recently, experimental and clinical studies have shown the autonomic nervous system participates in modulating visceral adipose tissue. The sympathetic nervous system is related to adipose tissue function and differentiation through beta1, beta2, beta3, alpha1, and alpha2 adrenergic receptors. The relation is bidirectional: sympathetic denervation of

  20. (-)-α-Bisabolol attenuates visceral nociception and inflammation in mice.

    PubMed

    Leite, Gerlânia de O; Leite, Laura H I; Sampaio, Renata de S; Araruna, Mariana Késsia A; de Menezes, Irwin Rose A; da Costa, José Galberto M; Campos, Adriana R

    2011-03-01

    The study examined the antiinflammatory and antinociceptive effects of the sesquiterpene (-)-α-bisabolol (BISA). The antiinflammatory effect was evaluated on acute models of dermatitis induced by Croton oil, arachidonic acid, phenol and capsaicin, respectively, in mouse ear. BISA inhibited the dermatitis induced by all noxious agents, except capsaicin. BISA was assessed in two established mouse models of visceral nociception. Mice were pretreated orally with BISA, and the pain-related behavioral responses to intraperitoneal cyclophosphamide or to intracolonic mustard oil were analyzed. BISA showed a dose-unrelated significant antinociception. Collectively, the results suggest that BISA may be an topical antiinflammatory and visceral antinociceptive agent.

  1. Intra-abdominal abscess and intractable sinus - a rare late complication after splenectomy

    PubMed Central

    Shrestha, Badri; Hampton, James

    2017-01-01

    Intra-abdominal abscess and an intractable abdominal wall sinus forty years after splenectomy is rare, which has not been described previously in the surgical literature. We report the management of a patient who had presented with an intractable sinus on his left hypochondrium forty years after having undergone splenectomy and cholecystectomy, which persisted for more than two years despite repeated surgery and courses of antibiotics and compromised quality of life significantly from pain. A sinogram and computerised tomographic scan followed by exploration and laying open of the sinus delivered multiple silk sutures used for ligation of splenic pedicle, led to complete resolution of the sinus. It is important to avoid using non-absorbable silk sutures during splenectomy when splenectomy is undertaken in a contaminated field. Appropriate imaging and exploration is mandatory for its resolution. PMID:28138442

  2. Intractable Seizures and Rehabilitation in Ciguatera Poisoning.

    PubMed

    Derian, Armen; Khurana, Seema; Rothenberg, Joshua; Plumlee, Charles

    2016-08-31

    Ciguatera fish poisoning is the most frequently reported seafood toxin illness associated with the ingestion of contaminated tropical fish. Diagnosis relies on a history of recent tropical fish ingestion and subsequent development of gastrointestinal, cardiovascular, and neurological symptoms. Ciguatera poisoning usually has a self-limited time course, and its management involves symptomatic control and supportive care. This case report presents an uncommon case of ciguatera poisoning with prolonged intractable seizures refractory to standard antiseizure medications. The patient also had significant functional decline that responded to rigorous inpatient rehabilitation not previously described in literature.

  3. Visceral hyperalgesia caused by peptide YY deletion and Y2 receptor antagonism

    PubMed Central

    Hassan, Ahmed M.; Jain, Piyush; Mayerhofer, Raphaela; Fröhlich, Esther E.; Farzi, Aitak; Reichmann, Florian; Herzog, Herbert; Holzer, Peter

    2017-01-01

    Altered levels of colonic peptide YY (PYY) have been reported in patients suffering from functional and inflammatory bowel disorders. While the involvement of neuropeptide Y (NPY) and Y receptors in the regulation of nociception is well established, the physiological role of PYY in somatic and visceral pain is poorly understood. In this work, the role of PYY in pain sensitivity was evaluated using PYY knockout (PYY(−/−)) mice and Y2 receptor ligands. PYY(−/−) mice were more sensitive to somatic thermal pain compared to wild type (WT) mice. Visceral pain was assessed by evaluating pain-related behaviors, mouse grimace scale (MGS) and referred hyperalgesia after intrarectal administration of allyl isothiocyanate (AITC, 1 or 2%) or its vehicle, peanut oil. The pain-related behaviors induced by AITC were significantly exaggerated by PYY deletion, whereas the MGS readout and the referred hyperalgesia were not significantly affected. The Y2 receptor antagonist, BII0246, increased pain-related behaviors in response to intrarectal AITC compared to vehicle treatment while the Y2 receptor agonist, PYY(3–36), did not have a significant effect. These results indicate that endogenous PYY has a hypoalgesic effect on somatic thermal and visceral chemical pain. The effect on visceral pain seems to be mediated by peripheral Y2 receptors. PMID:28106168

  4. Study on expression of laminin in patients with intractable epilepsy.

    PubMed

    Wu, Yuan; Feng, Yun; Pang, Jia-Rong; Tang, Mei; Liu, Xiu-Ying; Li, Jia-Quan; Wang, Xue-Feng

    2009-01-01

    In this study, we examined differences in serum laminin expression in patients with intractable epilepsy. Our results suggest that elevated laminin may contribute to the pathogenesis of intractable epilepsy. ELISA and western blots were used to measure laminin in the serum of 30 intractable epilepsy patients, 46 nonintractable epilepsy patients, and 20 normal subjects. By ELISA, serum laminin levels were greater in intractable epilepsy patients (177.396 +/- 30.602) and nonintractable epilepsy patients (121.915 +/- 35.215) than in normal control subjects (67.474 +/- 7.197); laminin was significantly greater in the intractable epilepsy group than in the nonintractable epilepsy group. In western blots, the optical density ratio of laminin to ss-actin was 0.871 +/- 0.032 for the intractable epilepsy group, 0.686 +/- 0.017 for the nonintractable epilepsy group, and 0.385 +/- 0.024 for the normal control group. The optical density ratios of the intractable and nonintractable epilepsy groups were higher than those for the normal control group, and the intractable epilepsy group was even greater than the nonintractable epilepsy group. Thus, laminin is significantly increased in epilepsy patients, and this increase is more profound in intractable epilepsy patients.

  5. Diagnosis of visceral leishmaniasis

    PubMed Central

    Srivastava, Pankaj; Dayama, Anand; Mehrotra, Sanjana; Sundar, Shyam

    2010-01-01

    Leishmaniasis is a vector-borne disease with up to 350 million people at risk of infection worldwide. Among its different clinical manifestations, visceral is the most severe form. Since clinical features of visceral leishmaniasis (VL) mimic several other common diseases, accurate diagnosis of VL is crucial as the treatment is associated with significant toxicity. Invasive and risky techniques involving demonstration of the parasites in stained preparations from splenic and bone marrow aspirate is still the gold standard for VL diagnosis. Serological tests using rk39 in ELISA or rapid immunochromatographic format, Direct Agglutination Test (DAT), immunoblotting have issues related to a significant proportion of asymptomatic individuals being positive with these tests and their inability to diagnose relapses as these remain positive for several months to years after cure. PCR is the most common molecular technique successfully used for diagnosis and differentiation of species. Through this review we focus extensively on the comparative utilities of the various diagnostic tools currently available for VL, describing in depth their advantages and disadvantages, addressing the recent advances attained in the field. A simple, rapid, non invasive, accurate and cost effective marker of active VL, which can be used in field conditions, is necessary to improve diagnosis of VL. PMID:21074233

  6. [Juvenile haemochromatosis presenting as intractable congestive heart failure].

    PubMed

    Vas, Katalin; Hubay, Marta; Tordai, Attila; Andrikovics, Hajnalka; Zoltán, Sápi; Jánosi, András

    2005-12-18

    Juvenile haemochromatosis is an autosomal, recessive inherited iron metabolism disorder. The rapid deterioration and malignant prognosis differentiate juvenile haemochromatosis from hereditary haemochromatosis. The authors summarize the history of a 25 year old man, who worked in Hungary as a guest worker living in Romania. No significant illness has occurred in his previous history. The abdominal pain was his first symptom and he was treated in different institutions, where cholecystitis, alcoholic hepatic disease, hepatic cirrhosis were considered as a cause of his symptoms. Some weeks later atrial tachycardia, and congestive heart failure were observed and he was sent to our Cardiology Department. The echocardiography revealed diffuse hypokinesis, serious systolic dysfunction (ejection fraction: 21%), grade II mitral and tricuspid insufficiency with pulmonary hypertension. Considering the rapid deterioration of his cardiac function, myocarditis was suspected. Myocardial biopsy and coronary arteriography were performed. Coronary arteries were normal. Ventricular fibrillation occurred during coronary arteriography. Myocardial biopsy revealed juvenile haemochromatosis. Special laboratory examinations (transferrin saturation) were made after biopsy, that also confirmed the diagnosis of juvenile haemochromatosis. Cardiac transplantation was planned. Some days after the diagnosis was made the patient died of cardiogenic shock and intractable heart failure. Autopsy revealed hypogonadism and serious haemochromatosis in different parenchymal organs. Juvenile haemochromatosis should be considered in every young patient with congestive heart failure of unknown etiology.

  7. The Gandhi Technique: A New Procedure for Intractable Problems.

    ERIC Educational Resources Information Center

    Schiff, Neil P.; Belson, Richard

    1988-01-01

    Notes problem of treating clients with intractable difficulties. Presents Gandhi Technique as simple, dramatic and seemingly effective procedure to resolve intractable difficulties. Describes technique and its application in different cases. Discusses several theories which may account for the efficacy of the technique. Proposes that Gandhi…

  8. [Visceral leishmaniasis: new drugs].

    PubMed

    Minodier, P; Robert, S; Retornaz, K; Garnier, J M

    2003-12-01

    The standard treatment of visceral leishmaniasis is pentavalent antimony (meglumine antimoniate or sodium stibogluconate), but toxicity is frequent with this drug. Moreover, antimony unresponsiveness is increasing, both in immunocompetent and in immunosuppressed patients. Amphotericin B is a polyene macrolide antibiotic that binds to sterols in cell membranes. It is the most active antileishmanial agent in use. Its infusion-related and renal toxicity may be reduced by lipid-based delivery. Liposomal amphotericin B (Ambisome) seems to be less toxic than other amphotericin B lipid formulations (Amphocil, Amphotec). Optimal drug regimens of Ambisome vary from one geographical area to another. In the Mediterranean Basin, a total dose of 18 to 24 mg/kg is safe and effective. Shortening the duration of treatment without decreasing the total dose (i.e., 10 mg/kg/day for 2 days) seems promising to reduce the global cost of the therapy.

  9. Intractable sneezing: is it always psychogenic?

    PubMed

    Sulemanji, Mustafa N; Kanbur, Nuray O; Derman, Orhan; Pehlivantürk, Berna; Hoşal, Sefik A; Sekerel, Bülent E

    2011-01-01

    Intractable sneezing is not a commonly encountered disorder. The clinical presentation of such patients may cause the physician to undertake several tests before making a diagnosis. Are the performed analytic tests a waste of the health service funds or are they really sufficient? In this case, after undergoing several tests to rule out potential causes of the prevailing symptoms, psychiatric evaluation revealed a triggering event that contributed to the diagnosis of psychogenic sneezing. This specific case demonstrates why the diagnosis of psychogenic sneezing is difficult. An overwhelming number of such patients may be linked to a psychogenic cause; nevertheless, organic lesions or causes should be carefully excluded. Addressing the psychosocial issues through psychotherapy and coincidental use of locally administered anesthesia assisted in resolving the symptoms.

  10. Oral Azithromycin for Treatment of Intractable Rosacea

    PubMed Central

    Kim, Jae-Hong; Oh, Yoon Seok

    2011-01-01

    Rosacea is a common chronic cutaneous disorder that primarily occurs on the convex surfaces of the central face and is often characterized by exacerbations and remissions. A case of a 52-yr-old woman visited our clinic in February 2008 complaining typical features of rosacea including multiple pinhead to rice-sized erythematous papules. We applied various conventional treatments including topical benzoyl peroxide and metronidazole as well as oral metronidazole, isotretinoin, and doxycycline. The lesions were not controlled but were rather aggravated by complications from these treatments. Therefore, we prescribed oral azithromycin, which has anti-inflammatory effects and reduces reactive oxygen species. Ten weeks after the administration of oral azithromycin, 500 mg per day for 2 weeks, the lesions had mostly disappeared and no specific side effects related to the azithromycin were noted. Oral azithromycin dosing 500 mg/day for 2 weeks is effective for treatment of intractable rosacea. PMID:21532865

  11. Microcatheter Embolization of Intractable Idiopathic Epistaxis

    SciTech Connect

    Leppaenen, Martti; Seppaenen, Seppo; Laranne, Jussi; Kuoppala, Katriina

    1999-11-15

    Purpose: To assess the efficacy and safety of microcatheter embolization in the treatment of intractable idiopathic epistaxis. Methods: Thirty-seven patients underwent microcatheter embolization in 1991-1998. We evaluated retrospectively the technical and clinical outcome, the number of complications, the duration of embolization in each case, and the number of blood transfusions needed. All embolizations were done with biplane digital subtraction angiography (DSA) equipment. The procedure was carried out under local anesthesia using transfemoral catheterization, except in one case where the translumbar route was used. Tracker 18 or 10 microcatheters were advanced as far as possible to the distal branches of the sphenopalatine artery. Polyvinyl alcohol (PVA) particles were used for embolization in most cases, while platinum coils or a combination of these two materials were occasionally used. The primary outcome was always assessed immediately by angiography. Follow-up data were obtained from patient records, by interviewing patients on the telephone or by postal questionnaires when necessary. The mean follow-up time was 21 months. Results: The embolization was technically successful in all 37 cases. A curative outcome was achieved in 33 cases (89%). The mean duration of the procedure was 110 min. Four patients (8%) had mild transient complications, but no severe or persistent complications were encountered. Twenty-three patients needed a blood transfusion. Slight rebleeding occurred in three patients during the follow-up; all responded to conservative treatment. One patient suffered two episodes of rebleeding within 2 months after primary embolization. Re-embolizations successfully stopped the bleeding. Conclusion: Embolization is the primary invasive modality for treating intractable idiopathic epistaxis. It proved both safe and effective over a relatively long follow-up.

  12. Visceral Infection Caused by Leishmania tropica in Veterans of Operation Desert Storm

    DTIC Science & Technology

    1993-05-13

    UNLIMITED Dist Special 13. ABSTRACT (Maximum 200 words) Abstract Background. Visceral leishmaniasis, usually cough , intermittent diarrhea, or abdominal...Visceral leishmaniasis, usually cough , intermittent diarrhea, or abdominal pain that began caused by Leishmania donovani, has rarely been reported up to...classic signs or symptoms of kala-azar. fever, rigors, nonproductive cough , and malaise one month after his return from Saudi Arabia. He had lived in an

  13. New insights into visceral hypersensitivity —clinical implications in IBS

    PubMed Central

    Zhou, QiQi; Verne, G. Nicholas

    2012-01-01

    A subset of patients with IBS have visceral hypersensitivity and/or somatic hypersensitivity. Visceral hypersensitivity might have use as a clinical marker of IBS and could account for symptoms of urgency for bowel movements, bloating and abdominal pain. The mechanisms that lead to chronic visceral hypersensitivity in patients who have IBS are unclear. However, several working models may be considered, including: nociceptive input from the colon that leads to hypersensitivity; increased intestinal permeability that induces a visceral nociceptive drive; and alterations in the expression of microRNAs in gastrointestinal tissue that might be delivered via blood microvesicles to other target organs, such as the peripheral and/or central nervous system. As such, the chronic visceral hypersensitivity that is present in a subset of patients with IBS might be maintained by both peripheral and central phenomena. The theories underlying the development of chronic visceral hypersensitivity in patients with IBS are supported by findings from new animal models in which hypersensitivity follows transient inflammation of the colon. The presence of somatic hypersensitivity and an alteration in the neuroendocrine system in some patients who have IBS suggests that multisystemic factors are involved in the overall disorder. Thus, IBS is similar to other chronic pain disorders, such as fibromyalgia, chronic regional pain disorder and temporomandibular joint disorder, as chronic nociceptive mechanisms are activated in all of these disorders. PMID:21643039

  14. Hyponatremia in visceral leishmaniasis.

    PubMed

    Verde, Frederico A Lima; Verde, Francisco A A Lima; Veronese, Francisco José V; Neto, Augusto S; Fuc, Galdino; Verde, Emir M Lima

    2010-01-01

    There are few reports linking hyponatremia and visceral leishmaniasis (kala-azar). This is a study of 55 consecutive kala-azar patients and 20 normal individuals as a control group. Hyponatremia and serum hypo-osmolality were detected in 100% of kala-azar patients. High first morning urine osmolality (750.0 ± 52.0 vs. 894.5 ± 30.0mOsm/kg H₂O, p < 0.05), and high 24-hour urine osmolality (426.0 ± 167.0 vs. 514.6 ± 132.0 mOsm/kg H₂O, p < 0.05) demonstrated persistent antidiuretic hormone secretion. Urinary sodium was high (82.3 ± 44.2 vs.110.3 ± 34.7 mEq/L, p < 0.05). Low seric uric acid occurred in 61.8% of patients and increased fractional urinary uric acid excretion was detected in 74.5% of them. Increased glomerular filtration rate was present in 25.4% of patients. There was no evidence of extracellular volume depletion. Normal plasma ADH levels were observed in kala-azar patients. No endocrine or renal dysfunction was detected. It is possible that most hyponatremic kala-azar patients present the syndrome of inappropriate antidiuretic hormone secretion.

  15. Intractable yawning associated with mature teratoma of the supramedial cerebellum.

    PubMed

    Saura, Hiroaki; Beppu, Takaaki; Matsuura, Hideki; Asahi, Shigeki; Uesugi, Noriyuki; Sasaki, Makoto; Ogasawara, Kuniaki

    2014-08-01

    Yawning occurs in various conditions such as hypoxia, epilepsy, and sleep disorders including sleep apnea. Intractable yawning associated with a brain tumor has been rarely reported. A 19-year-old woman presented with intractable yawning. Magnetic resonance imaging showed a tumor in the supramedial cerebellum that compressed the dorsal side of the midbrain and upper pons. After subtotal removal of the tumor, the yawning completely disappeared. Postoperative MRI showed resolution of compression of the brainstem. The tumor was histologically diagnosed as a mature teratoma. The present case suggested that the intractable yawning resulted from the tumor compressing the dorsal side of the junction between the midbrain and pons.

  16. Histone hyperacetylation modulates spinal type II metabotropic glutamate receptor alleviating stress-induced visceral hypersensitivity in female rats

    PubMed Central

    Cao, Dong-Yuan; Bai, Guang; Ji, Yaping; Karpowicz, Jane

    2016-01-01

    Stress is often a trigger to exacerbate chronic pain including visceral hypersensitivity associated with irritable bowel syndrome, a female predominant functional bowel disorder. Epigenetic mechanisms that mediate stress responses are a potential target to interfere with visceral pain. The purpose of this study was to examine the effect of a histone deacetylase inhibitor, suberoylanilide hydroxamic acid, on visceral hypersensitivity induced by a subchronic stressor in female rats and to investigate the involvement of spinal glutamate receptors. Three daily sessions of forced swim induced visceral hypersensitivity. Intrathecal suberoylanilide hydroxamic acid prevented or reversed the stress-induced visceral hypersensitivity, increased spinal histone 3 acetylation and increased mGluR2 and mGluR3 expression. Chromatin immunoprecipitation (ChIP) analysis revealed enrichment of H3K9Ac and H3K18Ac at several promoter Grm2 and Grm3 regions. The mGluR2/3 antagonist LY341495 reversed the inhibitory effect of suberoylanilide hydroxamic acid on the stress-induced visceral hypersensitivity. In surprising contrast, stress and/or suberoylanilide hydroxamic acid had no effect on spinal NMDA receptor expression or function. These data reveal histone modification modulates mGluR2/3 expression in the spinal cord to attenuate stress-induced visceral hypersensitivity. HDAC inhibitors may provide a potential approach to relieve visceral hypersensitivity associated with irritable bowel syndrome. PMID:27385724

  17. Transient Receptor Potential Ion Channel Function in Sensory Transduction and Cellular Signaling Cascades Underlying Visceral Hypersensitivity.

    PubMed

    Balemans, Dafne; Boeckxstaens, Guy E; Talavera, Karel; Wouters, Mira M

    2017-04-06

    Visceral hypersensitivity is an important mechanism underlying increased abdominal pain perception in functional gastrointestinal disorders (FGID) including functional dyspepsia, irritable bowel syndrome (IBS) and inflammatory bowel disease in remission. Although the exact pathophysiological mechanisms are poorly understood, recent studies described upregulation and altered functions of nociceptors and their signaling pathways in aberrant visceral nociception, in particular the transient receptor potential (TRP) channel family. A variety of TRP channels are present in the gastrointestinal tract (TRPV1, TRPV3, TRPV4, TRPA1, TRPM2, TRPM5 and TRPM8) and modulation of their function by increased activation or sensitization (decreased activation threshold) or altered expression in visceral afferents, have been reported in visceral hypersensitivity. TRP channels directly detect or transduce osmotic, mechanical, thermal and chemosensory stimuli. In addition, pro-inflammatory mediators released in tissue damage or inflammation can activate receptors of the G-protein coupled receptor (GPCR) superfamily leading to TRP channel sensitization and activation, which amplify pain and neurogenic inflammation. In this review, we highlight the current knowledge on the functional roles of neuronal TRP channels in visceral hypersensitivity and discuss the signaling pathways that underlie TRP channel modulation. We propose that a better understanding of TRP channels and their modulators may facilitate the development of more selective and effective therapies to treat visceral hypersensitivity.

  18. Main ion channels and receptors associated with visceral hypersensitivity in irritable bowel syndrome

    PubMed Central

    de Carvalho Rocha, Heraldo Arcela; Dantas, Bruna Priscilla Vasconcelos; Rolim, Thaísa Leite; Costa, Bagnólia Araújo; de Medeiros, Arnaldo Correia

    2014-01-01

    Irritable bowel syndrome (IBS) is a very frequent functional gastrointestinal disorder characterized by recurrent abdominal pain or discomfort and alteration of bowel habits. The IBS physiopathology is extremely complex. Visceral hypersensitivity plays an important role in the pathogenesis of abdominal pain in both in vitro and in vivo models of this functional disorder. In order to obtain a general view of the participation of the main ion channels and receptors regarding the visceral hypersensitivity in the IBS and to describe their chemical structure, a literature review was carried out. A bibliographical research in the following electronic databases: Pubmed and Virtual Library in Health (BVS) was fulfilled by using the search terms “ion channels” “or” “receptors” “and” “visceral hypersensitivity” “or” “visceral nociception” “and” “irritable bowel syndrome”. Original and review articles were considered for data acquisition. The activation of the ATP ion-gated channels, voltage-gated sodium (Nav) and calcium (Cav) channels, as well as the activation of protease-activated receptors (PAR2), transient receptor potential vanilloide-1, serotonin, cannabinoids and cholecystokinin are involved in the genesis of visceral hypersensitivity in IBS. The involvement of ion channels and receptors concerning visceral hypersensitivity is noteworthy in IBS models. PMID:24976114

  19. Diagnostic surgical neuropathology of intractable epilepsy.

    PubMed

    Arai, Nobutaka; Takahashi, Tatsuya; Komori, Takashi; Yagishita, Akira; Shimizu, Hiroyuki

    2007-12-01

    As neurosurgical treatments have been increasingly applied to patients who have intractable epilepsy, much knowledge on pathological changes in surgically removed brain tissues have become clearer in recent years, as well as on the neuroimaging findings which are analyzed with a variety of techniques, including computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), single photon emission computed tomography (SPECT) in combination with digital imaging and communication in medicine (DICOM), statistical parametric mapping (SPM), subtraction ictal SPECT coregistered to MRI (SISCOM) and/or PET-guided intraoperative navigation system, as mentioned in detain in another article in this issue by Maehara et al. Representative and relatively common diseases, treated by epilepsy-surgery, are as follows; hippocampal sclerosis, amygdaloid sclerosis, coarse and macroscopic brain malformation (focal cortical dysplasia, hemimegalencephaly, tuberous sclerosis), tumors (dysembryoplastic neuroepithelial tumor, ganglioglioma, etc.), destructive lesions and the others. It is a fact, however, that there remains many problems in the diagnostic criteria or histological grading systems, especially in various cortical dysplasias described above. On the other hand, histologically minor but clinically serious lesions have become to be known through careful observations on surgically removed tissues which showed no neuroradiological findings. A good well-known example is microdysgenesis of the cerebrum which is characterized by the presence of both the white mater ectopic neurons and the vascular meandering abnormalities with glial satellitosis. There must be another important histological phenotypes of microdysgenesis, except the above-mentioned ones, that are not yet established at present. Therefore, it is believed that there remains various problems on the diagnostic neuropathology of epileptic lesions with or without neuroimaging findings in which

  20. Reversal of visceral and somatic hypersensitivity in a subset of hypersensitive rats by intracolonic lidocaine

    PubMed Central

    Zhou, QiQi; Price, Donald D.; Verne, G. Nicholas

    2010-01-01

    Chronic abdominal pain is a common gastrointestinal symptom experienced by patients. We have previously shown that IBS patients with visceral hypersensitivity also have evidence of thermal hypersensitivity of the hand and foot that is reversed by rectal lidocaine jelly. We have also recently developed an animal model of chronic visceral and somatic hypersensitivity in rats treated with intracolonic trinitrobenzene sulfonic acid (TNBS). The objective of the current study was to determine the effects of intracolonic lidocaine on visceral/somatic hypersensitivity in TNBS-treated rats. A total of 20 hypersensitive rats received either 20 mg intracolonic lidocaine (n = 10) or saline jelly (n = 10). In comparison to saline jelly, intracolonic lidocaine jelly reduced responses to nociceptive visceral/somatic stimuli in hypersensitive rats. The effects were present within 5–30 min after administration of lidocaine and lasted for 6 h. Lidocaine had no effects on recovered rats or control rats that had originally been treated with intracolonic saline instead of TNBS. Local anesthetic blockade of peripheral impulse input from the colon reduces both visceral and somatic hypersensitivity in TNBS-treated rats, similar to results in IBS patients. The results provide further evidence that visceral and secondary somatic hypersensitivity in a subset of TNBS-treated rats reflect central sensitization mechanisms maintained by tonic impulse input from the colon. This study evaluates the reversal of visceral/somatic hypersensitivity in a subset of TNBS-treated rats with intracolonic lidocaine. This animal model may be used in the future to study the mechanisms of local anesthetic agents applied to the gut to reduce visceral pain. PMID:18486344

  1. Visceral scalloping on abdominal computed tomography due to abdominal tuberculosis

    PubMed Central

    Sharma, Vishal; Bhatia, Anmol; Malik, Sarthak; Singh, Navjeet; Rana, Surinder S.

    2017-01-01

    Objective: Scalloping of visceral organs is described in pseudomyxoma peritonei, malignant ascites, among other conditions, but not tuberculosis. Methods: We report findings from a retrospective study of patients with abdominal tuberculosis who had visceral scalloping on abdominal computed tomography (CT). Diagnosis of abdominal tuberculosis was made on the basis of combination of clinical, biochemical, radiological and microbiological criteria. The clinical data, hematological and biochemical parameters, and findings of chest X-ray, CT, Mantoux test, and HIV serology were recorded. Results: Of 72 patients with abdominal tuberculosis whose CT scans were included, seven patients had visceral scalloping. The mean age of these patients was 32.14 ± 8.43 years and four were men. While six patients had scalloping of liver, one had splenic scalloping. The patients presented with abdominal pain (all), abdominal distension (five patients), loss of weight or appetite (all), and fever (four patients). Mantoux test was positive in five, while none had HIV infection. The diagnosis was based on fluid (ascitic or collections) evaluation in four patients, ileo-cecal biopsy in one patient, fine needle aspiration from omental thickening in one patient, and sputum positivity for acid fast bacilli (AFB) in one patient. On CT examination, four patients had ascites, five had collections, one had lymphadenopathy, four had peritoneal involvement, three had pleural effusion, and two had ileo-cecal thickening. All except one patient received standard ATT for 6 months or 9 months (one patient). Pigtail drainage for collections was needed for two patients. Discussion: This report is the first description of visceral scalloping of liver and spleen in patients with abdominal tuberculosis. Previously, this finding has been reported primarily with pseudomyxoma peritonei and peritoneal carcinomatosis. Conclusion: Visceral scalloping may not conclusively distinguish peritoneal

  2. Visceral Infarction Following Aortic Surgery

    PubMed Central

    Johnson, Willard C.; Nabseth, Donald C.

    1974-01-01

    An experience with aortic surgery is reported which reveals that visceral ischemia is more frequent than expected and significantly contributes to operative mortality. Two of five deaths among 84 patients who had aorto-iliac occlusive disease and four of 40 deaths among 103 aneurysmectomies (both ruptured and elective) were related to visceral ischemia. A review of the literature reveals 99 cases of colonic ischemia in more than 6,100 cases of aortic surgery, an incidence of 1.5%. Only 10 cases of small bowel ischemia were recorded. The present experience with 9 cases of colon ischemia and one of small bowel ischemia is presented particularly with reference to pathophysiology and prevention. It is concluded that patients should be identified by appropriate angiography if considered a risk for visceral infarction, and, if present, visceral arterial reconstruction should be performed in addition to aortic reconstructive surgery. Colon infarction following aortic aneurysmal surgery is directly related to ligation of a patent IMA. Thus re-implantation of the patent IMA should be considered. ImagesFig. 1a. PMID:4277757

  3. Study on the Mechanism Underlying the Regulation of the NMDA Receptor Pathway in Spinal Dorsal Horns of Visceral Hypersensitivity Rats by Moxibustion

    PubMed Central

    Wang, L. D.; Zhao, J. M.; Huang, R. J.; Tan, L. Y.; Hu, Z. H.; Weng, Z. J.; Wang, K.; Wu, H. G.; Liu, H. R.

    2016-01-01

    Visceral hypersensitivity is enhanced in irritable bowel syndrome (IBS) patients. Treatment of IBS visceral pain by moxibustion methods has a long history and rich clinical experience. In the clinic, moxibustion on the Tianshu (ST25) and Shangjuxu (ST37) acupoints can effectively treat bowel disease with visceral pain and diarrhea symptoms. To investigate the regulatory function of moxibustion on the Tianshu (ST25) and Shangjuxu (ST37) acupoints on spinal cord NR1, NR2B, and PKCε protein and mRNA expression in irritable bowel syndrome (IBS) visceral hypersensitivity rats, we did some research. In the study, we found that moxibustion effectively relieved the IBS visceral hyperalgesia status of rats. Analgesic effect of moxibustion was similar to intrathecal injection of Ro 25-6981. The expression of NR1, NR2B, and PKCε in the spinal dorsal horns of IBS visceral hyperalgesia rats increased. Moxibustion on the Tianshu and Shangjuxu acupoints might inhibit the visceral hypersensitivity, simultaneously decreasing the expression of NR1, NR2B, and PKCε in spinal cord of IBS visceral hyperalgesia rats. Based on the above experimental results, we hypothesized NR1, NR2B, and PKCε of spinal cord could play an important role in moxibustion inhibiting the process of central sensitization and visceral hyperalgesia state. PMID:27200098

  4. Effects of psychological stress on the cerebral processing of visceral stimuli in healthy women.

    PubMed

    Rosenberger, C; Elsenbruch, S; Scholle, A; de Greiff, A; Schedlowski, M; Forsting, M; Gizewski, E R

    2009-07-01

    The aim of the study was to analyse effects of psychological stress on the neural processing of visceral stimuli in healthy women. The brain functional magnetic resonance imaging blood oxygen level-dependent response to non-painful and painful rectal distensions was recorded from 14 healthy women during acute psychological stress and a control condition. Acute stress was induced with a modified public speaking stress paradigm. State anxiety was assessed with the State-Trait-Anxiety Inventory; chronic stress was measured with the Perceived Stress Questionnaire. During non-painful distensions, activation was observed in the right posterior insular cortex (IC) and right S1. Painful stimuli revealed activation of the bilateral anterior IC, right S1, and right pregenual anterior cingulate cortex. Chronic stress score was correlated with activation of the bilateral amygdala, right posterior IC (post-IC), left periaqueductal grey (PAG), and right dorsal posterior cingulate gyrus (dPCC) during non-painful stimulation, and with activation of the right post-IC, right PAG, left thalamus (THA), and right dPCC during painful distensions. During acute stress, state anxiety was significantly higher and the acute stress - control contrast revealed activation of the right dPCC, left THA and right S1 during painful stimulation. This is the first study to demonstrate effects of acute stress on cerebral activation patterns during visceral pain in healthy women. Together with our finding that chronic stress was correlated wit the neural response to visceral stimuli, these results provide a framework for further studies addressing the role of chronic stress and emotional disturbances in the pathophysiology of visceral hyperalgesia.

  5. Grey matter heterotopia: an unusual association of intractable epilepsy.

    PubMed

    Stafford Johnson, D B; Brennan, P; Dwyer, A J; Toland, J

    1997-01-01

    Heterotopic grey matter is an abnormality of neuronal migration that has been reported in association with refractory epilepsy. In this study we reviewed the magnetic resonance (MR) imaging records of all patients undergoing MR scanning for evaluation of intractable epilepsy and identified sixteen patients who had grey matter heterotopia. The distribution of the grey matter heterotopia was periventricular in 9 patients, laminar in 3 and was in a "band" form in 4 patients. Congenital anomalies associated with grey matter heterotopia in this study included polymicrogyria in one patient and absence of the corpus callosum in 2 patients. Grey matter heterotopia is an important MR finding in patients with intractable epilepsy.

  6. Treatment of Mediterranean visceral leishmaniasis.

    PubMed Central

    Gradoni, L.; Bryceson, A.; Desjeux, P.

    1995-01-01

    Up-to-date information is given on the epidemiological situation of zoonotic visceral leishmaniasis (ZVL) in nine Mediterranean countries, and on drug regimens adopted in the management of ZVL patients in each country. Results of experimental and clinical trials on the efficacy and tolerability of liposomal amphotericin B in laboratory animals and in patients with ZVL are presented, as well as conclusions and recommendations on drug regimens to be used in the treatment of ZVL. PMID:7743590

  7. A rare case intractable diarrhea secondary to Clostridium difficile and cytomegalovirus coinfection

    PubMed Central

    John, Santhosh Gheevarghese; Dominguez, Cristian; Chandiramani, Vijay; Vemulappalli, Tejo

    2013-01-01

    Patient: Male, 63 Final Diagnosis: Cytomegalo virus (CMV) infection Symptoms: Diarrhea Medication:— Clinical Procedure:— Specialty: Infectious Diseases Objective: Unusual clinical course Background: Coinfection with cytomegalovirus in a patient with Clostridium difficile persistent diarrhea and colitis can lead to a delay in diagnosis and treatment. Case Report: A 63-year-old man with squamous cell carcinoma of the lower lip, status post surgical resection and currently on chemoradiation presented with intractable diarrhea and abdominal pain. Initial workup showed Clostridium difficile diarrhea with pancolitis. Diarrhea persisted despite being on antibiotics and bacteriological cure for C. difficile. Further noninvasive work up revealed associated cytomegalovirus infection, and patient had a dramatic response to ganciclovir without any relapse. Conclusions: Physicians should be cognizant about other causes of diarrhea and colitis in immunocompromised patient when treatment for primary diagnosis fails to resolve their symptoms. PMID:24298304

  8. Chronic Urogenital Pain in Men

    PubMed Central

    2008-01-01

    Current terminology uses the 2008 European Association of Urology guidelines, but variably used historical terms suggest inflammation or infection that is rarely found. Central sensitisation is important in causing visceral and muscle hyperalgesia throughout the pelvis. There can be considerable overlap between urogenital pain conditions. Men who have a chronic urological pain condition often have a disturbance of urinary, bowel and sexual function. Working with urologists as well as a multidisciplinary team is essential. PMID:26526127

  9. Intractable hiccup caused by medulla oblongata lesions: a study of an autopsy patient with possible neuromyelitis optica.

    PubMed

    Kobayashi, Zen; Tsuchiya, Kuniaki; Uchihara, Toshiki; Nakamura, Ayako; Haga, Chie; Yokota, Osamu; Ishizu, Hideki; Taki, Kazuhiro; Arai, Tetsuaki; Akiyama, Haruhiko; Mizusawa, Hidehiro

    2009-10-15

    We report the first autopsy verification of medulla oblongata lesions involving bilateral nucleus tractus solitarius (NTS) as a cause of intractable hiccup in an autopsy patient. The female patient first developed pain and weakness in the lower limbs and urinary incontinence at age 48, and was given a diagnosis of myelitis. Intractable hiccup was accompanied by urinary retention on the third attack. She died of respiratory failure when the fifth attack occurred at age 51. Autopsy disclosed severe involvement of the medulla oblongata and entire spinal cord. Optic nerve lesions were also identified unexpectedly. Dual involvement of the optic nerve and spinal cord, necrotic spinal cord lesions involving not only myelin but also neurons and axon, and marked extension of the spinal cord lesions in both the longitudinal and transverse directions suggested the diagnosis of neuromyelitis optica rather than multiple sclerosis. Although animal experiments have shown that NTS is a critical structure in the hiccup reflex, we demonstrated for the first time the involvement of the NTS in an autopsy patient with intractable hiccup.

  10. Adrenergic β2-receptors mediates visceral hypersensitivity induced by heterotypic intermittent stress in rats.

    PubMed

    Zhang, Chunhua; Rui, Yun-Yun; Zhou, Yuan-Yuan; Ju, Zhong; Zhang, Hong-Hong; Hu, Chuang-Ying; Xiao, Ying; Xu, Guang-Yin

    2014-01-01

    Chronic visceral pain in patients with irritable bowel syndrome (IBS) has been difficult to treat effectively partially because its pathophysiology is not fully understood. Recent studies show that norepinephrine (NE) plays an important role in the development of visceral hypersensitivity. In this study, we designed to investigate the role of adrenergic signaling in visceral hypersensitivity induced by heterotypical intermittent stress (HIS). Abdominal withdrawal reflex scores (AWRs) used as visceral sensitivity were determined by measuring the visceromoter responses to colorectal distension. Colon-specific dorsal root ganglia neurons (DRGs) were labeled by injection of DiI into the colon wall and were acutely dissociated for whole-cell patch-clamp recordings. Blood plasma level of NE was measured using radioimmunoassay kits. The expression of β2-adrenoceptors was measured by western blotting. We showed that HIS-induced visceral hypersensitivity was attenuated by systemic administration of a β-adrenoceptor antagonist propranolol, in a dose-dependent manner, but not by a α-adrenoceptor antagonist phentolamine. Using specific β-adrenoceptor antagonists, HIS-induced visceral hypersensitivity was alleviated by β2 adrenoceptor antagonist but not by β1- or β3-adrenoceptor antagonist. Administration of a selective β2-adrenoceptor antagonist also normalized hyperexcitability of colon-innervating DRG neurons of HIS rats. Furthermore, administration of β-adrenoceptor antagonist suppressed sustained potassium current density (IK) without any alteration of fast-inactivating potassium current density (IA). Conversely, administration of NE enhanced the neuronal excitability and produced visceral hypersensitivity in healthy control rats, and blocked by β2-adrenoceptor antagonists. In addition, HIS significantly enhanced the NE concentration in the blood plasma but did not change the expression of β2-adrenoceptor in DRGs and the muscularis externa of the colon. The

  11. Early Career Teacher Attrition: New Thoughts on an Intractable Problem

    ERIC Educational Resources Information Center

    Gallant, Andrea; Riley, Philip

    2014-01-01

    Early career exit from teaching has reached epidemic proportions and appears intractable. Previous attempts to find solutions are yet to make much of an inroad. The aim of the research was to discover what nine beginning teachers required to remain in the classroom, by adopting a phenomenological approach. The authors identified participants'…

  12. Rethinking intractable conflict: the perspective of dynamical systems.

    PubMed

    Vallacher, Robin R; Coleman, Peter T; Nowak, Andrzej; Bui-Wrzosinska, Lan

    2010-01-01

    Intractable conflicts are demoralizing. Beyond destabilizing the families, communities, or international regions in which they occur, they tend to perpetuate the very conditions of misery and hate that contributed to them in the first place. Although the common factors and processes associated with intractable conflicts have been identified through research, they represent an embarrassment of riches for theory construction. Thus, the current task in this area is integrating these diverse factors into an account that provides a coherent perspective yet allows for prediction and a basis for conflict resolution in specific conflict settings. We suggest that the perspective of dynamical systems provides such an account. This article outlines the key concepts and hypotheses associated with this approach. It is organized around a set of basic questions concerning intractable conflict for which the dynamical perspective offers fresh insight and testable propositions. The questions and answers are intended to provide readers with basic concepts and principles of complexity and dynamical systems that are useful for rethinking the nature of intractable conflict and the means by which such conflict can be transformed.

  13. Visceral hypersensitivity and electromechanical dysfunction as therapeutic targets in pediatric functional dyspepsia

    PubMed Central

    Rosen, John M; Cocjin, Jose T; Schurman, Jennifer V; Colombo, Jennifer M; Friesen, Craig A

    2014-01-01

    Functional gastrointestinal disorders (FGID) are common clinical syndromes diagnosed in the absence of biochemical, structural, or metabolic abnormalities. They account for significant morbidity and health care expenditures and are identifiable across variable age, geography, and culture. Etiology of abdominal pain associated FGIDs, including functional dyspepsia (FD), remains incompletely understood, but growing evidence implicates the importance of visceral hypersensitivity and electromechanical dysfunction. This manuscript explores data supporting the role of visceral hypersensitivity and electromechanical dysfunction in FD, with focus on pediatric data when available, and provides a summary of potential therapeutic targets. PMID:25133041

  14. Low back pain.

    PubMed Central

    Frank, A

    1993-01-01

    The studies reviewed here show that the duration and severity of individual episodes of back pain can be lessened, reducing recurrences and their cost in terms of suffering and lost work. Frank examines differential diagnosis; acute, chronic, and intractable pain; and service implications. Modern management emphasises self care, and bed rest should usually not be longer than 48 hours. A return to physical fitness and other activities, including employment, is actively encouraged. Medication has a role in facilitating these objectives. Two points are especially emphasised: strategies to manage low back pain must be long term and preventive; and the responsibility to keep fit, maintain an exercise programme, and remain relaxed so as to avoid physically stressing the spine is that of the individual, not of the professionals. Images FIG 2 PMID:8347190

  15. Schisandra chinensis reverses visceral hypersensitivity in a neonatal-maternal separated rat model.

    PubMed

    Yang, Jia-Ming; Xian, Yan-Fang; Ip, Paul S P; Wu, Justin C Y; Lao, Lixing; Fong, Harry H S; Sung, Joseph J Y; Berman, Brian; Yeung, John H K; Che, Chun-Tao

    2012-03-15

    Visceral hypersensitivity is an important characteristic feature of functional gastrointestinal disorders, such as irritable bowel syndrome (IBS). This study evaluated the effect of Schisandra chinensis on visceral hyperalgesia induced by neonatal maternal separation (NMS) in an IBS rat model. The visceromotor responses to colorectal balloon distension (CRD) were measured by abdominal withdrawal reflex (AWR) and electromyographic (EMG) activities. NMS control rats (receiving vehicle) underwent aggravated visceral pain in response to CRD as compared to normal rats, evidenced by the reduced pain threshold, enhanced AWR scores and EMG responses. Treatment with a 70% ethanol extract of S. chinensis (0.3g/kg and 1.5g/kg/day) for 7 days resulted in an increase in the pain threshold (NMS control: 19.1±1.0mmHg vs low-dose: 24.8±1.3mmHg and high-dose: 25.2±1.8mmHg, p<0.01), and abolished the elevated AWR and EMG responses to CRD in NMS rats (AUC values of EMG response curve were: 1952±202 in NMS control group vs 1074±90 in low-dose group and 1145±92 in high-dose group, p<0.001), indicating that S. chinensis could reverse the visceral hypersensitivity induced by early-life stress event. The result of ELSA measurement shows that the elevated serotonin (5-HT) level in the distal colon of NMS rats returned to normal level after treatment with S. chinensis. Moreover, the increase in pain threshold in rats treated with S. chinensis was associated with a decline of the mRNA level of 5-HT(3) receptor in the distal colon. All available results demonstrate that S. chinensis can reverse visceral hypersensitivity induced by neonatal-maternal separation, and the effect may be mediated through colonic 5-HT pathway in the rat.

  16. Schisandra chinensis reverses visceral hypersensitivity in a neonatal-maternal separated rat model

    PubMed Central

    Yang, Jia-Ming; Xian, Yan-Fang; Ip, Paul SP; Wu, Justin CY; Lao, Lixing; Fong, Harry HS; Sung, Joseph JY; Berman, Brian; Yeung, John HK; Che, Chun-Tao

    2012-01-01

    Visceral hypersensitivity is an important characteristic feature of functional gastrointestinal disorders, such as irritable bowel syndrome (IBS). This study evaluated the effect of Schisandra chinensis on visceral hyperalgesia induced by neonatal maternal separation (NMS) in an IBS rat model. The visceromotor responses to colorectal balloon distension (CRD) were measured by abdominal withdrawal reflex (AWR) and electromyographic activities (EMG). NMS control rats (receiving vehicle) underwent aggravated visceral pain in response to CRD as compared to normal rats, evidenced by the reduced pain threshold, enhanced AWR scores and EMG responses. Treatment with a 70% ethanol extract of S. chinensis (0.3 g/kg and 1.5 g/kg per day) for seven days resulted in an increase in the pain threshold (NMS control: 19.1 ± 1.0 mmHg vs low-dose: 24.8 ± 1.3 mmHg and high-dose: 25.2 ± 1.8 mmHg, p<0.01), and abolished the elevated AWR and EMG responses to CRD in NMS rats (AUC values of EMG response curve were: 1952 ± 202 in NMS control group vs 1074 ± 90 in low-dose group and 1145 ± 92 in high-dose group, p<0.001), indicating that S. chinensis could reverse the visceral hypersensitivity induced by early-life stress event. The result of ELSA measurement shows that the elevated serotonin (5-HT) level in the distal colon of NMS rats returned to normal level after treatment with S. chinensis. Moreover, the increase in pain threshold in rats treated with S. chinensis was associated with a decline of the mRNA level of 5-HT3 receptor in the distal colon. All available results demonstrate that S. chinensis can reverse visceral hypersensitivity induced by neonatal-maternal separation, and the effect may be mediated through colonic 5-HT pathway in the rat. PMID:22230486

  17. [A case of visceral leishmaniasis].

    PubMed

    Cruz-López, O; Tamariz-Cruz, O; Gándara-Ramírez, J L; Rojas-Domínguez, R; Cárdenas-Perea, M E

    1997-01-01

    A case of leishmaniasis (L. donovani) in a five year-old girl from Acatlan, State of Puebla, Mexico, is reported. She had had a 4-month history of malaise with 39 degrees C intermittent fever, hyporexia and a weight loss of 7 kg. She had spleen enlargement, and blood pancytopenia. A bone marrow study showed the Leishmania amastigotes; a positive blood culture on NNN media (Novy-Nicolle-MacNeal) confirmed the presence of promastigotes. A complete remission was achieved with methylglucamine. We present a review of the Mexican literature concerning visceral leishmaniasis.

  18. Hippocampal microglial activation and glucocorticoid receptor down-regulation precipitate visceral hypersensitivity induced by colorectal distension in rats.

    PubMed

    Zhang, Gongliang; Zhao, Bing-Xue; Hua, Rong; Kang, Jie; Shao, Bo-Ming; Carbonaro, Theresa M; Zhang, Yong-Mei

    2016-03-01

    Visceral hypersensitivity is a common characteristic in patients suffering from irritable bowel syndrome (IBS) and other disorders with visceral pain. Although the pathogenesis of visceral hypersensitivity remains speculative due to the absence of pathological changes, the long-lasting sensitization in neuronal circuitry induced by early life stress may play a critical role beyond the digestive system even after complete resolution of the initiating event. The hippocampus integrates multiple sources of afferent inputs and sculpts integrated autonomic outputs for pain and analgesia regulation. Here, we examined the hippocampal mechanism in the pathogenesis of visceral hypersensitivity with a rat model induced by neonatal and adult colorectal distensions (CRDs). Neither neonatal nor adult CRD evoked behavioral abnormalities in adulthood; however, adult re-exposure to CRD induced persistent visceral hypersensitivity, depression-like behaviors, and spatial learning impairment in rats that experienced neonatal CRD. Rats that experienced neonatal and adult CRDs presented a decrease in hippocampal glucocorticoid receptor (GR) immunofluorescence staining and protein expression, and increases in hippocampal microglial activation and cytokine (IL-1β and TNF-α) accumulation. The decrease in hippocampal GR expression and increase in hippocampal IL-1β and TNF-α accumulation could be prevented by hippocampal local infusion of minocycline, a microglial inhibitor. These results suggest that neonatal CRD can increase the vulnerability of hippocampal microglia, and adult CRD challenge facilitates the hippocampal cytokine release from the sensitized microglia, which down-regulates hippocampal GR protein expression and, subsequently, precipitates visceral hypersensitivity.

  19. Progress in the treatment of a neglected infectious disease: visceral leishmaniasis.

    PubMed

    Murray, Henry W

    2004-04-01

    Visceral leishmaniasis (kala-azar) is a disseminated intracellular protozoal infection. Most cases (90%) occur in the rural regions of five countries: India, Sudan, Nepal, Bangladesh and Brazil. As with other infectious diseases embedded in high-level poverty, developing and/or delivering new treatments for visceral leishmaniasis had been painfully slow or nonexistent. However, despite persistent unresolved obstacles (e.g., drug affordability), renewed interest in visceral leishmaniasis and numerous successful treatment trials have combined to turn a therapeutic corner in the past 5 years, yielding new alternatives to conventional pentavalent antimony. Advances include the use of low-cost generic pentavalent antimony, rediscovery of amphotericin B, short-course regimens via lipid formulations of amphotericin B, retesting injectible paromyomycin and, of clear-cut importance, identifying miltefosine (Impavido, Zentaris) as the first effective oral therapy for this neglected disease.

  20. Managing chronic pain with spinal cord stimulation.

    PubMed

    Epstein, Lawrence J; Palmieri, Marco

    2012-01-01

    Since its introduction as a procedure of last resort in a terminally ill patient with intractable cancer-related pain, spinal cord stimulation has been used to effectively treat chronic pain of varied origins. Spinal cord stimulation is commonly used for control of pain secondary to failed back surgery syndrome and complex regional pain syndrome, as well as pain from angina pectoris, peripheral vascular disease, and other causes. By stimulating one or more electrodes implanted in the posterior epidural space, the patient feels paresthesias in their areas of pain, which reduces the level of pain. Pain is reduced without the side effects associated with analgesic medications. Patients have improved quality of life and improved function, with many returning to work. Spinal cord stimulation has been shown to be cost effective as compared with conservative management alone. There is strong evidence for efficacy and cost effectiveness of spinal cord stimulation in the treatment of pain associated with intractable angina, failed back surgery syndrome, and complex regional pain syndrome. In this article, we review the history and pathophysiology of spinal cord stimulation, and the evidence (or lack thereof) for efficacy in common clinical practice.

  1. [Clinical managements for intractable pneumothorax with interstitial pneumonia].

    PubMed

    Kataoka, H; Kurihara, M

    2011-04-01

    Intractable pneumothorax with interstitial pneumonia (IP) is famous for the disease finally to lead to death in case of persistent air leakage. It is because severe infection, respiratory insufficiency and tissue healing insufficiency by treatments with steroid hormones and immune-suppressants on IP. Pleurodesis is generally performed although the effect of it is questionable. It is important to stop immune-suppressants and reduce steroid hormones before the treatments to succeed in thoracoscopic surgery and thoracographic fibrin glue sealing method (TGF) if possible. Less invasive interventional treatments like TGF are recommendable because intractable pneumothorax with IP is in the high risk group to need to avoid surgery. Hand suturing, looping, covering and putting TachoComb on the air leak point instead of end-stapling should be performed in order to stop air leakage when forced to choose thoracoscopic surgery.

  2. Intractable ascites in systemic mastocytosis treated by portal diversion.

    PubMed

    Bonnet, P; Smadja, C; Szekely, A M; Delage, Y; Calmus, Y; Poupon, R; Franco, D

    1987-02-01

    A 50-year-old male presented with intractable ascites due to systemic mastocytosis. The diagnosis of systemic mastocytosis was established by histology of the bone marrow which showed mast cell infiltration and fibrosis. Ascites was related to portal hypertension which was documented by esophageal varices at endoscopy and by an increase of wedged-free hepatic venous pressure gradient. Liver biopsy disclosed dense fibrosis of hepatic arterial and portal venule walls, resulting in complete obstruction of some portal radicles. Peliosis hepatis and fibrous deposits in the walls of hepatic venules were also present. Because of intractable ascites and significant malnutrition, a portacaval shunt was performed which cleared ascites and dramatically improved the general condition of the patient.

  3. PET MRI Coregistration in Intractable Epilepsy and Gray Matter Heterotopia.

    PubMed

    Seniaray, Nikhil; Jain, Anuj

    2017-03-01

    A 25-year-old woman with intractable seizures underwent FDG PET/MRI for seizure focus localization. MRI demonstrated bilateral carpetlike nodular subependymal gray matter and asymmetrical focal dilatation in the right temporal horn. PET/MRI showed increased FDG within subependymal gray matter with significant hypometabolism in right anterior temporal lobe. EEG and ictal semiology confirmed the right temporal seizure origin. This case highlights the importance of identification of gray matter heterotopia on FDG PET/MRI.

  4. Stereotactic radiofrequency thermocoagulation for hypothalamic hamartoma with intractable gelastic seizures.

    PubMed

    Homma, Junpei; Kameyama, Shigeki; Masuda, Hiroshi; Ueno, Takehiko; Fujimoto, Ayataka; Oishi, Makoto; Fukuda, Masafumi

    2007-08-01

    Management of hypothalamic hamartoma with intractable gelastic epilepsy remains controversial. We have used stereotactic thermocoagulation for treatment of hypothalamic hamartoma with intractable gelastic epilepsy since 1997. Herein, we review our experience in five cases to clarify the usefulness of this treatment. A total of five patients with hypothalamic hamartoma were treated by stereotactic thermocoagulation at our hospital during the period October 1997 through February 2004. In all patients, the hamartoma was less than 10mm in diameter and was located on the floor of the third ventricle with sessile attachment to the wall. To identify ictal onset, chronic intracranial electroencephalography was performed in three patients with the use of a depth electrode implanted in the hamartoma. Attempts were made to induce gelastic seizure by electrical stimulation of the hamartoma in three patients. After magnetic resonance imaging-guided targeting, radiofrequency thermocoagulation of the boundary between the hamartoma and normal hypothalamus was performed to achieve disconnection effects. Marked reductions in seizure frequency were obtained in all cases, with three patients becoming seizure-free after the procedure. No intraoperative complications occurred except in one patient who experienced acute and transient panidrosis with hot flushes during coagulation. Our results suggest that stereotactic thermocoagulation of hypothalamic hamartoma is an acceptable treatment option for patients with intractable gelastic seizures.

  5. Colonic mast cell infiltration in rats with TNBS-induced visceral hypersensitivity.

    PubMed

    Ohashi, Katsuyo; Sato, Yasushi; Iwata, Hiroshi; Kawai, Mitsuhisa; Kurebayashi, Yoichi

    2007-12-01

    Colonic mucosal mast cells are implicated in the pathogenesis of visceral hypersensitivity associated with irritable bowel syndromes. This study was designed to investigate the roles of mucosal mast cells in development of an experimental visceral hypersensitivity induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) in rats. TNBS, when injected into the proximal colon through laparotomy, produced a significant decrease in pain threshold of the distal colon to mechanical distention, indicating a visceral hypersensitivity. In the proximal colon that was directly insulted by TNBS, mucosal necrosis and extensive inflammatory cell infiltration were observed with concomitant increase in tissue myeloperoxide (MPO) activity. In the distal colon where distention stimuli were applied, the number of mucosal mast cells significantly increased following TNBS treatment, although neither mucosal injury nor increase in tissue MPO activity was observed. In an organ culture, spontaneous release of a mucosal mast cell-specific protease (RMCP-2) from the distal colon tissue of TNBS-treated rats was significantly larger than that of sham animals. Furthermore, TNBS-induced visceral hypersensitivity was significantly suppressed by subcutaneous pretreatment with a mast cell stabilizer doxantrazole in a dose-dependent manner. These findings suggest that prominent colonic mast cell infiltration associated with an enhanced spontaneous mediator release is responsible, at least partly, for development of visceral hypersensitivity induced by TNBS in rats.

  6. The treatment of chronic pain with psychotropic drugs

    PubMed Central

    Merskey, H.; Hester, R. A.

    1972-01-01

    The treatment is described of thirty patients with chronic nervous system lesion causing intractable pain. Moderately good relief of pain was obtained with a combination of phenothiazines (especially pericyazine), antidepressant drugs and antihistamines. The theoretical implications of this are discussed and it is suggested that the drugs in question act partly by virtue of an effect on the multisynaptic neuronal systems whose activities are related to the experience of pain. PMID:4404064

  7. Persistent visceral allodynia in rats exposed to colorectal irradiation is reversed by mesenchymal stromal cell treatment.

    PubMed

    Durand, Christelle; Pezet, Sophie; Eutamène, Hélène; Demarquay, Christelle; Mathieu, Noëlle; Moussa, Lara; Daudin, Rachel; Holler, Valérie; Sabourin, Jean-Christophe; Milliat, Fabien; François, Agnès; Theodorou, Vassilia; Tamarat, Radia; Benderitter, Marc; Sémont, Alexandra

    2015-08-01

    Each year, millions of people worldwide are treated for primary or recurrent pelvic malignancies, involving radiotherapy in almost 50% of cases. Delayed development of visceral complications after radiotherapy is recognized in cancer survivors. Therapeutic doses of radiation may lead to the damage of healthy tissue around the tumor and abdominal pain. Because of the lack of experimental models, the underlying mechanisms of radiation-induced long-lasting visceral pain are still unknown. This makes managing radiation-induced pain difficult, and the therapeutic strategies proposed are mostly inefficient. The aim of our study was to develop an animal model of radiation-induced visceral hypersensitivity to (1) analyze some cellular and molecular mechanisms involved and (2) to test a therapeutic strategy using mesenchymal stromal cells (MSCs). Using a single 27-Grays colorectal irradiation in rats, we showed that such exposure induces a persistent visceral allodynia that is associated with an increased spinal sensitization (enhanced p-ERK neurons), colonic neuroplasticity (as increased density of substance P nerve fibers), and colonic mast cell hyperplasia and hypertrophy. Mast cell stabilization by ketotifen provided evidence of their functional involvement in radiation-induced allodynia. Finally, intravenous injection of 1.5 million MSCs, 4 weeks after irradiation, induced a time-dependent reversion of the visceral allodynia and a reduction of the number of anatomical interactions between mast cells and PGP9.5+ nerve fibers. Moreover, unlike ketotifen, MSC treatment has the key advantage to limit radiation-induced colonic ulceration. This work provides new insights into the potential use of MSCs as cellular therapy in the treatment of pelvic radiation disease.

  8. Evidence-based Clinical Practice Guidelines for Interventional Pain Management in Cancer Pain

    PubMed Central

    Bhatnagar, Sushma; Gupta, Maynak

    2015-01-01

    Intractable cancer pain not amenable to standard oral or parenteral analgesics is a horrifying truth in 10–15% of patients. Interventional pain management techniques are an indispensable arsenal in pain physician's armamentarium for severe, intractable pain and can be broadly classified into neuroablative and neuromodulation techniques. An array of neurolytic techniques (chemical, thermal, or surgical) can be employed for ablation of individual nerve fibers, plexuses, or intrathecalneurolysis in patients with resistant pain and short life-expectancy. Neuraxial administration of drugs and spinal cord stimulation to modulate or alter the pain perception constitutes the most frequently employed neuromodulation techniques. Lately, there is a rising call for early introduction of interventional techniques in carefully selected patients simultaneously or even before starting strong opioids. After decades of empirical use, it is the need of the hour to head towards professionalism and standardization in order to secure credibility of specialization and those practicing it. Even though the interventional management has found a definite place in cancer pain, there is a dearth of evidence-based practice guidelines for interventional therapies in cancer pain. This may be because of paucity of good quality randomized controlled trials (RCTs) evaluating their safety and efficacy in cancer pain. Laying standardized guidelines based on existing and emerging evidence will act as a foundation step towards strengthening, credentialing, and dissemination of the specialty of interventional cancer pain management. This will also ensure an improved decision-making and quality of life (QoL) of the suffering patients. PMID:26009665

  9. Evidence-based Clinical Practice Guidelines for Interventional Pain Management in Cancer Pain.

    PubMed

    Bhatnagar, Sushma; Gupta, Maynak

    2015-01-01

    Intractable cancer pain not amenable to standard oral or parenteral analgesics is a horrifying truth in 10-15% of patients. Interventional pain management techniques are an indispensable arsenal in pain physician's armamentarium for severe, intractable pain and can be broadly classified into neuroablative and neuromodulation techniques. An array of neurolytic techniques (chemical, thermal, or surgical) can be employed for ablation of individual nerve fibers, plexuses, or intrathecalneurolysis in patients with resistant pain and short life-expectancy. Neuraxial administration of drugs and spinal cord stimulation to modulate or alter the pain perception constitutes the most frequently employed neuromodulation techniques. Lately, there is a rising call for early introduction of interventional techniques in carefully selected patients simultaneously or even before starting strong opioids. After decades of empirical use, it is the need of the hour to head towards professionalism and standardization in order to secure credibility of specialization and those practicing it. Even though the interventional management has found a definite place in cancer pain, there is a dearth of evidence-based practice guidelines for interventional therapies in cancer pain. This may be because of paucity of good quality randomized controlled trials (RCTs) evaluating their safety and efficacy in cancer pain. Laying standardized guidelines based on existing and emerging evidence will act as a foundation step towards strengthening, credentialing, and dissemination of the specialty of interventional cancer pain management. This will also ensure an improved decision-making and quality of life (QoL) of the suffering patients.

  10. Intractable hiccups caused by esophageal diverticular candidiasis in an immunocompetent adult: a case report

    PubMed Central

    Yahata, Shinsuke; Kenzaka, Tsuneaki; Kushida, Saeko; Nishisaki, Hogara; Akita, Hozuka

    2017-01-01

    Introduction Various causes of intractable hiccups have been reported; however, to the best of our knowledge, there are no previous reports of either intractable hiccups due to esophageal candidiasis in an immunocompetent adult or improvement following antifungal therapy. Case presentation An 87-year-old man presented with intractable hiccups. Although the patient was immunocompetent, he used proton pump inhibitors. An esophagogastroduodenos-copy revealed several white deposits throughout the esophagus and extensive white deposits in the midesophageal diverticulum. A mucosal culture showed candidiasis, which was suspected to be the cause of the intractable hiccups. After oral fluconazole had been prescribed, the candidiasis resolved and the hiccups improved. Therefore, we concluded that esophageal diverticular candidiasis was the cause of his intractable hiccups. Conclusion Physicians should consider esophageal candidiasis as one of the differential diagnoses for intractable hiccups, even in immunocompetent adults. PMID:28243153

  11. Sex Differences in Functional Brain Activation during Noxious Visceral Stimulation in Rats

    PubMed Central

    Bradesi, Sylvie; Labus, Jennifer S.; Maarek, Jean-Michel I.; Lee, Kevin; Winchester, Wendy J.; Mayer, Emeran A.; Holschneider, Daniel P.

    2009-01-01

    Studies in healthy human subjects and patients with irritable bowel syndrome suggest sex differences in cerebral nociceptive processing. Here we examine sex differences in functional brain activation in the rat during colorectal distention (CRD), a preclinical model of acute visceral pain. [14C]-iodoantipyrine was injected intravenously in awake, nonrestrained female rats during 60-mmHg or 0-mmHg CRD while electromyographic abdominal activity (EMG) and pain behavior were recorded. Regional cerebral blood flow related tissue radioactivity was analyzed by statistical parametric mapping from autoradiographic images of 3-dimensionally reconstructed brains. Sex differences were addressed by comparing current data with our previously published data collected from male rats. While sex differences in EMG and pain scores were modest, significant differences were noted in functional brain activation. Females showed widespread changes in limbic (amygdala, hypothalamus) and paralimbic structures (ventral striatum, nucleus accumbens, raphe), while males demonstrated broad cortical changes. Sex differences were apparent in the homeostatic afferent network (parabrachial nucleus, thalamus, insular and dorsal anterior cingulate cortices), in an emotional-arousal network (amygdala, locus coeruleus complex), and in cortical areas modulating these networks (prefrontal cortex). Greater activation of the ventromedial prefrontal cortex and broader limbic/paralimbic changes in females suggest greater engagement of affective mechanisms during visceral pain. Greater cortical activation in males is consistent with the concept of greater cortical inhibitory effects on limbic structures in males, which may relate to differences in attentional and cognitive attribution to visceral stimuli. These findings show remarkable similarities to reported sex differences in brain responses to visceral stimuli in humans. PMID:19560270

  12. Holistic approach to treatment of intractable central neuropathic itch.

    PubMed

    Curtis, Ashley R; Tegeler, Charles; Burdette, Jonathan; Yosipovitch, Gil

    2011-05-01

    Central neuropathic itch can be a lifelong debilitating condition and treatment challenge. We report a patient with a traumatic brain injury with severe intractable pruritus who failed extensive pharmacologic and nonpharmacologic treatment but responded to a holistic approach using healing touch. We discuss the complexity of this type of neuropathic itch and present a holistic approach as an adjunct to therapy in reducing itch intensity. This case presentation along with the literature discussed suggests a therapeutic strategy for the management of complicated central neuropathic itch.

  13. Efficacy of the Atkins diet as therapy for intractable epilepsy.

    PubMed

    Kossoff, Eric H; Krauss, Gregory L; McGrogan, Jane R; Freeman, John M

    2003-12-23

    The ketogenic diet is effective for treating seizures in children with epilepsy. The Atkins diet can also induce a ketotic state, but has fewer protein and caloric restrictions, and has been used safely by millions of people worldwide for weight reduction. Six patients, aged 7 to 52 years, were started on the Atkins diet for the treatment of intractable focal and multifocal epilepsy. Five patients maintained moderate to large ketosis for periods of 6 weeks to 24 months; three patients had seizure reduction and were able to reduce antiepileptic medications. This provides preliminary evidence that the Atkins diet may have a role as therapy for patients with medically resistant epilepsy.

  14. Biomarkers for visceral hypersensitivity identified by classification of electroencephalographic frequency alterations

    NASA Astrophysics Data System (ADS)

    Graversen, Carina; Brock, Christina; Mohr Drewes, Asbjørn; Farina, Dario

    2011-10-01

    Abdominal pain is frequently related to visceral hypersensitivity. This is associated with increased neuronal excitability in the central nervous system (CNS), which can be manifested as discrete electroencephalographic (EEG) alterations. In the current placebo-controlled study, visceral hypersensitivity was evoked by chemical irritation of the esophagus with acid and capsaicin perfusion. The resulting hyperexcitability of the CNS was evaluated by evoked brain potentials following painful electrical stimulations of a remote organ—the rectosigmoid colon. Alterations in individual EEG power distributions between baseline and after perfusion were quantified by extracting features from the evoked brain potentials using an optimized discrete wavelet transform. Visceral hypersensitivity was identified as increased EEG power in the delta, theta and alpha frequency bands. By applying a support vector machine in regression mode, the individual baseline corrected alterations after sensitization were discriminated from alterations caused by placebo perfusions. An accuracy of 91.7% was obtained (P < 0.01). The regression value representing the overall alteration of the EEG correlated with the degree of hyperalgesia (P = 0.03). In conclusion, this study showed that classification of EEG can be used to detect biomarkers reflecting central neuronal changes. In the future, this may be used in studies of pain physiology and pharmacological interventions.

  15. Spinothalamic fibres, pain conduction and cordotomy.

    PubMed

    Moffie, D

    1975-01-01

    Description of four cases of cordotomy for intractable pain in which autopsy could be performed. In two of the cases the lesion had been placed (unintentionally) in the posterior quadrant of the spinal cord with good results as to the abolishing of pain. It is concluded that the conduction of pain and temperature stimuli is not restricted to the anterolateral part of the spinal cord but that this conduction may also take place along fibres in the posterolateral quadrant. A further conclusion is that the results of cordotomy are related to the number of cut fibres.

  16. Haloperidol: a possible medication for the treatment of exacerbation of intractable psychogenic sneezing.

    PubMed

    Guner, Sukru Nail; Gokcen, Cem; Gokturk, Bahar; Topal, Ozgul

    2010-10-01

    Sneezing is one of the physiological defense mechanisms that develops generally due to nasal irritation. But intractable sneezing episodes are uncommon and generally detected among the adolescents. It is difficult to distinguish physiologic sneezing from psychogenic sneezing. Herein, we report a 12-year-old girl who was complaint with intractable sneezing. She was diagnosed as intractable psychogenic sneezing and haloperidol treatment was started. All symptoms had resolved completely within 2 weeks. As a result, haloperidol can be considered as a different treatment modality for intractable psychogenic sneezing.

  17. Abolishment of TNBS-induced visceral hypersensitivity in mast cell deficient rats.

    PubMed

    Ohashi, Katsuyo; Sato, Yasushi; Kawai, Mitsuhisa; Kurebayashi, Yoichi

    2008-02-13

    Mucosal mast cells are implicated in visceral hypersensitivity associated with irritable bowel syndrome (IBS). In this study, we investigated the role of mast cells in the development of visceral hypersensitivity by using mast cell deficient (Ws/Ws) rats and their control (W+/W+). In W+/W+ rats, an injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS) into the proximal colon produced a significant decrease in pain threshold of the distal colon. Severe mucosal necrosis and inflammatory cell infiltration with concomitant increase in tissue myeloperoxidase activity were observed in the proximal colon that was directly insulted by TNBS, whereas neither necrosis nor increased myeloperoxidase activity occurred in the distal colon, indicating that TNBS-induced hypersensitivity is not caused by the local tissue damage or inflammation in the region of the gut where distention stimuli were applied. On the other hand, TNBS failed to elicit visceral hypersensitivity in Ws/Ws rats. This finding indicates that mast cells are essential for development of TNBS-induced visceral hypersensitivity in rats. Since the severity of TNBS-induced proximal colon injury and MPO activity was not affected by mast cell deficiency, it is unlikely that abolishment of visceral hypersensitivity in mast cell deficient rats was a result of altered development of the primary injury in the proximal colon. There was no difference between sham-operated Ws/Ws and W+/W+ rats in colonic pain threshold to distention stimuli, indicating that mast cells play no modulatory roles in normal colonic nociception. The present results support the view that mucosal mast cells play key roles in the pathogenesis of IBS.

  18. Investigational Drugs for Visceral Leishmaniasis

    PubMed Central

    Sundar, Shyam; Chakravarty, Jaya

    2014-01-01

    Introduction The armamentarium of antileishmanials is small. It is further being threatened by development of resistance and decreasing sensitivity to the available drugs. Development of newer drugs are sorely needed. Areas covered Literature search on investigational drugs for visceral leishmaniasis (VL) was done on PubMed. Those candidates with at least in vitro and in vivo activity against leishmania species causing VL were reviewed. Among the investigational drugs the nitroimidazole compound fexinidazole is the one of the few drugs which has reached phase II trials. Although the (S)-PA-824 is in phase II trials for the treatment of tuberculosis its R enantiomer has shown good antileishmanial activity. Development of sitamaquin, which has completed phase II studies has been stopped for VL due to its low efficacy. Many novel delivery system and oral formulations of Amphotericin B which are cheap and less toxic are in investigational stages, and will go a long way in improving the treatment of VL. Expert opinion Very few new drugs have reached the clinical stage in the treatment of this neglected tropical disease. Thus, there is an urgent need for support from public private partnerships to ensure that drug candidates are promptly taken forward into development. PMID:25409760

  19. Visceral basidiobolomycosis: An overlooked infection in immunocompetent children

    PubMed Central

    Mandhan, Parkash; Hassan, Kamal Osman; Samaan, Sandra Moustafa; Ali, Mansour J

    2015-01-01

    Visceral basidiobolomycosis is an unusual fungal infection of viscera caused by saprophyte Basidiobolus ranarum. It is very rare in healthy children and poses a diagnostic challenge due to the non-specific clinical presentation and the absence of predisposing factors. We report a case of gastrointestinal basidiobolomycosis in a 4-year-old healthy girl who presented with a short history of abdominal pain, bleeding per rectum, fever, and weight loss. The diagnosis was based on high eosinophilic count, classical histopathology findings of fungal hyphae (the Splendore-Hoeppli phenomenon), and positive fungal culture from a tissue biopsy. Fungal infection was successfully eradicated with a combined approach of surgical resection of the infected tissue and a well-monitored course of antifungal therapy. The atypical clinical presentation, diagnostic techniques, and the role of surgery in the management of a rare and lethal fungal disease in an immunocompetent child are discussed. PMID:26612126

  20. Motive attribution asymmetry for love vs. hate drives intractable conflict.

    PubMed

    Waytz, Adam; Young, Liane L; Ginges, Jeremy

    2014-11-04

    Five studies across cultures involving 661 American Democrats and Republicans, 995 Israelis, and 1,266 Palestinians provide previously unidentified evidence of a fundamental bias, what we term the "motive attribution asymmetry," driving seemingly intractable human conflict. These studies show that in political and ethnoreligious intergroup conflict, adversaries tend to attribute their own group's aggression to ingroup love more than outgroup hate and to attribute their outgroup's aggression to outgroup hate more than ingroup love. Study 1 demonstrates that American Democrats and Republicans attribute their own party's involvement in conflict to ingroup love more than outgroup hate but attribute the opposing party's involvement to outgroup hate more than ingroup love. Studies 2 and 3 demonstrate this biased attributional pattern for Israelis and Palestinians evaluating their own group and the opposing group's involvement in the current regional conflict. Study 4 demonstrates in an Israeli population that this bias increases beliefs and intentions associated with conflict intractability toward Palestinians. Finally, study 5 demonstrates, in the context of American political conflict, that offering Democrats and Republicans financial incentives for accuracy in evaluating the opposing party can mitigate this bias and its consequences. Although people find it difficult to explain their adversaries' actions in terms of love and affiliation, we suggest that recognizing this attributional bias and how to reduce it can contribute to reducing human conflict on a global scale.

  1. Qualitative and Quantitative Hippocampal MRI Assessments in Intractable Epilepsy

    PubMed Central

    Singh, Paramdeep; Kaur, Rupinderjeet; Saggar, Kavita; Singh, Gagandeep; Kaur, Amarpreet

    2013-01-01

    Aims. To acquire normative data of hippocampal volumes and T2 relaxation times, to evaluate and compare qualitative and quantitative assessments in evaluating hippocampi in patients with different durations of intractable epilepsy, and to propose an imaging protocol based on performance of these techniques. Methods. MRI analysis was done in 50 nonepileptic controls and 30 patients with intractable epilepsy on 1.5T scanner. Visual assessment and hippocampal volumetry were done on oblique coronal IR/T2W and T1W MP-RAGE images, respectively. T2 relaxation times were measured using 16-echo Carr-Purcell-Meiboom-Gill sequence. Volumetric data was normalized for variation in head size between individuals. Patients were divided into temporal (n = 20) and extratemporal (n = 10) groups based on clinical and EEG localization. Results. In controls, right hippocampal volume was slightly more than the left with no effect of age or gender. In TLE patients, hippocampal volumetry provided maximum concordance with EEG. Visual assessment of unilateral pathology concurred well with measured quantitative values but poorly in cases with bilateral pathologies. There were no significant differences of mean values between extratemporal group and controls group. Quantitative techniques detected mild abnormalities, undetected on visual assessment. Conclusions. Quantitative techniques are more sensitive to diagnose bilateral and mild unilateral hippocampal abnormalities. PMID:23984369

  2. Treatment of Pain and Autonomic Dysreflexia in Spinal Cord Injury with Deep Brain Stimulation

    DTIC Science & Technology

    2015-10-01

    Subcortical electrical stimulation for control of intractable pain in humans. Report of 122 cases (1970-1984). J Neurosurg. 64, 543-53. Levy, R., Deer ...posterior commissure; RN, red nucleus; SC, superior colliculus; V3, 3rd ventricle. Figure 2. Time courses of pain in the two subjects. Weekly scores for

  3. Pain Syndromes—The Use of Nerve Block in Diagnosis and Treatment

    PubMed Central

    Brechner, Verne L.

    1967-01-01

    There are four distinct pain entities which may be treated by injection of local anesthetic or neurolytic agents. These entities are somatic, visceral, sympathetic mediated and myofascial pain. Each entity should be recognized as separate from other types of pain and the appropriate therapeutic approach prescribed. PMID:4382956

  4. The Laparoscopic Implantation of Neuroprothesis (LION) Procedure to Control Intractable Abdomino-Pelvic Neuralgia.

    PubMed

    Possover, Marc; Baekelandt, Jan; Chiantera, Vito

    2007-01-01

    Objective.  To present different aspects and advantages of the laparoscopic implantation of a peripheral nerve stimulator adjacent to the pelvic nerves, aimed at treating intractable pelvic neuralgia by means of neuromodulation-the laparoscopic implantation of neuroprothesis (LION) procedure. Materials and Methods.  We report here a series of three patients with different types and etiologies of chronic pelvic neuralgia who underwent laparoscopy for implantation of a peripheral nerve stimulator for neuromodulation, the first for neuromodulation of the ilioinguinal and pudendal nerves, the second for neuromodulation of the sciatic nerve, and the third for neuromodulation of the sacral nerve roots. In all three patients, the neuralgia was refractory to medical management and had profound socioeconomic consequences for the patients. Results.  Laparoscopic implantation of neuroelectrodes was successfully performed in all three patients and resulted significant diminution of pain without need for further medical treatment. Conclusions.  Laparoscopy allows optimal implantation of electrodes on all pelvic nerves through a minimally invasive approach. In addition, it permits new applications of neuromodulation for pelvic polyneuropathies or mononeuropathy, not covered by classical spinal cord or transcutaneous techniques.

  5. Occipital nerve stimulation for the treatment of intractable chronic migraine headache: ONSTIM feasibility study

    PubMed Central

    Saper, Joel R; Dodick, David W; Silberstein, Stephen D; McCarville, Sally; Sun, Mark; Goadsby, Peter J

    2011-01-01

    Background: Medically intractable chronic migraine (CM) is a disabling illness characterized by headache ≥15 days per month. Methods: A multicenter, randomized, blinded, controlled feasibility study was conducted to obtain preliminary safety and efficacy data on occipital nerve stimulation (ONS) in CM. Eligible subjects received an occipital nerve block, and responders were randomized to adjustable stimulation (AS), preset stimulation (PS) or medical management (MM) groups. Results: Seventy-five of 110 subjects were assigned to a treatment group; complete diary data were available for 66. A responder was defined as a subject who achieved a 50% or greater reduction in number of headache days per month or a three-point or greater reduction in average overall pain intensity compared with baseline. Three-month responder rates were 39% for AS, 6% for PS and 0% for MM. No unanticipated adverse device events occurred. Lead migration occurred in 12 of 51 (24%) subjects. Conclusion: The results of this feasibility study offer promise and should prompt further controlled studies of ONS in CM. PMID:20861241

  6. [Sleep, emotions and the visceral control].

    PubMed

    Pigarev, I N; Pigareva, M L

    2013-01-01

    It is known that sleep is connected with sensory isolation of the brain, inactivation of the consciousness and reorganization of the electrical activity in all cerebral cortical areas. On the other hand, sleep deprivation leads to pathology in visceral organs and finally to the death of animals, while there are no obvious changes in the brain itself. It stays the opened question how the changes in the brain activity during sleep could be con- nected with the visceral health? We proposed that the same brain areas and the same neurons, which in wakefulness process the information coming from the distant and proprioreceptors, switch during sleep to the processing of the interoceptive information. Thus, central nervous system is involved into the regulation of the life support functions of the body during sleep. Results of our experiments supported this hypothesis, explained many observations obtained in somnology and offered the mechanisms of several pathological states connected with sleep. However, at the present level of the visceral sleep theory there were no understanding of the well known link between the emotional states of the organisms and transition from wakefulness to sleep, and sleep quality. In this study the attempt is undertaken to combine the visceral theory of sleep with the need- informational theory ofemotions, proposed by P. Simonov. The visceral theory of sleep proposes that in living organisms there is a constant monitoring of the correspondence of the visceral parameters to the genetically determined values. Mismatch signals evoke the feeling of tiredness and the need of sleep. This sleep need en- ters the competition with the other actual needs of the organism. In according with the theory of P. Simonov emotions connected with a particular need play important role in their ranking for satisfaction. We propose that emotional estimation of the sleep need, based on the visceral signals, is realized in the same brain structures which undertake this

  7. Visceral hypersensitivity in inflammatory bowel diseases and irritable bowel syndrome: The role of proteases

    PubMed Central

    Ceuleers, Hannah; Van Spaendonk, Hanne; Hanning, Nikita; Heirbaut, Jelena; Lambeir, Anne-Marie; Joossens, Jurgen; Augustyns, Koen; De Man, Joris G; De Meester, Ingrid; De Winter, Benedicte Y

    2016-01-01

    Proteases, enzymes catalyzing the hydrolysis of peptide bonds, are present at high concentrations in the gastrointestinal tract. Besides their well-known role in the digestive process, they also function as signaling molecules through the activation of protease-activated receptors (PARs). Based on their chemical mechanism for catalysis, proteases can be classified into several classes: serine, cysteine, aspartic, metallo- and threonine proteases represent the mammalian protease families. In particular, the class of serine proteases will play a significant role in this review. In the last decades, proteases have been suggested to play a key role in the pathogenesis of visceral hypersensitivity, which is a major factor contributing to abdominal pain in patients with inflammatory bowel diseases and/or irritable bowel syndrome. So far, only a few preclinical animal studies have investigated the effect of protease inhibitors specifically on visceral sensitivity while their effect on inflammation is described in more detail. In our accompanying review we describe their effect on gastrointestinal permeability. On account of their promising results in the field of visceral hypersensitivity, further research is warranted. The aim of this review is to give an overview on the concept of visceral hypersensitivity as well as on the physiological and pathophysiological functions of proteases herein. PMID:28058009

  8. Vaccines for visceral leishmaniasis: A review.

    PubMed

    Jain, Keerti; Jain, N K

    2015-07-01

    Visceral leishmaniasis, which is also known as Kala-Azar, is one of the most severely neglected tropical diseases recognized by the World Health Organization (WHO). The threat of this debilitating disease continues due to unavailability of promising drug therapy or human vaccine. An extensive research is undergoing to develop a promising vaccine to prevent this devastating disease. In this review we compiled the findings of recent research with a view to facilitate knowledge on experimental vaccinology for visceral leishmaniasis. Various killed or attenuated parasite based first generation vaccines, second generation vaccines based on antigenic protein or recombinant protein, and third generation vaccines derived from antigen-encoding DNA plasmids including heterologous prime-boost Leishmania vaccine have been examined for control and prevention of visceral leishmaniasis. Vaccines based on recombinant protein and antigen-encoding DNA plasmids have given promising results and few vaccines including Leishmune®, Leishtec, and CaniLeish® have been licensed for canine visceral leishmaniasis. A systematic investigation of these vaccine candidates can lead to development of promising vaccine for human visceral leishmaniasis, most probably in the near future.

  9. Peace Education in Societies Involved in Intractable Conflicts: Direct and Indirect Models

    ERIC Educational Resources Information Center

    Bar-Tal, Daniel; Rosen, Yigal

    2009-01-01

    The present article deals with the crucial question: Can peace education facilitate change in the sociopsychological infrastructure that feeds continued intractable conflict and then how the change can be carried? Intractable conflicts still rage in various parts of the globe, and they not only cause local misery and suffering but also threaten…

  10. Noncardiac chest pain: current treatment.

    PubMed

    Schey, Ron; Villarreal, Autumn; Fass, Ronnie

    2007-04-01

    Noncardiac chest pain (NCCP) is very common, affecting up to 25% of the adult population in the United States. Treatment for NCCP has markedly evolved in the past decade and is presently focused on gastroesophageal reflux disease (GERD) and visceral hypersensitivity. Aggressive treatment with proton pump inhibitors has become the standard of care for GERD-related NCCP. Pain modulators such as tricyclics, trazodone, and selective serotonin reuptake inhibitors are considered the mainstay of therapy for non-GERD-related NCCP Other therapeutic modalities such as botulinum toxin injections and hypnotherapy have demonstrated promise in small clinical trials.

  11. Systematic mechanism-orientated approach to chronic pancreatitis pain

    PubMed Central

    Bouwense, Stefan AW; de Vries, Marjan; Schreuder, Luuk TW; Olesen, Søren S; Frøkjær, Jens B; Drewes, Asbjørn M; van Goor, Harry; Wilder-Smith, Oliver HG

    2015-01-01

    Pain in chronic pancreatitis (CP) shows similarities with other visceral pain syndromes (i.e., inflammatory bowel disease and esophagitis), which should thus be managed in a similar fashion. Typical causes of CP pain include increased intrapancreatic pressure, pancreatic inflammation and pancreatic/extrapancreatic complications. Unfortunately, CP pain continues to be a major clinical challenge. It is recognized that ongoing pain may induce altered central pain processing, e.g., central sensitization or pro-nociceptive pain modulation. When this is present conventional pain treatment targeting the nociceptive focus, e.g., opioid analgesia or surgical/endoscopic intervention, often fails even if technically successful. If central nervous system pain processing is altered, specific treatment targeting these changes should be instituted (e.g., gabapentinoids, ketamine or tricyclic antidepressants). Suitable tools are now available to make altered central processing visible, including quantitative sensory testing, electroencephalograpy and (functional) magnetic resonance imaging. These techniques are potentially clinically useful diagnostic tools to analyze central pain processing and thus define optimum management approaches for pain in CP and other visceral pain syndromes. The present review proposes a systematic mechanism-orientated approach to pain management in CP based on a holistic view of the mechanisms involved. Future research should address the circumstances under which central nervous system pain processing changes in CP, and how this is influenced by ongoing nociceptive input and therapies. Thus we hope to predict which patients are at risk for developing chronic pain or not responding to therapy, leading to improved treatment of chronic pain in CP and other visceral pain disorders. PMID:25574079

  12. Groin pain

    MedlinePlus

    Pain - groin; Lower abdominal pain; Genital pain; Perineal pain ... Common causes of groin pain include: Pulled muscle, tendon, or ligaments in the leg: This problem often occurs in people who play sports such as ...

  13. Vagus nerve stimulation for the treatment of intractable epilepsy.

    PubMed

    Amar, Arun Paul

    2007-12-01

    Vagus nerve stimulation is a safe and reliable treatment adjunct for patients with medically intractable epilepsy. It is both a preventive and abortive form of therapy, potentially effective against both partial and generalized seizures in adults and children. Vagus nerve stimulation also has a number of serendipitous effects on mood, memory and attention, and has been approved for the treatment of refractory depression. Owing to its pleiotropic effects, it also holds promise for several other diseases. Its principal limitations are its unknown mechanism of action, the low likelihood of complete cure and the inability to predict which patients will derive substantial benefit. This article reviews the theoretical rationale, practical background and clinical applications of vagus nerve stimulation therapy.

  14. Total lymphoid irradiation for treatment of intractable cardiac allograft rejection

    SciTech Connect

    Hunt, S.A.; Strober, S.; Hoppe, R.T.; Stinson, E.B. )

    1991-03-01

    The ability of postoperative total lymphoid irradiation to reverse otherwise intractable cardiac allograft rejection was examined in a group of 10 patients in whom conventional rejection therapy (including pulsed steroids and monoclonal or polyclonal anti-T-cell antibody therapy) had failed to provide sustained freedom from rejection. Follow-up periods range from 73 to 1119 days since the start of total lymphoid irradiation. No patient died or sustained serious morbidity because of the irradiation. Three patients have had no further rejection (follow-up periods, 105 to 365 days). Two patients died--one in cardiogenic shock during the course of total lymphoid irradiation, the other with recurrent rejection caused by noncompliance with his medical regimen. Total lymphoid irradiation appears to be a safe and a moderately effective immunosuppressive modality for 'salvage' therapy of cardiac allograft rejection unresponsive to conventional therapy.

  15. Intractable chronic inflammatory demyelinating polyneuropathy treated successfully with ciclosporin

    PubMed Central

    Odaka, M; Tatsumoto, M; Susuki, K; Hirata, K; Yuki, N

    2005-01-01

    Background: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a heterogeneous disorder and both clinical course and response to treatment vary widely. Because of the propensity for relapse, CIDP requires maintenance therapy after the initial response to treatment. There is no consensus regarding this in the published literature. Present report: A patient with CIDP was treated with oral prednisolone and cyclophosphamide pulse therapy but required repeated plasma exchange and intravenous immunoglobulin (IVIg). Treatment with ciclosporin freed the patient from repeated IVIg administration. Therapeutic responses in 14 subsequent cases including three patients who showed improvement with ciclosporin are also presented along with an algorithm of the authors' suggested protocol for treatment. Conclusion: Ciclosporin should be considered for patients with intractable CIDP who require repeated IVIg. PMID:16024890

  16. [Estimated numbers of patients with intractable respiratory diseases].

    PubMed

    Hashimoto, S; Tatsumi, K; Osamu, O; Tanabe, N; Kimura, H; Kuriyama, T; Tamakoshi, A; Kawamura, T; Ohno, Y

    1998-12-01

    To estimate the number of patients with intractable respiratory diseases, we conducted a two-stage nationwide epidemiological survey in 1997. The first survey was performed at randomly sampled hospitals to identify the number of patients treated. The second survey sought detailed clinico-epidemiological data on the patients reported in the first survey. The response rates were 54% for the first survey and 62% for the second. Based on the survey findings, we derived the following nationwide estimates: 450 patients (95% confidence interval: 360-530) with chronic thromboembolic pulmonary hypertension; 230 (200-260) with primary pulmonary hypertension; 180 (150-210) with obesity-associated hypoventilation syndrome; 40 (30-50) with primary alveolar hypoventilation syndrome; 160 (140-180) with histiocytosis X; and 190 (150-230) with juvenile pulmonary emphysema.

  17. [Visceral leishmaniasis in adults: about twelve cases].

    PubMed

    Benbella, Imane; Aich, Fatima; Elkhiyat, Majdouline; Khalki, Hanane; Khermach, Assya; Bergui, Imane; Tlemçani, Imane; Hassani, Moncef Amrani

    2016-01-01

    Visceral leishmaniasis is a vector-borne disease essentially associated with Leishmania infantum infection in the Mediterranean basin. Although rare in adults, its prevalence has recently increased even among immunocompetent individuals. The aim of our study is to reveal the epidemiological features of visceral leishmaniasis in adults and the importance of biological diagnostic in the identification of this disease. Our study spanned six years from January 2009 to January 2014 and data were collected from twelve patients hospitalized at University Hospital Hassan II, Fez. Alteration of general state and splenomegaly dominated the clinical picture. Biologically, anemia was almost constant. Diagnosis was confirmed by parasite identification at the level of bone marrow. The response to treatment was favorable for all our patients. Thus, visceral leishmaniasis recrudescence in adults and its nonspecific clinical picture must lead the clinicians to suspect it when fever accompanying splenomegaly occurs, thus enabling early diagnosis and therapeutic management.

  18. Specific alteration of rhythm in temperature-stressed rats possess features of abdominal pain in IBS patients.

    PubMed

    Itomi, Yasuo; Kawamura, Toru; Tsukimi, Yasuhiro

    2015-09-01

    It is known that specific alteration of rhythm in temperature (SART) stress produces somatic pain. However, it remains to be investigated whether SART stress induces visceral pain. In this study, we investigated the visceral hypersensitivity in the SART stress model by pharmacological tools and heterotopical nociception. Four-week-old Sprague-Dawley rats were exposed to repeated cold stress. Visceral pain was measured by visceromotor response to colorectal distension, and the effects of alosetron and duloxetine on visceral pain were investigated in SART rats. Heterotopical nociception was given by capsaicin injection into the left forepaw to induce diffuse noxious inhibitory controls (DNIC). SART stress induced visceral hypersensitivity that was sustained at minimum for one week. In pharmacological analysis, alosetron and duloxetine improved SART stress-induced visceral hypersensitivity. Heterotopical nociception induced DNIC in normal conditions, but was disrupted in SART rats. On the other hand, RMCP-II mRNA in distal colon was not affected by SART stress. In conclusion, SART rats exhibit several features of visceral pain in IBS, and may be a useful model for investigating the central modification of pain control in IBS.

  19. Dragon's blood from Croton urucurana (Baill.) attenuates visceral nociception in mice.

    PubMed

    Rao, Vietla S; Gurgel, Luilma A; Lima-Júnior, Roberto C P; Martins, Domingos T O; Cechinel-Filho, Valdir; Santos, Flávia A

    2007-09-05

    Dragon's blood, the red sap from Croton urucurana Baill. (Euphorbiaceae) has a profound history of traditional use in conditions such as inflammation, diarrhoea and gastrointestinal distress. Previous studies established its anti-inflammatory, antidiarrhoeal and analgesic properties and in this study we verified its potential to suppress visceral pain, using capsaicin- and cyclophosphamide-induced models of visceral nociception. Mice that received intra-colonic capsaicin (0.3%, 50 microl/animal) or intraperitoneal injection of cyclophosphamide (400 mg/kg) manifested spontaneous nociceptive behaviors or crises, which were significantly suppressed in animal groups treated with red sap (200 and 400 mg/kg, p.o.) or that received N-acetylcysteine (750 mg/kg, i.p.) or morphine (7.5 mg/kg, s.c.), as positive controls. In capsaicin model, the antinociception produced by 200 mg/kg red sap was found to be naloxone-sensitive (2 mg/kg, i.p.), suggesting an opioid mechanism. In tests of open-field and pentobarbital-sleeping time, mice received 200mg/kg red sap showed no significant alterations in either locomotion frequency or on sleeping time, indicating that the observed antinociception is not a consequence of sedation or motor abnormality. These findings highlight the visceral antinociceptive property of Croton urucurana sap and further support its ethno-medical use to alleviate pain associated with gastrointestinal and other related disorders.

  20. Classification and Differential Diagnosis of Oral and Maxillofacial Pain.

    PubMed

    Scrivani, Steven J; Spierings, Egilius L H

    2016-08-01

    Pain in the orofacial region is a common presenting symptom. The majority of symptoms are related to dental disease and the cause can readily be established, the problem dealt with, and the pain eliminated. However, pain may persist and defy attempts at treatment. Intractable oral or facial pain can be diagnostically challenging. To make a definitive diagnosis and initiate proper treatment, a rigorous protocol for evaluation includes a thorough history and an appropriate comprehensive clinical examination and diagnostic testing, including chief complaint, history of present illness, medical history, physical examination, diagnostic studies, including imaging, and psychosocial evaluation.

  1. Does anterior trunk pain predict a different course of recovery in chronic low back pain?

    PubMed

    Panagopoulos, John; Hancock, Mark J; Kongsted, Alice; Hush, Julia; Kent, Peter

    2014-05-01

    Patient characteristics associated with the course and severity of low back pain (LBP) and disability have been the focus of extensive research, however, known characteristics do not explain much of the variance in outcomes. The relationship between anterior trunk pain (ATP) and LBP has not been explored, though mechanisms for visceral referred pain have been described. Study objectives were: (1) determine prevalence of ATP in chronic LBP patients, (2) determine whether ATP is associated with increased pain and disability in these patients, and (3) evaluate whether ATP predicts the course of pain and disability in these patients. In this study, spinal outpatient department patients mapped the distribution of their pain and patients describing pain in their chest, abdomen or groin were classified with ATP. Generalized estimating equations were performed to investigate the relationship between ATP and LBP outcomes. A total of 2974 patients were included and 19.6% of patients reported ATP. At all time points, there were significant differences in absolute pain intensity and disability in those with ATP compared with those without. The presence of ATP did not affect the clinical course of LBP outcomes. The results of this study suggest that patients who present with LBP and ATP have higher pain and disability levels than patients with localised LBP. Visceral referred pain mechanisms may help to explain some of this difference.

  2. Percutaneous destructive pain procedures on the upper spinal cord and brain stem in cancer pain: CT-guided techniques, indications and results.

    PubMed

    Kanpolat, Y

    2007-01-01

    In the century of science and technology, the average life span has increased, bringing with it an increase in the incidence of degenerative and cancer disease. Intractable pain is usually the main symptom of cancer. With the advancement in technology, there is a large group of patients with intractable pain problems who can benefit from special help medically or surgically. Destructive pain procedures are necessary to control the cancer pain and are based on the lesioning of the pain conducting pathways. Percutaneous cordotomy, trigeminal tractotomy and extralemniscal myelotomy are special methods based on lesioning of the pain conducting pathways. The procedure consists of obtaining direct morphological appearance of the upper spinal cord and surrounding structures by computed tomography (CT). The next step is functional evaluation of the target and its environment by impedance measurement and stimulation. The final step is terminated with controlled lesioning obtained by a radiofrequency system (generator, needles, electrode system). In the last two decades, CT-guided destructive procedures were used as minimally invasive procedures as follows: percutaneous cordotomy (207 patients), trigeminal tractotomy-nucleotomy (65 patients), and extralemniscal myelotomy (16 patients). Most of these patients had cancer pain. Minimally invasive CT-guided destructive pain procedures are still safe and effective operations for relieving intractable cancer pain in selected cases.

  3. Ultrasound detection of visceral adhesion after intraperitoneal ventral hernia treatment: a comparative study of protected versus unprotected meshes.

    PubMed

    Arnaud, J P; Hennekinne-Mucci, S; Pessaux, P; Tuech, J J; Aube, C

    2003-06-01

    Intraperitoneal (IP) ventral hernia repair has been proposed with the advantages of reducing dissection, operative time, and postoperative pain. The IP position of the mesh is suspected of increasing the risk of visceral adhesion and inducing complications. To overcome these drawbacks, a mesh protected on one side by a hydrophilic resorbable film (Parietex Composite) has been validated. Using a previously described ultrasound procedure, the purpose of this study was to compare the rate of visceral adhesion after intraperitoneal placement of a polyester mesh versus this protected mesh. Fifty-one patients who received a Parietex Composite mesh were prospectively compared to a retrospective series of 22 consecutive asymptomatic patients who received a Mersilene mesh. To objectively assess visceral adhesion toward the abdominal wall, an ultrasound (US) specific examination was firstly validated and secondly used to evaluate the adhesion incidence in both groups. Both groups were equivalent in terms of inclusion criteria and body mass index (BMI). Pre-operative US versus perioperative macroscopical findings determined the following parameters: sensitivity 83%, accuracy 78%, negative predictive value 81%. Using this procedure, 77% of the patients exhibited visceral adhesion to the mesh in the Mersilene group, against 18% in the Parietex Composite group (P<0.001, chi-square). US examination represents a suitable tool to evaluate postoperative adhesions to the abdominal wall. Using this procedure, a significant reduction of visceral adhesion in the Parietex Composite group was shown.

  4. Effects of chlorpheniramine and ranitidine on the visceral nociception induced by acetic acid in rats: role of opioid system.

    PubMed

    Zanboori, A; Tamaddonfard, E; Mojtahedein, A

    2008-10-15

    In this study, effects of chlorpheniramine (H1-receptor blocker), ranitidine (H2-receptor blocker), morphine (an opioid agonist) and naloxone (an opioid antagonist) in separate and combined treatments were investigated on the visceral nociception in rats. Visceral nociception was induced by intraperitoneal injection of acetic acid (1 mL, 1%). The latency time to the beginning of the first abdominal wall contraction (first writhe) was measured and the numbers of writhes were counted for 1 h after acetic acid injection. Intraperitoneal injections of chlorpheniramine and ranitidine significantly (p < 0.05) increased the latency time to the beginning of the first writhe and also significantly (p < 0.05) decreased the numbers of writhes. The same results were obtained after subcutaneous injection of morphine. Subcutaneous injection of naloxone did not change the intensity of visceral nociception, but significantly (p < 0.05) prevented the morphine-induced antinociception. Intraperitoneal injection of chlorpheniramine significantly (p < 0.05) enhanced the morphine-induced analgesia, but did not reverse the effect of naloxone on nociceptive responses. Intraperitoneal injection of ranitidine, with no effect on the morphine-induced antinociception, significantly (p < 0.05) reversed the effect of naloxone on pain responses. These results suggest that both chlorpheniramine and ranitidine exert antinociceptive effect in the visceral nociception. In addition, morphine through a naloxone-dependent mechanism produces visceral antinociception. Moreover, the endogenous opioid system may participate in the chlorpheniramine- but not in the ranitidine-induced antinociception.

  5. TRPV1-mediated presynaptic transmission in basolateral amygdala contributes to visceral hypersensitivity in adult rats with neonatal maternal deprivation

    PubMed Central

    Xiao, Ying; Chen, Xiaoqi; Zhang, Ping-An; Xu, Qiya; Zheng, Hang; Xu, Guang-Yin

    2016-01-01

    The central mechanisms of visceral hypersensitivity remain largely unknown. It’s reported that there are highest densities of TRPV1 labeled neurons within basolateral amygdala (BLA). The aim of this study was to explore the role and mechanisms of TRPV1 in BLA in development of visceral hypersensitivity. Visceral hypersensitivity was induced by neonatal maternal deprivation (NMD) and was quantified by abdominal withdrawal reflex. Expression of TRPV1 was determined by Western blot. The synaptic transmission of neurons in BLA was recorded by patch clamping. It was found that the expression of TRPV1 in BLA was significantly upregulated in NMD rats; glutamatergic synaptic activities in BLA were increased in NMD rats; application of capsazepine (TRPV1 antagonist) decreased glutamatergic synaptic activities of BLA neurons in NMD slices through a presynaptic mechanism; application of capsaicin (TRPV1 agonist) increased glutamatergic synaptic activities of BLA neurons in control slices through presynaptic mechanism without affecting GABAergic synaptic activities; microinjecting capsazepine into BLA significantly increased colonic distension threshold both in control and NMD rats. Our data suggested that upregulation of TRPV1 in BLA contributes to visceral hypersensitivity of NMD rats through enhancing excitation of BLA, thus identifying a potential target for treatment of chronic visceral pain. PMID:27364923

  6. The Role of Visceral Hypersensitivity in Irritable Bowel Syndrome: Pharmacological Targets and Novel Treatments

    PubMed Central

    Farzaei, Mohammad H; Bahramsoltani, Roodabeh; Abdollahi, Mohammad; Rahimi, Roja

    2016-01-01

    Irritable bowel syndrome (IBS) is the most common disorder referred to gastroenterologists and is characterized by altered bowel habits, abdominal pain, and bloating. Visceral hypersensitivity (VH) is a multifactorial process that may occur within the peripheral or central nervous systems and plays a principal role in the etiology of IBS symptoms. The pharmacological studies on selective drugs based on targeting specific ligands can provide novel therapies for modulation of persistent visceral hyperalgesia. The current paper reviews the cellular and molecular mechanisms underlying therapeutic targeting for providing future drugs to protect or treat visceroperception and pain sensitization in IBS patients. There are a wide range of mediators and receptors participating in visceral pain perception amongst which substances targeting afferent receptors are attractive sources of novel drugs. Novel therapeutic targets for the management of VH include compounds which alter gut-brain pathways and local neuroimmune pathways. Molecular mediators and receptors participating in pain perception and visceroperception include histamine-1 receptors, serotonin (5-hydrodytryptamine) receptors, transient receptor potential vanilloid type I, tachykinins ligands, opioid receptors, voltage-gated channels, tyrosine receptor kinase receptors, protease-activated receptors, adrenergic system ligands, cannabinoid receptors, sex hormones, and glutamate receptors which are discussed in the current review. Moreover, several plant-derived natural compounds with potential to alleviate VH in IBS have been highlighted. VH has an important role in the pathology and severity of complications in IBS. Therefore, managing VH can remarkably modulate the symptoms of IBS. More preclinical and clinical investigations are needed to provide efficacious and targeted medicines for the management of VH. PMID:27431236

  7. Sexual and vertical transmission of visceral leishmaniasis.

    PubMed

    Turchetti, Andreia P; Souza, Tayse D; Paixão, Tatiane A; Santos, Renato L

    2014-04-15

    Visceral leishmaniasis (VL) is an important zoonosis caused by Leishmania infantum, which has in the domestic dog its principal vertebrate host. VL is usually transmitted by phlebotomine sand flies, however atypical routes of transmission have been described. In this review we discuss the the role of sexual and vertical transmissions, and their role in the maintenance of VL in canine populations.

  8. Intrathecal baclofen for spasticity-related pain in amyotrophic lateral sclerosis: efficacy and factors associated with pain relief.

    PubMed

    McClelland, Shearwood; Bethoux, Francois A; Boulis, Nicholas M; Sutliff, Matthew H; Stough, Darlene K; Schwetz, Kathleen M; Gogol, Danuta M; Harrison, Michelle; Pioro, Erik P

    2008-03-01

    Clinical signs and symptoms of spasticity include hypertonia, involuntary movements (spasms, clonus), decreased range of motion, contractures, and often spasm-related pain. When spasticity is refractory to medical management, patients may be referred for intrathecal baclofen (ITB) pump placement. We reviewed a cohort of amyotrophic lateral sclerosis (ALS) patients with intractable spasticity requiring ITB to further define the impact of ITB on pain relief in this patient population. From 2003 to 2005, eight patients (mean age 43.8 years; 5 men, 3 women) with ALS received ITB for pain associated with intractable spasticity at our institution. Mean disease duration preoperatively was 47.4 months, mean follow-up was 9.8 months, and pain was evaluated using a 0-10 scoring system. All patients experienced spasticity relief in response to a preoperative bolus test injection of ITB (25-50 microg) via lumbar puncture. Following ITB pump placement, the average reduction of pain was 54% (P = 0.0082). Six patients (75%) experienced pain score reduction, three of whom had complete pain relief. Postoperative pain reduction was predicted by the degree of pain reduction following preoperative ITB test injection. These results support ITB as a treatment modality for pain associated with spasticity in ALS.

  9. Treating Intractable Post-Amputation Phantom Limb Pain with Ambulatory Continuous Peripheral Nerve Blocks

    DTIC Science & Technology

    2014-01-01

    crave food all the time.   19) Concentration Difficulty: 0 You can concentrate as...protocol.  These  data  forms  incorporate  the  four   questionnaires  used  in  the  study.  The  data  forms... questionnaires  are  attached  on  the  following  pages  8-­‐11.           8   Version:  3/30/2013   Beck

  10. Surgical treatment of intractable pelvic, groin, and perineal neuropathic pain in a gynaecologic patient: triple neurectomy.

    PubMed

    Farrell, Scott A; Clermont, Marie-Eve

    2015-02-01

    Contexte : Les gynécologues à qui l’on demande d’évaluer des patientes qui présentent des douleurs affectant les organes génitaux ne disposent généralement pas de la formation qui leur permettrait de tenir compte des causes neurogènes de la douleur; d’ordre général, les interventions chirurgicales permettant d’éliminer cette douleur ne leur sont également pas familières. Cas : Une femme de 54 ans qui avait subi de multiples laparotomies (césarienne, hystérectomie abdominale, prise en charge de kystes ovariens et libération d’adhérences) par l’intermédiaire d’une approche abdominale transversale connaissait de graves douleurs neuropathiques inguinales, labiales et périnéales affectant le côté gauche depuis 7-8 mois. Une neurectomie visant les nerfs ilio-hypogastrique, ilio-inguinal et génitocrural a été menée. À la suite de l’intervention, la patiente en est venue à connaître une résolution totale de la douleur. Conclusion : La présence de douleurs neuropathiques devrait être envisagée dans le cadre du diagnostic différentiel chez les femmes qui présentent des antécédents importants de chirurgie abdominale basse. La neurectomie constitue alors un traitement efficace.

  11. Pathophysiology of human visceral obesity: an update.

    PubMed

    Tchernof, André; Després, Jean-Pierre

    2013-01-01

    Excess intra-abdominal adipose tissue accumulation, often termed visceral obesity, is part of a phenotype including dysfunctional subcutaneous adipose tissue expansion and ectopic triglyceride storage closely related to clustering cardiometabolic risk factors. Hypertriglyceridemia; increased free fatty acid availability; adipose tissue release of proinflammatory cytokines; liver insulin resistance and inflammation; increased liver VLDL synthesis and secretion; reduced clearance of triglyceride-rich lipoproteins; presence of small, dense LDL particles; and reduced HDL cholesterol levels are among the many metabolic alterations closely related to this condition. Age, gender, genetics, and ethnicity are broad etiological factors contributing to variation in visceral adipose tissue accumulation. Specific mechanisms responsible for proportionally increased visceral fat storage when facing positive energy balance and weight gain may involve sex hormones, local cortisol production in abdominal adipose tissues, endocannabinoids, growth hormone, and dietary fructose. Physiological characteristics of abdominal adipose tissues such as adipocyte size and number, lipolytic responsiveness, lipid storage capacity, and inflammatory cytokine production are significant correlates and even possible determinants of the increased cardiometabolic risk associated with visceral obesity. Thiazolidinediones, estrogen replacement in postmenopausal women, and testosterone replacement in androgen-deficient men have been shown to favorably modulate body fat distribution and cardiometabolic risk to various degrees. However, some of these therapies must now be considered in the context of their serious side effects. Lifestyle interventions leading to weight loss generally induce preferential mobilization of visceral fat. In clinical practice, measuring waist circumference in addition to the body mass index could be helpful for the identification and management of a subgroup of overweight or obese

  12. Growth hormone used to control intractable bleeding caused by radiation-induced gastritis.

    PubMed

    Zhang, Liang; Xia, Wen-Jie; Zhang, Zheng-Sen; Lu, Xin-Liang

    2015-08-21

    Intractable bleeding caused by radiation-induced gastritis is rare. We describe a 69-year-old man with intractable hemorrhagic gastritis induced by postoperative radiotherapy for the treatment of esophageal carcinoma. Although anti-secretory therapy with or without octreotide was initiated for hemostasis over three months, melena still occurred off and on, and the patient required blood transfusions to maintain stable hemoglobin. Finally growth hormone was used in the treatment of hemorrhage for two weeks, and hemostasis was successfully achieved. This is the first report that growth hormone has been used to control intractable bleeding caused by radiation-induced gastritis.

  13. Chronic Pain

    MedlinePlus

    ... a problem you need to take care of. Chronic pain is different. The pain signals go on for ... there is no clear cause. Problems that cause chronic pain include Headache Low back strain Cancer Arthritis Pain ...

  14. Abdominal pain

    MedlinePlus

    Stomach pain; Pain - abdomen; Belly ache; Abdominal cramps; Bellyache; Stomachache ... Almost everyone has pain in the abdomen at some point. Most of the time, it is not serious. How bad your pain is ...

  15. Flank pain

    MedlinePlus

    Pain - side; Side pain ... Flank pain can be a sign of a kidney problem. But, since many organs are in this area, other causes are possible. If you have flank pain and fever , chills, blood in the urine, or ...

  16. Heel pain

    MedlinePlus

    Pain - heel ... Heel pain is most often the result of overuse. However, it may be caused by an injury. Your heel ... on the heel Conditions that may cause heel pain include: Swelling and pain in the Achilles tendon ...

  17. Sustained improvement of intractable rheumatoid arthritis after total lymphoid irradiation

    SciTech Connect

    Field, E.H.; Strober, S.; Hoppe, R.T.; Calin, A.; Engleman, E.G.; Kotzin, B.L.; Tanay, A.S.; Calin, H.J.; Terrell, C.P.; Kaplan, H.S.

    1983-08-01

    Total lymphoid irradiation (TLI) was administered to 11 patients who had intractable rheumatoid arthritis that was unresponsive to conventional medical therapy, including aspirin, multiple nonsteroidal antiinflammatory drugs, gold salts, and D-penicillamine. Total lymphoid irradiation was given as an alternative to cytotoxic drugs such as azathioprine and cyclophosphamide. After radiotherapy, 9 of the 11 patients showed a marked improvement in clinical disease activity as measured by morning stiffness, joint tenderness, joint swelling, and overall functional abilities. The mean improvement of disease activity in all patients ranged from 40-70 percent and has persisted throughout a 13-28 month followup period. This improvement permitted the mean daily steroid dose to be reduced by 54%. Complications included severe fatigue and other constitutional symptoms during radiotherapy, development of Felty's syndrome in 1 patient, and an exacerbation of rheumatoid lung disease in another. After therapy, all patients exhibited a profound T lymphocytopenia, and a reversal in their T suppressor/cytotoxic cell to helper cell ratio. The proliferative responses of peripheral blood mononuclear cells to phytohemagglutinin, concanavalin A, and allogeneic leukocytes (mixed leukocyte reaction) were markedly reduced, as was in vitro immunoglobulin synthesis after stimulation with pokeweed mitogen. Alterations in T cell numbers and function persisted during the entire followup period, except that the mixed leukocyte reaction showed a tendency to return to normal values.

  18. Treatment of intractable rheumatoid arthritis with total lymphoid irradiation

    SciTech Connect

    Kotzin, B.L.; Strober, S.; Engleman, E.G.; Calin, A.; Hoppe, R.T.; Kansas, G.S.; Terrell, C.P.; Kaplan, H.S.

    1981-10-01

    Eleven patients with intractable rheumatoid arthritis were treated with total lymphoid irradiation (total dose, 2000 rad) in an uncontrolled feasibility study, as an alternative to long-term therapy with cytotoxic drugs such as cyclophosphamide and azathioprine. During a follow-up period of five to 18 months after total lymphoid irradiation, there was a profound and sustained suppression of the absolute lymphocyte count and in vitro lymphocyte function, as well as an increase in the ratio of Leu-2 (suppressor/cytotoxic) to Leu-3 (helper) T cells in the blood. Persistent circulating suppressor cells of the mixed leukocyte response and of pokeweed mitogen-induced immunoglobulin secretion developed in most patients. In nine of the 11 patients, these changes in immune status were associated with relief of joint tenderness and swelling and with improvement in function scores. Maximum improvement occurred approximately six months after irradiation and continued for the remainder of the observation period. Few severe or chronic side effects were associated with the radiotherapy.

  19. Treatment of intractable rheumatoid arthritis with total lymphoid irradiation

    SciTech Connect

    Kotzin, B.L.; Strober, S.; Engleman, E.G.; Calin, A.; Hoppe, R.T.; Kansas, G.S.; Terrell, C.P.; Kaplan, H.S.

    1981-10-22

    Eleven patients with intractable rheumatoid arthritis were treated with total lymphoid irradiation (total dose, 2000 rad) in an uncontrolled feasibility study, as an alternative to long-term therapy with cytotoxic drugs such as cyclophosphamide and azathioprine. During a follow-up period of five to 18 months after total lymphoid irradiation, there was a profound and sustained suppression of the absolute lymphocyte count and in vitro lymphocyte function, as well as an increase in the ratio of Leu-2 (suppressor/cytotoxic) to Leu-3 (helper) T cells in the blood. Persistent circulating suppressor cells of the mixed leukocyte response and of pokeweek mitogen-induced immunoglobulin secretion developed in most patients. In nine of the 11 patients, these changes in immune status were associated with relief of joint tenderness and swelling and with improvement in function scores. Maximum improvement occurred approximately six months after irradiation and continued for the remainder of the observation period. Few severe or chronic side effects were associated with the radiotherapy.

  20. Emergent bronchofiberoptic bronchial occlusion for intractable pneumothorax with severe emphysema.

    PubMed

    Okada, S; Kano, K; Yamauchi, H; Satoh, S

    1998-11-01

    Emergent bronchofiberoptic bronchial occlusion using fibrin glue and woven polyglycolic acid mesh for persistent pneumothorax with severe emphysema is described. A 74-year-old man who had severe pulmonary dysfunction accompanying chronic emphysema was admitted with a complaint of sudden severe dyspnea. The chest X-ray on admission revealed collapse of the right lung. The patient was placed on a mechanical ventilator because of acute respiratory failure. In spite of continuous suction through a chest drainage tube, air leakage persisted. On the seventh hospital day, subcutaneous emphysema was apparent in the face and scrotum in addition to the chest. First, a double-lumen catheter was inserted into the right B5 bronchus, and fibrin glue was infused into the drainage bronchus via the double-lumen catheter. However, the procedure failed. Next, a combination of fibrin glue and woven polyglycolic acid mesh which had been cut into small pieces was introduced and pushed into the B5 bronchus using forceps. The air leakage stopped immediately after the administration. This procedure is simple and a minimally invasive method for the treatment of intractable pneumothorax in a compromised patient on a mechanical ventilator.

  1. Update on the use of rituximab for intractable rheumatoid arthritis

    PubMed Central

    Looney, R John

    2009-01-01

    It has been 3 years since rituximab, a mouse x human chimeric anti-CD20 monoclonal antibody that selectively depleted B cells, was approved by the FDA for the treatment of moderate to severe rheumatoid arthritis (RA) with an inadequate response to anti-TNF therapies. Since approval rituximab has become a part of standard treatment, and additional data have become available on long-term efficacy and safety both from clinical trials and from post-marketing surveillance. In open long-term follow-up from clinical trials, patients treated with multiple courses of rituximab continued to respond in terms of signs and symptoms, and damage assessed radiographically was significantly inhibited. Moreover, the rate of serious infectious events was not increased as the number of courses increased. However, because of case reports of progressive multifocal leukoencephalopathy in patients treated with rituximab for non-malignant conditions, a black box warning has been added. Studies on the immunologic correlates of response to rituximab treatment including B cell subsets in peripheral blood and synovial biopsies are providing clues into how rituximab works for autoimmune disease. However, at this time we are not able to explain why some patients do not respond and cannot predict who will respond. Future challenges for the further development of rituximab for intractable RA will be discussed. PMID:27789983

  2. National Registry of Designated Intractable Diseases in Japan: Present Status and Future Prospects

    PubMed Central

    KANATANI, Yasuhiro; TOMITA, Naoko; SATO, Yoko; ETO, Akiko; OMOE, Hiroe; MIZUSHIMA, Hiroshi

    2017-01-01

    Japan promotes research related to intractable diseases and financially supports patients with these diseases. Intractable diseases are designated as those that fulfill the following criteria: (1) rarity (affecting less than 0.1% of the population in Japan), (2) unknown etiology, (3) lack of effective treatment, (4) necessity of long-term treatment, and (5) existence of objective diagnostic criteria and not necessarily equal to rare diseases in other countries. The construction of a national database is required to promote research to clarify the pathogenesis of these diseases and to develop pharmaceutical products and medical devices. The Ministry of Health, Labor, and Welfare launched an online registration system in 2001, but many problems associated with gathering and utilizing information on patients with intractable diseases remain. In this paper, we describe the present status of the national registry of designated intractable diseases in Japan and discuss future prospects. PMID:27666154

  3. [Disseminated metastatic tumor at dorsal surface of medulla oblongata presenting intractable hiccups. A case report].

    PubMed

    Arishima, Hidetaka; Kikuta, Ken-ichirou

    2011-04-01

    We report the case of disseminated metastatic tumor at dorsal surface of medulla oblongata presenting intractable hiccups. A 73-year-old man has a history of for metastatic lung tumor of the left tempral lobe. Although 3 surgeries and 4 radiotherapies were performed in the last 8 years, residual tumor grew slowly. He presented with intractable hiccups. His hiccups continued for 30 minutes, sometimes for 3 hours with obstruction of eating. Contrast-enhanced Magnetic resonance (MR) imaging demonstrated the dissemination of metastatic lung tumor at dorsal surface of medulla oblongata and ventral surface of midbrain. Some literatures reported the patients with intractable hiccups caused by dorsal medullary lesions. Therefore, we thought that the small disseminated tumor at dorsal surface of medulla oblongata caused the hiccups. Evaluation of dorsal medullay area by MR imaging is important to reveal the cause of intractable hiccups.

  4. Partial internal biliary diversion: a solution for intractable pruritus in progressive familial intrahepatic cholestasis type 1.

    PubMed

    Ganesh, Ramaswamy; Suresh, Natarajan; Sathiyasekeran, Malathi; Ramachandran, Priya

    2011-01-01

    Biliary diversion offers a potential option for intractable pruritus in children with chronic cholestatic disorders. Progressive familial intrahepatic cholestasis (PFIC) is an inherited disorder of impaired bile acid transport and excretion, which presents with jaundice and pruritus in the first few months of life and progresses to cirrhosis by infancy or adolescence. We report a child with PFIC type 1 who underwent internal biliary diversion for intractable pruritus and was relieved of his symptoms.

  5. Irritable bowel syndrome and visceral hypersensitivity : risk factors and pathophysiological mechanisms.

    PubMed

    Deiteren, A; de Wit, A; van der Linden, L; De Man, J G; Pelckmans, P A; De Winter, B Y

    2016-03-01

    Irritable bowel syndrome (IBS) is a common functional gastro-intestinal disorder, characterized by abdominal pain and altered intestinal motility. Visceral hypersensitivity is an important hallmark feature of IBS and is believed to underlie abdominal pain in patients with IBS. The two main risk factors associated with the development of IBS are gastrointestinal inflammation and psychological distress. On a peripheral level, visceral sensitivity seems to be modulated by several mechanisms. Immune cells in the mucosal wall, such as mast cells, and enterochromaffin cells may sensitize afferent nerves by release of their mediators. Furthermore, increased mucosal permeability, altered intestinal microflora and dietary habits may contribute to this feature. On a central level, an increased prevalence of psychiatric comorbidities is demonstrated in IBS patients, alongside alterations in the hormonal brain-gut axis, increased vigilance towards intestinal stimuli and functional and structural changes in the brain. The pathogenesis of IBS is complicated and multifactorial and the treatment remains clinically challenging. Dietary measures and symptomatic control are the cornerstones for IBS treatment and may be sufficient for patients experiencing mild symptoms, alongside education, reassurance and an effective therapeutic physician-patient relationship. New pharmacological therapies are aimed at interfering with mediator release and/or blockade of the relevant receptors within the gut wall, while modulation of the intestinal flora and diet may also be of therapeutic benefit. Tricyclic anti-depressants and serotonin reuptake inhibitors act both on a central and peripheral level by modulating pain signalling pathways.

  6. Esophageal hypersensitivity in noncardiac chest pain.

    PubMed

    Min, Yang Won; Rhee, Poong-Lyul

    2016-09-01

    Noncardiac chest pain (NCCP) is an often-encountered clinical problem. Although many patients suffer from persistent or recurrent chest pain, treatment remains a challenge owing to its various possible etiologies. Gastroesophageal reflux disease (GERD) is the most common cause of NCCP. In GERD-related NCCP, proton pump inhibitor treatment appears to be effective. However, the pathophysiology remains to be fully elucidated in NCCP patients without GERD. Treatment for non-GERD-related NCCP has been aimed at esophageal motility disorders and visceral hypersensitivity. As there is growing evidence that esophageal visceral hypersensitivity plays a role in NCCP, pain modulators have become the mainstay of therapy in patients with non-GERD-related NCCP. However, there is an unmet need for the treatment of esophageal hypersensitivity in NCCP due to modest evidence for the benefit of pain modulators, including antidepressants, in non-GERD-related NCCP. Recent studies have demonstrated that esophageal mast cell infiltration and impaired mucosal integrity are related to visceral hypersensitivity in patients with NCCP. Thus, esophageal mast cell stabilization and restoration of esophageal mucosal integrity could be considered potential therapeutic targets in selected NCCP patients with hypersensitivity. However, further observations are necessary to shed light on esophageal hypersensitivity in NCCP.

  7. Melatonin and sleep-related problems in children with intractable epilepsy.

    PubMed

    Elkhayat, Hamed A; Hassanein, Sahar M; Tomoum, Hoda Y; Abd-Elhamid, Iman A; Asaad, Tarek; Elwakkad, Amany S

    2010-04-01

    Children with epilepsy have high rates of sleep problems. Melatonin has been advocated in treatment of sleep disorders, and its beneficial effect has been confirmed in insomnia. The aim of this study was to assess melatonin levels in children with intractable epilepsy and its relation to pattern of sleep and characteristics of seizure disorder, as well as the effect of melatonin therapy on those parameters. The study was conducted on 23 children with intractable epilepsy and 14 children with controlled seizures. Patients were evaluated by psychometric sleep assessment and assay of diurnal and nocturnal melatonin levels. Children with intractable epilepsy received oral melatonin before bedtime. They were reassessed after 3 months. Children with intractable epilepsy had higher scores for each category of sleep walking, forcible teeth grinding, and sleep apnea. At the end of therapeutic trial, patients with intractable epilepsy exhibited significant improvement in bedtime resistance, sleep duration, sleep latency, frequent nocturnal arousals, sleep walking, excessive daytime sleepiness, nocturnal enuresis, forcible teeth grinding, sleep apnea, and Epworth sleepiness scores. There was also significant reduction in seizure severity. Thus, use of melatonin in patients with intractable seizures was associated with improvement of both many sleep-related phenomena and the severity of seizures.

  8. Characteristics and safety assessment of intractable proteins in genetically modified crops.

    PubMed

    Bushey, Dean F; Bannon, Gary A; Delaney, Bryan F; Graser, Gerson; Hefford, Mary; Jiang, Xiaoxu; Lee, Thomas C; Madduri, Krishna M; Pariza, Michael; Privalle, Laura S; Ranjan, Rakesh; Saab-Rincon, Gloria; Schafer, Barry W; Thelen, Jay J; Zhang, John X Q; Harper, Marc S

    2014-07-01

    Genetically modified (GM) crops may contain newly expressed proteins that are described as "intractable". Safety assessment of these proteins may require some adaptations to the current assessment procedures. Intractable proteins are defined here as those proteins with properties that make it extremely difficult or impossible with current methods to express in heterologous systems; isolate, purify, or concentrate; quantify (due to low levels); demonstrate biological activity; or prove equivalency with plant proteins. Five classes of intractable proteins are discussed here: (1) membrane proteins, (2) signaling proteins, (3) transcription factors, (4) N-glycosylated proteins, and (5) resistance proteins (R-proteins, plant pathogen recognition proteins that activate innate immune responses). While the basic tiered weight-of-evidence approach for assessing the safety of GM crops proposed by the International Life Sciences Institute (ILSI) in 2008 is applicable to intractable proteins, new or modified methods may be required. For example, the first two steps in Tier I (hazard identification) analysis, gathering of applicable history of safe use (HOSU) information and bioinformatics analysis, do not require protein isolation. The extremely low level of expression of most intractable proteins should be taken into account while assessing safety of the intractable protein in GM crops. If Tier II (hazard characterization) analyses requiring animal feeding are judged to be necessary, alternatives to feeding high doses of pure protein may be needed. These alternatives are discussed here.

  9. Development of Vaccines against Visceral Leishmaniasis

    PubMed Central

    Evans, Krystal J.; Kedzierski, Lukasz

    2012-01-01

    Leishmaniasis is a neglected disease resulting in a global morbidity of 2,090 thousand Disability-Adjusted Life Years and a mortality rate of approximately 60,000 per year. Among the three clinical forms of leishmaniasis (cutaneous, mucosal, and visceral), visceral leishmaniasis (VL) accounts for the majority of mortality, as if left untreated VL is almost always fatal. Caused by infection with Leishmania donovani or L. infantum, VL represents a serious public health problem in endemic regions and is rapidly emerging as an opportunistic infection in HIV patients. To date, no vaccine exists for VL or any other form of leishmaniasis. In endemic areas, the majority of those infected do not develop clinical symptoms and past infection leads to robust immunity against reinfection. Thus the development of vaccine for Leishmania is a realistic public health goal, and this paper summarizes advances in vaccination strategies against VL. PMID:21912561

  10. American Visceral Leishmaniasis in Chiapas, Mexico

    PubMed Central

    Pastor-Santiago, Jorge A.; Chávez-López, Susana; Guzmán-Bracho, Carmen; Flisser, Ana; Olivo-Díaz, Angélica

    2012-01-01

    We report the results of a study conducted during 1990–2006 with 89 cases of American visceral leishmaniasis in Chiapas State in southeastern Mexico and a seroprevalence study performed with 726 persons and 224 dogs that lived near cases of American visceral leishmaniasis. Clinical aspects, epidemiologic profiles, and risk factors are described. Most cases were in children ≤ 5 years of age, the prevalence of seropositive persons was 77%. The main risk factors associated with this disease were having 1–3 rooms in a house compared with ≥ 4 rooms, having a roof that was not made of cement, and having domestic animals. In contrast, only 19% of dogs were seropositive, suggesting that this species is not important in the transmission cycle of Leishmania. These data indicate that active transmission is taking place in the central valley of Chiapas State, Mexico, in communities located < 1,000 meters above sea level near the Grijalva River. PMID:22232459

  11. Focused suggestion with somatic anchoring technique: rapid self-hypnosis for pain management.

    PubMed

    Donatone, Brooke

    2013-04-01

    This article details a self-hypnosis technique designed to teach patients how to manage acute or chronic pain through directed focus. The focused suggestion with somatic anchoring technique has been used with various types of pain, including somatic pain (arthritis, post-injury pain from bone breaks, or muscle tears), visceral pain (related to irritable bowel disease), and neuropathic pain (related to multiple sclerosis). This technique combines cognitive restructuring and mindfulness meditation with indirect and direct suggestions during hypnosis. The case examples demonstrate how the focused suggestion with somatic anchoring technique is used with both acute and chronic pain conditions when use of long-term medication has been relatively ineffective.

  12. Recovery of heavy metals from intractable wastes: A thermal approach

    SciTech Connect

    Kirk, D.W.

    1996-12-31

    The generation of industrial solid wastes containing leachable species of environmental concern is a problem for developing and developed nations alike. These materials arise from direct processing of mineral ores, from production of metals and minerals, from manufacturing operations, and from air and water pollution treatment processes. The general characteristics that make these wastes intractable is that their content of hazardous species is not easily liberated from the waste yet is not bound so tightly that they are safe for landfill disposal or industrial use. The approach taken in this work is a thermal treatment that separates the inorganic contaminants from the wastes. The objective is to provide recovery and reuse of both the residual solids and liberated contaminants. The results from operating this technique using two very different types of waste are described. The reasons that the process will work for a wide variety of wastes are explored. By using the knowledge of the thermodynamic stability of the phases found from the characterization analyses, a thermal regime was found that allowed separation of the contaminants without capturing the matrix materials. Bench scale studies were carried out using a tube furnace. Samples of the wastes were heated in crucible boats from 750 to 1150{degrees}C in the presence of various chlorinating agents. The offgas contained 90{sup +}% of the targeted contaminants despite their complex matrix form. The residue was free of contamination. As a result of the efficient concentrating mechanism of the process, the contaminants in the offgas solids are attractive for reuse in metallurgical industries. As an additional benefit, the organic contaminants of the residues were eliminated. Dioxin traces in the solids before treatment were absent after treatment. 15 refs., 4 figs., 4 tabs.

  13. Visceral adiposity, insulin resistance and cancer risk

    PubMed Central

    2011-01-01

    Background There is a well established link between obesity and cancer. Emerging research is characterising this relationship further and delineating the specific role of excess visceral adiposity, as opposed to simple obesity, in promoting tumorigenesis. This review summarises the evidence from an epidemiological and pathophysiological perspective. Methods Relevant medical literature was identified from searches of PubMed and references cited in appropriate articles identified. Selection of articles was based on peer review, journal and relevance. Results Numerous epidemiological studies consistently identify increased risk of developing carcinoma in the obese. Adipose tissue, particularly viscerally located fat, is metabolically active and exerts systemic endocrine effects. Putative pathophysiological mechanisms linking obesity and carcinogenesis include the paracrine effects of adipose tissue and systemic alterations associated with obesity. Systemic changes in the obese state include chronic inflammation and alterations in adipokines and sex steroids. Insulin and the insulin-like growth factor axis influence tumorigenesis and also have a complex relationship with adiposity. There is evidence to suggest that insulin and the IGF axis play an important role in mediating obesity associated malignancy. Conclusions There is much evidence to support a role for obesity in cancer progression, however further research is warranted to determine the specific effect of excess visceral adipose tissue on tumorigenesis. Investigation of the potential mechanisms underpinning the association, including the role of insulin and the IGF axis, will improve understanding of the obesity and cancer link and may uncover targets for intervention. PMID:21696633

  14. Stress-Related Alterations of Visceral Sensation: Animal Models for Irritable Bowel Syndrome Study

    PubMed Central

    Mulak, Agata; Taché, Yvette

    2011-01-01

    Stressors of different psychological, physical or immune origin play a critical role in the pathophysiology of irritable bowel syndrome participating in symptoms onset, clinical presentation as well as treatment outcome. Experimental stress models applying a variety of acute and chronic exteroceptive or interoceptive stressors have been developed to target different periods throughout the lifespan of animals to assess the vulnerability, the trigger and perpetuating factors determining stress influence on visceral sensitivity and interactions within the brain-gut axis. Recent evidence points towards adequate construct and face validity of experimental models developed with respect to animals' age, sex, strain differences and specific methodological aspects such as non-invasive monitoring of visceromotor response to colorectal distension as being essential in successful identification and evaluation of novel therapeutic targets aimed at reducing stress-related alterations in visceral sensitivity. Underlying mechanisms of stress-induced modulation of visceral pain involve a combination of peripheral, spinal and supraspinal sensitization based on the nature of the stressors and dysregulation of descending pathways that modulate nociceptive transmission or stress-related analgesic response. PMID:21860814

  15. Cancer pain

    SciTech Connect

    Swerdlow, M.; Ventafridda, V.

    1987-01-01

    This book contains 13 chapters. Some of the chapter titles are: Importance of the Problem; Neurophysiology and Biochemistry of Pain; Assessment of Pain in Patients with Cancer; Drug Therapy; Chemotherapy and Radiotherapy for Cancer Pain; Sympton Control as it Relates to Pain Control; and Palliative Surgery in Cancer Pain Treatment.

  16. Sarcopenia and Visceral Obesity in Esophageal and Gastric Cancer

    ClinicalTrials.gov

    2017-02-17

    Esophageal Cancer; Gastric Cancer; Sarcopenia; Sarcopenic Obesity; Obesity; Visceral Obesity; Quality of Life; Surgery; Complication of Treatment; Chemotherapeutic Toxicity; Physical Activity; Oncology

  17. Interactions between visceral afferent signaling and stimulus processing

    PubMed Central

    Critchley, Hugo D.; Garfinkel, Sarah N.

    2015-01-01

    Visceral afferent signals to the brain influence thoughts, feelings and behavior. Here we highlight the findings of a set of empirical investigations in humans concerning body-mind interaction that focus on how feedback from states of autonomic arousal shapes cognition and emotion. There is a longstanding debate regarding the contribution of the body to mental processes. Recent theoretical models broadly acknowledge the role of (autonomically-mediated) physiological arousal to emotional, social and motivational behaviors, yet the underlying mechanisms are only partially characterized. Neuroimaging is overcoming this shortfall; first, by demonstrating correlations between autonomic change and discrete patterns of evoked, and task-independent, neural activity; second, by mapping the central consequences of clinical perturbations in autonomic response and; third, by probing how dynamic fluctuations in peripheral autonomic state are integrated with perceptual, cognitive and emotional processes. Building on the notion that an important source of the brain's representation of physiological arousal is derived from afferent information from arterial baroreceptors, we have exploited the phasic nature of these signals to show their differential contribution to the processing of emotionally-salient stimuli. This recent work highlights the facilitation at neural and behavioral levels of fear and threat processing that contrasts with the more established observations of the inhibition of central pain processing during baroreceptors activation. The implications of this body-brain-mind axis are discussed. PMID:26379481

  18. Capsaicin, Nociception and Pain.

    PubMed

    Frias, Bárbara; Merighi, Adalberto

    2016-06-18

    Capsaicin, the pungent ingredient of the hot chili pepper, is known to act on the transient receptor potential cation channel vanilloid subfamily member 1 (TRPV1). TRPV1 is involved in somatic and visceral peripheral inflammation, in the modulation of nociceptive inputs to spinal cord and brain stem centers, as well as the integration of diverse painful stimuli. In this review, we first describe the chemical and pharmacological properties of capsaicin and its derivatives in relation to their analgesic properties. We then consider the biochemical and functional characteristics of TRPV1, focusing on its distribution and biological effects within the somatosensory and viscerosensory nociceptive systems. Finally, we discuss the use of capsaicin as an agonist of TRPV1 to model acute inflammation in slices and other ex vivo preparations.

  19. [Case of acute exacerbation of neuropathic cancer pain rapidly relieved by simultaneous oral intake of immediate release oxycodone and pregabalin].

    PubMed

    Baba, Mika; Gomwo, Ikuo

    2012-10-01

    Cancer pain consists of continuous pain lasting almost all day and transient exacerbation of pain called breakthrough pain. Breakthrough pain is classified as somatic pain and visceral pain, neuropathic pain according to the character of pain. Although the immediate release opioid is used as the first treatment of choice to breakthrough pain, the effect is not enough when it shows the character of neuropathic pain. Pregabalin has become the first medicine for the treatment of neuropathic pain, and it sometimes reveals prompt analgesic effect based on its pharmacological profile. It has also been reported that pregabalin used with oxycodine reveals analgesic effect with smaller dosage than pregabalin alone. We experienced a young patient with lung cancer suffering from sudden exacerbation of symptomatic sciatica, whose pain was markedly reduced within 30 minutes by taking immediate release oxycodone 5 mg and pregabalin 75 mg simultaneously. Conclusions : Pregabalin with immediate release oxycodone simultaneously may be able to improve acute exacerbation of neuropathic cancer pain rapidly.

  20. Foetal pain?

    PubMed

    Derbyshire, Stuart W G

    2010-10-01

    The majority of commentary on foetal pain has looked at the maturation of neural pathways to decide a lower age limit for foetal pain. This approach is sensible because there must be a minimal necessary neural development that makes pain possible. Very broadly, it is generally agreed that the minimal necessary neural pathways for pain are in place by 24 weeks gestation. Arguments remain, however, as to the possibility of foetal pain before or after 24 weeks. Some argue that the foetus can feel pain earlier than 24 weeks because pain can be supported by subcortical structures. Others argue that the foetus cannot feel pain at any stage because it is maintained in a state of sedation in the womb and lacks further neural and conceptual development necessary for pain. Much of this argument rests on the definition of terms such as 'wakefulness' and 'pain'. If a behavioural and neural reaction to a noxious stimulus is considered sufficient for pain, then pain is possible from 24 weeks and probably much earlier. If a conceptual subjectivity is considered necessary for pain, however, then pain is not possible at any gestational age. Regardless of how pain is defined, it is clear that pain for conceptual beings is qualitatively different than pain for non-conceptual beings. It is therefore a mistake to draw an equivalence between foetal pain and pain in the older infant or adult.

  1. Neck Pain

    MedlinePlus

    ... injuries and conditions that cause pain and restrict motion. Neck pain causes include: Muscle strains. Overuse, such ... body then forms bone spurs that affect joint motion and cause pain. Nerve compression. Herniated disks or ...

  2. Ankle pain

    MedlinePlus

    Pain - ankle ... Ankle pain is often due to an ankle sprain. An ankle sprain is an injury to the ligaments, which ... the joint. In addition to ankle sprains, ankle pain can be caused by: Damage or swelling of ...

  3. Knee pain

    MedlinePlus

    Pain - knee ... Knee pain can have different causes. Being overweight puts you at greater risk for knee problems. Overusing your knee can trigger knee problems that cause pain. If you have a history of arthritis, it ...

  4. Elbow pain

    MedlinePlus

    Pain - elbow ... Elbow pain can be caused by many problems. A common cause in adults is tendinitis . This is inflammation and ... a partial dislocation ). Other common causes of elbow pain are: Bursitis -- inflammation of a fluid-filled cushion ...

  5. Eye pain

    MedlinePlus

    Ophthalmalgia; Pain - eye ... Pain in the eye can be an important symptom of a health problem. Make sure you tell your health care provider if you have eye pain that does not go away. Tired eyes or ...

  6. Wrist pain

    MedlinePlus

    Pain - wrist; Pain - carpal tunnel; Injury - wrist; Arthritis - wrist; Gout - wrist; Pseudogout - wrist ... Carpal tunnel syndrome: A common cause of wrist pain is carpal tunnel syndrome . You may feel aching, ...

  7. Foot pain

    MedlinePlus

    Pain - foot ... Foot pain may be due to: Aging Being on your feet for long periods of time Being overweight A ... sports activity Trauma The following can cause foot pain: Arthritis and gout . Common in the big toe, ...

  8. Phantom Pain

    MedlinePlus

    ... be an effective treatment for some types of chronic pain. In acupuncture, the practitioner inserts extremely fine, sterilized ... and Stroke. http://www.ninds.nih.gov/disorders/chronic_pain/detail_chronic_pain.htm. Accessed Sept. 16, 2014. ...

  9. Hip pain

    MedlinePlus

    ... pain involves any pain in or around the hip joint. You may not feel pain from your hip ... 2012:chap 48. Read More Hip fracture surgery Hip joint replacement Patient Instructions Hip fracture - discharge Hip or ...

  10. Depression, Pain, and Pain Behavior.

    ERIC Educational Resources Information Center

    Keefe, Francis J.; And Others

    1986-01-01

    Examined the degree to which depression predicted pain and pain behavior. The Beck Depression Inventory was administered to 207 low back pain patients. Depression and physical findings were the most important predictors of pain and pain behavior. Depression proved significant even after controlling for important demographic and medical status…

  11. A good preoperative response to transcutaneous electrical nerve stimulation predicts a better therapeutic effect of implanted occipital nerve stimulation in pharmacologically intractable headaches.

    PubMed

    Nguyen, Jean-Paul; Nizard, Julien; Kuhn, Emmanuelle; Carduner, Florence; Penverne, Frédérique; Verleysen-Robin, Marie-Christine; Terreaux, Luc; de Gaalon, Solène; Raoul, Sylvie; Lefaucheur, Jean-Pascal

    2016-02-01

    Occipital nerve stimulation (ONS) is a surgical approach to treat patients with medically intractable chronic headache disorders. However, no preoperative test has been yet validated to allow candidates to be selected for implantation. In this study, the analgesic efficacy of transcutaneous electrical nerve stimulation (TENS) was tested for 1 to 3 months in 41 patients with pharmacologically intractable headache disorders of various origins, using a new technique of electrode placement over the occipital nerve. ONS electrodes were subsequently implanted in 33 patients (occipital neuralgia [n=15], cervicogenic headache [n=7], cluster headache [n=6], chronic migraine [n=5]) who had responded at least moderately to TENS. Assessment was performed up to five years after implantation (three years on average), based on the mean and maximum daily pain intensity scored on a 0-10 visual analogue scale and the number of headache days per month. Both TENS and chronic ONS therapy were found to be efficacious (57-76% improvement compared to baseline on the various clinical variables). The efficacy of ONS was better in cases of good or very good preoperative response to TENS than in cases of moderate response to TENS. Implanted ONS may be a valuable therapeutic option in the long term for patients with pharmacologically intractable chronic headache. Although we cannot conclude in patients with poor or no response to TENS, a good or very good response to TENS can support the indication of ONS therapy. This preoperative test could particularly be useful in patients with chronic migraine, in whom it may be difficult to indicate an invasive technique of cranial neurostimulation.

  12. Visceral Obesity If Associated with Gallbladder Polyps

    PubMed Central

    Lee, Jun Kyu; Hahn, Suk Jae; Kang, Hyoun Woo; Jung, Jae Gu; Choi, Han Seok; Lee, Jin Ho; Han, In Woong; Jung, Jin-Hee; Kwon, Jae Hyun

    2016-01-01

    Background/Aims Gallbladder polyps (GBP) are a common clinical finding and may possess malignant potential. We conducted this study to determine whether visceral obesity is a risk factor for GBP. Methods We retrospectively reviewed records of subjects who received both ultrasonography and computed tomography with measurements of the areas of visceral adipose tissue and total adipose tissue (TAT) on the same day as health checkups. Results Ninety-three of 1,615 subjects (5.8%) had GBP and were compared with 186 age- and sex-matched controls. VAT (odds ratio [OR], 2.941; 95% confidence interval [CI], 1.325 to 6.529; p=0.008 for the highest quartile vs the lowest quartile) and TAT (OR, 3.568; 95% CI, 1.625 to 7.833; p=0.002 for the highest quartile vs the lowest quartile) were independent risk factors together with hypertension (OR, 2.512; 95% CI, 1.381 to 4.569; p=0.003), diabetes mellitus (OR, 2.942; 95% CI, 1.061 to 8.158; p=0.038), hepatitis B virus positivity (OR, 3.548; 95% CI, 1.295 to 9.716; p=0.014), and a higher level of total cholesterol (OR, 2.232; 95% CI, 1.043 to 4.778; p=0.039 for <200 mg/dL vs ≥240 mg/dL). Body mass index and waist circumference were not meaningful variables. Conclusions Visceral obesity measured by VAT and TAT was associated with GBP irrespective of body mass index or waist circumference. PMID:26260756

  13. Cerebral stimulation for the affective component of neuropathic pain

    PubMed Central

    Machado, Andre G.; Baker, Kenneth B.; Plow, Ela; Malone, Donald A.

    2012-01-01

    Objective To review the current state of cerebral stimulation for neuropathic pain and to propose that cerebral stimulation should aim at the affective sphere of chronic pain rather than solely focusing on the primary sensory-discriminative sphere. Methods The past and current goals of cerebral stimulation are reviewed as well as its limitations. A novel deep brain stimulation approach is proposed to evaluate this conceptual shift fromsomatosensory to affective sphere of pain targeting Approach Thalamic and other central pain syndromes aretypically intractable to current treatment methods, including cerebral neuromodulation of somatosensory pathways, leading to long-term distress and disability. Our modern understanding of chronic pain pathophysiology is based largely on the neuromatrix theory, where cognitive, affective and sensory-discriminative spheres contribute equally to the overall pain experience. During the last decade, the safety and feasibility of chronic stimulation of neural pathways related to mood and affect has been explored with promising results. Here, we propose a novel approach to modulate the affective sphere of chronic pain by targeting similar networks in patients with treatment-refractory central pain. Our primary goal is not to produce (or measure) analgesia, but rather to modulate the affective burden of chronic. Discussion Cerebral neuromodulation for neuropathic pain has had limited efficacy thus far. Shifting our aim to neural networks related to the affective sphere of pain may allow us to reduce pain conditioning and pain-related disability. Our ultimate goal is to promote rehabilitation from chronic pain - social and occupational. PMID:23094938

  14. Immune regulation during chronic visceral leishmaniasis.

    PubMed

    Faleiro, Rebecca J; Kumar, Rajiv; Hafner, Louise M; Engwerda, Christian R

    2014-07-01

    Visceral leishmaniasis is a chronic parasitic disease associated with severe immune dysfunction. Treatment options are limited to relatively toxic drugs, and there is no vaccine for humans available. Hence, there is an urgent need to better understand immune responses following infection with Leishmania species by studying animal models of disease and clinical samples from patients. Here, we review recent discoveries in these areas and highlight shortcomings in our knowledge that need to be addressed if better treatment options are to be developed and effective vaccines designed.

  15. Psychophysiological responses to pain identify reproducible human clusters.

    PubMed

    Farmer, Adam D; Coen, Steven J; Kano, Michiko; Paine, Peter A; Shwahdi, Mustafa; Jafari, Jafar; Kishor, Jessin; Worthen, Sian F; Rossiter, Holly E; Kumari, Veena; Williams, Steven C R; Brammer, Michael; Giampietro, Vincent P; Droney, Joanne; Riley, Julia; Furlong, Paul L; Knowles, Charles H; Lightman, Stafford L; Aziz, Qasim

    2013-11-01

    Pain is a ubiquitous yet highly variable experience. The psychophysiological and genetic factors responsible for this variability remain unresolved. We hypothesised the existence of distinct human pain clusters (PCs) composed of distinct psychophysiological and genetic profiles coupled with differences in the perception and the brain processing of pain. We studied 120 healthy subjects in whom the baseline personality and anxiety traits and the serotonin transporter-linked polymorphic region (5-HTTLPR) genotype were measured. Real-time autonomic nervous system parameters and serum cortisol were measured at baseline and after standardised visceral and somatic pain stimuli. Brain processing reactions to visceral pain were studied in 29 subjects using functional magnetic resonance imaging (fMRI). The reproducibility of the psychophysiological responses to pain was assessed at year. In group analysis, visceral and somatic pain caused an expected increase in sympathetic and cortisol responses and activated the pain matrix according to fMRI studies. However, using cluster analysis, we found 2 reproducible PCs: at baseline, PC1 had higher neuroticism/anxiety scores (P ≤ 0.01); greater sympathetic tone (P<0.05); and higher cortisol levels (P ≤ 0.001). During pain, less stimulus was tolerated (P ≤ 0.01), and there was an increase in parasympathetic tone (P ≤ 0.05). The 5-HTTLPR short allele was over-represented (P ≤ 0.005). PC2 had the converse profile at baseline and during pain. Brain activity differed (P ≤ 0.001); greater activity occurred in the left frontal cortex in PC1, whereas PC2 showed greater activity in the right medial/frontal cortex and right anterior insula. In health, 2 distinct reproducible PCs exist in humans. In the future, PC characterization may help to identify subjects at risk for developing chronic pain and may reduce variability in brain imaging studies.

  16. Visceral fit: While in a visceral state, associated states of the world seem more likely.

    PubMed

    Risen, Jane L; Critcher, Clayton R

    2011-05-01

    We propose that visceral states can influence beliefs through "visceral fit": People will judge states of the world associated with their current visceral experience as more likely. We found that warmth influenced belief in global warming (Studies 1-3) and that thirst impacted forecasts of drought and desertification (Study 5). These effects emerged in a naturalistic setting (Study 1) and in experimental lab settings (Studies 2, 3, and 5). Studies 2-6 distinguished between 3 mechanistic accounts: temperature as information (Studies 2 and 3), conceptual accessibility (Studies 4 and 5), and fluency of simulation (Studies 6a and 6b). Studies 2 and 3 ruled out the temperature as information account. Feeling warm enhanced belief in global warming even when temperature was manipulated in an uninformative indoor setting, when participants' attention was first directed to the indoor temperature, and when participants' belief about the current outdoor temperature was statistically controlled. Studies 4 and 5 ruled out conceptual accessibility as the key mediator: Priming the corresponding concepts did not produce analogous effects on judgment. Studies 6a and 6b used a causal chain design and found support for a "simulational fluency" account. Participants experiencing the visceral state of warmth constructed more fluent mental representations of hot (vs. cold) outdoor images, and those who were led to construe the same hot outdoor images more fluently believed more in global warming. Together, the results suggest that visceral states can influence one's beliefs by making matching states of the world easier to simulate and therefore seem more likely.

  17. Neuronal correlates of gastric pain induced by fundus distension: a 3T-fMRI study.

    PubMed

    Lu, C-L; Wu, Y-T; Yeh, T-C; Chen, L-F; Chang, F-Y; Lee, S-D; Ho, L-T; Hsieh, J-C

    2004-10-01

    Visceral hypersensitivity in gastric fundus is a possible pathogenesis for functional dyspepsia. The cortical representation of gastric fundus is still unclear. Growing evidence shows that the insula, but not the primary or secondary somatosensory region (SI or SII), may be the cortical target for visceral pain. Animal studies have also demonstrated that amygdala plays an important role in processing visceral pain. We used fMRI to study central projection of stomach pain from fundus balloon distension. We also tested the hypothesis that there will be neither S1 nor S2 activation, but amygdala activation with the fundus distension. A 3T-fMRI was performed on 10 healthy subjects during baseline, fullness (12.7 +/- 0.6 mmHg) and moderate gastric pain (17.0 +/- 0.8 mmHg). fMRI signal was modelled by convolving the predetermined psychophysical response. Statistical comparisons were performed between conditions on a group level. Gastric pain activated a wide range of cortical and subcortical structures, including thalamus and insula, anterior and posterior cingulate cortices, basal ganglia, caudate nuclei, amygdala, brain stem, cerebellum and prefrontal cortex (P < 0.001). A subset of these neuronal substrates was engaged in the central processing of fullness sensation. SI and SII were not activated during the fundus stimulation. In conclusion, the constellation of neuronal structures activated by fundus distension overlaps the pain matrices induced musculocutaneous pain, with the exception of the absence of SI or SII activation. This may account for the vague nature of visceral sensation/pain. Our data also confirms that the insula and amygdala may act as the central role in visceral sensation/pain, as well as in the proposed sensory-limbic model of learning and memory of pain.

  18. Visceral and Somatic Hypersensitivity in TNBS induced Colitis in Rats

    PubMed Central

    Zhou, QiQi; Price, Donald D.; Caudle, Robert M.; Verne, G. Nicholas

    2010-01-01

    Inflammation of visceral structures in rats has been shown to produce visceral/somatic hyperalgesia. Our objectives were to determine if trinitrobenzene sulfonic acid (TNBS) induced colitis in rats leads to visceral/somatic hypersensitivity. Male Sprague-Dawley rats (200g–250g) were treated with 20 mg of TNBS in 50% ethanol (n=40) or an equivalent volume of ethanol (n=40) or saline (n=25) via the colon. Colonic distension, Von-Frey, Hargreaves, and tail reflex test were used to evaluate for visceral, mechanical, and thermal sensitivity. The rats demonstrated visceral hypersensitivity at 2–28 days following TNBS (p<0.0001). The ethanol treated rats also demonstrated visceral hypersensitivity that resolved after day 14. TNBS treated rats demonstrated somatic hypersensitivity at days 14–28 (p<0.0001) in response to somatic stimuli of the hind-paw. TNBS colitis is associated with visceral and somatic hypersensitivity in areas of somatotopic overlap. This model of colitis should allow further investigation into the mechanisms of visceral and somatic hypersensitivity. PMID:17703363

  19. Treatment Options for Visceral Leishmaniasis and HIV Coinfection.

    PubMed

    Monge-Maillo, Begoña; López-Vélez, Rogelio

    2016-01-01

    Leishmania and HIV coinfection is a major health problem in more than 35 countries worldwide. The impaired immune function of visceral leishmaniasis/HIV-coinfected patients may: (i) favor the reactivation of latent Leishmania infection; (ii) induce a more severe presentation of visceral leishmaniasis; (iii) cause a poorer therapeutic response; and (iv) increase the risk of relapse after treatment. One of the major challenges in the management of visceral leishmaniasis/HIV coinfection is developing an effective drug therapy that not only resolves the first episode of visceral leishmaniasis but also prevents relapse. However, scarce evidence and data are available on the optimal therapy for visceral leishmaniasis/HIV coinfection. In our study we reviewed the efficacy of several drugs currently employed for visceral leishmaniasis in HIV patients and current knowledge of secondary prophylaxis. Additionally, we reviewed a set of ongoing clinical trials that are being performed to evaluate the efficacy of new therapeutic regimens for visceral leishmaniasis in patients with and without HIV. Finally, other therapeutic strategies based on immunotherapy, vaccination, or screening for latent leishmaniasis infection in HIV patients are reviewed. Apart from being potentially useful in clinical practice, the results obtained in our study highlight the need for further research on the management of visceral leishmaniasis/HIV coinfection.

  20. Autochthonous Outbreak and Expansion of Canine Visceral Leishmaniasis, Uruguay

    PubMed Central

    Satragno, Dinora; Faral-Tello, Paula; Canneva, Bruno; Verger, Lorenzo; Lozano, Alejandra; Vitale, Edgardo; Greif, Gonzalo; Soto, Carlos

    2017-01-01

    We report an outbreak of canine visceral leishmaniasis in Uruguay. Blood specimens from 11/45 dogs tested positive for Leishmania spp. Specimens of Lutzomyia longipalpis sand flies were captured; typing revealed Leishmania infantum. Our findings document an expansion of visceral leishmaniasis to southern South America and risk for vectorborne transmission to humans. PMID:28221113

  1. Autochthonous Outbreak and Expansion of Canine Visceral Leishmaniasis, Uruguay.

    PubMed

    Satragno, Dinora; Faral-Tello, Paula; Canneva, Bruno; Verger, Lorenzo; Lozano, Alejandra; Vitale, Edgardo; Greif, Gonzalo; Soto, Carlos; Robello, Carlos; Basmadjián, Yester

    2017-03-01

    We report an outbreak of canine visceral leishmaniasis in Uruguay. Blood specimens from 11/45 dogs tested positive for Leishmania spp. Specimens of Lutzomyia longipalpis sand flies were captured; typing revealed Leishmania infantum. Our findings document an expansion of visceral leishmaniasis to southern South America and risk for vectorborne transmission to humans.

  2. Expression of laminin beta1 in hippocampi of patients with intractable epilepsy.

    PubMed

    Wu, Yuan; Wang, Xue-feng; Mo, Xue-an; Sun, Hong-bin; Li, Jin-mei; Zeng, Yan; Lin, Tao; Yuan, Jie; Xi, Zhi-qin; Zhu, Xi; Zheng, Jin-ou

    2008-10-10

    We investigated laminin beta1 expression in the hippocampi of patients with intractable epilepsy and explored the role of laminin beta1 in the pathogenesis of this condition. Fluorescence quantitative PCR, immunofluorescence, immunohistochemistry and Western blotting were used to measure laminin beta1 expression in surgically removed hippocampi of patients with intractable epilepsy, and the results were compared with control hippocampi. Fluorescence quantitative PCR showed increased expression of laminin beta1 mRNA in patient hippocampi compared with control tissues. Immunohistochemical staining demonstrated that laminin beta1 protein expression was significantly increased in patient hippocampi, and immunofluorescence microscopy showed accumulation of laminin beta1 in the cell membrane and cytoplasm of patient hippocampi. These findings were confirmed by Western blotting of protein preparations from patient hippocampi. Elevated expression of laminin beta1 mRNA and protein in the hippocampus suggests that laminin beta1 may play a role in the development of epileptic seizures in patients with intractable epilepsy.

  3. Genetically modified organisms and visceral leishmaniasis.

    PubMed

    Chhajer, Rudra; Ali, Nahid

    2014-01-01

    Vaccination is the most effective method of preventing infectious diseases. Since the eradication of small pox in 1976, many other potentially life compromising if not threatening diseases have been dealt with subsequently. This event was a major leap not only in the scientific world already burdened with many diseases but also in the mindset of the common man who became more receptive to novel treatment options. Among the many protozoan diseases, the leishmaniases have emerged as one of the largest parasite killers of the world, second only to malaria. There are three types of leishmaniasis namely cutaneous (CL), mucocutaneous (ML), and visceral (VL), caused by a group of more than 20 species of Leishmania parasites. Visceral leishmaniasis, also known as kala-azar is the most severe form and almost fatal if untreated. Since the first attempts at leishmanization, we have killed parasite vaccines, subunit protein, or DNA vaccines, and now we have live recombinant carrier vaccines and live attenuated parasite vaccines under various stages of development. Although some research has shown promising results, many more potential genes need to be evaluated as live attenuated vaccine candidates. This mini-review attempts to summarize the success and failures of genetically modified organisms used in vaccination against some of major parasitic diseases for their application in leishmaniasis.

  4. Endemic Transmission of Visceral Leishmaniasis in Bhutan

    PubMed Central

    Yangzom, Thinley; Cruz, Israel; Bern, Caryn; Argaw, Daniel; den Boer, Margriet; Vélez, Iván Dario; Bhattacharya, Sujit K.; Molina, Ricardo; Alvar, Jorge

    2012-01-01

    Visceral leishmaniasis was first reported in Bhutan in 2006. We conducted studies of the parasite, possible vectors and reservoirs, and leishmanin skin test and risk factor surveys in three villages. Nineteen cases were reported from seven districts. Parasite typing yielded two novel microsatellite sequences, both related to Indian L. donovani. In one case village, 40 (18.5%) of 216 participants had positive leishmanin skin test results, compared with 3 (4.2%) of 72 in the other case village and 0 of 108 in the control village. Positive results were strongly associated with the village and increasing age. None of the tested dogs were infected. Eighteen sand flies were collected, 13 Phlebotomus species and 5 Sergentomyia species; polymerase chain reaction for leishmanial DNA was negative. This assessment suggests that endemic visceral leishmaniasis transmission has occurred in diverse locations in Bhutan. Surveillance, case investigations, and further parasite, vector, and reservoir studies are needed. The potential protective impact of bed nets should be evaluated. PMID:23091191

  5. Visceral Leishmaniasis in Ethiopia: An Evolving Disease

    PubMed Central

    Leta, Samson; Dao, Thi Ha Thanh; Mesele, Frehiwot; Alemayehu, Gezahegn

    2014-01-01

    Visceral leishmaniasis (also known as kala-azar) is classified as one of the most neglected tropical diseases. It is becoming a growing health problem in Ethiopia, with endemic areas that are continually spreading. The annual burden of visceral leishmaniasis (VL) in Ethiopia is estimated to be between 4,500 and 5,000 cases, and the population at risk is more than 3.2 million. There has been a change in the epidemiology of VL in Ethiopia. Over the last decades, almost all cases and outbreaks of VL were reported from arid and semi-arid parts of the country; however, recent reports indicated the introduction of this disease into the highlands. Migration of labourers to and from endemic areas, climatic and environmental changes, and impaired immunity due to HIV/AIDS and malnutrition resulted in the change of VL epidemiology. HIV spurs the spread of VL by increasing the risk of progression from asymptomatic infection towards full VL. Conversely, VL accelerates the onset of AIDS. In Ethiopia, VL epidemiology remains complex because of the diversity of risk factors involved, and its control is becoming an increasing challenge. This paper reviews the changes in epidemiology of VL in Ethiopia and discusses some of the possible explanations for these changes. The prospects for novel approaches to VL control are discussed, as are the current and future challenges facing Ethiopia's public health development program. PMID:25188253

  6. Shoulder pain

    MedlinePlus

    Pain - shoulder ... changes around the rotator cuff can cause shoulder pain. You may have pain when lifting the arm above your head or ... The most common cause of shoulder pain occurs when rotator cuff tendons ... The tendons become inflamed or damaged. This condition ...

  7. Pelvic Pain

    MedlinePlus

    Pelvic pain occurs mostly in the lower abdomen area. The pain might be steady, or it might come and go. If the pain is severe, it might get in the way ... re a woman, you might feel a dull pain during your period. It could also happen during ...

  8. Late-onset of immunodysregulation, polyendocrinopathy, enteropathy, x-linked syndrome (IPEX) with intractable diarrhea.

    PubMed

    Zama, Daniele; Cocchi, Ilaria; Masetti, Riccardo; Specchia, Fernando; Alvisi, Patrizia; Gambineri, Eleonora; Lima, Mario; Pession, Andrea

    2014-10-18

    The syndrome of immune dysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) is a rare disorder caused by mutations in the FOXP3 gene. Diarrhea, diabetes and dermatitis are the hallmark of the disease, with a typical onset within the first months of life. We describe the case of a twelve-year old male affected by a very late-onset IPEX with intractable enteropathy, which markedly improved after starting Sirolimus as second-line treatment. This case suggests that IPEX should always be considered in the differential diagnosis of watery intractable diarrhea, despite its unusual onset.

  9. Intractable diarrhoea caused by cytomegalovirus enterocolitis in an immunocompetent term neonate.

    PubMed

    Gupta, Amit Kumar; Maria, Arti; Goyal, Deepak; Verma, Arushi

    2013-12-01

    Symptomatic cytomegalovirus (CMV) infection mainly affects preterm and immunocompromised infants and usually manifest as rash, pneumonia, hepatospleenomegaly or encephalitis. To our knowledge intractable diarrhoea at two weeks of age caused by postnatally acquired CMV in immunocompetent term neonate is not reported. An unusual case of postnatally acquired CMV enterocolitis manifesting as protracted diarrhoea in an immunocompetent baby in neonatal period is reported. We conclude that CMV should be considered in the differential diagnosis of intractable diarrhoea in neonatal period and treatment with intravenous ganciclovir for CMV enterocolitis is not only indicated but is therapeutic.

  10. Nerve growth factor-mediated neuronal plasticity in spinal cord contributes to neonatal maternal separation-induced visceral hypersensitivity in rats.

    PubMed

    Tsang, S W; Zhao, M; Wu, J; Sung, J J Y; Bian, Z-X

    2012-04-01

    Visceral hyperalgesia is a multifactorial gastrointestinal disorder which featured with alterations of abdominal motility and/or gut sensitivity, and is believed to be triggered by environmental stressor or psychological factors. However, its etiology remains incompletely understood. In this study, we aimed to investigate whether nerve growth factor (NGF)-mediated neuronal plasticity is involved in neonatal maternal separation (NMS)-induced visceral hypersensitivity in adult rats, and whether NGF antagonist can attenuate or block such development. In our experiments, animals subjected to NMS were developed with visceral hyperalgesia at age of 8 weeks. The threshold for visceral pain among these NMS rats was remarkably lowered than that of the normal handling (NH) rats; however, the expression levels of NGF, c-fos, calcitonin gene-related peptide (CGRP), Substance P, and tyrosine kinases A (TrkA) were notably elevated in lumbosacral spinal cord and/or dorsal root ganglion (DRG) when comparing to those of the NH rats. Further, as intra-peritoneal administration of NGF (10 μl at 1 μg/kg/day) was given to NH rats during neonatal period, effects that comparable to NMS induction were observed in the adulthood. In contrast, when NMS rats were treated with NGF antagonist K252a (10 μl/day from postnatal days 2-14), which acts against tyrosine kinases, the neonatal stress-induced down-shifted visceral pain threshold was restored and neuronal activation, specifically NGF and neuropeptide production, was attenuated. In conclusion, our data strongly suggest that NGF triggers neuronal plasticity and plays a crucial role in NMS-induced visceral hypersensitivity in which NGF antagonism provides positive inhibition via blocking the tyrosine phosphorylation of TrkA.

  11. A sterile-female technique proposed for control of Striga hermonthica and other intractable weeds: Advantages, shortcomings, and risk management

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Weeds have posed intractable challenges to farmers since the dawn of agriculture. This article describes in detail a proposed control strategy based on the introduction of genes conferring female-sterility into the genomes of intractable target weeds. Spread of these genes through target populations...

  12. [Non pharmacologic treatment of neuropathic pain].

    PubMed

    Guastella, Virginie; Mick, Gérard; Laurent, Bernard

    2008-02-01

    Nondrug treatments of neuropathic pain should always begin at the same time as pharmacologic treatment. There are three types of nondrug treatment for neuropathic pain: physical, surgical, and "psychocorporal" and psychotherapeutic treatment. Transcutaneous electrical nerve stimulation (TENS) is a simple physical treatment that strengthens local inhibitory controls and is indicated in focal neuropathic pain when upstream stimulation is possible for a superficial sensitive nerve trunk. Destructive surgery is represented today by "DREZotomy", destruction of nociceptive fibers and their dorsal root entry zones. It is indicated essentially in intractable pain due to plexus avulsion. Functional surgery is implanted electric stimulation--either spinal or central (encephalic)--of structures that exert inhibitory control on the pain pathways. Spinal stimulation is performed at the level of the posterior spinal cord and is indicated essentially in segmental mononeuropathies refractory to drug treatment. Central stimulation is performed at the motor cortex and is indicated for refractory central pain. "Psychocorporal" techniques (relaxation, sophrology, hypnosis) are useful to reduce anxiety and neurovegetative hypertonicity, both factors that aggravate neuropathic pain.

  13. Visceral States Call for Visceral Measures: Verbal Overshadowing of Hunger Ratings Across Assessment Modalities.

    PubMed

    Creswell, Kasey G; Sayette, Michael A; Schooler, Jonathan W; Wright, Aidan G C; Pacilio, Laura E

    2016-04-27

    We introduce a nonverbal "visceral" measure of hunger (i.e., squeezing a handheld dynamometer) and provide the first evidence of verbal overshadowing effects in this visceral domain. We presented 106 participants with popcorn and recorded their hunger levels in one of three conditions: (1) first report hunger using a traditional self-report rating scale (i.e., verbal measure) and then indicate hunger by squeezing a dynamometer (i.e., nonverbal measure), (2) first indicate hunger verbally and then indicate hunger nonverbally, or (3) indicate hunger only nonverbally. As hypothesized, nonverbal measures of hunger predicted subsequent eating behavior when they were uncontaminated by verbal measures-either because they preceded verbal measures of hunger or because they were the sole measure of hunger. Moreover, nonverbal measures of hunger were a better predictor of eating behavior than verbal measures. Implications of the study for communicating embodied experiences in a way that escapes the confines of symbolic representations are discussed.

  14. Lymphoid irradiation in intractable rheumatoid arthritis. Long-term followup of patients treated with 750 rads or 2,000 rads

    SciTech Connect

    Soden, M.; Hassan, J.; Scott, D.L.; Hanly, J.G.; Moriarty, M.; Whelan, A.; Feighery, C.; Bresnihan, B.

    1989-05-01

    Twenty patients with intractable rheumatoid arthritis were randomized to receive 750 or 2,000 rads of lymphoid irradiation (LI) in a double-blind comparative study, and were followed for a maximum of 48 months (mean 40 months) after treatment. During followup, sustained immunomodulation (including lymphopenia, particularly of the T helper cell subset; reduced ratio of helper cells to suppressor cells; and impaired in vitro lymphocyte proliferation in response to phytohemagglutinin and pokeweed mitogen) was observed. Significant improvements in early morning stiffness, Ritchie articular index, pain score, grip strength, and 15-meter walk time were observed in both treatment groups, but these were not sustained through the followup period. Progressive joint damage was observed radiologically in both groups during followup. Thus, LI induced sustained immunosuppression, but resulted in only short-lived clinical improvement and was associated with progressive joint erosion in these patients.

  15. Intractable intraoperative bleeding requiring platelet transfusion during emergent cholecystectomy in a patient with dual antiplatelet therapy after drug-eluting coronary stent implantation (with video)

    PubMed Central

    Fujikawa, Takahisa; Noda, Tomohiro; Tada, Seiichiro; Tanaka, Akira

    2013-01-01

    We report a case of a 76-year-old man, receiving dual antiplatelet therapy (DAPT) with aspirin and ticlopidine for the past 6 years after implantation of drug-eluting coronary stent, developed a severe hypochondriac pain. After diagnosing severe acute cholecystitis by an enhanced CT, emergent laparotomy under continuation of DAPT was attempted. During the operation, intractable bleeding from the adhesiolysed liver surface was encountered, which required platelet transfusion. Subtotal cholecystectomy with abdominal drainage was performed, and the patient recovered without any postoperative bleeding or thromboembolic complications. Like the present case, the final decision should be made to perform platelet transfusion when life-threatening DAPT-induced intraoperative bleeding occurs during an emergent surgery, despite the elevated risk of stent thrombosis. PMID:23536626

  16. Dendritic spine dysgenesis in neuropathic pain.

    PubMed

    Tan, Andrew M; Waxman, Stephen G

    2015-08-05

    Neuropathic pain is a significant unmet medical need in patients with variety of injury or disease insults to the nervous system. Neuropathic pain often presents as a painful sensation described as electrical, burning, or tingling. Currently available treatments have limited effectiveness and narrow therapeutic windows for safety. More powerful analgesics, e.g., opioids, carry a high risk for chemical dependence. Thus, a major challenge for pain research is the elucidation of the mechanisms that underlie neuropathic pain and developing targeted strategies to alleviate pathological pain. The mechanistic link between dendritic spine structure and circuit function could explain why neuropathic pain is difficult to treat, since nociceptive processing pathways are adversely "hard-wired" through the reorganization of dendritic spines. Several studies in animal models of neuropathic pain have begun to reveal the functional contribution of dendritic spine dysgenesis in neuropathic pain. Previous reports have demonstrated three primary changes in dendritic spine structure on nociceptive dorsal horn neurons following injury or disease, which accompany chronic intractable pain: (I) increased density of dendritic spines, particularly mature mushroom-spine spines, (II) redistribution of spines toward dendritic branch locations close to the cell body, and (III) enlargement of the spine head diameter, which generally presents as a mushroom-shaped spine. Given the important functional implications of spine distribution, density, and shape for synaptic and neuronal function, the study of dendritic spine abnormality may provide a new perspective for investigating pain, and the identification of specific molecular players that regulate spine morphology may guide the development of more effective and long-lasting therapies.

  17. Visceral disease in castration-resistant prostate cancer.

    PubMed

    Pezaro, Carmel J; Omlin, Aurelius; Lorente, David; Nava Rodrigues, Daniel; Ferraldeschi, Roberta; Bianchini, Diletta; Mukherji, Deborah; Riisnaes, Ruth; Altavilla, Amelia; Crespo, Mateus; Tunariu, Nina; de Bono, Johann S; Attard, Gerhardt

    2014-02-01

    Metastatic involvement of the viscera in men with advanced castration-resistant prostate cancer (CRPC) has been poorly characterised to date. In 359 CRPC patients treated between June 2003 and December 2011, the frequency of radiologically detected visceral metastases before death was 32%. Of the 92 patients with computed tomography performed within 3 mo of death, 49% had visceral metastases. Visceral metastases most commonly involved the liver (20%) and lung (13%). Median survival from diagnosis of visceral disease was 7.1 mo (95% confidence interval, 5.9-8.3). Survival was affected by the degree of bone involvement at detection of visceral disease, varying from 6.1 mo in men with more than six bone metastases to 18.2 mo in men with no bone metastases (p=0.001). Heterogeneity was noted in clinical phenotypes and prostate-specific antigen trends at development of visceral metastases. Visceral metastases are now more commonly detected in men with CRPC, likely due to the introduction of novel survival-prolonging treatments.

  18. Growth Failure in Children with Intractable Epilepsy Is Not Due to Increased Resting Energy Expenditure

    ERIC Educational Resources Information Center

    Bergqvist, A. G. Christina; Trabulsi, Jillian; Schall, Joan I.; Stallings, Virginia A.

    2008-01-01

    The aim of this study was to evaluate the resting energy expenditure (REE) of children with intractable epilepsy (IE) compared with healthy children, and to determine factors that contribute to the pattern of REE. REE, growth status, and body composition were assessed in 25 prepubertal children with IE (15 males, 10 females; mean age 5y 5mo [SD 2y…

  19. Fibrin glue-infiltrating hemostasis for intractable bleeding from the liver or spleen during liver transplantation

    PubMed Central

    Jung, Dong-Hwan; Song, Gi-Won; Ha, Tae-Yong; Jwa, Eun-Kyeong; Lee, Sung-Gyu

    2016-01-01

    Portal hypertension induces congestion of the liver and spleen, thus any capsular or parenchymal injury to these organs can produce intractable bleeding which generally is not easily controlled. To cope with intractable bleeding such as being encountered during liver transplantation, we developed an infiltrating hemostasis technique as a conceptual shift from conventional application methods, in which fibrin glue is locally injected into the bleeding area on the liver or spleen. This technique, which uses a fibrin glue kit (2 ml kit; Greenplast, Green Cross, Seoul, Korea), consists of inserting the needle 0.5-1 cm deep at the bleeding point, forcefully injecting 1 ml of fibrin glue contained in the fibrin glue kit, and then slowly withdrawing the needle with continuous forceful injection of the remaining 1 ml of fibrin glue. We have successfully performed this procedure in 6 cases of living donor liver transplantation and in 2 cases of non-transplant resection of the cirrhotic livers with hepatocellular carcinoma. This technique was also successfully applied to one liver transplant recipient in which intractable bleeding occurred from a small laceration at the spleen. Our fibrin glue-infiltrating hemostasis would be indicated to intractable bleeding from the hepatic or splenic cut surface. In such a situation, it would be applicable as a second-line rescue method for hemostasis. PMID:28261700

  20. Preliminary observation with dronabinol in patients with intractable pruritus secondary to cholestatic liver disease.

    PubMed

    Neff, Guy W; O'Brien, Christopher B; Reddy, K Rajender; Bergasa, Nora V; Regev, Arie; Molina, Enrique; Amaro, Rafael; Rodriguez, Miguel J; Chase, VeEtta; Jeffers, Lennox; Schiff, Eugene

    2002-08-01

    Pruritus due to cholestatic liver disease can be particularly difficult to manage and frequently is intractable to a variety of medical therapies. The aim of our study is to evaluate the efficacy of delta-9-tetrahydrocannabinol (delta-9-THC) for intractable cholestatic related pruritus (ICRP) that has failed conventional (and unconventional) remedies. Three patients were evaluated for plasmapheresis because of ICRP. All 3 patients had previously been extensively treated with standard therapies for ICRP including: diphenhydramine, chlorpheniramine, cholestyramine, rifampicin, phenobarbital, doxepin, naltrexone, UV therapy, and topical lotions. Even multiple courses of plasmapheresis were performed without any benefit for the intractable pruritus. All patients reported significant decreases in their quality of life, including lack of sleep, depression, inability to work, and suicidal ideations. All patients were started on 5 mg of delta-9-THC (Marinol) at bedtime. All 3 patients reported a decrease in pruritus, marked improvement in sleep, and eventually were able to return to work. Resolution of depression occurred in two of three. Side effects related to the drug include one patient experiencing a disturbance in coordination. Marinol dosage was decreased to 2.5 mg in this patient with resolution of symptoms. The duration of antipruritic effect is approximately 4-6 hrs in all three patients suggesting the need for more frequent dosing. Delta-9-tetrahydrocannabinol may be an effective alternative in patients with intractable cholestatic pruritus.

  1. Secondary Voice Restoration After Laryngotracheal Separation (LTS) for Dysphagia with Intractable Aspiration.

    PubMed

    Bonte, Katrien; Huvenne, Wouter; De Loof, Marie; Deron, Philippe; Viaene, Annick; Duprez, Fréderic; Vermeersch, Hubert

    2015-12-01

    Intractable aspiration is a serious, often life-threatening condition due to its potential impact on pulmonary function. Aspiration requires therapeutic measures, starting with conservative management but often necessitating surgical treatment. The basic surgical principle is to separate the alimentary and respiratory tracts through a variety of procedures which, unfortunately, nearly all result in the loss of phonation, with the exception of total laryngectomy (TL) which includes the placement of an indwelling voice prosthesis. In this study, we present a modified laryngotracheal separation (LTS) technique that, we believe, offers multiple advantages compared to standard TL. After reviewing the medical records of 35 patients with intractable aspiration who have undergone LTS, we describe the surgical technique and present the postoperative result. In a second surgical procedure about two months following LTS, we aimed to achieve voice restoration by placement of an indwelling voice prosthesis. Intractable aspiration was successfully treated in all patients. Placement of an indwelling voice prosthesis during a second operation was successful in 15 patients, representing the largest reported cohort thus far. LTS is a reliable surgical technique to treat intractable aspiration, with restoration of oral intake, thereby improving the general condition and quality of life of these unfortunate patients. Furthermore, voice restoration can be achieved in selected patients, by placement of a voice prosthesis.

  2. Fibrin glue-infiltrating hemostasis for intractable bleeding from the liver or spleen during liver transplantation.

    PubMed

    Hwang, Shin; Jung, Dong-Hwan; Song, Gi-Won; Ha, Tae-Yong; Jwa, Eun-Kyeong; Lee, Sung-Gyu

    2016-11-01

    Portal hypertension induces congestion of the liver and spleen, thus any capsular or parenchymal injury to these organs can produce intractable bleeding which generally is not easily controlled. To cope with intractable bleeding such as being encountered during liver transplantation, we developed an infiltrating hemostasis technique as a conceptual shift from conventional application methods, in which fibrin glue is locally injected into the bleeding area on the liver or spleen. This technique, which uses a fibrin glue kit (2 ml kit; Greenplast, Green Cross, Seoul, Korea), consists of inserting the needle 0.5-1 cm deep at the bleeding point, forcefully injecting 1 ml of fibrin glue contained in the fibrin glue kit, and then slowly withdrawing the needle with continuous forceful injection of the remaining 1 ml of fibrin glue. We have successfully performed this procedure in 6 cases of living donor liver transplantation and in 2 cases of non-transplant resection of the cirrhotic livers with hepatocellular carcinoma. This technique was also successfully applied to one liver transplant recipient in which intractable bleeding occurred from a small laceration at the spleen. Our fibrin glue-infiltrating hemostasis would be indicated to intractable bleeding from the hepatic or splenic cut surface. In such a situation, it would be applicable as a second-line rescue method for hemostasis.

  3. Lessons to Be Learned From Research on Peace Education in the Context of Intractable Conflict

    ERIC Educational Resources Information Center

    Kupermintz, Haggai; Salomon, Gavriel

    2005-01-01

    Recent research on peace education entails important practical lessons about educational work in regions of intractable conflict. Peace education in this context must deal with collective narratives and deeply rooted historical memories and societal beliefs. Research findings from a series of studies with Israeli and Palestinian students and…

  4. Intractable Postpartum Hemorrhage Resulting from Uterine Artery Pseudoaneurysm: Superselective Arteriographic Embolization via the Collateral Route

    SciTech Connect

    Doenmez, Halil Oztuerk, M. Halil; Guergen, Fatma; Soylu, Serra O.; Hekimoglu, Baki

    2007-04-15

    We present a patient with intractable postpartum hemorrhage resulting from uterine artery pseudoaneurysm despite bilateral hypogastric artery ligation who was successfully treated by an endovascular approach via the collateral route. Although there is a good argument for postponing surgery until transcatheter embolization has been attempted, this case shows that embolization can still be successful even if the iliac vessels have been ligated.

  5. Developing Agency through Peacebuilding in the Midst of Intractable Conflict: The Case of Israel and Palestine

    ERIC Educational Resources Information Center

    Plonski, Sharri

    2005-01-01

    This paper discusses the presence of "peacebuilding islands" within civil society as potential agents of transformation in the midst of intractable conflict. Focusing on the particular case of the Israeli-Palestinian conflict, the argument stems from a deconstruction of the legacy of national myopia perpetuated through social and…

  6. Disseminated visceral coccidiosis in sandhill cranes.

    PubMed

    Carpenter, J W; Novilla, M N; Fayer, R; Iverson, G C

    1984-12-01

    Disseminated visceral coccidiosis (DVC) caused by Eimeria spp was first recognized as a disease entity in captive sandhill cranes (Grus canadensis) and whooping cranes (G americana) at the Patuxent Wildlife Research Center. Because cranes produced at the Center are reintroduced to the wild to augment wild populations, studies involving both experimentally induced and natural infections were initiated to determine the potential or actual occurrence of DVC in wild Gruidae. Nine sandhill cranes dosed orally with eimerian oocysts of wild origin developed lesions characteristic of DVC. Extraintestinal granulomas associated with developing schizonts were found in 6 birds. Similar lesions were observed in wild sandhill cranes throughout parts of midwestern United States, Alaska, and Saskatchewan. These studies revealed the wide geographic distribution and the high frequency of occurrence of DVC in wild cranes.

  7. Disseminated visceral coccidiosis in sandhill cranes

    USGS Publications Warehouse

    Carpenter, J.W.; Novilla, M.N.; Fayer, R.; Iverson, G.C.

    1984-01-01

    Disseminated visceral coccidiosis (DVC) caused by Eimeria spp was first recognized as a disease entity in captive sandhill cranes (Grus canadensis) and whooping cranes (G americana) at the Patuxent Wildlife Research Center. Because cranes produced at the Center are reintroduced to the wild to augment wild populations, studies involving both experimentally induced and natural infections were initiated to determine the potential or actual occurrence of DVC in wild Gruidae. Nine sandhill cranes dosed orally with eimerian oocysts of wild origin developed lesions characteristic of DVC. Extraintestinal granulomas associated with developing schizonts were found in 6 birds. Similar lesions were observed in wild sandhill cranes throughout parts of midwestern United States, Alaska, and Saskatchewan. These studies revealed the wide geographic distribution and the high frequency of occurrence of DVC in wild cranes.

  8. Role of satellite glial cells in gastrointestinal pain.

    PubMed

    Hanani, Menachem

    2015-01-01

    Gastrointestinal (GI) pain is a common clinical problem, for which effective therapy is quite limited. Sensations from the GI tract, including pain, are mediated largely by neurons in the dorsal root ganglia (DRG), and to a smaller extent by vagal afferents emerging from neurons in the nodose/jugular ganglia. Neurons in rodent DRG become hyperexcitable in models of GI pain (e.g., gastric or colonic inflammation), and can serve as a source for chronic pain. Glial cells are another element in the pain signaling pathways, and there is evidence that spinal glial cells (microglia and astrocytes) undergo activation (gliosis) in various pain models and contribute to pain. Recently it was found that satellite glial cells (SGCs), the main type of glial cells in sensory ganglia, might also contribute to chronic pain in rodent models. Most of that work focused on somatic pain, but in several studies GI pain was also investigated, and these are discussed in the present review. We have shown that colonic inflammation induced by dinitrobenzene sulfonic acid (DNBS) in mice leads to the activation of SGCs in DRG and increases gap junction-mediated coupling among these cells. This coupling appears to contribute to the hyperexcitability of DRG neurons that innervate the colon. Blocking gap junctions (GJ) in vitro reduced neuronal hyperexcitability induced by inflammation, suggesting that glial GJ participate in SGC-neuron interactions. Moreover, blocking GJ by carbenoxolone and other agents reduces pain behavior. Similar changes in SGCs were also found in the mouse nodose ganglia (NG), which provide sensory innervation to most of the GI tract. Following systemic inflammation, SGCs in these ganglia were activated, and displayed augmented coupling and greater sensitivity to the pain mediator ATP. The contribution of these changes to visceral pain remains to be determined. These results indicate that although visceral pain is unique, it shares basic mechanisms with somatic pain

  9. Role of satellite glial cells in gastrointestinal pain

    PubMed Central

    Hanani, Menachem

    2015-01-01

    Gastrointestinal (GI) pain is a common clinical problem, for which effective therapy is quite limited. Sensations from the GI tract, including pain, are mediated largely by neurons in the dorsal root ganglia (DRG), and to a smaller extent by vagal afferents emerging from neurons in the nodose/jugular ganglia. Neurons in rodent DRG become hyperexcitable in models of GI pain (e.g., gastric or colonic inflammation), and can serve as a source for chronic pain. Glial cells are another element in the pain signaling pathways, and there is evidence that spinal glial cells (microglia and astrocytes) undergo activation (gliosis) in various pain models and contribute to pain. Recently it was found that satellite glial cells (SGCs), the main type of glial cells in sensory ganglia, might also contribute to chronic pain in rodent models. Most of that work focused on somatic pain, but in several studies GI pain was also investigated, and these are discussed in the present review. We have shown that colonic inflammation induced by dinitrobenzene sulfonic acid (DNBS) in mice leads to the activation of SGCs in DRG and increases gap junction-mediated coupling among these cells. This coupling appears to contribute to the hyperexcitability of DRG neurons that innervate the colon. Blocking gap junctions (GJ) in vitro reduced neuronal hyperexcitability induced by inflammation, suggesting that glial GJ participate in SGC-neuron interactions. Moreover, blocking GJ by carbenoxolone and other agents reduces pain behavior. Similar changes in SGCs were also found in the mouse nodose ganglia (NG), which provide sensory innervation to most of the GI tract. Following systemic inflammation, SGCs in these ganglia were activated, and displayed augmented coupling and greater sensitivity to the pain mediator ATP. The contribution of these changes to visceral pain remains to be determined. These results indicate that although visceral pain is unique, it shares basic mechanisms with somatic pain

  10. Involvement of cannabinoid receptors in gut motility and visceral perception

    PubMed Central

    Hornby, Pamela J; Prouty, Stephen M

    2004-01-01

    From a historical perspective to the present day, all the evidence suggests that activation of cannabinoid receptors (CBRs) is beneficial for gut discomfort and pain, which are symptoms related to dysmotility and visceral perception. CBRs comprise G-protein coupled receptors that are predominantly in enteric and central neurones (CB1R) and immune cells (CB2R). In the last decade, evidence obtained from the use of selective agonists and inverse agonists/antagonists indicates that manipulation of CB1R can alter (1) sensory processing from the gut, (2) brain integration of brain-gut axis, (3) extrinsic control of the gut and (4) intrinsic control by the enteric nervous system. The extent to which activation of CB1R is most critical at these different levels is related to the region of the GI tract. The upper GI tract is strongly influenced by CB1R activation on central vagal pathways, whereas intestinal peristalsis can be modified by CB1R activation in the absence of extrinsic input. Actions at multiple levels make the CB1R a target for the treatment of functional bowel disorders, such as IBS. Since low-grade inflammation may act as a trigger for occurrence of IBS, CB2R modulation could be beneficial, but there is little supporting evidence for this yet. The challenge is to accomplish CBR activation while minimizing adverse effects and abuse liabilities. Potential therapeutic strategies involve increasing signaling by endocannabinoids (EC). The pathways involved in the biosynthesis, uptake and degradation of EC provide opportunities for modulation of CB1R and some recent evidence with inhibitors of EC uptake and metabolism suggest that these could be exploited for therapeutic gain. PMID:15100166

  11. Ancient origin of somatic and visceral neurons

    PubMed Central

    2013-01-01

    Background A key to understanding the evolution of the nervous system on a large phylogenetic scale is the identification of homologous neuronal types. Here, we focus this search on the sensory and motor neurons of bilaterians, exploiting their well-defined molecular signatures in vertebrates. Sensorimotor circuits in vertebrates are of two types: somatic (that sense the environment and respond by shaping bodily motions) and visceral (that sense the interior milieu and respond by regulating vital functions). These circuits differ by a small set of largely dedicated transcriptional determinants: Brn3 is expressed in many somatic sensory neurons, first and second order (among which mechanoreceptors are uniquely marked by the Brn3+/Islet1+/Drgx+ signature), somatic motoneurons uniquely co-express Lhx3/4 and Mnx1, while the vast majority of neurons, sensory and motor, involved in respiration, blood circulation or digestion are molecularly defined by their expression and dependence on the pan-visceral determinant Phox2b. Results We explore the status of the sensorimotor transcriptional code of vertebrates in mollusks, a lophotrochozoa clade that provides a rich repertoire of physiologically identified neurons. In the gastropods Lymnaea stagnalis and Aplysia californica, we show that homologues of Brn3, Drgx, Islet1, Mnx1, Lhx3/4 and Phox2b differentially mark neurons with mechanoreceptive, locomotory and cardiorespiratory functions. Moreover, in the cephalopod Sepia officinalis, we show that Phox2 marks the stellate ganglion (in line with the respiratory — that is, visceral— ancestral role of the mantle, its target organ), while the anterior pedal ganglion, which controls the prehensile and locomotory arms, expresses Mnx. Conclusions Despite considerable divergence in overall neural architecture, a molecular underpinning for the functional allocation of neurons to interactions with the environment or to homeostasis was inherited from the urbilaterian ancestor by

  12. [Visceral leishmaniasis in an HIV positive patient].

    PubMed

    Rossiere-Echazarreta, Natalia Lorena; Rodríguez-Campos, Esther Alicia; Morales-Esponda, Mario; Domínguez-Moreno, Rogelio; Cruz-Ortiz, Margarita; Rodríguez-Guzmán, Leoncio Miguel

    2013-01-01

    Introducción: la leishmaniasis visceral o kala azar es la presentación clínica más grave. En México, es una enfermedad rara por lo que su diagnóstico es tardío y generalmente culmina en la muerte del paciente. Se describe a un paciente VIH positivo que desarrolló leishmaniasis visceral. El objetivo es explicar sus características fisiopatológicas y de su tratamiento. Caso clínico: hombre de 45 años de edad, quien ingresó al hospital por cuadro crónico de diarrea sanguinolenta, distensión abdominal, dolor tipo cólico, pérdida de peso y fiebre. A la exploración física se identificó paciente febril con dolor en fosa iliaca derecha y hepatoesplenomegalia. La prueba ELISA para VIH resultó positiva y el ultrasonido hizo evidente una tumoración en ciego, por lo que se realizó biopsia. El informe histopatológico indicó que se trataba de leishmaniasis. Conclusiones: en los pacientes con leishmaniasis e infección por VIH existe pobre respuesta al tratamiento y la mortalidad es alta, causada por la menor respuesta inmune del huésped. En la literatura especializada se sugiere el tratamiento establecido para la infección por VIH combinado con miltefosine y anfotericina B liposomal para la leishmaniasis.

  13. Sexual pain.

    PubMed

    Boardman, Lori A; Stockdale, Colleen K

    2009-12-01

    Sexual pain is an underrecognized and poorly treated constellation of disorders that significantly impact affected women and their partners. Recognized as a form of chronic pain, sexual pain disorders are heterogeneous and include dyspareunia (superficial and deep), vaginismus, vulvodynia, vestibulitis, and noncoital sexual pain disorder. Women too often tolerate pain in the belief that this will meet their partners' needs. This article provides a review of the terminology and definition of the condition, theories on the pathophysiology, diagnostic considerations, and recommendations on the management of female sexual pain.

  14. Serodiagnosis of visceral leishmaniasis in an American Peace Corps volunteer.

    PubMed

    Chaulk, C P; Smith, P W; Sass, H J

    1986-08-01

    A case of visceral leishmaniasis in a young American Peace Corps volunteer is reported. Both clinical and epidemiologic evidence strongly supported the diagnosis; however, hepatic and splenic aspirates for the causative organism were negative. The diagnosis was eventually confirmed through serology, employing indirect immunofluorescence and complement fixation testing of serum. The patient clinically responded dramatically to sodium stibogluconate, the drug of choice for the treatment of visceral leishmaniasis. This case is significant because it alerts the physician to an unusual cause of fever of unknown origin in residents of the Western nations and demonstrates the potential usefulness of serology in diagnosing visceral leishmaniasis when the infecting organism cannot be isolated.

  15. Fibromyalgia patients show an abnormal dopamine response to pain.

    PubMed

    Wood, Patrick B; Schweinhardt, Petra; Jaeger, Erik; Dagher, Alain; Hakyemez, Helene; Rabiner, Eugenii A; Bushnell, M Catherine; Chizh, Boris A

    2007-06-01

    Fibromyalgia is characterized by chronic widespread pain and bodily tenderness and is often accompanied by affective disturbances. Accumulating evidence indicates that fibromyalgia may involve a dysfunction of modulatory systems in the brain. While brain dopamine is best known for its role in pleasure, motivation and motor control, recent evidence suggests that it is also involved in pain modulation. Because dopamine is implicated in both pain modulation and affective processing, we hypothesized that fibromyalgia may involve a disturbance of dopaminergic neurotransmission. Fibromyalgia patients and matched healthy control subjects were subjected to deep muscle pain produced by injection of hypertonic saline into the anterior tibialis muscle. In order to determine the endogenous release of dopamine in response to painful stimulation, we used positron emission tomography to examine binding of [(11)C]-raclopride (D2/D3 ligand) in the brain during injection of painful hypertonic saline and nonpainful normal saline. Fibromyalgia patients experienced the hypertonic saline as more painful than healthy control subjects. Control subjects released dopamine in the basal ganglia during the painful stimulation, whereas fibromyalgia patients did not. In control subjects, the amount of dopamine release correlated with the amount of perceived pain but in fibromyalgia patients no such correlation was observed. These findings provide the first direct evidence that fibromyalgia patients have an abnormal dopamine response to pain. The disrupted dopaminergic reactivity in fibromyalgia patients could be a critical factor underlying the widespread pain and discomfort in fibromyalgia and suggests that the therapeutic effects of dopaminergic treatments for this intractable disorder should be explored.

  16. Calcified cysticercotic lesions and intractable epilepsy: a cross sectional study of 512 patients

    PubMed Central

    Velasco, T R; Zanello, P A; Dalmagro, C L; Araújo, D; Santos, A C; Bianchin, M M; Alexandre, V; Walz, R; Assirati, J A; Carlotti, C G; Takayanagui, O M; Sakamoto, A C; Leite, J P

    2006-01-01

    Background Neurocysticercosis is a major cause of epilepsy in developing countries and is endemic in Brazil. To test the hypothesis that the aetiological profile of patients with intractable epilepsy in Brazil includes neurocysticercosis, we conducted a cross sectional study investigating the aetiology of intractable epilepsy. Methods A total of 512 patients evaluated at the outpatient clinic for intractable epilepsy at the Ribeirão Preto School of Medicine were included in the survey. Medical intractability was determined on the basis of seizure incidence and severity, and response to appropriate epilepsy management. Neuroimaging included brain CT with non‐contrasted and contrasted phases and high resolution MRI. Patients were divided into neurocysticercosis and non‐neurocysticercosis groups according to previous diagnostic criteria. Results The most common epileptogenic lesions were mesial temporal sclerosis (MTS; 56.0%), malformations of cortical development (12.1%), and brain tumours (9.9%). Neuroimaging was normal in 8.7% of patients. Calcifications were found in 27% of patients and were significantly more common in patients with MTS than in those without MTS (p<0.001). Isolated neurocysticercosis was found in only eight patients (1.56%). Conclusions These data suggest that neurocysticercosis is an uncommon cause of intractable epilepsy, even in an endemic region such as Brazil, and that it may only represent a coexistent pathology. However, an analysis of our findings reveals that neurocysticercosis was more common in patients with MTS. This finding could suggest either that there is a cause‐effect relationship between MTS and neurocysticercosis, or that MTS and neurocysticercosis co‐vary with a missing variable, such as socio‐economic status. PMID:16543527

  17. Mechanisms of pain from urinary tract infection.

    PubMed

    Rosen, John M; Klumpp, David J

    2014-04-01

    and CCR2 at the level of pain maintenance. Together, these findings show that transient infection with E. coli might result in chronic visceral pain with the hallmarks of neuropathic pain. This pattern of behaviors mimics the spectrum of interstitial cystitis symptoms, thus supporting the possibility of an infectious etiology of interstitial cystitis.

  18. Pain Assessment

    MedlinePlus

    ... acupuncture, chiropractic care, massage or other manual therapies, yoga, herbal and nutritional therapies, or others. This information helps the health care provider understand the nature of the pain or the potential benefits of treatment. The goals of the comprehensive pain ...

  19. Anal Pain

    MedlinePlus

    ... change in bowel habit or rectal bleeding. A hemorrhoid that develops quickly or is particularly painful may ... your doctor. The blood clot of a thrombosed hemorrhoid, although painful, can't break loose and travel, ...

  20. Back Pain

    MedlinePlus

    ... specific points on the body. Some people with low back pain report that acupuncture helps relieve their symptoms. Massage. ... Accessed May 29, 2015. Adult acute and subacute low back pain. Bloomington, Minn.: Institute for Clinical Systems Improvement. http:// ...

  1. Period Pain

    MedlinePlus

    ... You may also have other symptoms, such as lower back pain, nausea, diarrhea, and headaches. Period pain is not ... Taking a hot bath Doing relaxation techniques, including yoga and meditation You might also try taking over- ...

  2. Finger pain

    MedlinePlus

    Pain - finger ... Nearly everyone has had finger pain at some time. You may have: Tenderness Burning Stiffness Numbness Tingling Coldness Swelling Change in skin color Redness Many conditions, such ...

  3. Back Pain

    MedlinePlus

    ... Oh, my aching back!", you are not alone. Back pain is one of the most common medical problems, ... 10 people at some point during their lives. Back pain can range from a dull, constant ache to ...

  4. Breast Pain

    MedlinePlus

    ... before your period and sometimes continuing through your menstrual cycle. The pain may be moderate or severe, and ... breasts. Throughout the month, not related to your menstrual cycle. Postmenopausal women sometimes have breast pain, but breast ...

  5. Hip Pain

    MedlinePlus

    ... clues about the underlying cause. Problems within the hip joint itself tend to result in pain on the ... tendons and other soft tissues that surround your hip joint. Hip pain can sometimes be caused by diseases ...

  6. Patellofemoral Pain.

    PubMed

    Dutton, Rebecca A; Khadavi, Michael J; Fredericson, Michael

    2016-02-01

    Patellofemoral pain is characterized by insidious onset anterior knee pain that is exaggerated under conditions of increased patellofemoral joint stress. A variety of risk factors may contribute to the development of patellofemoral pain. It is critical that the history and physical examination elucidate those risk factors specific to an individual in order to prescribe an appropriate and customized treatment plan. This article aims to review the epidemiology, risk factors, diagnosis, and management of patellofemoral pain.

  7. VEGF induces sensory and motor peripheral plasticity, alters bladder function, and promotes visceral sensitivity

    PubMed Central

    2012-01-01

    neural plasticity in the pelvis and enhanced VEGF content may be associated with visceral hyperalgesia, abdominal discomfort, and/or pelvic pain. PMID:23249422

  8. Ziconotide infusion for severe chronic pain: case series of patients with neuropathic pain.

    PubMed

    Wermeling, Daniel P; Berger, Joseph R

    2006-03-01

    Ziconotide intrathecal infusion was recently approved by the United States Food and Drug Administration for the treatment of intractable severe chronic pain. Patients with neuropathic pain make up a significant population among those who experience chronic pain for which there are less than optimal pharmacotherapeutic options. Published clinical trials provide a global view of ziconotide efficacy and safety. A subset of patients in clinical trials obtained complete pain relief, a remarkable finding given the history of drug treatment for neuropathic pain. To provide more information regarding those who respond to ziconotide therapy, we discuss three patients with neuropathic pain who received ziconotide infusion. Two patients with longstanding neuropathic pain, one with complex regional pain syndrome (formerly known as reflex sympathetic dystrophy) of the leg and one with lumbar radiculitis, achieved temporary but complete pain relief from single 5- and 10-microg epidural test doses. In the third case, a patient with longstanding bilateral leg and foot neuropathic pain from acquired immunodeficiency syndrome and antiretroviral drug therapy achieved considerable pain relief from a long-term continuous intrathecal infusion. The patients who received a single dose had mild central nervous system adverse effects such as sedation, somnolence, nausea, headache, and lightheadedness. The patient who received the intrathecal infusion experienced mild-to-severe adverse effects depending on the rate of infusion; these effects included sedation, confusion, memory impairment, slurred speech, and double vision. This patient could sense impending adverse effects and made rate adjustments or suspended infusion to avert untoward symptoms. In all three cases, patients achieved considerable pain relief that was long-lasting and persisted well after dose administration or suspension of infusion.

  9. Mechanisms of Acupuncture-Electroacupuncture on Persistent Pain

    PubMed Central

    Zhang, Ruixin; Lao, Lixing; Ren, Ke; Berman, Brian M.

    2014-01-01

    In the last decade, preclinical investigations of electroacupuncture mechanisms on persistent tissue-injury (inflammatory), nerve-injury (neuropathic), cancer, and visceral pain have increased. These studies show that electroacupuncture activates the nervous system differently in health than in pain conditions, alleviates both sensory and affective inflammatory pain, and inhibits inflammatory and neuropathic pain more effectively at 2–10 Hz than at 100 Hz. Electroacupuncture blocks pain by activating a variety of bioactive chemicals through peripheral, spinal, and supraspinal mechanisms. These include opioids, which desensitize peripheral nociceptors and reduce pro-inflammatory cytokines peripherally and in the spinal cord, and serotonin and norepinephrine, which decrease spinal n-methyl-d-aspartate receptor subunit GluN1 phosphorylation. Additional studies suggest that electroacupuncture, when combined with low dosages of conventional analgesics, provides effective pain management that can forestall the side effects of often-debilitating pharmaceuticals. PMID:24322588

  10. Visceral ischemia: could it be segmental arterial mediolysis.

    PubMed

    Agarwal, Sunil; Stephen, Edwin; Selvaraj, Dheepak; Mathur, Kapil; Keshava, Shyamkumar; Chandy, Sunil Thomas

    2009-01-01

    We present two cases of segmental arterial mediolysis, which can present with dissecting aneurysms or thrombosis of the visceral branches of the abdominal aorta. Segmental arterial mediolysis (SAM) causes ischemic bowel disease and has characteristic CT and angiographic features.

  11. Maternal Separation Induced Visceral Hypersensitivity from Childhood to Adulthood

    PubMed Central

    Yi, Lisha; Zhang, Haiqin; Sun, Huihui; Zhou, Lu; Chen, Ying; Xuan, Liqian; Jiang, Yuanxi; Xu, Shuchang

    2017-01-01

    Background/Aims Early adverse life events (EALs) are relevant to irritable bowel syndrome in adulthood. Maternal separation (MS), as one of the EALs, has proved to induce visceral hypersensitivity in adult rats. However, the effect of MS on visceral hypersensitvity from the post-weaning period to adulthood remains unknown. Methods One hundred and ten neonatal Sprague-Dawley rats were randomly divided into 2 groups: rats in the MS group were exposed to 3 hours daily MS on postnatal day (PND) 2–14; the normal control (NC) group remained undisturbed. Visceral sensitivity was determined by measuring the visceromotor response to colorectal distention on PND21, 35, and 56. Anxiety-like behaviors were measured by the open field test. Results Compared with NC rats, MS rats showed significant visceral hypersensitivity from the post-weaning period to adult. The proportion of visceral hypersensitive rats decreased with age from 87.5% to 70.0% in the female MS group and from 90.0% to 66.7% in the male MS group. The relative VMR ratio of MS and NC on PND21 was higher than PND35 and PND56. MS rats showed decreased ability of movement and exploration to the novel environment in the post-weaning period, obesity in the prepubertal period, and more anxiety-like behaviors in adulthood. Conclusions MS can significantly affect visceral sensitivity and behaviors of rats in different age stages, especially in the post-weaning period. Visceral hypersensitivity of MS rats is more pronounced in the post-weaning period and slightly restored in adults. Thus, visceral hypersensitivity in the post-weaning period might play a more meaningful pathophysiologic role in the formation of adult irritable bowel syndrome. PMID:28238254

  12. Estrogen-dependent visceral hypersensitivity following stress in rats

    PubMed Central

    Hubbard, Catherine S; Karpowicz, Jane M; Furman, Andrew J; da Silva, Joyce Teixeira; Traub, Richard J

    2016-01-01

    We used functional MRI and a longitudinal design to investigate the brain mechanisms in a previously reported estrogen-dependent visceral hypersensitivity model. We hypothesized that noxious visceral stimulation would be associated with activation of the insula, anterior cingulate cortex, and amygdala, and that estrogen-dependent, stress-induced visceral hypersensitivity would both enhance activation of these regions and recruit activation of other brain areas mediating affect and reward processing. Ovariectomized rats were treated with estrogen (17 β-estradiol, E2) or vehicle (n = 5 per group) and scanned in a 7T MRI at three different time points: pre-stress (baseline), 2 days post-stress, and 18 days post-stress. Stress was induced via a forced-swim paradigm. In a separate group of ovariectomized rats, E2 treatment induced visceral hypersensitivity at the 2 days post-stress time point, and this hypersensitivity returned to baseline at the 18 days post-stress time point. Vehicle-treated rats show no hypersensitivity following stress. During the MRI scans, rats were exposed to noxious colorectal distention. Across groups and time points, noxious visceral stimulation led to activations in the insula, anterior cingulate, and left amygdala, parabrachial nuclei, and cerebellum. A group-by-time interaction was seen in the right amygdala, ventral striatum-pallidum, cerebellum, hippocampus, mediodorsal thalamus, and pontine nuclei. Closer inspection of the data revealed that vehicle-treated rats showed consistent activations and deactivations across time, whereas estrogen-treated animals showed minimal deactivation with noxious visceral stimulation. This unexpected finding suggests that E2 may dramatically alter visceral nociceptive processing in the brain following an acute stressor. This study is the first to examine estrogen-stress dependent interactions in response to noxious visceral stimulation using functional MRI. Future studies that include other control

  13. Effect of intraperitoneal local anesthetic on pain characteristics after laparoscopic cholecystectomy

    PubMed Central

    Choi, Geun Joo; Kang, Hyun; Baek, Chong Wha; Jung, Yong Hun; Kim, Dong Rim

    2015-01-01

    AIM: To systematically evaluate the effect of intraperitoneal local anesthetic on pain characteristics after laparoscopic cholecystectomy (LC). METHODS: We searched MEDLINE, EMBASE, and the Cochrane Library. Randomized controlled trials in English that compared the effect of intraperitoneal administration of local anesthetics on pain with that of placebo or nothing after elective LC under general anesthesia were included. The primary outcome variables analyzed were the combined scores of abdominal, visceral, parietal, and shoulder pain after LC at multiple time points. We also extracted pain scores at resting and dynamic states. RESULTS: We included 39 studies of 3045 patients in total. The administration of intraperitoneal local anesthetic reduced pain intensity in a resting state after laparoscopic cholecystectomy: abdominal [standardized mean difference (SMD) = -0.741; 95%CI: -1.001 to -0.48, P < 0.001]; visceral (SMD = -0.249; 95%CI: -0.493 to -0.006, P = 0.774); and shoulder (SMD = -0.273; 95%CI: -0.464 to -0.082, P = 0.097). Application of intraperitoneal local anesthetic significantly reduced the incidence of shoulder pain (RR = 0.437; 95%CI: 0.299 to 0.639, P < 0.001). There was no favorable effect on resting parietal or dynamic abdominal pain. CONCLUSION: Intraperitoneal local anesthetic as an analgesic adjuvant in patients undergoing laparoscopic cholecystectomy exhibited beneficial effects on postoperative abdominal, visceral, and shoulder pain in a resting state. PMID:26715824

  14. Temporomandibular pain

    PubMed Central

    Prasad, S Raghavendra; Kumar, N Ravi; Shruthi, HR; Kalavathi, SD

    2016-01-01

    Temporomandibular joint pain has various medical and dental etiological factors. The etiology of the temporomandibular joint pain is enigmatic, no single etiological factor is regarded as the cause. Its distribution is also not confined to a single area. This article presents the basic etiologic factors, its epidemiology, distribution of pain, classification of patients and the psychosocial behavior of patients suffering with temporomandibular pain. As overwhelming majority of medical and dental conditions/issues related to etiology of temporomandibular pain in patients have traditionally been presented and interpreted from the clinician's point of view. PMID:27601822

  15. Visceral urate deposition in a little bittern (Ixobrychus minutus)

    PubMed Central

    Rahimi, Morad; Minoosh, Zahra; Haghighi, Siavosh

    2015-01-01

    Visceral urate deposition (visceral gout) is a common finding during post-mortem examination of poultry. Rare cases of visceral gout may occur in wild birds. A rare case of visceral urate deposition in a little bittern (Ixobrychus minutus) is reported here. In May 2013, carcass of a little bittern was submitted for necropsy to the Clinic of Poultry Diseases (Faculty of Veterinary Medicine, Razi University) by local authorities of Iran Department of Environment. At necropsy, white chalky deposits were observed on the heart and thoracic air sacs of the bird. To confirm the presence of urates, chalky deposits were collected from pericardium and tested by muerxide test. Heart and kidneys were sampled, preserved in 10% neutral-buffered formalin solution and submitted to laboratory for histopathology. Murexide test was positive for presence of uric acid in chalky deposits collected from pericardium. Light microscopy of affected organs confirmed the condition as visceral urate deposition. To the best of our knowledge, this is the first report on the occurrence of visceral urate deposition in a little bittern. PMID:26261716

  16. Ion channels, ion channel receptors, and visceral hypersensitivity in irritable bowel syndrome.

    PubMed

    Fuentes, I M; Christianson, J A

    2016-11-01

    Ion channels are expressed throughout the gastrointestinal system and regulate nearly every aspect of digestion, including fluid secretion and absorption, motility, and visceral sensitivity. It is therefore not surprising that in the setting of functional bowel disorders, such as irritable bowel syndrome (IBS), ion channels are often altered in terms of expression level and function and are a target of pharmacological intervention. This is particularly true of their role in driving abdominal pain through visceral hypersensitivity (VH), which is the main reason IBS patients seek medical care. In the study by Scanzi et al., in the current issue of this journal, they provide evidence that the T-type voltage-gated calcium channel (Cav ) Cav 3.2 is upregulated in human IBS patients, and is necessary for the induction of an IBS-like disease state in mice. In this mini-review, we will discuss the contribution of specific ion channels to VH in IBS, both in human patients and rodent models. We will also discuss how Cav 3.2 may play a role as an integrator of multiple environmental stimuli contributing toward VH.

  17. Transcending intractable conflict in health care: an exploratory study of communication and conflict management among anesthesia providers.

    PubMed

    Jameson, Jessica Katz

    2003-01-01

    This paper explores the contrast between the longstanding, intractable conflict between two anesthesia providers and the cooperation of many individual nurse anesthetists and anesthesiologists working side-by-side to provide safe, effective anesthesia. Analysis of interview transcripts reveals that communication among anesthesia nurses and anesthesiologists may enact or transcend the conflict. This article proposes recommendations for improving communication between anesthesiologists and certified registered nurse anesthetists in particular and de-escalating intractable conflict in general. It also contributes to communication theory in intractable conflict by examining how individual, interpersonal conflict management interactions lead to either transcendence or enactment of the larger group conflict.

  18. Resiniferatoxin for Pain Treatment: An Interventional Approach to Personalized Pain Medicine

    PubMed Central

    Iadarola, Michael J.; Gonnella, Gian Luigi

    2015-01-01

    This review examines existing preclinical and clinical studies related to resiniferatoxin (RTX) and its potential uses in pain treatment. Like capsaicin, RTX is a vanilloid receptor (TRPV1) agonist, only more potent. This increased potency confers both quantitative and qualitative advantages in terms of drug action on the TRPV1 containing nerve terminal, which result in an increased efficacy and a long duration of action. RTX can be delivered by a central route of administration through injection into the subarachnoid space around the lumbosacral spinal cord. It can also be administered peripherally into a region of skin or deep tissue where primary afferents nerves terminate, or directly into a nerve trunk or a dorsal root ganglion. The central route is currently being evaluated as a treatment for intractable pain in patients with advanced cancer. Peripheral administration offers the possibility to treat a wide diversity of pain problems because of the ability to bring the treatment to the site of the pain (the peripheral generator). While not all pain disorders are appropriate for RTX, tailoring treatment to an individual patient's needs via a selective and local intervention that chemically targets a specific population of nerve terminals provides a new capability for pain therapy and a simplified and effective approach to personalized pain medicine. PMID:26779292

  19. Abdominal Pain (Stomach Pain), Short-Term

    MedlinePlus

    ... myhealthfinder Immunization Schedules Nutrient Shortfall Questionnaire Abdominal Pain (Stomach Pain), Short-termJust about everyone has had a " ... time or another. But sudden severe abdominal pain (stomach pain), also called acute pain, shouldn't be ...

  20. Effects of Combined Opioids on Pain and Mood in Mammals

    PubMed Central

    Rech, Richard H.; Mokler, David J.; Briggs, Shannon L.

    2012-01-01

    The authors review the opioid literature for evidence of increased analgesia and reduced adverse side effects by combining mu-opioid-receptor (MOR) agonists, kappa-opioid-receptor (KOR) agonists, and nonselective low-dose-opioid antagonists (LD-Ant). We tested fentanyl (MOR agonist) and spiradoline (KOR agonist), singly and combined, against somatic and visceral pain models. Combined agonists induced additive analgesia in somatic pain and synergistic analgesia in visceral pain. Other investigators report similar effects and reduced tolerance and dependence with combined MOR agonist and KOR agonist. LD-Ant added to either a MOR agonist or KOR agonist markedly enhanced analgesia of either agonist. In accordance with other place-conditioning (PC) studies, our PC investigations showed fentanyl-induced place preference (CPP) and spiradoline-induced place aversion (CPA). We reduced fentanyl CPP with a low dose of spiradoline and reduced spiradoline CPA with a low dose of fentanyl. We propose combined MOR agonist, KOR agonist, and LD-Ant to produce superior analgesia with reduced adverse side effects, particularly for visceral pain. PMID:22550575

  1. TRPA1 in the spinal dorsal horn is involved in post-inflammatory visceral hypersensitivity: in vivo study using TNBS-treated rat model

    PubMed Central

    Li, Qian; Guo, Cheng-Hao; Chowdhury, Mohammed Ali; Dai, Tao-Li; Han, Wei

    2016-01-01

    Introduction The transient receptor potential ankyrin-1 (TRPA1) channel, a pain transducer and amplifier, is drawing increasing attention in the field of visceral hypersensitivity, commonly seen in irritable bowel syndrome and inflammatory bowel disease. However, the role of TRPA1 in visceral nociception during post-inflammatory states is not well defined. Here, we explore the correlation between TRPA1 expression in the spinal dorsal horn (SDH) and persistent post-inflammatory visceral hypersensitivity. Methods We injected rats intracolonically with 2,4,6-trinitrobenzene sulfonic acid (TNBS) or vehicle (n=12 per group). Post-inflammatory visceral hypersensitivity was assessed by recording the electromyographic activity of the external oblique muscle in response to colorectal distension. TRPA1 expression and distribution in the spinal cord and colon were examined by Western blotting and immunohistochemistry. Results Animals exposed to TNBS had more abdominal contractions than vehicle-injected controls (P<0.05), which corresponded to a lower nociceptive threshold. Expression of TRPA1 in the SDH (especially in the substantia gelatinosa) and the colon was significantly greater in the TNBS-treated group than in controls (P<0.05). In the SDH, the number of TRPA1-immunopositive neurons was 25.75±5.12 in the control group and 34.25±7.89 in the TNBS-treated group (P=0.023), and integrated optical density values of TRPA1 in the control and TNBS-treated groups were 14,544.63±6,525.54 and 22,532.75±7,608.11, respectively (P=0.041). Conclusion Our results indicate that upregulation of TRPA1 expression in the SDH is associated with persistent post-inflammatory visceral hypersensitivity in the rat and provides insight into potential therapeutic targets for the control of persistent visceral hypersensitivity. PMID:27980434

  2. Segmental arterial mediolysis: unrecognized cases culled from cases of ruptured aneurysm of abdominal visceral arteries reported in the Japanese literature.

    PubMed

    Inada, Kiyoshi; Maeda, Matsuyoshi; Ikeda, Tsuneko

    2007-01-01

    Segmental arterial mediolysis (SAM) is a rare nonatherosclerotic and noninflammatory arteriopathy that was proposed by Slavin et al. [Segmental mediolytic arteritis. A clinical pathologic study, Lab. Invest. 35 (1976) 23-29]. It mainly involves abdominal visceral arteries and is characterized by lytic degeneration of the media, resulting in intraabdominal bleeding. We collected 27 unrecognized cases of SAM by reviewing microscopic slides of cases of ruptured aneurysms of visceral arteries, except splenic and hepatic aneurysms, reported in the Japanese literature. This paper describes the pathological and clinical features of these cases. The symptom at onset was abdominal pain associated with intraabdominal bleeding in all cases. The most involved artery was the middle colic artery, accounting for 14 (50%), followed by gastric and gastroepiploic arteries, (6 and 5, respectively). Seventy-eight percent of aneurysms were of dissecting type and the rest of pseudoaneurysm type, except for one. Multiple aneurysms were found in 9 cases (33.3%). Pathological lesions were acute in all. The outcome of those who had surgery was good, even in those who had surgery for 1 ruptured aneurysm, leaving the others unmanaged. The relationship of SAM to fibromuscular dysplasia is discussed. Secondary changes in the wall of the accompanying vein to the affected artery are briefly described. It is emphasized that the majority of aneurysms of abdominal visceral arteries are gathered together as SAM as a definite clinical and pathological entity.

  3. Transient receptor potential (TRP) A1 activated currents in TRPV1 and cholecystokinin-sensitive cranial visceral afferent neurons.

    PubMed

    Choi, Myung-Jin; Jin, Zhenhua; Park, Yong Seek; Rhee, Young Kyoung; Jin, Young-Ho

    2011-04-06

    Culinary use of the pungent spices has potential health benefits including a reduction in food intake. Pungent spices often contain ingredients that activate members of the transient receptor potential (TRP) family A1 and evoke pain from capsaicin-sensitive somatosensory neurons. TRPA1 channel have also been identified on cranial visceral afferent neurons but their distribution and functional contributions are poorly understood. Visceral vagal neurons transduce mechanical and chemical signals from peripheral organs to the nucleus tractus solitarii. Many capsaicin-sensitive vagal afferents participate in peripheral satiety signaling that includes cholecystokinin (CCK) sensitive neurons. To assess signaling, the TRPA1 selective agonist allyl isothiocyanate (AITC) was tested together with CCK and capsaicin (200nM), a TRPV1 specific agonist. In isolated nodose neurons, AITC (0.05-0.2mM) evoked concentration-dependent inward currents in 38% of the tested neurons. The TRPA1 specific antagonist HC-030031 (10μM) blocked AITC responses. TRPA1 responses were mixed across neurons that were capsaicin-sensitive and -insensitive. However CCK evoked inward currents only on capsaicin-sensitive neurons and 28% of the CCK-sensitive neurons expressed TRPA1. Our results indicate that TRPA1 is co-expressed with TRPV1 in CCK-sensitive nodose neurons. The findings indicate a potential mechanism by which spices can act within cranial visceral afferent pathways mediating satiety and contribute to the reduction of the food intake associated with spiced diets.

  4. Pain anticipatory phenomena in patients with central poststroke pain: a magnetoencephalography study.

    PubMed

    Gopalakrishnan, Raghavan; Burgess, Richard C; Lempka, Scott F; Gale, John T; Floden, Darlene P; Machado, Andre G

    2016-09-01

    Central poststroke pain (CPSP) is characterized by hemianesthesia associated with unrelenting chronic pain. The final pain experience stems from interactions between sensory, affective, and cognitive components of chronic pain. Hence, managing CPSP will require integrated approaches aimed not only at the sensory but also the affective-cognitive spheres. A better understanding of the brain's processing of pain anticipation is critical for the development of novel therapeutic approaches that target affective-cognitive networks and alleviate pain-related disability. We used magnetoencephalography (MEG) to characterize the neural substrates of pain anticipation in patients suffering from intractable CPSP. Simple visual cues evoked anticipation while patients awaited impending painful (PS), nonpainful (NPS), or no stimulus (NOS) to their nonaffected and affected extremities. MEG responses were studied at gradiometer level using event-related fields analysis and time-frequency oscillatory analysis upon source localization. On the nonaffected side, significantly greater responses were recorded during PS. PS (vs. NPS and NOS) exhibited significant parietal and frontal cortical activations in the beta and gamma bands, respectively, whereas NPS (vs. NOS) displayed greater activation in the orbitofrontal cortex. On the affected extremity, PS (vs. NPS) did not show significantly greater responses. These data suggest that anticipatory phenomena can modulate neural activity when painful stimuli are applied to the nonaffected extremity but not the affected extremity in CPSP patients. This dichotomy may stem from the chronic effects of pain on neural networks leading to habituation or saturation. Future clinically effective therapies will likely be associated with partial normalization of the neurophysiological correlates of pain anticipation.

  5. Human visceral leishmaniasis: a picture from Italy.

    PubMed

    Abdalmaula, Giuma Harun; Barbadoro, Pamela; Marigliano, Anna; Illuminati, Diego; Di Stanislao, Francesco; D'Errico, Marcello Mario; Prospero, Emilia

    2013-12-01

    The aim of our study was to describe the distribution of Visceral Leishmaniasis (VL) in Italy, focusing on HIV-infected patients, to estimate the burden of the disease and the public health actions that should be undertaken. A review of official notifications and hospitalization data has been performed. From 2006 to 2008, a total of 289 cases of VL were notified; the overall notification rate was 1.63/1,000,000 (95% CI 1.45-1.83). In total, 1192 VL-associated hospitalizations were detected, with a hospitalization rate of 6.71/1,000,000 (95% CI 6.34-7.10). For the age group "≤ 24 years", a statistically significant increase was detected (p<0.05). A total of 68.9% (n = 821) of hospitalizations were detected in HIV-positive patients. The geographic distribution of rates revealed a significant increase in the north-eastern area of the country. Our study confirms that the epidemiological pattern of VL is changing and that, in Italy, control measures and preventive strategies should be based on not only the official notification system but also hospital data. This would lead to the identification of areas of parasite spread and to the creation of awareness campaigns geared toward general practitioners in the affected areas. Easy case detection would allow for timely public health actions and strategies for the implementation of more effective interventions for reservoir control.

  6. Visceral-locomotory pistoning in crawling caterpillars.

    PubMed

    Simon, Michael A; Woods, William A; Serebrenik, Yevgeniy V; Simon, Sharotka M; van Griethuijsen, Linnea I; Socha, John J; Lee, Wah-Keat; Trimmer, Barry A

    2010-08-24

    Animals with an open coelom do not fully constrain internal tissues, and changes in tissue or organ position during body movements cannot be readily discerned from outside of the body. This complicates modeling of soft-bodied locomotion, because it obscures potentially important changes in the center of mass as a result of internal tissue movements. We used phase-contrast synchrotron X-ray imaging and transmission light microscopy to directly visualize internal soft-tissue movements in freely crawling caterpillars. Here we report a novel visceral-locomotory piston in crawling Manduca sexta larvae, in which the gut slides forward in advance of surrounding tissues. The initiation of gut sliding is synchronous with the start of the terminal prolegs' swing phase, suggesting that the animal's center of mass advances forward during the midabdominal prolegs' stance phase and is therefore decoupled from visible translations of the body. Based on synchrotron X-ray data and transmission light microscopy results, we present evidence for a two-body mechanical system with a nonlinear elastic gut that changes size and translates between the anterior and posterior of the animal. The proposed two-body system--the container and the contained--is unlike any form of legged locomotion previously reported and represents a new feature in our emerging understanding of crawling.

  7. Dietary and pharmacological treatment of abdominal pain in IBS.

    PubMed

    Camilleri, Michael; Boeckxstaens, Guy

    2017-02-23

    This review introduces the principles of visceral sensation and appraises the current approaches to management of visceral pain in functional GI diseases, principally IBS. These approaches include dietary measures including fibre supplementation, low fermentable oligosaccharides, disaccharides, monosaccharides and polyols diet, and pharmacological approaches such as antispasmodics, peppermint oil, antidepressants (tricyclic agents, selective serotonin reuptake inhibitors), 5-HT3 receptor antagonists (alosetron, ondansetron, ramosetron), non-absorbed antibiotic (rifaximin), secretagogues (lubiprostone, linaclotide), μ-opioid receptor (OR) and κ-OR agonist, δ-OR antagonist (eluxadoline), histamine H1 receptor antagonist (ebastine), neurokinin-2 receptor antagonist (ibodutant) and GABAergic agents (gabapentin and pregabalin). Efficacy and safety are discussed based on pivotal trials or published systematic reviews and meta-analysis, expressing ORs or relative risks and their 95% CIs. Potential new approaches may be based on recent insights on mucosal expression of genes, and microRNA and epigenetic markers in human biopsies and in animal models of visceral hypersensitivity.The objectives of this review are to appraise the physiology and anatomy of gut sensation and the efficacy in the relief of visceral pain (typically in IBS) of several classes of therapies. These include fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) and different classes of medications (box 1). Box 1Classes of pharmacological agents for visceral painAntidepressants (tricyclic agents, selective serotonin reuptake inhibitors)Peppermint oil5-HT3 receptor antagonists (alosetron, ondansetron, ramosetron)Non-absorbed antibiotic (rifaximin)Secretagogues (lubiprostone, linaclotide)μ-Opioid receptor (OR) and κ-OR agonist and δ-OR antagonist (eluxadoline)Histamine H1 receptor antagonist (ebastine)Neurokinin-2 receptor antagonist (ibodutant)GABAergic agents

  8. Mirror movements following cortical resection of polymicrogyria in a child with intractable epilepsy.

    PubMed

    RamachandranNair, Rajesh; Otsubo, Hiroshi; Ochi, Ayako; Rutka, James; Donner, Elizabeth J

    2006-02-01

    Mirror movements may be congenital or acquired. There are few reports of acquired mirror movements in pediatric patients. Further, mirror movements in children with epilepsy have rarely been reported. A 9-year old male, with intractable partial epilepsy resulting from polymicrogyria of the right hemisphere, underwent cortical resection of the right frontotemporoparietal region for a malformation of cortical development. He developed left hemiplegia and mirror movements in the left hand in the postoperative period. Four months after surgery, he remained seizure-free with mild residual left-sided hemiplegia and persistent mirror movements. Mechanisms postulated for mirror movements include aberrant pyramidal tract development and transcallosal inhibitory pathways. The latter mechanism might have contributed to the mirror movements observed in this child. This study is the first report of mirror movements following focal cortical resection for intractable epilepsy due to polymicrogyria.

  9. Cinacalcet hydrochloride relieves hypercalcemia in Japanese patients with parathyroid cancer and intractable primary hyperparathyroidism.

    PubMed

    Takeuchi, Yasuhiro; Takahashi, Shunsuke; Miura, Daishu; Katagiri, Makoto; Nakashima, Noriaki; Ohishi, Hiroko; Shimazaki, Ryutaro; Tominaga, Yoshihiro

    2016-11-21

    Pharmacological treatment of hypercalcemia is essential for patients with parathyroid carcinoma and intractable primary hyperparathyroidism (PHPT). Use of the calcimimetic cinacalcet hydrochloride (cinacalcet) is an option to treat such patients. We investigated the efficacy and safety of cinacalcet in Japanese patients with parathyroid carcinoma and intractable PHPT. Five Japanese patients with parathyroid carcinoma and two with intractable PHPT were enrolled in an open-label, single-arm study consisting of titration and maintenance phases. Cinacalcet doses were titrated until the albumin-corrected serum calcium concentration decreased to 10.0 mg/dL or less or until dose escalation was considered not necessary or feasible. Serum calcium concentration at the baseline was 12.1 ± 1.3 mg/dL (mean ± standard deviation; range 10.4-14.6 mg/dL) and decreased to 10.1 ± 1.6 mg/dL (range 8.6-13.3 mg/dL) at the end of the titration phase with cinacalcet at a dosage of up to 75 mg three times a day. At the end of the titration phase, at least a 1 mg/dL reduction in serum calcium concentration from the baseline was observed in five patients (three with carcinoma and two with PHPT), and it decreased to the normocalcemic range in five patients (three with carcinoma and two with PHPT). Common adverse events were nausea and vomiting. One patient discontinued participation in the study because of an adverse event, liver disorder. Cinacalcet effectively relieved hypercalcemia in 60% of the Japanese patients with parathyroid carcinoma and might be effective in those with intractable PHPT. The drug might be tolerable and safe at a dosage of at most 75 mg three times a day.

  10. Intractable colitis associated with chronic granulomatous disease in a young girl.

    PubMed

    Yaman, Aytaç; Kuloğlu, Zarife; Doğu, Figen; İkincioğulları, Aydan; Ensari, Arzu; Çiftçi, Ergin; Kansu, Aydan

    2015-01-01

    Chronic granulomatous disease (CGD) is an autosomal recessive or X-linked disorder caused by NADPH oxidase deficiency leading to an impaired ability of reactive superoxide anion and metabolite formation and recurring severe bacterial and fungal infections, with a high mortality rate. Diarrhea, colitis, ileus, perirectal abscess formation and anal fissures are reported gastrointestinal findings in these patients. We report a case of intractable colitis associated with CGD in a young girl.

  11. Percutaneous Cyanoacrylate Glue Injection into the Renal Pseudoaneurysm to Control Intractable Hematuria After Percutaneous Nephrolithotomy

    SciTech Connect

    Lal, Anupam Kumar, Ajay; Prakash, Mahesh; Singhal, Manphool; Agarwal, Mayank Mohan; Sarkar, Debansu; Khandelwal, Niranjan

    2009-07-15

    We report a case of a 43-year-old man who developed intractable hematuria after percutaneous nephrolithotomy. Angiography detected a pseudoaneurysm arising from the lower polar artery; however, embolization could not be performed because of unfavorable vascular anatomy. A percutaneous thrombin injection under ultrasound guidance initially controlled the bleeding, but hematuria subsequently recurred as a result of recanalization of the aneurysm. The case was successfully managed with ultrasound- and fluoroscopic-guided direct injection of cyanoacrylate glue into the pseudoaneurysm.

  12. Percutaneous cyanoacrylate glue injection into the renal pseudoaneurysm to control intractable hematuria after percutaneous nephrolithotomy.

    PubMed

    Lal, Anupam; Kumar, Ajay; Prakash, Mahesh; Singhal, Manphool; Agarwal, Mayank Mohan; Sarkar, Debansu; Khandelwal, Niranjan

    2009-07-01

    We report a case of a 43-year-old man who developed intractable hematuria after percutaneous nephrolithotomy. Angiography detected a pseudoaneurysm arising from the lower polar artery; however, embolization could not be performed because of unfavorable vascular anatomy. A percutaneous thrombin injection under ultrasound guidance initially controlled the bleeding, but hematuria subsequently recurred as a result of recanalization of the aneurysm. The case was successfully managed with ultrasound- and fluoroscopic-guided direct injection of cyanoacrylate glue into the pseudoaneurysm.

  13. Can We Break Intractability Using Randomization or the Average Case Setting?

    DTIC Science & Technology

    1993-09-30

    Although the physicists at Los Alamos did not know about computational complexity, they realized they could not solve certain problems. This led to the...fined below, this has led to proven (not conjectured) intractability and unsolvability results which we’ll describe in Section 2. Because of the basic...winthtinith inJtegration probles, randomizaein s rprncate. wormselortutio roat inteation, a ot- thskid) makes the computautional Rtandomizhatriponakmlt(ivaa

  14. Safety trial using the Leishmune vaccine against canine visceral leishmaniasis in Brazil.

    PubMed

    Parra, L E; Borja-Cabrera, G P; Santos, F N; Souza, L O P; Palatnik-de-Sousa, C B; Menz, I

    2007-03-08

    A group of 600 healthy and asymptomatic dogs from Brazilian canine visceral leishmaniasis endemic areas was vaccinated with three sc doses of Leishmune which is the industrialized formulation of the FML-saponin, recently licensed for commercialization in Brazil, which previously showed 76-80% vaccine efficacy against canine visceral leishmaniasis. Safety evaluation was performed for 14 days after each vaccine injection and disclosed transient reactions of local pain (40.87%), anorexia (20.48%), apathy (24.17%), local swelling reactions (15.90%), vomit (2.4%) and diarrhoea (1.5%). All effects showed significantly correlating declines, from the first to the third dose (p<0.0001). Most of the noticed reactions of pain (73%), anorexia (79%) and local swelling (84.7%) were mild. No significant differences between puppies and adults dogs were found in the number of adverse reactions. Adult dogs developed however, 94.5% of the small swelling reactions (<3 cm), and indicating that they are more resistant to the inflammatory response promoted by the saponins. No dead by anaphylaxis occurred, and only two dogs (0.1%) showed allergic reactions (facial oedema and itching) after the third dose. Transient alopecia on injection site occurred in only five poodles (0.28%) with total recovery and no need of treatment. All the mild adverse events in response to Leishmune injection were transient and disappeared before the injection of the following vaccine dose, confirming the tolerability of the vaccine. The Leishmune preparation was less haemolytic (HD(50)=180 microg/ml) than expected for a QS21 saponin-containing vaccine, indicating that its formulation with the FML antigen diminished the potential in vitro toxicity.

  15. Intractable itch relieved by 4-phenylbutyrate therapy in patients with progressive familial intrahepatic cholestasis type 1

    PubMed Central

    2014-01-01

    Background Progressive familial intrahepatic cholestasis type 1 (PFIC1), an inherited liver disease caused by mutations in ATP8B1, progresses to severe cholestasis with a sustained intractable itch. Currently, no effective therapy has been established for PFIC1. Decreased function of the bile salt export pump (BSEP) in hepatocytes is suggested to be responsible for the severe cholestasis observed in PFIC1. We found a previously unidentified pharmacological effect of 4-phenylbutyrate (4PB) that increases the expression and function of BSEP. Here, we tested 4PB therapy in three patients with PFIC1. Methods The therapeutic potency of 4PB in these patients was tested by oral administration of this drug with gradually increasing dosage (200, 350, and 500 mg/kg/day) for 6 months. Biochemical, histological, and clinical data were collected. Results 4PB therapy had no beneficial effect on the patients’ liver functions, as assessed by biochemical and histological analyses, despite an increase in hepatic BSEP expression. However, therapy with 4PB at a dosage of 350 or 500 mg/kg/day significantly relieved the intractable itch. Serum levels of potential pruritogens in cholestasis were much higher than the reference ranges during the 4PB therapy. Conclusions 4PB therapy may be a new medication for patients with intractable cholestatic pruritus and may improve quality of life for patients and their families. PMID:25022842

  16. Research Progress on the Role of ABC Transporters in the Drug Resistance Mechanism of Intractable Epilepsy

    PubMed Central

    Xiong, Jie; Mao, Ding-an; Liu, Li-qun

    2015-01-01

    The pathogenesis of intractable epilepsy is not fully clear. In recent years, both animal and clinical trials have shown that the expression of ATP-binding cassette (ABC) transporters is increased in patients with intractable epilepsy; additionally, epileptic seizures can lead to an increase in the number of sites that express ABC transporters. These findings suggest that ABC transporters play an important role in the drug resistance mechanism of epilepsy. ABC transporters can perform the funcions of a drug efflux pump, which can reduce the effective drug concentration at epilepsy lesions by reducing the permeability of the blood brain barrier to antiepileptic drugs, thus causing resistance to antiepileptic drugs. Given the important role of ABC transporters in refractory epilepsy drug resistance, antiepileptic drugs that are not substrates of ABC transporters were used to obtain ABC transporter inhibitors with strong specificity, high safety, and few side effects, making them suitable for long-term use; therefore, these drugs can be used for future clinical treatment of intractable epilepsy. PMID:26491660

  17. Intractable hiccup as the presenting symptom of cavernous hemangioma in the medulla oblongata: a case report and literature review.

    PubMed

    Lee, Kyung-Hwa; Moon, Kyung-Sub; Jung, Min-Young; Jung, Shin

    2014-06-01

    A case of intractable hiccup developed by cavernous hemangioma in the medulla oblongata is reported. There have been only five previously reported cases of medullary cavernoma that triggered intractable hiccup. The patient was a 28-year-old man who was presented with intractable hiccup for 15 days. It developed suddenly, then aggravated progressively and did not respond to any types of medication. On magnetic resonance images, a well-demarcated and non-enhancing mass with hemorrhagic changes was noted in the left medulla oblongata. Intraoperative findings showed that the lesion was fully embedded within the brain stem and pathology confirmed the diagnosis of cavernous hemangioma. The hiccup resolved completely after the operation. Based on the presumption that the medullary cavernoma may trigger intractable hiccup by displacing or compression the hiccup arc of the dorsolateral medulla, surgical excision can eliminate the symptoms, even in the case totally buried in brainstem.

  18. Low back pain - chronic

    MedlinePlus

    Nonspecific back pain; Backache - chronic; Lumbar pain - chronic; Pain - back - chronic; Chronic back pain - low ... Low back pain is common. Almost everyone has back pain at some time in their life. Often, the exact cause of ...

  19. Correlations between social-emotional feelings and anterior insula activity are independent from visceral states but influenced by culture

    PubMed Central

    Immordino-Yang, Mary Helen; Yang, Xiao-Fei; Damasio, Hanna

    2014-01-01

    The anterior insula (AI) maps visceral states and is active during emotional experiences, a functional confluence that is central to neurobiological accounts of feelings. Yet, it is unclear how AI activity correlates with feelings during social emotions, and whether this correlation may be influenced by culture, as studies correlating real-time AI activity with visceral states and feelings have focused on Western subjects feeling physical pain or basic disgust. Given psychological evidence that social-emotional feelings are cognitively constructed within cultural frames, we asked Chinese and American participants to report their feeling strength to admiration and compassion-inducing narratives during fMRI with simultaneous electrocardiogram recording. Trial-by-trial, cardiac arousal and feeling strength correlated with ventral and dorsal AI activity bilaterally but predicted different variance, suggesting that interoception and social-emotional feeling construction are concurrent but dissociable AI functions. Further, although the variance that correlated with cardiac arousal did not show cultural effects, the variance that correlated with feelings did. Feeling strength was especially associated with ventral AI activity (the autonomic modulatory sector) in the Chinese group but with dorsal AI activity (the visceral-somatosensory/cognitive sector) in an American group not of Asian descent. This cultural group difference held after controlling for posterior insula (PI) activity and was replicated. A bi-cultural East-Asian American group showed intermediate results. The findings help elucidate how the AI supports feelings and suggest that previous reports that dorsal AI activation reflects feeling strength are culture related. More broadly, the results suggest that the brain's ability to construct conscious experiences of social emotion is less closely tied to visceral processes than neurobiological models predict and at least partly open to cultural influence and

  20. Deep brain stimulation for chronic pain.

    PubMed

    Boccard, Sandra G J; Pereira, Erlick A C; Aziz, Tipu Z

    2015-10-01

    Deep brain stimulation (DBS) is a neurosurgical intervention popularised in movement disorders such as Parkinson's disease, and also reported to improve symptoms of epilepsy, Tourette's syndrome, obsessive compulsive disorders and cluster headache. Since the 1950s, DBS has been used as a treatment to relieve intractable pain of several aetiologies including post stroke pain, phantom limb pain, facial pain and brachial plexus avulsion. Several patient series have shown benefits in stimulating various brain areas, including the sensory thalamus (ventral posterior lateral and medial), the periaqueductal and periventricular grey, or, more recently, the anterior cingulate cortex. However, this technique remains "off label" in the USA as it does not have Federal Drug Administration approval. Consequently, only a small number of surgeons report DBS for pain using current technology and techniques and few regions approve it. Randomised, blinded and controlled clinical trials that may use novel trial methodologies are desirable to evaluate the efficacy of DBS in patients who are refractory to other therapies. New imaging techniques, including tractography, may help optimise electrode placement and clinical outcome.

  1. Neuropathic pain

    PubMed Central

    Colloca, Luana; Ludman, Taylor; Bouhassira, Didier; Baron, Ralf; Dickenson, Anthony H.; Yarnitsky, David; Freeman, Roy; Truini, Andrea; Attal, Nadine; Finnerup, Nanna B.; Eccleston, Christopher; Kalso, Eija; Bennett, David L.; Dworkin, Robert H.; Raja, Srinivasa N.

    2017-01-01

    Neuropathic pain is caused by a lesion or disease of the somatosensory system, including peripheral fibres (Aβ, Aδ and C fibres) and central neurons, and affects 7–10% of the general population. Multiple causes of neuropathic pain have been described and its incidence is likely to increase owing to the ageing global population, increased incidence of diabetes mellitus and improved survival from cancer after chemotherapy. Indeed, imbalances between excitatory and inhibitory somatosensory signalling, alterations in ion channels and variability in the way that pain messages are modulated in the central nervous system all have been implicated in neuropathic pain. The burden of chronic neuropathic pain seems to be related to the complexity of neuropathic symptoms, poor outcomes and difficult treatment decisions. Importantly, quality of life is impaired in patients with neuropathic pain owing to increased drug prescriptions and visits to health care providers, as well as the morbidity from the pain itself and the inciting disease. Despite challenges, progress in the understanding of the pathophysiology of neuropathic pain is spurring the development of new diagnostic procedures and personalized interventions, which emphasize the need for a multidisciplinary approach to the management of neuropathic pain. PMID:28205574

  2. Central pain.

    PubMed

    Singh, Supreet

    2014-12-01

    Questions from patients about pain conditions and analgesic pharmacotherapy and responses from authors are presented to help educate patients and make them more effective self-advocates. The topic addressed in this issue is central pain, a neuropathic pain syndrome caused by a lesion in the brain or spinal cord that sensitizes one's perception of pain. It is a debilitating condition caused by various diseases such as multiple sclerosis, strokes, spinal cord injuries, or brain tumors. Varied symptoms and the use of pharmacological medicines and nonpharmacological therapies will be addressed.

  3. Emerging roles of microRNAs in chronic pain.

    PubMed

    Sakai, Atsushi; Suzuki, Hidenori

    2014-11-01

    Chronic pain is a debilitating syndrome caused by a variety of disorders, and represents a major clinical problem because of the lack of adequate medication. In chronic pain, massive changes in gene expression are observed in a variety of cells, including neurons and glia, in the overall somatosensory system from the sensory ganglia to the higher central nervous system. The protein expressions of hundreds of genes are thought to be post-transcriptionally regulated by a single type of microRNA in a sequence-specific manner. Recently, critical roles of microRNAs in the pathophysiology of chronic pain have been emerging. Genome-wide screenings of microRNA expression changes have been reported in a variety of painful conditions, including peripheral nerve injury, inflammatory diseases, cancer and spinal cord injury. The data obtained suggest that a wide range of microRNAs change their expressions in individual pain conditions, although the pathological significance of individual microRNAs as causal mediators in distinct pain conditions remains to be revealed for a limited number of microRNAs. Insights into the roles of microRNAs in chronic pain will enhance our understanding of the pathophysiology of chronic pain and allow prompt therapeutic application of microRNA-related drugs against intractable persistent pain.

  4. Chronic Pain, Psychopathology, and DSM-5 Somatic Symptom Disorder.

    PubMed

    Katz, Joel; Rosenbloom, Brittany N; Fashler, Samantha

    2015-04-01

    Unlike acute pain that warns us of injury or disease, chronic or persistent pain serves no adaptive purpose. Though there is no agreed on definition of chronic pain, it is commonly referred to as pain that is without biological value, lasting longer than the typical healing time, not responsive to treatments based on specific remedies, and of a duration greater than 6 months. Chronic pain that is severe and intractable has detrimental consequences, including psychological distress, job loss, social isolation, and, not surprisingly, it is highly comorbid with depression and anxiety. Historically, pain without an apparent anatomical or neurophysiological origin was labelled as psychopathological. This approach is damaging to the patient and provider alike. It pollutes the therapeutic relationship by introducing an element of mutual distrust as well as implicit, if not explicit, blame. It is demoralizing to the patient who feels at fault, disbelieved, and alone. Moreover, many medically unexplained pains are now understood to involve an interplay between peripheral and central neurophysiological mechanisms that have gone awry. The new Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, somatic symptom disorder overpsychologizes people with chronic pain; it has low sensitivity and specificity, and it contributes to misdiagnosis, as well as unnecessary stigma. Adjustment disorder remains the most appropriate, accurate, and acceptable diagnosis for people who are overly concerned about their pain.

  5. Chronic Pain, Psychopathology, and DSM-5 Somatic Symptom Disorder

    PubMed Central

    Katz, Joel; Rosenbloom, Brittany N; Fashler, Samantha

    2015-01-01

    Unlike acute pain that warns us of injury or disease, chronic or persistent pain serves no adaptive purpose. Though there is no agreed on definition of chronic pain, it is commonly referred to as pain that is without biological value, lasting longer than the typical healing time, not responsive to treatments based on specific remedies, and of a duration greater than 6 months. Chronic pain that is severe and intractable has detrimental consequences, including psychological distress, job loss, social isolation, and, not surprisingly, it is highly comorbid with depression and anxiety. Historically, pain without an apparent anatomical or neurophysiological origin was labelled as psychopathological. This approach is damaging to the patient and provider alike. It pollutes the therapeutic relationship by introducing an element of mutual distrust as well as implicit, if not explicit, blame. It is demoralizing to the patient who feels at fault, disbelieved, and alone. Moreover, many medically unexplained pains are now understood to involve an interplay between peripheral and central neurophysiological mechanisms that have gone awry. The new Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, somatic symptom disorder overpsychologizes people with chronic pain; it has low sensitivity and specificity, and it contributes to misdiagnosis, as well as unnecessary stigma. Adjustment disorder remains the most appropriate, accurate, and acceptable diagnosis for people who are overly concerned about their pain. PMID:26174215

  6. Targeting Epigenetic Mechanisms for Chronic Pain: A Valid Approach for the Development of Novel Therapeutics.

    PubMed

    Ligon, Casey O; Moloney, Rachel D; Greenwood-Van Meerveld, Beverley

    2016-04-01

    Chronic pain is a multifaceted and complex condition. Broadly classified into somatic, visceral, or neuropathic pain, it is poorly managed despite its prevalence. Current drugs used for the treatment of chronic pain are limited by tolerance with long-term use, abuse potential, and multiple adverse side effects. The persistent nature of pain suggests that epigenetic machinery may be a critical factor driving chronic pain. In this review, we discuss the latest insights into epigenetic processes, including DNA methylation, histone modifications, and microRNAs, and we describe their involvement in the pathophysiology of chronic pain and whether epigenetic modifications could be applied as future therapeutic targets for chronic pain. We provide evidence from experimental models and translational research in human tissue that have enhanced our understanding of epigenetic processes mediating nociception, and we then speculate on the potential future use of more specific and selective agents that target epigenetic mechanisms to attenuate pain.

  7. [Facial pain].

    PubMed

    Makhinov, K A; Barinov, A N; Zhestikova, M G; Mingazova, L R; Parkhomenko, E V

    2015-01-01

    Diagnosis and treatment of facial pain is a problem for physicians of different specialties (neurologists, dentists, surgeons, oculists, otolaryngologists and psychiatrists). A classification of this pathology is far from ideal and an interdisciplinary comprehensive approach is needed. Current approaches to etiotropic, symptomatic and pathogenetic treatment of patients with most frequent variants of orofacial pain are presented.

  8. [Heel pain].

    PubMed

    Cizmár, I; Svizenská, I; Pilný, J; Repko, M; Ira, D

    2005-01-01

    Heel pain is quite frequent clinical symptom in our population. Successful therapy derives from the problem aetiology. The most frequent source of pain is the mechanical basis, both on dorsal and plantar side of calcaneum. Therapy includes a variety of procedures, from routine measures to surgical intervention.

  9. Treatment of pain symptoms in irritable bowel syndrome patients.

    PubMed

    Gupta, Vishal; Moshiree, Baharak; Verne, G Nicholas

    2004-10-01

    Irritable bowel syndrome represents a common gastrointestinal disorder that significantly impacts patients' lives. It is defined by Rome II criteria and characterized by abdominal pain and bloating associated with changes in bowel habit. Visceral hypersensitivity is currently considered a biological marker for the disease. Current therapeutic treatments include the use of fiber supplements, antidiarrheal agents, laxatives, antispasmodics, tricyclic antidepressants and serotonergic agents. Through a proper understanding of the diagnostic criteria, pathophysiology and treatment options, this disorder can be treated effectively in many patients.

  10. Disodium cromoglycate reverses colonic visceral hypersensitivity and influences colonic ion transport in a stress-sensitive rat strain.

    PubMed

    Carroll, Siobhan Yvonne; O'Mahony, Siobhain Mary; Grenham, Susan; Cryan, John Francis; Hyland, Niall Patrick

    2013-01-01

    The interface between psychiatry and stress-related gastrointestinal disorders (GI), such as irritable bowel syndrome (IBS), is well established, with anxiety and depression the most frequently occurring comorbid conditions. Moreover, stress-sensitive Wistar Kyoto (WKY) rats, which display anxiety- and depressive-like behaviors, exhibit GI disturbances akin to those observed in stress-related GI disorders. Additionally, there is mounting preclinical and clinical evidence implicating mast cells as significant contributors to the development of abdominal visceral pain in IBS. In this study we examined the effects of the rat connective tissue mast cell (CTMC) stabiliser, disodium cromoglycate (DSCG) on visceral hypersensitivity and colonic ion transport, and examined both colonic and peritoneal mast cells from stress-sensitive WKY rats. DSCG significantly decreased abdominal pain behaviors induced by colorectal distension in WKY animals independent of a reduction in colonic rat mast cell mediator release. We further demonstrated that mast cell-stimulated colonic ion transport was sensitive to inhibition by the mast cell stabiliser DSCG, an effect only observed in stress-sensitive rats. Moreover, CTMC-like mast cells were significantly increased in the colonic submucosa of WKY animals, and we observed a significant increase in the proportion of intermediate, or immature, peritoneal mast cells relative to control animals. Collectively our data further support a role for mast cells in the pathogenesis of stress-related GI disorders.

  11. Visceral organ cross-sensitization - an integrated perspective.

    PubMed

    Brumovsky, P R; Gebhart, G F

    2010-02-16

    Viscero-somatic referral and sensitization has been well documented clinically and widely investigated, whereas viscero-visceral referral and sensitization (termed cross-organ sensitization) has only recently received attention as important to visceral disease states. Because second order neurons in the CNS have been extensively shown to receive convergent input from different visceral organs, it has been assumed that cross-organ sensitization arises by the same convergence-projection mechanism as advanced for viscero-somatic referral and sensitization. However, increasing evidence also suggests participation of peripheral mechanisms to explain referral and sensitization. We briefly summarize behavioral, morphological and physiological support of and focus on potential mechanisms underlying cross-organ sensitization.

  12. Effects of tramadol on viscero-visceral hyperalgesia in a rat model of endometriosis plus ureteral calculosis.

    PubMed

    Lopopolo, Mariangela; Affaitati, Giannapia; Fabrizio, Alessandra; Massimini, Francesca; Lapenna, Domenico; Giamberardino, Maria Adele; Costantini, Raffaele

    2014-06-01

    The effects of tramadol versus placebo administration on behavioral indicators of ureteral pain, pelvic pain and referred lumbar muscle hyperalgesia were investigated in a rat model of viscero-visceral hyperalgesia from endometriosis plus ureteral calculosis (endo + stone). Fifty female Sprague-Dawley rats underwent surgical induction of endometriosis and, 2 weeks later, were randomly assigned to five groups (10 each), to be treated i.p., twice a day, with tramadol (0.625, 1.25, 2.5, or 5 mg/kg) or saline for 5 days (14-18th day postendometriosis; prestone treatment). On the 21st day, they underwent laparotomy for stone formation in the upper left ureter (dental cement injection). All were video-taped 24 h nonstop for 7 days before and 4 days after stone formation (14-25th day postendometriosis) to record ureteral and pelvic pain behaviors. Lumbar sensitivity (L1) was tested bilaterally, daily over the same period, by verifying presence/absence of vocalization upon muscle pinching at a predefined pressure (calibrated forceps). Additional fifty endo + stone rats underwent the same protocol, except that treatment was performed on 21st-25th day (poststone treatment). Tramadol vs. saline significantly reduced number and duration of ureteral crises, duration of pelvic behavior, and incidence of muscle hyperalgesia (P < 0.0001), with a dose-dependent effect. Prestone treatment was significantly more effective than poststone treatment for the 1.25 dose for all parameters and 2.5 dose for pelvic and muscle parameters (0.003 > P < 0.02). Tramadol, even at low doses, is thus highly protective against pain from 'viscero-visceral hyperalgesia' in endometriosis plus ureteral calculosis; it can represent a valid therapeutic approach in women with these comorbidities.

  13. Gender, variation in opioid receptor genes and sensitivity to experimental pain

    PubMed Central

    2013-01-01

    Background Pain tolerance is subject to considerable inter-individual variation, which may be influenced by a number of genetic and non-genetic factors. The mu, delta and kappa opioid receptors play a role in pain perception and are thought to mediate different pain modalities. The aim of this study was to explore associations between pain thresholds and gender and genetic variants in the three opioid receptor genes (OPRM, OPRD and OPRK). Experimental multi-modal pain data from previously published studies carried out in healthy Caucasian volunteers were used in order to limit the number of confounders to the study outcome. Data on thermal skin pain (n=36), muscle pressure pain (n=31) and mechanical visceral pain (n=50)) tolerance thresholds were included. Results Nineteen genetic polymorphisms were included in linear regression modeling. Males were found to tolerate higher thermal and muscle pressure pain than females (p=0.003 and 0.02). Thirty four percent of variability in thermal skin pain was accounted for by a model consisting of OPRK rs6473799 and gender. This finding was just outside significance when correction for multiple testing was applied. Variability in muscle pressure pain tolerance was associated with OPRK rs7016778 and rs7824175. These SNPs accounted for 43% of variability in muscle pressure pain sensitivity and these findings remained significant after adjustment for multiple testing. No association was found with mechanical visceral pain. Conclusion This is a preliminary and hypothesis generating study due to the relatively small study size. However, significant association between the opioid receptor genes and experimental pain sensitivity supports the influence of genetic variability in pain perception. These findings may be used to generate hypotheses for testing in larger clinical trials of patients with painful conditions. PMID:23570317

  14. Brain responses to expectation and delivery of a visceral stimulus in IBS reflect visceral sensitivity thresholds

    PubMed Central

    Larsson, MBO; Tillisch, K; Craig, A.D. (Bud); Engström, M; Labus, J; Naliboff, B; Lundberg, P; Ström, M; Mayer, EA; Walter, SA

    2011-01-01

    Background & aims Only a fraction of IBS patients show increased perceptual sensitivity to rectal distension, suggesting possible differences in processing and/or modulation of visceral afferent signals within this group. The aim was to identify brain mechanisms which may underlie these perceptual differences. Methods 44 women with IBS and 20 female healthy control subjects (HCs) were included. Symptom severity in IBS was determined by Severity Scoring System (IBS-SSS). Anxiety and depression symptoms were assessed using the Hospital anxiety & depression score (HAD). Blood oxygen level dependent (BOLD) signals were measured by functional Magnetic Resonance Imaging (fMRI) during expectation and delivery of high (45mmHg) and low (15mmHg) intensity rectal distensions. Perception thresholds to rectal distension were determined in the scanner. Brain imaging data from 18 normosensitive, 15 hypersensitive IBS patients and 18 HCs were compared. Results were reported significant if peak p-value ≤ 0.05 with family wise error correction in regions of interest. Results The two IBS subgroups were similar in age, symptom duration, psychological symptoms and IBS symptom severity. While brain responses to distension were similar in normosensitive patients and HCs, hypersensitive IBS demonstrated greater activation of insula and reduced deactivation in pregenual anterior cingulate cortex during noxious rectal distensions, compared to both HCs and normosensitive IBS. During expectation of rectal distension, normosensitive IBS had more activation in right hippocampus than HCs. Conclusions Despite similarities in symptoms, hyper- and normosensitive IBS patients differed substantially in cerebral response to standardized rectal distensions and their expectation, consistent with differences in ascending visceral afferent input. PMID:22108191

  15. Pediatric visceral leishmaniasis in northwest of Iran.

    PubMed

    Abdinia, Babak; Oliaei-Motlagh, Mohammad; Teimouri-Dereshki, Amir

    2016-11-01

    Leishmaniasis is one of the major health problems in Iran. Although the incidence of visceral leishmaniasis (VL) is reported almost everywhere, the northwestern Iran is one of the major endemic regions.To do this study, clinical, laboratory as well as disease characteristics of children admitted to Children Cure and Health Hospital, Tabriz University of Medical Sciences, were examined as the reference hospital for the treatment of VL in northwestern Iran.In this study, 156 children hospitalized in a pediatric hospital from 2000 to 2015 for VL were included. Gender, age, anemia, thrombocytopenia, increase in the erythrocyte sedimentation rate (ESR), alanine transaminase (SGPT), and aspartate transaminase (SGOT), major clinical manifestations such as fever, splenomegaly, hepatomegaly, treatment type, and the disease were studied.Among 156 patients examined in this study, 88 (56.41%) and 68 (43.59%) participants were male and female, respectively. The minimum and maximum ages of the infection were 4.5 months and 6 years, respectively. The mean age of the infected children was 17.94 months. Fever (94.24%) and splenomegaly (86.53%) were the most common symptoms of this disease among children. In addition, 49 (31.41%), 64 (41.02%), 18 (11.53%), 33 (21.15%), and 40 (25.64%) participants had leukopenia, hemoglobin count below 8, ESR above 100, ESR above 60, and platelets below 100,000, respectively. Moreover, 39 (25%) and 17 (10.89%) patients had high aspartate transaminase (AST) and alanine transaminase (ALT). Also, 96.2% of the participants responded to the treatment with glucantime. The rate of mortality in this study was 3.2%.Clinically, almost all children had fever and splenomegaly at the onset of the disease. In addition, hepatic involvement was observed in all cases of mortality, cases with a lack of initial response, and those in need of auxiliary medication. Hepatic involvement appears to be related to the prognosis of the disease. In our study, bone marrow

  16. Functional dyspepsia: the role of visceral hypersensitivity in its pathogenesis.

    PubMed

    Keohane, John; Quigley, Eamonn M M

    2006-05-07

    Functional, or non-ulcer, dyspepsia (FD) is one of the most common reasons for referral to gastroenterologists. It is associated with significant morbidity and impaired quality of life. Many authorities believe that functional dyspepsia and irritable bowel syndrome represent part of the spectrum of the same disease process. The pathophysiology of FD remains unclear but several theories have been proposed including visceral hypersensitivity, gastric motor dysfunction, Helicobacter pylori infection and psychosocial factors. In this review, we look at the evidence, to date, for the role of visceral hypersensitivity in the aetiology of FD.

  17. Spontaneous dissections of multiple visceral arteries: an extremely rare case

    PubMed Central

    Le, Trong Binh; Hong, Kee Chun; Cho, Soon Gu; Park, Keun-Myoung

    2017-01-01

    Spontaneous dissections of visceral arteries without aortic involvement are very rare. The etiologies of these entities are unclear and their clinical managements remain controversial. We report a case of spontaneous multiple dissections affecting 4 visceral arteries including the superior mesenteric artery, the celiac artery and the bilateral renal arteries. The patient was managed conservatively and endovascularly. The clinical manifestation markedly improved and laboratory tests returned to normal limits within 1 week. The regular follow-up suggested a good clinical and radiological outcome until 84 months. PMID:28382296

  18. Animal reservoirs for visceral leishmaniasis in densely populated urban areas.

    PubMed

    Diniz, Soraia A; Silva, Fabiana L; Carvalho Neta, Alcina C; Bueno, Regina; Guerra, Rita M S N C; Abreu-Silva, Ana L; Santos, Renato L

    2008-02-01

    Leishmaniasis is a zoonotic disease of major public health and veterinary importance, affecting 88 countries with up to 2 million cases per year. This review emphasizes the animal reservoirs and spreading of visceral leishmaniasis (VL) in urban areas, particularly in two Brazilian metropolitan areas, namely São Luis and Belo Horizonte, where the disease has become endemic in the past few years. Urbanization of visceral leishmaniasis in Brazil during the last decades has created favorable epidemiological conditions for maintenance of the disease, with dense human populations sharing a tropical environment with abundant populations of the mammalian reservoir and the invertebrate vector, facilitating transmission of the disease.

  19. Interventional modalities to treat cancer-related pain.

    PubMed

    Moeschler, Susan M; Rosenberg, Casandra; Trainor, Drew; Rho, Richard H; Mauck, W David

    2014-12-01

    Cancer-related pain is a significant cause of morbidity in those affected by both primary and metastatic disease. Although oral, transdermal, and parenteral opioid medications are an integral part of the World Health Organization's analgesic ladder, their use may be limited by side effects. Fortunately, there are advanced interventional pain management strategies effective in reducing pain in the cancer patient while mitigating the aforementioned side effects. Celiac plexus blocks and neurolysis have been proven effective in treating cancers of the abdominal viscera (ie, pancreas). Transversus abdominis plane blocks, neurolysis, and catheter placement can be used to treat cancer pain associated with the abdominal wall. Peripheral nerve blocks and catheter placement at the brachial and lumbosacral plexus or peripheral nerves treat cancer pain associated with the upper and lower limbs, whereas paravertebral and intercostal blocks treat cancer pain associated with the chest wall and ribs. Finally, alternate drug delivery methods such as intrathecal drug delivery systems concentrate medication at central opioid receptors without affecting the peripheral receptors implicated in unwanted side effects. This article provides an overview of these interventions, including indications, contraindications, and potential complications of advanced interventional pain management options available for the treatment of intractable cancer-related pain.

  20. Water-cooled radiofrequency neuroablation for sacroiliac joint dysfunctional pain

    PubMed Central

    Biswas, Binay Kumar; Dey, Samarjit; Biswas, Saumya; Mohan, Varinder Kumar

    2016-01-01

    Sacroiliac (SI) joint dysfunction is a common source of chronic low-back pain. Recent evidences from different parts of the world suggest that cooled radiofrequency (RF) neuroablation of sacral nerves supplying SI joints has superior pain alleviating properties than available existing treatment options for SI joint dysfunctional pain. A 35-year-old male had intractable bilateral SI joint pain (numeric rating scale [NRS] – 9/10) with poor treatment response to intra-articular steroid therapy. Bilateral water cooled = RF was applied for neuroablation of nerves supplying both SI joints. Postprocedure pain intensity was 5/10 and after 7 days it was 2/10. On 18th-month follow-up, he is pain free except for mild pain (NRS 2/10) on occasional extreme twisting of the back. This case attempts to highlight that sacral neuroablation based on cooled RF technique can be a long lasting remedial option for chronic SI joint pain unresponsive to conventional treatment. PMID:28096589

  1. Water-cooled radiofrequency neuroablation for sacroiliac joint dysfunctional pain.

    PubMed

    Biswas, Binay Kumar; Dey, Samarjit; Biswas, Saumya; Mohan, Varinder Kumar

    2016-01-01

    Sacroiliac (SI) joint dysfunction is a common source of chronic low-back pain. Recent evidences from different parts of the world suggest that cooled radiofrequency (RF) neuroablation of sacral nerves supplying SI joints has superior pain alleviating properties than available existing treatment options for SI joint dysfunctional pain. A 35-year-old male had intractable bilateral SI joint pain (numeric rating scale [NRS] - 9/10) with poor treatment response to intra-articular steroid therapy. Bilateral water cooled = RF was applied for neuroablation of nerves supplying both SI joints. Postprocedure pain intensity was 5/10 and after 7 days it was 2/10. On 18(th)-month follow-up, he is pain free except for mild pain (NRS 2/10) on occasional extreme twisting of the back. This case attempts to highlight that sacral neuroablation based on cooled RF technique can be a long lasting remedial option for chronic SI joint pain unresponsive to conventional treatment.

  2. Cannabinoids in the management of difficult to treat pain.

    PubMed

    Russo, Ethan B

    2008-02-01

    This article reviews recent research on cannabinoid analgesia via the endocannabinoid system and non-receptor mechanisms, as well as randomized clinical trials employing cannabinoids in pain treatment. Tetrahydrocannabinol (THC, Marinol((R))) and nabilone (Cesamet((R))) are currently approved in the United States and other countries, but not for pain indications. Other synthetic cannabinoids, such as ajulemic acid, are in development. Crude herbal cannabis remains illegal in most jurisdictions but is also under investigation. Sativex((R)), a cannabis derived oromucosal spray containing equal proportions of THC (partial CB(1) receptor agonist ) and cannabidiol (CBD, a non-euphoriant, anti-inflammatory analgesic with CB(1) receptor antagonist and endocannabinoid modulating effects) was approved in Canada in 2005 for treatment of central neuropathic pain in multiple sclerosis, and in 2007 for intractable cancer pain. Numerous randomized clinical trials have demonstrated safety and efficacy for Sativex in central and peripheral neuropathic pain, rheumatoid arthritis and cancer pain. An Investigational New Drug application to conduct advanced clinical trials for cancer pain was approved by the US FDA in January 2006. Cannabinoid analgesics have generally been well tolerated in clinical trials with acceptable adverse event profiles. Their adjunctive addition to the pharmacological armamentarium for treatment of pain shows great promise.

  3. Cannabinoids in the management of difficult to treat pain

    PubMed Central

    Russo, Ethan B

    2008-01-01

    This article reviews recent research on cannabinoid analgesia via the endocannabinoid system and non-receptor mechanisms, as well as randomized clinical trials employing cannabinoids in pain treatment. Tetrahydrocannabinol (THC, Marinol®) and nabilone (Cesamet®) are currently approved in the United States and other countries, but not for pain indications. Other synthetic cannabinoids, such as ajulemic acid, are in development. Crude herbal cannabis remains illegal in most jurisdictions but is also under investigation. Sativex®, a cannabis derived oromucosal spray containing equal proportions of THC (partial CB1 receptor agonist ) and cannabidiol (CBD, a non-euphoriant, anti-inflammatory analgesic with CB1 receptor antagonist and endocannabinoid modulating effects) was approved in Canada in 2005 for treatment of central neuropathic pain in multiple sclerosis, and in 2007 for intractable cancer pain. Numerous randomized clinical trials have demonstrated safety and efficacy for Sativex in central and peripheral neuropathic pain, rheumatoid arthritis and cancer pain. An Investigational New Drug application to conduct advanced clinical trials for cancer pain was approved by the US FDA in January 2006. Cannabinoid analgesics have generally been well tolerated in clinical trials with acceptable adverse event profiles. Their adjunctive addition to the pharmacological armamentarium for treatment of pain shows great promise. PMID:18728714

  4. [Musculoskeletal pain].

    PubMed

    Casser, H-R; Schaible, H-G

    2015-10-01

    Among the clinically relevant pain conditions, pain in the musculoskeletal system is most frequent. This article reports extensive epidemiological data on musculoskeletal system pain in Germany and worldwide. Since back pain is most frequent, the diagnostics and therapeutic algorithms of acute, recurring, and chronic lower back pain in Germany will be particularly addressed. The importance of the physiologic-organic, the cognitive-emotional, the behavioral, and the social level to diagnostics and treatment will be discussed. We will also focus on osteoarthritic pain and address its epidemiology, clinical importance, and significance for the health care system. This article will list some reasons why the musculoskeletal system in particular is frequently the site of chronic pain. The authors believe that these reasons are to be sought in the complex structures of the musculoskeletal system; in the particular sensitivity of the deep somatic nociceptive system for long-term sensitization processes, as well as the ensuing nervous system reactions; and in the interactions between the nervous and immune systems. The article will give some insights into the research carried out on this topic in Germany.

  5. Fetal pain?

    PubMed

    Vanhatalo, S; van Nieuwenhuizen, O

    2000-05-01

    During the last few years a vivid debate, both scientifically and emotionally, has risen in the medical literature as to whether a fetus is able to feel pain during abortion or intrauterine surgery. This debate has mainly been inspired by the demonstration of various hormonal or motor reactions to noxious stimuli at very early stages of fetal development. The aims of this paper are to review the literature on development of the pain system in the fetus, and to speculate about the relationship between "sensing" as opposed to "feeling" pain and the number of reactions associated with painful stimuli. While a cortical processing of pain theoretically becomes possible after development of the thalamo-cortical connections in the 26th week of gestation, noxious stimuli may trigger complex reflex reactions much earlier. However, more important than possible painfulness is the fact that the noxious stimuli, by triggering stress responses, most likely affect the development of an individual at very early stages. Hence, it is not reasonable to speculate on the possible emotional experiences of pain in fetuses or premature babies. A clinically relevant aim is rather to avoid and/or treat any possibly noxious stimuli, and thereby prevent their potential adverse effects on the subsequent development.

  6. Treatment of chronic regional pain syndrome type 1 with palmitoylethanolamide and topical ketamine cream: modulation of nonneuronal cells

    PubMed Central

    Keppel Hesselink, Jan M; Kopsky, David J

    2013-01-01

    Chronic regional pain syndrome (CRPS) can be intractable to treat and patients sometimes suffer for many years. Therefore, new treatment strategies are needed to alleviate symptoms in CRPS patients. This case report describes a patient suffering from intractable CRPS type 1 for 13 years. Due to her swollen painful feet and left knee she is wheelchair-bound. The combination of palmitoylethanolamide and ketamine 10% cream reduced her pain by more than 50% after 1 month of treatment, and a marked reduction in swelling and skin discoloration was noticed. Furthermore, she could walk independently again and she experienced no side effects. Thus, palmitoylethanolamide and topical ketamine could be a combination therapy option for treating CRPS patients. PMID:23658493

  7. Antinociceptive effect of botulinum toxin type A on experimental abdominal pain.

    PubMed

    Drinovac, Višnja; Bach-Rojecky, Lidija; Babić, Ana; Lacković, Zdravko

    2014-12-15

    Visceral pain, especially in the abdominal region, represents one of the most common types of pain. Its chronic form is usually very hard to treat by conventional analgesic agents and adjuvants. We investigated the antinociceptive effect of botulinum toxin type A (BTX-A) in male Wistar rats in two models of visceral pain: peritonitis induced by intraperitoneal injection of 1% acetic acid and colitis induced by intracolonic instillation of 0.1% capsaicin. Pain was measured as the number of abdominal writhes. Additionally, referred mechanical sensitivity in the ventral abdominal area was evaluated by von Frey test and the extent of spinal c-Fos expression was immunohistochemically examined. BTX-A significantly reduced the number of abdominal writhes in both models of visceral pain after intrathecal application in a dose of 2 U/kg. In the experimental colitis model, BTX-A (2 U/kg) reduced both referred mechanical allodynia and c-Fos expression in the dorsal horn of the spinal cord (S2/S3 segments). In contrast to intrathecal administration, BTX-A (2 U/kg) administered into the cisterna magna had no effect on pain suggesting that the primary site of its action is a spinal cord.

  8. Resting-State Functional MR Imaging for Determining Language Laterality in Intractable Epilepsy.

    PubMed

    DeSalvo, Matthew N; Tanaka, Naoaki; Douw, Linda; Leveroni, Catherine L; Buchbinder, Bradley R; Greve, Douglas N; Stufflebeam, Steven M

    2016-10-01

    Purpose To measure the accuracy of resting-state functional magnetic resonance (MR) imaging in determining hemispheric language dominance in patients with medically intractable focal epilepsies against the results of an intracarotid amobarbital procedure (IAP). Materials and Methods This study was approved by the institutional review board, and all subjects gave signed informed consent. Data in 23 patients with medically intractable focal epilepsy were retrospectively analyzed. All 23 patients were candidates for epilepsy surgery and underwent both IAP and resting-state functional MR imaging as part of presurgical evaluation. Language dominance was determined from functional MR imaging data by calculating a laterality index (LI) after using independent component analysis. The accuracy of this method was assessed against that of IAP by using a variety of thresholds. Sensitivity and specificity were calculated by using leave-one-out cross validation. Spatial maps of language components were qualitatively compared among each hemispheric language dominance group. Results Measurement of hemispheric language dominance with resting-state functional MR imaging was highly concordant with IAP results, with up to 96% (22 of 23) accuracy, 96% (22 of 23) sensitivity, and 96% (22 of 23) specificity. Composite language component maps in patients with typical language laterality consistently included classic language areas such as the inferior frontal gyrus, the posterior superior temporal gyrus, and the inferior parietal lobule, while those of patients with atypical language laterality also included non-classical language areas such as the superior and middle frontal gyri, the insula, and the occipital cortex. Conclusion Resting-state functional MR imaging can be used to measure language laterality in patients with medically intractable focal epilepsy. (©) RSNA, 2016 Online supplemental material is available for this article.

  9. Cinacalcet Reduces Serum Calcium Concentrations in Patients with Intractable Primary Hyperparathyroidism

    PubMed Central

    Marcocci, Claudio; Chanson, Philippe; Shoback, Dolores; Bilezikian, John; Fernandez-Cruz, Laureano; Orgiazzi, Jacques; Henzen, Christoph; Cheng, Sunfa; Sterling, Lulu Ren; Lu, John; Peacock, Munro

    2009-01-01

    Context: Patients with persistent primary hyperparathyroidism (PHPT) after parathyroidectomy or with contraindications to parathyroidectomy often require chronic treatment for hypercalcemia. Objective: The objective of the study was to assess the ability of the calcimimetic, cinacalcet, to reduce serum calcium in patients with intractable PHPT. Design: This was an open-label, single-arm study comprising a titration phase of variable duration (2–16 wk) and a maintenance phase of up to 136 wk. Setting: The study was conducted at 23 centers in Europe, the United States, and Canada. Patients: The study included 17 patients with intractable PHPT and serum calcium greater than 12.5 mg/dl (3.1 mmol/liter). Intervention: During the titration phase, cinacalcet dosages were titrated every 2 wk (30 mg twice daily to 90 mg four times daily) for 16 wk until serum calcium was 10 mg/dl or less (2.5 mmol/liter). If serum calcium increased during the maintenance phase, additional increases in the cinacalcet dose were permitted. Main Outcome Measure: The primary end point was the proportion of patients experiencing a reduction in serum calcium of 1 mg/dl or greater (0.25 mmol/liter) at the end of the titration phase. Results: Mean ± sd baseline serum calcium was 12.7 ± 0.8 mg/dl (3.2 ± 0.2 mmol/liter). At the end of titration, a 1 mg/dl or greater reduction in serum calcium was achieved in 15 patients (88%). Fifteen patients (88%) experienced treatment-related adverse events, none of which were serious. The most common adverse events were nausea, vomiting, and paresthesias. Conclusions: In patients with intractable PHPT, cinacalcet reduces serum calcium, is generally well tolerated, and has the potential to fulfill an unmet medical need. PMID:19470620

  10. What a Pain! Kids and Growing Pains

    MedlinePlus

    ... What Happens in the Operating Room? What a Pain! Kids and Growing Pains KidsHealth > For Kids > What a Pain! Kids and ... something doctors call growing pains . What Are Growing Pains? Growing pains aren't a disease. You probably ...

  11. What a Pain! Kids and Growing Pains

    MedlinePlus

    ... dientes Video: Getting an X-ray What a Pain! Kids and Growing Pains KidsHealth > For Kids > What a Pain! Kids and ... something doctors call growing pains . What Are Growing Pains? Growing pains aren't a disease. You probably ...

  12. From psychosurgery to neuromodulation: deep brain stimulation for intractable Tourette syndrome.

    PubMed

    Neuner, Irene; Podoll, Klaus; Janouschek, Hildegard; Michel, Tanja M; Sheldrick, Abigail J; Schneider, Frank

    2009-01-01

    Tourette syndrome is a neuropsychiatric disorder characterized by motor and vocal tics. It is often associated with depression, obsessive-compulsive symptoms, self-injurious behaviour and attention deficit-hyperactivity disorder (ADHD). In intractable patients, neuromodulation using deep brain stimulation (DBS) has widely replaced psychosurgery. Three different key structures are defined for DBS, the medial portion of the thalamus, the globus pallidus internus and the anterior limb of the internal capsule/nucleus accumbens. This is a comprehensive overview on the effect of DBS on motor and non-motor symptoms using different case series and two larger studies.

  13. Albumin liver dialysis as pregnancy-saving procedure in cholestatic liver disease and intractable pruritus.

    PubMed

    Lemoine, Maud; Revaux, Aurelie; Francoz, Claire; Ducarme, Guillaume; Brechignac, Sabine; Jacquemin, Emmanuel; Uzan, Michele; Ganne-Carrie, Nathalie

    2008-11-14

    Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a rare cholestatic liver disease. Such liver disease can get worse by female hormone disorder. Albumin dialysis or Molecular Adsorbent Recirculating System (MARS) has been reported to reverse severe cholestasis-linked pruritus. Here, we report the first use of MARS during a spontaneous pregnancy and its successful outcome in a patient with PFIC3 and intractable pruritus. Albumin dialysis could be considered as a pregnancy-saving procedure in pregnant women with severe cholestasis and refractory pruritus.

  14. A general resolution of intractable problems in polynomial time through DNA Computing.

    PubMed

    Sanches, C A A; Soma, N Y

    2016-12-01

    Based on a set of known biological operations, a general resolution of intractable problems in polynomial time through DNA Computing is presented. This scheme has been applied to solve two NP-Hard problems (Minimization of Open Stacks Problem and Matrix Bandwidth Minimization Problem) and three co-NP-Complete problems (associated with Hamiltonian Path, Traveling Salesman and Hamiltonian Circuit), which have not been solved with this model. Conclusions and open questions concerning the computational capacity of this model are presented, and research topics are suggested.

  15. Chronic Pelvic Pain

    MedlinePlus

    ... Events Advocacy For Patients About ACOG Chronic Pelvic Pain Home For Patients Search FAQs Chronic Pelvic Pain ... Pain FAQ099, August 2011 PDF Format Chronic Pelvic Pain Gynecologic Problems What is chronic pelvic pain? What ...

  16. Chronic pain - resources

    MedlinePlus

    Pain - resources; Resources - chronic pain ... The following organizations are good resources for information on chronic pain: American Chronic Pain Association -- theacpa.org National Fibromyalgia and Chronic Pain Association -- www.fmcpaware.org National ...

  17. Pain Management

    MedlinePlus

    ... analgesia, identify new targets for analgesic drugs, and test the efficacy and adverse reactions of newly developed or currently used drugs to treat pain. Researchers are currently using these technologies to discover the mechanisms by which drugs such ...

  18. Urination - painful

    MedlinePlus

    ... and vagina Other causes of painful urination include: Interstitial cystitis Prostate infection ( prostatitis ) Radiation cystitis - damage to the ... Editorial team. Related MedlinePlus Health Topics Bladder ... Cystitis Prostate Diseases Sexually Transmitted Diseases Urinary Tract Infections ...

  19. Joint pain

    MedlinePlus

    ... that may be done include: CBC or blood differential C-reactive protein Joint x-ray Sedimentation rate ... chap 256. Schaible H-G. Joint pain: basic mechanisms. In: McMahon SB, Koltzenburg M, Tracey I, Turk ...

  20. Testicle pain

    MedlinePlus

    ... be caused by a hernia or kidney stone. Testicular cancer is almost always painless. But any testicle lump ... Read More Abdominal pain Scrotum Testes Testicle lump Testicular cancer Testicular torsion Review Date 8/31/2015 Updated ...

  1. Chest Pain

    MedlinePlus

    ... causes Chest pain can also be caused by: Panic attack. If you have periods of intense fear accompanied ... fear of dying, you may be experiencing a panic attack. Shingles. Caused by a reactivation of the chickenpox ...

  2. Chronic Pain

    MedlinePlus

    ... Strategy Current Research Research Funded by NINDS Basic Neuroscience Clinical Research Translational Research Research at NINDS Focus ... pain has done. Scientists believe that advances in neuroscience will lead to more and better treatments for ...

  3. [Abdominal pain].

    PubMed

    Gschossmann, J M; Holtmann, G; Netzer, P; Essig, M; Balsiger, B M; Scheurer, U

    2005-10-01

    Abdominal pain can result from a variety of different intra- and extra-abdominal disorders. Given the wide variety of etiological triggers for this pain, the primary task during the first stage of the diagnostic work-up is to determine as soon as possible the underlying cause and the degree of emergency. The aim of this evaluation is to adapt the therapeutic measures which are necessary for a causal treatment to the individual situation. Contrary to somatic causes of abdominal pain, the availability of such a causal therapy for functional bowel disorders is still very limited. Given this dilemma, the therapeutic focus of abdominal pain associated with these functional syndromes has to be placed on symptom-oriented treatment.

  4. Fetal pain.

    PubMed

    Rokyta, Richard

    2008-12-01

    The fetus reacts to nociceptive stimulations through different motor, autonomic, vegetative, hormonal, and metabolic changes relatively early in the gestation period. With respect to the fact that the modulatory system does not yet exist, the first reactions are purely reflexive and without connection to the type of stimulus. While the fetal nervous system is able to react through protective reflexes to potentially harmful stimuli, there is no accurate evidence concerning pain sensations in this early period. Cortical processes occur only after thalamocortical connections and pathways have been completed at the 26th gestational week. Harmful (painful) stimuli, especially in fetuses have an adverse effect on the development of humans regardless of the processes in brain. Moreover, pain activates a number of subcortical mechanisms and a wide spectrum of stress responses influence the maturation of thalamocortical pathways and other cortical activation which are very important in pain processing.

  5. Breast pain

    MedlinePlus

    ... chocolate in your diet helps reduce breast pain. Vitamin E, thiamine, magnesium, and evening primrose oil are not harmful, but most studies have not shown any benefit. Talk to your health care provider before starting ...

  6. Role of Neuromodulation and Optogenetic Manipulation in Pain Treatment

    PubMed Central

    Liu, Sufang; Li, Changsheng; Xing, Ying; Wang, Yanqing; Tao, Feng

    2016-01-01

    Neuromodulation, including invasive and non-invasive stimulation, has been used to 
treat intractable chronic pain. However, the mechanisms by which neuromodulation produces antinociceptive effect still remain uncertain. Optogenetic manipulation, a recently developed novel approach, has already proven its value to clinicians by providing new insights into mechanisms of current clinical neuromodulation methods as well as pathophysiology of nervous system diseases at the circuit level. Here, we discuss the principles of two neuromodulation methods (deep brain stimulation and motor cortex stimulation) and their applications in pain treatment. More important, we summarize the new information from recent studies regarding optogenetic manipulation in neuroscience research and its potential utility in pain study. PMID:26935535

  7. Intrathecal therapy for chronic pain: current trends and future needs.

    PubMed

    Hayek, Salim M; Hanes, Michael C

    2014-01-01

    The management of chronic pain continues to pose many challenges to healthcare providers. Intrathecal drug delivery systems (IDDS) provide an effective therapy for patients suffering from chronic pain intractable to medical management. However, the clinical growth of intrathecal therapy continues to face many challenges, and is likely underutilized secondary to its high-complexity and limited reimbursement. The clinical utility of IDDS remains limited by lack of prospective randomized, placebo-controlled studies. In addition, there remains a need to enhance physician knowledge on the pharmacodynamics and pharmacokinetics of intrathecal drug delivery and promote further research into this field and drug delivery modalities. The purpose of this article is to provide a comprehensive review of the determinants of successful intrathecal drug delivery with an emphasis on its use in noncancer pain.

  8. Modulation of enteric neurons by interleukin-6 and corticotropin-releasing factor contributes to visceral hypersensitivity and altered colonic motility in a rat model of irritable bowel syndrome

    PubMed Central

    Buckley, Maria M; O'Halloran, Ken D; Rae, Mark G; Dinan, Timothy G; O'Malley, Dervla

    2014-01-01

    Abstract The search for effective therapeutic strategies for irritable bowel syndrome (IBS) is hampered by an incomplete understanding of its underlying pathophysiology. Stress and altered plasma cytokine profiles indicative of immune activation are characteristic of the disorder. The neuromodulatory effects of interleukin-6 (IL-6) and corticotropin-releasing factor receptor (CRFR) 1 in visceral pain and stress-induced defecation in the Wistar Kyoto (WKY) rat model of IBS were investigated. Sprague Dawley and WKY rats were administered anti-IL-6 receptor antibodies (xIL-6R, 0.5 mg kg−1 i.p) with or without the CRFR1 antagonist antalarmin (10 mg kg−1 i.p). Post-intervention, the pain threshold to colorectal distension and stress-induced faecal output were compared and changes in colonic mucosal protein expression were investigated. The neuro-stimulatory effects of IBS plasma on the myenteric plexus is mediated by IL-6, IL-8 and CRF. The stimulatory effects of these soluble factors on myenteric neuron excitability and colonic contractility were additive. Moreover, inhibition of IL-6 and CRF1 receptors in vivo in the WKY IBS rat model normalized stress-induced defecation (P < 0.01) and visceral pain sensitivity (P < 0.001) with associated changes in protein expression of the tight junction proteins occludin and claudin 2, the visceral pain-associated T-type calcium channel CaV3.2 and intracellular signalling molecules STAT3, SOCS3 and ERK1/2. These studies demonstrate the additive effects of immune and stress factors on myenteric neuronal excitability. Moreover, combined targeting of peripheral IL-6 and CRF1 receptors is effective in alleviating IBS-like symptoms in the WKY rat. Thus, crosstalk between stress and immune factors during IBS flares may underlie symptom exacerbation. PMID:25260633

  9. Pain Relief and Health-Related Quality-of-Life Improvement After Microsurgical Decompression of Entrapped Peripheral Nerves in Patients With Painful Diabetic Peripheral Neuropathy.

    PubMed

    Yang, Wenqiang; Guo, Zhuangli; Yu, Yanbing; Xu, Jun; Zhang, Li

    Surgery had been shown to be effective for superimposed peripheral nerve entrapment syndrome in patients with diabetic peripheral neuropathy (DPN), with pain relief and sensation restored. Few studies, however, have reported the quality-of-life outcomes of surgery for the treatment of painful DPN (PDPN). The objective of the present study was to evaluate the effects of microsurgical decompression of multiple entrapped peripheral nerves on pain and health-related quality of life in patients with refractory PDPN of the lower limbs. Eleven patients with intractable PDPN of the lower limbs were recruited for the present study. All the patients underwent microsurgical decompression of the common peroneal nerve, deep peroneal nerve, and posterior tibial nerve. The pain intensity was assessed using the visual analog scale and health-related quality of life was measured using the short-form 36-item quality-of-life survey. Six (54.6%) patients experienced >50% pain relief (both daytime pain and nocturnal pain) at 2 weeks after the decompression procedure and 8 (72.7%) patients at 24 months postoperatively. Two (18.2%) patients experienced a >50% decrease in peak pain at the 2 weeks after the procedure and 8 (72.7%) patients at 24 months. Additionally, the scores from the short-form 36-item quality-of-life survey were significantly improved in the following 2 domains: bodily pain and general health at 2 weeks after the decompression procedure. Also, at 24 months postoperatively, 6 domains had significantly improved, including physical function, bodily pain, general health, social function, role emotional, and mental health. No significant side effects were recorded during the study. Microsurgical decompression of peripheral nerves is an effective and safe therapy for intractable PDPN with superimposed nerve compression.

  10. Neonatal pain

    PubMed Central

    Walker, Suellen M

    2014-01-01

    Effective management of procedural and postoperative pain in neonates is required to minimize acute physiological and behavioral distress and may also improve acute and long-term outcomes. Painful stimuli activate nociceptive pathways, from the periphery to the cortex, in neonates and behavioral responses form the basis for validated pain assessment tools. However, there is an increasing awareness of the need to not only reduce acute behavioral responses to pain in neonates, but also to protect the developing nervous system from persistent sensitization of pain pathways and potential damaging effects of altered neural activity on central nervous system development. Analgesic requirements are influenced by age-related changes in both pharmacokinetic and pharmacodynamic response, and increasing data are available to guide safe and effective dosing with opioids and paracetamol. Regional analgesic techniques provide effective perioperative analgesia, but higher complication rates in neonates emphasize the importance of monitoring and choice of the most appropriate drug and dose. There have been significant improvements in the understanding and management of neonatal pain, but additional research evidence will further reduce the need to extrapolate data from older age groups. Translation into improved clinical care will continue to depend on an integrated approach to implementation that encompasses assessment and titration against individual response, education and training, and audit and feedback. PMID:24330444

  11. Neonatal pain.

    PubMed

    Walker, Suellen M

    2014-01-01

    Effective management of procedural and postoperative pain in neonates is required to minimize acute physiological and behavioral distress and may also improve acute and long-term outcomes. Painful stimuli activate nociceptive pathways, from the periphery to the cortex, in neonates and behavioral responses form the basis for validated pain assessment tools. However, there is an increasing awareness of the need to not only reduce acute behavioral responses to pain in neonates, but also to protect the developing nervous system from persistent sensitization of pain pathways and potential damaging effects of altered neural activity on central nervous system development. Analgesic requirements are influenced by age-related changes in both pharmacokinetic and pharmacodynamic response, and increasing data are available to guide safe and effective dosing with opioids and paracetamol. Regional analgesic techniques provide effective perioperative analgesia, but higher complication rates in neonates emphasize the importance of monitoring and choice of the most appropriate drug and dose. There have been significant improvements in the understanding and management of neonatal pain, but additional research evidence will further reduce the need to extrapolate data from older age groups. Translation into improved clinical care will continue to depend on an integrated approach to implementation that encompasses assessment and titration against individual response, education and training, and audit and feedback.

  12. Sonographic evaluation of visceral and subcutaneous fat in obese children*

    PubMed Central

    Sakuno, Telma; Tomita, Letícia Mary; Tomita, Carolina Mywa; Giuliano, Isabela de Carlos Back; Ibagy, Amanda; Perin, Nilza Maria Medeiros; Poeta, Lisiane Schilling

    2014-01-01

    Objective To evaluate sonographic measurements of visceral and subcutaneous fat in children, and to investigate the usefulness of preperitoneal fat (PF) and the abdominal wall fat index (AFI) as parameters to determine visceral fat and presence of nonalcoholic fatty liver disease (NAFLD) in obese children. Materials and Methods A case-control study of a sample including 44 children (22 cases and 22 controls) matched by sex and age. The Student t test and the Fisher exact test were utilized in the descriptive and bivariate analysis. Results The sonographic parameters evaluated - subcutaneous cell tissue, PF and intraperitoneal fat, and NAFLD - presented high statistical association with body mass index. NAFLD was observed in eight obese patients (36.36%), and PF and AFI were the variables with highest statistical significance, with p < 0.0001. Conclusion Ultrasonography is useful tool in the differentiation and quantification of visceral and subcutaneous fat in children. The measures of PF and AFI are useful in the assessment of visceral fat and NAFLD in obese children. PMID:25741071

  13. Antimony to Cure Visceral Leishmaniasis Unresponsive to Liposomal Amphotericin B.

    PubMed

    Morizot, Gloria; Jouffroy, Romain; Faye, Albert; Chabert, Paul; Belhouari, Katia; Calin, Ruxandra; Charlier, Caroline; Miailhes, Patrick; Siriez, Jean-Yves; Mouri, Oussama; Yera, Hélène; Gilquin, Jacques; Tubiana, Roland; Lanternier, Fanny; Mamzer, Marie-France; Legendre, Christophe; Peyramond, Dominique; Caumes, Eric; Lortholary, Olivier; Buffet, Pierre

    2016-01-01

    We report on 4 patients (1 immunocompetent, 3 immunosuppressed) in whom visceral leishmaniasis had become unresponsive to (or had relapsed after) treatment with appropriate doses of liposomal amphotericin B. Under close follow-up, full courses of pentavalent antimony were administered without life-threatening adverse events and resulted in rapid and sustained clinical and parasitological cure.

  14. The pathology associated with visceral toxicosis of catfish

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Visceral toxicosis of catfish (VTC) syndrome was recognized in the late 1990s and recently has been associated with exposure to Clostridium botulinum type E neurotoxin. Tentative diagnosis is based on clinical presentation and ross findings, and is confirmed by bioassay. In April 2009, channel cat...

  15. Visceral Pedagogies: Pornography, Affect, and Safety in the University Classroom

    ERIC Educational Resources Information Center

    Paasonen, Susanna

    2016-01-01

    This article addresses the pedagogical choices and the visceral reverberations involved in teaching porn in the university classroom. The author discusses different aims and goals for teaching pornography, as well as the some key pedagogical considerations and options involved in this, drawing on her own experiences teaching porn in Finnish gender…

  16. Peroxisome proliferator-activated receptor agonists modulate neuropathic pain: a link to chemokines?

    PubMed Central

    Freitag, Caroline M.; Miller, Richard J.

    2014-01-01

    Chronic pain presents a widespread and intractable medical problem. While numerous pharmaceuticals are used to treat chronic pain, drugs that are safe for extended use and highly effective at treating the most severe pain do not yet exist. Chronic pain resulting from nervous system injury (neuropathic pain) is common in conditions ranging from multiple sclerosis to HIV-1 infection to type II diabetes. Inflammation caused by neuropathy is believed to contribute to the generation and maintenance of neuropathic pain. Chemokines are key inflammatory mediators, several of which (MCP-1, RANTES, MIP-1α, fractalkine, SDF-1 among others) have been linked to chronic, neuropathic pain in both human conditions and animal models. The important roles chemokines play in inflammation and pain make them an attractive therapeutic target. Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear receptors known for their roles in metabolism. Recent research has revealed that PPARs also play a role in inflammatory gene repression. PPAR agonists have wide-ranging effects including inhibition of chemokine expression and pain behavior reduction in animal models. Experimental evidence suggests a connection between the pain ameliorating effects of PPAR agonists and suppression of inflammatory gene expression, including chemokines. In early clinical research, one PPARα agonist, palmitoylethanolamide (PEA), shows promise in relieving chronic pain. If this link can be better established, PPAR agonists may represent a new drug therapy for neuropathic pain. PMID:25191225

  17. Giardia duodenalis induces paracellular bacterial translocation and causes postinfectious visceral hypersensitivity.

    PubMed

    Halliez, Marie C M; Motta, Jean-Paul; Feener, Troy D; Guérin, Gaetan; LeGoff, Laetitia; François, Arnaud; Colasse, Elodie; Favennec, Loic; Gargala, Gilles; Lapointe, Tamia K; Altier, Christophe; Buret, André G

    2016-04-15

    Irritable bowel syndrome (IBS) is the most frequent functional gastrointestinal disorder. It is characterized by abdominal hypersensitivity, leading to discomfort and pain, as well as altered bowel habits. While it is common for IBS to develop following the resolution of infectious gastroenteritis [then termed postinfectious IBS (PI-IBS)], the mechanisms remain incompletely understood. Giardia duodenalis is a cosmopolitan water-borne enteropathogen that causes intestinal malabsorption, diarrhea, and postinfectious complications. Cause-and-effect studies using a human enteropathogen to help investigate the mechanisms of PI-IBS are sorely lacking. In an attempt to establish causality between giardiasis and postinfectious visceral hypersensitivity, this study describes a new model of PI-IBS in neonatal rats infected with G. duodenalis At 50 days postinfection with G. duodenalis (assemblage A or B), long after the parasite was cleared, rats developed visceral hypersensitivity to luminal balloon distension in the jejunum and rectum, activation of the nociceptive signaling pathway (increased c-fos expression), histological modifications (villus atrophy and crypt hyperplasia), and proliferation of mucosal intraepithelial lymphocytes and mast cells in the jejunum, but not in the rectum. G. duodenalis infection also disrupted the intestinal barrier, in vivo and in vitro, which in turn promoted the translocation of commensal bacteria. Giardia-induced bacterial paracellular translocation in vitro correlated with degradation of the tight junction proteins occludin and claudin-4. The extensive observations associated with gut hypersensitivity described here demonstrate that, indeed, in this new model of postgiardiasis IBS, alterations to the gut mucosa and c-fos are consistent with those associated with PI-IBS and, hence, offer avenues for new mechanistic research in the field.

  18. Convergence of visceral and somatic inputs onto subnucleus reticularis dorsalis neurones in the rat medulla.

    PubMed Central

    Roy, J C; Bing, Z; Villanueva, L; Le Bars, D

    1992-01-01

    convergence of noxious inputs onto single SRD neurones. 4. It is suggested that neurones with total nociceptive convergence could be a link in spino-bulbospinal loops involved in autonomic reactions to strong visceral stimulation. In addition, SRD neurones could be an important supraspinal relay in the mechanisms of visceral pain. PMID:1302266

  19. Mechanism of acupuncture regulating visceral sensation and mobility.

    PubMed

    Rong, Peijing; Zhu, Bing; Li, Yuqing; Gao, Xinyan; Ben, Hui; Li, Yanhua; Li, Liang; He, Wei; Liu, Rupeng; Yu, Lingling

    2011-06-01

    Chinese ancient medical scientists have long focused on the internal and external contacts between acupoints on the surface of the body and the viscera. The Miraculous Pivot (it is one of the earliest medical classics in China) stated, "Twelve regular channels belong to the zang-fu organs internally, and connect to the extremities and joints externally." Traditional Chinese medicine considers acupoints as defined areas where the Qi of viscera and meridians are transfused. These include the reaction points of visceral diseases on the body surface as well as the acupuncture trigger points that promote the flow of Qi and blood, and regulate visceral function. Chinese ancient medical scientists classified the specificity of the main acupoints in the body based on the meridian doctrine, which has been instructing clinical application for about 2000 years. Laws on the domino effect of acupoints have mainly focused on conclusions to clinical experiences. Indications of some acupoints exceed the practical paradigm since the excessive extension occurred during theory derivation. The current research direction on acupuncture focuses on three aspects: the effectiveness of acupuncture and moxibustion; the relevances and associations between meridians and viscera; and the physical and chemical properties and relevant physical basis of acupoints. The relevance between meridians and viscera is the central theory in the meridian doctrine, and acupoints are regarded as an important link in the relationship between meridians and viscera. Specific relationships between acupoints and target organs exist. Stimulating different acupoints on the body surface can help deal with different diseases, especially visceral diseases. In addition, acupoints have a dual function of reflecting and treating visceral diseases. There is no systemic research available on acupoint specificity, despite current knowledge and clinical experiences, which results in a weak foundation for acupuncture theory

  20. Long-term follow-up of chronic spinal cord stimulation for medically intractable orthostatic tremor.

    PubMed

    Blahak, Christian; Sauer, Tamara; Baezner, Hansjoerg; Wolf, Marc E; Saryyeva, Assel; Schrader, Christoph; Capelle, Hans-Holger; Hennerici, Michael G; Krauss, Joachim K

    2016-11-01

    Orthostatic tremor (OT) is a rare form of tremor occurring in the legs when standing upright. Medical treatment frequently is unsatisfactory, thus in selected cases, surgical treatment, such as spinal cord stimulation (SCS) or thalamic deep brain stimulation has been proposed. We report the long-term results (follow-up (FU) 34-133 months) of SCS in four patients with medically intractable OT. Outcome was assessed by recording the time tolerated to stand still pre- and post-operatively and by a patient self-rating (PSR) scale (0 = poor to 6 = excellent). Furthermore, surface electromyography (EMG) recordings of different leg muscles were performed to estimate tremor activity with and without SCS post-operatively. With chronic SCS, all four patients showed an improvement of unsteadiness occurring in the presence of stimulation-induced paraesthesia of the legs. The mean standing time improved from 51 s (SD 47 s, range 4-120 s) pre-operatively to 220 s (SD 184 s, range 10-480 s) with SCS at last available FU. Tremor activity in the EMG of the anterior tibial muscle was reduced by 30-60 % with SCS compared with off SCS. PSR score was 4 or 5 in three patients and 3 in the other. In conclusion, SCS is an effective long-term treatment option in patients with otherwise intractable OT.

  1. De novo mutations of KIAA2022 in females cause intellectual disability and intractable epilepsy

    PubMed Central

    de Lange, Iris M; Helbig, Katherine L; Weckhuysen, Sarah; Møller, Rikke S; Velinov, Milen; Dolzhanskaya, Natalia; Marsh, Eric; Helbig, Ingo; Devinsky, Orrin; Tang, Sha; Mefford, Heather C; Myers, Candace T; van Paesschen, Wim; Striano, Pasquale; van Gassen, Koen; van Kempen, Marjan; de Kovel, Carolien G F; Piard, Juliette; Minassian, Berge A; Nezarati, Marjan M; Pessoa, André; Jacquette, Aurelia; Maher, Bridget; Balestrini, Simona; Sisodiya, Sanjay; Warde, Marie Therese Abi; De St Martin, Anne; Chelly, Jamel; van ‘t Slot, Ruben; Van Maldergem, Lionel; Brilstra, Eva H; Koeleman, Bobby P C

    2016-01-01

    Background Mutations in the KIAA2022 gene have been reported in male patients with X-linked intellectual disability, and related female carriers were unaffected. Here, we report 14 female patients who carry a heterozygous de novo KIAA2022 mutation and share a phenotype characterised by intellectual disability and epilepsy. Methods Reported females were selected for genetic testing because of substantial developmental problems and/or epilepsy. X-inactivation and expression studies were performed when possible. Results All mutations were predicted to result in a frameshift or premature stop. 12 out of 14 patients had intractable epilepsy with myoclonic and/or absence seizures, and generalised in 11. Thirteen patients had mild to severe intellectual disability. This female phenotype partially overlaps with the reported male phenotype which consists of more severe intellectual disability, microcephaly, growth retardation, facial dysmorphisms and, less frequently, epilepsy. One female patient showed completely skewed X-inactivation, complete absence of RNA expression in blood and a phenotype similar to male patients. In the six other tested patients, X-inactivation was random, confirmed by a non-significant twofold to threefold decrease of RNA expression in blood, consistent with the expected mosaicism between cells expressing mutant or normal KIAA2022 alleles. Conclusions Heterozygous loss of KIAA2022 expression is a cause of intellectual disability in females. Compared with its hemizygous male counterpart, the heterozygous female disease has less severe intellectual disability, but is more often associated with a severe and intractable myoclonic epilepsy. PMID:27358180

  2. A Monte Carlo Metropolis-Hastings algorithm for sampling from distributions with intractable normalizing constants.

    PubMed

    Liang, Faming; Jin, Ick-Hoon

    2013-08-01

    Simulating from distributions with intractable normalizing constants has been a long-standing problem in machine learning. In this letter, we propose a new algorithm, the Monte Carlo Metropolis-Hastings (MCMH) algorithm, for tackling this problem. The MCMH algorithm is a Monte Carlo version of the Metropolis-Hastings algorithm. It replaces the unknown normalizing constant ratio by a Monte Carlo estimate in simulations, while still converges, as shown in the letter, to the desired target distribution under mild conditions. The MCMH algorithm is illustrated with spatial autologistic models and exponential random graph models. Unlike other auxiliary variable Markov chain Monte Carlo (MCMC) algorithms, such as the Møller and exchange algorithms, the MCMH algorithm avoids the requirement for perfect sampling, and thus can be applied to many statistical models for which perfect sampling is not available or very expensive. The MCMH algorithm can also be applied to Bayesian inference for random effect models and missing data problems that involve simulations from a distribution with intractable integrals.

  3. Typhoid fever as a triggering factor in acute and intractable bronchial asthma attack.

    PubMed

    Wardhana; Surachmanto, Eko E; Datau, E A

    2013-10-01

    Typhoid fever is an enteric infection caused by Salmonella typhi. In Indonesia, typhoid fever is endemic with high incidence of the disease. In daily practice we frequently have patients with bronchial asthma, and it is becoming worse when these patients get typhoid fever. After oral ingestion, Salmonella typhi invades the the intestine mucosa after conducted by microbial binding to epithelial cells, destroying the microfold cells (M cell) then passed through the lamina propria and detected by dendritic cells (DC) which express a variety of pathogen recognition receptors on the surfaces, including Toll-Like Receptor (TLR). expressed on macrophages and on intestinal epithelial cells inducing degradation of IB, and translocation of NF-B (Nuclear Factor-Kappa Beta). This process initiates the induction of pro-inflammatory gene expression profile adhesion molecules, chemokines, adhesion molecules, and other proteins that induce and perpetuate the inflammation in host cells then will induce acute ant intractable attack of bronchial asthma. The role of typhoid fever in bronchial asthma, especially in persons with acute attack of bronchial asthma, is not well understood. In this article, we will discuss the role of typhoid fever in the bronchial asthma patients which may cause bronchial asthma significantly become more severe even triggering the acute and intractable attack of bronchial asthma. This fact makes an important point, to treat completely the typhoid fever in patients with bronchial asthma.

  4. Endoscopic ligation of the internal maxillary artery for treatment of intractable posterior epistaxis.

    PubMed

    Pritikin, J B; Caldarelli, D D; Panje, W R

    1998-02-01

    Lack of universal success with both transantral ligation of the internal maxillary artery and percutaneous embolization of the distal branches of the internal maxillary distribution has led to consideration of alternative techniques to control intractable posterior epistaxis. One such technique takes advantage of advances in endoscopic technology and instrumentation, as well as a nearly constant anatomic configuration. The internal maxillary artery divides into terminal branches within the pterygomaxillary fossa, sending branches through the bony maxilla to exit the posterolateral nasal wall in the posterior aspect of the middle meatus. Endoscopic identification and ligation of these terminal branches of the internal maxillary artery (the sphenopalatine and nasopalatine arteries) as they exit the maxilla has been performed on 10 patients with a 100% success rate and no morbidity or mortality associated with the procedure. These results compare favorably to the average reported success rates of 89% for transantral ligation and 94% for percutaneous embolization, and average complication rates of 28% and 27%, respectively. This endonasal procedure has been performed for spontaneous epistaxis as well as postsurgical nasal bleeding with equal success. The ascending scale of treatment previously outlined in the literature may be amended, as a potentially definitive procedure is available, and we believe that this technique is easier to perform, has less associated morbidity, and has equal efficacy in comparison to transantral ligation or percutaneous embolization in the treatment of intractable posterior epistaxis.

  5. Efficacy and safety of zonisamide in Thai children and adolescents with intractable seizures.

    PubMed

    Thampratankul, Lunliya; Khongkhatithum, Chaiyos; Visudtibhan, Anannit

    2015-03-01

    This retrospective study examined the efficacy and safety of zonisamide for Thai children and adolescents with intractable seizures. The medical records of 24 patients (13 male, 11 female), aged 2 to 18 years (median 11.5, mean 10.4) who received zonisamide were reviewed. The underlying illness, etiology of epilepsy, seizure types, previous and concomitant antiepileptic drugs, dosage, and adverse effects of the drug were collected. Zonisamide's efficacy was evaluated on the basis of seizure reduction rates. At final evaluation, 7 patients were still taking zonisamide from 4.7 to 10.3 mg/kg/d (median 8). One patient became seizure-free and the other 6 experienced favorable seizure control. The median duration of zonisamide therapy was 23.75 months (range 20.5-25 months). Minor adverse effects were reported in 41.6% of patients during the first 3 months of therapy. Zonisamide is an option for the treatment of intractable seizures with favorable seizure control in children and adolescents.

  6. Effect of molecular adsorbent recirculating system in hepatitis C virus-related intractable pruritus.

    PubMed

    Doria, Cataldo; Mandalá, Lucio; Smith, Jan; Vitale, Claudio H; Lauro, Augusto; Gruttadauria, Salvatore; Marino, Ignazio R; Foglieni, Carlo Scotti; Magnone, Mario; Scott, Victor L

    2003-04-01

    Intractable pruritus is more common in cholestatic liver diseases and may be the presenting symptom and/or major complaint of hepatitis C and/or hepatitic C virus-related cirrhosis. From September 2000 to May 2002, three patients affected by intractable pruritus secondary to hepatitis C cirrhosis that failed medical treatment were treated with a molecular adsorbent recirculating system (MARS). MARS is an artificial liver support system that aims to clear the blood of metabolic waste products normally metabolized by the liver. Each patient underwent seven MARS sessions. Liver function tests, the 36-Item Short Form quality-of-life test, visual analog scale for itching, and bile acid measurement in the serum, albumin circuit and ultrafiltrate were performed before and after each MARS session. Moreover, at hospital admission, each patient underwent a psychological workup and abdominal imaging study. Subjective improvement in pruritus and quality of life, along with a decrease in serum bile acid concentration, was observed in every patient; no patient underwent retreatment and/or liver transplantation up to a 9-month follow-up. One patient died 201 days after MARS treatment. Although we observed a decreased level of serum bile acids, one cannot conclude that this was the mechanism of action for the reduction in pruritus intensity in patients in our series. Different toxins and/or a placebo effect might have had a role in this setting.

  7. Oesophageal sensation assessed by electrical stimuli and brain evoked potentials--a new model for visceral nociception.

    PubMed Central

    Frøbert, O; Arendt-Nielsen, L; Bak, P; Funch-Jensen, P; Bagger, J P

    1995-01-01

    Sensory thresholds and brain evoked potentials were determined in 12 healthy volunteers using electrical stimulation of the oesophagus 28 and 38 cm from the nares. The peaks of the evoked potentials were designated N for negative deflections and P for positive. Continuous electrical stimulation (40 Hz) at the 38 cm position resembled heartburn (five of 12 subjects) while non-specific ('electrical') sensations were provoked at 28 cm (10 of 12). Thresholds of sensation and of pain were lower at the initial than the second determination, but did not differ with respect to stimulation site. The pain summation threshold to repeated stimuli (2 Hz, 5 stimuli) was determined for the first time in a viscus. This threshold was lower than the pain threshold to single stimuli at 38 cm (p < 0.02). Evoked potential latencies did not change significantly over a six month period while the N1/P2 amplitude was higher at the first measurement (p < 0.05). P1 and N1 latencies were significantly shorter 38 cm (medians 100 and 141 ms) than 28 cm from the nares (102 and 148 ms) (p = 0.04 and p = 0.008). Electrical stimulation of the oesophagus may serve as a human experimental model for visceral pain. Longer evoked potential latencies from the proximal compared with distal stimulations provide new information about the sensory pathways of the oesophagus. PMID:8549932

  8. Protein expression of phospho-lim kinase-1 in patients and an experimental rat model with intractable temporal lobe epilepsy

    PubMed Central

    Huang, Hao; Wang, Heng; Yuan, Jinxian; Wu, Xuling; Huang, Yunyi; Zhou, Xin; Chen, Yangmei

    2015-01-01

    Lim kinase-1 (LIMK1) plays a critical role in dendritic spine morphogenesis and brain function. The protein expression pattern of phospho-LIMK1 (p-LIMK1), the active form of LIMK1, in intractable temporal lobe epilepsy (TLE), however, is unknown. Here we measured p-LIMK1 protein expression in thirty temporal neocortex tissue samples from intractable TLE patients, fifteen histologically normal temporal neocortex tissue samples from trauma patients without epilepsy, in the hippocampi of lithium chloride/pilocarpine-induced TLE rats, and in controls. We found that p-LIMK1 was expressed mainly in the cytoplasm of neurons. The protein expression of p-LIMK1 was significantly higher in the TLE patients and rats than in the control groups. Our results suggest that p-LIMK1 might be involved in the pathogenesis of intractable TLE. PMID:25785037

  9. Curative effect and costs of surgical and gamma knife treatments on intractable epilepsy caused by temporal-hippocampal sclerosis.

    PubMed

    Han, Z T; Chen, Q X

    2015-07-31

    This study aimed to investigate the curative effect and costs of surgical and gamma knife treatments on intractable epilepsy caused by temporal-hippocampal sclerosis. The subjects comprised patients who suffered from intractable epilepsy caused by temporal-hippocampal sclerosis and received treatment in the Department of Neurosurgery of our hospital between 2010 and 2011. After obtaining their consent, patients were evaluated and selected to receive surgical or gamma knife treatments. In the surgical group, the short-term curative rate was 92.60% and the average cost was US$ 1311.50 while in the gamma knife group, the short-term curative rate was 53.79%, and the average cost was US$ 2786.90. Both surgical and gamma knife treatments of intractable epilepsy caused by temporal-hippocampal sclerosis are safe and effective, but the short-term curative effect of surgical treatment is better than that of gamma knife, and its cost is lower.

  10. Esophageal Mast Cell Infiltration in a 32-Year-Old Woman with Noncardiac Chest Pain.

    PubMed

    Lee, Keol; Kwon, Hee Jin; Kim, In Young; Yoo, Kwai Han; Lee, Seulkee; Min, Yang Won; Rhee, Poong-Lyul

    2016-01-01

    Noncardiac chest pain (NCCP) is one of the most common esophageal symptoms and lacks a clearly defined mechanism. The most common cause of NCCP is gastroesophageal reflux disease (GERD). One of the accepted mechanisms of NCCP in a patient without GERD has been altered visceral sensitivity. Mast cells may play a role in visceral hypersensitivity in irritable bowel syndrome. In this case, a patient with NCCP and dysphagia who was unresponsive to proton pump inhibitor treatment had an increased esophageal mast cell infiltration and responded to 14 days of antihistamine and antileukotriene treatment. We suggest that there may be a relationship between esophageal symptoms such as NCCP and esophageal mast cell infiltration.

  11. Unmyelinated visceral afferents exhibit frequency dependent action potential broadening while myelinated visceral afferents do not.

    PubMed

    Li, Bai-Yan; Feng, Bin; Tsu, Hwa Y; Schild, John H

    2007-06-21

    Sensory information arising from visceral organ systems is encoded into action potential trains that propagate along afferent fibers to target nuclei in the central nervous system. These information streams range from tight patterns of action potentials that are well synchronized with the sensory transduction event to irregular, patternless discharge with no clear correlation to the sensory input. In general terms these afferent pathways can be divided into unmyelinated and myelinated fiber types. Our laboratory has a long standing interest in the functional differences between these two types of afferents in terms of the preprocessing of sensory information into action potential trains (synchrony, frequency, duration, etc.), the reflexogenic consequences of this sensory input to the central nervous system and the ionic channels that give rise to the electrophysiological properties of these unique cell types. The aim of this study was to determine whether there were any functional differences in the somatic action potential characteristics of unmyelinated and myelinated vagal afferents in response to different rates of sensory nerve stimulation. Our results showed that activity and frequency-dependent widening of the somatic action potential was quite prominent in unmyelinated but not myelinated vagal afferents. Spike broadening often leads to increased influx of Ca(2+) ions that has been associated with a diverse range of modulatory mechanisms both at the cell body and central synaptic terminations (e.g. increased neurotransmitter release.) We conclude that our observations are indicative of fundamentally different mechanisms for neural integration of sensory information arising from unmyelinated and myelinated vagal afferents.

  12. A case report of stellate ganglion block in the treatment of epileptic pain

    PubMed Central

    Wang, Shengtao; Zhu, Yangzi

    2017-01-01

    Abstract Rationale: Stellate ganglion blocks have been shown to provide effective pain relief in a number of different conditions, but no one had reported stellate ganglion blocks for the treatment of epileptic pain. We describe a case report of the successful use of stellate ganglion block in the treatment of epileptic pain in the patient. Patient concerns: A 8-year-old girl who had experienced severe paroxysmal pain in her right upper limb. Diagnoses: She was diagnosed as drug-resistant partial epilepsy. Interventions: The patient received stellate ganglion blocks with lidocaine for 2 courses with 2 weeks in a course of treatment and oral carbamazepine once a day. Outcomes: Carbamazepine dosage gradually tapered until stop and epileptic pain attacks become less and less, eventually disappear. Lessons: Stellate ganglion block may be an effective treatment of intractable partial epilepsy. However, more research is now needed to verify the validity. PMID:28178147

  13. Low back pain - acute

    MedlinePlus

    Backache; Low back pain; Lumbar pain; Pain - back; Acute back pain; Back pain - new; Back pain - short-term; Back strain - new ... lower back supports most of your body's weight. Low back pain is the number two reason that Americans see ...

  14. Evaluation of Prevalent Phytocannabinoids in the Acetic Acid Model of Visceral Nociception

    PubMed Central

    Booker, Lamont; Naidu, Pattipati S.; Razdan, Raj K.; Mahadevan, Anu; Lichtman, Aron H.

    2009-01-01

    Considerable preclinical research has demonstrated the efficacy of Δ9-tetrahydrocannabinol (Δ9-THC), the primary psychoactive constituent of Cannabis sativa, in a wide variety of animal models of pain, but few studies have examined other phytocannabinoids. Indeed, other plant-derived cannabinoids, including cannabidiol (CBD), cannabinol (CBN), and cannabichromene (CBC) elicit antinociceptive effects in some assays. In contrast, tetrahydrocannabivarin (THCV), another component of cannabis, antagonizes the pharmacological effects of Δ9-THC. These results suggest that various constituents of this plant may interact in a complex manner to modulate pain. The primary purpose of the present study was to assess the antinociceptive effects of these other prevalent phytocannabinoids in the acetic acid stretching test, a rodent visceral pain model. Of the cannabinoid compounds tested, Δ9-THC and CBN bound to the CB1 receptor and produced antinociceptive effects. The CB1 receptor antagonist, rimonabant, but not the CB2 receptor antagonist, SR144528, blocked the antinociceptive effects of both compounds. Although THCV bound to the CB1 receptor with similar affinity as Δ9-THC, it had no effects when administered alone, but antagonized the antinociceptive effects of Δ9-THC when both drugs were given in combination. Importantly, the antinociceptive effects of Δ9-THC and CBN occurred at lower doses than those necessary to produce locomotor suppression, suggesting motor dysfunction did not account for the decreases in acetic acid-induced abdominal stretching. These data raise the intriguing possibility that other constituents of cannabis can be used to modify the pharmacological effects of Δ9-THC by either eliciting antinociceptive effects (i.e., CBN) or antagonizing (i.e., THCV) the actions of Δ9-THC. PMID:19679411

  15. Central sensitization: implications for the diagnosis and treatment of pain.

    PubMed

    Woolf, Clifford J

    2011-03-01

    Nociceptor inputs can trigger a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways, the phenomenon of central sensitization. Central sensitization manifests as pain hypersensitivity, particularly dynamic tactile allodynia, secondary punctate or pressure hyperalgesia, aftersensations, and enhanced temporal summation. It can be readily and rapidly elicited in human volunteers by diverse experimental noxious conditioning stimuli to skin, muscles or viscera, and in addition to producing pain hypersensitivity, results in secondary changes in brain activity that can be detected by electrophysiological or imaging techniques. Studies in clinical cohorts reveal changes in pain sensitivity that have been interpreted as revealing an important contribution of central sensitization to the pain phenotype in patients with fibromyalgia, osteoarthritis, musculoskeletal disorders with generalized pain hypersensitivity, headache, temporomandibular joint disorders, dental pain, neuropathic pain, visceral pain hypersensitivity disorders and post-surgical pain. The comorbidity of those pain hypersensitivity syndromes that present in the absence of inflammation or a neural lesion, their similar pattern of clinical presentation and response to centrally acting analgesics, may reflect a commonality of central sensitization to their pathophysiology. An important question that still needs to be determined is whether there are individuals with a higher inherited propensity for developing central sensitization than others, and if so, whether this conveys an increased risk in both developing conditions with pain hypersensitivity, and their chronification. Diagnostic criteria to establish the presence of central sensitization in patients will greatly assist the phenotyping of patients for choosing treatments that produce analgesia by normalizing hyperexcitable central neural activity. We have certainly come a long way since the

  16. Inflammation-induced pain sensitization in men and women: does sex matter in experimental endotoxemia?

    PubMed

    Wegner, Alexander; Elsenbruch, Sigrid; Rebernik, Laura; Roderigo, Till; Engelbrecht, Elisa; Jäger, Marcus; Engler, Harald; Schedlowski, Manfred; Benson, Sven

    2015-10-01

    A role of the innate immune system is increasingly recognized as a mechanism contributing to pain sensitization. Experimental administration of the bacterial endotoxin lipopolysaccharide (LPS) constitutes a model to study inflammation-induced pain sensitization, but all existing human evidence comes from male participants. We assessed visceral and musculoskeletal pain sensitivity after low-dose LPS administration in healthy men and women to test the hypothesis that women show greater LPS-induced hyperalgesia compared with men. In this randomized, double-blind, placebo-controlled crossover study, healthy men (n = 20) and healthy women using oral contraceptives (n = 20) received an intravenous injection of 0.4 ng/kg body weight LPS or placebo. Pain sensitivity was assessed with established visceral and musculoskeletal pain models (ie, rectal pain thresholds; pressure pain thresholds for different muscle groups), together with a heartbeat perception (interoceptive accuracy) task. Plasma cytokines (tumor necrosis factor-α and interleukin-6) were measured along with state anxiety at baseline and up to 6-hour postinjection. Lipopolysaccharide application led to significant increases in plasma cytokines and state anxiety and decreased interoceptive awareness in men and women (P < 0.001, condition effects), with more pronounced LPS-induced cytokine increases in women (P < 0.05, interaction effects). Although both rectal and pressure pain thresholds were significantly decreased in the LPS condition (all P < 0.05, condition effect), no sex differences in endotoxin-induced sensitization were observed. In summary, LPS-induced systemic immune activation leads to visceral and musculoskeletal hyperalgesia, irrespective of biological sex. These findings support the broad applicability of experimental endotoxin administration as a translational preclinical model of inflammation-induced pain sensitization in both sexes.

  17. The genetic influences on oxycodone response characteristics in human experimental pain.

    PubMed

    Olesen, Anne E; Sato, Hiroe; Nielsen, Lecia M; Staahl, Camilla; Droney, Joanne; Gretton, Sophy; Branford, Ruth; Drewes, Asbjørn M; Arendt-Nielsen, Lars; Riley, Julia; Ross, Joy

    2015-08-01

    Human experimental pain studies are of value to study basic pain mechanisms under controlled conditions. The aim of this study was to investigate whether genetic variation across selected mu-, kappa- and delta-opioid receptor genes (OPRM1, OPRK1and OPRD1, respectively) influenced analgesic response to oxycodone in healthy volunteers. Experimental multimodal, multitissue pain data from previously published studies carried out in Caucasian volunteers were used. Data on thermal skin pain tolerance threshold (PTT) (n = 37), muscle pressure PTT (n = 31), mechanical visceral PTT (n = 43) and thermal visceral PTT (n = 41) were included. Genetic associations with pain outcomes were explored. Nineteen opioid receptor genetic polymorphisms were included in this study. Variability in oxycodone response to skin heat was associated with OPRM1 single-nucleotide polymorphisms (SNPs) rs589046 (P < 0.0001) and rs563649 (P < 0.0001). Variability in oxycodone response to visceral pressure was associated with four OPRM1 SNPs: rs589046 (P = 0.015), rs1799971 (P = 0.045), rs9479757 (P = 0.009) and rs533586 (P = 0.046). OPRM1 SNPs were not associated with oxycodone visceral heat threshold, however, one OPRD1 rs419335 reached significance (P = 0.015). Another OPRD1 SNP rs2234918 (P = 0.041) was associated with muscle pressure. There were no associations with OPRK1 SNPs and oxycodone response for any of the pain modalities. Associations were found between analgesic effects of oxycodone and OPRM1 and OPRD1 SNPs; therefore, variation in opioid receptor genes may partly explain responder characteristics to oxycodone.

  18. Case report: a case of intractable Meniere's disease treated with autogenic training

    PubMed Central

    Goto, Fumiyuki; Nakai, Kimiko; Kunihiro, Takanobu; Ogawa, Kaoru

    2008-01-01

    Background Psychological stress plays an important role in the onset and course of Meniere's disease. Surgical therapy and intratympanic gentamicin treatment are options for cases that are intractable to conventional medical therapy. Psychotherapy, however, including autogenic training (AT), which can be used for general relaxation, is not widely accepted. This paper describes the successful administration of AT in a subject suffering from intractable Meniere's disease. Case presentation A 51-year-old male patient has suffered from fluctuating right sensorineural hearing loss with vertigo since 1994. In May 2002, he was first admitted to our hospital due to a severe vertigo attack accompanied by right sensorineural hearing loss. Spontaneous nystagmus toward the right side was observed. Since April 2004, he has experienced vertigo spells with right-sided tinnitus a few times per month that are intractable to conventional medical therapy. After four months, tympanic tube insertion was preformed in the right tympanic membrane. Intratympanic injection of dexamethasone was ineffective. He refused Meniett therapy and intratympanic gentamicin injection. In addition to his vertigo spells, he suffered from insomnia, tinnitus, and anxiety. Tranquilizers such as benzodiazepines and antidepressants such as serotonin selective re-uptake inhibitors (SSRIs) failed to stop the vertigo and only slightly improved his insomnia. In December 2006, the patient began psychological counseling with a psychotherapist. After brief psychological counseling along with cognitive behavior therapy (CBT), he began AT. He diligently and regularly continued his AT training in his home according to a written timetable. His insomnia, tinnitus, and vertigo spells disappeared within a few weeks after only four psychotherapy sessions. In order to master the six standard formulas of AT, he underwent two more sessions. Thereafter, he underwent follow-up for 9 months with no additional treatment. He is now

  19. Gastrointestinal (GI) permeability is associated with trait anxiety in children with functional abdominal pain (FAP) and Irritable Bowel Syndrome (IBS)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    FAP and IBS affect 10-15% of school age children and bear many physiological similarities to irritable bowel syndrome (IBS) in adults (e.g., functional pain, visceral hyperalgesia). Animal models of IBS have suggested a relationship between neonatal stress and increased GI permeability later in life...

  20. Abdominal Pain

    MedlinePlus

    ... call your doctor. In Spanish— Dolor abdominal en niños menores de 12 años What is recurrent abdominal ... Functional abdominal pain (FAP) typically affects kids ages 4-12, and is quite common, affecting up to ...

  1. [Elbow pain].

    PubMed

    Viikari-Juntura, Eira; Miintyselkii, Pekka; Havulinna, Jouni

    2010-01-01

    Pain and disability in the elbow are not as common as in the neck, shoulder or wrist, for example. The elbow may, however, present disorders that may in a prolonged state be difficult and cause significant loss of working capacity. These include epicondylitis, osteoarthritis and entrapment of the ulnar nerve.

  2. Achilles Pain.

    ERIC Educational Resources Information Center

    Connors, G. Patrick

    Five ailments which can cause pain in the achilles tendon area are: (1) muscular strain, involving the stretching or tearing of muscle or tendon fibers; (2) a contusion, inflammation or infection called tenosynovitis; (3) tendonitis, the inflammation of the tendon; (4) calcaneal bursitis, the inflammation of the bursa between the achilles tendon…

  3. Neck pain

    MedlinePlus

    ... neck. If neck pain involves compression of your nerves, you may feel numbness, tingling, or weakness in your arm or ... When to Contact a Medical Professional ... fever and headache, and your neck is so stiff that you cannot touch your chin to your chest. This may be ...

  4. Consistent sex-dependent effects of PKMζ gene ablation and pharmacological inhibition on the maintenance of referred pain

    PubMed Central

    Nasir, Hibatulnaseer; Mahboubi, Hicham; Gyawali, Sandeep; Ding, Stephanie; Mickeviciute, Aiste; Ragavendran, J Vaigunda; Laferrière, André; Stochaj, Ursula

    2016-01-01

    Background Persistently active PKMζ has been implicated in maintaining spinal nociceptive sensitization that underlies pain hypersensitivity. However, evidence for PKMζ in the maintenance of pain hypersensitivity comes exclusively from short-term studies in males using pharmacological agents of questionable selectivity. The present study examines the contribution of PKMζ to long-lasting allodynia associated with neuropathic, inflammatory, or referred visceral and muscle pain in males and females using pharmacological inhibition or genetic ablation. Results Pharmacological inhibition or genetic ablation of PKMζ reduced mild formalin pain and slowly developing contralateral allodynia in nerve-injured rats, but not moderate formalin pain or ipsilateral allodynia in models of neuropathic and inflammatory pain. Pharmacological inhibition or genetic ablation of PKMζ also effectively reduced referred visceral and muscle pain in male, but not in female mice and rats. Conclusion We show pharmacological inhibition and genetic ablation of PKMζ consistently attenuate long-lasting pain hypersensitivity. However, differential effects in models of referred versus inflammatory and neuropathic pain, and in males versus females, highlight the roles of afferent input-dependent masking and sex differences in the maintenance of pain hypersensitivity. PMID:27899695

  5. Renal histopathological findings in dogs with visceral leishmaniasis.

    PubMed

    Rigo, Rosangela Silva; Carvalho, Cristiano Marcelo Espínola; Honer, Michael Robin; Andrade, Gisele Braziliano de; Silva, Iandara Shetter; Rigo, Leonardo; Figueiredo, Helen Rezende; Barreto, Wanessa Teixeira Gomes

    2013-01-01

    Visceral leishmaniasis affects various organs including the kidneys; which can lead to renal failure and death. In order to verify this renal involvement, material was evaluated from 100 dogs naturally infected and with serological diagnosis of canine visceral leishmaniasis (CVL). Inflammatory changes were present in 25.3% of the tubules, in 67.0% of interstitium and in 52.0% of glomeruli. There was no significant difference (p > 0.05) between the presence of glomerulonephritis in symptomatic and oligosymptomatic dogs. The membranous and membranoproliferative glomerulonephritis were the most frequent, both with 18.0% frequency, followed by focal segmental glomerulosclerosis with 14.0%. Changes such as cylindruria, tubular and fibrosis hypertrophy, periglomerular inflammatory infiltrate, and multifocal and diffuse peritubular inflammatory infiltrate were observed. The findings are consistent with those of other authors indicating that renal involvement is common in CVL and the standards of membranous and membranoploriferative glomerulonephritis, as well as the tubulointerstitial involvement, are frequent.

  6. Visceral leishmaniasis: Revisiting current treatments and approaches for future discoveries.

    PubMed

    No, Joo Hwan

    2016-03-01

    The current treatments for visceral leishmaniasis are old and toxic with limited routes of administration. The emergence of drug-resistant Leishmania threatens the efficacy of the existing reservoir of antileishmanials, leading to an urgent need to develop new treatments. It is particularly important to review and understand how the current treatments act against Leishmania in order to identify valid drug targets or essential pathways for next-generation antileishmanials. It is equally important to adapt newly emerging biotechnologies to facilitate the current research on the development of novel antileishmanials in an efficient fashion. This review covers the basic background of the current visceral leishmaniasis treatments with an emphasis on the modes of action. It briefly discusses the role of the immune system in aiding the chemotherapy of leishmaniasis, describes potential new antileishmanial drug targets and pathways, and introduces recent progress on the utilization of high-throughput phenotypic screening assays to identify novel antileishmanial compounds.

  7. Visceral leishmaniasis in captive wild canids in Brazil.

    PubMed

    Luppi, Marcela M; Malta, Marcelo C C; Silva, Teane M A; Silva, Fabiana L; Motta, Rafael O C; Miranda, Ildikó; Ecco, Roselene; Santos, Renato L

    2008-08-01

    Visceral leishmaniasis (VL) is endemic in Belo Horizonte (State of Minas Gerais, Brazil). Leishmania sp. can naturally infect several species of mammals, and the domestic dog is the most important reservoir of the disease in South America. This report describes five cases of visceral leishmaniasis in Brazilian canids. Among 15 animals kept in captivity in a zoo in Belo Horizonte (State of Minas Gerais, Brazil), two animals, a bush dog (Spheotos venaticos) and a hoary zorro (Lycalopex vetulus) were serologically positive and developed clinical signs of VL, whereas three other canids, including a crab-eating fox (Cerdocyon thous), a maned wolf (Chrysocyon brachyurus), and a hoary zorro (Lycalopex vetulus) had positive serological results without clinical signs.

  8. Visceral Leishmaniasis with Endobronchial Involvement in an Immunocompetent Adult

    PubMed Central

    Kotsifas, Konstantinos; Metaxas, Eugenios; Koutsouvelis, Ioannis; Skoutelis, Athanassios; Kara, Panayiota; Tatsis, George

    2011-01-01

    Visceral leishmaniasis is characterized by fever, cachexia, hepatosplenomegaly, pancytopenia, and hypergammaglobulinemia. Cough may be a presenting symptom as well. However, pulmonary involvement is considered rare and mainly described in immunocompromised patients. We describe a case of an immunocompetent adult whose clinical presentation was dominated by cough and hemoptysis. Bronchoscopy revealed a discreet polypoid mucosal endobronchial lesion whose biopsy yielded Leishmania amastigotes within histiocytes. Transbronchial needle biopsy of a right paratracheal lymph node was also positive. Leishmania amastigotes were also found on bone marrow and liver biopsies. Treatment with IV Amphotericin B was successful. In conclusion, cough should not be overlooked as a presenting symptom of visceral leishmaniasis and may be a sign of pulmonary involvement. PMID:21577261

  9. Could kDNA-PCR in Peripheral Blood Replace the Examination of Bone Marrow for the Diagnosis of Visceral Leishmaniasis?

    PubMed

    de Godoy, Natalia Souza; Andrino, Marcos Luiz Alves; de Souza, Regina Maia; Gakiya, Erika; Amato, Valdir Sabbaga; Lindoso, José Ângelo Lauletta; Almeida Braz, Lucia Maria

    2016-01-01

    The aim of this study was to evaluate whether the molecular (kDNA-PCR) and parasitological diagnosis in peripheral blood (PB) could replace the invasive and painful bone marrow collection (BM) in the diagnosis of visceral leishmaniasis (VL). PB from suspected VL patients was evaluated by parasitological and molecular techniques using as the gold standard (GS) a combination of clinical, epidemiological, and immunochromatographic test (PB-rK39) results and parasitological examination of BM. Based on the GS, 38 samples from 32 patients were grouped: Group 1, 20 samples of VL cases, and Group 2, 18 samples of non-VL cases. In order to evaluate the parasitological and molecular techniques in PB, the samples were examined. From Group 1, PB kDNA-PCR was positive in 20 samples and in 19 of 20 in BM kDNA-PCR examination. However, the parasitological examination of buffy coat was insensitive, being able to detect only 4 cases from Group 1. All samples from Group 2 were negative. We concluded that, for the diagnosis of visceral leishmaniasis, the parasitological examination of peripheral blood was not useful; however, molecular diagnosis by kDNA-PCR, performed in peripheral blood, could be useful to replace the parasitological examination of bone marrow.

  10. Could kDNA-PCR in Peripheral Blood Replace the Examination of Bone Marrow for the Diagnosis of Visceral Leishmaniasis?

    PubMed Central

    de Godoy, Natalia Souza; Andrino, Marcos Luiz Alves; de Souza, Regina Maia; Gakiya, Erika; Amato, Valdir Sabbaga; Lindoso, José Ângelo Lauletta

    2016-01-01

    The aim of this study was to evaluate whether the molecular (kDNA-PCR) and parasitological diagnosis in peripheral blood (PB) could replace the invasive and painful bone marrow collection (BM) in the diagnosis of visceral leishmaniasis (VL). PB from suspected VL patients was evaluated by parasitological and molecular techniques using as the gold standard (GS) a combination of clinical, epidemiological, and immunochromatographic test (PB-rK39) results and parasitological examination of BM. Based on the GS, 38 samples from 32 patients were grouped: Group 1, 20 samples of VL cases, and Group 2, 18 samples of non-VL cases. In order to evaluate the parasitological and molecular techniques in PB, the samples were examined. From Group 1, PB kDNA-PCR was positive in 20 samples and in 19 of 20 in BM kDNA-PCR examination. However, the parasitological examination of buffy coat was insensitive, being able to detect only 4 cases from Group 1. All samples from Group 2 were negative. We concluded that, for the diagnosis of visceral leishmaniasis, the parasitological examination of peripheral blood was not useful; however, molecular diagnosis by kDNA-PCR, performed in peripheral blood, could be useful to replace the parasitological examination of bone marrow. PMID:27597892

  11. Adrenergic stimulation sensitizes TRPV1 through upregulation of cystathionine β-synthetase in a rat model of visceral hypersensitivity

    PubMed Central

    Zhu, Liyan; Zhao, Liting; Qu, Ruobing; Zhu, Hong-Yan; Wang, Yongmeng; Jiang, Xinghong; Xu, Guang-Yin

    2015-01-01

    The pathogenesis of pain in irritable bowel syndrome (IBS) is poorly understood and treatment remains difficult. The present study was designed to investigate roles of adrenergic signaling and the endogenous hydrogen sulfide producing enzyme cystathionine β-synthetase (CBS) in a previously validated rat model of IBS induced by neonatal colonic inflammation (NCI). Here we showed that NCI-induced visceral hypersensitivity (VH) was significantly attenuated by β2 subunit inhibitor but not by β1 or β3 or α subunit inhibitor. NCI markedly elevated plasma norepinephrine (NE) concentration without alteration in expression of β2 subunit receptors in dorsal root ganglion (DRGs) innervating the colon. In addition, NCI markedly enhanced TRPV1 and CBS expression in the colon DRGs. CBS inhibitor AOAA reversed the upregulation of TRPV1 in NCI rats. In vitro experiments showed that incubation of DRG cells with NE markedly enhanced expression of TRPV1, which was reversed by application of AOAA. Incubation of DRG cells with the H2S donor NaHS greatly enhanced TRPV1 expression. Collectively, these data suggest that activation of adrenergic signaling by NCI sensitizes TRPV1 channel activity, which is likely mediated by upregulation of CBS expression in peripheral sensory neurons, thus contributing to chronic visceral hypersensitivity. PMID:26527188

  12. Dynamic statistical parametric mapping for analyzing ictal magnetoencephalographic spikes in patients with intractable frontal lobe epilepsy

    PubMed Central

    Tanaka, Naoaki; Cole, Andrew J.; von Pechmann, Deidre; Wakeman, Daniel G.; Hämäläinen, Matti S.; Liu, Hesheng; Madsen, Joseph R.; Bourgeois, Blaise F.; Stufflebeam, Steven M.

    2009-01-01

    The purpose of this study is to assess the clinical value of spatiotemporal source analysis for analyzing ictal magnetoencephalography (MEG). Ictal MEG and simultaneous scalp EEG was recorded in five patients with medically intractable frontal lobe epilepsy. Dynamic statistical parametric maps (dSPMs) were calculated at the peak of early ictal spikes for the purpose of estimating the spatiotemporal cortical source distribution. DSPM solutions were mapped onto a cortical surface, which was derived from each patient's MRI. Equivalent current dipoles (ECDs) were calculated using a single-dipole model for comparison with dSPMs. In all patients, dSPMs tended to have a localized activation, consistent with the clinically-determined ictal onset zone, whereas most ECDs were considered to be inappropriate sources according to their goodness-of-fit values. Analyzing ictal MEG spikes by using dSPMs may provide useful information in presurgical evaluation of epilepsy. PMID:19394198

  13. Dynamic statistical parametric mapping for analyzing ictal magnetoencephalographic spikes in patients with intractable frontal lobe epilepsy.

    PubMed

    Tanaka, Naoaki; Cole, Andrew J; von Pechmann, Deidre; Wakeman, Daniel G; Hämäläinen, Matti S; Liu, Hesheng; Madsen, Joseph R; Bourgeois, Blaise F; Stufflebeam, Steven M

    2009-08-01

    The purpose of this study is to assess the clinical value of spatiotemporal source analysis for analyzing ictal magnetoencephalography (MEG). Ictal MEG and simultaneous scalp EEG was recorded in five patients with medically intractable frontal lobe epilepsy. Dynamic statistical parametric maps (dSPMs) were calculated at the peak of early ictal spikes for the purpose of estimating the spatiotemporal cortical source distribution. DSPM solutions were mapped onto a cortical surface, which was derived from each patient's MRI. Equivalent current dipoles (ECDs) were calculated using a single-dipole model for comparison with dSPMs. In all patients, dSPMs tended to have a localized activation, consistent with the clinically determined ictal onset zone, whereas most ECDs were considered to be inappropriate sources according to their goodness-of-fit values. Analyzing ictal MEG spikes by using dSPMs may provide useful information in presurgical evaluation of epilepsy.

  14. Successful management of intractable cryptosporidial diarrhea with intravenous octreotide, a somatostatin analogue.

    PubMed

    Kreinik, G; Burstein, O; Landor, M; Bernstein, L; Weiss, L M; Wittner, M

    1991-06-01

    A 38-year-old man with AIDS and intractable large-volume diarrhea due to a cryptosporidial infection was successfully treated with intravenous octreotide, a somatostatin analogue. The volume of diarrhea, 10-12 liters with 8-13 movements per day, was reduced to three to four semi-formed to formed stools per day when the patient was treated with 400 micrograms intravenous octreotide daily. The patient's intravenous hyperalimentation was discontinued and he returned to oral feeding. He quickly regained his normal weight and has now resumed his normal activities. For those patients who cannot tolerate subcutaneous administration, intravenous octreotide therapy may not only be life-saving but may also markedly increase the quality of life. Roxithromycin, a macrolide antibiotic, was also administered to this patient with cryptosporidiosis but efficacy was not demonstrated.

  15. Intractable hypoglycaemia in a patient with advanced carcinoid syndrome successfully treated with hepatic embolization.

    PubMed

    Kyriacou, Angelos; Mansoor, Was; Lawrance, Jeremy; Trainer, Peter J

    2016-01-01

    A male patient presented at the age of 54 years with metastatic pancreatic neuroendocrine tumour (NET). He was managed with interferon and multiple courses of MIBG therapy which controlled his disease for about seven years. He then developed symptomatic hypoglycaemia which resolved with the introduction of somatostatin analogue treatment and further therapeutic MIBG. However, three years later he was admitted to hospital with severe and intractable hypoglycaemia, which persisted despite treatment with dietary manipulation, diazoxide, long-acting octreotide injections, intravenous infusion of dextrose and octreotide and everolimus. Bland hepatic embolization was attempted as a last resort and resulted in prompt and dramatic improvement of his condition with no hypoglycaemia for five months. We recommend that hepatic embolization should be considered in patients with advanced and metastatic NETs accompanied by refractory hypoglycaemia, with the aim of symptomatic relief and palliation, and possibly some survival benefit.

  16. Perceptions of a changing world induce hope and promote peace in intractable conflicts.

    PubMed

    Cohen-Chen, Smadar; Crisp, Richard J; Halperin, Eran

    2015-04-01

    The importance of hope in promoting conciliatory attitudes has been asserted in the field of conflict resolution. However, little is known about conditions inducing hope, especially in intractable conflicts, where reference to the outgroup may backfire. In the current research, five studies yielded convergent support for the hypothesis that hope for peace stems from a general perception of the world as changing. In Study 1, coders observed associations between belief in a changing world, hope regarding peace, and support for concessions. Study 2 revealed the hypothesized relations using self-reported measures. Studies 3 and 4 established causality by instilling a perception of the world as changing (vs. unchanging) using narrative and drawing manipulations. Study 5 compared the changing world message with a control condition during conflict escalation. Across studies, although the specific context was not referred to, the belief in a changing world increased support for concessions through hope for peace.

  17. [A case of intractable epilepsy showing frequent gelastic seizures by administration of clobazam].

    PubMed

    Iwasaki, Toshiyuki; Miura, Hisao; Sunaoshi, Wataru; Hosoda, Nozomi; Takei, Kenji; Katayama, Fumihiko

    2003-09-01

    A 13-year-old boy patient had severe mental retardation and spastic quadriplegia due to fetal distress and hypoxic-ischemic brain damage in the perinatal period. He suffered from West syndrome at the age of 7 months, and subsequently was diagnosed as having symptomatic localization-related epilepsy. His intractable epileptic seizures were not controlled by combination of various antiepileptic drugs. After prescribing nitrazepam and zonisamide for more than 1 year, we added clobazam (CLB), which has been marketed in Japan since 2000, to this combination therapy. After the introduction of CLB, tonic seizures disappeared. However, gelastic seizures laughing with a stiff face and a wry mouth appeared frequently before falling asleep, and sleep disturbance worsened subsequently. It has not been reported previously that gelastic seizures are a side effect of CLB, although irritability and sleep disturbance have been described.

  18. Effectiveness of cerebral hemispherotomy for improving behavioral disorders associated with intractable post-traumatic seizures.

    PubMed

    Morino, Michiharu; Shimizu, Hiroyuki; Ishibashi, Kenichi; Sakamoto, Shinichi; Tsuyuguchi, Naohiro; Ohata, Kenji; Hara, Mitsuhiro

    2006-04-01

    A 25-year-old man presented with intractable post-traumatic seizures after suffering cerebral contusion in a traffic accident at age 5 years. Cerebral hemispherotomy was performed to transect the neuronal fibers to interrupt connections between seizure foci in wide areas of the brain, and to minimize the resected brain parenchyma. His seizures resolved and behavioral disorders improved, which had been impaired since age 8 years. Increased glucose metabolism in the normal frontal lobe detected by interictal fluorodeoxyglucose-positron emission tomography was correlated with the improvements in behavioral disorders. These findings suggest that the effects of seizures may be reversible in brain areas connected with, but remote from, the epileptogenic cortex.

  19. Intrastromal corneal tattooing as treatment in a case of intractable strabismic diplopia (double binocular vision).

    PubMed

    Laria, Carlos; Alió, Jorge L; Piñero, David N

    2010-01-01

    We present the case of a 29 man complaining of intractable diplopia during the last 5 years. He had undergone several surgical procedures for the treatment of his infantile strabismus since age 6 years. After surgery, the patient had been treated on 4 occasions with Botox. He also performed antisuppression exercises to encourage binocular vision. On our examination, the patient showed a 20/20 visual acuity in both eyes and a strabismic dysfunction with slight alphabet pattern, which induced a disturbing constant diplopia. Several treatment options were considered as occlusion therapy or cosmetic contact lenses, but they were not used because they were not acceptable esthetically or not tolerated. Finally, an optical penalization was induced by means of a black corneal tattooing placed at the centre of the cornea. The patient was followed for a period of 18 months, showing a complete elimination of diploia with esthetical acceptance and no inflammatory signs.

  20. Melanosomal sequestration of cytotoxic drugs contributes to the intractability of malignant melanomas

    NASA Astrophysics Data System (ADS)

    Chen, Kevin G.; Valencia, Julio C.; Lai, Barry; Zhang, Guofeng; Paterson, Jill K.; Rouzaud, François; Berens, Werner; Wincovitch, Stephen M.; Garfield, Susan H.; Leapman, Richard D.; Hearing, Vincent J.; Gottesman, Michael M.

    2006-06-01

    Multidrug resistance mechanisms underlying the intractability of malignant melanomas remain largely unknown. In this study, we demonstrate that the development of multidrug resistance in melanomas involves subcellular sequestration of intracellular cytotoxic drugs such as cis-diaminedichloroplatinum II (cisplatin; CDDP). CDDP is initially sequestered in subcellular organelles such as melanosomes, which significantly reduces its nuclear localization when compared with nonmelanoma/KB-3-1 epidermoid carcinoma cells. The melanosomal accumulation of CDDP remarkably modulates melanogenesis through a pronounced increase in tyrosinase activity. The altered melanogenesis manifested an 8-fold increase in both intracellular pigmentation and extracellular transport of melanosomes containing CDDP. Thus, our experiments provide evidence that melanosomes contribute to the refractory properties of melanoma cells by sequestering cytotoxic drugs and increasing melanosome-mediated drug export. Preventing melanosomal sequestration of cytotoxic drugs by inhibiting the functions of melanosomes may have great potential as an approach to improving the chemosensitivity of melanoma cells. cancer | melanosomes | skin | tumor therapy | multidrug resistance

  1. Perceptions of a Changing World Induce Hope and Promote Peace in Intractable Conflicts

    PubMed Central

    Cohen-Chen, Smadar; Crisp, Richard J.; Halperin, Eran

    2015-01-01

    The importance of hope in promoting conciliatory attitudes has been asserted in the field of conflict resolution. However, little is known about conditions inducing hope, especially in intractable conflicts, where reference to the outgroup may backfire. In the current research, five studies yielded convergent support for the hypothesis that hope for peace stems from a general perception of the world as changing. In Study 1, coders observed associations between belief in a changing world, hope regarding peace, and support for concessions. Study 2 revealed the hypothesized relations using self-reported measures. Studies 3 and 4 established causality by instilling a perception of the world as changing (vs. unchanging) using narrative and drawing manipulations. Study 5 compared the changing world message with a control condition during conflict escalation. Across studies, although the specific context was not referred to, the belief in a changing world increased support for concessions through hope for peace. PMID:25713171

  2. Blood pressure rhythmicity and visceral fat in children with hypertension.

    PubMed

    Niemirska, Anna; Litwin, Mieczysław; Feber, Janusz; Jurkiewicz, Elżbieta

    2013-10-01

    Primary hypertension is associated with disturbed activity of the sympathetic nervous system and altered blood pressure rhythmicity. We analyzed changes in cardiovascular rhythmicity and its relation with target organ damage during 12 months of antihypertensive treatment in 50 boys with hypertension (median, 15.0 years). The following parameters were obtained before and after 12 months of antihypertensive treatment: 24-hour ambulatory blood pressure, left ventricular mass, carotid intima-media thickness, and MRI for visceral and subcutaneous adipose tissue. Amplitudes and acrophases of mean arterial pressure and heart rate rhythms were obtained for 24-, 12-, and 8-hour periods. After 1 year of treatment, 68% of patients were normotensive, and left ventricular mass and carotid intima-media thickness decreased in 60% and 62% of patients, respectively. Blood pressure and heart rate rhythmicity patterns did not change. Changes in blood pressure amplitude correlated with the decrease of waist circumference (P=0.035). Moreover, the decrease of visceral fat correlated with the decrease of 24-hour mean arterial pressure and heart rate acrophases (both P<0.05). There were no differences in changes of blood pressure and heart rate rhythms between patients who achieved or did not achieve normotension and regression of left ventricular mass and carotid intima-media thickness. It was concluded that abnormal cardiovascular rhythmicity persists in children with primary hypertension despite effective antihypertensive treatment, which suggests that it may be the primary abnormality. The correlation between changes in cardiovascular rhythmicity and visceral obesity may indicate that the visceral fat plays an important role in the sympathetic activity of adolescents with hypertension.

  3. Visceral leishmaniasis: immunology and prospects for a vaccine.

    PubMed

    Kaye, P M; Aebischer, T

    2011-10-01

    Human visceral leishmaniasis (HVL) is the most severe clinical form of a spectrum of neglected tropical diseases caused by protozoan parasites of the genus Leishmania. Caused mainly by L. donovani and L. infantum/chagasi, HVL accounts for more than 50 000 deaths every year. Drug therapy is available but costly, and resistance against several drug classes has evolved. Here, we review our current understanding of the immunology of HVL and approaches to and the status of vaccine development against this disease.

  4. Irritable bowel syndrome in childhood: visceral hypersensitivity and psychosocial aspects.

    PubMed

    Iovino, P; Tremolaterra, F; Boccia, G; Miele, E; Ruju, F M; Staiano, A

    2009-09-01

    Visceral hypersensitivity is often considered to play a major etiologic role in the pathophysiology of irritable bowel syndrome in adults, and some authors argue that this increased sensitivity is mainly due to psychological factors. In contrast, there are no data in children with irritable bowel syndrome which confirm this relationship. The aim of the study was to evaluate the relationship between psychosocial aspects and sensorymotor function in children affected by irritable bowel syndrome. Ten children fulfilling the Rome II criteria for irritable bowel syndrome and seven healthy controls were enrolled. We studied the thresholds and the perception of visceral stimuli in the rectum by means of an electronic barostat (isobaric phasic distentions, 3 mmHg/1 min, interval 1 min) and a validated questionnaire. Personality features were evaluated by means of the Big Five Questionnaire for Children. Sleep, mood disturbance, anxiety and individual performance (missed school days, school results and social activities) were also evaluated. Children with irritable bowel syndrome showed significantly lower thresholds for discomfort (14.8 +/- 3.5 vs 22.3 +/- 6.9 mmHg, P = 0.010) and a higher cumulative perception score (28.2 +/- 11.1 vs 12.3 +/- 8.0, P = 0.005) compared with healthy controls. A higher emotional instability (57.8 +/- 7.0 vs 48.7 +/- 10.1, P = 0.047), sleep disturbance (7.2 +/- 1.0 vs 9.3 +/- 0.5, P = 0.004) and anxiety (6.3 +/- 2.0 vs 2.3 +/- 1.7, P = 0.009) were observed in irritable bowel syndrome patients. Moreover, in a multivariate analysis, the cumulative perception score was significantly related to emotional instability (P = 0.042). In conclusion children with irritable bowel syndrome exhibit visceral hypersensitivity and psychosocial impairment. Emotional instability, as a personality feature in these children, seems to modulate the perception response to visceral stimulations.

  5. Employees with Chronic Pain

    MedlinePlus

    ... Home | Accommodation and Compliance Series: Employees with Chronic Pain By Beth Loy, Ph.D. Preface Introduction Information ... at http://AskJAN.org/soar. Information about Chronic Pain How prevalent is chronic pain? Chronic pain has ...

  6. Complex Regional Pain Syndrome

    MedlinePlus

    Complex regional pain syndrome (CRPS) is a chronic pain condition. It causes intense pain, usually in the arms, hands, legs, or feet. ... in skin temperature, color, or texture Intense burning pain Extreme skin sensitivity Swelling and stiffness in affected ...

  7. When Sex Is Painful

    MedlinePlus

    ... AQ FREQUENTLY ASKED QUESTIONS GYNECOLOGIC PROBLEMS FAQ020 When Sex Is Painful • How common is painful sex? • What causes pain during sex? • Where is pain during sex felt? • When should ...

  8. A rare case of dysembryoplastic neuroepithelial tumor combined with encephalocraniocutaneous lipomatosis and intractable seizures

    PubMed Central

    Han, Jee-Yeon; Yum, Mi-Sun; Kim, Eun-Hee; Hong, Seokho

    2016-01-01

    Encephalocraniocutaneous lipomatosis (ECCL) is a rare neurocutaneous syndrome that affects ectomesodermal tissues (skin, eyes, adipose tissue, and brain). The neurologic manifestations associated with ECCL are various including seizures. However, ECCL patients very rarely develop brain tumors that originate from the neuroepithelium. This is the first described case of ECCL in combination with dysembryoplastic neuroepithelial tumor (DNET) that presented with intractable seizures. A 7-year-old girl was admitted to our center because of ECCL and associated uncontrolled seizures. She was born with right anophthalmia and lipomatosis in the right temporal area and endured right temporal lipoma excision at 3 years of age. Seizures began when she was 3 years old, but did not respond to multiple antiepileptic drugs. Brain magnetic resonance (MR) imaging performed at 8 and 10 years of age revealed an interval increase of multifocal hyperintense lesions in the basal ganglia, thalamus, cerebellum, periventricular white matter, and, especially, the right temporal area. A nodular mass near the right hippocampus demonstrated the absence of N-acetylaspartate decrease on brain MR spectroscopy and mildly increased methionine uptake on brain positron emission tomography, suggesting low-grade tumor. Twenty-four-hour video electroencephalographic monitoring also indicated seizures originating from the right temporal area. Right temporal lobectomy was performed without complications, and the nodular lesion was pathologically identified as DNET. The patient has been seizure-free for 14 months since surgery. Although ECCL-associated brain tumors are very rare, careful follow-up imaging and surgical resection is recommended for patients with intractable seizures. PMID:28018467

  9. Immediate and long term outcome after infrathalamic and thalamic lesioning for intractable Tourette's syndrome

    PubMed Central

    Babel, T; Warnke, P; Ostertag, C

    2001-01-01

    OBJECTIVE—The surgical treatment of intractable Tourette's syndrome is controversial. Experience with 17 consecutive patients treated between 1970 and 1998 is reviewed and the efficacy and safety of surgical treatment is assessed.
METHODS—These patients were retrospectively reclassified into subtypes according to the protocol of the Tourette's Syndrome Study Group. One patient was excluded from the study. Ventriculography based stereotactic zona incerta (ZI) and ventrolateral/ lamella medialis thalamotomy (VL/LM) were performed on all patients. The preoperative, postoperative, and late tic severities were assessed by the tic severity rating scale. The median follow up of 11 patients (65%) was 7 years (range 3.5-17 years) and six patients were lost to long term follow up.
RESULTS—Median age was 23 years (range 11-40) at the time of surgery. Median duration of illness was 14 years (range 3-33). The mean preoperative motor and vocal tic severities were estimated to be 4.44 (SD 0.63) and 3.81 (SD 0.66), respectively. Unilateral ZI lesioning and VL/LM lesioning selected by asymmetry of symptoms provide an effective control of tic severity (p motor and vocal<0.001). In attenuation of contralateral symptoms, a second surgical intervention in the relevant side could reduce tic severity sufficiently (p motor<0.01; p vocal<0.005). Transient complications occurred in 68% of patients. Only one permanent complication was registered in six patients followed up after unilateral surgery. Two out of five patients followed up after bilateral surgery had disabling side effects of surgery.
CONCLUSIONS—ZI and VL/LM lesioning provide a significant long term reduction of tic severity in intractable Tourette's syndrome. Adequate selection of the side of first intervention might prevent the patient from increased risk of bilateral surgery.

 PMID:11309463

  10. The effect of leucotomy in intractable adolescent weight phobia (primary anorexia nervosa)

    PubMed Central

    Crisp, A. H.; Kalucy, R. S.

    1973-01-01

    Anorexia nervosa is best construed as a phobic avoidance response to the psychosocial maturational implications of adolescent weight. Within this state, surrender to the impulse to eat and consequent weight gain is associated with panic, depression and sometimes specific intense fear of loss of control. So long as the avoidance posture can be maintained the experience of such turmoil is largely avoided. Complicated ritualistic behaviour may arise to promote and secure the posture. However, its unrewarding and lonely nature still increasingly leaves the individual liable to the experience of depression. Established treatment procedures often assist recovery from the illness but intractable cases arise and it is amongst these that the majority of deaths occur either from inanition or suicide. The basis for the changes characteristically induced by leucotomy is complex. The procedure often leads to reduced tension and release of appetitive behaviour. This is taken to be due to some direct effect of the cerebral lesion and possibly the intervention may also be construed by some patients as a licence to behave differently. In patients with anorexia nervosa such appetitive release can be expected to promote considerable weight gain. However, the adverse psychological implications of such weight gain for the patient do not appear always to be so immediately or easily relieved. They may still experience panic, shame or depression and new patterns of social avoidance, or vomiting behaviour may develop. Intensive help of a psychotherapeutic and rehabilitative kind is then still required if the patient is to have the best chance of adjusting healthily to her newly found potential for a more normal nutritional status. Four patients who have undergone such treatment are described in this paper. It is concluded that leucotomy has a small but definite place in the treatment of patients with intractable anorexia nervosa. ImagesFig. 2 PMID:4806268

  11. Expression of laminin β1 and integrin α2 in the anterior temporal neocortex tissue of patients with intractable epilepsy.

    PubMed

    Wu, Yuan; Wang, Xue-feng; Mo, Xue-an; Li, Jing-mei; Yuan, Jie; Zheng, Jin-ou; Feng, Yun; Tang, Mei

    2011-06-01

    We investigated the expression of laminin β1 and integrin α2 in the anterior temporal neocortex tissue of patients with intractable epilepsy and explored the role of these molecules in the pathogenesis of this disease. Immunohistochemistry and immunofluorescence were used to test the expression of laminin β1 and integrin α2 in samples (from the brain bank of our department, n=32) of surgically removed anterior temporal neocortex tissues from intractable epilepsy patients, and the results were compared with those of controls (n=10). We found that laminin β1 and integrin α2 protein expression was significantly increased in the anterior temporal neocortex as compared with controls (immunohistochemistry optical density: laminin β1 = 0.36 ± 0.01 vs. 0.10 ± 0.03 for control; integrin α2=0.42 ± 0.02 vs. 0.04 ± 0.01 for control; p<.05). Immunofluorescence staining indicated that laminin β1 and integrin α2 accumulated in the plasma membrane and cytoplasm, with strong fluorescence intensity in the anterior temporal neocortex tissue of patients with intractable epilepsy. Thus, our work demonstrates that laminin β1 and integrin α2 expression is elevated in the anterior temporal neocortex tissue from patients with intractable epilepsy.

  12. Oral Mycostatin as a possible alternative treatment for intractable Ménière's disease: preliminary cohort study.

    PubMed

    Leong, A C; Pothier, D D; Rutka, J A

    2014-03-19

    Background: The potential efficacy of antifungal agents (e.g. Mycostatin) in treating acute attacks of Ménière's disease was first suggested in 1983 but few data have been published. Oral Mycostatin has been used as second-line medical treatment for intractable Ménière's disease at our institution for many years. Objective: This preliminary cohort study investigated the role of oral Mycostatin in intractable Ménière's disease. Methods: A retrospective review of patients with intractable Ménière's disease who started oral Mycostatin treatment between 2010 and 2012 was conducted. Results: Of 256 patients presenting with vertiginous disorders, 26 had definite Ménière's disease and had not responded to standard first-line treatment. Following oral Mycostatin treatment, improvements were reported for vertigo (n = 8), aural fullness (n = 7), tinnitus (n = 3) and subjective hearing loss (n = 3). Half of those with symptom improvement persisted with oral Mycostatin for two years and continued to remain asymptomatic. Conclusion: The use of oral Mycostatin to alleviate symptoms of intractable Ménière's disease showed promising results in this case series. Mycostatin may offer a safe and useful alternative for the management of Ménière's disease for patients with chronic unremitting symptoms in whom first-line treatment options have failed.

  13. Physical Feature Encoding and Word Recognition Abilities Are Altered in Children with Intractable Epilepsy: Preliminary Neuromagnetic Evidence

    PubMed Central

    Pardos, Maria; Korostenskaja, Milena; Xiang, Jing; Fujiwara, Hisako; Lee, Ki H.; Horn, Paul S.; Byars, Anna; Vannest, Jennifer; Wang, Yingying; Hemasilpin, Nat; Rose, Douglas F.

    2015-01-01

    Objective evaluation of language function is critical for children with intractable epilepsy under consideration for epilepsy surgery. The purpose of this preliminary study was to evaluate word recognition in children with intractable epilepsy by using magnetoencephalography (MEG). Ten children with intractable epilepsy (M/F 6/4, mean ± SD 13.4 ± 2.2 years) were matched on age and sex to healthy controls. Common nouns were presented simultaneously from visual and auditory sensory inputs in “match” and “mismatch” conditions. Neuromagnetic responses M1, M2, M3, M4, and M5 with latencies of ~100 ms, ~150 ms, ~250 ms, ~350 ms, and ~450 ms, respectively, elicited during the “match” condition were identified. Compared to healthy children, epilepsy patients had both significantly delayed latency of the M1 and reduced amplitudes of M3 and M5 responses. These results provide neurophysiologic evidence of altered word recognition in children with intractable epilepsy. PMID:26146459

  14. Evaluating Eve: visceral states influence the evaluation of impulsive behavior.

    PubMed

    Nordgren, Loran F; van der Pligt, Joop; van Harreveld, Frenk

    2007-07-01

    Impulsive behavior is a common source of stigma. The authors argue that people often stigmatize impulsive behavior because they fail to appreciate the influence visceral impulses have on behavior. Because people tend to underestimate the motivational force of cravings for sex, drugs, food, and so forth, they are prone to stigmatize those who act on these impulses. In line with this reasoning, in 4 studies, the authors found that participants who were in a cold state (e.g., not hungry) made less favorable evaluations of a related impulsive behavior (impulsive eating) than did participants who were in a hot state (e.g., hungry). This empathy gap effect was tested with 3 different visceral states--fatigue, hunger, and sexual arousal--and was found both when participants evaluated others' impulsive behavior (Studies 1 & 2) and when participants evaluated their own impulsive behavior (Study 3). Study 3 also demonstrated that the empathy gap effect is due to different perceptions of the strength of the visceral state itself. Finally, Study 4 revealed that this effect is state specific: Hungry people, for example, evaluated only hunger-driven impulses, and not other forms of impulse, more favorably.

  15. Role of Nampt and Visceral Adiposity in Esophagogastric Junction Adenocarcinoma

    PubMed Central

    Li, Haijun; Bai, E.; Zhang, Yong; Jia, Zhuoqi

    2017-01-01

    Nampt including eNampt and iNampt may contribute to mediating obesity-associated cancers. This study investigated the role of Nampt in esophagogastric junction adenocarcinoma (EGA), a cancer strongly correlated with obesity. Visceral adiposity was defined by waist circumference or VFA. eNampt in sera were measured by enzyme-linked immunosorbent assay. iNampt expression in EGA was determined by PCR, western blot, and immunohistochemistry. Sera eNampt were significantly elevated in these overweight and obese patients, especially for viscerally obese patients, and positively correlated with BMI, waist circumference, VFA, and also primary tumor, regional lymph nodes, and TNM stage (P < 0.05). iNampt expression in both the mRNA and protein levels was upregulated in EGAs (P < 0.05). iNampt staining was found primarily in the cytoplasm and nuclei and significantly associated with tumor, lymph nodes, and TNM stage and also correlated positively with serum eNampt, BMI, total fat area, VFA, superficial fat area, and waist circumference (P < 0.05). iNampt, eNampt, tumor, lymph nodes, and TNM stage correlated to the survival of EGAs, and iNampt expression and TNM stage affected the prognosis independently (P < 0.05). This study highlighted the association of eNampt/iNampt with visceral obesity and a potential impact on the biology of EGA. PMID:28168205

  16. Cortical processing of human somatic and visceral sensation.

    PubMed

    Aziz, Q; Thompson, D G; Ng, V W; Hamdy, S; Sarkar, S; Brammer, M J; Bullmore, E T; Hobson, A; Tracey, I; Gregory, L; Simmons, A; Williams, S C

    2000-04-01

    Somatic sensation can be localized precisely, whereas localization of visceral sensation is vague, possibly reflecting differences in the pattern of somatic and visceral input to the cerebral cortex. We used functional magnetic resonance imaging to study the cortical processing of sensation arising from the proximal (somatic) and distal (visceral) esophagus in six healthy male subjects. Esophageal stimulation was performed by phasic distension of a 2 cm balloon at 0.5 Hz. For each esophageal region, five separate 30 sec periods of nonpainful distension were alternated with five periods of similar duration without distension. Gradient echoplanar images depicting bold contrast were acquired using a 1.5 T GE scanner. Distension of the proximal esophagus was localized precisely to the upper chest and was represented in the trunk region of the left primary somatosensory cortex. In contrast, distension of the distal esophagus was perceived diffusely over the lower chest and was represented bilaterally at the junction of the primary and secondary somatosensory cortices. Different activation patterns were also observed in the anterior cingulate gyrus with the proximal esophagus being represented in the right midanterior cingulate cortex (BA 24) and the distal esophagus in the perigenual area (BA32). Differences in the activation of the dorsolateral prefrontal cortex and cerebellum were also observed for the two esophageal regions. These findings suggest that cortical specialization in the sensory-discriminative, affective, and cognitive areas of the cortex accounts for the perceptual differences observed between the two sensory modalities.

  17. Genitofemoral neuralgia: adding to the burden of chronic vulvar pain

    PubMed Central

    Verstraelen, Hans; De Zutter, Eline; De Muynck, Martine

    2015-01-01

    The vulva is a particularly common locus of chronic pain with neuropathic characteristics that occurs in women of any age, though most women with neuropathic type chronic vulvar pain will remain undiagnosed even following multiple physician visits. Here, we report on an exemplary case of a middle-aged woman who was referred to the Vulvovaginal Disease Clinic with debilitating vulvar burning and itching over the right labium majus that had been persisting for 2 years and was considered intractable. Careful history taking and clinical examination, followed by electrophysiological assessment through somatosensory evoked potentials was consistent with genitofemoral neuralgia, for which no obvious cause could be identified. Adequate pain relief was obtained with a serotonin–noradrenaline reuptake inhibitor and topical gabapentin cream. We briefly discuss the epidemiology, diagnosis, and treatment of genitofemoral neuralgia and provide a series of clues to guide clinicians in obtaining a presumptive diagnosis of specific neuropathic pain syndromes that may underlie chronic vulvar pain. We further aim to draw attention to the tremendous burden of chronic, unrecognized vulvar pain. PMID:26664155

  18. Percutaneous renal sympathetic nerve ablation for loin pain haematuria syndrome.

    PubMed

    Gambaro, Giovanni; Fulignati, Pierluigi; Spinelli, Alessio; Rovella, Valentina; Di Daniele, Nicola

    2013-09-01

    Loin pain haematuria syndrome (LPHS) is a severe renal pain condition of uncertain origin and often resistant to treatment. Nephrectomy and renal autotrasplantation have occasionally been performed in very severe cases. Its pathogenesis is controversial. A 40-year-old hypertensive lady was diagnosed with LPHS after repeated diagnostic imaging procedures had ruled out any renal, abdominal or spinal conditions to justify pain. Notwithstanding treatment with three drugs, she had frequent hypertensive crises during which the loin pain was dramatically exacerbated. Vascular causes of the pain and hypertension were investigated and excluded. Her renal function was normal. The patient was referred to a multidisciplinary pain clinic, but had no significant improvement in her pain symptoms despite the use of non-steroidal anti-inflammatory drugs, adjuvant antidepressants and opioid-like agents. The pain and the discomfort were so severe that her quality of life was very poor, and her social and professional activities were compromised. Nephrectomy and renal autotransplantation have occasionally been performed in these cases. Since visceral pain signals flow through afferent sympathetic fibres, we felt that percutaneous catheter-based radiofrequency ablation of the renal sympathetic nerve fibres (recently introduced for the treatment of drug-resistant hypertension) could be valuable for pain relief. We treated the patient with radiofrequency ablation (Medtronic Symplicity Catheter) applied only to the right renal artery. After a 6-month follow-up, the patient is pain free and normotensive with all drugs withdrawn. She has experienced no hypertensive crises in the meantime. This observation suggests that percutaneous sympathetic denervation could prove to be an effective mini-invasive strategy for the treatment of chronic renal pain, and LPHS in particular.

  19. The role of surgery in the treatment of typical and atypical facial pain.

    PubMed

    Broggi, G; Ferroli, P; Franzini, A; Galosi, L

    2005-05-01

    Effective management of facial pain syndromes requires a correct clinical diagnosis. The temporal pattern of chronic pain is the most important aspect to be considered. It allows the identification of three groups of patients: (1) those who have paroxysmal pain, (2) those with mixed paroxysmal and constant pain, and (3) those with strictly constant pain. The less is the paroxysmal component, the more likely it seems to be that surgical intervention is useless or even dangerous. In particular, when the diagnosis is atypical facial pain, that is, a diffuse, nonanatomic orofacial pain of unknown pathophysiology, none of the surgical strategies that can cure trigeminal neuralgia should be used. Trigeminal neuralgia patients are often referred to neurosurgeons because of their well-known capability to obtain pain relief through many different procedures such as microvascular decompression, percutaneous balloon microcompression, thermorizotomy, drug injection within the trigeminal cistern and radiosurgery. Since all these procedure can cure patients with typical trigeminal neuralgia, the ideal algorithm of treatment is still under debate. We report on our 20 year-long experience with the surgical treatment of facial pain in general and trigeminal neuralgia in particular. Our treatment algorithm for trigeminal neuralgia is presented. Some ideas to offer a possible surgical help to patients with less typical, medically intractable, chronic facial pain are also given.

  20. Neck pain

    PubMed Central

    2008-01-01

    Introduction Non-specific neck pain has a postural or mechanical basis and affects about two thirds of people at some stage, especially in middle age. Acute neck pain resolves within days or weeks, but may become chronic in about 10% of people. Whiplash injuries follow sudden acceleration–deceleration of the neck, such as in road traffic or sporting accidents. Up to 40% of people continue to report symptoms 15 years after the accident, although this varies between countries. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for people with non-specific neck pain without severe neurological deficit? What are the effects of treatments for acute whiplash injury? What are the effects of treatments for chronic whiplash injury? What are the effects of treatments for neck pain with radiculopathy? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2007 (BMJ Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 91 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of the evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: acupuncture, biofeedback, drug treatments (analgesics, antidepressants, epidural steroid injections, muscle relaxants, non-steroidal anti-inflammatory drugs [NSAIDs]), early mobilisation, early return to normal activity, exercise, heat or cold, manipulation (alone or plus exercise), mobilisation, multimodal treatment, patient education, percutaneous radiofrequency neurotomy

  1. Role of voltage gated Ca2+ channels in rat visceral hypersensitivity change induced by 2,4,6-trinitrobenzene sulfonic acid

    PubMed Central

    2013-01-01

    Background Visceral pain is common symptom involved in many gastrointestinal disorders such as inflammatory bowel disease. The underlying molecular mechanisms remain elusive. We investigated the molecular mechanisms and the role for voltage gated calcium channel (VGCC) in the pathogenesis in a rat model of 2,4,6-trinitrobenzenesulfonic acid (TNBS) induced visceral inflammatory hypersensitivity. Results Using Agilent cDNA arrays, we found 172 genes changed significantly in dorsal root ganglia (DRG) of TNBS treated rats. Among these changed genes, Cav1.2 and Cav2.3 were significantly up-regulated. Then the RT-PCR and Western blot further confirmed the up-regulation of Cav1.2 and Cav2.3. The whole cell patch clamp recording of acutely dissociated colonic specific DRG neurons showed that the peak IBa density was significantly increased in colonic neurons of TNBS treated rats compared with control rats (−127.82 ± 20.82 pA/pF Vs −91.67 ± 19.02 pA/pF, n = 9, *P < 0.05). To distinguish the different type of calcium currents with the corresponding selective channel blockers, we found that L-type (−38.56 ± 3.97 pA/pF Vs −25.75 ± 3.35 pA/pF, n = 9, * P < 0.05) and R-type (−13.31 ± 1.36 pA/pF Vs −8.60 ± 1.25 pA/pF, n = 9, * P < 0.05) calcium current density were significantly increased in colonic DRG neurons of TNBS treated rats compared with control rats. In addition, pharmacological blockade with L-type antagonist (nimodipine) and R-type antagonist (SNX-482) with intrathecal injection attenuates visceral pain in TNBS induced inflammatory visceral hypersensitivity. Conclusion Cav1.2 and Cav2.3 in colonic primary sensory neurons play an important role in visceral inflammatory hyperalgesia, which maybe the potential therapeutic targets. PMID:23537331

  2. The future of GI and liver research: editorial perspectives. IV. Visceral afferents: an update.

    PubMed

    Raybould, Helen E

    2003-06-01

    The number of articles published in American Journal of Physiology Gastrointestinal and Liver Physiology over the last 15 years on visceral afferents has increased dramatically. This reflects our growing ability to study the characteristics and function of visceral afferents and also the recognition of their importance in the maintenance of homeostasis and also in a number of pathophysiological conditions. However, there are several key unanswered questions concerning the function of visceral afferents that await further investigation.

  3. Modulation of visceral nociception, inflammation and gastric mucosal injury by cinnarizine.

    PubMed

    Abdel-Salam, Omar M E

    2007-01-01

    The effect of cinnarizine, a drug used for the treatment of vertigo was assessed in animal models of visceral nociception, inflammation and gastric mucosal injury. Cinnarizine (1.25-20 mg/kg, s.c.) caused dose-dependent inhibition of the abdominal constrictions evoked by i.p. injection of acetic acid by 38.7-99.4%. This effect of cinnarizine (2.5 mg/kg) was unaffected by co-administration of the centrally acting dopamine D2 receptor antagonists, sulpiride, haloperidol or metoclopramide, the peripherally acting D2 receptor antagonist domperidone, but increased by the D2 receptor agonist bromocryptine and by the non-selective dopamine receptor antagonist chlorpromazine. The antinociception caused by cinnarizine was naloxone insenstive, but enhanced by propranolol, atropine and by yohimbine. The antinociceptive effect of cinnarizine was prevented by co-treatment with the adenosine receptor blocker theophylline or by the ATP-sensitive potassium channel (K(ATP)) blocker glibenclamide. Cinnarizine at 2.5 mg/kg reversed the baclofen-induced antinociception. Cinnarizine at 2.5 mg/kg reduced immobility time in the Porsolt's forced-swimming test by 24%. Cinnarizine inhibited the paw oedema response to carrageenan and reduced gastric mucosal lesions caused by indomethacin in rats. It is suggested that cinnarizine exerts anti-inflammatory, antinociceptive and gastric protective properties. The mechanism by which cinnarizine modulates pain transmission is likely to involve adenosine receptors and K(ATP) channels.

  4. Pain Management: Post-Amputation Pain

    MedlinePlus

    Pain Management Post-Amputation Pain Volume 8 · Issue 2 · March/April 1998 Text size Larger text Smaller text Java Required Print page Save and share ... by G. Edward Jeffries, MD, FACS Post-Amputation Pain Post-amputation pain is one of the most ...

  5. Causes of Aseptic Persistent Pain after Total Knee Arthroplasty

    PubMed Central

    Lim, Hong-An; Seon, Jong-Keun; Park, Kyung-Soon; Shin, Young-Joo; Yang, Hong-Yeol

    2017-01-01

    Background Persistent pain after total knee arthroplasty (TKA) is dissatisfying to the patient and frustrating to the surgeon. The purpose of this study is to evaluate the aseptic causes and clinical course of intractable pain following TKA. Methods Of the total 2,534 cases of primary TKA reviewed, 178 cases were classified as having aseptic persistent pain that was not resolved within 1 year after surgery. Except for the cases with periprosthetic fracture (56 knees), 122 cases of aseptic painful TKA were divided into two groups: intra-articular group (83 knees) and extra-articular group (39 knees). Results In the intra-articular group, the main reasons for pain were aseptic loosening (n = 40), polyethylene wear (n = 16), instability (n = 10), recurrent hemarthrosis (n = 5), patellar maltracking (n = 4), tendon ruptures (n = 4), and stiffness (n = 2). In the extraarticular group, 10 knees (25.6%) were found to have nerve entrapment in the spine, 6 knees (15.4%) were found to have hip osteoarthritis or femoral head avascular necrosis. The reasons for persistent knee pain in the remaining 23 knees (59.0%) still remain elusive. Conclusions Persistent pain after TKA originated from pathology of extra-articular origin in a considerable number of cases in this study. Therefore, it is important to perform thorough preoperative evaluations to reduce pain resulting from extra-articular causes. Furthermore, meticulous surgical procedures and optimal alignment are required to reduce pain of intra-articular origin related to implant wear, instability, and patellar maltracking. PMID:28261427

  6. Physical therapy management of female chronic pelvic pain: Anatomic considerations.

    PubMed

    George, Susan E; Clinton, Susan C; Borello-France, Diane F

    2013-01-01

    The multisystem nature of female chronic pelvic pain (CPP) makes this condition a challenge for physical therapists and other health care providers to manage. This article uses a case scenario to illustrate commonly reported somatic, visceral, and neurologic symptoms and their associated health and participation impact in a female with CPP. Differential diagnosis of pain generators requires an in-depth understanding of possible anatomic and physiologic contributors to this disorder. This article provides a detailed discussion of the relevant clinical anatomy with specific attention to complex interrelationships between anatomic structures potentially leading to the patient's pain. In addition, it describes the physical therapy management specific to this case, including examination, differential diagnosis, and progression of interventions.

  7. Undertreatment of caner pain.

    PubMed

    Wang, Cheng-Hsu; Lee, Shiu-Yu C

    2015-06-01

    Pain is a burdensome symptom that can commonly exist chronically along the cancer trajectory. Uncontrolled pain will impact on cancer patients' quality of life, even further negatively affect cancer survivors' employment. Based on systemic reviews of studies for past 10 years, the paper reported that although there is enormous advancement on the knowledge of cancer pain and pain management, studies still documented undertreatment of cancer pain globally. Additionally, pain distress a significant portion of cancer survivors. The pain in cancer survivors distinct from the pain related with cancer, instead emphasize on pain related with cancer treatment, such as neuropathic pain, muscular syndrome. Evidence-based pain management with common pain problems in cancer survivors is lacking. Further studies are needed to understand the pain in cancer survivors and to develop effective strategies in helping cancer survivors to manage their pain.

  8. Long-term seizure and psychosocial outcomes of vagus nerve stimulation for intractable epilepsy.

    PubMed

    Wasade, Vibhangini S; Schultz, Lonni; Mohanarangan, Karthik; Gaddam, Aryamaan; Schwalb, Jason M; Spanaki-Varelas, Marianna

    2015-12-01

    Vagus nerve stimulation (VNS) is a widely used adjunctive treatment option for intractable epilepsy. Most studies have demonstrated short-term seizure outcomes, usually for up to 5 years, and thus far, none have reported psychosocial outcomes in adults. We aimed to assess long-term seizure and psychosocial outcomes in patients with intractable epilepsy on VNS therapy for more than 15 years. We identified patients who had VNS implantation for treatment of intractable epilepsy from 1997 to 2013 at our Comprehensive Epilepsy Program and gathered demographics including age at epilepsy onset and VNS implantation, epilepsy type, number of antiepilepsy drugs (AEDs) and seizure frequency before VNS implantation and at the last clinic visit, and the most recent stimulation parameters from electronic medical records (EMR). Phone surveys were conducted by research assistants from May to November 2014 to determine patients' current seizure frequency and psychosocial metrics, including driving, employment status, and use of antidepressants. Seizure outcomes were based on modified Engel classification (I: seizure-free/rare simple partial seizures; II: >90% seizure reduction (SR), III: 50-90% SR, IV: <50% SR; classes I to III (>50% SR)=favorable outcome). A total of 207 patients underwent VNS implantation, 15 of whom were deceased at the time of the phone survey, and 40 had incomplete data for medical abstraction. Of the remaining 152, 90 (59%) were contacted and completed the survey. Of these, 51% were male, with the mean age at epilepsy onset of 9.4 years (range: birth to 60 years). There were 35 (39%) patients with extratemporal epilepsy, 19 (21%) with temporal, 18 (20%) with symptomatic generalized, 5 (6%) with idiopathic generalized, and 13 (14%) with multiple types. Final VNS settings showed 16 (18%) patients with an output current >2 mA and 14 (16%) with rapid cycling. Of the 80 patients with seizure frequency information, 16 (20%) had a modified Engel class I outcome, 14

  9. Continuous Ilioinguinal-iliohypogastric Nerve Block for Groin Pain in a Breast-feeding Patient after Cesarean Delivery

    PubMed Central

    Kim, Eun Soo; Baik, Ji Seok; Ji, Young Tae

    2016-01-01

    Ilioinguinal and iliohypogastric (II/IH) nerve injury is one of the most common nerve injuries following pelvic surgery, especially with the Pfannenstiel incision. We present a case of intractable groin pain, successfully treated with a continuous II/IH nerve block. A 33-year-old woman, following emergency cesarean section due to cephalopelvic disproportion, presented numbness in left inguinal area and severe pain on the labia on the second postoperative day. The pain was burning, lancinating, and exacerbated by standing or movement. However, she didn't want to take additional medicine because of breast-feeding. A diagnostic II/IH nerve block produced a substantial decrease in pain. She underwent a continuous II/IH nerve block with a complete resolution of pain within 3 days. A continuous II/IH nerve block might be a goodoption for II/IH neuropathy with intractable groin pain in breast-feeding mothers without adverse drug reactions in their infants. PMID:27413486

  10. Opioids in chronic noncancer pain: More faces from the crowd

    PubMed Central

    Watson, C Peter N

    2012-01-01

    BACKGROUND: The use of opioids for chronic noncancer pain (CNCP) remains very controversial. There are several randomized controlled trials, mostly in neuropathic pain, reporting efficacy and safety in the short term, but more long-term data are needed. Randomized controlled trials may be limited in providing data about the patients who benefit from often high-dose opioids over the long term. The present article provides details of these patients and adds to a previous case series. METHODS: The present article contains 17 case reports of 11 CNCP conditions (followed to 2011) selected to illustrate specific issues from a survey of 84 patients with intractable CNCP treated with opioids and followed every three months for a median of 11 years. The previous published survey of this group reported outcomes of pain severity, adverse effects, pain relief, satisfaction, mood, problematic opioid use, tolerance, physical dependency, functional status, health-related quality of life (HRQL), immune status and sexual function. The outcome measures for that study included a numerical rating scale for pain, the Hospital Anxiety and Depression Scale, the Brief Pain Inventory Interference Scale, the Pain Disability Index and, for HRQL, the Short-Form Health Survey 12 version 2. Most patients in the total sample reported 50% or greater relief and a moderate improvement in disability. Scores for functional status and HRQL were not severely affected. Problematic use, tolerance and serious adverse effects, including constipation, were not major issues. These selected patient reports were chosen, not to illustrate optimal results, but rather important aspects of the diagnoses, opioids and doses, the paucity of intolerable adverse effects, particular issues (concurrent addiction history, bipolar disorder and combination therapy), disease-specific and other outcomes and duration of follow-up with complex pain problems. RESULTS: Opioids were found to be safe and useful in the long term for

  11. Definitions and Types of Pain

    MedlinePlus

    ... Therapy Pain Management Recommendations References April 15, 2017 Definitions and Types of Pain Defining Pain Pain is ... there are many mechanisms involved in nociception. More definitions ... Classifying Pain Pain can be "acute" or "chronic." ...

  12. Association of subcutaneous and visceral fat mass with serum concentrations of adipokines in subjects with type 2 diabetes mellitus.

    PubMed

    Saito, Tomoyuki; Murata, Miho; Otani, Taeko; Tamemoto, Hiroyuki; Kawakami, Masanobu; Ishikawa, San-E

    2012-01-01

    The goal of the study was to examine the association of subcutaneous and visceral fat mass with serum concentrations of adipokines in 130 subjects with type 2 diabetes mellitus. The levels of serum high sensitivity C-reactive protein (HS-CRP), adiponectin, high-molecular-weight (HMW) adiponectin, interleukin-18, and retinol-binding protein 4 were measured. Percentage body fat was determined by dual energy X-ray absorptiometry, and subcutaneous and visceral fat areas were measured by abdominal CT. HS-CRP had significant positive correlations with percentage body fat and subcutaneous fat area, and a particularly significant positive correlation with visceral fat area. Serum adiponectin had a negative correlation with the subcutaneous and visceral fat areas, with the strongest correlation with the visceral fat area. Similar results were obtained for HMW adiponectin. Serum adiponectin had a negative correlation with visceral fat area in subjects with a visceral fat area < 100 cm², but not in those with a visceral fat area ≥ 100 cm². In contrast, serum HS-CRP showed a positive correlation with visceral fat area in subjects with visceral fat area ≥ 100 cm², but not in those with a visceral fat area < 100 cm². These findings indicate that an increased visceral fat area is associated with inflammatory changes, and that inflammatory reactions may alter the functional properties of visceral fat in type 2 diabetes mellitus.

  13. [On the Differential Diagnosis of Intractable Psychogenic Chronic Cough: Neuropathic Larynx Irritable - Gabapentin's Antitussive Action].

    PubMed

    Bonnet, U; Ossowski, A; Schubert, M; Gall, H; Steinkamp, I; Richter, L E; Khalil-Boutros, Y; Nefedev, A; Kuhlmann, R

    2015-10-01

    We present the case of a 76 year old female inpatient who suffered from a chronic intractable cough which arose simultaneously to a severe major depression and was secondary to an exorbitant psychological distress. Chronic cough had never been experienced before and was initially considered to have a mere psychogenic origin since a comprehensive and guideline-based diagnostic screening did not reveal any underlying somatic cause. However, several factors cast doubt on the solitary psychic genesis of the chronic cough: i) occurrence immediately after a penetrant cold, ii) embedding in other complaints of laryngeal hyperreagibility (larynx irritable), such as persistent globus pharyngeus sensation, throat clearing and episodic dysphonia, iii) first occurrence on old life, iv) erupting from sleep as well, v) persistence despite remission of the major depression, and v) no sustaining benefit from specific psychotherapy and speech therapy. Therefore, diagnostics were extended to apparative tools for objective evaluation of swallowing by using fiberoptic videoendoscopic (FEES) and videofluoroscopic (VFS) techniques, which revealed signs of laryngeal neuropathy but without evidence of penetration or aspiration. A co-existing small goiter and an impaired glucose tolerance along with a putative intracellular vitamin B12 or folate deficiency (as indirectly derived from an apparent hyperhomocysteinemia) were assumed to be responsible for the neuropathy and underwent specific treatments. The impaired glucose tolerance and putative vitamin deficit were compatible with a distal symmetric sensorimotoric, even subclinical polyneuropathy of the lower extremities. The larynx irritable improved under gabapentin being confirmed by drug removals several times, and finally calmed down almost completely under gabapentin, which was in line with the scant literature of this topic. Re-examination of the larynx per FEES nine months later showed no deficits any more under the well

  14. Modulation of adipocyte lipoprotein lipase expression as a strategy for preventing or treating visceral obesity.

    PubMed

    McCarty, M F

    2001-08-01

    As compared to subcutaneous adipocytes, visceral adipocytes have high basal lipolysis, are highly sensitive to catecholamines, and are poorly sensitive to insulin; these traits are amplified when visceral adipocytes hypertrophy. As a result, enlarged visceral fat stores tend to flood the portal circulation with free fatty acids at metabolically inappropriate times when fatty acids are unlikely to be oxidized, thus exposing tissues to excessive free fatty acid levels and giving rise to the insulin resistance syndrome. A logical approach to preventing or correcting visceral obesity is to down-regulate the lipoprotein lipase (LPL) activity of visceral adipocytes relative to that expressed in subcutaneous adipocytes and skeletal muscle. IGF-I activity appears to be a primary determinant of visceral LPL activity in humans; systemic IGF-I activity is decreased when diurnal insulin secretion is low, when hepatocytes detect a relative paucity of certain essential amino acids, and when estrogens are administered orally. The ability of alpha-glucosidase inhibitor therapy to selectively reduce visceral adiposity suggests that down-regulation of diurnal insulin secretion and/or IGF-I activity may indeed have a greater impact on LPL activity in visceral fat than in subcutaneous fat. Thus, low-glycemic-index, vegan, high-protein, or hypocaloric diets can be expected to decrease visceral LPL activity, as can postmenopausal estrogen therapy. Furthermore, estrogen enhances the LPL activity of non-pathogenic gluteofemoral fat cells, whereas testosterone decreases visceral LPL activity in men; this may explain why sex hormone replacement in middle-aged people of both sexes has a favorable impact on visceral fat and insulin sensitivity. Beta-adrenergic activity suppresses transcription of LPL in adipocytes; this phenomenon may contribute to the favorable impact of exercise training on visceral obesity; conceivably, preadministration of safe drugs that boost catecholamine activity

  15. Modest Visceral Fat Gain Causes Endothelial Dysfunction In Healthy Humans

    PubMed Central

    Romero-Corral, Abel; Sert-Kuniyoshi, Fatima H.; Sierra-Johnson, Justo; Orban, Marek; Gami, Apoor; Davison, Diane; Singh, Prachi; Pusalavidyasagar, Snigdha; Huyber, Christine; Votruba, Susanne; Lopez-Jimenez, Francisco; Jensen, Michael D.; Somers, Virend K.

    2014-01-01

    Objective This study sought to determine the impact of fat gain and its distribution on endothelial function in lean healthy humans. Background Endothelial dysfunction has been identified as an independent predictor of cardiovascular events. Whether fat gain impairs endothelial function is unknown. Methods A randomized controlled study to assess the effects of fat gain on endothelial function. We recruited 43 normal weight healthy volunteers (mean age 29 years; 18 women). Subjects were assigned to gain weight (approximately 4 kg) (n=35) or to maintain weight (n=8). Endothelial function (brachial artery flow mediated dilation -FMD) was measured at baseline, after fat gain (8 weeks) and after weight loss (16 weeks) for fat-gainers and at baseline and follow-up (8 weeks) for weight-maintainers. Body composition was measured by DXA and abdominal CT scans. Results After an average weight gain of 4.1 kg, fat-gainers significantly increased their total, visceral and subcutaneous fat. Blood pressure and overnight polysomnography did not change after fat gain or loss. FMD remained unchanged in weight-maintainers. FMD decreased in fat-gainers (9.1 ± 3% vs. 7.8 ± 3.2%, p =0.003), but recovered to baseline when subjects shed the gained weight. There was a significant correlation between the decrease in FMD and the increase in visceral fat gain (rho = −0.42, p=0.004), but not with subcutaneous fat gain (rho = −0.22, p=0.15). Conclusions In normal weight healthy young subjects, modest fat gain results in impaired endothelial function, even in the absence of changes in blood pressure. Endothelial function recovers after weight loss. Increased visceral rather than subcutaneous fat predicts endothelial dysfunction. PMID:20705223

  16. Accounting for False Positive HIV Tests: Is Visceral Leishmaniasis Responsible?

    PubMed Central

    Shanks, Leslie; Ritmeijer, Koert; Piriou, Erwan; Siddiqui, M. Ruby; Kliescikova, Jarmila; Pearce, Neil; Ariti, Cono; Muluneh, Libsework; Masiga, Johnson; Abebe, Almaz

    2015-01-01

    Background Co-infection with HIV and visceral leishmaniasis is an important consideration in treatment of either disease in endemic areas. Diagnosis of HIV in resource-limited settings relies on rapid diagnostic tests used together in an algorithm. A limitation of the HIV diagnostic algorithm is that it is vulnerable to falsely positive reactions due to cross reactivity. It has been postulated that visceral leishmaniasis (VL) infection can increase this risk of false positive HIV results. This cross sectional study compared the risk of false positive HIV results in VL patients with non-VL individuals. Methodology/Principal Findings Participants were recruited from 2 sites in Ethiopia. The Ethiopian algorithm of a tiebreaker using 3 rapid diagnostic tests (RDTs) was used to test for HIV. The gold standard test was the Western Blot, with indeterminate results resolved by PCR testing. Every RDT screen positive individual was included for testing with the gold standard along with 10% of all negatives. The final analysis included 89 VL and 405 non-VL patients. HIV prevalence was found to be 12.8% (47/ 367) in the VL group compared to 7.9% (200/2526) in the non-VL group. The RDT algorithm in the VL group yielded 47 positives, 4 false positives, and 38 negatives. The same algorithm for those without VL had 200 positives, 14 false positives, and 191 negatives. Specificity and positive predictive value for the group with VL was less than the non-VL group; however, the difference was not found to be significant (p = 0.52 and p = 0.76, respectively). Conclusion The test algorithm yielded a high number of HIV false positive results. However, we were unable to demonstrate a significant difference between groups with and without VL disease. This suggests that the presence of endemic visceral leishmaniasis alone cannot account for the high number of false positive HIV results in our study. PMID:26161864

  17. Loin to groin pain: The importance of a differential diagnosis

    PubMed Central

    Smith, Alexander E.P.; Bhatti, Ibrahim N.; Hester, Thomas; Ritchie, James F.S.

    2015-01-01

    Introduction Ureteric colic frequently presents as loin to groin pain and accounts for a significant proportion of emergency urological admissions. However, a number of differential diagnoses should be considered in a systematic approach when assessing patients. Presentation of case We report a case of a 30 year old man admitted with severe unilateral loin to groin pain following lumbar specific weightlifting exercises. After a significant delay due to initial mis-diagnosis he was diagnosed with acute paravertebral lumbar compartment syndrome (PVCS) and managed conservatively. Discussion Exertional PVCS is a rare and potentially life threatening condition arising following lumbar specific exercise that has only been recorded a handful of times previously. Patients typically present with intractable lumbar pain and rhabdomyolysis 6–12 h following exercise. Due to initial diagnostic delay our case was managed conservatively with fluid resuscitation and monitoring of renal function. Conclusion Assessment of patients with loin pain requires a systematic approach. PVCS is a rare cause of lumbar back and loin pain but one that should be considered, particularly in active young males. Early diagnosis is key to prevent the potential sequalae of untreated rhabdomyolysis. There is currently no consensus on management option for PVCS with only a few cases being reported in the literature. We describe successful management with supportive non operative treatment. PMID:26453939

  18. 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.

  19. The painless brain: lobotomy, psychiatry, and the treatment of chronic pain and terminal illness.

    PubMed

    Raz, Mical

    2009-01-01

    This article examines the use of lobotomy as a treatment for chronic intractable pain and reconstructs then-common perceptions of pain and of the patients who suffered from it. It delineates the social expectations and judgments implicit in physicians' descriptions of the patients, analyzing what was expected from such patients and how the medical establishment responded to non-normative expressions of suffering. I argue that the medicalized response to an expectation for normativity demonstrates the convergence between psychiatric and palliative interventions. Based on a historically informed perspective of psychiatric interventions in the field of pain medicine, I examine the use of psychiatric medications for pain syndromes today and evaluate the interface between depression, chronic pain, and terminal illness. While not detracting from the medical imperative to alleviate pain, I question the usage of social criteria and normative judgments in the clinical decision of how to treat pain. What normalizing social function does the use of psychiatric interventions in pain treatment fulfill? This approach leads to a reexamination of perceptions of dualism in pain medicine.

  20. Effect of Spinal Cord Stimulation on Gait in a Patient with Thalamic Pain

    PubMed Central

    Shin, Masahiro; Ishi, Kazuhiko; Osumi, Michihiro; Katsuhira, Junji; Chiba, Ryosuke; Haga, Nobuhiko

    2016-01-01

    Thalamic pain is a central neuropathic pain disorder which occurs after stroke. Its severe chronic pain is often intractable to pharmacotherapies and affects the patients' activities of daily living (ADL) and quality of life (QOL). Recently, spinal cord stimulation (SCS) has been reported to be effective in relieving the pain of thalamic pain; however, the effect of SCS on gait performance in patients is unknown. Therefore, we evaluated the gait performance before and after SCS in a case with thalamic pain. A 73-year-old male with thalamic pain participated in this study. We evaluated the gait of the patient two times: before SCS insertion and after 6 days of SCS. At the second evaluation, we measured the gait in three conditions: stimulation off, comfortable stimulation, and strong stimulation. SCS succeeded in improving the pain from 7 to 2 on an 11-point numerical rating scale. Step frequency and the velocity of gait tended to increase between pre- and poststimulation periods. There were no apparent differences in gait among the three stimulation conditions (off, comfortable, and strong) at the poststimulation period. SCS may be effective on gait in patients with thalamic pain. PMID:27579198