Can a single pulse transcranial magnetic stimulation targeted to the motor cortex interrupt pain processing?

PubMed Central

Kisler, Lee-Bareket; Gurion, Ilan; Granovsky, Yelena; Sinai, Alon; Sprecher, Elliot; Shamay-Tsoory, Simone

2018-01-01

The modulatory role of the primary motor cortex (M1), reflected by an inhibitory effect of M1-stimulation on clinical pain, motivated us to deepen our understanding of M1’s role in pain modulation. We used Transcranial Magnetic Stimulation (TMS)-induced virtual lesion (VL) to interrupt with M1 activity during noxious heat pain. We hypothesized that TMS-VL will effect experimental pain ratings. Three VL protocols were applied consisting of single-pulse TMS to transiently interfere with right M1 activity: (1) VLM1- TMS applied to 11 subjects, 20 msec before the individual’s first pain-related M1 peak activation, as determined by source analysis (sLORETA), (2) VL-50 (N = 16; TMS applied 50 ms prior to noxious stimulus onset), and (3) VL+150 (N = 16; TMS applied 150 ms after noxious stimulus onset). Each protocol included 3 conditions ('pain-alone', ' TMS-VL', and ‘SHAM-VL’), each consisted of 30 noxious heat stimuli. Pain ratings were compared, in each protocol, for TMS-VL vs. SHAM-VL and vs. pain-alone conditions. Repeated measures analysis of variance, corrected for multiple comparisons revealed no significant differences in the pain ratings between the different conditions within each protocol. Therefore, our results from this exploratory study suggest that a single pulse TMS-induced VL that is targeted to M1 failed to interrupt experimental pain processing in the specific three stimulation timing examined here. PMID:29630681

Can a single pulse transcranial magnetic stimulation targeted to the motor cortex interrupt pain processing?

PubMed

Kisler, Lee-Bareket; Gurion, Ilan; Granovsky, Yelena; Sinai, Alon; Sprecher, Elliot; Shamay-Tsoory, Simone; Weissman-Fogel, Irit

2018-01-01

The modulatory role of the primary motor cortex (M1), reflected by an inhibitory effect of M1-stimulation on clinical pain, motivated us to deepen our understanding of M1's role in pain modulation. We used Transcranial Magnetic Stimulation (TMS)-induced virtual lesion (VL) to interrupt with M1 activity during noxious heat pain. We hypothesized that TMS-VL will effect experimental pain ratings. Three VL protocols were applied consisting of single-pulse TMS to transiently interfere with right M1 activity: (1) VLM1- TMS applied to 11 subjects, 20 msec before the individual's first pain-related M1 peak activation, as determined by source analysis (sLORETA), (2) VL-50 (N = 16; TMS applied 50 ms prior to noxious stimulus onset), and (3) VL+150 (N = 16; TMS applied 150 ms after noxious stimulus onset). Each protocol included 3 conditions ('pain-alone', ' TMS-VL', and 'SHAM-VL'), each consisted of 30 noxious heat stimuli. Pain ratings were compared, in each protocol, for TMS-VL vs. SHAM-VL and vs. pain-alone conditions. Repeated measures analysis of variance, corrected for multiple comparisons revealed no significant differences in the pain ratings between the different conditions within each protocol. Therefore, our results from this exploratory study suggest that a single pulse TMS-induced VL that is targeted to M1 failed to interrupt experimental pain processing in the specific three stimulation timing examined here.

Astrocytic Ca2+ responses in the spinal dorsal horn by noxious stimuli to the skin.

PubMed

Yoshihara, Kohei; Matsuda, Tsuyoshi; Kohro, Yuta; Tozaki-Saitoh, Hidetoshi; Inoue, Kazuhide; Tsuda, Makoto

2018-05-03

The role of astrocytes in the spinal dorsal horn (SDH) for sensory information processing under normal conditions is poorly understood. In this study, we investigated whether SDH astrocytes respond to noxious and innocuous stimuli to the skin of normal mice using in vivo two-photon Ca 2+ imaging under anesthesia. We found that noxious stimulation evoked by intraplantar formalin injection provoked an elevation in intracellular Ca 2+ levels in SDH astrocytes. By contrast, neither instantaneous noxious pinching nor innocuous stimuli (cooling or brushing) to the hindpaw elicited astrocytic Ca 2+ responses. Thus, SDH astrocytes could respond preferentially to a strong and/or sustained noxious stimulus. Copyright © 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Autonomic responses to tonic pain are more closely related to stimulus intensity than to pain intensity.

PubMed

Nickel, Moritz M; May, Elisabeth S; Tiemann, Laura; Postorino, Martina; Ta Dinh, Son; Ploner, Markus

2017-11-01

Pain serves the protection of the body by translating noxious stimulus information into a subjective percept and protective responses. Such protective responses rely on autonomic responses that allocate energy resources to protective functions. However, the precise relationship between objective stimulus intensity, subjective pain intensity, autonomic responses, and brain activity is not fully clear yet. Here, we addressed this question by continuously recording pain ratings, skin conductance, heart rate, and electroencephalography during tonic noxious heat stimulation of the hand in 39 healthy human subjects. The results confirmed that pain intensity dissociates from stimulus intensity during 10 minutes of noxious stimulation. Furthermore, skin conductance measures were significantly related to stimulus intensity but not to pain intensity. Correspondingly, skin conductance measures were significantly related to alpha and beta oscillations in contralateral sensorimotor cortex, which have been shown to encode stimulus intensity rather than pain intensity. No significant relationships were found between heart rate and stimulus intensity or pain intensity. The findings were consistent for stimulation of the left and the right hands. These results suggest that sympathetic autonomic responses to noxious stimuli in part directly result from nociceptive rather than from perceptual processes. Beyond, these observations support concepts of pain and emotions in which sensory, motor, and autonomic components are partially independent processes that together shape emotional and painful experiences.

Tonic pain and continuous EEG: prediction of subjective pain perception by alpha-1 power during stimulation and at rest.

PubMed

Nir, Rony-Reuven; Sinai, Alon; Moont, Ruth; Harari, Eyal; Yarnitsky, David

2012-03-01

Pain neurophysiology has been chiefly characterized via event-related potentials (ERPs), which are exerted using brief, phase-locked noxious stimuli. Striving for objectively characterizing clinical pain states using more natural, prolonged stimuli, tonic pain has been recently associated with the individual peak frequency of alpha oscillations. This finding encouraged us to explore whether alpha power, reflecting the magnitude of the synchronized activity within this frequency range, will demonstrate a corresponding relationship with subjective perception of tonic pain. Five-minute-long continuous EEG was recorded in 18 healthy volunteers under: (i) resting-state; (ii) innocuous temperature; and (iii) psychophysically-anchored noxious temperature. Numerical pain scores (NPSs) collected during the application of tonic noxious stimuli were tested for correlation with alpha-1 and alpha-2 power. NPSs and alpha power remained stable throughout the recording conditions (Ps⩾0.381). In the noxious condition, alpha-1 power obtained at the bilateral temporal scalp was negatively correlated with NPSs (Ps⩽0.04). Additionally, resting-state alpha-1 power recorded at the bilateral temporal scalp was negatively correlated with NPSs reported during the noxious condition (Ps⩽0.038). Current findings suggest alpha-1 power may serve as a direct, objective and experimentally stable measure of subjective perception of tonic pain. Furthermore, resting-state alpha-1 power might reflect individuals' inherent tonic pain responsiveness. The relevance of alpha-1 power to tonic pain perception may deepen the understanding of the mechanisms underlying the processing of prolonged noxious stimulation. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Noxious lingual stimulation influences the excitability of the face primary motor cerebral cortex (face MI) in the rat.

PubMed

Adachi, K; Murray, G M; Lee, J-C; Sessle, B J

2008-09-01

The mechanisms whereby orofacial pain affects motor function are poorly understood. The aims were to determine whether 1) lingual algesic chemical stimulation affected face primary motor cerebral cortex (face MI) excitability defined by intracortical microstimulation (ICMS); and 2) any such effects were limited to the motor efferent MI zones driving muscles in the vicinity of the noxious stimulus. Ketamine-anesthetized Sprague-Dawley male rats were implanted with electromyographic (EMG) electrodes into anterior digastric, masseter, and genioglossus muscles. In 38 rats, three microelectrodes were located in left face MI at ICMS-defined sites for evoking digastric and/or genioglossus responses. ICMS thresholds for evoking EMG activity from each site were determined every 15 min for 1 h, then the right anterior tongue was infused (20 microl, 120 microl/h) with glutamate (1.0 M, n = 18) or isotonic saline (n = 7). Subsequently, ICMS thresholds were determined every 15 min for 4 h. In intact control rats (n = 13), ICMS thresholds were recorded over 5 h. Only left and right genioglossus ICMS thresholds were significantly increased (< or =350%) in the glutamate infusion group compared with intact and isotonic saline groups (P < 0.05). These dramatic effects of glutamate on ICMS-evoked genioglossus activity contrast with its weak effects only on right genioglossus activity evoked from the internal capsule or hypoglossal nucleus. This is the first documentation that intraoral noxious stimulation results in prolonged neuroplastic changes manifested as a decrease in face MI excitability. These changes appear to occur predominantly in those parts of face MI that provide motor output to the orofacial region receiving the noxious stimulation.

Assessment of nociception and pain in participants with unresponsive or minimally conscious state after acquired brain injury: the relationship between the Coma Recovery Scale-Revised and the Nociception Coma Scale-Revised.

PubMed

Chatelle, Camille; Hauger, Solveig L; Martial, Charlotte; Becker, Frank; Eifert, Bernd; Boering, Dana; Giacino, Joseph T; Laureys, Steven; Løvstad, Marianne; Maurer-Karattup, Petra

2018-04-10

Investigate the relationship between consciousness and nociceptive responsiveness (i.e., Nociception Coma Scale-Revised [NCS-R]), examine the suitability of the NCS-R for assessing nociception in participants with disorders of consciousness (DoC) and replicate previous findings on psychometric properties of the scale. We prospectively assessed consciousness with the Coma Recovery Scale-Revised (CRS-R). Responses during baseline, non-noxious and noxious stimulations were scored with the NCS-R, CRS-R oromotor and motor subscales. Specialized DoC program and university hospitals. Eighty-five participants diagnosed with DoCs. Correlation between CRS-R total scores and CRS-R and NCS-R (sub)scores to noxious stimulation, proportion of grimace and/or cry in participants with minimally consciousness (MCS) and unresponsive wakefulness syndrome (UWS) during non-noxious and noxious conditions. Not applicable RESULTS: CRS-R total scores correlated with NCS-R total scores and subscores. CRS-R motor subscale correlated with NCS-R total scores and motor subscale and CRS-R oromotor subscale correlated with NCS-R total scores, as well as verbal and facial expression. There was a difference between participants with UWS and MCS in the proportion of grimace and/or crying during the noxious condition. We replicated previous findings on psychometric properties of the scale, but found a different score as the best threshold for nociception. We report a strong relationship between responsiveness to nociception and the level of consciousness. The NCS-R seems to offer a valuable tool to assess nociception in an efficient manner, but additional studies are needed to allow recommendations for clinical assessment of subjective pain experience. Copyright © 2018 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Differential induction of c-Fos and phosphorylated ERK by a noxious stimulus after peripheral nerve injury.

PubMed

Tabata, Mitsuyasu; Terayama, Ryuji; Maruhama, Kotaro; Iida, Seiji; Sugimoto, Tomosada

2018-03-01

In this study, we compared induction of c-Fos and phosphorylated extracellular signal-regulated kinase (p-ERK) in the spinal dorsal horn after peripheral nerve injury. We examined the spinal dorsal horn for noxious heat-induced c-Fos and p-ERK protein-like immunoreactive (c-Fos- and p-ERK-IR) neuron profiles after tibial nerve injury. The effect of administration of a MEK 1/2 inhibitor (PD98059) on noxious heat-induced c-Fos expression was also examined after tibial nerve injury. A large number of c-Fos- and p-ERK-IR neuron profiles were induced by noxious heat stimulation to the hindpaw in sham-operated animals. A marked reduction in the number of c-Fos- and p-ERK-IR neuron profiles was observed in the medial 1/3 (tibial territory) of the dorsal horn at 3 and 7 days after nerve injury. Although c-Fos-IR neuron profiles had reappeared by 14 days after injury, the number of p-ERK-IR neuron profiles remained decreased in the tibial territory of the superficial dorsal horn. Double immunofluorescence labeling for c-Fos and p-ERK induced by noxious heat stimulation to the hindpaw at different time points revealed that a large number of c-Fos-IR, but not p-ERK-IR, neuron profiles were distributed in the tibial territory after injury. Although administration of a MEK 1/2 inhibitor to the spinal cord suppressed noxious heat-induced c-Fos expression in the peroneal territory, this treatment did not alter c-Fos induction in the tibial territory after nerve injury. ERK phosphorylation may be involved in c-Fos induction in normal nociceptive responses, but not in exaggerated c-Fos induction after nerve injury.

Multi-modal pain measurements in infants

PubMed Central

Worley, A.; Fabrizi, L.; Boyd, S.; Slater, R.

2012-01-01

A non-invasive integrated method was developed to measure neural and behavioural responses to peripheral sensory and noxious stimulation in human infants. The introduction of a novel event-detection interface allows synchronous recording of: (i) muscle and central nervous system activity with surface electromyography (EMG), scalp electroencephalography (EEG) and near-infrared spectroscopy (NIRS); (ii) behavioural responses with video-recording and (iii) autonomic responses (heart rate, oxygen saturation, respiratory rate and cardiovascular activity) with electrocardiography (ECG) and pulse oximetry. The system can detect noxious heel lance and touch stimuli with precision (33 μs and 624 μs respectively) and accuracy (523 μs and 256 μs) and has 100% sensitivity and specificity for both types of stimulation. Its ability to detect response latencies accurately was demonstrated by a shift in latency of the vertex potential of 20.7 ± 15.7 ms (n = 6 infants), following touch of the heel and of the shoulder, reflecting the distance between the two sites. This integrated system has provided reliable and reproducible measurements of responses to sensory and noxious stimulation in human infants on more than 100 test occasions. PMID:22285660

Multi-modal pain measurements in infants.

PubMed

Worley, A; Fabrizi, L; Boyd, S; Slater, R

2012-04-15

A non-invasive integrated method was developed to measure neural and behavioural responses to peripheral sensory and noxious stimulation in human infants. The introduction of a novel event-detection interface allows synchronous recording of: (i) muscle and central nervous system activity with surface electromyography (EMG), scalp electroencephalography (EEG) and near-infrared spectroscopy (NIRS); (ii) behavioural responses with video-recording and (iii) autonomic responses (heart rate, oxygen saturation, respiratory rate and cardiovascular activity) with electrocardiography (ECG) and pulse oximetry. The system can detect noxious heel lance and touch stimuli with precision (33 μs and 624 μs respectively) and accuracy (523 μs and 256 μs) and has 100% sensitivity and specificity for both types of stimulation. Its ability to detect response latencies accurately was demonstrated by a shift in latency of the vertex potential of 20.7 ± 15.7 ms (n=6 infants), following touch of the heel and of the shoulder, reflecting the distance between the two sites. This integrated system has provided reliable and reproducible measurements of responses to sensory and noxious stimulation in human infants on more than 100 test occasions. Copyright © 2012 Elsevier B.V. All rights reserved.

Can crayfish take the heat? Procambarus clarkii show nociceptive behaviour to high temperature stimuli, but not low temperature or chemical stimuli

PubMed Central

Puri, Sakshi; Faulkes, Zen

2015-01-01

Nociceptors are sensory neurons that are tuned to tissue damage. In many species, nociceptors are often stimulated by noxious extreme temperatures and by chemical agonists that do not damage tissue (e.g., capsaicin and isothiocyanate). We test whether crustaceans have nociceptors by examining nociceptive behaviours and neurophysiological responses to extreme temperatures and potentially nocigenic chemicals. Crayfish (Procambarus clarkii) respond quickly and strongly to high temperatures, and neurons in the antenna show increased responses to transient high temperature stimuli. Crayfish showed no difference in behavioural response to low temperature stimuli. Crayfish also showed no significant changes in behaviour when stimulated with capsaicin or isothiocyanate compared to controls, and neurons in the antenna did not change their firing rate following application of capsaicin or isothiocyanate. Noxious high temperatures appear to be a potentially ecologically relevant noxious stimulus for crayfish that can be detected by sensory neurons, which may be specialized nociceptors. PMID:25819841

Interaction of the adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) and opioid receptors in spinal cord nociceptive reflexes.

PubMed

Ramos-Zepeda, Guillermo; Herrero, Juan F

2013-08-14

We previously observed that the adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) is a very effective antinociceptive agent on intact but not on spinalized adult rats with inflammation. Since a close connection between opioid and adenosine A1 receptors has been described, we studied a possible relationship between these systems in the spinal cord. CPA-mediated antinociception was challenged by the selective adenosine A1 receptor antagonist 8-cyclopentyl-1, 3-dimethylxanthine (CPT) and by the opioid receptor antagonist naloxone on male adult Wistar rats with carrageenan-induced inflammation. Withdrawal reflexes activated by noxious mechanical and electrical stimulation were recorded using the single motor technique in intact and sham-spinalized animals. CPA was very effective in intact and sham spinalized rats but not in spinalized animals. Full reversal of CPA antinociception was observed with i.v. 1mg/kg of naloxone but not with 20mg/kg of CPT i.v. in responses to noxious mechanical and electrical stimulation. CPT fully prevented CPA from any antinociceptive action whereas naloxone did not modify CPA activity. These results suggest a centrally-mediated action, since CPA depressed the wind-up phenomenon which is derived of the activity of spinal cord neurons. The present study provides strong in vivo evidence of an antinociceptive activity mediated by the adenosine A1 receptor system in the spinal cord, linked to an activation of opioid receptors in adult animals with inflammation. © 2013.

Local subcutaneous injection of chlorogenic acid inhibits the nociceptive trigeminal spinal nucleus caudalis neurons in rats.

PubMed

Kakita, Kaede; Tsubouchi, Hirona; Adachi, Mayu; Takehana, Shiori; Shimazu, Yoshihito; Takeda, Mamoru

2017-11-29

Acute administration of chlorogenic acid (CGA) in vitro was recently shown to modulate potassium channel conductance and acid-sensing ion channels (ASICs) in the primary sensory neurons; however, in vivo peripheral effects of CGA on the nociceptive mechanical stimulation of trigeminal neuronal activity remains to be determined. The present study investigated whether local administration of CGA in vivo attenuates mechanical stimulation-induced excitability of trigeminal spinal nucleus caudalis neuronal (SpVc) activity in rats. Extracellular single-unit recordings were made of SpVc wide-dynamic range (WDR) neuronal activity elicited by non-noxious and noxious orofacial mechanical stimulation in pentobarbital anesthetized rats. The mean number of SpVc WDR neuronal firings responding to both non-noxious and noxious mechanical stimuli were significantly and dose-dependently inhibited by local subcutaneous administration of CGA (0.1-10mM), with the maximal inhibition of discharge frequency revealed within 10min and reversed after approximately 30min. The mean frequency of SpVc neuronal discharge inhibition by CGA was comparable to that by a local anesthetic, the sodium channel blocker, 1% lidocaine. These results suggest that local CGA injection into the peripheral receptive field suppresses the excitability of SpVc neurons, possibly via the activation of voltage-gated potassium channels and modulation of ASICs in the nociceptive nerve terminal of trigeminal ganglion neurons. Therefore, local injection of CGA could contribute to local anesthetic agents for the treatment of trigeminal nociceptive pain. Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

Sucrose-induced analgesia during early life modulates adulthood learning and memory formation.

PubMed

Nuseir, Khawla Q; Alzoubi, Karem H; Alabwaini, Jehad; Khabour, Omar F; Kassab, Manal I

2015-06-01

This study is aimed at examining the long-term effects of chronic pain during early life (postnatal day 0 to 8weeks), and intervention using sucrose, on cognitive functions during adulthood in rats. Pain was induced in rat pups via needle pricks of the paws. Sucrose solution or paracetamol was administered for analgesia before the paw prick. Control groups include tactile stimulation to account for handling and touching the paws, and sucrose alone was used. All treatments were started on day one of birth and continued for 8weeks. At the end of the treatments, behavioral studies were conducted to test the spatial learning and memory using radial arm water maze (RAWM), as well as pain threshold via foot-withdrawal response to a hot plate apparatus. Additionally, the hippocampus was dissected, and blood was collected. Levels of neurotrophins (BDNF, IGF-1 and NT-3) and endorphins were assessed using ELISA. The results show that chronic noxious stimulation resulted in comparable foot-withdrawal latency between noxious and tactile groups. On the other hand, pretreatment with sucrose or paracetamol increased pain threshold significantly both in naive rats and noxiously stimulated rats (P<0.05). Chronic pain during early life impaired short-term memory, and sucrose treatment prevented such impairment (P<0.05). Sucrose significantly increased serum levels of endorphin and enkephalin. Chronic pain decreased levels of BDNF in the hippocampus and this decrease was prevented by sucrose and paracetamol treatments. Hippocampal levels of NT-3 and IGF-1 were not affected by any treatment. In conclusion, chronic pain induction during early life induced short memory impairment, and pretreatment with sucrose prevented this impairment via mechanisms that seem to involve BDNF. As evident in the results, sucrose, whether alone or in the presence of pre-noxious stimulation, increases pain threshold in such circumstances; most likely via a mechanism that involves an increase in endogenous opioids. Copyright © 2015 Elsevier Inc. All rights reserved.

Chronic naltrindole administration does not modify the inhibitory effect of morphine on vocalization responses in the tail electric stimulation test in rats.

PubMed

Fernández, B; Alberti, I; Kitchen, I; Paz Viveros, M

1999-01-29

To address the existence of possible functional interactions between delta- and mu- receptors in relation to the affective component of pain, we have studied the effects of functional blockade of delta-receptors by a chronic treatment with naltrindole (1 mg/kg, 8 consecutive days) on antinociceptive responses to morphine (2 and 5 mg/kg) in the tail electric stimulation test, in adult male rats. The thresholds for the motor response (tail withdrawal), vocalization during stimulus and vocalization afterdischarge were assessed. These responses are considered to be integrated at spinal, medulla oblongata and diencephalon-rhinencephalon levels, respectively. The results show that the vocalization during stimulus and the vocalization afterdischarge were significantly affected by morphine in a dose dependent manner, the latter response being the most sensitive to the effects of the mu-opioid agonist. However, no significant effect was observed on motor responses at the doses used in this study. Chronic naltrindole treatment did not modify the inhibitory effect of morphine on the vocalization responses. Since the vocalization afterdischarge is related to the affective component of pain, the data suggest that the delta-opioid receptor is not involved in the supraspinal mechanisms at which these responses are organized and that there is not a mu-delta interaction in the modulation of the affective responses to noxious electrical stimulation.

Premature infants display increased noxious-evoked neuronal activity in the brain compared to healthy age-matched term-born infants.

PubMed

Slater, Rebeccah; Fabrizi, Lorenzo; Worley, Alan; Meek, Judith; Boyd, Stewart; Fitzgerald, Maria

2010-08-15

This study demonstrates that infants who are born prematurely and who have experienced at least 40days of intensive or special care have increased brain neuronal responses to noxious stimuli compared to healthy newborns at the same postmenstrual age. We have measured evoked potentials generated by noxious clinically-essential heel lances in infants born at term (8 infants; born 37-40weeks) and in infants born prematurely (7 infants; born 24-32weeks) who had reached the same postmenstrual age (mean age at time of heel lance 39.2+/-1.2weeks). These noxious-evoked potentials are clearly distinguishable from shorter latency potentials evoked by non-noxious tactile sensory stimulation. While the shorter latency touch potentials are not dependent on the age of the infant at birth, the noxious-evoked potentials are significantly larger in prematurely-born infants. This enhancement is not associated with specific brain lesions but reflects a functional change in pain processing in the brain that is likely to underlie previously reported changes in pain sensitivity in older ex-preterm children. Our ability to quantify and measure experience-dependent changes in infant cortical pain processing will allow us to develop a more rational approach to pain management in neonatal intensive care. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Dysmenorrhoea is associated with central changes in otherwise healthy women.

PubMed

Vincent, Katy; Warnaby, Catherine; Stagg, Charlotte J; Moore, Jane; Kennedy, Stephen; Tracey, Irene

2011-09-01

Patients with chronic pain conditions demonstrate altered central processing of experimental noxious stimuli, dysfunction of the hypothalamic-pituitary-adrenal axis, and reduced quality of life. Dysmenorrhoea is not considered a chronic pain condition, but is associated with enhanced behavioural responses to experimental noxious stimuli. We used behavioural measures, functional magnetic resonance imaging, and serum steroid hormone levels to investigate the response to experimental thermal stimuli in otherwise healthy women, with and without dysmenorrhoea. Women with dysmenorrhoea reported increased pain to noxious stimulation of the arm and abdomen throughout the menstrual cycle; no menstrual cycle effect was observed in either group. During menstruation, deactivation of brain regions in response to noxious stimulation was observed in control women but not in women with dysmenorrhoea. Without background pain (ie, in nonmenstrual phases), activity in the entorhinal cortex appeared to mediate the increased responses in women with dysmenorrhoea. Mean cortisol was significantly lower in women with dysmenorrhoea and was negatively correlated with the duration of the symptom. Additionally, women with dysmenorrhoea reported significantly lower physical but not mental quality of life. Thus, many features of chronic pain conditions are also seen in women with dysmenorrhoea: specifically a reduction in quality of life, suppression of the hypothalamic-pituitary-adrenal axis, and alterations in the central processing of experimental noxious stimuli. These alterations persist when there is no background pain and occur in response to stimuli at a site distant from that of the clinical pain. These findings indicate the potential importance of early and adequate treatment of dysmenorrhoea. Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Test-retest reliability of evoked heat stimulation BOLD fMRI.

PubMed

Upadhyay, Jaymin; Lemme, Jordan; Anderson, Julie; Bleakman, David; Large, Thomas; Evelhoch, Jeffrey L; Hargreaves, Richard; Borsook, David; Becerra, Lino

2015-09-30

To date, the blood oxygenated-level dependent (BOLD) functional magnetic resonance imaging (fMRI) technique has enabled an objective and deeper understanding of pain processing mechanisms embedded within the human central nervous system (CNS). In order to further comprehend the benefits and limitations of BOLD fMRI in the context of pain as well as the corresponding subjective pain ratings, we evaluated the univariate response, test-retest reliability and confidence intervals (CIs) at the 95% level of both data types collected during evoked stimulation of 40°C (non-noxious), 44°C (mildly noxious) and a subject-specific temperature eliciting a 7/10 pain rating. The test-retest reliability between two scanning sessions was determined by calculating group-level interclass correlation coefficients (ICCs) and at the single-subject level. Across the three stimuli, we initially observed a graded response of increasing magnitude for both VAS (visual analog score) pain ratings and fMRI data. Test-retest reliability was observed to be highest for VAS pain ratings obtained during the 7/10 pain stimulation (ICC=0.938), while ICC values of pain fMRI data for a distribution of CNS structures ranged from 0.5 to 0.859 (p<0.05). Importantly, the upper and lower confidence interval CI bounds reported herein could be utilized in subsequent trials involving healthy volunteers to hypothesize the magnitude of effect required to overcome inherent variability of either VAS pain ratings or BOLD responses evoked during innocuous or noxious thermal stimulation. Copyright © 2015 Elsevier B.V. All rights reserved.

Dissociable Effects of the Cannabinoid Receptor Agonists Δ9-Tetrahydrocannabinol and CP55940 on Pain-Stimulated Versus Pain-Depressed Behavior in Rats

PubMed Central

Kwilasz, Andrew J.

2012-01-01

Cannabinoid receptor agonists produce reliable antinociception in most preclinical pain assays but have inconsistent analgesic efficacy in humans. This disparity suggests that conventional preclinical assays of nociception are not sufficient for the prediction of cannabinoid effects related to clinical analgesia. To extend the range of preclinical cannabinoid assessment, this study compared the effects of the marijuana constituent and low-efficacy cannabinoid agonist Δ9-tetrahydrocannabinol (THC) and the high-efficacy synthetic cannabinoid agonist 3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol (CP55940) in assays of pain-stimulated and pain-depressed behavior. Intraperitoneal injection of dilute lactic acid (1.8% in 1 ml/kg) stimulated a stretching response or depressed intracranial self-stimulation (ICSS) in separate groups of male Sprague-Dawley rats. THC (0.1–10 mg/kg) and CP55940 (0.0032–0.32 mg/kg) dose-dependently blocked acid- stimulated stretching but only exacerbated acid-induced depression of ICSS at doses that also decreased control ICSS in the absence of a noxious stimulus. Repeated THC produced tolerance to sedative rate-decreasing effects of THC on control ICSS in the absence of the noxious stimulus but failed to unmask antinociception in the presence of the noxious stimulus. THC and CP55940 also failed to block pain-related depression of feeding in rats, although THC did attenuate satiation-related depression of feeding. In contrast to the effects of the cannabinoid agonists, the clinically effective analgesic and nonsteroidal anti-inflammatory drug ketoprofen (1 mg/kg) blocked acid-stimulated stretching and acid-induced depression of both ICSS and feeding. The poor efficacy of THC and CP55940 to block acute pain-related depression of behavior in rats agrees with the poor efficacy of cannabinoids to treat acute pain in humans. PMID:22892341

Physiologic and biochemical measurements and response to noxious stimulation at various concentrations of MS-222 in koi (Cyprinus carpio).

PubMed

Stockman, Jonathan; Weber, Ernest Scott P; Kass, Philip H; Pascoe, Peter J; Paul-Murphy, Joanne

2013-01-01

To evaluate the physiological effect and response to noxious stimulation at five concentrations of MS-222 in koi (Cyprinus carpio). Prospective experimental study. Twenty-one healthy adult unknown sex koi fish weighing mean 450±SD 120 g. Each fish was exposed to five different concentrations of MS-222 (50, 70, 110, 150 and 190 mg L(-1) ) in a random sequence during the same anaesthetic event. For each concentration of MS-222, vital functions such as heart rate (HR) (via Doppler) and opercular rate (OpR) were recorded after a standardized induction period. Response to two noxious stimuli in the form of haemostat clamp pressure applied on the tail and the lip was evaluated, and blood was drawn to measure biochemical and blood gas values. Decrease in response to noxious stimulation with an increase of MS-222 concentration both for the lip (p=0.0027) and the tail (p<0.0001) stimulus was observed. Biochemical values were unaffected by the concentration of MS-222 with the exception of lactate concentration which was weakly correlated with the duration of anaesthesia (r=0.31, p<0.001) and the number of times the fish was clamped or bled prior to sampling (r=0.23, p<0.001). Opercular rate decreased with the increase in anaesthetic concentration, and HR was not affected. Our results indicated a decrease in response to stimulus and a decrease in OpR that were associated with increased concentrations of MS-222. This may assist in establishing anaesthetic protocols using MS-222 in fish and supports the use of supramaximal pressure stimuli to teleost fish under variable MS-222 concentrations as a model for future studies. © 2012 The Authors. Veterinary Anaesthesia and Analgesia. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.

ConceFT for Time-Varying Heart Rate Variability Analysis as a Measure of Noxious Stimulation During General Anesthesia.

PubMed

Lin, Yu-Ting; Wu, Hau-Tieng

2017-01-01

Heart rate variability (HRV) offers a noninvasive way to peek into the physiological status of the human body. When this physiological status is dynamic, traditional HRV indices calculated from power spectrum do not resolve the dynamic situation due to the issue of nonstationarity. Clinical anesthesia is a typically dynamic situation that calls for time-varying HRV analysis. Concentration of frequency and time (ConceFT) is a nonlinear time-frequency (TF) analysis generalizing the multitaper technique and the synchrosqueezing transform. The result is a sharp TF representation capturing the dynamics inside HRV. Companion indices of the commonly applied HRV indices, including time-varying low-frequency power (tvLF), time-varying high-frequency power, and time-varying low-high ratio, are considered as measures of noxious stimulation. To evaluate the feasibility of the proposed indices, we apply these indices to study two different types of noxious stimulation, the endotracheal intubation and surgical skin incision, under general anesthesia. The performance was compared with traditional HRV indices, the heart rate reading, and indices from electroencephalography. The results indicate that the tvLF index performs best and outperforms not only the traditional HRV index, but also the commonly used heart rate reading. With the help of ConceFT, the proposed HRV indices are potential to provide a better quantification of the dynamic change of the autonomic nerve system. Our proposed scheme of time-varying HRV analysis could contribute to the clinical assessment of analgesia under general anesthesia.

Cat's medullary reticulospinal and subnucleus reticularis dorsalis noxious neurons form a coupled neural circuit through collaterals of descending axons

PubMed Central

Leiras, Roberto; Martín-Cora, Francisco; Velo, Patricia; Liste, Tania

2015-01-01

Animals and human beings sense and react to real/potential dangerous stimuli. However, the supraspinal mechanisms relating noxious sensing and nocifensive behavior are mostly unknown. The collateralization and spatial organization of interrelated neurons are important determinants of coordinated network function. Here we electrophysiologically studied medial medullary reticulospinal neurons (mMRF-RSNs) antidromically identified from the cervical cord of anesthetized cats and found that 1) more than 40% (79/183) of the sampled mMRF-RSNs emitted bifurcating axons running within the dorsolateral (DLF) and ventromedial (VMF) ipsilateral fascicles; 2) more than 50% (78/151) of the tested mMRF-RSNs with axons running in the VMF collateralized to the subnucleus reticularis dorsalis (SRD) that also sent ipsilateral descending fibers bifurcating within the DLF and the VMF. This percentage of mMRF collateralization to the SRD increased to more than 81% (53/65) when considering the subpopulation of mMRF-RSNs responsive to noxiously heating the skin; 3) reciprocal monosynaptic excitatory relationships were electrophysiologically demonstrated between noxious sensitive mMRF-RSNs and SRD cells; and 4) injection of the anterograde tracer Phaseolus vulgaris leucoagglutinin evidenced mMRF to SRD and SRD to mMRF projections contacting the soma and proximal dendrites. The data demonstrated a SRD-mMRF network interconnected mainly through collaterals of descending axons running within the VMF, with the subset of noxious sensitive cells forming a reverberating circuit probably amplifying mutual outputs simultaneously regulating motor activity and spinal noxious afferent input. The results provide evidence that noxious stimulation positively engages a reticular SRD-mMRF-SRD network involved in pain-sensory-to-motor transformation and modulation. PMID:26581870

Noxious electrical stimulation of the pelvic floor and vagina induces transient voiding dysfunction in a rabbit survival model of pelvic floor dystonia.

PubMed

Dobberfuhl, Amy D; Spettel, Sara; Schuler, Catherine; Levin, Robert M; Dubin, Andrew H; De, Elise J B

2015-12-01

Existing data supports a relationship between pelvic floor dysfunction and lower urinary tract symptoms. We developed a survival model of pelvic floor dysfunction in the rabbit and evaluated cystometric (CMG), electromyographic (EMG) and ambulatory voiding behavior. Twelve female adult virgin rabbits were housed in metabolic cages to record voiding and defecation. Anesthetized CMG/EMG was performed before and after treatment animals (n=9) received bilateral tetanizing needle stimulation to the pubococcygeous (PC) muscle and controls (n=3) sham needle placement. After 7 days all animals were subjected to tetanizing transvaginal stimulation and CMG/EMG. After 5 days a final CMG/EMG was performed. Of rabbits that underwent needle stimulation 7 of 9 (78%) demonstrated dysfunctional CMG micturition contractions versus 6 of 12 (50%) after transvaginal stimulation. Needle stimulation of the PC musculature resulted in significant changes in: basal CMG pressure, precontraction pressure change, contraction pressure, interval between contractions and postvoid residual; with time to 3rd contraction increased from 38 to 53 minutes (p=0.008 vs. prestimulation). Vaginal noxious stimulation resulted in significant changes in: basal CMG pressure and interval between contractions; with time to 3rd contraction increased from 37 to 46 minutes (p=0.008 vs. prestimulation). Changes in cage parameters were primarily seen after direct needle stimulation. In a majority of animals, tetanizing electrical stimulation of the rabbit pelvic floor resulted in voiding changes suggestive of pelvic floor dysfunction as characterized by a larger bladder capacity, longer interval between contractions and prolonged contraction duration.

Gain of postural responses increases in response to real and anticipated pain.

PubMed

Hodges, Paul W; Tsao, Henry; Sims, Kevin

2015-09-01

This study tested two contrasting theories of adaptation of postural control to pain. One proposes alteration to the postural strategy including inhibition of muscles that produce painful movement; another proposes amplification of the postural adjustment to recruit strategies normally reserved for higher load. This study that aimed to determine which of these alternatives best explains pain-related adaptation of the hip muscle activity associated with stepping down from steps of increasing height adaptation of postural control to increasing load was evaluated from hip muscle electromyography (fine-wire and surface electrodes) as ten males stepped from steps of increasing height (i.e. increasing load). In one set of trials, participants stepped from a low step (5 cm) and pain was induced by noxious electrical stimulation over the sacrum triggered from foot contact with a force plate or was anticipated. Changes in EMG amplitude and onset timing were compared between conditions. Hip muscle activation was earlier and larger when stepping from higher steps. Although ground reaction forces (one of the determinants of joint load) were unchanged before, during and after pain, trials with real or anticipated noxious stimulation were accompanied by muscle activity indistinguishable from that normally reserved for higher steps (EMG amplitude increased from 9 to 17 % of peak). These data support the notion that muscle activation for postural control is augmented when challenged by real/anticipated noxious stimulation. Muscle activation was earlier and greater than that required for the task and is likely to create unnecessary joint loading. This could have long-term consequences if maintained.

Drosophila Nociceptors Mediate Larval Aversion to Dry Surface Environments Utilizing Both the Painless TRP Channel and the DEG/ENaC Subunit, PPK1

PubMed Central

Johnson, Wayne A.; Carder, Justin W.

2012-01-01

A subset of sensory neurons embedded within the Drosophila larval body wall have been characterized as high-threshold polymodal nociceptors capable of responding to noxious heat and noxious mechanical stimulation. They are also sensitized by UV-induced tissue damage leading to both thermal hyperalgesia and allodynia very similar to that observed in vertebrate nociceptors. We show that the class IV multiple-dendritic(mdIV) nociceptors are also required for a normal larval aversion to locomotion on to a dry surface environment. Drosophila melanogaster larvae are acutely susceptible to desiccation displaying a strong aversion to locomotion on dry surfaces severely limiting the distance of movement away from a moist food source. Transgenic inactivation of mdIV nociceptor neurons resulted in larvae moving inappropriately into regions of low humidity at the top of the vial reflected as an increased overall pupation height and larval desiccation. This larval lethal desiccation phenotype was not observed in wild-type controls and was completely suppressed by growth in conditions of high humidity. Transgenic hyperactivation of mdIV nociceptors caused a reciprocal hypersensitivity to dry surfaces resulting in drastically decreased pupation height but did not induce the writhing nocifensive response previously associated with mdIV nociceptor activation by noxious heat or harsh mechanical stimuli. Larvae carrying mutations in either the Drosophila TRP channel, Painless, or the degenerin/epithelial sodium channel subunit Pickpocket1(PPK1), both expressed in mdIV nociceptors, showed the same inappropriate increased pupation height and lethal desiccation observed with mdIV nociceptor inactivation. Larval aversion to dry surfaces appears to utilize the same or overlapping sensory transduction pathways activated by noxious heat and harsh mechanical stimulation but with strikingly different sensitivities and disparate physiological responses. PMID:22403719

Neuronal hyperexcitability in the ventral posterior thalamus of neuropathic rats: modality selective effects of pregabalin

PubMed Central

Dickenson, Anthony H.

2016-01-01

Neuropathic pain represents a substantial clinical challenge; understanding the underlying neural mechanisms and back-translation of therapeutics could aid targeting of treatments more effectively. The ventral posterior thalamus (VP) is the major termination site for the spinothalamic tract and relays nociceptive activity to the somatosensory cortex; however, under neuropathic conditions, it is unclear how hyperexcitability of spinal neurons converges onto thalamic relays. This study aimed to identify neural substrates of hypersensitivity and the influence of pregabalin on central processing. In vivo electrophysiology was performed to record from VP wide dynamic range (WDR) and nociceptive-specific (NS) neurons in anesthetized spinal nerve-ligated (SNL), sham-operated, and naive rats. In neuropathic rats, WDR neurons had elevated evoked responses to low- and high-intensity punctate mechanical stimuli, dynamic brushing, and innocuous and noxious cooling, but less so to heat stimulation, of the receptive field. NS neurons in SNL rats also displayed increased responses to noxious punctate mechanical stimulation, dynamic brushing, noxious cooling, and noxious heat. Additionally, WDR, but not NS, neurons in SNL rats exhibited substantially higher rates of spontaneous firing, which may correlate with ongoing pain. The ratio of WDR-to-NS neurons was comparable between SNL and naive/sham groups, suggesting relatively few NS neurons gain sensitivity to low-intensity stimuli leading to a “WDR phenotype.” After neuropathy was induced, the proportion of cold-sensitive WDR and NS neurons increased, supporting the suggestion that changes in frequency-dependent firing and population coding underlie cold hypersensitivity. In SNL rats, pregabalin inhibited mechanical and heat responses but not cold-evoked or elevated spontaneous activity. PMID:27098028

Neuronal hyperexcitability in the ventral posterior thalamus of neuropathic rats: modality selective effects of pregabalin.

PubMed

Patel, Ryan; Dickenson, Anthony H

2016-07-01

Neuropathic pain represents a substantial clinical challenge; understanding the underlying neural mechanisms and back-translation of therapeutics could aid targeting of treatments more effectively. The ventral posterior thalamus (VP) is the major termination site for the spinothalamic tract and relays nociceptive activity to the somatosensory cortex; however, under neuropathic conditions, it is unclear how hyperexcitability of spinal neurons converges onto thalamic relays. This study aimed to identify neural substrates of hypersensitivity and the influence of pregabalin on central processing. In vivo electrophysiology was performed to record from VP wide dynamic range (WDR) and nociceptive-specific (NS) neurons in anesthetized spinal nerve-ligated (SNL), sham-operated, and naive rats. In neuropathic rats, WDR neurons had elevated evoked responses to low- and high-intensity punctate mechanical stimuli, dynamic brushing, and innocuous and noxious cooling, but less so to heat stimulation, of the receptive field. NS neurons in SNL rats also displayed increased responses to noxious punctate mechanical stimulation, dynamic brushing, noxious cooling, and noxious heat. Additionally, WDR, but not NS, neurons in SNL rats exhibited substantially higher rates of spontaneous firing, which may correlate with ongoing pain. The ratio of WDR-to-NS neurons was comparable between SNL and naive/sham groups, suggesting relatively few NS neurons gain sensitivity to low-intensity stimuli leading to a "WDR phenotype." After neuropathy was induced, the proportion of cold-sensitive WDR and NS neurons increased, supporting the suggestion that changes in frequency-dependent firing and population coding underlie cold hypersensitivity. In SNL rats, pregabalin inhibited mechanical and heat responses but not cold-evoked or elevated spontaneous activity. Copyright © 2016 the American Physiological Society.

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

PubMed Central

Nencini, Sara; Ivanusic, Jason J.

2016-01-01

Pain is associated with most bony pathologies. Clinical and experimental observations suggest that bone pain can be derived from noxious stimulation of the periosteum or bone marrow. Sensory neurons are known to innervate the periosteum and marrow cavity, and most of these have a morphology and molecular phenotype consistent with a role in nociception. However, little is known about the physiology of these neurons, and therefore information about mechanisms that generate and maintain bone pain is lacking. The periosteum has received greater attention relative to the bone marrow, reflecting the easier access of the periosteum for experimental assessment. With the electrophysiological preparations used, investigators have been able to record from single periosteal units in isolation, and there is a lot of information available about how they respond to different stimuli, including those that are noxious. In contrast, preparations used to study sensory neurons that innervate the bone marrow have been limited to recording multi-unit activity in whole nerves, and whilst they clearly report responses to noxious stimulation, it is not possible to define responses for single sensory neurons that innervate the bone marrow. There is only limited evidence that peripheral sensory neurons that innervate bone can be sensitized or that they can be activated by multiple stimulus types, and at present this only exists in part for periosteal units. In the central nervous system, it is clear that spinal dorsal horn neurons can be activated by noxious stimuli applied to bone. Some can be sensitized under pathological conditions and may contribute in part to secondary or referred pain associated with bony pathology. Activity related to stimulation of sensory nerves that innervate bone has also been reported in neurons of the spinoparabrachial pathway and the somatosensory cortices, both known for roles in coding information about pain. Whilst these provide some clues as to the way information about bone pain is centrally coded, they need to be expanded to further our understanding of other central territories involved. There is a lot more to learn about the physiology of peripheral sensory neurons that innervate bone and their central projections. PMID:27199772

The Effects of Mechanical and Thermal Stimuli on Local Field Potentials and Single Unit Activity in Parkinson's Disease Patients.

PubMed

Belasen, Abigail; Youn, Youngwon; Gee, Lucy; Prusik, Julia; Lai, Brant; Ramirez-Zamora, Adolfo; Rizvi, Khizer; Yeung, Philip; Shin, Damian S; Argoff, Charles; Pilitsis, Julie G

2016-10-01

Chronic pain is a major, debilitating symptom of Parkinson's disease (PD). Although, deep brain stimulation (DBS) has been shown to improve pain outcomes, the mechanisms underlying this phenomenon are unclear. Microelectrode recording allows us to measure both local field potentials (LFPs) and single neuronal unit activity (SUA). In this study, we examined how single unit and LFP oscillatory activity in the basal ganglia are impacted by mechanical and thermal sensory stimuli and explored their role in pain modulation. We assessed changes in LFPs and SUAs in the subthalamic nucleus (STN), globus pallidus interna (Gpi), and globus pallidus externa (Gpe) following exposure with mechanical or thermal stimuli. Sensory thresholds were determined pre-operatively using quantitative sensory testing. Based on these data, patients were exposed to innocuous and noxious mechanical, pressure, and thermal stimuli at individualized thresholds. In the STN, LFP alpha oscillatory activity and SUA increased in response to innocuous mechanical stimuli; SUA further increased in response to noxious mechanical, noxious pressure, and noxious thermal stimuli (p < 0.05). In the Gpe, LFP low betaactivity and SUA increased with noxious thermal stimuli; SUA also increased in response to innocuous thermal stimuli (p < 0.05). In the Gpi, innocuous thermal stimuli increased LFP gammaactivity; noxious pressure stimuli decreased low betaactivity; SUA increased in response to noxious thermal stimuli (p < 0.05). Our study is the first to demonstrate that mechanical and thermal stimuli alter basal ganglia LFPs and SUAs in PD. While STN SUA increases nearly uniformly to all sensory stimuli, SUA in the pallidal nuclei respond solely to thermal stimuli. Similarly, thermal stimuli yield increases in pallidal LFP activity, but not STN activity. We speculate that DBS may provide analgesia through suppression of stimuli-specific changes in basal ganglia activity, supporting a role for these nuclei in sensory and pain processing circuits. © 2016 International Neuromodulation Society.

A novel paradigm to evaluate conditioned pain modulation in fibromyalgia.

PubMed

Schoen, Cynthia J; Ablin, Jacob N; Ichesco, Eric; Bhavsar, Rupal J; Kochlefl, Laura; Harris, Richard E; Clauw, Daniel J; Gracely, Richard H; Harte, Steven E

2016-01-01

Application of noxious stimulation to one body area reduces pain sensitivity in a remote body area through activation of an endogenous pain-inhibitory network, a behavioral phenomenon referred to as conditioned pain modulation (CPM). The efficiency of CPM is predictive of a variety of health outcomes, while impaired CPM has been associated with various chronic pain conditions. Current methods used to assess CPM vary widely, and interest in CPM method development remains strong. Here, we evaluated a novel method for assessing CPM in healthy controls and fibromyalgia (FM) patients using thumb pressure as both a test and conditioning stimulus. Sixteen female FM patients and 14 matched healthy controls underwent CPM testing with thumbnail pressure as the test stimulus, and either cold water or noxious pressure as the conditioning stimulus. CPM magnitude was evaluated as the difference in pain rating of the test stimulus applied before and during the conditioning stimulus. In healthy controls, application of either pressure or cold water conditioning stimulation induced CPM as evidenced by a significant reduction in test stimulus pain rating during conditioning ( P =0.007 and P =0.021, respectively). In contrast, in FM patients, neither conditioning stimulus induced a significant CPM effect ( P >0.274). There was a significant difference in CPM magnitude for FM patients compared to healthy controls with noxious pressure conditioning stimulation ( P =0.023); however, no significant difference in CPM was found between groups using cold water as a conditioning stimulus ( P =0.269). The current study demonstrates that thumbnail pressure can be used as both a test and conditioning stimulus in the assessment of CPM. This study further confirms previous findings of attenuated CPM in FM patients compared with healthy controls.

A novel paradigm to evaluate conditioned pain modulation in fibromyalgia

PubMed Central

Schoen, Cynthia J; Ablin, Jacob N; Ichesco, Eric; Bhavsar, Rupal J; Kochlefl, Laura; Harris, Richard E; Clauw, Daniel J; Gracely, Richard H; Harte, Steven E

2016-01-01

Introduction Application of noxious stimulation to one body area reduces pain sensitivity in a remote body area through activation of an endogenous pain-inhibitory network, a behavioral phenomenon referred to as conditioned pain modulation (CPM). The efficiency of CPM is predictive of a variety of health outcomes, while impaired CPM has been associated with various chronic pain conditions. Current methods used to assess CPM vary widely, and interest in CPM method development remains strong. Here, we evaluated a novel method for assessing CPM in healthy controls and fibromyalgia (FM) patients using thumb pressure as both a test and conditioning stimulus. Methods Sixteen female FM patients and 14 matched healthy controls underwent CPM testing with thumbnail pressure as the test stimulus, and either cold water or noxious pressure as the conditioning stimulus. CPM magnitude was evaluated as the difference in pain rating of the test stimulus applied before and during the conditioning stimulus. Results In healthy controls, application of either pressure or cold water conditioning stimulation induced CPM as evidenced by a significant reduction in test stimulus pain rating during conditioning (P=0.007 and P=0.021, respectively). In contrast, in FM patients, neither conditioning stimulus induced a significant CPM effect (P>0.274). There was a significant difference in CPM magnitude for FM patients compared to healthy controls with noxious pressure conditioning stimulation (P=0.023); however, no significant difference in CPM was found between groups using cold water as a conditioning stimulus (P=0.269). Conclusion The current study demonstrates that thumbnail pressure can be used as both a test and conditioning stimulus in the assessment of CPM. This study further confirms previous findings of attenuated CPM in FM patients compared with healthy controls. PMID:27713648

Effects of age and mild cognitive impairment on the pain response system.

PubMed

Kunz, Miriam; Mylius, Veit; Schepelmann, Karsten; Lautenbacher, Stefan

2009-01-01

Both age and dementia have been shown to have an effect on nociception and pain processing. The question arises whether mild cognitive impairment (MCI), which is thought to be a transitional stage between normal ageing and dementia, is also associated with alterations in pain processing. The aim of the present study was to answer this question by investigating the impact of age and MCI on the pain response system. Forty young subjects, 45 cognitively unimpaired elderly subjects and 42 subjects with MCI were investigated by use of an experimental multi-method approach. The subjects were tested for their subjective (pain ratings), motor (RIII reflex), facial (Facial Action Coding System) and their autonomic (sympathetic skin response and evoked heart rate response) responses to noxious electrical stimulation of the nervus suralis. We found significant group differences in the autonomic responses to noxious stimulation. The sympathetic skin response amplitude was significantly reduced in the cognitively unimpaired elderly subjects compared to younger subjects and to an even greater degree in subjects with MCI. The evoked heart rate response was reduced to a similar degree in both groups of aged subjects. Regression analyses within the two groups of the elderly subjects revealed that age and, in the MCI group, cognitive status were significant predictors of the decrease in autonomic responsiveness to noxious stimulation. Except for the autonomic parameters, no other pain parameter differed between the three groups. The pain response system appeared to be quite unaltered in MCI patients compared to cognitively unimpaired individuals of the same age. Only the sympathetic responsiveness qualified as an indicator of early aging effects as well as of pathophysiology associated with MCI, which both seemed to affect the pain system independently from each other.

The clitoral activation paradox - Claimed outcomes from different methods of its stimulation.

PubMed

Levin, Roy J

2018-07-01

This article reviews clitoral structures, their functions and how they are activated during the stages of female life. The paradox that occurs is that different procedures of activation are claimed by some to favor 'noxious outcomes' to the physical and psychic health of women who use it to achieve sexual arousal/orgasm with or without penile vaginal intercourse. A number of the difficulties and inconsistencies in relation to these claims are explored. The proposed justification for the 'noxious outcomes' is that 'evolution' punishes sexual arousals other than by coitus because it is the only one that leads to gene propagation. In this context, however, the new, evolutionary interpretation of clitoral function in the fertile years as a fundamental proximate mechanism for facilitating female reproductive fitness makes such a justification improbable. The role of coital alignment technique (CAT) in the treatment of female orgasmic disorder is discussed in relation to its features of introital, clitoral and periurethral glans stimulation. Attempts to control female sexuality through various 'clitoridectomies' are examined, and unanswered questions about clitoral stimulation are listed. Clin. Anat. 31:650-660, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Standardizing procedures to study sensitization of human spinal nociceptive processes: comparing parameters for temporal summation of the nociceptive flexion reflex (TS-NFR).

PubMed

Terry, Ellen L; France, Christopher R; Bartley, Emily J; Delventura, Jennifer L; Kerr, Kara L; Vincent, Ashley L; Rhudy, Jamie L

2011-09-01

Temporal summation of pain (TS-pain) is the progressive increase in pain ratings during a series of noxious stimulations. TS-pain has been used to make inferences about sensitization of spinal nociceptive processes; however, pain report can be biased thereby leading to problems with this inference. Temporal summation of the nociceptive flexion reflex (TS-NFR, a physiological measure of spinal nociception) can potentially overcome report bias, but there have been few attempts (generally with small Ns) to standardize TS-NFR procedures. In this study, 50 healthy participants received 25 series of noxious electric stimulations to evoke TS-NFR and TS-pain. Goals were to: 1) determine the stimulation frequency that best elicits TS-NFR and reduces electromyogram (EMG) contamination from muscle tension, 2) determine the minimum number of stimulations per series before NFR summation asymptotes, 3) compare NFR definition intervals (90-150ms vs. 70-150ms post-stimulation), and 4) compare TS-pain and TS-NFR when different stimulation frequencies are used. Results indicated TS-NFR should be elicited by a series of three stimuli delivered at 2.0Hz and TS-NFR should be defined from a 70-150ms post-stimulation scoring interval. Unfortunately, EMG contamination from muscle tension was greatest during 2.0Hz series. Discrepancies were noted between TS-NFR and TS-pain which raise concerns about using pain ratings to infer changes in spinal nociceptive processes. And finally, some individuals did not have reliable NFRs when the stimulation intensity was set at NFR threshold during TS-NFR testing; therefore, a higher intensity is needed. Implications of findings are discussed. Copyright © 2011 Elsevier B.V. All rights reserved.

Brain processing of pain in patients with unresponsive wakefulness syndrome

PubMed Central

Markl, Alexandra; Yu, Tao; Vogel, Dominik; Müller, Friedemann; Kotchoubey, Boris; Lang, Simone

2013-01-01

By definition, patients with unresponsive wakefulness syndrome (UWS) do not experience pain, but it is still not completely understood how far their brain can process noxious stimuli. The few positron emission tomography studies that have examined pain processing did not yield a clear and consistent result. We performed an functional magnetic resonance imaging scan in 30 UWS patients of nontraumatic etiology and 15 age- and sex-matched healthy control participants (HC). In a block design, noxious electrical stimuli were presented at the patients' left index finger, alternating with a resting baseline condition. Sixteen of the UWS patients (53%) showed neural activation in at least one subsystem of the pain-processing network. More specifically, 15 UWS patients (50%) showed responses in the sensory-discriminative pain network, 30% in the affective pain network. The data indicate that some patients completely fulfilling the clinical UWS criteria have the neural substrates of noxious stimulation processing, which resemble that in control individuals. We therefore suppose that at least some of these patients can experience pain. PMID:23533065

Corticomotor excitability during a noxious stimulus before and after exercise in women with fibromyalgia.

PubMed

Hoeger Bement, Marie K; Weyer, Andy D; Yoon, Tejin; Hunter, Sandra K

2014-02-01

The purposes of this study were to assess corticomotor excitability in people with fibromyalgia during a noxious stimulus before and after fatiguing exercise and examine associations with pain perception. Fifteen women with fibromyalgia completed three sessions: one familiarization and two experimental. The experimental sessions were randomized and involved measurement of pain perception and motor evoked potentials before and after (1) quiet rest and (2) isometric contraction of the elbow flexor muscles. Motor evoked potential amplitude of brachioradialis muscle was measured following transcranial magnetic stimulation delivered before, during, and after a noxious mechanical stimulus. After quiet rest, there was no change in pain perception. After the submaximal contraction, there was considerable variability in the pain response. Based on the changes in the experimental pain, subjects were divided into three groups (increase, decrease, and no change in pain). There was an interaction between pain response and the pain-induced change in motor evoked potentials. Those individuals who had an increase in motor evoked potentials during the pain test had an increase in pain after exercise. Thus, women with fibromyalgia were classified based on their pain response to exercise, and this response was associated with the change in corticomotor excitability during the application of a noxious stimulus.

Effects of noxious stimulation and pain expectations on neuromuscular control of the spine in patients with chronic low back pain.

PubMed

Henchoz, Yves; Tétreau, Charles; Abboud, Jacques; Piché, Mathieu; Descarreaux, Martin

2013-10-01

Alterations of the neuromuscular control of the lumbar spine have been reported in patients with chronic low back pain (LBP). During trunk flexion and extension tasks, the reduced myoelectric activity of the low back extensor musculature observed during full trunk flexion is typically absent in patients with chronic LBP. To determine whether pain expectations could modulate neuromuscular responses to experimental LBP to a higher extent in patients with chronic LBP compared with controls. A cross-sectional, case-control study. Twenty-two patients with nonspecific chronic LBP and 22 age- and sex-matched control participants. Trunk flexion-extension tasks were performed under three experimental conditions: innocuous heat, noxious stimulation with low pain expectation, and noxious stimulation with high pain expectation. Noxious stimulations were delivered using a contact heat thermode applied on the skin of the lumbar region (L4-L5), whereas low or high pain expectations were induced by verbal and visual instructions. Surface electromyography of erector spinae at L2-L3 and L4-L5, as well as lumbopelvic kinematic variables were collected during the tasks. Pain was evaluated using a numerical rating scale. Pain catastrophizing, disability, anxiety, and fear-avoidance beliefs were measured using validated questionnaires. Two-way mixed analysis of variance revealed that pain was significantly different among the three experimental conditions (F2,84=317.5; p<.001). Increased myoelectric activity of the low back extensor musculature during full trunk flexion was observed in the high compared with low pain expectations condition at the L2-L3 level (F2,84=9.5; p<.001) and at the L4-L5 level (F2,84=3.7; p=.030). At the L4-L5 level, this effect was significantly more pronounced for the control participants compared with patients with chronic LBP (F2,84=3.4; p=.045). Pearson correlation analysis revealed that increased lumbar muscle activity in full flexion induced by expectations was associated with higher pain catastrophizing in patients with chronic LBP (r=0.54; p=.012). Repeated exposure to pain appears to generate rigid and less variable patterns of muscle activation in patients with chronic LBP, which attenuate their response to pain expectations. Patients with high levels of pain catastrophizing show higher myoelectric activity of lumbar muscles in full flexion and exhibit greater neuromechanical changes when expecting strong pain. Copyright © 2013 Elsevier Inc. All rights reserved.

Impact of stress, fear and anxiety on the nociceptive responses of larval zebrafish.

PubMed

Lopez-Luna, Javier; Al-Jubouri, Qussay; Al-Nuaimy, Waleed; Sneddon, Lynne U

2017-01-01

Both adult and larval zebrafish have been demonstrated to show behavioural responses to noxious stimulation but also to potentially stress- and fear or anxiety- eliciting situations. The pain or nociceptive response can be altered and modulated by these situations in adult fish through a mechanism called stress-induced analgesia. However, this phenomenon has not been described in larval fish yet. Therefore, this study explores the behavioural changes in larval zebrafish after noxious stimulation and exposure to challenges that can trigger a stress, fear or anxiety reaction. Five-day post fertilization zebrafish were exposed to either a stressor (air emersion), a predatory fear cue (alarm substance) or an anxiogenic (caffeine) alone or prior to immersion in acetic acid 0.1%. Pre- and post-stimulation behaviour (swimming velocity and time spent active) was recorded using a novel tracking software in 25 fish at once. Results show that larvae reduced both velocity and activity after exposure to the air emersion and alarm substance challenges and that these changes were attenuated using etomidate and diazepam, respectively. Exposure to acetic acid decreased velocity and activity as well, whereas air emersion and alarm substance inhibited these responses, showing no differences between pre- and post-stimulation. Therefore, we hypothesize that an antinociceptive mechanism, activated by stress and/or fear, occur in 5dpf zebrafish, which could have prevented the larvae to display the characteristic responses to pain.

Electroacupuncture Reduces the Effects of Acute Noxious Stimulation on the Electrical Activity of Pain-Related Neurons in the Hippocampus of Control and Neuropathic Pain Rats

PubMed Central

Wang, Jun-Ying; Chen, Renbo; Feng, Xiu-Mei; Yan, Yaxia; Lippe, Irmgard Th.

2016-01-01

To study the effects of acupuncture analgesia on the hippocampus, we observed the effects of electroacupuncture (EA) and mitogen-activated protein kinase (MEK) inhibitor on pain-excited neurons (PENs) and pain-inhibited neurons (PINs) in the hippocampal area CA1 of sham or chronic constrictive injury (CCI) rats. The animals were randomly divided into a control, a CCI, and a U0126 (MEK1/2 inhibitor) group. In all experiments, we briefly (10-second duration) stimulated the sciatic nerve electrically and recorded the firing rates of PENs and PINs. The results showed that in both sham and CCI rats brief sciatic nerve stimulation significantly increased the electrical activity of PENs and markedly decreased the electrical activity of PINs. These effects were significantly greater in CCI rats compared to sham rats. EA treatment reduced the effects of the noxious stimulus on PENs and PINs in both sham and CCI rats. The effects of EA treatment could be inhibited by U0126 in sham-operated rats. The results suggest that EA reduces effects of acute sciatic nerve stimulation on PENs and PINs in the CA1 region of the hippocampus of both sham and CCI rats and that the ERK (extracellular regulated kinase) signaling pathway is involved in the modulation of EA analgesia. PMID:27833763

Central noradrenergic mechanisms and the acute stress response during painful stimulation.

PubMed

Chapman, C Richard; Bradshaw, David H; Donaldson, Gary W; Jacobson, Robert C; Nakamura, Yoshio

2014-12-01

Events that threaten tissue integrity including noxious stimulation activate central noradrenergic circuits, particularly locus coeruleus and its projections. Recent advances in theory hold that an adaptive, defensive shift in brain activity takes place in response to threat. In principle, this shift may accentuate the autonomic and central biomarkers of the perception of painful events and the experience of pain itself. We have examined the effects of an alpha-2 agonist on pupil dilation responses, skin conductance responses, near field somatosensory evoked potentials and pain reports in normal volunteers undergoing repeated trials of painful fingertip stimulation delivered at low, medium and high intensities. In a double-blinded study, 114 healthy male and female volunteers underwent repeated noxious stimulation under baseline, placebo and active drug conditions where the active drug was the alpha-2 agonist tizanidine 4 mg. In contrast to baseline and placebo conditions, tizanidine 4 mg significantly reduced the magnitudes of the mean pupil dilation response, the mean skin conductance response, the mean near field somatosensory evoked potential peak-to-peak amplitude and the mean pain intensity rating. Stimulus intensity significantly altered all three biomarkers and the pain report in a graded fashion. There were no sex differences. These findings support the hypotheses that painful events activate central noradrenergic circuits, and that these circuits play a role in the autonomic and central arousal associated with pain. © The Author(s) 2014.

Influence of local noxious heat stimulation on sensory nerve activity in the feline dental pulp.

PubMed

Ahlberg, K F

1978-05-01

The present investigation was undertaken to develop an experimental model in which noxious heat stimulation was used to produce increased intradental sensory nerve activity in canine teeth of anesthetized cats. Two techniques were evaluated in which both the method of recording and the nature of the stimulus varied. Slow heating (approx 1 degree C/s) to 47 degree C of the tooth surface (combined with recording from electrodes in open dentinal cavities) did not produce any persistent nerve activity. Repeated periods of brief intense heating (approx 60 degrees C/s) (combined with recording from amalgam electrodes placed on cavity floors) resulted in an immediate response and an afterdischarge (phase 3) generally persisting for 20--60 min. Maximum phase 3 activity was characteristic for the individual cat and ranged from 0.2 to 50.2 imp/s. mean value 10.6 imp/s (S.D. +/- 9.2). A systematically higher phase 3 activity was recorded in lower compared to upper canine teeth (p less than 0.05). The maximum phase 3 response generally occurred after 3-8 stimulations; the median number of required stimuli was 3. Repeated brief heat stimulations combined with the closed cavity recording technique may be used as an experimental model by which the mechanisms behind increases in intradental sensory nerve activity associated with tissue damage can be studied.

Effects of the noncompetitive N-methyl-d-aspartate receptor antagonists ketamine and MK-801 on pain-stimulated and pain-depressed behaviour in rats.

PubMed

Hillhouse, T M; Negus, S S

2016-09-01

Pain is a significant public health concern, and current pharmacological treatments have problematic side effects and limited effectiveness. N-methyl-d-aspartate (NMDA) glutamate receptor antagonists have emerged as one class of candidate treatments for pain because of the significant contribution of glutamate signalling in nociceptive processing. This study compared effects of the NMDA receptor antagonists ketamine and MK-801 in assays of pain-stimulated and pain-depressed behaviour in rats. The nonsteroidal anti-inflammatory drug ketoprofen was examined for comparison as a positive control. Intraperitoneal injection of dilute acid served as an acute visceral noxious stimulus to stimulate a stretching response or depress intracranial self-stimulation (ICSS) in male Sprague-Dawley rats. Ketamine (1.0-10.0 mg/kg) blocked acid-stimulated stretching but failed to block acid-induced depression of ICSS, whereas MK-801 (0.01-0.1 mg/kg) blocked both acid-stimulated stretching and acid-induced depression of ICSS. These doses of ketamine and MK-801 did not alter control ICSS in the absence of the noxious stimulus; however, higher doses of ketamine (10 mg/kg) and MK-801 (0.32 mg/kg) depressed all behaviour. Ketoprofen (1.0 mg/kg) blocked both acid-induced stimulation of stretching and depression of ICSS without altering control ICSS. These results support further consideration of NMDA receptor antagonists as analgesics; however, some NMDA receptor antagonists are more efficacious at attenuating pain-depressed behaviours. NMDA receptor antagonists produce dissociable effects on pain-depressed behaviour. Provides evidence that pain-depressed behaviours should be considered and evaluated when determining the antinociceptive effects of NMDA receptor antagonists. © 2016 European Pain Federation - EFIC®

Effects of the noncompetitive N-methyl-D-aspartate receptor antagonists ketamine and MK-801 on pain-stimulated and pain-depressed behaviour in rats

PubMed Central

Hillhouse, T.M.; Negus, S.S.

2017-01-01

Background Pain is a significant public health concern, and current pharmacological treatments have problematic side effects and limited effectiveness. N-methyl-D-aspartate (NMDA) glutamate receptor antagonists have emerged as one class of candidate treatments for pain because of the significant contribution of glutamate signalling in nociceptive processing. Methods This study compared effects of the NMDA receptor antagonists ketamine and MK-801 in assays of pain-stimulated and pain-depressed behaviour in rats. The nonsteroidal anti-inflammatory drug ketoprofen was examined for comparison as a positive control. Intraperitoneal injection of dilute acid served as an acute visceral noxious stimulus to stimulate a stretching response or depress intracranial self-stimulation (ICSS) in male Sprague–Dawley rats. Results Ketamine (1.0–10.0 mg/kg) blocked acid-stimulated stretching but failed to block acid-induced depression of ICSS, whereas MK-801 (0.01–0.1 mg/kg) blocked both acid-stimulated stretching and acid-induced depression of ICSS. These doses of ketamine and MK-801 did not alter control ICSS in the absence of the noxious stimulus; however, higher doses of ketamine (10 mg/kg) and MK-801 (0.32 mg/kg) depressed all behaviour. Ketoprofen (1.0 mg/kg) blocked both acid-induced stimulation of stretching and depression of ICSS without altering control ICSS. Conclusion These results support further consideration of NMDA receptor antagonists as analgesics; however, some NMDA receptor antagonists are more efficacious at attenuating pain-depressed behaviours. What does this study add? NMDA receptor antagonists produce dissociable effects on pain-depressed behaviour. Provides evidence that pain-depressed behaviours should be considered and evaluated when determining the antinociceptive effects of NMDA receptor antagonists. PMID:26914635

Substance P release and neurokinin 1 receptor activation in the rat spinal cord increase with the firing frequency of C-fibers.

PubMed

Adelson, D; Lao, L; Zhang, G; Kim, W; Marvizón, J C G

2009-06-30

Both the firing frequency of primary afferents and neurokinin 1 receptor (NK1R) internalization in dorsal horn neurons increase with the intensity of noxious stimulus. Accordingly, we studied how the pattern of firing of primary afferent influences NK1R internalization. In rat spinal cord slices, electrical stimulation of the dorsal root evoked NK1R internalization in lamina I neurons by inducing substance P release from primary afferents. The stimulation frequency had pronounced effects on NK1R internalization, which increased up to 100 Hz and then diminished abruptly at 200 Hz. Peptidase inhibitors increased NK1R internalization at frequencies below 30 Hz, indicating that peptidases limit the access of substance P to the receptor at moderate firing rates. NK1R internalization increased with number of pulses at all frequencies, but maximal internalization was substantially lower at 1-10 Hz than at 30 Hz. Pulses organized into bursts produced the same NK1R internalization as sustained 30 Hz stimulation. To determine whether substance P release induced at high stimulation frequencies was from C-fibers, we recorded compound action potentials in the sciatic nerve of anesthetized rats. We observed substantial NK1R internalization when stimulating at intensities evoking a C-elevation, but not at intensities evoking only an Adelta-elevation. Each pulse in trains at frequencies up to 100 Hz evoked a C-elevation, demonstrating that C-fibers can follow these high frequencies. C-elevation amplitudes declined progressively with increasing stimulation frequency, which was likely caused by a combination of factors including temporal dispersion. In conclusion, the instantaneous firing frequency in C-fibers determines the amount of substance P released by noxious stimuli.

Substance P release and neurokinin 1 receptor activation in the rat spinal cord increases with the firing frequency of C-fibers

PubMed Central

Adelson, David; Lao, Lijun; Zhang, Guohua; Kim, Woojae; Marvizón, Juan Carlos G.

2009-01-01

Both the firing frequency of primary afferents and neurokinin 1 receptor (NK1R) internalization in dorsal horn neurons increase with the intensity of noxious stimulus. Accordingly, we studied how the pattern of firing of primary afferent influences NK1R internalization. In rat spinal cord slices, electrical stimulation of the dorsal root evoked NK1R internalization in lamina I neurons by inducing substance P release from primary afferents. The stimulation frequency had pronounced effects on NK1R internalization, which increased up to 100 Hz and then diminished abruptly at 200 Hz. Peptidase inhibitors increased NK1R internalization at frequencies below 30 Hz, indicating that peptidases limit the access of substance P to the receptor at moderate firing rates. NK1R internalization increased with number of pulses at all frequencies, but maximal internalization was substantially lower at 1–10 Hz than at 30 Hz. Pulses organized into bursts produced the same NK1R internalization as sustained 30 Hz stimulation. To determine whether substance P release induced at high stimulation frequencies was from C-fibers, we recorded compound action potentials in the sciatic nerve of anesthetized rats. We observed substantial NK1R internalization when stimulating at intensities evoking a C-elevation, but not at intensities evoking only an Aδ-elevation. Each pulse in trains at frequencies up to 100 Hz evoked a C-elevation, demonstrating that C-fibers can follow these high frequencies. C-elevation amplitudes declined progressively with increasing stimulation frequency, which was likely caused by a combination of factors including temporal dispersion. In conclusion, the instantaneous firing frequency in C-fibers determines the amount of substance P released by noxious stimuli. PMID:19336248

The spino-bulbar-cerebellar pathway: Activation of neurons projecting to the lateral reticular nucleus in the rat in response to noxious mechanical stimuli.

PubMed

Huma, Zilli; Ireland, Kirsty; Maxwell, David J

2015-03-30

It is now well established that the cerebellum receives input from nociceptors which may serve to adjust motor programmes in response to pain and injury. In this study, we investigated the possibility that spinoreticular neurons (SRT) which project to a pre-cerebellar nucleus, the lateral reticular nucleus (LRt), respond to noxious mechanical stimulation. Seven adult male rats received stereotaxic injections of the b subunit of cholera toxin in the LRt. Following a 5 day interval, animals were anesthetised with urethane and a noxious mechanical stimulus was applied to the right hind paw. Animals were fixed by perfusion 5min following application of the stimulus. Retrogradely labelled SRT neurons of the lumbar spinal cord were examined for immunoreactivity for phosphorylated ERK (pERK) and the neurokinin-1 (NK-1) receptor. Approximately 15% of SRT cells in deep laminae (IV-VII and X) expressed pERK ipsilateral to the site of the stimulus. Around 60% of SRT cells with the NK-1 receptor expressed pERK but 5% of pERK expressing cells were negatively labelled for NK-1. It is concluded that a significant proportion of SRT cells projecting to the LRt respond to noxious mechanical stimuli and that one of the functions of this pathway may be to provide the cerebellum with nociceptive information. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Clinical evidence of parietal cortex dysfunction and correlation with extent of allodynia in CRPS type 1.

PubMed

Cohen, H; McCabe, C; Harris, N; Hall, J; Lewis, J; Blake, D R

2013-04-01

Unusual symptoms such as digit misidentification and neglect-like phenomena have been reported in complex regional pain syndrome (CRPS), which we hypothesized could be explained by parietal lobe dysfunction. Twenty-two patients with chronic CRPS attending an in-patient rehabilitation programme underwent standard neurological examination followed by clinical assessment of parietal lobe function and detailed sensory testing. Fifteen (68%) patients had evidence of parietal lobe dysfunction. Six (27%) subjects failed six or more test categories and demonstrated new clinical signs consistent with their parietal testing impairments, which were impacting significantly on activities of daily living. A higher incidence was noted in subjects with >1 limb involvement, CRPS affecting the dominant side and in left-handed subjects. Eighteen patients (82%) had mechanical allodynia covering 3-57.5% of the body surface area. Allochiria (unilateral tactile stimulation perceived only in the analogous location on the opposite limb), sensory extinction (concurrent bilateral tactile stimulation perceived only in one limb), referred sensations (unilateral tactile stimulation perceived concurrently in another discrete body area) and dysynchiria (unilateral non-noxious tactile stimulation perceived bilaterally as noxious) were present in some patients. Greater extent of body surface allodynia was correlated with worse parietal function (Spearman's rho = -0.674, p = 0.001). In patients with chronic CRPS, detailed clinical examination may reveal parietal dysfunction, with severity relating to the extent of allodynia. © 2012 European Federation of International Association for the Study of Pain Chapters.

When Pain Hurts: Nociceptive Stimulation Induces a State of Maladaptive Plasticity and Impairs Recovery after Spinal Cord Injury.

PubMed

Grau, James W; Huang, Yung-Jen; Turtle, Joel D; Strain, Misty M; Miranda, Rajesh C; Garraway, Sandra M; Hook, Michelle A

2017-05-15

Spinal cord injury (SCI) is often accompanied by other tissue damage (polytrauma) that provides a source of pain (nociceptive) input. Recent findings are reviewed that show SCI places the caudal tissue in a vulnerable state that exaggerates the effects nociceptive stimuli and promotes the development of nociceptive sensitization. Stimulation that is both unpredictable and uncontrollable induces a form of maladaptive plasticity that enhances nociceptive sensitization and impairs spinally mediated learning. In contrast, relational learning induces a form of adaptive plasticity that counters these adverse effects. SCI sets the stage for nociceptive sensitization by disrupting serotonergic (5HT) fibers that quell overexcitation. The loss of 5HT can enhance neural excitability by reducing membrane-bound K + -Cl - cotransporter 2, a cotransporter that regulates the outward flow of Cl - . This increases the intracellular concentration of Cl - , which reduces the hyperpolarizing (inhibitory) effect of gamma-aminobutyric acid. Uncontrollable noxious stimulation also undermines the recovery of locomotor function, and increases behavioral signs of chronic pain, after a contusion injury. Nociceptive stimulation has a greater effect if experienced soon after SCI. This adverse effect has been linked to a downregulation in brain-derived neurotrophic factor and an upregulation in the cytokine, tumor necrosis factor. Noxious input enhances tissue loss at the site of injury by increasing the extent of hemorrhage and apoptotic/pyroptotic cell death. Intrathecal lidocaine blocks nociception-induced hemorrhage, cellular indices of cell death, and its adverse effect on behavioral recovery. Clinical implications are discussed.

Analysis of transient receptor potential ankyrin 1 (TRPA1) in frogs and lizards illuminates both nociceptive heat and chemical sensitivities and coexpression with TRP vanilloid 1 (TRPV1) in ancestral vertebrates.

PubMed

Saito, Shigeru; Nakatsuka, Kazumasa; Takahashi, Kenji; Fukuta, Naomi; Imagawa, Toshiaki; Ohta, Toshio; Tominaga, Makoto

2012-08-31

Transient receptor potential ankyrin 1 (TRPA1) and TRP vanilloid 1 (V1) perceive noxious temperatures and chemical stimuli and are involved in pain sensation in mammals. Thus, these two channels provide a model for understanding how different genes with similar biological roles may influence the function of one another during the course of evolution. However, the temperature sensitivity of TRPA1 in ancestral vertebrates and its evolutionary path are unknown as its temperature sensitivities vary among different vertebrate species. To elucidate the functional evolution of TRPA1, TRPA1s of the western clawed (WC) frogs and green anole lizards were characterized. WC frog TRPA1 was activated by heat and noxious chemicals that activate mammalian TRPA1. These stimuli also activated native sensory neurons and elicited nocifensive behaviors in WC frogs. Similar to mammals, TRPA1 was functionally co-expressed with TRPV1, another heat- and chemical-sensitive nociceptive receptor, in native sensory neurons of the WC frog. Green anole TRPA1 was also activated by heat and noxious chemical stimulation. These results suggest that TRPA1 was likely a noxious heat and chemical receptor and co-expressed with TRPV1 in the nociceptive sensory neurons of ancestral vertebrates. Conservation of TRPV1 heat sensitivity throughout vertebrate evolution could have changed functional constraints on TRPA1 and influenced the functional evolution of TRPA1 regarding temperature sensitivity, whereas conserving its noxious chemical sensitivity. In addition, our results also demonstrated that two mammalian TRPA1 inhibitors elicited different effect on the TRPA1s of WC frogs and green anoles, which can be utilized to clarify the structural bases for inhibition of TRPA1.

Analysis of Transient Receptor Potential Ankyrin 1 (TRPA1) in Frogs and Lizards Illuminates Both Nociceptive Heat and Chemical Sensitivities and Coexpression with TRP Vanilloid 1 (TRPV1) in Ancestral Vertebrates*

PubMed Central

Saito, Shigeru; Nakatsuka, Kazumasa; Takahashi, Kenji; Fukuta, Naomi; Imagawa, Toshiaki; Ohta, Toshio; Tominaga, Makoto

2012-01-01

Transient receptor potential ankyrin 1 (TRPA1) and TRP vanilloid 1 (V1) perceive noxious temperatures and chemical stimuli and are involved in pain sensation in mammals. Thus, these two channels provide a model for understanding how different genes with similar biological roles may influence the function of one another during the course of evolution. However, the temperature sensitivity of TRPA1 in ancestral vertebrates and its evolutionary path are unknown as its temperature sensitivities vary among different vertebrate species. To elucidate the functional evolution of TRPA1, TRPA1s of the western clawed (WC) frogs and green anole lizards were characterized. WC frog TRPA1 was activated by heat and noxious chemicals that activate mammalian TRPA1. These stimuli also activated native sensory neurons and elicited nocifensive behaviors in WC frogs. Similar to mammals, TRPA1 was functionally co-expressed with TRPV1, another heat- and chemical-sensitive nociceptive receptor, in native sensory neurons of the WC frog. Green anole TRPA1 was also activated by heat and noxious chemical stimulation. These results suggest that TRPA1 was likely a noxious heat and chemical receptor and co-expressed with TRPV1 in the nociceptive sensory neurons of ancestral vertebrates. Conservation of TRPV1 heat sensitivity throughout vertebrate evolution could have changed functional constraints on TRPA1 and influenced the functional evolution of TRPA1 regarding temperature sensitivity, whereas conserving its noxious chemical sensitivity. In addition, our results also demonstrated that two mammalian TRPA1 inhibitors elicited different effect on the TRPA1s of WC frogs and green anoles, which can be utilized to clarify the structural bases for inhibition of TRPA1. PMID:22791718

An equine pain face

PubMed Central

Gleerup, Karina B; Forkman, Björn; Lindegaard, Casper; Andersen, Pia H

2015-01-01

Objective The objective of this study was to investigate the existence of an equine pain face and to describe this in detail. Study design Semi-randomized, controlled, crossover trial. Animals Six adult horses. Methods Pain was induced with two noxious stimuli, a tourniquet on the antebrachium and topical application of capsaicin. All horses participated in two control trials and received both noxious stimuli twice, once with and once without an observer present. During all sessions their pain state was scored. The horses were filmed and the close-up video recordings of the faces were analysed for alterations in behaviour and facial expressions. Still images from the trials were evaluated for the presence of each of the specific pain face features identified from the video analysis. Results Both noxious challenges were effective in producing a pain response resulting in significantly increased pain scores. Alterations in facial expressions were observed in all horses during all noxious stimulations. The number of pain face features present on the still images from the noxious challenges were significantly higher than for the control trial (p = 0.0001). Facial expressions representative for control and pain trials were condensed into explanatory illustrations. During pain sessions with an observer present, the horses increased their contact-seeking behavior. Conclusions and clinical relevance An equine pain face comprising ‘low’ and/or ‘asymmetrical’ ears, an angled appearance of the eyes, a withdrawn and/or tense stare, mediolaterally dilated nostrils and tension of the lips, chin and certain facial muscles can be recognized in horses during induced acute pain. This description of an equine pain face may be useful for improving tools for pain recognition in horses with mild to moderate pain. PMID:25082060

Pain assessment by continuous EEG: association between subjective perception of tonic pain and peak frequency of alpha oscillations during stimulation and at rest.

PubMed

Nir, Rony-Reuven; Sinai, Alon; Raz, Einat; Sprecher, Elliot; Yarnitsky, David

2010-07-16

Recordings of neurophysiological brain responses to noxious stimuli have been traditionally based on short stimuli, in the order of milliseconds, which induce distinct event-related potentials (ERPs). However, using such stimuli in the experimental setting is disadvantageous as they are too brief to faithfully simulate clinical pain. We aimed at utilizing continuous EEG to investigate the properties of peak alpha frequency (PAF) as an objective cortical measure associated with subjective perception of tonic pain. Five minute long continuous EEG was recorded in 18 healthy volunteers under: (i) resting-state; (ii) innocuous temperature; and (iii) psychophysically-anchored noxious temperature. Numerical pain scores (NPSs) collected during the application of tonic noxious stimuli were tested for correlation with peak frequencies of alpha power-curves derived from central, temporal and frontal electrodes. NPSs and PAFs remained stable throughout the recording conditions (RM-ANOVAs; Ps>0.51). In the noxious condition, PAFs obtained at the bilateral temporal scalp were correlated with NPSs (Ps<0.001). Moreover, resting-state PAFs recorded at the bilateral temporal scalp were correlated with NPSs reported during the noxious condition (Ps<0.01). These psychophysical-neurophysiological relations attest to the properties of PAF as a novel cortical objective measure of subjective perception of tonic pain. Moreover, resting-state PAFs might hold inherent pain modulation attributes, possibly enabling the prediction of individual responsiveness to prolonged pain. The relevance of PAF to the neural processing of tonic pain may indicate its potential to advance pain research as well as clinical pain characterization. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Emotional modulation of experimental pain: a source imaging study of laser evoked potentials

PubMed Central

Stancak, Andrej; Fallon, Nicholas

2013-01-01

Negative emotions have been shown to augment experimental pain. As induced emotions alter brain activity, it is not clear whether pain augmentation during noxious stimulation would be related to neural activation existing prior to onset of a noxious stimulus or alternatively, whether emotional stimuli would only alter neural activity during the period of nociceptive processing. We analyzed the spatio-temporal patterns of laser evoked potentials (LEPs) occurring prior to and during the period of cortical processing of noxious laser stimuli during passive viewing of negative, positive, or neutral emotional pictures. Independent component analysis (ICA) was applied to series of source activation volumes, reconstructed using local autoregressive average model (LAURA). Pain was the strongest when laser stimuli were associated with negative emotional pictures. Prior to laser stimulus and during the first 100 ms after onset of laser stimulus, activations were seen in the left and right medial temporal cortex, cerebellum, posterior cingulate, and rostral cingulate/prefrontal cortex. In all these regions, positive or neutral pictures showed stronger activations than negative pictures. During laser stimulation, activations in the right and left anterior insula, temporal cortex and right anterior and posterior parietal cortex were stronger during negative than neutral or positive emotional pictures. Results suggest that negative emotional stimuli increase activation in the left and right anterior insula and temporal cortex, and right posterior and anterior parietal cortex only during the period of nociceptive processing. The role of background brain activation in emotional modulation of pain appears to be only permissive, and consisting in attenuation of activation in structures maintaining the resting state of the brain. PMID:24062659

The effects of morphine on the temporal structure of Wistar rat behavioral response to pain in hot-plate.

PubMed

Casarrubea, Maurizio; Faulisi, Fabiana; Magnusson, Magnus S; Crescimanno, Giuseppe

2016-08-01

The largest amount of researches on the hot-plate test was carried out using quantitative assessments. However, the evaluation of the relationships among the different elements that compose the behavioral response to pain requires different approaches. Although previous studies have provided clear information on the behavioral structure of the response, no data are available on its temporal structure. The objective of this study was to investigate the temporal structure of the behavioral response to pain in Wistar rat tested in hot-plate and how this structure was influenced by morphine-induced analgesia. The behavior of four groups of subjects tested in hot-plate, one administered saline and three with different doses (3, 6, 12 mg/kg) of morphine IP, was analyzed by means of quantitative and t-pattern analyses. The latter is a multivariate technique able to detect the existence of statistically significant temporal relationships among the behavioral events in time. A clear-cut influence of morphine on quantitative parameters of the response to the noxious stimulation was observed. T-pattern analysis evidenced profound structural changes of behavior. Twenty-four different t-patterns were identified following saline, whereas a dose-dependent reduction was observed following morphine. Such a reduction was accompanied by a decrease of the total amount of t-patterns detected. Morphine, by reducing the effects of the noxious stimulation, orients animal behavior prevalently toward exploratory t-patterns. In addition, it is suggested that the temporal structure of the response is very quickly organized and adapted to environmental noxious cues.

Nicotine aversion: Neurobiological mechanisms and relevance to tobacco dependence vulnerability

PubMed Central

Fowler, Christie D.; Kenny, Paul J.

2013-01-01

Nicotine stimulates brain reward circuitries, most prominently the mesocorticolimbic dopamine system, and this action is considered critical in establishing and maintaining the tobacco smoking habit. Compounds that attenuate nicotine reward are considered promising therapeutic candidates for tobacco dependence, but many of these agents have other actions that limit their potential utility. Nicotine is also highly noxious, particularly at higher doses, and aversive reactions to nicotine after initial exposure can decrease the likelihood of developing a tobacco habit in many first time smokers. Nevertheless, relatively little is known about the mechanisms of nicotine aversion. The purpose of this review is to present recent new insights into the neurobiological mechanisms that regulate avoidance of nicotine. First, the role of the mesocorticolimbic system, so often associated with nicotine reward, in regulating nicotine aversion is highlighted. Second, genetic variation that modifies noxious responses to nicotine and thereby influences vulnerability to tobacco dependence, in particular variation in the CHRNA5-CHRNA3-CHRNB4 nicotinic acetylcholine receptor (nAChR) subunit gene cluster, will be discussed. Third, the role of the habenular complex in nicotine aversion, primarily medial habenular projections to the interpeduncular nucleus (IPN) but also lateral habenular projections to rostromedial tegmental nucleus (RMTg) and ventral tegmental area (VTA) are reviewed. Forth, brain circuits that are enriched in nAChRs, but whose role in nicotine avoidance has not yet been assessed, will be proposed. Finally, the feasibility of developing novel therapeutic agents for tobacco dependence that act not by blocking nicotine reward but by enhancing nicotine avoidance will be considered. PMID:24055497

Neural Responses to Injury: Prevention, Protection, and Repair.

DTIC Science & Technology

1998-10-01

opioid-sensitive circuitry by electroacupuncture can suppress c-fos expression (21). Anesthetic agents and system- ically administered morphine can...ders Co., 1995, pp 397-460. 21. Lee JH, Beitz AJ: Electroacupuncture modifies the expression of c-fos in the spinal cord induced by noxious

The behavioural importance of dynamically activated descending inhibition from the nucleus reticularis gigantocellularis pars alpha.

PubMed

Azami, J; Green, D L; Roberts, M H; Monhemius, R

2001-05-01

We have recently demonstrated (J Physiol 506 (1998) 459) that the dynamic activation of descending inhibition of the nociceptive response of spinal multireceptive cells occurs in the nucleus reticularis gigantocellularis pars alpha (GiA). In the same paper we have shown that Lamina I dorsal horn cells are responsible for activating this inhibition via a pathway which runs in the contralateral dorsolateral funiculus. The effects of dynamically activating this system by noxious stimulation on behavioural responses to noxious stimuli have not been established. Here we demonstrate the effects of GiA on the behavioural response during application of standardized noxious stimuli. As this system is activated in response to noxious stimulation (J Physiol 506 (1998) 459), it is possible that chronic pain states may also activate GiA. We have therefore investigated this possibility in animals following partial sciatic nerve ligation (an animal model of chronic pain; Pain 43 (1990) 205). Male Wistar rats (280-310 g) were anaesthetized with halothane (0.5-2% in O(2)). Guide cannulae for microinjections were stereotaxically placed above GiA. In one group of animals the sciatic nerve was partially ligated. Animals were allowed to recover for 4-6 days. The responses of each animal during the formalin test (Pain 4 (1977) 161) and the tail flick test (Pain 12 (1982) 229) were recorded on different days. Microinjections (0.5 microl) of either gamma-aminobutyric acid (GABA, 200 mM), D-L homocysteic acid (DLH, 25 mM) or 0.9% saline (as control) into GiA were performed during these tests in a randomized, blind manner. In animals without sciatic nerve ligation, microinjection of GABA to GiA did not significantly affect the animal's response during the tail flick test. However microinjection of DLH significantly increased the latency of tail flick from 6.2 +/- 0.8 to 8.4 +/- 0.5 s for up to 15 min (n = 7, P < 0.01, Mann-Whitney U-test). Microinjection of GABA to GiA increased the behavioural response to formalin between 10 and 20 min post-injection, while microinjection of DLH reduced this response at all time points except 10 min post-injection (n = 8, P < 0.05, Mann-Whitney U-test). In animals with sciatic nerve ligation, microinjections (0.5 microl) of either GABA (200 mM), or saline (as control) into GiA contralateral to the partial sciatic ligation were performed during these tests in a randomized, blind manner. Partial sciatic ligation significantly reduced the behavioural response to contralaterally applied formalin from 15 min post-injection onwards, compared to controls without sciatic nerve ligation. Microinjection of GABA to GiA significantly increased the behavioural response to formalin from 20 to 50 min post-injection. The inactivation of GiA only causes behavioural effects in nociceptive tests of a long enough duration to activate the system (i.e. the formalin test but not the tail flick test). Chemical activation of the system affects both tests. These data strongly support the concept of an important analgesic system which is activated in response to noxious stimulation, and subsequently acts to reduce behavioural responses to noxious stimuli.

Investigation of human frontal cortex under noxious thermal stimulation of temporo-mandibular joint using functional near infrared spectroscopy

NASA Astrophysics Data System (ADS)

Yennu, Amarnath; Rawat, Rohit; Manry, Michael T.; Gatchel, Robert; Liu, Hanli

2013-03-01

According to American Academy of Orofacial Pain, 75% of the U.S. population experiences painful symptoms of temporo-mandibular joint and muscle disorder (TMJMD) during their lifetime. Thus, objective assessment of pain is crucial for efficient pain management. We used near infrared spectroscopy (NIRS) as a tool to explore hemodynamic responses in the frontal cortex to noxious thermal stimulation of temporomadibular joint (TMJ). NIRS experiments were performed on 9 healthy volunteers under both low pain stimulation (LPS) and high pain stimulation (HPS), using a temperature-controlled thermal stimulator. To induce thermal pain, a 16X16 mm2 thermode was strapped onto the right TMJ of each subject. Initially, subjects were asked to rate perceived pain on a scale of 0 to 10 for the temperatures from 41°C to 47°C. For the NIRS measurement, two magnitudes of temperatures, one rated as 3 and another rated as 7, were chosen as LPS and HPS, respectively. By analyzing the temporal profiles of changes in oxy-hemoglobin concentration (HbO) using cluster-based statistical tests, we were able to identify several regions of interest (ROI), (e.g., secondary somatosensory cortex and prefrontal cortex), where significant differences (p<0.05) between HbO responses to LPS and HPS are shown. In order to classify these two levels of pain, a neural-network-based classification algorithm was used. With leave-one-out cross validation from 9 subjects, the two levels of pain were identified with 100% mean sensitivity, 98% mean specificity and 99% mean accuracy to high pain. From the receiver operating characteristics curve, 0.99 mean area under curve was observed.

Motor cortex stimulation suppresses cortical responses to noxious hindpaw stimulation after spinal cord lesion in rats.

PubMed

Jiang, Li; Ji, Yadong; Voulalas, Pamela J; Keaser, Michael; Xu, Su; Gullapalli, Rao P; Greenspan, Joel; Masri, Radi

2014-01-01

Motor cortex stimulation (MCS) is a potentially effective treatment for chronic neuropathic pain. The neural mechanisms underlying the reduction of hyperalgesia and allodynia after MCS are not completely understood. To investigate the neural mechanisms responsible for analgesic effects after MCS. We test the hypothesis that MCS attenuates evoked blood oxygen-level dependent signals in cortical areas involved in nociceptive processing in an animal model of chronic neuropathic pain. We used adult female Sprague-Dawley rats (n = 10) that received unilateral electrolytic lesions of the right spinal cord at the level of C6 (SCL animals). In these animals, we performed magnetic resonance imaging (fMRI) experiments to study the analgesic effects of MCS. On the day of fMRI experiment, 14 days after spinal cord lesion, the animals were anesthetized and epidural bipolar platinum electrodes were placed above the left primary motor cortex. Two 10-min sessions of fMRI were performed before and after a session of MCS (50 μA, 50 Hz, 300 μs, for 30 min). During each fMRI session, the right hindpaw was electrically stimulated (noxious stimulation: 5 mA, 5 Hz, 3 ms) using a block design of 20 s stimulation off and 20 s stimulation on. A general linear model-based statistical parametric analysis was used to analyze whole brain activation maps. Region of interest (ROI) analysis and paired t-test were used to compare changes in activation before and after MCS in these ROI. MCS suppressed evoked blood oxygen dependent signals significantly (Family-wise error corrected P < 0.05) and bilaterally in 2 areas heavily implicated in nociceptive processing. These areas consisted of the primary somatosensory cortex and the prefrontal cortex. These findings suggest that, in animals with SCL, MCS attenuates hypersensitivity by suppressing activity in the primary somatosensory cortex and prefrontal cortex. Copyright © 2014. Published by Elsevier Inc.

Duodenal afferent input converges onto T9-T10 spinal neurons responding to gastric distension in rats.

PubMed

Qin, Chao; Chen, Jiande D Z; Zhang, Jing; Foreman, Robert D

2007-12-01

Clinically, the overlap of gastroduodenal symptoms, such as visceral pain or hypersensitivity, is often observed in functional gastrointestinal disorders. The underlying mechanism may be related to intraspinal neuronal processing of noxious convergent inputs from the stomach and the intestine. The purpose of this study was to examine whether single low thoracic (T9-T10) spinal neurons responded to both gastric and duodenal mechanical stimulation. Extracellular potentials of single T9-T10 spinal neurons were recorded in pentobarbital anesthetized, paralyzed, and ventilated male rats. Graded gastric distensions (GD, 20, 40, 60 mm Hg, 20 s) were induced by air inflation of a latex balloon surgically placed in the stomach. Graded duodenal distensions (DD, 0.2, 0.4, 0.6 ml, 20 s) were produced by water inflation of a latex balloon placed into the duodenum. Of 70 deeper (depth from dorsal surface of spinal cord: 0.3-1.2 mm) spinal neurons responsive to noxious GD (> or =40 mm Hg), 44(63%) also responded to noxious DD (> or =0.4 ml). Similarly, 13/17 (76%) superficial neurons (depth <0.3 mm) responded to both GD and DD. Of 57 gastroduodenal convergent neurons, 41 (72%) had excitatory and 6 had inhibitory responses to both GD and DD; the remaining neurons exhibited multiple patterns of excitation and inhibition. 43/57 (75%) gastroduodenal convergent neurons had low-threshold (< or =20 mm Hg) responses to GD, whereas 42/57 (74%) of these neurons had high-threshold (> or =0.4 ml) responses to DD. In addition, 34/40 (85%) gastroduodenal convergent neurons had somatic receptive fields on the back, flank, and medial/lateral abdominal areas. These results suggested that superficial and deeper T9-T10 spinal neurons received innocuous and/or noxious convergent inputs from mechanical stimulation of the stomach and duodenum. Gastroduodenal convergent spinal neurons might contribute to intraspinal sensory transmission for cross-organ afferent-afferent communication between the stomach and duodenum and play a role in visceral nociception and reflexes.

A Simple fMRI Compatible Robotic Stimulator to Study the Neural Mechanisms of Touch and Pain.

PubMed

Riillo, F; Bagnato, C; Allievi, A G; Takagi, A; Fabrizi, L; Saggio, G; Arichi, T; Burdet, E

2016-08-01

This paper presents a simple device for the investigation of the human somatosensory system with functional magnetic imaging (fMRI). PC-controlled pneumatic actuation is employed to produce innocuous or noxious mechanical stimulation of the skin. Stimulation patterns are synchronized with fMRI and other relevant physiological measurements like electroencephalographic activity and vital physiological parameters. The system allows adjustable regulation of stimulation parameters and provides consistent patterns of stimulation. A validation experiment demonstrates that the system safely and reliably identifies clusters of functional activity in brain regions involved in the processing of pain. This new device is inexpensive, portable, easy-to-assemble and customizable to suit different experimental requirements. It provides robust and consistent somatosensory stimulation, which is of crucial importance to investigating the mechanisms of pain and its strong connection with the sense of touch.

Theta-frequency phase-locking of single anterior cingulate cortex neurons and synchronization with the medial thalamus are modulated by visceral noxious stimulation in rats.

PubMed

Wang, J; Cao, B; Yu, T R; Jelfs, B; Yan, J; Chan, R H M; Li, Y

2015-07-09

The rodent anterior cingulate cortex (ACC) is critical for visceral pain and pain-related aversive response in chronic visceral hypersensitive (VH) state. Long-term potentiation (LTP), induced by theta burst stimulation (TBS) in the medial thalamus (MT)-ACC pathway, is blocked in VH rats. However, the neuronal intrinsic firing characteristics and the MT-ACC connectivity have not been investigated in visceral pain. Using repetitive distension of the colon and rectum (rCRD) as a sensitization paradigm, we have identified that the spontaneous firing rates of ACC neurons and the CRD-stimulated neuronal firings were increased after repetitive visceral noxious stimulation. This correlates with increases in visceral pain responses (visceromotor responses, VMRs). Two multichannel arrays of electrodes were implanted in the MT and ACC. Recordings were performed in free-moving rats before and after repeated CRD treatment. Power spectral density analysis showed that the local field potential (LFP) recorded in the ACC displayed increases in theta band power (4-10 Hz) that were modulated by rCRD. Neural spike activity in the ACC becomes synchronized with ongoing theta oscillations of LFP. Furthermore, cross correlation analysis showed augmented synchronization of thalamo-ACC theta band LFPs, which was consistent with an increase of neuronal communication between the two regions. In conclusion, these results reveal theta oscillations and theta-frequency phase-locking as prominent features of neural activity in the ACC and a candidate neural mechanism underlying acute visceral pain. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

The Influence of Trigeminal Stimulation on Children's Judgements of Odor.

ERIC Educational Resources Information Center

Engen, Trygg; Moskowitz, Linda

Children's preference for odors, some of which presumably had marked trigeminal (noxious) effects, was assessed with the use of the method of pair comparison. Although the children, from 4 to 7 years old, were able to discriminate between the intensities of the odors, they were neither attracted nor repelled by them as much as the adults. In other…

Portable infrared pupillometry: a review.

PubMed

Larson, Merlin D; Behrends, Matthias

2015-06-01

Portable infrared pupillometers provide an objective measure of pupil size and pupillary reflexes, which for most clinicians was previously only a visual impression. But despite the fact that pupillometry can uncover aspects of how the human pupil reacts to drugs and noxious stimulation, the use of pupillometry has not gained widespread use among anesthesiologists and critical care physicians. The present review is an introduction to the physiology of pupillary reflexes and the currently established clinical applications of infrared pupillometry, which will hopefully encourage physicians to use this diagnostic tool in their clinical practice. Portable infrared pupillometry was introduced in 1989. The technology involves flooding the eye with infrared light and then measuring the reflected image on an infrared sensor. Pupil size, along with variables of the pupillary light reflex and pupillary reflex dilation, is calculated by the instrument and displayed on a screen immediately after each time-stamped measurement. Use of these instruments has uncovered aspects of how the human pupil reacts to drugs and noxious stimulation. The primary clinical applications for portable pupillometry have been in the assessment of brainstem function. Portable pupillometry is useful in the management of pain because it allows for assessments of the effect of opioids and in the titration of combined regional-general anesthetics.

Emotion-focused coping and distraction: sex differences in the influence of anxiety sensitivity during noxious heat stimulation.

PubMed

Thompson, T; Keogh, E; Chen, M J-L; French, C C

2012-03-01

While previous research has indicated that the relative efficacy of attentional strategies on pain may be influenced by anxiety sensitivity (AS) and sex, no study appears to have examined this within the context of an emotion-focus versus distraction paradigm. The present study compared the effect of attentional emotion-focus and distraction instructions on pain response with noxious heat stimulation in 114 healthy adults (62 women and 52 men) varying in levels of AS. Results indicated that men reported a significantly higher mean tolerance time than women. Moderated regression analysis also revealed a significant strategy × anxiety sensitivity × sex interaction on pain tolerance. For those low in AS, relative efficacy was dependent upon sex, with distraction superior to emotion-focusing in women, but with strategies equivalent in men. For those high in AS, however, distraction resulted in uniformly greater pain tolerance than attentional emotion-focusing. These results indicate that AS and sex may be influential in determining the relative effectiveness of distraction and emotion-based attentional strategies for pain management. © 2011 European Federation of International Association for the Study of Pain Chapters.

Effects of Repeated Morphine on Intracranial Self-Stimulation in Male Rats In the Absence or Presence of a Noxious Pain Stimulus

PubMed Central

Miller, Laurence L.; Altarifi, Ahmad A.; Negus, S. Stevens

2015-01-01

Research on opioid analgesics such as morphine suggests that expression of abuse-related effects increases with repeated exposure. Repeated exposure to opioids often occurs clinically in the context of pain management, and a major concern for clinicians is the risk of iatrogenic addiction and dependence in patients receiving opioids for treatment of pain. This study compared abuse-related morphine effects in male rats in an intracranial self-stimulation (ICSS) procedure after repeated treatment either with morphine alone or with morphine in combination with a repeated noxious stimulus (intraperitoneal administration of dilute acid). The study also permitted comparison of morphine potency and effectiveness to block acid-induced depression of ICSS (antinociception) and to produce enhanced facilitation of ICSS (abuse-related effect). There were three main findings. First, initial morphine exposure to drug naïve rats did not produce abuse-related ICSS facilitation. Second, repeated daily treatment with 3.2 mg/kg/day morphine for six days increased expression of ICSS facilitation. This occurred whether morphine was administered in the absence or presence of the noxious stimulus. Finally, a lower dose of 1.0 mg/kg/day morphine was sufficient to produce antinociception during repeated acid treatment, but this lower dose did not reliably increase abuse-related morphine effects. Taken together, these results suggest that prior morphine exposure can increase abuse liability of subsequent morphine treatments even when that morphine exposure occurs in the context of a pain state. However, it may be possible to relieve pain with relatively low morphine doses that do not produce increases in abuse-related morphine effects. PMID:26375515

Effects of repeated morphine on intracranial self-stimulation in male rats in the absence or presence of a noxious pain stimulus.

PubMed

Miller, Laurence L; Altarifi, Ahmad A; Negus, S Stevens

2015-10-01

Research on opioid analgesics such as morphine suggests that expression of abuse-related effects increases with repeated exposure. Repeated exposure to opioids often occurs clinically in the context of pain management, and a major concern for clinicians is the risk of iatrogenic addiction and dependence in patients receiving opioids for treatment of pain. This study compared abuse-related morphine effects in male rats in an intracranial self-stimulation (ICSS) procedure after repeated treatment either with morphine alone or with morphine in combination with a repeated noxious stimulus (intraperitoneal administration of dilute acid). The study also permitted comparison of morphine potency and effectiveness to block acid-induced depression of ICSS (antinociception) and to produce enhanced facilitation of ICSS (abuse-related effect). There were 3 main findings. First, initial morphine exposure to drug naïve rats did not produce abuse-related ICSS facilitation. Second, repeated daily treatment with 3.2 mg/kg/day morphine for 6 days increased expression of ICSS facilitation. This occurred whether morphine was administered in the absence or presence of the noxious stimulus. Finally, a lower dose of 1.0 mg/kg/day morphine was sufficient to produce antinociception during repeated acid treatment, but this lower dose did not reliably increase abuse-related morphine effects. Taken together, these results suggest that prior morphine exposure can increase abuse liability of subsequent morphine treatments even when that morphine exposure occurs in the context of a pain state. However, it may be possible to relieve pain with relatively low morphine doses that do not produce increases in abuse-related morphine effects. (c) 2015 APA, all rights reserved).

Strychnine-sensitive modulation is selective for non-noxious somatosensory input in the spinal cord of the rat.

PubMed

Sherman, S E; Loomis, C W

1996-08-01

Touch-evoked allodynia, an important symptom of clinical neural injury pain, can be modelled acutely and reversibly in the urethane-anesthetized rat using intrathecal (i.t.) strychnine (STR). Allodynia, after i.t. STR (40 micrograms), is manifest as a significant enhancement of cardiovascular and motor responses evoked by normally innocuous brushing of the hair (hair deflection), as compared to responses evoked by either hair deflection after i.t. saline (SAL), or to i.t. STR (40 micrograms) with no tactile stimulus. The present study investigated: (1) the pharmacology of afferent neural inputs involved in STR-dependent allodynia using neonatal capsaicin and the non-NMDA receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline (NBQX); and (2) the effect of i.t. STR on responses evoked by peripheral noxious stimulation. Neonatal capsaicin (25 mg/kg, s.c., post-natal day (PND) 1, and 50 mg/kg, s.c., PND 2, 3, 4, 11, 25, 55 and 85) significantly attenuated the responses evoked by noxious mechanical, thermal or chemical stimuli, but had no effect on STR-dependent allodynia. All hair deflection-evoked, STR-dependent responses were dose-dependently inhibited by i.t. NBQX. The ED50 values and 95% confidence intervals were 10.4 micrograms (5.5-19.6) for the motor withdrawal response, 14.4 micrograms (8.6-24.0) for changes in MAP and 12.2 micrograms (6.8-21.8) for changes in HR. Cortical EEG synchrony was unchanged by i.t. NBQX confirming its spinal locus of action. Intrathecal STR neither reduced nor enhanced the responses elicited by noxious stimuli in capsaicin- or vehicle-pretreated rats. These results indicate that STR-dependent allodynia is initiated by primary afferents not normally involved in nociception (possibly A beta-fibers), and that STR-sensitive modulation in the spinal cord is selective for non-noxious sensory input. The sensitivity of STR-dependent allodynia to non-NMDA receptor antagonists, and the failure of i.t. STR to produce hyperalgesia to mechanical, thermal or chemical noxious stimuli, confirm the independence of nociceptive pathways and STR-sensitive afferent inputs in this model.

Thalamic VPM nucleus in the behaving monkey. III. Effects of reversible inactivation by lidocaine on thermal and mechanical discrimination.

PubMed

Duncan, G H; Bushnell, M C; Oliveras, J L; Bastrash, N; Tremblay, N

1993-11-01

1. The present study evaluates the necessity of the ventroposterior medial thalamic nucleus (VPM) for discrimination of the intensity of noxious heating, innocuous cooling, and innocuous tactile (airpuff) stimulation of the maxillary skin. 2. Two rhesus monkeys were trained to detect small differences (< 1.0 degrees C) in the intensity of noxious heat (near 46 degrees C) and innocuous cold (near 30 degrees C) as well as differences in the force of an airpuff applied to the skin over the maxilla. As a control the monkeys also detected small differences in the intensity of a white light. Lidocaine hydrochloride (2%) was microinjected into regions of thalamus where single-unit recordings had identified neuronal responses to the noxious heating and/or cooling stimuli. The effectiveness of the anesthetic blockade was monitored by multiunit recordings using microelectrodes positioned 1-3 mm from the orifice of the injection cannula. The monkey's ability to detect near-threshold changes in stimulus intensity was compared before and after each injection. 3. During six experimental sessions, single injections of 1-4 microliters lidocaine near the dorsomedial border of VPM did not significantly alter the monkey's ability to detect small changes in the intensity of noxious heat, cool, airpuff, or visual stimuli despite neurophysiological evidence that spontaneous neuronal activity was blocked within parts of VPM. 4. During three experiments, dual simultaneous microinjections of lidocaine (delivered through 2 microcannulae separated by approximately 1 mm) resulted in profound deficits in noxious heat discrimination, with lesser deficits in cool and airpuff discrimination; visual discrimination was never altered. Monitoring of adjacent microelectrodes revealed that although activity ventral to the injection sites was blocked, activity in medial thalamic nuclei, implicated in nociceptive processing, was probably not altered by these injections. 5. These data suggest that VPM is important for the perception of noxious and innocuous thermal stimuli as well as for the perception of tactile stimuli. However, considering the ineffectiveness of small single microinjections of lidocaine, it appears that some critical proportion of VPM must be inactivated to disrupt thermal or tactile discrimination, possibly because of overlapping receptive field properties of neurons in different areas of the nucleus.

Spinal cord stimulation modulates intraspinal colorectal visceroreceptive transmission in rats

PubMed Central

Qin, C.; Lehew, R.T.; Khan, K.A.; Wienecke, G.M.; Foreman, R.D.

2007-01-01

Previous studies have shown that spinal cord stimulation (SCS) of upper lumbar segments decreases visceromotor responses to mechanical stimuli in a sensitized rat colon and reduces symptoms of irritable bowel syndrome in patients. SCS applied to the upper cervical spinal dorsal column reduces pain of chronic refractory angina. Further, chemical stimulation of C1-C2 propriospinal neurons in rats modulates the responses of lumbosacral spinal neurons to colorectal distension. The present study was designed to compare the effects of upper cervical and lumbar SCS on activity of lumbosacral neurons receiving noxious colorectal input. Extracellular potentials of L6-S2 spinal neurons were recorded in pentobarbital anesthetized, paralyzed and ventilated male rats. SCS (50 Hz, 0.2 ms) at low intensity (90% of motor threshold) was applied to the dorsal column of upper cervical (C1-C2) or upper lumbar (L2-L3) ipsilateral spinal segments. Colorectal distension (CRD, 20, 40, 60 mmHg, 20 s) was produced by air inflation of a latex balloon. Results showed that SCS applied to L2-L3 and C1-C2 segments significantly reduced the excitatory responses to noxious CRD from 417.6±68.0 imp to 296.3±53.6 imp (P<0.05, n=24) and from 336.2±64.5 imp to 225.0±73.3 imp (P<0.05, n= 18), respectively. Effects of L2-L3 and C1-C2 SCS lasted 10.2±1.9 min and 8.0±0.9 min after offset of CRD. Effects of SCS were observed on spinal neurons with either high or low threshold excitatory responses to CRD. However, L2-L3 or C1-C2 SCS did not significantly affect inhibitory neuronal responses to CRD. C1-C2 SCS-induced effects were abolished by cutting the C7-C8 dorsal column but not by spinal transection at cervicomedullary junction. These data demonstrated that upper cervical or lumbar SCS modulated responses of lumbosacral spinal neurons to noxious mechanical stimulation of the colon, thereby, proved two loci for a potential therapeutic effect of SCS in patients with irritable bowel syndrome and other colonic disorders. PMID:17324482

Peripheral Opioid Analgesia

DTIC Science & Technology

1999-07-16

central nervous system by neurons called primary afferent nociceptors (PANs). These neurons have their cell bodies in the dorsal root ganglia (ORG... neurons , and in particular their role in the generation, propagation and modulation of noxious stimulation will be summarized. The final section of...and processing of each opioid peptide is discussed below. The human POMC gene is 7665 base pairs (bp) long which contains three exons and two

Do pain-associated contexts increase pain sensitivity? An investigation using virtual reality.

PubMed

Harvie, Daniel S; Sterling, Michele; Smith, Ashley D

2018-04-30

Pain is not a linear result of nociception, but is dependent on multisensory inputs, psychological factors, and prior experience. Since nociceptive models appear insufficient to explain chronic pain, understanding non-nociceptive contributors is imperative. Several recent models propose that cues associatively linked to painful events might acquire the capacity to augment, or even cause, pain. This experiment aimed to determine whether contexts associated with pain, could modulate mechanical pain thresholds and pain intensity. Forty-eight healthy participants underwent a contextual conditioning procedure, where three neutral virtual reality contexts were paired with either unpredictable noxious stimulation, unpredictable vibrotactile stimulation, or no stimulation. Following the conditioning procedure, mechanical pain thresholds and pain evoked by a test stimulus were examined in each context. In the test phase, the effect of expectancy was equalised across conditions by informing participants when thresholds and painful stimuli would be presented. Contrary to our hypothesis, scenes that were associated with noxious stimulation did not increase mechanical sensitivity (p=0.08), or increase pain intensity (p=0.46). However, an interaction with sex highlighted the possibility that pain-associated contexts may alter pain sensitivity in females but not males (p=0.03). Overall, our data does not support the idea that pain-associated contexts can alter pain sensitivity in healthy asymptomatic individuals. That an effect was shown in females highlights the possibility that some subgroups may be susceptible to such an effect, although the magnitude of the effect may lack real-world significance. If pain-associated cues prove to have a relevant pain augmenting effect, in some subgroups, procedures aimed at extinguishing pain-related associations may have therapeutic potential.

Dural stimulation in rats causes BDNF-dependent priming to subthreshold stimuli including a migraine trigger

PubMed Central

Burgos-Vega, Carolina C.; Quigley, Lilyana D.; Avona, Amanda; Price, Theodore; Dussor, Gregory

2016-01-01

Migraine is one of the most common and most disabling disorders. Between attacks, migraine patients are otherwise normal but are sensitized to non-noxious events known as triggers. The purpose of these studies was to investigate whether a headache-like event causes sensitization, or priming, to subsequent subthreshold events. Interleukin-6 (IL-6) was applied to the rat cranial dura mater which produced cutaneous facial and hindpaw allodynia that lasted 24 hours. At 72-hours, IL-6 treated rats developed allodynia in response to dural stimulation with either a pH 6.8 or pH 7.0 solution and to a systemic nitric oxide (NO) donor, a well-known migraine trigger. Vehicle-treated rats did not respond to either pH stimulus nor to the NO donor, demonstrating that IL-6 exposure primes rats to subthreshold stimuli. Inhibitors of brain-derived neurotrophic factor (BDNF) signaling given either systemically or intracisternally 24-hours after IL-6 eliminated responses to dural pH stimulation at 72 hours. Additionally, intracisternal administration of BDNF without prior dural stimulation produced allodynia and once resolved, animals were primed to dural pH 6.8/pH 7.0 and a systemic NO donor. Finally, hindpaw IL-6 produced paw allodynia but not priming to paw injection of pH 7.0 at 72 hours demonstrating differences in priming depending on location. These data indicate that afferent input from the meninges produces BDNF-dependent priming of the dural nociceptive system. This primed state mimics the interictal period of migraine where attacks can be triggered by normally non-noxious events and suggests that BDNF-dependent plasticity may contribute to migraine. PMID:27841839

Cannabinoid CB1 receptor facilitation of substance P release in the rat spinal cord, measured as neurokinin 1 receptor internalization

PubMed Central

Zhang, Guohua; Chen, Wenling; Lao, Lijun; Marvizón, Juan Carlos G.

2010-01-01

The contribution of CB1 receptors in the spinal cord to cannabinoid analgesia is still unclear. The objective of this study was to investigate the effect of CB1 receptors on substance P release from primary afferent terminals in the spinal cord. Substance P release was measured as NK1 receptor internalization in lamina I neurons. It was induced in spinal cord slices by dorsal root stimulation and in live rats by a noxious stimulus. In spinal cord slices, the CB1 receptor antagonists AM251, AM281 and rimonabant partially but potently inhibited NK1 receptor internalization induced by electrical stimulation of the dorsal root. This was due to an inhibition of substance P release and not of NK1 receptor internalization itself, because AM251 and AM281 did not inhibit NK1 receptor internalization induced by exogenous substance P. The CB1 receptor agonist ACEA increased NK1 receptor internalization evoked by dorsal root stimulation. The effects of AM251 and ACEA cancelled each other. In vivo, AM251 injected intrathecally decreased NK1 receptor internalization in spinal segments L5 and L6 induced by noxious hind paw clamp. Intrathecal AM251 also produced analgesia to radiant heat stimulation of the paw. The inhibition by AM251 of NK1 receptor internalization was reversed by antagonists of μ-opioid and GABAB receptors. This indicates that CB1 receptors facilitate substance P release by inhibiting the release of GABA and opioids next to primary afferent terminals, producing disinhibition. This results in a pronociceptive effect of CB1 receptors in the spinal cord. PMID:20074214

Determinants of endogenous analgesia magnitude in a diffuse noxious inhibitory control (DNIC) paradigm: do conditioning stimulus painfulness, gender and personality variables matter?

PubMed

Granot, Michal; Weissman-Fogel, Irit; Crispel, Yonathan; Pud, Dorit; Granovsky, Yelena; Sprecher, Elliot; Yarnitsky, David

2008-05-01

Descending modulation of pain can be demonstrated psychophysically by dual pain stimulation. This study evaluates in 31 healthy subjects the association between parameters of the conditioning stimulus, gender and personality, and the endogenous analgesia (EA) extent assessed by diffuse noxious inhibitory control (DNIC) paradigm. Contact heat pain was applied as the test stimulus to the non-dominant forearm, with stimulation temperature at a psychophysical intensity score of 60 on a 0-100 numerical pain scale. The conditioning stimulus was a 60s immersion of the dominant hand in cold (12, 15, 18 degrees C), hot (44 and 46.5 degrees C), or skin temperature (33 degrees C) water. The test stimulus was repeated on the non-dominant hand during the last 30s of the conditioning immersion. EA extent was calculated as the difference between pain scores of the two test stimuli. State and trait anxiety and pain catastrophizing scores were assessed prior to stimulation. EA was induced only for the pain-generating conditioning stimuli at 46.5 degrees C (p=0.011) and 12 degrees C (p=0.003). EA was independent of conditioning pain modality, or personality, but a significant gender effect was found, with greater EA response in males. Importantly, pain scores of the conditioning stimuli were not correlated with EA extent. The latter is based on both our study population, and on additional 82 patients, who participated in another study, in which EA was induced by immersion at 46.5 degrees C. DNIC testing, thus, seems to be relatively independent of the stimulation conditions, making it an easy to apply tool, suitable for wide range applications in pain psychophysics.

Centralization of Noxious Stimulus-induced Analgesia (NSIA) is Related to Activity at Inhibitory Synapses in the Spinal Cord

PubMed Central

Tambeli, Claudia H.; Levine, Jon D.; Gear, Robert W.

2009-01-01

The duration of noxious stimulus-induced antinociception (NSIA) has been shown to outlast the pain stimulus that elicited it, however, the mechanism that determines the duration of analgesia is unknown. We evaluated the role of spinal excitatory and inhibitory receptors (NMDA, mGluR-5, mu-opioid, GABA-A, and GABA-B), previously implicated in NSIA initiation, in its maintenance. As in our previous studies, the supraspinal trigeminal jaw-opening reflex (JOR) in the rat was used for nociceptive testing because of its remoteness from the region of drug application, the lumbar spinal cord. NSIA was reversed by antagonists for two inhibitory receptors (GABA-B and mu-opioid) but not by antagonists for either of the two excitatory receptors (NMDA and mGluR-5), indicating that NSIA is maintained by ongoing activity at inhibitory synapses in the spinal cord. Furthermore, spinal administration of the GABA-B agonist baclofen mimicked NSIA in that it could be blocked by prior injection of the mu-opioid receptor antagonist H-D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) in nucleus accumbens. CTAP also blocked baclofen antinociception when administered in the spinal cord. We conclude that analgesia induced by noxious stimulation is maintained by activity in spinal inhibitory receptors. PMID:19375225

Internal validity of inter-digital web pinching as a model for perceptual diffuse noxious inhibitory controls-induced hypoalgesia in healthy humans.

PubMed

Streff, Anouk; Michaux, Gilles; Anton, Fernand

2011-01-01

Hot and ice-water immersions are commonly used for heterotopic noxious counter-stimulation (HNCS) in investigations on endogenous pain modulation. However, coincident sympathetic thermoregulatory activity does not allow to differentiate between perceptual hypoalgesia related to baroreflex sensitivity (BRS) or diffuse noxious inhibitory controls (DNIC). The present study analysed the internal validity of another supposedly less confounded tonic pain model (inter-digital web pinching; IWP) regarding its potential as DNIC trigger. We performed a randomized controlled study in 24 healthy gender-matched drug-free volunteers aged 21-54 (median 25) years. The study protocol comprised the assessment of mechanical and thermal perceptual wind-up before and after an IWP (15N) or hot water immersion trial (HIT; 47.5°C) of 2 min duration. Wind-up was induced either by 10 repetitive (1Hz) contact heat (max. 49°C; 5×5 mm thermode) or ballistic impact stimuli (0.5g at 9 m/s) on the phalanges of the non-dominant hand. Cardiovascular activity, pain experience and corrugator muscle activity were continuously monitored. Although both HNCS forms produced a similar pain experience (45% of scale), a more pronounced cardiovascular activity was observable for the HIT (P<0.01). This indicates a higher baroreceptor activity and stronger contamination of painful water immersion by BRS-related hypoalgesia. Regardless of pain modality, wind-up was significantly reduced by HNCS, although this was stronger for painful water immersion than for noxious pinching (P<0.01). The HNCS types allow a differentiation between BRS-related and DNIC-like hypoalgesia. IWP proved its validity for DNIC induction, being practically non-confounded by BRS. Copyright © 2010 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.

The local effect of octreotide on mechanical pain sensitivity is more sensitive in DA rats than DA.1U rats.

PubMed

Yao, Fan-Rong; Wang, Hui-Sheng; Guo, Yuan; Zhao, Yan

2016-02-01

A recent study by the authors indicated that major histocompatibility complex (MHC) genes are associated with the differences in basal pain sensitivity and in formalin model between Dark-Agouti (DA) and novel congenic DA.1U rats, which have the same genetic background as DA rats except for the u alleles of MHC. The objective of the present study is to investigate whether there is a difference in the pristane-induced arthritis (PIA) model and local analgesic effect of octreotide (OCT) between DA and DA.1U rats. The hindpaw mechanical withdrawal threshold (MWT) and heat withdrawal latency (HWL) were observed. The C unit firings of the tibial nerve evoked by non-noxious and noxious toe movements were recorded by electrophysiological methods in normal and PIA models in DA and DA.1U rats before and after local OCT administration. The expression of somatostatin receptor 2A (SSTR2A) was observed by immunohistochemistry. The results demonstrate that DA rats have a higher mechanical sensitivity than DA.1U rats after PIA. Local OCT administration significantly elevated MWT in DA rats under normal and PIA sate, but not in DA.1U rats. The electrophysiological experiments showed OCT significantly attenuated the firings of C units evoked by non-noxious and noxious stimulation in DA rats more than those in DA.1U rats both in normal and PIA states. In addition, the expression of SSTR2A in the dorsal horn of the spinal cord was significantly higher in DA than in DA.1U rats. All of the findings suggest a higher local analgesic effect of OCT in DA rats than DA.1U rats, which might be associated with the MHC genes. © 2016 John Wiley & Sons Australia, Ltd.

Electrical neurostimulation with imbalanced waveform mitigates dissolution of platinum electrodes

PubMed Central

Kumsa, Doe; Hudak, Eric M; Montague, Fred W; Kelley, Shawn C; Untereker, Darrel F; Hahn, Benjamin P; Condit, Chris; Cholette, Martin; Lee, Hyowon; Bardot, Dawn; Takmakov, Pavel

2017-01-01

Objective Electrical neurostimulation has traditionally been limited to the use of charge-balanced waveforms. Charge-imbalanced and monophasic waveforms are not used to deliver clinical therapy, because it is believed that these stimulation paradigms may generate noxious electrochemical species that cause tissue damage. Approach In this study, we investigated the dissolution of platinum as one of such irreversible reactions over a range of charge densities up to 160 µC cm−2 with current-controlled first phase, capacitive discharge second phase waveforms of both cathodic-first and anodic-first polarity. We monitored the concentration of platinum in solution under different stimulation delivery conditions including charge-balanced, charge-imbalanced, and monophasic pulses. Main results We observed that platinum dissolution decreased during charge-imbalanced and monophasic stimulation when compared to charge-balanced waveforms. Significance This observation provides an opportunity to re-evaluate the charge-balanced waveform as the primary option for sustainable neural stimulation. PMID:27650936

Basal μ-opioid receptor availability in the amygdala predicts the inhibition of pain-related brain activity during heterotopic noxious counter-stimulation.

PubMed

Piché, Mathieu; Watanabe, Nobuhiro; Sakata, Muneyuki; Oda, Keiichi; Toyohara, Jun; Ishii, Kenji; Ishiwata, Kiichi; Hotta, Harumi

2014-01-01

The aim of this study was to investigate the association between the magnitude of anti-nociceptive effects induced by heterotopic noxious counter-stimulation (HNCS) and the basal μ-opioid receptor availability in the amygdala. In 8 healthy volunteers (4 females and 4 males), transcutaneous electrical stimulation was applied to the right sural nerve to produce the nociceptive flexion reflex (RIII-reflex), moderate pain, and scalp somatosensory evoked potentials (SEPs). Immersion of the left hand in cold water for 20min was used as HNCS. In a separate session, basal μ-opioid receptor availability was measured using positron emission tomography with the radiotracer [(11)C]carfentanil. HNCS produced a reduction of the P260 amplitude (p<0.05), a late component of SEP that reflects activity in the anterior cingulate cortex. This reduction was associated with higher basal μ-opioid receptor availability in the amygdala on the right (R(2)=0.55, p=0.03) with a similar trend on the left (R(2)=0.24, p=0.22). Besides, HNCS did not induce significant changes in pain and RIII-reflex amplitude (p>0.05). These results suggest that activation of μ-opioid receptors in the amygdala may contribute to the anti-nociceptive effects of HNCS. The lack of RIII-reflex modulation further suggests that μ-opioid receptor activation in the amygdala contributes to decrease pain-related brain activity through a cerebral mechanism independent of descending modulation. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

A Regional Guidebook for Applying the Hydrogeomorphic Approach to Assessing the Functions of Tidal Fringe Wetlands Along the Mississippi and Alabama Gulf Coast

DTIC Science & Technology

2007-04-01

philoxeroides Alligatorweed Alabama Class C noxious weed Imperata cylindrica Cogongrass Alabama Class A noxious weed; Mississippi noxious weed Ipomoea...Invasive Species Alternanthera philoxeroides Phragmites australis Cuscuta spp. Imperata cylindrica ...weed Cuscuta spp. Dodder Alabama Class A noxious weed Imperata cylindrica Cogongrass Alabama Class A noxious weed; MS noxious weed Ipomoea

Hormonal and molecular effects of restraint stress on formalin-induced pain-like behavior in male and female mice.

PubMed

Long, Caela C; Sadler, Katelyn E; Kolber, Benedict J

2016-10-15

The evolutionary advantages to the suppression of pain during a stressful event (stress-induced analgesia (SIA)) are obvious, yet the reasoning behind sex-differences in the expression of this pain reduction are not. The different ways in which males and females integrate physiological stress responses and descending pain inhibition are unclear. A potential supraspinal modulator of stress-induced analgesia is the central nucleus of the amygdala (CeA). This limbic brain region is involved in both the processing of stress and pain; the CeA is anatomically and molecularly linked to regions of the hypothalamic pituitary adrenal (HPA) axis and descending pain network. The CeA exhibits sex-based differences in response to stress and pain that may differentially induce SIA in males and females. Here, sex-based differences in behavioral and molecular indices of SIA were examined following noxious stimulation. Acute restraint stress in male and female mice was performed prior to intraplantar injections of formalin, a noxious inflammatory agent. Spontaneous pain-like behaviors were measured for 60min following formalin injection and mechanical hypersensitivity was evaluated 120 and 180min post-injection. Restraint stress altered formalin-induced spontaneous behaviors in male and female mice and formalin-induced mechanical hypersensitivity in male mice. To assess molecular indices of SIA, tissue samples from the CeA and blood samples were collected at the 180min time point. Restraint stress prevented formalin-induced increases in extracellular signal regulated kinase 2 (ERK2) phosphorylation in the male CeA, but no changes associated with pERK2 were seen with formalin or restraint in females. Sex differences were also seen in plasma corticosterone concentrations 180min post injection. These results demonstrate sex-based differences in behavioral, molecular, and hormonal indices of acute stress in mice that extend for 180min after stress and noxious stimulation. Copyright © 2016 Elsevier Inc. All rights reserved.

7 CFR 360.304 - Denial of an application for a permit to move a noxious weed; cancelation of a permit to move a...

Code of Federal Regulations, 2012 CFR

2012-01-01

... noxious weed; cancelation of a permit to move a noxious weed. 360.304 Section 360.304 Agriculture..., DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.304 Denial of an application for a permit to move a noxious weed; cancelation of a permit to move a noxious weed. (a) The Administrator may deny an...

7 CFR 360.304 - Denial of an application for a permit to move a noxious weed; cancelation of a permit to move a...

Code of Federal Regulations, 2014 CFR

2014-01-01

... noxious weed; cancelation of a permit to move a noxious weed. 360.304 Section 360.304 Agriculture..., DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.304 Denial of an application for a permit to move a noxious weed; cancelation of a permit to move a noxious weed. (a) The Administrator may deny an...

7 CFR 360.304 - Denial of an application for a permit to move a noxious weed; cancelation of a permit to move a...

Code of Federal Regulations, 2013 CFR

2013-01-01

... noxious weed; cancelation of a permit to move a noxious weed. 360.304 Section 360.304 Agriculture..., DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.304 Denial of an application for a permit to move a noxious weed; cancelation of a permit to move a noxious weed. (a) The Administrator may deny an...

Cutaneous stimulation of discrete regions of the sole during locomotion produces “sensory steering” of the foot

PubMed Central

2014-01-01

Background While the neural and mechanical effects of whole nerve cutaneous stimulation on human locomotion have been previously studied, there is less information about effects evoked by activation of discrete skin regions on the sole of the foot. Electrical stimulation of discrete foot regions evokes position-modulated patterns of cutaneous reflexes in muscles acting at the ankle during standing but data during walking are lacking. Here, non-noxious electrical stimulation was delivered to five discrete locations on the sole of the foot (heel, and medial and lateral sites on the midfoot and forefoot) during treadmill walking. EMG activity from muscles acting at the hip, knee and ankle were recorded along with movement at these three joints. Additionally, 3 force sensing resistors measuring continuous force changes were placed at the heel, and the medial and lateral aspects of the right foot sole. All data were sorted based on stimulus occurrence in twelve step-cycle phases, before being averaged together within a phase for subsequent analysis. Methods Non-noxious electrical stimulation was delivered to five discrete locations on the sole of the foot (heel, and medial and lateral sites on the midfoot and forefoot) during treadmill walking. EMG activity from muscles acting at the hip, knee and ankle were recorded along with movement at these three joints. Additionally, 3 force sensing resistors measuring continuous force changes were placed at the heel, and the medial and lateral aspects of the right foot sole. All data were sorted based on stimulus occurrence in twelve step-cycle phases, before being averaged together within a phase for subsequent analysis. Results The results demonstrate statistically significant dynamic changes in reflex amplitudes, kinematics and foot sole pressures that are site-specific and phase-dependent. The general trends demonstrate responses producing decreased underfoot pressure at the site of stimulation. Conclusions The responses to stimulation of discrete locations on the foot sole evoke a kind of “sensory steering” that may promote balance and maintenance of locomotion through the modulation of limb loading and foot placement. These results have implications for using sensory stimulation as a therapeutic modality during gait retraining (e.g. after stroke) as well as for footwear design and implementation of foot sole contact surfaces during gait. PMID:25202452

Noxious inhibition of temporal summation is impaired in chronic tension-type headache.

PubMed

Cathcart, Stuart; Winefield, Anthony H; Lushington, Kurt; Rolan, Paul

2010-03-01

To examine effects of stress on noxious inhibition and temporal summation (TS) in tension-type headache. Stress is the most commonly reported trigger of a chronic tension-type headache (CTH) episode; however, the mechanisms underlying this are unclear. Stress affects pain processing throughout the central nervous system, including, potentially, mechanisms of TS and diffuse noxious inhibitory controls (DNIC), both of which may be abnormal in CTH sufferers (CTH-S). No studies have examined TS of pressure pain or DNIC of TS in CTH-S to date. Similarly, effects of stress on TS or DNIC of TS have not been reported in healthy subjects or CTH-S to date. The present study measured TS and DNIC of TS in CTH-S and healthy controls (CNT) exposed to an hour-long stressful mental task, and in CTH-S exposed to an hour-long neutral condition. TS was elicited at finger and shoulder via 10 pulses from a pressure algometer, applied before and during stimulation from an occlusion cuff at painful intensity. Algometer pain ratings increased more in the CTH compared with the CNT group, and were inhibited during occlusion cuff more in the CNT compared with CTH groups. Task effects on TS or DNIC were not significant. The results indicate increased TS to pressure pain and impaired DNIC of TS in CTH-S. Stress does not appear to aggravate abnormal TS or DNIC mechanisms in CTH-S.

Repeated noxious stimulation of the skin enhances cutaneous pain perception of migraine patients in-between attacks: clinical evidence for continuous sub-threshold increase in membrane excitability of central trigeminovascular neurons.

PubMed

Weissman-Fogel, Irit; Sprecher, Elliot; Granovsky, Yelena; Yarnitsky, David

2003-08-01

Recent clinical studies showed that acute migraine attacks are accompanied by increased periorbital and bodily skin sensitivity to touch, heat and cold. Parallel pre-clinical studies showed that the underlying mechanism is sensitization of primary nociceptors and central trigeminovascular neurons. The present study investigates the sensory state of neuronal pathways that mediate skin pain sensation in migraine patients in between attacks. The assessments of sensory perception included (a) mechanical and thermal pain thresholds of the periorbital area, electrical pain threshold of forearm skin, (b) pain scores to phasic supra-threshold stimuli in the same modalities and areas as above, and (c) temporal summation of pain induced by applying noxious tonic heat pain and brief trains of noxious mechanical and electrical pulses to the above skin areas. Thirty-four pain-free migraine patients and 28 age- and gender-matched controls were studied. Patients did not differ from controls in their pain thresholds for heat (44+/-2.6 vs. 44.6+/-1.9 degrees C), and electrical (4.8+/-1.6 vs. 4.3+/-1.6 mA) stimulation, and in their pain scores for supra-threshold phasic stimuli for all modalities. They did, however, differ in their pain threshold for mechanical stimulation, just by one von Frey filament (P=0.01) and in their pain scores of the temporal summation tests. Increased summation of pain was found in migraineurs for repeated mechanical stimuli (delta visual analog scale (VAS) +2.32+/-0.73 in patients vs. +0.16+/-0.83 in controls, P=0.05) and repeated electrical stimuli (delta VAS +3.83+/-1.91 vs -3.79+/-2.31, P=0.01). Increased summation corresponded with more severe clinical parameters of migraine and tended to depend on interval since last migraine attack. The absence of clinically or overt laboratory expressed allodynia suggests that pain pathways are not sensitized in the pain-free migraine patients. Nevertheless, the increased temporal summation, and the slight decrease in mechanical pain thresholds, suggest that central nociceptive neurons do express activation-dependent plasticity. These findings may point to an important pathophysiological change in membrane properties of nociceptive neurons of migraine patients; a change that may hold a key to more effective prophylactic treatment.

7 CFR 360.305 - Disposal of noxious weeds when permits are canceled.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 5 2011-01-01 2011-01-01 false Disposal of noxious weeds when permits are canceled... AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.305 Disposal of noxious weeds when permits are canceled. When a permit for the movement of a noxious weed is...

7 CFR 360.300 - Notice of restrictions on movement of noxious weeds.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 5 2011-01-01 2011-01-01 false Notice of restrictions on movement of noxious weeds... AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.300 Notice of restrictions on movement of noxious weeds. No person may move a Federal noxious weed into or...

7 CFR 360.305 - Disposal of noxious weeds when permits are canceled.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 5 2014-01-01 2014-01-01 false Disposal of noxious weeds when permits are canceled... AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.305 Disposal of noxious weeds when permits are canceled. When a permit for the movement of a noxious weed is...

7 CFR 360.300 - Notice of restrictions on movement of noxious weeds.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 5 2014-01-01 2014-01-01 false Notice of restrictions on movement of noxious weeds... AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.300 Notice of restrictions on movement of noxious weeds. No person may move a Federal noxious weed into or...

7 CFR 360.300 - Notice of restrictions on movement of noxious weeds.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 5 2013-01-01 2013-01-01 false Notice of restrictions on movement of noxious weeds... AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.300 Notice of restrictions on movement of noxious weeds. No person may move a Federal noxious weed into or...

7 CFR 360.300 - Notice of restrictions on movement of noxious weeds.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 5 2012-01-01 2012-01-01 false Notice of restrictions on movement of noxious weeds... AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.300 Notice of restrictions on movement of noxious weeds. No person may move a Federal noxious weed into or...

7 CFR 360.305 - Disposal of noxious weeds when permits are canceled.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 5 2013-01-01 2013-01-01 false Disposal of noxious weeds when permits are canceled... AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.305 Disposal of noxious weeds when permits are canceled. When a permit for the movement of a noxious weed is...

7 CFR 360.305 - Disposal of noxious weeds when permits are canceled.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 5 2012-01-01 2012-01-01 false Disposal of noxious weeds when permits are canceled... AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.305 Disposal of noxious weeds when permits are canceled. When a permit for the movement of a noxious weed is...

Oily Bilgewater Separators

DTIC Science & Technology

2011-11-01

International Convention for the Prevention of Pollution From Ships, 1973 as modified by the Protocol of 1978 (MARPOL 73/78). Under MARPOL, all ships...of oily bilgewater discharge from vessels are based on Annex I of the International Convention for the Prevention of Pollution from Ships, 1973 as...to the Convention . MARPOL includes six annexes, covering six categories of vessel discharges: oil (Annex I), noxious liquid substances (Annex II

Mild Social Stress in Mice Produces Opioid-Mediated Analgesia in Visceral but Not Somatic Pain States.

PubMed

Pitcher, Mark H; Gonzalez-Cano, Rafael; Vincent, Kathleen; Lehmann, Michael; Cobos, Enrique J; Coderre, Terence J; Baeyens, José M; Cervero, Fernando

2017-06-01

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 mouse (stranger) in an adjacent cubicle of a standard transparent observation box produced elevated plasma corticosterone levels compared with 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 in mildly stressful conditions (ie, beside an unfamiliar stranger). Compared with 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. In mice, mild social stress due to the presence of an unfamiliar conspecific mouse reduces pain behavior associated with noxious visceral but not somatic stimulation, suggesting that stress responsiveness may be enhanced in visceral pain versus somatic pain states. Published by Elsevier Inc.

7 CFR 360.303 - Approval of an application for a permit to move a noxious weed; conditions specified in permit.

Code of Federal Regulations, 2011 CFR

2011-01-01

... noxious weed; conditions specified in permit. 360.303 Section 360.303 Agriculture Regulations of the... NOXIOUS WEED REGULATIONS § 360.303 Approval of an application for a permit to move a noxious weed... noxious weed. If the application is approved, the Administrator will issue the permit including any...

7 CFR 360.303 - Approval of an application for a permit to move a noxious weed; conditions specified in permit.

Code of Federal Regulations, 2014 CFR

2014-01-01

... noxious weed; conditions specified in permit. 360.303 Section 360.303 Agriculture Regulations of the... NOXIOUS WEED REGULATIONS § 360.303 Approval of an application for a permit to move a noxious weed... noxious weed. If the application is approved, the Administrator will issue the permit including any...

7 CFR 360.303 - Approval of an application for a permit to move a noxious weed; conditions specified in permit.

Code of Federal Regulations, 2012 CFR

2012-01-01

... noxious weed; conditions specified in permit. 360.303 Section 360.303 Agriculture Regulations of the... NOXIOUS WEED REGULATIONS § 360.303 Approval of an application for a permit to move a noxious weed... noxious weed. If the application is approved, the Administrator will issue the permit including any...

7 CFR 360.303 - Approval of an application for a permit to move a noxious weed; conditions specified in permit.

Code of Federal Regulations, 2013 CFR

2013-01-01

... noxious weed; conditions specified in permit. 360.303 Section 360.303 Agriculture Regulations of the... NOXIOUS WEED REGULATIONS § 360.303 Approval of an application for a permit to move a noxious weed... noxious weed. If the application is approved, the Administrator will issue the permit including any...

Asymmetric pain processing in Parkinson's disease.

PubMed

Granovsky, Y; Schlesinger, I; Fadel, S; Erikh, I; Sprecher, E; Yarnitsky, D

2013-10-01

Reduced endogenous pain inhibition, as part of the degenerative process, is presumed to be the mechanism underlying the common presence of pain in patients with Parkinson's disease (PD). The present study aimed to assess an endogenous pain inhibitory system in PD using the conditioned pain modulation paradigm. Twenty-six predominantly unilateral PD patients and 19 controls underwent psychophysical pain assessment before and after patients' morning dopaminergic medication. An unexpected increase in several parameters of pain perception for PD patients was found after dopaminergic medication (e.g. for 49°C noxious heat stimulation an increase from 70.6 ± 4.0 to 77.6 ± 4.0 on the numerical pain scale, P < 0.001). This increase was seen in patients with predominantly left-sided PD, regardless of the stimulated side (for 49°C noxious heat stimulation, predominantly left-sided PD patients, pain perception increased from 73.5 ± 6.8 to 85.0 ± 6.8, P < 0.001, whereas predominantly right-sided PD patients did not show a significant increase, 68.3 ± 6.8 to 70.4 ± 6.5, P = 0.777). Baseline efficiency of conditioned pain modulation inversely correlated with age at disease onset (r = -0.522; P = 0.009) and disease severity (Unified PD Rating Scale, r = 0.447; P = 0.032) but did not differ between patients and controls. Increased sensory response causing hyperalgesia occurs after dopaminergic medication in patients with predominantly left-sided PD. © 2013 The Author(s) European Journal of Neurology © 2013 EFNS.

The nucleus raphe magnus OFF-cells are involved in diffuse noxious inhibitory controls.

PubMed

Chebbi, R; Boyer, N; Monconduit, L; Artola, A; Luccarini, P; Dallel, R

2014-06-01

Diffuse noxious inhibitory controls (DNIC) are very powerful long-lasting descending inhibitory controls which are pivotal in modulating the activity of spinal and trigeminal nociceptive neurons. DNIC are subserved by a loop involving supraspinal structures such as the lateral parabrachial nucleus and the subnucleus reticularis dorsalis. Surprisingly, though, whether the nucleus raphe magnus (NRM), another supraspinal area which is long known to be important in pain modulation, is involved in DNIC is still a matter of discussion. Here, we reassessed the role of the NRM neurons in DNIC by electrophysiologically recording from wide dynamic range (WDR) neurons in the trigeminal subnucleus oralis and pharmacologically manipulating the NRM OFF- and ON-cells. In control conditions, C-fiber-evoked responses in trigeminal WDR neurons are inhibited by a conditioning noxious heat stimulation applied to the hindpaw. We show that inactivating the NRM by microinjecting the GABAA receptor agonist, muscimol, both facilitates C-fiber-evoked responses of trigeminal WDR neurons and strongly attenuates their inhibition by heat applied to the hindpaw. Interestingly, selective blockade of ON-cells by microinjecting the broad-spectrum excitatory amino acid antagonist, kynurenate, into the NRM neither affects C-fiber-evoked responses nor attenuates DNIC of trigeminal WDR neurons. These results indicate that the NRM tonically inhibits trigeminal nociceptive inputs and is involved in the neuronal network underlying DNIC. Moreover, within NRM, OFF-cells might be more specifically involved in both the tonic and phasic descending inhibitory controls of trigeminal nociception. Copyright © 2014 Elsevier Inc. All rights reserved.

Nonpainful wide-area compression inhibits experimental pain.

PubMed

Honigman, Liat; Bar-Bachar, Ofrit; Yarnitsky, David; Sprecher, Elliot; Granovsky, Yelena

2016-09-01

Compression therapy, a well-recognized treatment for lymphoedema and venous disorders, pressurizes limbs and generates massive non-noxious afferent sensory barrages. The aim of this study was to study whether such afferent activity has an analgesic effect when applied on the lower limbs, hypothesizing that larger compression areas will induce stronger analgesic effects, and whether this effect correlates with conditioned pain modulation (CPM). Thirty young healthy subjects received painful heat and pressure stimuli (47°C for 30 seconds, forearm; 300 kPa for 15 seconds, wrist) before and during 3 compression protocols of either SMALL (up to ankles), MEDIUM (up to knees), or LARGE (up to hips) compression areas. Conditioned pain modulation (heat pain conditioned by noxious cold water) was tested before and after each compression protocol. The LARGE protocol induced more analgesia for heat than the SMALL protocol (P < 0.001). The analgesic effect interacted with gender (P = 0.015). The LARGE protocol was more efficient for females, whereas the MEDIUM protocol was more efficient for males. Pressure pain was reduced by all protocols (P < 0.001) with no differences between protocols and no gender effect. Conditioned pain modulation was more efficient than the compression-induced analgesia. For the LARGE protocol, precompression CPM efficiency positively correlated with compression-induced analgesia. Large body area compression exerts an area-dependent analgesic effect on experimental pain stimuli. The observed correlation with pain inhibition in response to robust non-noxious sensory stimulation may suggest that compression therapy shares similar mechanisms with inhibitory pain modulation assessed through CPM.

Trigeminal activation using chemical, electrical, and mechanical stimuli.

PubMed

Iannilli, E; Del Gratta, C; Gerber, J C; Romani, G L; Hummel, T

2008-10-15

Tactile, proprioceptive, and nociceptive information, including also chemosensory functions are expressed in the trigeminal nerve sensory response. To study differences in the processing of different stimulus qualities, we performed a study based on functional magnetic resonance imaging. The first trigeminal branch (ophthalmic nerve) was activated by (a) intranasal chemical stimulation with gaseous CO2 which produces stinging and burning sensations, but is virtually odorless, (b) painful, but not nociceptive specific cutaneous electrical stimulation, and (c) cutaneous mechanical stimulation using air puffs. Eighteen healthy subjects participated (eight men, 10 women, mean age 31 years). Painful stimuli produced patterns of activation similar to what has been reported for other noxious stimuli, namely activation in the primary and secondary somatosensory cortices, anterior cingulate cortex, insular cortex, and thalamus. In addition, analyses indicated intensity-related activation in the prefrontal cortex which was specifically involved in the evaluation of stimulus intensity. Importantly, the results also indicated similarities between activation patterns after intranasal chemosensory trigeminal stimulation and patterns usually found following intranasal odorous stimulation, indicating the intimate connection between these two systems in the processing of sensory information.

7 CFR 360.301 - Information required for applications for permits to move noxious weeds.

Code of Federal Regulations, 2012 CFR

2012-01-01

... move noxious weeds. 360.301 Section 360.301 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.301 Information required for applications for permits to move noxious weeds. (a) Permit to import...

7 CFR 360.301 - Information required for applications for permits to move noxious weeds.

Code of Federal Regulations, 2013 CFR

2013-01-01

... move noxious weeds. 360.301 Section 360.301 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.301 Information required for applications for permits to move noxious weeds. (a) Permit to import...

7 CFR 360.301 - Information required for applications for permits to move noxious weeds.

Code of Federal Regulations, 2011 CFR

2011-01-01

... move noxious weeds. 360.301 Section 360.301 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.301 Information required for applications for permits to move noxious weeds. (a) Permit to import...

7 CFR 360.301 - Information required for applications for permits to move noxious weeds.

Code of Federal Regulations, 2014 CFR

2014-01-01

... move noxious weeds. 360.301 Section 360.301 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.301 Information required for applications for permits to move noxious weeds. (a) Permit to import...

Preferential distribution of nociceptive input to motoneurons with muscle units in the cranial portion of the upper trapezius muscle.

PubMed

Dideriksen, Jakob L; Holobar, Ales; Falla, Deborah

2016-08-01

Pain is associated with changes in the neural drive to muscles. For the upper trapezius muscle, surface electromyography (EMG) recordings have indicated that acute noxious stimulation in either the cranial or the caudal region of the muscle leads to a relative decrease in muscle activity in the cranial region. It is, however, not known if this adaption reflects different recruitment thresholds of the upper trapezius motor units in the cranial and caudal region or a nonuniform nociceptive input to the motor units of both regions. This study investigated these potential mechanisms by direct motor unit identification. Motor unit activity was investigated with high-density surface EMG signals recorded from the upper trapezius muscle of 12 healthy volunteers during baseline, control (intramuscular injection of isotonic saline), and painful (hypertonic saline) conditions. The EMG was decomposed into individual motor unit spike trains. Motor unit discharge rates decreased significantly from control to pain conditions by 4.0 ± 3.6 pulses/s (pps) in the cranial region but not in the caudal region (1.4 ± 2.8 pps; not significant). These changes were compatible with variations in the synaptic input to the motoneurons of the two regions. These adjustments were observed, irrespective of the location of noxious stimulation. These results strongly indicate that the nociceptive synaptic input is distributed in a nonuniform way across regions of the upper trapezius muscle. Copyright © 2016 the American Physiological Society.

Preferential distribution of nociceptive input to motoneurons with muscle units in the cranial portion of the upper trapezius muscle

PubMed Central

Dideriksen, Jakob L.; Holobar, Ales

2016-01-01

Pain is associated with changes in the neural drive to muscles. For the upper trapezius muscle, surface electromyography (EMG) recordings have indicated that acute noxious stimulation in either the cranial or the caudal region of the muscle leads to a relative decrease in muscle activity in the cranial region. It is, however, not known if this adaption reflects different recruitment thresholds of the upper trapezius motor units in the cranial and caudal region or a nonuniform nociceptive input to the motor units of both regions. This study investigated these potential mechanisms by direct motor unit identification. Motor unit activity was investigated with high-density surface EMG signals recorded from the upper trapezius muscle of 12 healthy volunteers during baseline, control (intramuscular injection of isotonic saline), and painful (hypertonic saline) conditions. The EMG was decomposed into individual motor unit spike trains. Motor unit discharge rates decreased significantly from control to pain conditions by 4.0 ± 3.6 pulses/s (pps) in the cranial region but not in the caudal region (1.4 ± 2.8 pps; not significant). These changes were compatible with variations in the synaptic input to the motoneurons of the two regions. These adjustments were observed, irrespective of the location of noxious stimulation. These results strongly indicate that the nociceptive synaptic input is distributed in a nonuniform way across regions of the upper trapezius muscle. PMID:27226455

77 FR 3729 - Notice of Request for Extension of Approval of an Information Collection; Plant Pest, Noxious...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-25

... Collection; Plant Pest, Noxious Weed, and Garbage Regulations AGENCY: Animal and Plant Health Inspection... with plant pest, noxious weed, and garbage regulations. DATES: We will consider all comments that we... pest, noxious weed, and garbage regulations, contact Dr. Shirley Wager- Pag[eacute], Chief, Pest Permit...

7 CFR 360.302 - Consideration of applications for permits to move noxious weeds.

Code of Federal Regulations, 2013 CFR

2013-01-01

... noxious weeds. 360.302 Section 360.302 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.302 Consideration of applications for permits to move noxious weeds. Upon the receipt of an application made in...

7 CFR 360.302 - Consideration of applications for permits to move noxious weeds.

Code of Federal Regulations, 2014 CFR

2014-01-01

... noxious weeds. 360.302 Section 360.302 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.302 Consideration of applications for permits to move noxious weeds. Upon the receipt of an application made in...

7 CFR 360.302 - Consideration of applications for permits to move noxious weeds.

Code of Federal Regulations, 2012 CFR

2012-01-01

... noxious weeds. 360.302 Section 360.302 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.302 Consideration of applications for permits to move noxious weeds. Upon the receipt of an application made in...

7 CFR 360.302 - Consideration of applications for permits to move noxious weeds.

Code of Federal Regulations, 2011 CFR

2011-01-01

... noxious weeds. 360.302 Section 360.302 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.302 Consideration of applications for permits to move noxious weeds. Upon the receipt of an application made in...

7 CFR 360.300 - General prohibitions and restrictions on the movement of noxious weeds; permits.

Code of Federal Regulations, 2010 CFR

2010-01-01

... of noxious weeds; permits. 360.300 Section 360.300 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.300 General prohibitions and restrictions on the movement of noxious weeds; permits. (a) No...

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/pelvic afferent nerve fibers to the spinal cord. The sensory neurons of this spinal afferent pathway lie primarily in the lumbosacral region of the spinal cord, between L6 and S1.

Visceral and somatic pain modalities reveal NaV1.7‐independent visceral nociceptive pathways

PubMed Central

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

2017-01-01

Key points Voltage‐gated sodium channels play a fundamental role in determining neuronal excitability.Specifically, voltage‐gated sodium channel subtype NaV1.7 is required for sensing acute and inflammatory somatic pain in mice and humans but its significance in pain originating from the viscera is unknown.Using comparative behavioural models evoking somatic and visceral pain pathways, we identify the requirement for NaV1.7 in regulating somatic (noxious heat pain threshold) but not in visceral pain signalling.These results enable us to better understand the mechanisms underlying the transduction of noxious stimuli from the viscera, suggest that the investigation of pain pathways should be undertaken in a modality‐specific manner and help to direct drug discovery efforts towards novel visceral analgesics. Abstract Voltage‐gated sodium channel NaV1.7 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 NaV1.7 in visceral pain processing and the development of referred hyperalgesia using a conditional nociceptor‐specific NaV1.7 knockout mouse (NaV1.7Nav1.8) and selective small‐molecule NaV1.7 antagonist PF‐5198007. NaV1.7Nav1.8 mice showed normal nociceptive behaviours in response 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 NaV1.7Nav1.8 and littermate controls. Loss, or blockade, of NaV1.7 did not affect afferent responses to noxious mechanical and chemical stimuli in nerve–gut preparations in mouse, or following antagonism of NaV1.7 in resected human appendix stimulated by noxious distending pressures. However, expression analysis of voltage‐gated sodium channel α subunits revealed NaV1.7 mRNA transcripts in nearly all retrogradely labelled colonic neurons, suggesting redundancy in function. By contrast, using comparative somatic behavioural models we identify that genetic deletion of NaV1.7 (in NaV1.8‐expressing neurons) regulates noxious heat pain threshold and that this can be recapitulated by the selective NaV1.7 antagonist PF‐5198007. Our data demonstrate that NaV1.7 (in NaV1.8‐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 advocate that pharmacological block of NaV1.7 alone in the viscera may be insufficient in targeting chronic visceral pain. PMID:28105664

Comparison between the analgesic effects of morphine and tramadol delivered epidurally in cats receiving a standardized noxious stimulation.

PubMed

Castro, Douglas S; Silva, Marta F A; Shih, Andre C; Motta, Pedro P A; Pires, Marcos V M; Scherer, Paulo O

2009-12-01

This study compared the analgesic effects of epidural tramadol versus morphine in six healthy cats. Under general anesthesia, each cat received an epidural injection of saline 0.22 ml/kg (control treatment, CT), tramadol 1mg/kg (tramadol treatment, TT), or morphine 0.1mg/kg (morphine treatment, MT). After cats had recovered from anesthesia a simple descriptive scale (SDS), visual analog scale (VAS) and physiological parameters (respiratory and heart rate) were used to assess analgesia level to a noxious stimulus (base of the tail skin fold clamping) at 1, 2, 3, 4, 6, 8, 10, and 12h post-epidural. Group TT had a higher SDS and VAS score when compared to MT at 8, 10 and 12h post-epidural. CT had higher SDS and VAS score at all time points when compared to TT and MT. In conclusion both morphine and tramadol provided analgesia in this model for the first 6h; with epidural morphine resulting in longer lasting analgesia when compared to tramadol.

36 CFR 222.8 - Cooperation in control of estray or unbranded livestock, animal diseases, noxious farm weeds, and...

Code of Federal Regulations, 2010 CFR

2010-07-01

... estray or unbranded livestock, animal diseases, noxious farm weeds, and use of pesticides. 222.8 Section... unbranded livestock, animal diseases, noxious farm weeds, and use of pesticides. (a) Insofar as it involves... application and enforcement of all laws and regulations relating to livestock diseases, sanitation and noxious...

36 CFR 222.8 - Cooperation in control of estray or unbranded livestock, animal diseases, noxious farm weeds, and...

Code of Federal Regulations, 2011 CFR

2011-07-01

... estray or unbranded livestock, animal diseases, noxious farm weeds, and use of pesticides. 222.8 Section... unbranded livestock, animal diseases, noxious farm weeds, and use of pesticides. (a) Insofar as it involves... application and enforcement of all laws and regulations relating to livestock diseases, sanitation and noxious...

36 CFR 222.8 - Cooperation in control of estray or unbranded livestock, animal diseases, noxious farm weeds, and...

Code of Federal Regulations, 2013 CFR

2013-07-01

... estray or unbranded livestock, animal diseases, noxious farm weeds, and use of pesticides. 222.8 Section... unbranded livestock, animal diseases, noxious farm weeds, and use of pesticides. (a) Insofar as it involves... application and enforcement of all laws and regulations relating to livestock diseases, sanitation and noxious...

36 CFR 222.8 - Cooperation in control of estray or unbranded livestock, animal diseases, noxious farm weeds, and...

Code of Federal Regulations, 2014 CFR

2014-07-01

... estray or unbranded livestock, animal diseases, noxious farm weeds, and use of pesticides. 222.8 Section... unbranded livestock, animal diseases, noxious farm weeds, and use of pesticides. (a) Insofar as it involves... application and enforcement of all laws and regulations relating to livestock diseases, sanitation and noxious...

36 CFR 222.8 - Cooperation in control of estray or unbranded livestock, animal diseases, noxious farm weeds, and...

Code of Federal Regulations, 2012 CFR

2012-07-01

... estray or unbranded livestock, animal diseases, noxious farm weeds, and use of pesticides. 222.8 Section... unbranded livestock, animal diseases, noxious farm weeds, and use of pesticides. (a) Insofar as it involves... application and enforcement of all laws and regulations relating to livestock diseases, sanitation and noxious...

7 CFR 360.501 - Petitions to remove a taxon from the noxious weed lists.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 5 2013-01-01 2013-01-01 false Petitions to remove a taxon from the noxious weed...) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.501 Petitions to remove a taxon from the noxious weed lists. A person may petition the Administrator to remove a...

Propofol, more than halothane, depresses electroencephalographic activation resulting from electrical stimulation in reticular formation.

PubMed

Antognini, J F; Bravo, E; Atherley, R; Carstens, E

2006-09-01

Halothane and propofol depress the central nervous system, and this is partly manifested by a decrease in electroencephalographic (EEG) activity. Little work has been performed to determine the differences between these anesthetics with regard to their effects on evoked EEG activity. We examined the effects of halothane and propofol on EEG responses to electrical stimulation of the reticular formation. Rats (n= 12) were anesthetized with either halothane or propofol, and EEG responses were recorded before and after electrical stimulation of the reticular formation. Two anesthetic concentrations were used (0.8 and 1.2 times the amount needed to prevent gross, purposeful movement in response to supramaximal noxious stimulation), and both anesthetics were studied in each rat using a cross-over design. Electrical stimulation in the reticular formation increased the spectral edge (SEF) and median edge (MEF) frequencies by approximately 1-2 Hz during halothane anesthesia at low and high concentrations. During propofol anesthesia, MEF increased at the low propofol infusion rate, but SEF was unaffected. At the high propofol infusion rate, SEF and MEF decreased following electrical stimulation in the reticular formation. At immobilizing concentrations, propofol produces a larger decrease than halothane in EEG responses to reticular formation stimulation, consistent with propofol having a more profound depressant effect on cortical and subcortical structures.

Nonpainful wide-area compression inhibits experimental pain

PubMed Central

Honigman, Liat; Bar-Bachar, Ofrit; Yarnitsky, David; Sprecher, Elliot; Granovsky, Yelena

2016-01-01

Abstract Compression therapy, a well-recognized treatment for lymphoedema and venous disorders, pressurizes limbs and generates massive non-noxious afferent sensory barrages. The aim of this study was to study whether such afferent activity has an analgesic effect when applied on the lower limbs, hypothesizing that larger compression areas will induce stronger analgesic effects, and whether this effect correlates with conditioned pain modulation (CPM). Thirty young healthy subjects received painful heat and pressure stimuli (47°C for 30 seconds, forearm; 300 kPa for 15 seconds, wrist) before and during 3 compression protocols of either SMALL (up to ankles), MEDIUM (up to knees), or LARGE (up to hips) compression areas. Conditioned pain modulation (heat pain conditioned by noxious cold water) was tested before and after each compression protocol. The LARGE protocol induced more analgesia for heat than the SMALL protocol (P < 0.001). The analgesic effect interacted with gender (P = 0.015). The LARGE protocol was more efficient for females, whereas the MEDIUM protocol was more efficient for males. Pressure pain was reduced by all protocols (P < 0.001) with no differences between protocols and no gender effect. Conditioned pain modulation was more efficient than the compression-induced analgesia. For the LARGE protocol, precompression CPM efficiency positively correlated with compression-induced analgesia. Large body area compression exerts an area-dependent analgesic effect on experimental pain stimuli. The observed correlation with pain inhibition in response to robust non-noxious sensory stimulation may suggest that compression therapy shares similar mechanisms with inhibitory pain modulation assessed through CPM. PMID:27152691

Upper thoracic respiratory interneurons integrate noxious somatic and visceral information in rats.

PubMed

Qin, Chao; Chandler, Margaret J; Foreman, Robert D; Farber, Jay P

2002-11-01

The aim of this study was to determine if thoracic respiratory interneurons (TRINs) might receive peripheral noxious somatic and visceral inputs. Extracellular potentials of 78 respiration-related T(3) neurons, whose activity was driven by central respiratory output, were recorded from the intermediate zone in pentobarbital anesthetized, paralyzed, and ventilated male rats. These neurons were identified as interneurons by their locations and by the absence of antidromic activation from the cervical sympathetic trunk and cerebellum. Thoracic esophageal distension (ED) was produced by water inflation of a latex balloon (0.1-0.5 ml, 20 s). A catheter was placed in the pericardial sac to administer 0.2 ml bradykinin (10(-5) M) for noxious cardiac stimulation. Of 78 TRINs examined for ED, activity of 24 TRINs increased and activity of 8 TRINs decreased. Intrapericardial bradykinin increased activity in 26/65 TRINs tested and decreased activity in 5 TRINs. Seventy-four TRINs were tested for effects of brush, pressure, and pinch of the chest and upper back areas. No TRINs responded to brushing hair. Low-threshold responses to pressure were observed in 27 TRINs. Fourteen TRINs were wide dynamic range and 4 TRINs had high-threshold responses. Peripheral stimuli affected all types of TRINs, including inspiratory, expiratory, and biphasic neurons. Simultaneous phrenic recordings showed that effects of various somatic and visceral stimuli on TRINs were independent of central respiratory drive. Various somatovisceral and viscerovisceral patterns of input were observed in TRINs. The results suggested that TRINs participate in intraspinal processing and integration of nociceptive information from somatic fields and visceral organs.

7 CFR 360.304 - Denial of an application for a permit to move a noxious weed; cancelation of a permit to move a...

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 5 2011-01-01 2011-01-01 false Denial of an application for a permit to move a noxious weed; cancelation of a permit to move a noxious weed. 360.304 Section 360.304 Agriculture..., DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.304 Denial of an application for a permit to move a...

GLP-1 acts on habenular avoidance circuits to control nicotine intake.

PubMed

Tuesta, Luis M; Chen, Zuxin; Duncan, Alexander; Fowler, Christie D; Ishikawa, Masago; Lee, Brian R; Liu, Xin-An; Lu, Qun; Cameron, Michael; Hayes, Matthew R; Kamenecka, Theodore M; Pletcher, Matthew; Kenny, Paul J

2017-05-01

Tobacco smokers titrate their nicotine intake to avoid its noxious effects, sensitivity to which may influence vulnerability to tobacco dependence, yet mechanisms of nicotine avoidance are poorly understood. Here we show that nicotine activates glucagon-like peptide-1 (GLP-1) neurons in the nucleus tractus solitarius (NTS). The antidiabetic drugs sitagliptin and exenatide, which inhibit GLP-1 breakdown and stimulate GLP-1 receptors, respectively, decreased nicotine intake in mice. Chemogenetic activation of GLP-1 neurons in NTS similarly decreased nicotine intake. Conversely, Glp1r knockout mice consumed greater quantities of nicotine than wild-type mice. Using optogenetic stimulation, we show that GLP-1 excites medial habenular (MHb) projections to the interpeduncular nucleus (IPN). Activation of GLP-1 receptors in the MHb-IPN circuit abolished nicotine reward and decreased nicotine intake, whereas their knockdown or pharmacological blockade increased intake. GLP-1 neurons may therefore serve as 'satiety sensors' for nicotine that stimulate habenular systems to promote nicotine avoidance before its aversive effects are encountered.

Evoked potentials after painful cutaneous electrical stimulation depict pain relief during a conditioned pain modulation.

PubMed

Höffken, Oliver; Özgül, Özüm S; Enax-Krumova, Elena K; Tegenthoff, Martin; Maier, Christoph

2017-08-29

Conditioned pain modulation (CPM) evaluates the pain modulating effect of a noxious conditioning stimulus (CS) on another noxious test stimulus (TS), mostly based solely on subjective pain ratings. We used painful cutaneous electrical stimulation (PCES) to induce TS in a novel CPM-model. Additionally, to evaluate a more objective parameter, we recorded the corresponding changes of cortical evoked potentials (PCES-EP). We examined the CPM-effect in 17 healthy subjects in a randomized controlled cross-over design during immersion of the non-dominant hand into 10 °C or 24 °C cold water (CS). Using three custom-built concentric surface electrodes, electrical stimuli were applied on the dominant hand, inducing pain of 40-60 on NRS 0-100 (TS). At baseline, during and after CS we assessed the electrically induced pain intensity and electrically evoked potentials recorded over the central electrode (Cz). Only in the 10 °C-condition, both pain (52.6 ± 4.4 (baseline) vs. 30.3 ± 12.5 (during CS)) and amplitudes of PCES-EP (42.1 ± 13.4 μV (baseline) vs. 28.7 ± 10.5 μV (during CS)) attenuated during CS and recovered there after (all p < 0.001). In the 10 °C-condition changes of subjective pain ratings during electrical stimulation and amplitudes of PCES-EP correlated significantly with each other (r = 0.5) and with CS pain intensity (r = 0.5). PCES-EPs are a quantitative measure of pain relief, as changes in the electrophysiological response are paralleled by a consistent decrease in subjective pain ratings. This novel CPM paradigm is a feasible method, which could help to evaluate the function of the endogenous pain modulation processes. German Clinical Trials Register DRKS-ID: DRKS00012779 , retrospectively registered on 24 July 2017.

Inhibition of Pain and Pain-Related Brain Activity by Heterotopic Noxious Counter-Stimulation and Selective Attention in Chronic Non-Specific Low Back Pain.

PubMed

Ladouceur, Alexandra; Rustamov, Nabi; Dubois, Jean-Daniel; Tessier, Jessica; Lehmann, Alexandre; Descarreaux, Martin; Rainville, Pierre; Piché, Mathieu

2017-10-10

The aim of the present study was to assess inhibition of pain and somatosensory-evoked potentials (SEPs) by heterotopic noxious counter-stimulation (HNCS) and by selective attention in patients with chronic non-specific LBP. Seventeen patients and age/sex-matched controls were recruited (10 men, 7 women; mean age ± SD: 43.3 ± 10.4 and 42.7 ± 11.1, respectively). On average, patients with LBP reported pain duration of 7.6 ± 6.5 years, light to moderate disability (19.3 ± 5.7/100) and low clinical pain intensity (21.8 ± 1.5/100), while pain catastrophizing, state and trait anxiety and depressive symptoms were not significantly different between groups (all p's >0.05). HNCS and selective attention had differential inhibitory effects on pain and SEP, but no difference was observed between groups. Across both groups, HNCS decreased pain (p = 0.06) as well as the N100 and the N150 components of SEP (p's <0.001), while selective attention only decreased pain (p < 0.01) and the N100 (p<0.001). In contrast, the P260 was decreased by HNCS only when attention was directed toward the HNCS stimulus (p<0.01). This indicates that patients with the characteristics described above do not show altered pain inhibitory mechanisms involved in HNCS and selective attention. Importantly, this experiment was carefully designed to control for non-specific effects associated with the repetition of the test stimulus and the effect of an innocuous counter-stimulation. It remains to be determined if these results hold for patients with severe LBP and psychological symptoms or whether symptom severity may be associated with pain inhibition deficits. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Machine-learned analysis of quantitative sensory testing responses to noxious cold stimulation in healthy subjects.

PubMed

Weyer-Menkhoff, I; Thrun, M C; Lötsch, J

2018-05-01

Pain in response to noxious cold has a complex molecular background probably involving several types of sensors. A recent observation has been the multimodal distribution of human cold pain thresholds. This study aimed at analysing reproducibility and stability of this observation and further exploration of data patterns supporting a complex background. Pain thresholds to noxious cold stimuli (range 32-0 °C, tonic: temperature decrease -1 °C/s, phasic: temperature decrease -8 °C/s) were acquired in 148 healthy volunteers. The probability density distribution was analysed using machine-learning derived methods implemented as Gaussian mixture modeling (GMM), emergent self-organizing maps and self-organizing swarms of data agents. The probability density function of pain responses was trimodal (mean thresholds at 25.9, 18.4 and 8.0 °C for tonic and 24.5, 18.1 and 7.5 °C for phasic stimuli). Subjects' association with Gaussian modes was consistent between both types of stimuli (weighted Cohen's κ = 0.91). Patterns emerging in self-organizing neuronal maps and swarms could be associated with different trends towards decreasing cold pain sensitivity in different Gaussian modes. On self-organizing maps, the third Gaussian mode emerged as particularly distinct. Thresholds at, roughly, 25 and 18 °C agree with known working temperatures of TRPM8 and TRPA1 ion channels, respectively, and hint at relative local dominance of either channel in respective subjects. Data patterns suggest involvement of further distinct mechanisms in cold pain perception at lower temperatures. Findings support data science approaches to identify biologically plausible hints at complex molecular mechanisms underlying human pain phenotypes. Sensitivity to pain is heterogeneous. Data-driven computational research approaches allow the identification of subgroups of subjects with a distinct pattern of sensitivity to cold stimuli. The subgroups are reproducible with different types of noxious cold stimuli. Subgroups show pattern that hints at distinct and inter-individually different types of the underlying molecular background. © 2018 European Pain Federation - EFIC®.

Pokes, Sunburn, and Hot Sauce: Drosophila as an Emerging Model for the Biology of Nociception

PubMed Central

Im, Seol Hee; Galko, Michael J.

2012-01-01

The word “nociception” is derived from the Latin “nocere,” which means “to harm.” Nociception refers to the sensory perception of noxious stimuli that have the potential to cause tissue damage. Since the perception of such potentially harmful stimuli often results in behavioral escape responses, nociception provides a protective mechanism that allows an organism to avoid incipient (or further) damage to the tissue. It appears to be universal in metazoans as a variety of escape responses can be observed in both mammalian and non-mammalian vertebrates, as well as diverse invertebrates such as leeches, nematodes, and fruit flies (Sneddon [2004] Brain Research Review 46:123–130; Tobin and Bargmann [2004] Journal of Neurobiology 61:161–174; Smith and Lewin [2009] Journal of Comparative Physiology 195:1089–1106). Several types of stimuli can trigger nociceptive sensory transduction, including noxious heat, noxious chemicals, and harsh mechanical stimulation. Such high-threshold stimuli induce the firing of action potentials in peripheral nociceptors, the sensory neurons specialized for their detection (Basbaum et al. [2009] Cell 139:267–284). In vertebrates, these action potentials can either be relayed directly to a spinal motor neuron to provoke escape behavior (the so-called monosynaptic reflex) or can travel via spinal cord interneurons to higher-order processing centers in the brain. This review will cover the establishment of Drosophila as a system to study various aspects of nociceptive sensory perception. We will cover development of the neurons responsible for detecting noxious stimuli in larvae, the assays used to assess the function(s) of these neurons, and the genes that have been found to be required for both thermal and mechanical nociception. Along the way, we will highlight some of the genetic tools that make the fly such a powerful system for studies of nociception. Finally, we will cover recent studies that introduce new assays employing adult Drosophila to study both chemical and thermal nociception and provide an overview of important unanswered questions in the field. PMID:21932321

Guidelines for management of noxious weeds at Hanford

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roos, R.C.; Malady, M.B.

1995-10-27

Integrated Pest Management Services is responsible for management and control of noxious weeds on the Hanford Site. Weed species and populations are prioritized and objective defined, according to potential site and regional impact. Population controls are implemented according to priority. An integrated approach is planned for noxious weed control in which several management options are considered and implemented separately or in coordination to best meet management objectives. Noxious weeds are inventories and monitored to provide information for planning and program review.

Effect of ketamine on endogenous pain modulation in healthy volunteers.

PubMed

Niesters, Marieke; Dahan, Albert; Swartjes, Maarten; Noppers, Ingeborg; Fillingim, Roger B; Aarts, Leon; Sarton, Elise Y

2011-03-01

Inhibitory and facilitatory descending pathways, originating at higher central nervous system sites, modulate activity of dorsal horn nociceptive neurons, and thereby influence pain perception. Dysfunction of inhibitory pain pathways or a shift in the balance between pain facilitation and pain inhibition has been associated with the development of chronic pain. The N-methyl-d-aspartate receptor antagonist ketamine has a prolonged analgesic effect in chronic pain patients. This effect is due to desensitization of sensitized N-methyl-d-aspartate receptors. Additionally, ketamine may modulate or enhance endogenous inhibitory control of pain perception. Diffuse noxious inhibitory control (DNIC) and offset analgesia (OA) are 2 mechanisms involved in descending inhibition. The present study investigates the effect of a ketamine infusion on subsequent DNIC and OA responses to determine whether ketamine has an influence on descending pain control. Ten healthy subjects (4 men/6 women) received a 1-hour placebo or S(+)-ketamine (40mg per 70kg) infusion on 2 separate occasions in random order. Upon the termination of the infusion, DNIC and OA responses were obtained. After placebo treatment, significant descending inhibition of pain responses was present for DNIC and OA. In contrast, after ketamine infusion, no DNIC was observed, but rather a significant facilitatory pain response (P<0.01); the OA response remained unchanged. These findings suggest that the balance between pain inhibition and pain facilitation was shifted by ketamine towards pain facilitation. The absence of an effect of ketamine on OA indicates differences in the mechanisms and neurotransmitter influences between OA and DNIC. Diffuse noxious inhibitory control responses following a 1-hour low-dose ketamine treatment displayed facilitation of pain in response to experimental noxious thermal stimulation. Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

7 CFR 360.100 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-01-01

..., DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.100 Definitions. As used in this part, words in the... in this definition. Noxious weed. Any plant or plant product that can directly or indirectly injure... Administrator to move plants, plant products, biological control organisms, plant pests, noxious weeds, or...

7 CFR 360.100 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

..., DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.100 Definitions. As used in this part, words in the... in this definition. Noxious weed. Any plant or plant product that can directly or indirectly injure... Administrator to move plants, plant products, biological control organisms, plant pests, noxious weeds, or...

A Heat-Sensitive TRP Channel Expressed in Keratinocytes

NASA Astrophysics Data System (ADS)

Peier, Andrea M.; Reeve, Alison J.; Andersson, David A.; Moqrich, Aziz; Earley, Taryn J.; Hergarden, Anne C.; Story, Gina M.; Colley, Sian; Hogenesch, John B.; McIntyre, Peter; Bevan, Stuart; Patapoutian, Ardem

2002-06-01

Mechanical and thermal cues stimulate a specialized group of sensory neurons that terminate in the skin. Three members of the transient receptor potential (TRP) family of channels are expressed in subsets of these neurons and are activated at distinct physiological temperatures. Here, we describe the cloning and characterization of a novel thermosensitive TRP channel. TRPV3 has a unique threshold: It is activated at innocuous (warm) temperatures and shows an increased response at noxious temperatures. TRPV3 is specifically expressed in keratinocytes; hence, skin cells are capable of detecting heat via molecules similar to those in heat-sensing neurons.

How Plantar Exteroceptive Efficiency Modulates Postural and Oculomotor Control: Inter-Individual Variability.

PubMed

Foisy, Arnaud; Kapoula, Zoï

2016-01-01

In a previous experiment, we showed that among young and healthy subjects, thin plantar inserts improve postural control and modify vergence amplitudes. In this experiment, however, significant inter-individual variability was observed. We hypothesize that its origin could be attributed to a different reliance upon feet cutaneous afferents. In order to test this hypothesis, we re-analyzed the data relative to 31 young (age 25.7 ± 3.8) and healthy subjects who participated in the first experiment after having classified them into two groups depending on their Plantar Quotient (PQ = Surface area of CoPfoam/Surface area of CoPfirm ground × 100). Foam decreases the information arising from the feet, normally resulting in a PQ > 100. Hence, the PQ provides information on the weight of plantar cutaneous afferents used in postural control. Twelve people were Plantar-Independent Subjects, as indicated by a PQ < 100. These individuals did not behave like the Normal Plantar Quotient Subjects: they were almost insensitive to the plantar stimulations in terms of postural control and totally insensitive in terms of oculomotor control. We conclude that the inter-individual variability observed in our first experiment is explained by the subjects' degree of plantar reliance. We propose that plantar independence is a dysfunctional situation revealing inefficiency in plantar cutaneous afferents. The latter could be due to a latent somatosensory dysfunction generating a noise which prevents the CNS from correctly processing and using feet somatosensory afferents both for balance and vergence control: Plantar Irritating Stimulus. Considering the non-noxious nature and prevalence of this phenomenon, these results can be of great interest to researchers and clinicians who attempt to trigger postural or oculomotor responses through mechanical stimulation of the foot sole.

The economic cost of noxious weeds on Montana grazing lands

USDA-ARS?s Scientific Manuscript database

We distributed a 16-question survey concerning noxious weed abundances, impacts and management to livestock producers grazing on privately-owned or leased grazing lands in Montana. The noxious weeds most commonly reported as being present on respondents’ grazing units were Canada thistle (64% of gra...

7 CFR 352.3 - Enforcement and administration.

Code of Federal Regulations, 2013 CFR

2013-01-01

... administration. (a) Plants, plant products, plant pests, noxious weeds, soil, and other products and articles... pests, noxious weeds, soil, or other products or articles in violation of this part will be subject to... of plants, plant products, plant pests, noxious weeds, soil, or other products or articles subject to...

7 CFR 352.10 - Inspection; safeguards; disposal.

Code of Federal Regulations, 2013 CFR

2013-01-01

... specified by him to prevent plant pest or noxious weed dissemination. In the case of prohibited or... commensurate with the risk of plant pest or noxious weed dissemination required to transfer the products or... of the inspector, considerations of risk of plant pest or noxious weed dissemination require, such...

7 CFR 352.3 - Enforcement and administration.

Code of Federal Regulations, 2014 CFR

2014-01-01

... administration. (a) Plants, plant products, plant pests, noxious weeds, soil, and other products and articles... pests, noxious weeds, soil, or other products or articles in violation of this part will be subject to... of plants, plant products, plant pests, noxious weeds, soil, or other products or articles subject to...

7 CFR 352.3 - Enforcement and administration.

Code of Federal Regulations, 2011 CFR

2011-01-01

... administration. (a) Plants, plant products, plant pests, noxious weeds, soil, and other products and articles... pests, noxious weeds, soil, or other products or articles in violation of this part will be subject to... of plants, plant products, plant pests, noxious weeds, soil, or other products or articles subject to...

7 CFR 301.1 - Purpose and scope.

Code of Federal Regulations, 2014 CFR

2014-01-01

... noxious weeds if the Secretary has issued a regulation or order to prevent the dissemination of the biological control organism, plant pest, or noxious weed within the United States. The only exceptions to..., plant products, biological control organisms, plant pests, or noxious weeds that are in addition to the...

7 CFR 352.3 - Enforcement and administration.

Code of Federal Regulations, 2012 CFR

2012-01-01

... administration. (a) Plants, plant products, plant pests, noxious weeds, soil, and other products and articles... pests, noxious weeds, soil, or other products or articles in violation of this part will be subject to... of plants, plant products, plant pests, noxious weeds, soil, or other products or articles subject to...

7 CFR 352.10 - Inspection; safeguards; disposal.

Code of Federal Regulations, 2014 CFR

2014-01-01

... specified by him to prevent plant pest or noxious weed dissemination. In the case of prohibited or... commensurate with the risk of plant pest or noxious weed dissemination required to transfer the products or... of the inspector, considerations of risk of plant pest or noxious weed dissemination require, such...

7 CFR 301.1 - Purpose and scope.

Code of Federal Regulations, 2012 CFR

2012-01-01

... noxious weeds if the Secretary has issued a regulation or order to prevent the dissemination of the biological control organism, plant pest, or noxious weed within the United States. The only exceptions to..., plant products, biological control organisms, plant pests, or noxious weeds that are in addition to the...

7 CFR 352.10 - Inspection; safeguards; disposal.

Code of Federal Regulations, 2012 CFR

2012-01-01

... specified by him to prevent plant pest or noxious weed dissemination. In the case of prohibited or... commensurate with the risk of plant pest or noxious weed dissemination required to transfer the products or... of the inspector, considerations of risk of plant pest or noxious weed dissemination require, such...

7 CFR 301.1 - Purpose and scope.

Code of Federal Regulations, 2013 CFR

2013-01-01

... noxious weeds if the Secretary has issued a regulation or order to prevent the dissemination of the biological control organism, plant pest, or noxious weed within the United States. The only exceptions to..., plant products, biological control organisms, plant pests, or noxious weeds that are in addition to the...

7 CFR 352.10 - Inspection; safeguards; disposal.

Code of Federal Regulations, 2011 CFR

2011-01-01

... specified by him to prevent plant pest or noxious weed dissemination. In the case of prohibited or... commensurate with the risk of plant pest or noxious weed dissemination required to transfer the products or... of the inspector, considerations of risk of plant pest or noxious weed dissemination require, such...

Not in whose backyard? Minority population concentrations and noxious facility sites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nieves, L.A.

1992-04-01

The NIMBY (not in may backyard) syndrome has become the nemesis of facility siting efforts in the USA. Given people`s reluctance to live near noxious facilities, in whose backyard are such facilities located? This study employs US county-level data to examine relative concentrations of minorities living near noxious facilities. Facility types analyzed include electric generating plants, manufacturing plants, Superfund sites, and radioactive waste disposal sites. While this study does not address which cam first, the minority population concentration or the noxious facilities, it documents their current degree of association.

Not in whose backyard Minority population concentrations and noxious facility sites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nieves, L.A.

1992-01-01

The NIMBY (not in may backyard) syndrome has become the nemesis of facility siting efforts in the USA. Given people's reluctance to live near noxious facilities, in whose backyard are such facilities located This study employs US county-level data to examine relative concentrations of minorities living near noxious facilities. Facility types analyzed include electric generating plants, manufacturing plants, Superfund sites, and radioactive waste disposal sites. While this study does not address which cam first, the minority population concentration or the noxious facilities, it documents their current degree of association.

Corticospinal excitability is dependent on the parameters of peripheral electric stimulation: a preliminary study.

PubMed

Chipchase, Lucy S; Schabrun, Siobhan M; Hodges, Paul W

2011-09-01

To evaluate the effect of 6 electric stimulation paradigms on corticospinal excitability. Using a same subject pre-post test design, transcranial magnetic stimulation (TMS) was used to measure the responsiveness of corticomotor pathway to biceps and triceps brachii muscles before and after 30 minutes of electric stimulation over the biceps brachii. Six different electric stimulation paradigms were applied in random order, at least 3 days apart. Motor control research laboratory. Healthy subjects (N=10; 5 women, 5 men; mean age ± SD, 26 ± 3.6y). Six different electric stimulation paradigms with varied stimulus amplitude, frequency, and ramp settings. Amplitudes of TMS-induced motor evoked potentials at biceps and triceps brachii normalized to maximal M-wave amplitudes. Electric stimulation delivered at stimulus amplitude sufficient to evoke a sensory response at both 10 Hz and 100 Hz, and stimulus amplitude to create a noxious response at 10 Hz decreased corticomotor responsiveness (all P<0.01). Stimulation sufficient to induce a motor contraction (30 Hz) applied in a ramped pattern to mimic a voluntary activation increased corticomotor responsiveness (P=0.002), whereas constant low- and high-intensity motor stimulation at 10 Hz did not. Corticomotor excitability changes were similar for both the stimulated muscle and its antagonist. Stimulus amplitude (intensity) and the nature (muscle flicker vs contraction) of motor stimulation have a significant impact on changes in corticospinal excitability induced by electric stimulation. Here, we demonstrate that peripheral electric stimulation at stimulus amplitude to create a sensory response reduces corticomotor responsiveness. Conversely, stimulus amplitude to create a motor response increases corticomotor responsiveness, but only the parameters that create a motor response that mimics a voluntary muscle contraction. Copyright © 2011 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

7 CFR 360.501 - Petitions to remove a taxon from the noxious weed lists.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 5 2014-01-01 2014-01-01 false Petitions to remove a taxon from the noxious weed lists. 360.501 Section 360.501 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.501...

7 CFR 360.501 - Petitions to remove a taxon from the noxious weed lists.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 5 2011-01-01 2011-01-01 false Petitions to remove a taxon from the noxious weed lists. 360.501 Section 360.501 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.501...

7 CFR 360.501 - Petitions to remove a taxon from the noxious weed lists.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 5 2012-01-01 2012-01-01 false Petitions to remove a taxon from the noxious weed lists. 360.501 Section 360.501 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.501...

7 CFR 360.600 - Preemption of State and local laws.

Code of Federal Regulations, 2014 CFR

2014-01-01

... INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.600 Preemption of State and... subdivision of a State may not regulate in foreign commerce any noxious weed in order to control it, eradicate... prohibitions or restrictions upon the movement in interstate commerce of noxious weeds if the Secretary has...

7 CFR 352.2 - Purpose; relation to other regulations; applicability; preemption of State and local laws.

Code of Federal Regulations, 2012 CFR

2012-01-01

... local laws. (a) Importations of plants, plant products, plant pests, noxious weeds, soil, and other products and articles that may be infested or infected by or contain plant pests or noxious weeds are... article, means of conveyance, plant, biological control organism, plant pest, noxious weed, or plant...

7 CFR 360.600 - Preemption of State and local laws.

Code of Federal Regulations, 2013 CFR

2013-01-01

... INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.600 Preemption of State and... subdivision of a State may not regulate in foreign commerce any noxious weed in order to control it, eradicate... prohibitions or restrictions upon the movement in interstate commerce of noxious weeds if the Secretary has...

7 CFR 352.6 - Application for permit and approval or denial thereof.

Code of Federal Regulations, 2014 CFR

2014-01-01

... noxious weeds). Except as otherwise provided in this paragraph, any person desiring to unload or land, or... to eliminate danger of plant pest or noxious weed dissemination may be specified in the permit, or... is not possible to prescribe conditions adequate to prevent danger of plant pest or noxious weed...

7 CFR 352.2 - Purpose; relation to other regulations; applicability; preemption of State and local laws.

Code of Federal Regulations, 2014 CFR

2014-01-01

... local laws. (a) Importations of plants, plant products, plant pests, noxious weeds, soil, and other products and articles that may be infested or infected by or contain plant pests or noxious weeds are... article, means of conveyance, plant, biological control organism, plant pest, noxious weed, or plant...

7 CFR 352.6 - Application for permit and approval or denial thereof.

Code of Federal Regulations, 2012 CFR

2012-01-01

... noxious weeds). Except as otherwise provided in this paragraph, any person desiring to unload or land, or... to eliminate danger of plant pest or noxious weed dissemination may be specified in the permit, or... is not possible to prescribe conditions adequate to prevent danger of plant pest or noxious weed...

7 CFR 352.6 - Application for permit and approval or denial thereof.

Code of Federal Regulations, 2013 CFR

2013-01-01

... noxious weeds). Except as otherwise provided in this paragraph, any person desiring to unload or land, or... to eliminate danger of plant pest or noxious weed dissemination may be specified in the permit, or... is not possible to prescribe conditions adequate to prevent danger of plant pest or noxious weed...

7 CFR 360.600 - Preemption of State and local laws.

Code of Federal Regulations, 2011 CFR

2011-01-01

... INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.600 Preemption of State and... subdivision of a State may not regulate in foreign commerce any noxious weed in order to control it, eradicate... prohibitions or restrictions upon the movement in interstate commerce of noxious weeds if the Secretary has...

7 CFR 360.600 - Preemption of State and local laws.

Code of Federal Regulations, 2012 CFR

2012-01-01

... INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.600 Preemption of State and... subdivision of a State may not regulate in foreign commerce any noxious weed in order to control it, eradicate... prohibitions or restrictions upon the movement in interstate commerce of noxious weeds if the Secretary has...

7 CFR 352.2 - Purpose; relation to other regulations; applicability; preemption of State and local laws.

Code of Federal Regulations, 2013 CFR

2013-01-01

... local laws. (a) Importations of plants, plant products, plant pests, noxious weeds, soil, and other products and articles that may be infested or infected by or contain plant pests or noxious weeds are... article, means of conveyance, plant, biological control organism, plant pest, noxious weed, or plant...

7 CFR 360.400 - Preemption of State and local laws.

Code of Federal Regulations, 2010 CFR

2010-01-01

... INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.400 Preemption of State and... subdivision of a State may not regulate in foreign commerce any noxious weed in order to control it, eradicate... prohibitions or restrictions upon the movement in interstate commerce of noxious weeds if the Secretary has...

Involvement of ERK phosphorylation in brainstem neurons in modulation of swallowing reflex in rats

PubMed Central

Tsujimura, Takanori; Kondo, Masahiro; Kitagawa, Junichi; Tsuboi, Yoshiyuki; Saito, Kimiko; Tohara, Haruka; Ueda, Koichiro; Sessle, Barry J; Iwata, Koichi

2009-01-01

In order to evaluate the neuronal mechanisms underlying functional abnormalities of swallowing in orofacial pain patients, this study investigated the effects of noxious orofacial stimulation on the swallowing reflex, phosphorylated extracellular signal-regulated kinase (pERK) and γ-aminobutyric acid (GABA) immunohistochemical features in brainstem neurons, and also analysed the effects of brainstem lesioning and of microinjection of GABA receptor agonist or antagonist into the nucleus tractus solitarii (NTS) on the swallowing reflex in anaesthetized rats. The swallowing reflex elicited by topical administration of distilled water to the pharyngolaryngeal region was inhibited after capsaicin injection into the facial (whisker pad) skin or lingual muscle. The capsaicin-induced inhibitory effect on the swallowing reflex was itself depressed after the intrathecal administration of MAPK kinase (MEK) inhibitor. No change in the capsaicin-induced inhibitory effect was observed after trigeminal spinal subnucleus caudalis lesioning, but the inhibitory effect was diminished by paratrigeminal nucleus (Pa5) lesioning. Many pERK-like immunoreactive neurons in the NTS showed GABA immunoreactivity. The local microinjection of the GABAA receptor agonist muscimol into the NTS produced a significant reduction in swallowing reflex, and the capsaicin-induced depression of the swallowing reflex was abolished by microinjection of the GABAA receptor antagonist bicuculline into the NTS. The present findings suggest that facial skin–NTS, lingual muscle–NTS and lingual muscle–Pa5–NTS pathways are involved in the modulation of swallowing reflex by facial and lingual pain, respectively, and that the activation of GABAergic NTS neurons is involved in the inhibition of the swallowing reflex following noxious stimulation of facial and intraoral structures. PMID:19124539

Capturing Pain in the Cortex during General Anesthesia: Near Infrared Spectroscopy Measures in Patients Undergoing Catheter Ablation of Arrhythmias

PubMed Central

Yücel, Meryem A.; Steele, Sarah C.; Alexander, Mark E.; Boas, David A.; Borsook, David; Becerra, Lino

2016-01-01

The predictability of pain makes surgery an ideal model for the study of pain and the development of strategies for analgesia and reduction of perioperative pain. As functional near-infrared spectroscopy reproduces the known functional magnetic resonance imaging activations in response to a painful stimulus, we evaluated the feasibility of functional near-infrared spectroscopy to measure cortical responses to noxious stimulation during general anesthesia. A multichannel continuous wave near-infrared imager was used to measure somatosensory and frontal cortical activation in patients undergoing catheter ablation of arrhythmias under general anesthesia. Anesthetic technique was standardized and intraoperative NIRS signals recorded continuously with markers placed in the data set for the timing and duration of each cardiac ablation event. Frontal cortical signals only were suitable for analysis in five of eight patients studied (mean age 14 ± 1 years, weight 66.7 ± 17.6 kg, 2 males). Thirty ablative lesions were recorded for the five patients. Radiofrequency or cryoablation was temporally associated with a hemodynamic response function in the frontal cortex characterized by a significant decrease in oxyhemoglobin concentration (paired t-test, p<0.05) with the nadir occurring in the period 4 to 6 seconds after application of the ablative lesion. Cortical signals produced by catheter ablation of arrhythmias in patients under general anesthesia mirrored those seen with noxious stimulation in awake, healthy volunteers, during sedation for colonoscopy, and functional Magnetic Resonance Imaging activations in response to pain. This study demonstrates the feasibility and potential utility of functional near-infrared spectroscopy as an objective measure of cortical activation under general anesthesia. PMID:27415436

Capturing Pain in the Cortex during General Anesthesia: Near Infrared Spectroscopy Measures in Patients Undergoing Catheter Ablation of Arrhythmias.

PubMed

Kussman, Barry D; Aasted, Christopher M; Yücel, Meryem A; Steele, Sarah C; Alexander, Mark E; Boas, David A; Borsook, David; Becerra, Lino

2016-01-01

The predictability of pain makes surgery an ideal model for the study of pain and the development of strategies for analgesia and reduction of perioperative pain. As functional near-infrared spectroscopy reproduces the known functional magnetic resonance imaging activations in response to a painful stimulus, we evaluated the feasibility of functional near-infrared spectroscopy to measure cortical responses to noxious stimulation during general anesthesia. A multichannel continuous wave near-infrared imager was used to measure somatosensory and frontal cortical activation in patients undergoing catheter ablation of arrhythmias under general anesthesia. Anesthetic technique was standardized and intraoperative NIRS signals recorded continuously with markers placed in the data set for the timing and duration of each cardiac ablation event. Frontal cortical signals only were suitable for analysis in five of eight patients studied (mean age 14 ± 1 years, weight 66.7 ± 17.6 kg, 2 males). Thirty ablative lesions were recorded for the five patients. Radiofrequency or cryoablation was temporally associated with a hemodynamic response function in the frontal cortex characterized by a significant decrease in oxyhemoglobin concentration (paired t-test, p<0.05) with the nadir occurring in the period 4 to 6 seconds after application of the ablative lesion. Cortical signals produced by catheter ablation of arrhythmias in patients under general anesthesia mirrored those seen with noxious stimulation in awake, healthy volunteers, during sedation for colonoscopy, and functional Magnetic Resonance Imaging activations in response to pain. This study demonstrates the feasibility and potential utility of functional near-infrared spectroscopy as an objective measure of cortical activation under general anesthesia.

Altered nocifensive behavior in animal models of autism spectrum disorder: the role of the nicotinic cholinergic system

PubMed Central

Wang, Li; Almeida, Luis E.F.; Nettleton, Margaret; Khaibullina, Alfia; Albani, Sarah; Kamimura, Sayuri; Nouraie, Mehdi; Quezado, Zenaide M.N.

2016-01-01

Caretakers and clinicians alike have long recognized that individuals with autism spectrum disorder (ASD) can have altered sensory processing, which can contribute to its core symptoms. However, the pathobiology of sensory alterations in ASD is poorly understood. Here we examined nocifensive behavior in ASD mouse models, the BTBR T+Itpr3tf/J (BTBR) and the fragile-X mental retardation-1 knockout (Fmr1-KO) mice. We also examined the effects of nicotine on nocifensive behavior given that nicotine, a nicotinic cholinergic receptor (nAChR) agonist that has antinociceptive effects and was shown to improve social deficits and decrease repetitive behaviors in BTBR mice. Compared to respective controls, both BTBR and Fmr1-KO had hyporesponsiveness to noxious thermal stimuli and electrical stimulation of C-sensory fibers, normal responsiveness to electrical stimulation of Aβ- and Aδ-fiber, and hyperresponsiveness to visceral pain after acetic acid intraperitoneal injection. In BTBR, nicotine at lower doses increased, whereas at higher doses, it decreased hotplate latency compared to vehicle. In a significantly different effect pattern, in control mice, nicotine had antinociceptive effects to noxious heat only at the high dose. Interestingly, these nocifensive behavior alterations and differential responses to nicotine antinociceptive effects in BTBR mice were associated with significant downregulation of α3, α4, α5, α7, β2, β3, and β4 nAChR subunits in several cerebral regions both, during embryonic development and adulthood. Taken together, these findings further implicate nAChRs in behaviors alterations in the BTBR model and lend support to the hypothesis that nAChRs may be a target for treatment of behavior deficits and sensory dysfunction in ASD. PMID:27638450

Sucrose and naltrexone prevent increased pain sensitivity and impaired long-term memory induced by repetitive neonatal noxious stimulation: Role of BDNF and β-endorphin.

PubMed

Nuseir, Khawla Q; Alzoubi, Karem H; Alhusban, Ahmed; Bawaane, Areej; Al-Azzani, Mohammed; Khabour, Omar F

2017-10-01

Pain in neonates is associated with short and long-term adverse outcomes. Data demonstrated that long-term consequences of untreated pain are linked to the plasticity of the neonate's brain. Sucrose is effective and safe for reducing painful procedures from single events. However, the mechanism of sucrose-induced analgesia is not fully understood. The role of the opioid system in this analgesia using the opioid receptor antagonist Naltrexone was investigated, plus the long-term effects on learning and memory formation during adulthood. Pain was induced in rat pups via needle pricks of the paws. Sucrose solution and/or naltrexone were administered before the pricks. All treatments started on day one of birth and continued for two weeks. At the end of 8weeks, behavioral studies were conducted to test spatial learning and memory using radial arm water maze (RAWM), and pain threshold via foot-withdrawal response to a hot plate. The hippocampus was dissected; levels of brain derived neurotrophic factor (BDNF) and endorphins were assessed using ELISA. Acute repetitive neonatal pain increased pain sensitivity later in life, while naltrexone with sucrose decreased pain sensitivity. Naltrexone and/or sucrose prevented neonatal pain induced impairment of long-term memory, while neonatal pain decreased levels of BDNF in the hippocampus; this decrease was averted by sucrose and naltrexone. Sucrose with naltrexone significantly increased β-endorphin levels in noxiously stimulated rats. In conclusion, naltrexone and sucrose can reverse increased pain sensitivity and impaired long-term memory induced by acute repetitive neonatal pain probably by normalizing BDNF expression and increasing β-endorphin levels. Copyright © 2017 Elsevier Inc. All rights reserved.

Sugar Dehydration without Sulfuric Acid: No More Choking Fumes in the Classroom!

NASA Astrophysics Data System (ADS)

Silverstein, Todd P.; Zhang, Yi

1998-06-01

Sugar is a common reagent often used in colorful classroom demonstrations. It produces a growing column of black ash when dehydrated by concentrated sulfuric acid, and it produces a brilliant purple flame when combusted with potassium chlorate. Unfortunately, both of these reactions also produce copious quantities of noxious fumes which make them problematic as lecture demonstrations. We have modified and combined these two reactions. Our demonstration uses no sulfuric acid, yields relatively little smoke, and produces an exciting and unpredictable growing column of black carbon.

Characterization of the "deqi" response in acupuncture.

PubMed

Hui, Kathleen K S; Nixon, Erika E; Vangel, Mark G; Liu, Jing; Marina, Ovidiu; Napadow, Vitaly; Hodge, Steven M; Rosen, Bruce R; Makris, Nikos; Kennedy, David N

2007-10-31

Acupuncture stimulation elicits deqi, a composite of unique sensations that is essential for clinical efficacy according to traditional Chinese medicine (TCM). There is lack of adequate experimental data to indicate what sensations comprise deqi, their prevalence and intensity, their relationship to acupoints, how they compare with conventional somatosensory or noxious response. The objective of this study is to provide scientific evidence on these issues and to characterize the nature of the deqi phenomenon in terms of the prevalence of sensations as well as the uniqueness of the sensations underlying the deqi experience. Manual acupuncture was performed at LI4, ST36 and LV3 on the extremities in randomized order during fMRI in 42 acupuncture naïve healthy adult volunteers. Non-invasive tactile stimulation was delivered to the acupoints by gentle tapping with a von Frey monofilament prior to acupuncture to serve as a sensory control. At the end of each procedure, the subject was asked if each of the sensations listed in a questionnaire or any other sensations occurred during stimulation, and if present to rate its intensity on a numerical scale of 1-10. Statistical analysis including paired t-test, analysis of variance, Spearman's correlation and Fisher's exact test were performed to compare responses between acupuncture and sensory stimulation. The deqi response was elicited in 71% of the acupuncture procedures compared with 24% for tactile stimulation when thresholded at a minimum total score of 3 for all the sensations. The frequency and intensity of individual sensations were significantly higher in acupuncture. Among the sensations typically associated with deqi, aching, soreness and pressure were most common, followed by tingling, numbness, dull pain, heaviness, warmth, fullness and coolness. Sharp pain of brief duration that occurred in occasional subjects was regarded as inadvertent noxious stimulation. The most significant differences in the deqi sensations between acupuncture and tactile stimulation control were observed with aching, soreness, pressure and dull pain. Consistent with its prominent role in TCM, LI4 showed the most prominent response, the largest number of sensations as well as the most marked difference in the frequency and intensity of aching, soreness and dull pain between acupuncture and tactile stimulation control. Interestingly, the dull pain generally preceded or occurred in the absence of sharp pain in contrast to reports in the pain literature. An approach to summarize a sensation profile, called the deqi composite, is proposed and applied to explain differences in deqi among acupoints. The complex pattern of sensations in the deqi response suggests involvement of a wide spectrum of myelinated and unmyelinated nerve fibers, particularly the slower conducting fibers in the tendinomuscular layers. The study provides scientific data on the characteristics of the 'deqi' response in acupuncture and its association with distinct nerve fibers. The findings are clinically relevant and consistent with modern concepts in neurophysiology. They can provide a foundation for future studies on the deqi phenomenon.

Spinal NMDA-receptor dependent amplification of nociceptive transmission to rat primary somatosensory cortex (SI).

PubMed

Kalliomäki, Jarkko; Granmo, Marcus; Schouenborg, Jens

2003-07-01

The role of NMDA mechanisms in spinal pathways mediating acute nociceptive input to the somatosensory cortex is not clear. In this study, the effect of NMDA-antagonists on nociceptive C fibre transmission to the primary somatosensory cortex (SI) was investigated. Cortical field potentials evoked by CO(2)-laser stimulation of the skin were recorded in the halothane/nitrous oxide anaesthetized rat. The SI nociceptive evoked potential (EP) amplitudes were dependent on the frequency of noxious heat stimulation. The amplitudes of SI potentials evoked by CO(2)-laser pulses (duration 15-20 ms, stimulation energy 21-28 mJ/mm(2)) delivered at a frequency of 0.1 Hz were approximately 40% of the amplitudes of potentials evoked by 1.0 Hz stimulation. After intrathecal lumbar application of either of the NMDA-antagonists CPP or MK-801, the amplitudes of nociceptive SI potentials, evoked by 1.0 Hz stimulation of the contralateral hindpaw, were reduced to approximately 40% of controls. By contrast, field potentials evoked by 0.1 Hz stimulation of the hindpaw were unaffected by MK-801. SI potentials evoked by 1.0 Hz stimulation of the contralateral forepaw did not change after lumbar application of CPP or MK-801, indicating that the depression of hindpaw EPs was due to a segmental effect in the spinal cord. It is concluded that spinal NMDA-receptor mechanisms amplify the acute transmission of nociceptive C fiber input to SI in a frequency-dependent way.

Dalmatian toadflax, an invasive exotic noxious weed, threatens Flagstaff pennyroyal community following prescribed fire

Treesearch

Barbara Goodrich Phillips; Debra Crisp

2001-01-01

Many noxious weed infestations are initiated or increased by soil disturbance. With the recent emphasis on reintroduction of fire into natural ecosystems there has been increased interest in the effects of noxious weeds following fires. This paper discusses the effects of fire on Flagstaff pennyroyal, a Forest Service Region 3 sensitive plant, and the subsequent...

Behavioral and Functional Assays for Investigating Mechanisms of Noxious Cold Detection and Multimodal Sensory Processing in Drosophila Larvae

PubMed Central

Patel, Atit A.; Cox, Daniel N.

2017-01-01

To investigate cellular, molecular and behavioral mechanisms of noxious cold detection, we developed cold plate behavioral assays and quantitative means for evaluating the predominant noxious cold-evoked contraction behavior. To characterize neural activity in response to noxious cold, we implemented a GCaMP6-based calcium imaging assay enabling in vivo studies of intracellular calcium dynamics in intact Drosophila larvae. We identified Drosophila class III multidendritic (md) sensory neurons as multimodal sensors of innocuous mechanical and noxious cold stimuli and to dissect the mechanistic bases of multimodal sensory processing we developed two independent functional assays. First, we developed an optogenetic dose response assay to assess whether levels of neural activation contributes to the multimodal aspects of cold sensitive sensory neurons. Second, we utilized CaMPARI, a photo-switchable calcium integrator that stably converts fluorescence from green to red in presence of high intracellular calcium and photo-converting light, to assess in vivo functional differences in neural activation levels between innocuous mechanical and noxious cold stimuli. These novel assays enable investigations of behavioral and functional roles of peripheral sensory neurons and multimodal sensory processing in Drosophila larvae. PMID:28835907

Neuropeptide Y receptor-expressing dorsal horn neurons: role in nocifensive reflex and operant responses to aversive cold after CFA inflammation.

PubMed

Lemons, L L; Wiley, R G

2012-08-02

The spinal Neuropeptide Y (NPY) system is a potential target for development of new pain therapeutics. NPY and two of its receptors (Y1 and Y2) are found in the superficial dorsal horn of the spinal cord, a key area of nociceptive gating and modulation. Lumbar intrathecal injection of (NPY) is antinociceptive, reducing hyper-reflexia to thermal and mechanical stimulation, particularly after nerve injury and inflammation. We have also shown that intrathecal injection of the targeted cytotoxin, Neuropeptide Y-sap (NPY-sap), is also antinociceptive, reducing nocifensive reflex responses to noxious heat and formalin. In the present study, we sought to determine the role of dorsal horn Y1R-expressing neurons in pain by destroying them with NPY-sap and testing the rats on three operant tasks. Lumbar intrathecal NPY-sap (1) reduced Complete Freund's Adjuvant (CFA)-induced hyper-reflexia on the 10°C cold plate, (2) reduced cold aversion on the thermal preference and escape tasks, (3) was analgesic to noxious heat on the escape task, (4) reduced the CFA-induced allodynia to cold temperatures experienced on the thermal preference, feeding interference, and escape tasks, and (5) did not inhibit or interfere with morphine analgesia. Published by Elsevier Ltd.

Interaction of corneal nociceptive stimulation and lacrimal secretion.

PubMed

Situ, Ping; Simpson, Trefford L

2010-11-01

To investigate the interaction between corneal stimuli at different positions and tear secretion and to establish relationships between nociceptive stimuli detection thresholds and stimulated tearing. Using a computerized Belmonte-esthesiometer, mechanical and chemical stimuli, from 0% to 200% of the threshold in 50% steps, were delivered (in random order) to the central and peripheral (approximately 2-mm inside the limbus) cornea during four separate sessions to 15 subjects. Immediately after each stimulus, tear meniscus height (TMH) was measured using optical coherence tomography to quantify the amount of lacrimal secretion, and subjects reported whether they felt tears starting to accumulate in their eyes. Thresholds (50% detection) for detection of tearing were estimated. TMH increased with increasing stimulus intensity (P < 0.05), and the overall increase was higher with central stimulation than with peripheral stimulation (P < 0.05). The changes in TMH with threshold-scaled stimulus intensity depended on test location (P < 0.05) and stimulus modality (P < 0.05). The maximum intensity of mechanical stimulation of the central cornea induced the greatest TMH (all P < 0.05). For chemical stimulation, the stimulus intensity required to induce detectable tearing was higher than that required to detect a stimulus and higher in the periphery than at the center (all P < 0.05). Noxious mechanical and chemical stimuli evoked measurable tear secretion, with central corneal mechanical stimulation evoking the strongest lacrimation reflex. Central mechanical corneal stimulation is the most effective stimulus-position pairing and appears to be the major sensory driving force for reflex tear secretion by the lacrimal functional unit.

ERK-GluR1 phosphorylation in trigeminal spinal subnucleus caudalis neurons is involved in pain associated with dry tongue.

PubMed

Nakaya, Yuka; Tsuboi, Yoshiyuki; Okada-Ogawa, Akiko; Shinoda, Masamichi; Kubo, Asako; Chen, Jui Yen; Noma, Noboru; Batbold, Dulguun; Imamura, Yoshiki; Sessle, Barry J; Iwata, Koichi

2016-01-01

Dry mouth is known to cause severe pain in the intraoral structures, and many dry mouth patients have been suffering from intraoral pain. In development of an appropriate treatment, it is crucial to study the mechanisms underlying intraoral pain associated with dry mouth, yet the detailed mechanisms are not fully understood. To evaluate the mechanisms underlying pain related to dry mouth, the dry-tongue rat model was developed. Hence, the mechanical or heat nocifensive reflex, the phosphorylated extracellular signal-regulated kinase and phosphorylated GluR1-IR immunohistochemistries, and the single neuronal activity were examined in the trigeminal spinal subnucleus caudalis of dry-tongue rats. The head-withdrawal reflex threshold to mechanical, but not heat, stimulation of the tongue was significantly decreased on day 7 after tongue drying. The mechanical, but not heat, responses of trigeminal spinal subnucleus caudalis nociceptive neurons were significantly enhanced in dry-tongue rats compared to sham rats on day 7. The number of phosphorylated extracellular signal-regulated kinase-immunoreactive cells was also significantly increased in the trigeminal spinal subnucleus caudalis following noxious stimulation of the tongue in dry-tongue rats compared to sham rats on day 7. The decrement of the mechanical head-withdrawal reflex threshold (HWT) was reversed during intracisternal administration of the mitogen-activated protein kinase kinase 1 inhibitor, PD98059. The trigeminal spinal subnucleus caudalis neuronal activities and the number of phosphorylated extracellular signal-regulated kinase-immunoreactive cells following noxious mechanical stimulation of dried tongue were also significantly decreased following intracisternal administration of PD98059 compared to vehicle-administrated rats. Increased number of the phosphorylated GluR1-IR cells was observed in the trigeminal spinal subnucleus caudalis of dry-tongue rats, and the number of phosphorylated GluR1-IR cells was significantly reduced in PD98059-administrated rats compared to the vehicle-administrated tongue-dry rats. These findings suggest that the pERK-pGluR1 cascade is involved in central sensitization of trigeminal spinal subnucleus caudalis nociceptive neurons, thus resulting in tongue mechanical hyperalgesia associated with tongue drying. © The Author(s) 2016.

Fos expression in the rat brain and spinal cord evoked by noxious stimulation to low back muscle and skin.

PubMed

Ohtori, S; Takahashi, K; Chiba, T; Takahashi, Y; Yamagata, M; Sameda, H; Moriya, H

2000-10-01

Acute noxious stimulation delivered to lumbar muscles and skin of rats was used to study Fos expression patterns in the brain and spinal cord. The present study was conducted to determine the differences in Fos expression in the brain and spinal cord as evoked by stimuli delivered to lumbar muscles and skin in rats. Patients with low back pain sometimes show psychological symptoms, such as quiescence, loss of interest, decreased activities, appetite loss, and restlessness. The pathway of deep somatic pain to the brain has been reported to be different from that of cutaneous pain. However, Fos expression has not been studied in the central nervous systems after stimulation of low back muscles. Rats were injected with 100 L of 5% formalin into the multifidus muscle (deep pain group; n = 10) and into the back skin of the L5 dermatome (cutaneous pain group; n = 10). Two hours after injection, the distribution of Fos-immunoreactive neurons was studied in the brain and spinal cord. Fos-immunoreactive neurons were observed in laminae I-V in the spinal cord in the cutaneous pain group, but they were not seen in lamina II in the deep pain group. In the brain, Fos-immunoreactive neurons were significantly more numerous in the deep pain group than in the cutaneous pain group in the piriform cortex, the accumbens nucleus core, the basolateral nucleus of amygdala, the paraventricular hypothalamic nucleus, the ventral tegmental area, and the ventrolateral periaqueductal gray. The finding that Fos-immunoreactive neurons were absent from lamina II of the spinal cord in the deep pain group is similar to that of the projection pattern of the visceral pain pathway. Fos expression in the ventrolateral periaqueductal gray in the deep pain group may represent a reaction of quiescence and a loss of interest, activities, or appetite. Furthermore, the detection of large numbers of Fos-immunoreactive neurons in the core of accumbens nucleus, basolateral nucleus of amygdala, paraventricular hypothalamic nucleus, and ventral tegmental area in the deep pain group may suggest a dominant reaction of dopaminergic neurons to stress, and a different information processing pathway than from that of cutaneous pain.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hutchinson, Kenneth

To perform remedial vegetation management for keeping vegetation a safe distance away from electric power facilities and controlling noxious weeds within a section of BPA's Big Eddy-Ostrander Transmission Corridor. During a site review conducted in late fall of 2001, the inspector observed various species of hardwood trees resprouted from stumps. The new vegetative growth encroached on the required “Minimum Safe Distance” between the top of vegetation and the conductor cables. The management action is necessary to reduce the current and potential future hazards that tall-growing vegetation poses to transmission conductors. In addition, BPA will include weed control as part ofmore » their remedial vegetation management action. Noxious weeds occur within the corridor. Under a 1999 Executive Order, all federal agencies are required to detect and control noxious weeds. In addition, BPA is required under the 1990 amendment to the Noxious Weed Act (7 USC 2801-2814) to manage undesirable plants on federal land. Also, the Bonneville Power Administration (BPA) has responsibility to manage noxious weeds under the Transmission System Vegetation Management Program Final Environmental Impact Statement (FEIS).1 State statutes and regulations also mandate action by BPA and the USFS to control noxious weeds. The Oregon Department of Agriculture (ODA) has requested that agencies aggressively control these weeds before additional spread occurs.« less

Brain evoked potentials to noxious sural nerve stimulation in sciatalgic patients.

PubMed

Willer, J C; De Broucker, T; Barranquero, A; Kahn, M F

1987-07-01

In sciatalgic patients and before any treatment, the goal of this work was to compare the amplitude of the late component (N150-P220) of the brain evoked potential (BEP) between resting pain-free conditions and a neurological induced pain produced by the Lasègue manoeuvre. The study was carried out with 8 inpatients affected with a unilateral sciatica resulting from an X-ray identified dorsal root compression from discal origin. The sural nerve was electrically stimulated at the ankle level while BEPs were recorded monopolarly from the vertex. The stimulus intensity eliciting a liminal nociceptive reflex response in a knee-flexor muscle associated with a liminal pain was selected for this study. Both normal and affected side were alternatively stimulated during several conditions of controls and of Lasègue's manoeuvres performed on the normal and on the affected side. Results show that the Lasègue manoeuvre performed on the affected side induced a significant increase in the amplitude of N150-P220; performed on the normal side, this same manoeuvre resulted in a significant decrease of the N150-P220 amplitude. These variations were observed whatever was the side (normal or affected) under sural nerve stimulation. The possible neural mechanisms of these changes and clinical implications of these data are then discussed.

Electrical stimulation of dorsal root entry zone attenuates wide-dynamic range neuronal activity in rats

PubMed Central

Yang, Fei; Zhang, Chen; Xu, Qian; Tiwari, Vinod; He, Shao-Qiu; Wang, Yun; Dong, Xinzhong; Vera-Portocarrero, Louis P.; Wacnik, Paul W.; Raja, Srinivasa N.; Guan, Yun

2014-01-01

Objectives Recent clinical studies suggest that neurostimulation at the dorsal root entry zone (DREZ) may alleviate neuropathic pain. However, the mechanisms of action for this therapeutic effect are unclear. Here, we examined whether DREZ stimulation inhibits spinal wide-dynamic-range (WDR) neuronal activity in nerve-injured rats. Materials and Methods We conducted in vivo extracellular single-unit recordings of WDR neurons in rats after an L5 spinal nerve ligation (SNL) or sham surgery. We set bipolar electrical stimulation (50 Hz, 0.2 ms, 5 min) of the DREZ at the intensity that activated only Aα/β-fibers by measuring the lowest current at which DREZ stimulation evoked a peak antidromic sciatic Aα/β-compound action potential without inducing an Aδ/C-compound action potential (i.e., Ab1). Results The elevated spontaneous activity rate of WDR neurons in SNL rats [n=25; data combined from day 14–16 (n = 15) and day 45–75 post-SNL groups (n=10)] was significantly decreased from the pre-stimulation level (p<0.01) at 0–15 min and 30–45 min post-stimulation. In both sham-operated (n=8) and nerve-injured rats, DREZ stimulation attenuated the C-component, but not A-component, of the WDR neuronal response to graded intracutaneous electrical stimuli (0.1–10 mA, 2 ms) applied to the skin receptive field. Further, DREZ stimulation blocked windup (a short form of neuronal sensitization) to repetitive noxious stimuli (0.5 Hz) at 0–15 min in all groups (p<0.05). Conclusions Attenuation of WDR neuronal activity may contribute to DREZ stimulation-induced analgesia. This finding supports the notion that DREZ may be a useful target for neuromodulatory control of pain. PMID:25308522

The efficacy of alfaxalone for immersion anesthesia in koi carp (Cyprinus carpio).

PubMed

Minter, Larry J; Bailey, Kate M; Harms, Craig A; Lewbart, Gregory A; Posner, Lysa P

2014-07-01

To characterize the physiologic and behavioral effects of a single induction dose and two maintenance doses of alfaxalone delivered by water immersion in the anesthesia of koi (Cyprinus carpio). Prospective, within-subject complete crossover design. Six adult koi (Cyprinus carpio) with a median body weight of 344.5 g (range 292.0-405.0 g). Koi were immersed in water containing 10 mg L(-1) alfaxalone until immobile and then maintained with alfaxalone at either 1 or 2.5 mg L(-1) via a recirculating water system. Times for anesthetic induction and recovery periods were recorded. Physiologic and blood gas parameters were evaluated before, during and after the anesthetic trial. Response to noxious stimuli was also assessed. Median anesthesia induction time for all fish was 5.4 minutes. Median recovery time was 11.8 and 26.4 minutes in the 1.0 and 2.5 mg L(-1) doses, respectively, which were significantly different (p = 0.04). Cessation of opercular movement occurred in 0/6 and 4/6 fish exposed to 1.0 and 2.5 mg L(-1) dose respectively. No difference was observed in median heart rate over the duration of the anesthetic events. Response to noxious stimulation was 4/6 and 0/6 in the 1.0 and 2.5 mg L(-1) doses respectively. Oxygenation and ventilation did not change during the experiment, but there was a significant decrease in blood pH along with an increase in blood lactate concentration. Administration of alfaxalone, via water immersion, as an induction and maintenance anesthesia agent provided rapid and reliable anesthesia of koi with no mortality. The maintenance dose of 2.5 mg L(-1) was sufficient to prevent response to noxious stimuli but was associated with a clinically relevant depression in opercular rate. © 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

A functional magnetic resonance imaging study of human brain in pain-related areas induced by electrical stimulation with different intensities.

PubMed

Yuan, Wang; Ming, Zhang; Rana, Netra; Hai, Liu; Chen-wang, Jin; Shao-hui, Ma

2010-01-01

Pain-related studies have mainly been performed through traditional methods, which lack the rigorous analysis of anatomical locations. Functional magnetic resonance imaging (fMRI) is a noninvasive method detecting neural activity, and has the ability to precisely locate related activations in vivo. Moreover, few studies have used painful stimulation of changed intensity to investigate relevant functioning nuclei in the human brain. This study mainly focused on the pain-related activations induced by electrical stimulation with different intensities using fMRI. Furthermore, the electrophysiological characteristics of different pain-susceptible-neurons were analyzed to construct the pain modulatory network, which was corresponding to painful stimulus of changed intensity. Twelve volunteers underwent functional scanning receiving different electrical stimulation. The data were collected and analyzed to generate the corresponding functional activation maps and response time curves related to pain. The common activations were mainly located in several specific regions, including the secondary somatosensory cortex (SII), insula, anterior cingulate cortex (ACC), thalamus, and other cerebral regions. Moreover, innocuous electrical stimulation primarily activated the lateral portions of SII and thalamus, as well as the posterior insula, anterior ACC, whereas noxious electrical stimulation primarily activated the medial portions of SII and thalamus, as well as the anterior insula, the posterior ACC, with larger extensions and greater intensities. Several specified cerebral regions displayed different response patterns during electrical stimulation by means of fMRI, which implied that the corresponding pain-susceptible-neurons might process specific aspects of pain. Elucidation of functions on pain-related regions will help to understand the delicate pain modulation of human brain.

Noxious stimuli do not determine reflex cardiorespiratory effects in anesthetized rabbits.

PubMed

Raimondi, G; Legramante, J M; Iellamo, F; Frisardi, G; Cassarino, S; Peruzzi, G

1996-12-01

The main purpose of this study is to examine whether the stimulation of an exclusively pain-sensing receptive field (dental pulp) could determine cardiorespiratory effects in animals in which the cortical integration of the peripheral information is abolished by deep anesthesia. In 15 anesthetized (alpha-chloralose and urethan) rabbits, low (3-Hz)- and high-frequency (100-Hz) electrical dental pulp stimulation was performed. Because this stimulation caused dynamic and static reflex contractions of the digastric muscles leading to jaw opening jaw-opening reflex (JOR); an indirect sign of algoceptive fiber activation], experimentally induced direct dynamic and static contractions of the digastric muscle were also performed. The low- and high-frequency stimulation of the dental pulp determined cardiovascular [systolic arterial pressure (SAP): -21.7 +/- 4.6 and 10.8 +/- 4.7 mmHg, respectively] and respiratory [pulmonary ventilation (VE): 145.1 +/- 44.9 and 109.3 +/- 28.4 ml/min, respectively] reflex responses similar to those observed during experimentally induced dynamic (SAP: -17.5 +/- 4.2 mmHg; VE: 228.0 +/- 58.5 ml/min) and static (SAP: 5.8 +/- 1.5 mmHg; VE: 148.0 +/- 75.3 ml/min) muscular contractions. The elimination of digastric muscular contraction (JOR) obtained by muscular paralysis did away with the cardiovascular changes induced by dental pulp stimulation, the effectiveness of which in stimulating dental pulp receptors has been shown by recording trigeminal-evoked potentials in six additional rabbits. The main conclusion was that, in deeply anesthetized animals, an algesic stimulus is unable to determine cardiorespiratory effects, which appear to be exclusively linked to the stimulation of ergoreceptors induced by muscular contraction.

TRPV1 SUMOylation regulates nociceptive signaling in models of inflammatory pain.

PubMed

Wang, Yan; Gao, Yingwei; Tian, Quan; Deng, Qi; Wang, Yangbo; Zhou, Tian; Liu, Qiang; Mei, Kaidi; Wang, Yingping; Liu, Huiqing; Ma, Ruining; Ding, Yuqiang; Rong, Weifang; Cheng, Jinke; Yao, Jing; Xu, Tian-Le; Zhu, Michael X; Li, Yong

2018-04-18

Although TRPV1 channels represent a key player of noxious heat sensation, the precise mechanisms for thermal hyperalgesia remain unknown. We report here that conditional knockout of deSUMOylation enzyme, SENP1, in mouse dorsal root ganglion (DRG) neurons exacerbated thermal hyperalgesia in both carrageenan- and Complete Freund's adjuvant-induced inflammation models. TRPV1 is SUMOylated at a C-terminal Lys residue (K822), which specifically enhances the channel sensitivity to stimulation by heat, but not capsaicin, protons or voltage. TRPV1 SUMOylation is decreased by SENP1 but upregulated upon peripheral inflammation. More importantly, the reduced ability of TRPV1 knockout mice to develop inflammatory thermal hyperalgesia was rescued by viral infection of lumbar 3/4 DRG neurons of wild-type TRPV1, but not its SUMOylation-deficient mutant, K822R. These data suggest that TRPV1 SUMOylation is essential for the development of inflammatory thermal hyperalgesia, through a mechanism that involves sensitization of the channel response specifically to thermal stimulation.

Activation of planarian TRPA1 by reactive oxygen species reveals a conserved mechanism for nociception

PubMed Central

Arenas, Oscar M.; Zaharieva, Emanuela E.; Para, Alessia; Vásquez-Doorman, Constanza; Petersen, Christian P.; Gallio, Marco

2017-01-01

All animals must detect noxious stimuli to initiate protective behavior, but the evolutionary origin of nociceptive systems is not well understood. Here, we show that noxious heat and irritant chemicals elicit robust escape behaviors in the planarian Schmidtea mediterranea, and that the conserved ion channel TRPA1 is required for these responses. TRPA1 mutant flies (Drosophila) are also defective in noxious heat responses. Unexpectedly, we find that either planarian or human TRPA1 can restore noxious heat avoidance to TRPA1 mutant Drosophila, even though neither is directly activated by heat. Instead, our data suggest that TRPA1 activation is mediated by H2O2/Reactive Oxygen Species, early markers of tissue damage rapidly produced as a result of heat exposure. Together, our data reveal a core function for TRPA1 in noxious heat transduction, demonstrate its conservation from planarians to humans, and imply that animal nociceptive systems may share a common ancestry, tracing back to a progenitor that lived more than 500 million years ago. PMID:29184198

Noxious heat and scratching decrease histamine-induced itch and skin blood flow.

PubMed

Yosipovitch, Gil; Fast, Katharine; Bernhard, Jeffrey D

2005-12-01

The aim of this study was to assess the effect of thermal stimuli or distal scratching on skin blood flow and histamine-induced itch in healthy volunteers. Twenty-one healthy volunteers participated in the study. Baseline measurements of skin blood flow were obtained on the flexor aspect of the forearm. These measurements were compared with skin blood flow after various stimuli: heating the skin, cooling the skin, noxious cold 2 degrees C, noxious heat 49 degrees C, and scratching via a brush with controlled pressure. Afterwards histamine iontophoresis was performed and skin blood flow and itch intensity were measured immediately after the above-mentioned stimuli. Scratching reduced mean histamine-induced skin blood flow and itch intensity. Noxious heat pain increased basal skin blood flow but reduced histamine-induced maximal skin blood flow and itch intensity. Cold pain and cooling reduced itch intensity, but neither affected histamine-induced skin blood flow. Sub-noxious warming the skin did not affect the skin blood flow or itch intensity. These findings suggest that heat pain and scratching may inhibit itch through a neurogenic mechanism that also affects skin blood flow.

Dynamic Detection of Spinal Cord Position During Postural Changes Using Near-Infrared Reflectometry.

PubMed

Wolf, Erich W

2015-08-01

Motion of the spinal cord relative to a spinal cord stimulator epidural electrode array can cause suboptimal stimulation: either noxious, inefficient, or insufficient. Adaptive stimulation attempts to mitigate these effects by modulating stimulation parameters in a position-dependent fashion. Near-infrared (NIR) reflectometry is demonstrated to provide real-time direct measurement of spinal cord position at the site of stimulation, which can facilitate closed-loop adaptive stimulation during static and dynamic motion states. A miniature sensor array consisting of an NIR light emitting diode flanked by phototransistors potted in epoxy was placed in the dorsal epidural space of a human cadaver at the T8 level via laminotomy. Turgor of the subarachnoid space was maintained by intrathecal infusion of saline. NIR reflectance was measured as the cadaver was rotated about its longitudinal axis on a gantry. NIR reflectance was correlated with gantry position and velocity. NIR reflectometry suggests gravitational force is the primary determinant of cord position in static, ordinal positions. Under dynamic motion conditions, there was statistically significant cross-correlation between reflectometry data and the tangential velocity squared, suggesting that centripetal force was the primary determinant of cord position as the gantry was rotated. Reflectometry data strongly correlated with a simple geometric model of anticipated spinal cord precession within the spinal canal. Spinal cord position during dynamic motion has been shown to differ from static predictions due to additional influences such as centripetal force. These findings underscore limitations in extrapolating spinal cord position from surrogates such as body position or body acceleration at sites remote from the stimulating electrodes. NIR reflectometry offers a real-time direct measure of spinal cord position in both static and dynamic motion states, which may facilitate closed-loop adaptive stimulation applications. © 2015 International Neuromodulation Society.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hutchinson, Kenneth

Vegetation Management on sections of the McNary-Ross, McNary-Horse Heaven, Horse Heaven-Harvarlum, Harvarlum-Big Eddy, and Hanford-John Day Transmission lines. The treatment areas are identified in Step 1 of the Planning Steps shown below. The work will involve the control of noxious weeds in the subject rights-of-ways (ROWs). BPA, in cooperation with the various County Noxious Weed Control Boards and associated landowners, will provide resources to assist landowners in controlling noxious weeds on the subject ROWs. The Weed Board will perform all activities on behalf of BPA.

The effects of the TRPV1 receptor antagonist SB-705498 on trigeminovascular sensitisation and neurotransmission.

PubMed

Lambert, G A; Davis, J B; Appleby, J M; Chizh, B A; Hoskin, K L; Zagami, A S

2009-10-01

This report examines the effect of the transient receptor potential vanilloid 1 receptor antagonist SB-705498 on neurotransmission and inflammation-induced sensitisation in the trigeminovascular sensory system. A single-neuron electrophysiological animal model for neurovascular head pain was used to evaluate dural and facial noxious inputs and the effects of SB-705498 administered by intravenous (i.v.) injection. Electrical and mechanical stimulation of the dura mater and the facial skin activated second-order neurons in the trigeminal nucleus caudalis of cats, with A-delta latencies. Intravenous injection of SB-705498 (2 mg kg(-1)) produced a slowly developing and long-lasting suppression of responses to dural and skin stimulation. Maximum suppression occurred by 1 h and reached 41% for dura and 24% for skin. Intravenous injection of drug vehicle did not produce significant suppression of responses to stimulation of either dura or skin. Intravenous injection of SB-705498 produced a brief and small rise in blood pressure and dural blood flow, which both returned to normal before suppression of the responses to stimulation became manifest. Application of "inflammatory soup" to the dura mater produced a pronounced increase in dural blood flow and induced a slowly developing increase in the responses of neurons to both electrical and mechanical stimulations of their facial and dural receptive fields. This sensitisation reached a maximum in 60-90 min, at which time responses had risen to approximately twice that of control levels seen before the application of inflammatory soup. Intravenous injection of SB-705498 subsequent to the development of sensitisation produced a slowly developing, prolonged and statistically significant reversal of the sensitisation induced by inflammatory soup. Maximum reversal of sensitisation to electrical stimulation occurred by 150-180 min, when responses had fallen to, or below, control levels. At 70-85 min following injection of SB-705498, the responses of previously sensitised neurons to mechanical stimulation of dura mater and facial receptive field had also returned to near control levels. SB-705498 was also able to prevent the development of sensitisation; application of inflammatory soup to the dura mater induced a slowly developing increase in the responses of neurons to electrical stimulation of the skin and dura mater in cats which had received an i.v. injection of vehicle for SB-705498 but not in cats which had received the active drug. Blood levels of SB-705498 were maximal immediately following i.v. injection and declined over the following 2 h. Significant brain levels of SB-705498 were maintained for up to 9 h. These results suggest that SB-705498 may be an effective suppressant and reversal agent of the sensitisation to sensory input which follows inflammation in the trigeminovascular sensory distribution but may not be particularly useful in blocking primary pain processes such as migraine headache. SB-705498 could thus potentially prevent, modify or reverse the cutaneous trigeminal allodynia seen in certain migraine conditions, especially "transformed" migraine.

Noxious Weeds in the US and Canada

Science.gov Websites

projects • Comments Agricultural Research Service United States Department of Agriculture Noxious weeds in supported by the USDA Agricultural Research Service. Principal investigators: Dr. Kerri Skinner, University

Antinociceptive effects of long-acting nalbuphine decanoate after intramuscular administration to Hispaniolan Amazon parrots (Amazona ventralis).

PubMed

Sanchez-Migallon Guzman, David; Braun, Jana M; Steagall, Paulo V M; Keuler, Nicholas S; Heath, Timothy D; Krugner-Higby, Lisa A; Brown, Carolyn S; Paul-Murphy, Joanne R

2013-02-01

To evaluate the thermal antinociceptive effects and duration of action of nalbuphine decanoate after IM administration to Hispaniolan Amazon parrots (Amazona ventralis). 10 healthy adult Hispaniolan Amazon parrots of unknown sex. Nalbuphine decanoate (33.7 mg/kg) or saline (0.9% NaCl) solution was administered IM in a randomized complete crossover experimental design (periods 1 and 2). Foot withdrawal threshold to a noxious thermal stimulus was used to evaluate responses. Baseline thermal withdrawal threshold was recorded 1 hour before drug or saline solution administration, and thermal foot withdrawal threshold measurements were repeated 1, 2, 3, 6, 12, 24, 48, and 72 hours after drug administration. Nalbuphine decanoate administered IM at a dose of 33.7 mg/kg significantly increased thermal foot withdrawal threshold, compared with results after administration of saline solution during period 2, and also caused a significant change in withdrawal threshold for up to 12 hours, compared with baseline values. Nalbuphine decanoate increased the foot withdrawal threshold to a noxious thermal stimulus in Hispaniolan Amazon parrots for up to 12 hours and provided a longer duration of action than has been reported for other nalbuphine formulations. Further studies with other types of nociceptive stimulation, dosages, and dosing intervals as well as clinical trials are needed to fully evaluate the analgesic effects of nalbuphine decanoate in psittacine birds.

Allelopathic Activity and Chemical Composition of Rhynchosia minima (L.) DC. Essential Oil from Egypt.

PubMed

Abd El-Gawad, Ahmed M; El-Amier, Yasser A; Bonanomi, Giuliano

2018-01-01

Aromatic plants attract the attention of many researchers worldwide due to their worthy applications in agriculture, human prosperity, and the environment. Essential oil (EO) could be exploited as effective alternatives to synthetic compounds as it has several biological activities including allelopathy. The EO from the aerial parts of Rhynchosia minima was extracted by hydrodistillation and investigated by gas chromatography/mass spectrometry (GC/MS). Different concentrations (50, 100, 150 and 200 μL L -1 ) of the EO were prepared for investigation of their allelopathic potential on two weeds; Dactyloctenium aegyptium and Rumex dentatus. Twenty-eight compounds, mainly sesquiterpenes (69.13%) were determined. The major compounds are α-eudesmol, 2-allyl-5-tert-butylhydroquinone, caryophyllene oxide, trans-caryophyllene, and τ-cadinol. The EO from the R. minima showed a significant inhibition of D. aegyptium and R. dentatus germination, while the seedling growth was stimulated. Therefore, it is not recommended to treat these noxious weeds with the EO of R. minima before the germination. In contrast, the apparent stimulatory effect on the seedling growth offers further studies to use the EO of R. minima to enhance the fitness of different economic crops. However, characterization of green bio-herbicides such as EO (allelochemicals) from wild plants raises a new opportunity for the incorporation of new technology of bio-control against the noxious weeds. © 2018 Wiley-VHCA AG, Zurich, Switzerland.

Frontal Lobe Hemodynamic Responses to Painful Stimulation: A Potential Brain Marker of Nociception

PubMed Central

Steele, Sarah C.; Peng, Ke; Boas, David A.; Becerra, Lino; Borsook, David

2016-01-01

The purpose of this study was to use functional near-infrared spectroscopy (fNIRS) to examine patterns of both activation and deactivation that occur in the frontal lobe in response to noxious stimuli. The frontal lobe was selected because it has been shown to be activated by noxious stimuli in functional magnetic resonance imaging studies. The brain region is located behind the forehead which is devoid of hair, providing a relative ease of placement for fNIRS probes on this area of the head. Based on functional magnetic resonance imaging studies showing blood-oxygenation-level dependent changes in the frontal lobes, we evaluated functional near-infrared spectroscopy measures in response to two levels of electrical pain in awake, healthy human subjects (n = 10; male = 10). Each subject underwent two recording sessions separated by a 30-minute resting period. Data collected from 7 subjects were analyzed, containing a total of 38/36 low/high intensity pain stimuli for the first recording session and 27/31 pain stimuli for the second session. Our results show that there is a robust and significant deactivation in sections of the frontal cortices. Further development and definition of the specificity and sensitivity of the approach may provide an objective measure of nociceptive activity in the brain that can be easily applied in the surgical setting. PMID:27806119

Frontal Lobe Hemodynamic Responses to Painful Stimulation: A Potential Brain Marker of Nociception.

PubMed

Aasted, Christopher M; Yücel, Meryem A; Steele, Sarah C; Peng, Ke; Boas, David A; Becerra, Lino; Borsook, David

2016-01-01

The purpose of this study was to use functional near-infrared spectroscopy (fNIRS) to examine patterns of both activation and deactivation that occur in the frontal lobe in response to noxious stimuli. The frontal lobe was selected because it has been shown to be activated by noxious stimuli in functional magnetic resonance imaging studies. The brain region is located behind the forehead which is devoid of hair, providing a relative ease of placement for fNIRS probes on this area of the head. Based on functional magnetic resonance imaging studies showing blood-oxygenation-level dependent changes in the frontal lobes, we evaluated functional near-infrared spectroscopy measures in response to two levels of electrical pain in awake, healthy human subjects (n = 10; male = 10). Each subject underwent two recording sessions separated by a 30-minute resting period. Data collected from 7 subjects were analyzed, containing a total of 38/36 low/high intensity pain stimuli for the first recording session and 27/31 pain stimuli for the second session. Our results show that there is a robust and significant deactivation in sections of the frontal cortices. Further development and definition of the specificity and sensitivity of the approach may provide an objective measure of nociceptive activity in the brain that can be easily applied in the surgical setting.

C. elegans multi-dendritic sensory neurons: morphology and function

PubMed Central

Albeg, Adi; Smith, Cody; Chatzigeorgiou, Marios; Feitelson, Dror G.; Hall, David H.; Schafer, William R.; Miller, David M.; Treinin, Millet

2010-01-01

PVD and FLP sensory neurons envelope the body of the C. elegans adult with a highly branched network of thin sensory processes. Both PVD and FLP neurons are mechanosensors. PVD is known to mediate the response to high threshold mechanical stimuli. Thus PVD and FLP neurons are similar in both morphology and function to mammalian nociceptors. To better understand the function of these neurons we generated strains lacking them. Behavioral analysis shows that PVD and FLP regulate movement under normal growth conditions, as animals lacking these neurons demonstrate higher dwelling behavior. In addition, PVD—whose thin branches project across the body-wall muscles—may have a role in proprioception, as ablation of PVD leads to defective posture. Moreover, movement-dependent calcium transients are seen in PVD, a response that requires MEC-10, a subunit of the mechanosensory DEG/ENaC channel that is also required for maintaining wild-type posture. Hence, PVD senses both noxious and innocuous signals to regulate C. elegans behavior, and thus combines the functions of multiple mammalian somatosensory neurons. Finally, strong mechanical stimulation leads to inhibition of egg-laying, and this response also depends on PVD and FLP neurons. Based on all these results we suggest that noxious signals perceived by PVD and FLP promote an escape behavior consisting of increased speed, reduced pauses and reversals, and inhibition of egg-laying. PMID:20971193

CB1 receptor mediated analgesia from the Nucleus Reticularis Gigantocellularis pars alpha is activated in an animal model of neuropathic pain.

PubMed

Monhemius, R; Azami, J; Green, D L; Roberts, M H

2001-07-20

Cannabinoids are known to suppress responses to noxious stimulation in animals and man. Recent research has suggested a role for endogenous cannabinoids in the descending inhibition of dorsal horn cells via a supraspinal site of action. We have recently demonstrated [J. Physiol. 506(2) (1998) 459] that the nucleus reticularis gigantocellularis pars alpha (GiA) is a major source of such descending modulation, and importantly, that this system is activated in response to noxious stimulation. We have therefore investigated the role of CB1 receptor activation in mediating the antinociceptive effects of activation of GiA in models of acute and chronic pain. Microinjections (0.5 microl 60% DMSO) of either WIN 55,212-2 (5 microg, selective CB1 agonist), SR141716A (50 microg, competitive CB1 antagonist), both compounds together, or vehicle alone into GiA were performed prior to these tests in a randomised, blind manner. In control animals, WIN 55,212-2 markedly increased withdrawal latencies in the tail flick test and reduced responses to subcutaneous formalin. These effects were blocked by co-administration of SR141716A. These data suggest that activation of cannabinoid CB1 receptor subtypes in GiA leads to behavioural analgesia. In animals with partial sciatic nerve ligation, microinjection of drugs and injection of formalin were performed contralaterally to the site of ligation. Partial sciatic nerve ligation significantly reduced behavioural responses to contralaterally applied formalin. Microinjection of SR141716A to GiA reversed this inhibition of responses to formalin in animals with partial sciatic nerve ligation. These data provide evidence that endogenous CB1 receptor ligands are involved in GiA mediated antinociception, and that this system is important for the modulation of nociceptive transmission in an animal model of chronic neuropathic pain.

Serum C-reactive protein levels predict regional brain responses to noxious cold stimulation of the hand in chronic whiplash associated disorders.

PubMed

Sterling, Michele; Head, Jessica; Cabot, Peter J; Farrell, Michael

2016-04-01

Whiplash Associated Disorders (WAD) are a costly health burden. The condition is characterised by sensory disturbances such as widespread hyperalgesia likely indicative of central hyperexcitability. Recently elevated levels of pro-inflammatory biomarkers have also found in acute and chronic WAD. The aim of this cross-sectional study was to investigate the relationship between inflammatory biomarkers and pain processing in people with persistent whiplash associated disorders (WAD). Twenty one participants with chronic whiplash (>3 months) were recruited. Venous blood samples were collected and assays performed for C-reactive protein (CRP) and TNF-α. Blood oxygen level-dependent (BOLD) contrast images of the brain were acquired with a Siemens 1.5T MRI scanner during repeated 24s stimulus blocks of innocuous or painful stimuli (thumbnail pressure and cold stimulation of dorsum of hand) separated by 36s inter-stimulus intervals. Stimulus intensities used during scanning were at the level of participants' thresholds for moderate pain. Parameter estimates representing BOLD signal increases during painful events from each participant were tested for associations with inflammatory biomarkers. Clinically relevant levels of CRP and TNF-α were found in 33% and 38% of participants. Levels of CRP showed a positive correlation with levels of cold pain activation in brain regions including the anterior insula, posterior parietal cortex, caudate and thalamus (p corrected <0.05). Levels of TNF-α were not related to activation levels during either noxious pressure or cold. Pressure pain activations also did not show a relationship with CRP levels. Shared variance between inflammation and increased levels of regional pain-related activation in people with persistent whiplash symptoms is apparent for cold, but not pressure stimuli. The results highlight cold pain processing as an important aspect of whiplash chronicity, although the implications of this modality-specific effect are not readily apparent. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

Sympathetic activation of cat spinal neurons responsive to noxious stimulation of deep tissues in the low back.

PubMed

Gillette, R G; Kramis, R C; Roberts, W J

1994-01-01

Prior findings from diverse studies have indicated that activity in axons located in the lumbar sympathetic chains contributes to the activation of spinal pain pathways and to low back pain; these studies have utilized sympathetic blocks in patients, electrical stimulation of the chain in conscious humans, and neuroanatomical mapping of afferent fiber projections. In the present study, dorsal horn neurons receiving nociceptor input from lumbar paraspinal tissues were tested for activation by electrical stimulation of the lumbar sympathetic chain in anesthetized cats. Of 83 neurons tested, 70% were responsive to sympathetic trunk stimulation. Excitatory responses, observed in both nociceptive specific and wide-dynamic-range neurons, were differentiable into two classes: non-entrained and entrained responses. Non-entrained responses were attenuated or blocked by systemic administration of the alpha-adrenergic antagonist phentolamine and are thought to result from sympathetic efferent activation of primary afferents in the units' receptive fields. Entrained responses were unaffected by phentolamine and are thought to result from electrical activation of somatic and/or visceral afferent fibers ascending through the sympathetic trunk into the dorsal horn. These findings from nocireceptive neurons serving lumbar paraspinal tissues suggest that low back pain may be exacerbated by activity in both efferent and afferent fibers located in the lumbar sympathetic chain, the efferent actions being mediated indirectly through sympathetic-sensory interactions in somatic and/or visceral tissues.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hermeston, Mark W.

Franklin County noxious weed management along BPA rights-of-ways, transmission structures, roads, and switches listed in Attachment 1. Attachment 1 identifies the ROW, ROW width, and ROW length of the proposed action. Includes all BPA 115kV, 230kV, and 500 kV ROWs in Franklin County, Washington. BPA proposes to clear noxious and/or unwanted low-growing vegetation in all BPA ROWs in Franklin County, Washington. In a cooperative effort, BPA, through landowners and the Franklin County Weed Control Board, plan to eradicate noxious plants and other unwanted, low-growing vegetation within the ROW width including all structures and access roads. BPA’s overall goal is tomore » eradicate all noxious and unwanted vegetation through chemical treatment and reseeding. Selective and nonselective chemical treatment using spot, local and broadcast methods. All work will be executed in accordance with the National Electrical Safety Code and BPA standards. Work is to begin in March 2002.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hermeston, Mark W.

Benton County noxious weed management along BPA rights-of-ways, transmission structures, roads, and switches listed in Attachment 1. Attachment 1 identifies the ROW, ROW width, and ROW length of the proposed action. Includes all BPA 115kV, 230kV, 345kV and 500 kV ROWs in Benton County, Washington. BPA proposes to clear noxious and/or unwanted low-growing vegetation in all BPA ROWs in Benton County, Washington. In a cooperative effort, BPA, through landowners and the Benton County Weed Control Board, plan to eradicate noxious plants and other unwanted, low-growing vegetation within the ROW width including all structures and access roads. BPA’s overall goal ismore » to eradicate all noxious and unwanted vegetation through chemical treatment and reseeding. Selective and nonselective chemical treatment using spot, local and broadcast methods. All work will be executed in accordance with the National Electrical Safety Code and BPA standards. Work is to begin in March 2002.« less

Inflammatory Pain Reduces C Fiber Activity-Dependent Slowing in a Sex-Dependent Manner, Amplifying Nociceptive Input to the Spinal Cord

PubMed Central

McCormick, Barry; Lukito, Veny; Wilson, Kirsten L.

2017-01-01

C fibers display activity-dependent slowing (ADS), whereby repetitive stimulation (≥1 Hz) results in a progressive slowing of action potential conduction velocity, which manifests as a progressive increase in response latency. However, the impact of ADS on spinal pain processing has not been explored, nor whether ADS is altered in inflammatory pain conditions. To investigate, compound action potentials were made, from dorsal roots isolated from rats with or without complete Freund's adjuvant (CFA) hindpaw inflammation, in response to electrical stimulus trains. CFA inflammation significantly reduced C fiber ADS at 1 and 2 Hz stimulation rates. Whole-cell patch-clamp recordings in the spinal cord slice preparation with attached dorsal roots also demonstrated that CFA inflammation reduced ADS in the monosynaptic C fiber input to lamina I neurokinin 1 receptor-expressing neurons (1–10 Hz stimulus trains) without altering the incidence of synaptic response failures. When analyzed by sex, it was revealed that females display a more pronounced ADS that is reduced by CFA inflammation to a level comparable with males. Cumulative ventral root potentials evoked by long and short dorsal root stimulation lengths, to maximize and minimize the impact of ADS, respectively, demonstrated that reducing ADS facilitates spinal summation, and this was also sex dependent. This finding correlated with the behavioral observation of increased noxious thermal thresholds and enhanced inflammatory thermal hypersensitivity in females. We propose that sex/inflammation-dependent regulation of C fiber ADS can, by controlling the temporal relay of nociceptive inputs, influence the spinal summation of nociceptive signals contributing to sex/inflammation-dependent differences in pain sensitivity. SIGNIFICANCE STATEMENT The intensity of a noxious stimulus is encoded by the frequency of action potentials relayed by nociceptive C fibers to the spinal cord. C fibers conduct successive action potentials at progressively slower speeds, but the impact of this activity-dependent slowing (ADS) is unknown. Here we demonstrate that ADS is more prevalent in females than males and is reduced in an inflammatory pain model in females only. We also demonstrate a progressive delay of C fiber monosynaptic transmission to the spinal cord that is similarly sex and inflammation dependent. Experimentally manipulating ADS strongly influences spinal summation consistent with sex differences in behavioral pain thresholds. This suggests that ADS provides a peripheral mechanism that can regulate spinal nociceptive processing and pain sensation. PMID:28576935

Brain mediators of the effects of noxious heat on pain

PubMed Central

Atlas, Lauren Y.; Lindquist, Martin A.; Bolger, Niall; Wager, Tor D.

2014-01-01

Recent human neuroimaging studies have investigated the neural correlates of either noxious stimulus intensity or reported pain. While useful, analyzing brain relationships with stimulus intensity and behavior separately does not address how sensation and pain are linked in the central nervous system. In this paper, we used multi-level mediation analysis to identify brain mediators of pain—regions whose trial-by-trial responses to heat explained variability in the relationship between noxious stimulus intensity (across four levels) and pain. This approach has the potential to identify multiple circuits with complementary roles in pain genesis. Brain mediators of noxious heat effects on pain included targets of ascending nociceptive pathways (anterior cingulate, insula, SII, and medial thalamus) and also prefrontal and subcortical regions not associated with nociceptive pathways per se. Cluster analysis revealed that mediators were grouped into several distinct functional networks, including: a) somatosensory, paralimbic, and striatal-cerebellar networks that increased with stimulus intensity; and b) two networks co-localized with ‘default mode’ regions in which stimulus intensity-related decreases mediated increased pain. We also identified ‘thermosensory’ regions that responded to increasing noxious heat but did not predict pain reports. Finally, several regions did not respond to noxious input, but their activity predicted pain; these included ventromedial prefrontal cortex, dorsolateral prefrontal cortex, cerebellar regions, and supplementary motor cortices. These regions likely underlie both nociceptive and non-nociceptive processes that contribute to pain, such as attention and decision-making processes. Overall, these results elucidate how multiple distinct brain systems jointly contribute to the central generation of pain. PMID:24845572

78 FR 37777 - Notice of Request for Extension of Approval of an Information Collection; Cooperative...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-24

... pests, noxious weeds, and biological control agents, which may be used to control plant pests or noxious... detect, in collaboration with the National Plant Diagnostic Network and the U.S. Department of...

7 CFR 201.52 - Noxious-weed seeds.

Code of Federal Regulations, 2013 CFR

2013-01-01

... the bulk examined for noxious-weed seeds need not be noted: 1/2-gram purity working sample, 16 or more seeds; 1-gram purity working sample, 23 or more seeds; 2-gram purity working sample or larger, 30 or...

33 CFR 151.30 - Applicability.

Code of Federal Regulations, 2014 CFR

2014-07-01

....30 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER... Pertains to Pollution from Ships Noxious Liquid Substance Pollution § 151.30 Applicability. (a) Except as...

33 CFR 151.30 - Applicability.

Code of Federal Regulations, 2012 CFR

2012-07-01

....30 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER... Pertains to Pollution from Ships Noxious Liquid Substance Pollution § 151.30 Applicability. (a) Except as...

33 CFR 151.30 - Applicability.

Code of Federal Regulations, 2011 CFR

2011-07-01

....30 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER... Pertains to Pollution from Ships Noxious Liquid Substance Pollution § 151.30 Applicability. (a) Except as...

33 CFR 151.30 - Applicability.

Code of Federal Regulations, 2010 CFR

2010-07-01

....30 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER... Pertains to Pollution from Ships Noxious Liquid Substance Pollution § 151.30 Applicability. (a) Except as...

33 CFR 151.15 - Reporting requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND... Treaty as it Pertains to Pollution from Ships Oil Pollution § 151.15 Reporting requirements. (a) The... involves— (1) A discharge of oil, hazardous substances, marine pollutants, or noxious liquid substances...

33 CFR 151.15 - Reporting requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

...) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND... Treaty as it Pertains to Pollution from Ships Oil Pollution § 151.15 Reporting requirements. (a) The... involves— (1) A discharge of oil, hazardous substances, marine pollutants, or noxious liquid substances...

33 CFR 151.15 - Reporting requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND... Treaty as it Pertains to Pollution from Ships Oil Pollution § 151.15 Reporting requirements. (a) The... involves— (1) A discharge of oil, hazardous substances, marine pollutants, or noxious liquid substances...

75 FR 23220 - Notice of Revision and Request for Extension of Approval of an Information Collection...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-03

... data on plant pests, noxious weeds, and biological control agents, which may be used to control plant..., eradicate, suppress, control, prevent, or retard the spread of plant pests and noxious weeds that are new to...

Effects of reference analgesics and psychoactive drugs on the noxious heat threshold of mice measured by an increasing-temperature water bath.

PubMed

Boros, Melinda; Benkó, Rita; Bölcskei, Kata; Szolcsányi, János; Barthó, Loránd; Pethő, Gábor

2013-12-01

The study aimed at validating an increasing-temperature water bath suitable for determining the noxious heat threshold for use in mice. The noxious heat threshold was determined by immersing the tail of the gently held awake mouse into a water container whose temperature was near-linearly increased at a rate of 24°C/min. until the animal withdrew its tail, that is, heating attained the noxious threshold. The effects of standard analgesic, neuroleptic and anxiolytic drugs were investigated in a parallel way on both the noxious heat threshold and the psychomotor activity assessed by the open field test. Morphine, diclofenac and metamizol (dipyrone) elevated the heat threshold of mice with minimum effective doses of 6, 30 and 1000 mg/kg i.p., respectively. These doses of morphine and diclofenac failed to induce any remarkable effect on psychomotor activity in the open field test while that of metamizol exerted a profound inhibition. The anxiolytic diazepam and the neuroleptic droperidol at doses evoking a mild and moderate, respectively, psychomotor inhibition failed to alter the heat threshold. Combination of a subliminal dose of morphine (regarding both antinociceptive and psychomotor inhibitory action) with diclofenac, metamizol, diazepam or droperidol at doses also subliminal regarding the thermal antinociceptive effect elevated the noxious heat threshold without major additional effects in the open field test. It is concluded that the increasing-temperature water bath is suitable for studying the thermal antinociceptive effects of morphine and diclofenac as well as the morphine-sparing action of diclofenac, metamizol, droperidol and diazepam. Behavioural testing is recommended when testing analgesics. © 2013 Nordic Pharmacological Society. Published by John Wiley & Sons Ltd.

Assessment of Responsiveness to Everyday Non-Noxious Stimuli in Pain-Free Migraineurs With Versus Without Aura.

PubMed

Granovsky, Yelena; Shor, Merav; Shifrin, Alla; Sprecher, Elliot; Yarnitsky, David; Bar-Shalita, Tami

2018-03-27

Migraineurs with aura (MWA) express higher interictal response to non-noxious and noxious experimental sensory stimuli compared with migraineurs without aura (MWoA), but whether these differences also prevail in response to everyday non-noxious stimuli is not yet explored. This is a cross-sectional study testing 53 female migraineurs (30 MWA; 23 MWoA) who underwent a wide battery of noxious psychophysical testing at a pain-free phase, and completed a Sensory Responsiveness Questionnaire and pain-related psychological questionnaires. The MWA group showed higher questionnaire-based sensory over-responsiveness (P = .030), higher magnitude of pain temporal summation (P = .031) as well as higher monthly attack frequency (P = .027) compared with the MWoA group. Overall, 45% of migraineurs described abnormal sensory (hyper- or hypo-) responsiveness; its incidence was higher among MWA (19 of 30, 63%) versus MWoA (6 of 23, 27%, P = .012), with an odds ratio of 3.58 for MWA. Sensory responsiveness scores were positively correlated with attack frequency (r = .361, P = .008) and temporal summation magnitude (r = .390, P = .004), both regardless of migraine type. MWA express higher everyday sensory responsiveness than MWoA, in line with higher response to experimental noxious stimuli. Abnormal scores of sensory responsiveness characterize people with sensory modulation dysfunction, suggesting possible underlying mechanisms overlap, and possibly high incidence of both clinical entities. This article presents findings distinguishing MWA, showing enhanced pain amplification, monthly attack frequency, and over-responsiveness to everyday sensations, compared with MWoA. Further, migraine is characterized by a high incidence of abnormal responsiveness to everyday sensation, specifically sensory over-responsiveness, that was also found related to pain. Copyright © 2018 The American Pain Society. Published by Elsevier Inc. All rights reserved.

Brain mediators of the effects of noxious heat on pain.

PubMed

Atlas, Lauren Y; Lindquist, Martin A; Bolger, Niall; Wager, Tor D

2014-08-01

Recent human neuroimaging studies have investigated the neural correlates of either noxious stimulus intensity or reported pain. Although useful, analyzing brain relationships with stimulus intensity and behavior separately does not address how sensation and pain are linked in the central nervous system. In this study, we used multi-level mediation analysis to identify brain mediators of pain--regions in which trial-by-trial responses to heat explained variability in the relationship between noxious stimulus intensity (across 4 levels) and pain. This approach has the potential to identify multiple circuits with complementary roles in pain genesis. Brain mediators of noxious heat effects on pain included targets of ascending nociceptive pathways (anterior cingulate, insula, SII, and medial thalamus) and also prefrontal and subcortical regions not associated with nociceptive pathways per se. Cluster analysis revealed that mediators were grouped into several distinct functional networks, including the following: somatosensory, paralimbic, and striatal-cerebellar networks that increased with stimulus intensity; and 2 networks co-localized with "default mode" regions in which stimulus intensity-related decreases mediated increased pain. We also identified "thermosensory" regions that responded to increasing noxious heat but did not predict pain reports. Finally, several regions did not respond to noxious input, but their activity predicted pain; these included ventromedial prefrontal cortex, dorsolateral prefrontal cortex, cerebellar regions, and supplementary motor cortices. These regions likely underlie both nociceptive and non-nociceptive processes that contribute to pain, such as attention and decision-making processes. Overall, these results elucidate how multiple distinct brain systems jointly contribute to the central generation of pain. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Noxious heat threshold temperature and pronociceptive effects of allyl isothiocyanate (mustard oil) in TRPV1 or TRPA1 gene-deleted mice.

PubMed

Tékus, Valéria; Horváth, Ádám; Hajna, Zsófia; Borbély, Éva; Bölcskei, Kata; Boros, Melinda; Pintér, Erika; Helyes, Zsuzsanna; Pethő, Gábor; Szolcsányi, János

2016-06-01

To investigate the roles of TRPV1 and TRPA1 channels in baseline and allyl isothiocyanate (AITC)-evoked nociceptive responses by comparing wild-type and gene-deficient mice. In contrast to conventional methods of thermonociception measuring reflex latencies, we used our novel methods to determine the noxious heat threshold. It was revealed that the heat threshold of the tail measured by an increasing-temperature water bath is significantly higher in TRPV1(-/-), but not TRPA1(-/-), mice compared to respective wild-types. There was no difference between the noxious heat thresholds of the hind paw as measured by an increasing-temperature hot plate in TRPV1(-/-), TRPA1(-/-) and the corresponding wild-type mice. The withdrawal latency of the tail from 0°C water was prolonged in TRPA1(-/-), but not TRPV1(-/-), mice compared to respective wild-types. In wild-type animals, dipping the tail or paw into 1% AITC induced an 8-14°C drop of the noxious heat threshold (heat allodynia) of both the tail and paw, and 40-50% drop of the mechanonociceptive threshold (mechanical allodynia) of the paw measured by dynamic plantar esthesiometry. These AITC-evoked responses were diminished in TRPV1(-/-), but not TRPA1(-/-), mice. Tail withdrawal latency to 1% AITC was significantly prolonged in both gene-deleted strains. Different heat sensors determine the noxious heat threshold in distinct areas: a pivotal role for TRPV1 on the tail is contrasted with no involvement of either TRPV1 or TRPA1 on the hind paw. Noxious heat threshold measurement appears appropriate for preclinical screening of TRP channel ligands as novel analgesics. Copyright © 2016 Elsevier Inc. All rights reserved.

Self-soothing behaviors with particular reference to oxytocin release induced by non-noxious sensory stimulation.

PubMed

Uvnäs-Moberg, Kerstin; Handlin, Linda; Petersson, Maria

2014-01-01

Oxytocin, a hypothalamic nonapeptide, is linked to increased levels of social interaction, well-being and anti-stress effects. The effects of oxytocin that is released by sensory stimulation during different kinds of interactive behaviors are often underestimated or even forgotten. In fact, many of the positive effects caused during interaction, such a wellbeing, stress reduction and even health promotion, are indeed linked to oxytocin released in response to activation of various types of sensory nerves. Oxytocin is released in response to activation of sensory nerves during labor, breastfeeding and sexual activity. In addition oxytocin is released in response to low intensity stimulation of the skin, e.g., in response to touch, stroking, warm temperature, etc. Consequently oxytocin is not only released during interaction between mothers and infants, but also during positive interaction between adults or between humans and animals. Finally oxytocin is also released in response to suckling and food intake. Oxytocin released in the brain in response to sensory stimulation as a consequence of these types of interactive behaviors, contributes to every day wellbeing and ability to handle stress. Food intake or sex may be used or even abused to achieve oxytocin-linked wellbeing and stress relief to compensate for lack of good relationships or when the levels of anxiety are high. The present review article will summarize the role played by oxytocin released by sensory (in particular somatosensory) stimulation, during various kinds of interactive behaviors. Also the fact that the anti-stress effects of oxytocin are particularly strong when oxytocin is released in response to "low intensity" stimulation of the skin will be highlighted.

Effects of combined electrical stimulation of the dorsal column and dorsal roots on wide-dynamic range neuronal activity in nerve-injured rats

PubMed Central

Yang, Fei; Zhang, Tong; Tiwari, Vinod; Shu, Bin; Zhang, Chen; Wang, Yun; Vera-Portocarrero, Louis P.; Raja, Srinivasa N.; Guan, Yun

2015-01-01

Objectives Electrical stimulation at the dorsal column (DC) and dorsal root (DR) may inhibit spinal wide-dynamic-range (WDR) neuronal activity in nerve-injured rats. The objective of this study was to determine if applying electrical conditioning stimulation (CS) at both sites provides additive or synergistic benefits. Materials and Methods By conducting in vivo extracellular recordings of WDR neurons in rats that had undergone L5 spinal nerve ligation, we tested whether combining 50 Hz CS at the two sites in either a concurrent (2.5 minutes) or alternate (5 minutes) pattern inhibits WDR neuronal activity better than CS at DC alone (5 minutes). The intensities of CS were determined by recording antidromic compound action potentials to graded stimulation at the DC and DR. We measured the current thresholds that resulted in the first detectable Aα/β waveform (Ab0) and the peak Aα/β waveform (Ab1) to select CS intensity at each site. The same number of electrical pulses and amount of current were delivered in different patterns to allow comparison. Results At a moderate intensity of 50%(Ab0+Ab1), different patterns of CS all attenuated the C-component of WDR neurons in response to graded intracutaneous electrical stimuli (0.1-10 mA, 2 ms), and inhibited windup in response to repetitive noxious stimuli (0.5 Hz). However, the inhibitory effects did not differ significantly between different patterns. At the lower intensity (Ab0), no CS inhibited WDR neurons. Conclusions These findings suggest that combined stimulation of DC and DR may not be superior to DC stimulation alone for inhibition of WDR neurons. PMID:26307526

Self-soothing behaviors with particular reference to oxytocin release induced by non-noxious sensory stimulation

PubMed Central

Uvnäs-Moberg, Kerstin; Handlin, Linda; Petersson, Maria

2015-01-01

Oxytocin, a hypothalamic nonapeptide, is linked to increased levels of social interaction, well-being and anti-stress effects. The effects of oxytocin that is released by sensory stimulation during different kinds of interactive behaviors are often underestimated or even forgotten. In fact, many of the positive effects caused during interaction, such a wellbeing, stress reduction and even health promotion, are indeed linked to oxytocin released in response to activation of various types of sensory nerves. Oxytocin is released in response to activation of sensory nerves during labor, breastfeeding and sexual activity. In addition oxytocin is released in response to low intensity stimulation of the skin, e.g., in response to touch, stroking, warm temperature, etc. Consequently oxytocin is not only released during interaction between mothers and infants, but also during positive interaction between adults or between humans and animals. Finally oxytocin is also released in response to suckling and food intake. Oxytocin released in the brain in response to sensory stimulation as a consequence of these types of interactive behaviors, contributes to every day wellbeing and ability to handle stress. Food intake or sex may be used or even abused to achieve oxytocin-linked wellbeing and stress relief to compensate for lack of good relationships or when the levels of anxiety are high. The present review article will summarize the role played by oxytocin released by sensory (in particular somatosensory) stimulation, during various kinds of interactive behaviors. Also the fact that the anti-stress effects of oxytocin are particularly strong when oxytocin is released in response to “low intensity” stimulation of the skin will be highlighted. PMID:25628581

An expectancy-value theory approach to the long-term modification of smoking behavior.

PubMed

Rogers, R W; Deckner, C W; Mewborn, C R

1978-04-01

Despite the research interest in modifying smoking behavior, therapeutic treatments that can produce long-term cessation have not been demonstrated rigorously. A follow-up study of two attitude change experiments (N = 173) examined the effects of a fear appeal, that is, increasing smokers' awareness and appreciation of the highly noxious consequences of smoking. Although this familiar type of information may be an integral component of many smoking treatment programs, its long-term suppressive effect has not been demonstrated in well-controlled experiments. The results disclosed that 3 months and also 1 year after treatment, a high-fear manipulation had increased significantly the percentage of smokers who were able to stop smoking completely.

7 CFR 301.1 - Purpose and scope.

Code of Federal Regulations, 2011 CFR

2011-01-01

... articles, means of conveyance, plants, plant products, biological control organisms, plant pests, or... biological control organism, plant pest, or noxious weed within the United States. The only exceptions to..., plant products, biological control organisms, plant pests, or noxious weeds that are in addition to the...

7 CFR 301.1 - Purpose and scope.

Code of Federal Regulations, 2010 CFR

2010-01-01

... articles, means of conveyance, plants, plant products, biological control organisms, plant pests, or... biological control organism, plant pest, or noxious weed within the United States. The only exceptions to..., plant products, biological control organisms, plant pests, or noxious weeds that are in addition to the...

33 CFR 151.39 - Operating requirements: Category D NLS.

Code of Federal Regulations, 2014 CFR

2014-07-01

... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...

33 CFR 151.39 - Operating requirements: Category D NLS.

Code of Federal Regulations, 2013 CFR

2013-07-01

... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...

33 CFR 151.43 - Control of discharge of NLS residues.

Code of Federal Regulations, 2012 CFR

2012-07-01

... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...

33 CFR 151.43 - Control of discharge of NLS residues.

Code of Federal Regulations, 2014 CFR

2014-07-01

... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...

33 CFR 151.43 - Control of discharge of NLS residues.

Code of Federal Regulations, 2013 CFR

2013-07-01

... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...

33 CFR 151.43 - Control of discharge of NLS residues.

Code of Federal Regulations, 2011 CFR

2011-07-01

... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...

33 CFR 151.39 - Operating requirements: Category D NLS.

Code of Federal Regulations, 2011 CFR

2011-07-01

... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...

33 CFR 151.39 - Operating requirements: Category D NLS.

Code of Federal Regulations, 2012 CFR

2012-07-01

... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...

33 CFR 151.39 - Operating requirements: Category D NLS.

Code of Federal Regulations, 2010 CFR

2010-07-01

... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...

33 CFR 151.43 - Control of discharge of NLS residues.

Code of Federal Regulations, 2010 CFR

2010-07-01

... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...

A leptin-regulated circuit controls glucose mobilization during noxious stimuli.

PubMed

Flak, Jonathan N; Arble, Deanna; Pan, Warren; Patterson, Christa; Lanigan, Thomas; Goforth, Paulette B; Sacksner, Jamie; Joosten, Maja; Morgan, Donald A; Allison, Margaret B; Hayes, John; Feldman, Eva; Seeley, Randy J; Olson, David P; Rahmouni, Kamal; Myers, Martin G

2017-08-01

Adipocytes secrete the hormone leptin to signal the sufficiency of energy stores. Reductions in circulating leptin concentrations reflect a negative energy balance, which augments sympathetic nervous system (SNS) activation in response to metabolically demanding emergencies. This process ensures adequate glucose mobilization despite low energy stores. We report that leptin receptor-expressing neurons (LepRb neurons) in the periaqueductal gray (PAG), the largest population of LepRb neurons in the brain stem, mediate this process. Application of noxious stimuli, which often signal the need to mobilize glucose to support an appropriate response, activated PAG LepRb neurons, which project to and activate parabrachial nucleus (PBN) neurons that control SNS activation and glucose mobilization. Furthermore, activating PAG LepRb neurons increased SNS activity and blood glucose concentrations, while ablating LepRb in PAG neurons augmented glucose mobilization in response to noxious stimuli. Thus, decreased leptin action on PAG LepRb neurons augments the autonomic response to noxious stimuli, ensuring sufficient glucose mobilization during periods of acute demand in the face of diminished energy stores.

[Occupational digestive diseases in chemical industry workers of West Siberia].

PubMed

Pomytkina, T E; Pershin, A N

2010-01-01

The high incidence of chronic digestive diseases is recorded in chemical industry workers exposed to the isolated action of noxious substances. The aim of the investigation was to make a hygienic assessment of the risk for occupational digestive diseases in chemical industry workers exposed to a combination of noxious drugs. The working conditions and the prevalence of digestive diseases were studied in 4120 workers engaged in chemical and auxiliary processes. Under the isolated action of noxious substances, the workers had an average of 35% increase in the incidence of digestive diseases than unexposed ones (p < 0.05). Under the combined action of hazardous substances, the incidence of digestive diseases was 1.7-fold greater (p < 0.05) than in the unexposed subjects and 1.2-fold greater in those under isolated action. The odd ratio and relative risk for digestive diseases in the workers exposed to a combination of noxious substances were 4.0-11.1 and 3.5-10.7 times higher, respectively (p < 0.05) than in the unexposed subjects.

Adaptive Cellular Stress Pathways as Therapeutic Targets of Dietary Phytochemicals: Focus on the Nervous System

PubMed Central

Jo, Dong-Gyu; Park, Daeui; Chung, Hae Young

2014-01-01

During the past 5 decades, it has been widely promulgated that the chemicals in plants that are good for health act as direct scavengers of free radicals. Here we review evidence that favors a different hypothesis for the health benefits of plant consumption, namely, that some phytochemicals exert disease-preventive and therapeutic actions by engaging one or more adaptive cellular response pathways in cells. The evolutionary basis for the latter mechanism is grounded in the fact that plants produce natural antifeedant/noxious chemicals that discourage insects and other organisms from eating them. However, in the amounts typically consumed by humans, the phytochemicals activate one or more conserved adaptive cellular stress response pathways and thereby enhance the ability of cells to resist injury and disease. Examplesof such pathways include those involving the transcription factors nuclear factor erythroid 2-related factor 2, nuclear factor-κB, hypoxia-inducible factor 1α, peroxisome proliferator-activated receptor γ, and forkhead box subgroup O, as well as the production and action of trophic factors and hormones. Translational research to develop interventions that target these pathways may lead to new classes of therapeutic agents that act by stimulating adaptive stress response pathways to bolster endogenous defenses against tissue injury and disease. Because neurons are particularly sensitive to potentially noxious phytochemicals, we focus on the nervous system but also include findings from other cell types in which actions of phytochemicals on specific signal transduction pathways have been more thoroughly studied. PMID:24958636

The Itch-Producing Agents Histamine and Cowhage Activate Separate Populations of Primate Spinothalamic Tract Neurons

PubMed Central

Davidson, Steve; Zhang, Xijing; Yoon, Chul H.; Khasabov, Sergey G.; Simone, Donald A.; Giesler, Glenn J.

2010-01-01

Itch is an everyday sensation, but when associated with disease or infection it can be chronic and debilitating. Several forms of itch can be blocked using antihistamines, but others cannot and these constitute an important clinical problem. Little information is available on the mechanisms underlying itch that is produced by nonhistaminergic mechanisms. We examined the responses of spinothalamic tract neurons to histaminergic and, for the first time, nonhistaminergic forms of itch stimuli. Fifty-seven primate spinothalamic tract (STT) neurons were identified using antidromic activation techniques and examined for their responses to histamine and cowhage, the nonhistaminergic itch-producing spicules covering the pod of the legume Mucuna pruriens. Each examined neuron had a receptive field on the hairy skin of the hindlimb and responded to noxious mechanical stimulation. STT neurons were tested with both pruritogens applied in a random order and we found 12 that responded to histamine and seven to cowhage. Each pruritogen-responsive STT neuron was activated by the chemical algogen capsaicin and two-thirds responded to noxious heat stimuli, demonstrating that these neurons convey chemical, thermal, and mechanical nociceptive information as well. Histamine or cowhage responsive STT neurons were found in both the marginal zone and the deep dorsal horn and were classified as high threshold and wide dynamic range. Unexpectedly, histamine and cowhage never activated the same cell. Our results demonstrate that the spinothalamic tract contains mutually exclusive populations of neurons responsive to histamine or the nonhistaminergic itch-producing agent cowhage. PMID:17855615

Changes of spontaneous oscillatory activity to tonic heat pain.

PubMed

Peng, Weiwei; Hu, Li; Zhang, Zhiguo; Hu, Yong

2014-01-01

Transient painful stimuli could induce suppression of alpha oscillatory activities and enhancement of gamma oscillatory activities that also could be greatly modulated by attention. Here, we attempted to characterize changes in cortical activities during tonic heat pain perception and investigated the influence of directed/distracted attention on these responses. We collected 5-minute long continuous Electroencephalography (EEG) data from 38 healthy volunteers during four conditions presented in a counterbalanced order: (A) resting condition; (B) innoxious-distracted condition; (C) noxious-distracted condition; (D) noxious-attended condition. The effects of tonic heat pain stimulation and selective attention on oscillatory activities were investigated by comparing the EEG power spectra among the four experimental conditions and assessing the relationship between spectral power difference and subjective pain intensity. The change of oscillatory activities in condition D was characterized by stable and persistent decrease of alpha oscillation power over contralateral-central electrodes and widespread increase of gamma oscillation power, which were even significantly correlated with subjective pain intensity. Since EEG responses in the alpha and gamma frequency band were affected by attention in different manners, they are likely related to different aspects of the multidimensional sensory experience of pain. The observed contralateral-central alpha suppression (conditions D vs. B and D vs. C) may reflect primarily a top-down cognitive process such as attention, while the widespread gamma enhancement (conditions D vs. A) may partly reflect tonic pain processing, representing the summary effects of bottom-up stimulus-related and top-down subject-driven cognitive processes.

Changes of Spontaneous Oscillatory Activity to Tonic Heat Pain

PubMed Central

Zhang, Zhiguo; Hu, Yong

2014-01-01

Transient painful stimuli could induce suppression of alpha oscillatory activities and enhancement of gamma oscillatory activities that also could be greatly modulated by attention. Here, we attempted to characterize changes in cortical activities during tonic heat pain perception and investigated the influence of directed/distracted attention on these responses. We collected 5-minute long continuous Electroencephalography (EEG) data from 38 healthy volunteers during four conditions presented in a counterbalanced order: (A) resting condition; (B) innoxious-distracted condition; (C) noxious-distracted condition; (D) noxious-attended condition. The effects of tonic heat pain stimulation and selective attention on oscillatory activities were investigated by comparing the EEG power spectra among the four experimental conditions and assessing the relationship between spectral power difference and subjective pain intensity. The change of oscillatory activities in condition D was characterized by stable and persistent decrease of alpha oscillation power over contralateral-central electrodes and widespread increase of gamma oscillation power, which were even significantly correlated with subjective pain intensity. Since EEG responses in the alpha and gamma frequency band were affected by attention in different manners, they are likely related to different aspects of the multidimensional sensory experience of pain. The observed contralateral-central alpha suppression (conditions D vs. B and D vs. C) may reflect primarily a top-down cognitive process such as attention, while the widespread gamma enhancement (conditions D vs. A) may partly reflect tonic pain processing, representing the summary effects of bottom-up stimulus-related and top-down subject-driven cognitive processes. PMID:24603703

Perceived racial discrimination, but not mistrust of medical researchers, predicts the heat pain tolerance of African Americans with symptomatic knee osteoarthritis.

PubMed

Goodin, Burel R; Pham, Quyen T; Glover, Toni L; Sotolongo, Adriana; King, Christopher D; Sibille, Kimberly T; Herbert, Matthew S; Cruz-Almeida, Yenisel; Sanden, Shelley H; Staud, Roland; Redden, David T; Bradley, Laurence A; Fillingim, Roger B

2013-11-01

Studies have shown that perceived racial discrimination is a significant predictor of clinical pain severity among African Americans. It remains unknown whether perceived racial discrimination also alters the nociceptive processing of painful stimuli, which, in turn, could influence clinical pain severity. This study examined associations between perceived racial discrimination and responses to noxious thermal stimuli among African Americans and non-Hispanic Whites. Mistrust of medical researchers was also assessed given its potential to affect responses to the noxious stimuli. One-hundred and 30 (52% African American, 48% non-Hispanic White) community-dwelling older adults with symptomatic knee osteoarthritis completed two study sessions. In session one, individuals provided demographic, socioeconomic, physical and mental health information. They completed questionnaires related to perceived lifetime frequency of racial discrimination and mistrust of medical researchers. In session two, individuals underwent a series of controlled thermal stimulation procedures to assess heat pain sensitivity, particularly heat pain tolerance. African Americans were more sensitive to heat pain and reported greater perceived racial discrimination as well as greater mistrust of medical researchers compared with non-Hispanic Whites. Greater perceived racial discrimination significantly predicted lower heat pain tolerance for African Americans but not non-Hispanic Whites. Mistrust of medical researchers did not significantly predict heat pain tolerance for either racial group. These results lend support to the idea that perceived racial discrimination may influence the clinical pain severity of African Americans via the nociceptive processing of painful stimuli.

ThermoTRPs and Pain

PubMed Central

Laing, Robyn J; Dhaka, Ajay

2015-01-01

The ability of the body to perceive noxious stimuli lies in a heterogeneous group of primary somatosensory neurons termed nociceptors. The molecular receptors of noxious mechanical, temperature or chemical stimuli are expressed in these neurons and have drawn considerable attention as possible targets for analgesic development to improve treatment for the millions who suffer from chronic pain conditions. A number of thermoTRPs, a subset of the transient receptor potential family of ion channels, are activated by a wide range on noxious stimuli. In this review, we review the function of these channels and examine the evidence that thermoTRPs play a vital role in acute, inflammatory and neuropathic nociception. PMID:25608689

33 CFR 151.32 - Special areas for the purpose of Annex II.

Code of Federal Regulations, 2013 CFR

2013-07-01

... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...

7 CFR 201.16 - Noxious-weed seeds.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 3 2010-01-01 2010-01-01 false Noxious-weed seeds. 201.16 Section 201.16 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS Labeling Agricultural Seeds §...

7 CFR 201.52 - Noxious-weed seeds.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 3 2014-01-01 2014-01-01 false Noxious-weed seeds. 201.52 Section 201.52 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS Purity Analysis in the...

7 CFR 201.52 - Noxious-weed seeds.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 3 2011-01-01 2011-01-01 false Noxious-weed seeds. 201.52 Section 201.52 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS Purity Analysis in the...

7 CFR 201.52 - Noxious-weed seeds.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 3 2010-01-01 2010-01-01 false Noxious-weed seeds. 201.52 Section 201.52 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS Purity Analysis in the...

7 CFR 201.16 - Noxious-weed seeds.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 3 2012-01-01 2012-01-01 false Noxious-weed seeds. 201.16 Section 201.16 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS Labeling Agricultural Seeds §...

7 CFR 201.16 - Noxious-weed seeds.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 3 2011-01-01 2011-01-01 false Noxious-weed seeds. 201.16 Section 201.16 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS Labeling Agricultural Seeds §...

7 CFR 201.16 - Noxious-weed seeds.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 3 2013-01-01 2013-01-01 false Noxious-weed seeds. 201.16 Section 201.16 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS Labeling Agricultural Seeds §...

7 CFR 201.52 - Noxious-weed seeds.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 3 2012-01-01 2012-01-01 false Noxious-weed seeds. 201.52 Section 201.52 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS Purity Analysis in the...

33 CFR 151.32 - Special areas for the purpose of Annex II.

Code of Federal Regulations, 2012 CFR

2012-07-01

... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...

33 CFR 151.32 - Special areas for the purpose of Annex II.

Code of Federal Regulations, 2014 CFR

2014-07-01

... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...

33 CFR 151.32 - Special areas for the purpose of Annex II.

Code of Federal Regulations, 2011 CFR

2011-07-01

... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...

75 FR 23151 - Noxious Weeds; Old World Climbing Fern and Maidenhair Creeper

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-03

.... APHIS-2008-0097] Noxious Weeds; Old World Climbing Fern and Maidenhair Creeper AGENCY: Animal and Plant... adding Old World climbing fern (Lygodium microphyllum (Cavanilles) R. Brown) and maidenhair creeper... amended the regulations by adding Old World climbing fern (Lygodium microphyllum (Cavanilles) R. Brown...

33 CFR 151.32 - Special areas for the purpose of Annex II.

Code of Federal Regulations, 2010 CFR

2010-07-01

... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...

Cannabinoid system of dorsomedial telencephalon modulates behavioral responses to noxious stimulation in the fish Leporinus macrocephalus.

PubMed

Wolkers, Carla Patricia Bejo; Menescal-de-Oliveira, Leda; Hoffmann, Anette

2017-10-01

Fish dorsomedial telencephalon has been considered a pallial region homologous to mammals amygdala, being considered a possible substrate for nociception modulation in this animal group. The present study aimed to evaluate the participation of the cannabinoid system of Dm telencephalon on nociception modulation in the fish Leporinus macrocephalus. We demonstrated that cannabidiol microinjection in Dm telecephalon inhibits the behavioral nociceptive response to the subcutaneous injection of 3% formaldehyde, and this antinociception is blocked by previous treatment with AM251 microinjection. Furthermore, AM251 microinjection in Dm prior to restraint stress also blockades the stress-induced antinociception. These results reinforce the hypothesis that this pallial telencephalic structure has a pivotal role in nociception modulation in fish. Copyright © 2017 Elsevier Inc. All rights reserved.

7 CFR 361.6 - Noxious weed seeds.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 5 2010-01-01 2010-01-01 false Noxious weed seeds. 361.6 Section 361.6 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE... measured from the base of the rachilla. (3) Seeds of legumes (Fabaceae) with the seed coats entirely...

7 CFR 201.65 - Noxious-weed seeds in interstate commerce.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 3 2012-01-01 2012-01-01 false Noxious-weed seeds in interstate commerce. 201.65 Section 201.65 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS...

7 CFR 201.65 - Noxious weed seeds in interstate commerce.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 3 2010-01-01 2010-01-01 false Noxious weed seeds in interstate commerce. 201.65 Section 201.65 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS...

7 CFR 201.65 - Noxious-weed seeds in interstate commerce.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 3 2013-01-01 2013-01-01 false Noxious-weed seeds in interstate commerce. 201.65 Section 201.65 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS...

7 CFR 201.65 - Noxious-weed seeds in interstate commerce.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 3 2014-01-01 2014-01-01 false Noxious-weed seeds in interstate commerce. 201.65 Section 201.65 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS...

7 CFR 201.65 - Noxious weed seeds in interstate commerce.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 3 2011-01-01 2011-01-01 false Noxious weed seeds in interstate commerce. 201.65 Section 201.65 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS...

7 CFR 352.2 - Purpose; relation to other regulations; applicability; preemption of State and local laws.

Code of Federal Regulations, 2011 CFR

2011-01-01

... article, means of conveyance, plant, biological control organism, plant pest, noxious weed, or plant... prevent the introduction or dissemination of a biological control organism, plant pest, or noxious weed...) The provisions in this part apply whether the controls over arrival, temporary stay, unloading...

Connecting Model Species to Nature: Predator-Induced Long-Term Sensitization in "Aplysia Californica"

ERIC Educational Resources Information Center

Mason, Maria J.; Watkins, Amanda J.; Wakabayashi, Jordann; Buechler, Jennifer; Pepino, Christine; Brown, Michelle; Wright, William G.

2014-01-01

Previous research on sensitization in "Aplysia" was based entirely on unnatural noxious stimuli, usually electric shock, until our laboratory found that a natural noxious stimulus, a single sublethal lobster attack, causes short-term sensitization. We here extend that finding by demonstrating that multiple lobster attacks induce…

43 CFR 4120.5-2 - Cooperation with Tribal, state, county, and Federal agencies.

Code of Federal Regulations, 2011 CFR

2011-10-01

... laws and regulations relating to livestock, livestock diseases, sanitation, and noxious weeds... 1971 (16 U.S.C. 1331 et seq.); (b) County or other local weed control districts in analyzing noxious weed problems and developing control programs for areas of the public lands and other lands...

7 CFR 623.13 - Wetlands reserve plan of operations.

Code of Federal Regulations, 2012 CFR

2012-01-01

... program, including, but not limited to: (i) measures to control noxious weeds and insect pests in order to comply with applicable Federal, or State noxious weed and pest control laws; and (ii) measures to control other specified species of weeds, insects or pests; (3) Specify compatible land uses for personal...

7 CFR 623.13 - Wetlands reserve plan of operations.

Code of Federal Regulations, 2013 CFR

2013-01-01

... program, including, but not limited to: (i) Measures to control noxious weeds and insect pests in order to comply with applicable Federal, or State noxious weed and pest control laws; and (ii) Measures to control other specified species of weeds, insects or pests; (3) Specify compatible land uses for personal...

7 CFR 623.13 - Wetlands reserve plan of operations.

Code of Federal Regulations, 2014 CFR

2014-01-01

... program, including, but not limited to: (i) measures to control noxious weeds and insect pests in order to comply with applicable Federal, or State noxious weed and pest control laws; and (ii) measures to control other specified species of weeds, insects or pests; (3) Specify compatible land uses for personal...

33 CFR 151.49 - Category C and D Oil-like NLSs allowed for carriage.

Code of Federal Regulations, 2012 CFR

2012-07-01

... HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance...

33 CFR 151.49 - Category C and D Oil-like NLSs allowed for carriage.

Code of Federal Regulations, 2011 CFR

2011-07-01

... HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance...

33 CFR 151.49 - Category C and D Oil-like NLSs allowed for carriage.

Code of Federal Regulations, 2014 CFR

2014-07-01

... HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance...

33 CFR 151.33 - Certificates needed to carry Category C Oil-like NLS.

Code of Federal Regulations, 2012 CFR

2012-07-01

... HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance...

33 CFR 151.33 - Certificates needed to carry Category C Oil-like NLS.

Code of Federal Regulations, 2014 CFR

2014-07-01

... HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance...

33 CFR 151.49 - Category C and D Oil-like NLSs allowed for carriage.

Code of Federal Regulations, 2013 CFR

2013-07-01

... HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance...

33 CFR 151.33 - Certificates needed to carry Category C Oil-like NLS.

Code of Federal Regulations, 2011 CFR

2011-07-01

... HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance...

33 CFR 151.49 - Category C and D Oil-like NLSs allowed for carriage.

Code of Federal Regulations, 2010 CFR

2010-07-01

... HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance...

33 CFR 151.33 - Certificates needed to carry Category C Oil-like NLS.

Code of Federal Regulations, 2010 CFR

2010-07-01

... HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance...

A field guide for forest indicator plants, sensitive plants, and noxious weeds of the Shoshone National Forest, Wyoming

Treesearch

Kent E. Houston; Walter J. Hartung; Carol J. Hartung

2001-01-01

This field guide was designed for people with minimal botanical training. It is an identification aid to plant species that have ecological indicator value, are on sensitive species lists, or are considered noxious weeds. It contains illustrations and simplified taxonomic descriptions.

Brain Mechanisms Supporting Modulation of Pain by Mindfulness Meditation

PubMed Central

Zeidan, F.; Martucci, K.T.; Kraft, R.A.; Gordon, N.S.; McHaffie, J.G.; Coghill, R.C.

2011-01-01

The subjective experience of one’s environment is constructed by interactions among sensory, cognitive, and affective processes. For centuries, meditation has been thought to influence such processes by enabling a non-evaluative representation of sensory events. To better understand how meditation influences the sensory experience, we employed arterial spin labeling (ASL) functional magnetic resonance imaging to assess the neural mechanisms by which mindfulness meditation influences pain in healthy human participants. After four-days of mindfulness meditation training, meditating in the presence of noxious stimulation significantly reduced pain-unpleasantness by 57% and pain-intensity ratings by 40% when compared to rest. A two factor repeated measures analysis of variance was used to identify interactions between meditation and pain-related brain activation. Meditation reduced pain-related activation of the contra lateral primary somatosensory cortex. Multiple regression analysis was used to identify brain regions associated with individual differences in the magnitude of meditation-related pain reductions. Meditation-induced reductions in pain intensity ratings were associated with increased activity in the anterior cingulate cortex and anterior insula, areas involved in the cognitive regulation of nociceptive processing. Reductions in pain unpleasantness ratings were associated with orbitofrontal cortex activation, an area implicated in reframing the contextual evaluation of sensory events. Moreover, reductions in pain unpleasantness also were associated with thalamic deactivation, which may reflect a limbic gating mechanism involved in modifying interactions between afferent in put and executive-order brain areas. Taken together, these data indicate that meditation engages multiple brain mechanisms that alter the construction of the subjectively available pain experience from afferent information. PMID:21471390

An improved genetic algorithm for designing optimal temporal patterns of neural stimulation

NASA Astrophysics Data System (ADS)

Cassar, Isaac R.; Titus, Nathan D.; Grill, Warren M.

2017-12-01

Objective. Electrical neuromodulation therapies typically apply constant frequency stimulation, but non-regular temporal patterns of stimulation may be more effective and more efficient. However, the design space for temporal patterns is exceedingly large, and model-based optimization is required for pattern design. We designed and implemented a modified genetic algorithm (GA) intended for design optimal temporal patterns of electrical neuromodulation. Approach. We tested and modified standard GA methods for application to designing temporal patterns of neural stimulation. We evaluated each modification individually and all modifications collectively by comparing performance to the standard GA across three test functions and two biophysically-based models of neural stimulation. Main results. The proposed modifications of the GA significantly improved performance across the test functions and performed best when all were used collectively. The standard GA found patterns that outperformed fixed-frequency, clinically-standard patterns in biophysically-based models of neural stimulation, but the modified GA, in many fewer iterations, consistently converged to higher-scoring, non-regular patterns of stimulation. Significance. The proposed improvements to standard GA methodology reduced the number of iterations required for convergence and identified superior solutions.

The Effects of Noxious Subliminal Suggestion upon Smoking Attitudes and Behavior.

ERIC Educational Resources Information Center

Dutto, Franklin N.; Galli, Nicholas

The efforts of smoking cessation programs have met with various degrees of success and fresh approaches to the problem are needed. An innovative technique that interrupts the psychogenic drives of smokers was employed to determine the effect of noxious subliminal suggestion on smoking attitudes and behavior. Adult smokers (N=60) were shown…

33 CFR 151.35 - Certificates needed to carry Category D NLS and Category D Oil-like NLS.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution § 151.35 Certificates needed to carry Category D NLS and Category D Oil-like... GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID...

33 CFR 151.33 - Certificates needed to carry Category C Oil-like NLS.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution § 151.33 Certificates needed to carry Category C Oil-like NLS. (a) A U.S. oceangoing ship may not... HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL...

7 CFR 201.17 - Noxious-weed seeds in the District of Columbia.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 3 2013-01-01 2013-01-01 false Noxious-weed seeds in the District of Columbia. 201.17 Section 201.17 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS...

7 CFR 201.17 - Noxious-weed seeds in the District of Columbia.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 3 2014-01-01 2014-01-01 false Noxious-weed seeds in the District of Columbia. 201.17 Section 201.17 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS...

7 CFR 201.17 - Noxious-weed seeds in the District of Columbia.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 3 2011-01-01 2011-01-01 false Noxious-weed seeds in the District of Columbia. 201.17 Section 201.17 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS...

7 CFR 201.17 - Noxious-weed seeds in the District of Columbia.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 3 2010-01-01 2010-01-01 false Noxious-weed seeds in the District of Columbia. 201.17 Section 201.17 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS...

7 CFR 201.17 - Noxious-weed seeds in the District of Columbia.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 3 2012-01-01 2012-01-01 false Noxious-weed seeds in the District of Columbia. 201.17 Section 201.17 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS...

75 FR 1655 - Proposed Information Collection Request Submitted for Public Comment and Recommendations...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-12

... provide a safe environment for miners. Methane is liberated from the strata, and noxious gases and dusts from blasting and other mining activities may be present. The explosive and noxious gases and dusts... collection of information, including the validity of the methodology and assumptions used; Enhance the...

76 FR 43706 - Final Supplementary Rules To Require the Use of Certified Noxious-Weed-Free Forage and Straw on...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-21

... to use certified noxious-weed-free forage and straw. Restoration, rehabilitation, and stabilization... domestic ungulates, weaken rehabilitation and landscape restoration efforts, increase soil erosion and... consistent with and supportive of the statewide Conservation Plan for the Greater Sage- Grouse in Idaho...

33 CFR 151.35 - Certificates needed to carry Category D NLS and Category D Oil-like NLS.

Code of Federal Regulations, 2014 CFR

2014-07-01

... GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious...

33 CFR 151.31 - Where to find requirements applying to oceangoing ships carrying Category A, B, C, and D NLS.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of... Pollution from Ships Noxious Liquid Substance Pollution § 151.31 Where to find requirements applying to...

33 CFR 151.35 - Certificates needed to carry Category D NLS and Category D Oil-like NLS.

Code of Federal Regulations, 2012 CFR

2012-07-01

... GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious...

33 CFR 151.35 - Certificates needed to carry Category D NLS and Category D Oil-like NLS.

Code of Federal Regulations, 2011 CFR

2011-07-01

... GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious...

33 CFR 151.37 - Obtaining an Attachment for NLSs to the IOPP Certificate and obtaining an NLS Certificate.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of... Pollution from Ships Noxious Liquid Substance Pollution § 151.37 Obtaining an Attachment for NLSs to the...

33 CFR 151.31 - Where to find requirements applying to oceangoing ships carrying Category A, B, C, and D NLS.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of... Pollution from Ships Noxious Liquid Substance Pollution § 151.31 Where to find requirements applying to...

33 CFR 151.41 - Operating requirements for oceangoing ships with IOPP Certificates: Category C and D Oil-like NLSs.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of... Pollution from Ships Noxious Liquid Substance Pollution § 151.41 Operating requirements for oceangoing ships...

33 CFR 151.37 - Obtaining an Attachment for NLSs to the IOPP Certificate and obtaining an NLS Certificate.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of... Pollution from Ships Noxious Liquid Substance Pollution § 151.37 Obtaining an Attachment for NLSs to the...

33 CFR 151.31 - Where to find requirements applying to oceangoing ships carrying Category A, B, C, and D NLS.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of... Pollution from Ships Noxious Liquid Substance Pollution § 151.31 Where to find requirements applying to...

33 CFR 151.41 - Operating requirements for oceangoing ships with IOPP Certificates: Category C and D Oil-like NLSs.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of... Pollution from Ships Noxious Liquid Substance Pollution § 151.41 Operating requirements for oceangoing ships...

33 CFR 151.41 - Operating requirements for oceangoing ships with IOPP Certificates: Category C and D Oil-like NLSs.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of... Pollution from Ships Noxious Liquid Substance Pollution § 151.41 Operating requirements for oceangoing ships...

33 CFR 151.37 - Obtaining an Attachment for NLSs to the IOPP Certificate and obtaining an NLS Certificate.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of... Pollution from Ships Noxious Liquid Substance Pollution § 151.37 Obtaining an Attachment for NLSs to the...

33 CFR 151.41 - Operating requirements for oceangoing ships with IOPP Certificates: Category C and D Oil-like NLSs.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of... Pollution from Ships Noxious Liquid Substance Pollution § 151.41 Operating requirements for oceangoing ships...

33 CFR 151.37 - Obtaining an Attachment for NLSs to the IOPP Certificate and obtaining an NLS Certificate.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of... Pollution from Ships Noxious Liquid Substance Pollution § 151.37 Obtaining an Attachment for NLSs to the...

33 CFR 151.41 - Operating requirements for oceangoing ships with IOPP Certificates: Category C and D Oil-like NLSs.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of... Pollution from Ships Noxious Liquid Substance Pollution § 151.41 Operating requirements for oceangoing ships...

33 CFR 151.31 - Where to find requirements applying to oceangoing ships carrying Category A, B, C, and D NLS.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of... Pollution from Ships Noxious Liquid Substance Pollution § 151.31 Where to find requirements applying to...

33 CFR 151.35 - Certificates needed to carry Category D NLS and Category D Oil-like NLS.

Code of Federal Regulations, 2010 CFR

2010-07-01

... GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious...

Final Environmental Assessment for Expanding the North Military Operations in Urban Terrain (MOUT) Target Array at Avon Park Air Force Range, Florida

DTIC Science & Technology

2005-01-01

native groundcover vegetation. Specifically, natalgrass (Rhynchelytrum repens) and Cogan grass ( Imperata cylindrica ), both invasive exotics, have the...stability creates an environment conducive for noxious weeds. If noxious weeds establish, the EA acknowledges that they can be chemically treated

Fear appeals and attitude change: effects of a threat's noxiousness, probability of occurrence, and the efficacy of coping responses.

PubMed

Rogers, R W; Mewborn, C R

1976-07-01

Three factorial experiments examined the persuasive effects of the noxiousness of threatened event, its probability of occurrence, and the efficacy of recommended protective measures. A total of 176 students participated in separate studies on the topics of cigarette smoking, driving safety, and venereal disease. The results disclosed that increments in the efficacy variable increased intentions to adopt the efficacy variable increased intentions to adopt the recommended practices. Interaction effects revealed that when the preventive practices were effective, increments in the noxiousness and probability variables facilitated attitude change; however, when the coping responses were the preventive practices were effective, increments in the noxiousness and probability either had no effect or a deleterious effect, respectively. These interaction effects were discussed in terms of a defensive avoidance hypothesis, the crucial component of which was an inability to ward off the danger. Furthermore, the effect of the emotion of fear upon intentions was found to be mediated by the cognitive appraisal of severity of the threat. Finally, similarities with and extensions of previous studies were reviewed.

Effects of propofol anesthesia on the processing of noxious stimuli in the spinal cord and the brain.

PubMed

Lichtner, Gregor; Auksztulewicz, Ryszard; Kirilina, Evgeniya; Velten, Helena; Mavrodis, Dionysios; Scheel, Michael; Blankenburg, Felix; von Dincklage, Falk

2018-05-15

Drug-induced unconsciousness is an essential component of general anesthesia, commonly attributed to attenuation of higher-order processing of external stimuli and a resulting loss of information integration capabilities of the brain. In this study, we investigated how the hypnotic drug propofol at doses comparable to those in clinical practice influences the processing of somatosensory stimuli in the spinal cord and in primary and higher-order cortices. Using nociceptive reflexes, somatosensory evoked potentials and functional magnet resonance imaging (fMRI), we found that propofol abolishes the processing of innocuous and moderate noxious stimuli at low to medium concentration levels, but that intense noxious stimuli evoked spinal and cerebral responses even during deep propofol anesthesia that caused profound electroencephalogram (EEG) burst suppression. While nociceptive reflexes and somatosensory potentials were affected only in a minor way by further increasing doses of propofol after the loss of consciousness, fMRI showed that increasing propofol concentration abolished processing of intense noxious stimuli in the insula and secondary somatosensory cortex and vastly increased processing in the frontal cortex. As the fMRI functional connectivity showed congruent changes with increasing doses of propofol - namely the temporal brain areas decreasing their connectivity with the bilateral pre-/postcentral gyri and the supplementary motor area, while connectivity of the latter with frontal areas is increased - we conclude that the changes in processing of noxious stimuli during propofol anesthesia might be related to changes in functional connectivity. Copyright © 2018 Elsevier Inc. All rights reserved.

The visceromotor responses to colorectal distension and skin pinch are inhibited by simultaneous jejunal distension.

PubMed

Shafton, Anthony D; Furness, John B; Ferens, Dorota; Bogeski, Goce; Koh, Shir Lin; Lean, Nicholas P; Kitchener, Peter D

2006-07-01

Noxious stimuli that are applied to different somatic sites interact; often one stimulus diminishes the sensation elicited from another site. By contrast, inhibitory interactions between visceral stimuli are not well documented. We investigated the interaction between the effects of noxious distension of the colorectum and noxious stimuli applied to the jejunum, in the rat. Colorectal distension elicited a visceromotor reflex, which was quantified using electromyographic (EMG) recordings from the external oblique muscle of the upper abdomen. The same motor units were activated when a strong pinch was applied to the flank skin. Distension of the jejunum did not provoke an EMG response at this site, but when it was applied during colorectal distension it blocked the EMG response. Jejunal distension also inhibited the response to noxious skin pinch. The inhibition of the visceromotor response to colorectal distension was prevented by local application of tetrodotoxin to the jejunum, and was markedly reduced when nicardipine was infused into the local jejunal circulation. Chronic sub-diaphragmatic vagotomy had no effect on the colorectal distension-induced EMG activity or its inhibition by jejunal distension. The nicotinic antagonist hexamethonium suppressed phasic contractile activity in the jejunum, had only a small effect on the inhibition of visceromotor response by jejunal distension. It is concluded that signals that arise from skin pinch and colorectal distension converge in the central nervous system with pathways that are activated by jejunal spinal afferents; the jejunal signals strongly inhibit the abdominal motor activity evoked by noxious stimuli.

An inhibitory interaction of human cortical responses to stimuli preferentially exciting Aδ or C fibers

PubMed Central

Tran, Tuan D.; Matre, Dagfinn; Casey, Kenneth L.

2008-01-01

Finely myelinated (type Aδ) and unmyelinated (type C) fibers are the major afferent inputs to spinothalamic tract neurons mediating sensory and reflex responses to noxious and thermal stimuli. These two fiber types differ in their sensory and biophysical properties, raising questions about the interaction of their supraspinal responses. Therefore, we investigated the interaction of cortical responses to stimuli that preferentially excite these fibers in human subjects using evoked potential recordings in a paired conditioning stimulation (CS) and test stimulation (TS) paradigm. There were two experiments, one with Aδ as CS and C as TS (Aδ-C) and another with these stimuli reversed (C-Aδ). We used intra-epidermal electrical pulses applied to the dorsal left hand at 2 and 1 × pinprick threshold (pp) for the preferential stimulation of Aδ fibers and 37 – 50°C contact heat pulses applied to the left or right thenar and left hypothenar eminences for the preferential stimulation of C fibers. We found that the cortical response to preferential Aδ or C fiber stimulation was attenuated whenever either cortical response preceded the other. Standardized values of peak and integrated amplitudes were < 1 in all paring conditions and in all subjects in both experiments. The suppressive effect varied in magnitude with the intensity of the conditioning stimulus in both Aδ-C and C-Aδ experiments. Furthermore, intra-segmental interaction was differentially effective for Aδ conditioning, (peak amplitude, p < 0.008; ANOVA). Our experiments provide the first neurophysiological evidence for a somatotopically distributed, mutually suppressive interaction between cortical responses to preferentially activated Aδ and C afferents in humans. This suppressive interaction of cortical responses suggests contrasting and possibly mutually exclusive sensori-motor functions mediated through the Aδ and C fiber afferent channels. PMID:18308475

Magnetoencephalographic study of event-related fields and cortical oscillatory changes during cutaneous warmth processing.

PubMed

An, Kyung-Min; Lim, Sanghyun; Lee, Hyun Joon; Kwon, Hyukchan; Kim, Min-Young; Gohel, Bakul; Kim, Ji-Eun; Kim, Kiwoong

2018-05-01

Thermoreception is an important cutaneous sense, which plays a role in the maintenance of our body temperature and in the detection of potential noxious heat stimulation. In this study, we investigated event-related fields (ERFs) and neural oscillatory activities, which were modulated by warmth stimulation. We developed a warmth stimulator that could elicit a warmth sensation, without pain or tactile sensation, by using a deep-penetrating 980-nm diode laser. The index finger of each participant (n = 24) was irradiated with the laser warmth stimulus, and the cortical responses were measured using magnetoencephalography (MEG). The ERFs and oscillatory responses had late latencies (∼1.3 s and 1.0-1.5 s for ERFs and oscillatory responses, respectively), which could be explained by a slow conduction velocity of warmth-specific C-fibers. Cortical sources of warmth-related ERFs were seen in the bilateral primary and secondary somatosensory cortices (SI and SII), posterior part of the anterior cingulate cortex (pACC), ipsilateral primary motor, and premotor cortex. Thus, we suggested that SI, SII, and pACC play a role in processing the warmth sensation. Time-frequency analysis demonstrated the suppression of the alpha (8-13 Hz) and beta (18-23 Hz) band power in the bilateral sensorimotor cortex. We proposed that the suppressions in alpha and beta band power are involved in the automatic response to the input of warmth stimulation and sensorimotor interactions. The delta band power (1-4 Hz) increased in the frontal, temporal, and cingulate cortices. The power changes in delta band might be related with the attentional processes during the warmth stimulation. © 2018 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Cardiorespiratory and antinociceptive effects of two different doses of lidocaine administered to horses during a constant intravenous infusion of xylazine and ketamine

PubMed Central

2013-01-01

Background This study investigated the antinociceptive effects of a constant rate infusion (CRI) of lidocaine during xylazine and ketamine anesthesia in horses and aimed to correlate these effects with cardiorespiratory variables, bispectral index (BIS) and plasma lidocaine concentrations. Six adult crossbred mares weighing 320–400 kg were anesthetized on three different occasions. Sedation was performed with xylazine (0.75 mg/kg IV) and anesthetic induction with guaifenesin (75 mg/kg IV) and ketamine (2 mg/kg IV). Anesthesia was maintained with 37.5 μg/kg/min of xylazine and 87.5 μg/kg/min of ketamine both administered intravenously for 75 min. The three treatments consisted of: lidocaine (loading dose: 5 mg/kg, CRI: 100 μg/kg/min; THL); lidocaine (loading dose: 2.5 mg/kg; CRI: 50 μg/kg/min: TLL); and saline (TS); all given 15 min after induction and maintained for 1 h. Antinociception was measured by response to electrical stimulation and bispectral index (BIS) was recorded during anesthesia. Parametric and non-parametric data were compared using ANOVA followed by Student-Newman-Keuls and Friedman tests, respectively. Results Plasma lidocaine concentrations peaked at the end of lidocaine loading dose and was greater in THL (9.61 ± 2.75 μg/mL) vs TLL (4.50 ± 3.34 μg/mL). Electrical noxious stimulation caused purposeful movement in all horses from TS, but no response in THL. The BIS was decreased in THL only and was less when compared to the other treatments throughout anesthesia. Blood pressure, PaO2 and PaCO2 increased and heart rate (HR), respiratory rate (RR), pH, total plasma protein and temperature decreased during anesthesia in all treatments. PaCO2 and HR were greater and RR and pH less in THL compared to TLL and TS at 30 min during anesthesia. All recoveries were considered excellent. Time to standing was longer after THL (60 ± 20 min) than following TLL and TS (32 ± 17 and 30 ± 15 min, respectively). Conclusions At the highest dose administered (THL) lidocaine CRI during xylazine/ketamine anesthesia decreased BIS and motor response to noxious stimulation, and prolonged recovery time without significant added cardiorespiratory depression. PMID:24103634

Inflammatory Pain Reduces C Fiber Activity-Dependent Slowing in a Sex-Dependent Manner, Amplifying Nociceptive Input to the Spinal Cord.

PubMed

Dickie, Allen C; McCormick, Barry; Lukito, Veny; Wilson, Kirsten L; Torsney, Carole

2017-07-05

C fibers display activity-dependent slowing (ADS), whereby repetitive stimulation (≥1 Hz) results in a progressive slowing of action potential conduction velocity, which manifests as a progressive increase in response latency. However, the impact of ADS on spinal pain processing has not been explored, nor whether ADS is altered in inflammatory pain conditions. To investigate, compound action potentials were made, from dorsal roots isolated from rats with or without complete Freund's adjuvant (CFA) hindpaw inflammation, in response to electrical stimulus trains. CFA inflammation significantly reduced C fiber ADS at 1 and 2 Hz stimulation rates. Whole-cell patch-clamp recordings in the spinal cord slice preparation with attached dorsal roots also demonstrated that CFA inflammation reduced ADS in the monosynaptic C fiber input to lamina I neurokinin 1 receptor-expressing neurons (1-10 Hz stimulus trains) without altering the incidence of synaptic response failures. When analyzed by sex, it was revealed that females display a more pronounced ADS that is reduced by CFA inflammation to a level comparable with males. Cumulative ventral root potentials evoked by long and short dorsal root stimulation lengths, to maximize and minimize the impact of ADS, respectively, demonstrated that reducing ADS facilitates spinal summation, and this was also sex dependent. This finding correlated with the behavioral observation of increased noxious thermal thresholds and enhanced inflammatory thermal hypersensitivity in females. We propose that sex/inflammation-dependent regulation of C fiber ADS can, by controlling the temporal relay of nociceptive inputs, influence the spinal summation of nociceptive signals contributing to sex/inflammation-dependent differences in pain sensitivity. SIGNIFICANCE STATEMENT The intensity of a noxious stimulus is encoded by the frequency of action potentials relayed by nociceptive C fibers to the spinal cord. C fibers conduct successive action potentials at progressively slower speeds, but the impact of this activity-dependent slowing (ADS) is unknown. Here we demonstrate that ADS is more prevalent in females than males and is reduced in an inflammatory pain model in females only. We also demonstrate a progressive delay of C fiber monosynaptic transmission to the spinal cord that is similarly sex and inflammation dependent. Experimentally manipulating ADS strongly influences spinal summation consistent with sex differences in behavioral pain thresholds. This suggests that ADS provides a peripheral mechanism that can regulate spinal nociceptive processing and pain sensation. Copyright © 2017 Dickie et al.

Pain perception studies in tension-type headache.

PubMed

Bezov, David; Ashina, Sait; Jensen, Rigmor; Bendtsen, Lars

2011-02-01

Tension-type headache (TTH) is a disorder with high prevalence and significant impact on society. Understanding of pathophysiology of TTH is paramount for development of effective treatments and prevention of chronification of TTH. Our aim was to review the findings from pain perception studies of pathophysiology of TTH as well as to review the research of pathophysiology of TTH. Pain perception studies such as measurement of muscle tenderness, pain detection thresholds, pain tolerance thresholds, pain response to suprathreshold stimulation, temporal summation and diffuse noxious inhibitory control (DNIC) have played a central role in elucidating the pathophysiology of TTH. It has been demonstrated that continuous nociceptive input from peripheral myofascial structures may induce central sensitization and thereby chronification of the headache. Measurements of pain tolerance thresholds and suprathreshold stimulation have shown presence of generalized hyperalgesia in chronic tension-type headache (CTTH) patients, while DNIC function has been shown to be reduced in CTTH. One imaging study showed loss of gray matter structures involved in pain processing in CTTH patients. Future studies should aim to integrate pain perception and imaging to confirm this finding. Pharmacological studies have shown that drugs like tricyclic anti-depressant amitriptyline and nitric oxide synthase inhibitors can reverse central sensitization and the chronicity of headache. Finally, low frequency electrical stimulation has been shown to rapidly reverse central sensitization and may be a new modality in treatment of CTTH and other chronic pain disorders. © 2010 American Headache Society.

The differential effect of trigeminal vs. peripheral pain stimulation on visual processing and memory encoding is influenced by pain-related fear.

PubMed

Schmidt, K; Forkmann, K; Sinke, C; Gratz, M; Bitz, A; Bingel, U

2016-07-01

Compared to peripheral pain, trigeminal pain elicits higher levels of fear, which is assumed to enhance the interruptive effects of pain on concomitant cognitive processes. In this fMRI study we examined the behavioral and neural effects of trigeminal (forehead) and peripheral (hand) pain on visual processing and memory encoding. Cerebral activity was measured in 23 healthy subjects performing a visual categorization task that was immediately followed by a surprise recognition task. During the categorization task subjects received concomitant noxious electrical stimulation on the forehead or hand. Our data show that fear ratings were significantly higher for trigeminal pain. Categorization and recognition performance did not differ between pictures that were presented with trigeminal and peripheral pain. However, object categorization in the presence of trigeminal pain was associated with stronger activity in task-relevant visual areas (lateral occipital complex, LOC), memory encoding areas (hippocampus and parahippocampus) and areas implicated in emotional processing (amygdala) compared to peripheral pain. Further, individual differences in neural activation between the trigeminal and the peripheral condition were positively related to differences in fear ratings between both conditions. Functional connectivity between amygdala and LOC was increased during trigeminal compared to peripheral painful stimulation. Fear-driven compensatory resource activation seems to be enhanced for trigeminal stimuli, presumably due to their exceptional biological relevance. Copyright © 2016 Elsevier Inc. All rights reserved.

Early Detection Rapid Response Program Targets New Noxious Weed Species in Washington State

ERIC Educational Resources Information Center

Andreas, Jennifer E.; Halpern, Alison D.; DesCamp, Wendy C.; Miller, Timothy W.

2015-01-01

Early detection, rapid response is a critical component of invasive plant management. It can be challenging, however, to detect new invaders before they become established if landowners cannot identify species of concern. In order to increase awareness, eye-catching postcards were developed in Washington State as part of a noxious weed educational…

The Role of Physical Contact and Association in Early Contamination Sensitivity.

ERIC Educational Resources Information Center

Springer, Ken; Belk, Amy

1994-01-01

Children were asked whether someone would get sick from drinking juice placed near a bug. Some preschoolers and most seven- and eight-year olds recognized the need for physical contact with the bug to make the juice noxious, whereas some believed the mere presence of a contaminant made it noxious. Thus, associational contamination sometimes plays…

Impaired diffuse noxious inhibitory controls in specific alternation of rhythm in temperature-stressed rats.

PubMed

Itomi, Yasuo; Tsukimi, Yasuhiro; Kawamura, Toru

2016-08-05

Fibromyalgia is characterized by chronic widespread musculoskeletal pain. A hypofunction in descending pain inhibitory systems is considered to be involved in the chronic pain of fibromyalgia. We examined functional changes in descending pain inhibitory systems in rats with specific alternation of rhythm in temperature (SART) stress, by measuring the strength of diffuse noxious inhibitory controls (DNIC). Hindpaw withdrawal thresholds to mechanical von Frey filament or fiber-specific electrical stimuli by the Neurometer system were used to measure the pain response. To induce DNIC, capsaicin was injected into the intraplantar of the forepaw. SART-stressed rats were established by exposure to repeated cold stress for 4 days. In the control rats, heterotopic intraplantar capsaicin injection increased withdrawal threshold, indicative of analgesia by DNIC. The strength of DNIC was reduced by naloxone (μ-opioid receptor antagonist, intraperitoneally and intracerebroventricularly), yohimbine (α2-adrenoceptor antagonist, intrathecally), and WAY-100635 (5-HT1A receptor antagonist, intrathecally) in the von Frey test. In SART-stressed rats, capsaicin injection did not increase withdrawal threshold in the von Frey test, indicating deficits in DNIC. In the Neurometer test, deficient DNIC in SART-stressed rats were observed only for Aδ- and C-fibers, but not Aβ-fibers stimulation. Analgesic effect of intracerebroventricular morphine was markedly reduced in SART-stressed rats compared with the control rats. Taken together, in SART-stressed rats, capsaicin-induced DNIC were deficient, and a hypofunction of opioid-mediated central pain modulation system may cause the DNIC deficit. Copyright © 2016 Elsevier B.V. All rights reserved.

Acute spinal cord injury (SCI) transforms how GABA affects nociceptive sensitization.

PubMed

Huang, Yung-Jen; Lee, Kuan H; Murphy, Lauren; Garraway, Sandra M; Grau, James W

2016-11-01

Noxious input can sensitize pain (nociceptive) circuits within the spinal cord, inducing a lasting increase in spinal cord neural excitability (central sensitization) that is thought to contribute to chronic pain. The development of spinally-mediated central sensitization is regulated by descending fibers and GABAergic interneurons. The current study provides evidence that spinal cord injury (SCI) transforms how GABA affects nociceptive transmission within the spinal cord, recapitulating an earlier developmental state wherein GABA has an excitatory effect. In spinally transected rats, noxious electrical stimulation and inflammation induce enhanced mechanical reactivity (EMR), a behavioral index of nociceptive sensitization. Pretreatment with the GABA A receptor antagonist bicuculline blocked these effects. Peripheral application of an irritant (capsaicin) also induced EMR. Both the induction and maintenance of this effect were blocked by bicuculline. Cellular indices of central sensitization [c-fos expression and ERK phosphorylation (pERK)] were also attenuated. In intact (sham operated) rats, bicuculline had the opposite effect. Pretreatment with a GABA agonist (muscimol) attenuated nociceptive sensitization in intact, but not spinally injured, rats. The effect of SCI on GABA function was linked to a reduction in the Cl - transporter, KCC2, leading to a reduction in intracellular Cl - that would attenuate GABA-mediated inhibition. Pharmacologically blocking the KCC2 channel (with i.t. DIOA) in intact rats mimicked the effect of SCI. Conversely, a pharmacological treatment (bumetanide) that should increase intracellular Cl - levels blocked the effect of SCI. The results suggest that GABAergic neurons drive, rather than inhibit, the development of nociceptive sensitization after spinal injury. Copyright © 2016 Elsevier Inc. All rights reserved.

Bi-phasic activation of the primary motor cortex by pain and its relation to pain-evoked potentials - an exploratory study.

PubMed

Kisler, Lee-Bareket; Weissman-Fogel, Irit; Sinai, Alon; Sprecher, Elliot; Chistyakov, Andrei V; Shamay-Tsoory, Simone; Moscovitz, Nadav; Granovsky, Yelena

2017-06-15

The primary motor cortex (M1) is a known target for brain stimulation aimed at pain alleviation in chronic pain patients, yet the mechanisms through which analgesia occurs, and the exact pain-motor interrelations are not fully understood. We used noxious contact heat evoked potentials (CHEPs) and cortical source analysis to further explore the relevance of M1 in pain processing. Twenty-four healthy young females received brief noxious heat stimuli to their left non-dominant volar forearm, simultaneously with CHEPs recordings. Thereafter, the pain-evoked activity of M1 and a control area in the occipital cortex (OC) was analyzed and estimated using sLORETA (standardized low-resolution brain electromagnetic tomography). This analysis revealed two phases of M1 pain-evoked activation (phase 1: the peak at 261.5±25.7ms; phase 2: the peak at 381.3±28.3ms). Canonical correlations revealed that M1, but not the OC, was the main factor contributing to the relation with the CHEPs components. In detail, the activity magnitude of M1 first and second phases was related to the N2 and P2 amplitude, respectively. The latency of the second phase was associated with both N2 and P2 latencies. In relation to pain, the latency of M1's first activity phase was positively correlated with pain ratings, suggesting pain interference to synchronized activity in M1. Our results confirm the established relevance of the primary motor cortex to pain processing. Copyright © 2017 Elsevier B.V. All rights reserved.

The Absence of Sensory Axon Bifurcation Affects Nociception and Termination Fields of Afferents in the Spinal Cord

PubMed Central

Tröster, Philip; Haseleu, Julia; Petersen, Jonas; Drees, Oliver; Schmidtko, Achim; Schwaller, Frederick; Lewin, Gary R.; Ter-Avetisyan, Gohar; Winter, York; Peters, Stefanie; Feil, Susanne; Feil, Robert; Rathjen, Fritz G.; Schmidt, Hannes

2018-01-01

A cGMP signaling cascade composed of C-type natriuretic peptide, the guanylyl cyclase receptor Npr2 and cGMP-dependent protein kinase I (cGKI) controls the bifurcation of sensory axons upon entering the spinal cord during embryonic development. However, the impact of axon bifurcation on sensory processing in adulthood remains poorly understood. To investigate the functional consequences of impaired axon bifurcation during adult stages we generated conditional mouse mutants of Npr2 and cGKI (Npr2fl/fl;Wnt1Cre and cGKIKO/fl;Wnt1Cre) that lack sensory axon bifurcation in the absence of additional phenotypes observed in the global knockout mice. Cholera toxin labeling in digits of the hind paw demonstrated an altered shape of sensory neuron termination fields in the spinal cord of conditional Npr2 mouse mutants. Behavioral testing of both sexes indicated that noxious heat sensation and nociception induced by chemical irritants are impaired in the mutants, whereas responses to cold sensation, mechanical stimulation, and motor coordination are not affected. Recordings from C-fiber nociceptors in the hind limb skin showed that Npr2 function was not required to maintain normal heat sensitivity of peripheral nociceptors. Thus, the altered behavioral responses to noxious heat found in Npr2fl/fl;Wnt1Cre mice is not due to an impaired C-fiber function. Overall, these data point to a critical role of axonal bifurcation for the processing of pain induced by heat or chemical stimuli. PMID:29472841

Perceived racial discrimination, but not mistrust of medical researchers, predicts the heat pain tolerance of African Americans with symptomatic knee osteoarthritis

PubMed Central

Pham, Quyen T.; Glover, Toni L.; Sotolongo, Adriana; King, Christopher D.; Sibille, Kimberly T.; Herbert, Matthew S.; Cruz-Almeida, Yenisel; Sanden, Shelley H.; Staud, Roland; Redden, David T.; Bradley, Laurence A.; Fillingim, Roger B.

2014-01-01

Objective Studies have shown that perceived racial discrimination is a significant predictor of clinical pain severity among African Americans. It remains unknown whether perceived racial discrimination also alters the nociceptive processing of painful stimuli, which, in turn, could influence clinical pain severity. This study examined associations between perceived racial discrimination and responses to noxious thermal stimuli among African Americans and non-Hispanic whites. Mistrust of medical researchers was also assessed given its potential to affect responses to the noxious stimuli. Method One hundred and thirty (52% African American, 48% non-Hispanic white) community-dwelling older adults with symptomatic knee osteoarthritis completed two study sessions. In session one, individuals provided demographic, socioeconomic, physical and mental health information. They completed questionnaires related to perceived lifetime frequency of racial discrimination and mistrust of medical researchers. In session two, individuals underwent a series of controlled thermal stimulation procedures to assess heat pain sensitivity, particularly heat pain tolerance. Results African Americans were more sensitive to heat pain and reported greater perceived racial discrimination as well as greater mistrust of medical researchers compared to non-Hispanic whites. Greater perceived racial discrimination significantly predicted lower heat pain tolerance for African Americans but not non-Hispanic whites. Mistrust of medical researchers did not significantly predict heat pain tolerance for either racial group Conclusion These results lend support to the idea that perceived racial discrimination may influence the clinical pain severity of African Americans via the nociceptive processing of painful stimuli. PMID:24219416

Minocycline reduces mechanical allodynia and depressive-like behaviour in type-1 diabetes mellitus in the rat.

PubMed

Amorim, Diana; Puga, Sónia; Bragança, Rui; Braga, António; Pertovaara, Antti; Almeida, Armando; Pinto-Ribeiro, Filipa

2017-06-01

A common and devastating complication of diabetes mellitus is painful diabetic neuropathy (PDN) that can be accompanied by emotional disorders such as depression. A few studies have suggested that minocycline that inhibits microglia may attenuate pain hypersensitivity in PDN. Moreover, a recent study reported that minocycline has an acute antidepressive-like effect in diabetic animals. Here we studied whether (i) prolonged minocycline treatment suppresses pain behaviour in PDN, (ii) the minocycline effect varies with submodality of pain, and (iii) the suppression of pain behaviour by prolonged minocycline treatment is associated with antidepressive-like effect. The experiments were performed in streptozotocin-induced rat model of type-1 diabetes. Pain behaviour was evoked by innocuous (monofilaments) and noxious (paw pressure) mechanical stimulation, innocuous cold (acetone drops) and noxious heat (radiant heat). Depression-like behaviour was assessed using forced swimming test. Minocycline treatment (daily 80mg/kg per os) of three-week duration started four weeks after induction of diabetes. Diabetes induced mechanical allodynia and hyperalgesia, cold allodynia, heat hypoalgesia, and depression-like behaviour. Minocycline treatment significantly attenuated mechanical allodynia and depression-like behaviour, while it failed to produce significant changes in mechanical hyperalgesia, cold allodynia or heat hypoalgesia. The results indicate that prolonged per oral treatment with minocycline has a sustained mechanical antiallodynic and antidepressive-like effect in PDN. These results support the proposal that minocycline might provide a treatment option for attenuating sensory and comorbid emotional symptoms in chronic PDN. Copyright © 2017 Elsevier B.V. All rights reserved.

The Timing of Acupuncture Stimulation Does Not Influence Anesthetic Requirement

PubMed Central

Chernyak, Grigory; Sengupta, Papiya; Lenhardt, Rainer; Liem, Edwin; Doufas, Anthony G.; Sessler, Daniel I.; Akça, Ozan

2005-01-01

Studies suggest that acupuncture is more effective when induced before induction of general anesthesia than afterwards. We tested the hypothesis that electro-acupuncture initiated 30 minutes before induction reduces anesthetic requirement more than acupuncture initiated after induction. Seven volunteers were each anesthetized with desflurane on 3 study days. Needles were inserted percutaneously at 4 acupuncture points thought to produce analgesia in the upper abdominal area and provide generalized sedative and analgesic effects: Zusanli (St36), Sanyinjiao (Sp6), Liangqiu (St34), and Hegu (LI4). Needles were stimulated at 2-Hz and 10-Hz, with frequencies alternating at two-second intervals. On Preinduction day, electro-acupuncture was started 30 minutes before induction of anesthesia and maintained throughout the study. On At-induction day, needles were positioned before induction of anesthesia, but electro-acupuncture stimulation was not initiated until after induction. On Control day, electrodes were positioned near the acupoints, but needles were not inserted. Noxious electrical stimulation was administered via 25-G needles on the upper abdomen (70 mA, 100 Hz, 10 seconds). Desflurane concentration was increased 0.5% when movement occurred and decreased 0.5% when it did not. These up-and-down sequences continued until volunteers crossed from movement to no-movement 4 times. The P50 of logistic regression identified desflurane requirement. Desflurane requirement was similar on the Control (5.2±0.6%, mean±SD), Preinduction (5.0±0.8%), and At-induction (4.7±0.3%, P=0.125) days. This type of acupuncture is thus unlikely to facilitate general anesthesia or decrease the need for anesthetic drugs. PMID:15673863

Projections from the nucleus reticularis magnocellularis to the rat cervical cord using electrical stimulation and iontophoretic injection methods.

PubMed

Watanabe, Shigeo; Kitamura, Taiko; Watanabe, Lisa; Sato, Hitoshi; Yamada, Jinzo

2003-03-01

The aim of this study is to clarify the fiber distribution of the nucleus reticularis magnocellularis (NRMC) and adjacent areas in the rat spinal cord. Biotinylated dextran amine was injected iontophoretically through a glass capillary into the areas, in which a single cell responded to noxious electrical stimulation of the sciatic nerve and to a pinch of the thigh skin with multiple spikes. Labeled fibers descended bilaterally through the ventral funiculi of the medulla oblongata and then through the ventral and lateral funiculi of the cervical cord with an ipsilateral predominance, and terminated in the spinal gray (laminae I-X). A single fiber sometimes ran through several laminae while bifurcating many short branches with axon varicosities and terminal buttons in one transverse section, that is, through laminae V, VII and X, through laminae V, IIl-IV and I-II, and through laminae VII to I-II. The present study showed that the wide distribution of a single fiber and a mass of fibers descending from the NRMC and adjacent areas might modulate not only somatic sensory and motor functions but also autonomic functions in the spinal cord.

Gingerol activates noxious cold ion channel TRPA1 in gastrointestinal tract.

PubMed

Yang, Meng-Qi; Ye, Lin-Lan; Liu, Xiao-Ling; Qi, Xiao-Ming; Lv, Jia-Di; Wang, Gang; Farhan, Ulah-Khan; Waqas, Nawaz; Chen, Ding-Ding; Han, Lei; Zhou, Xiao-Hui

2016-06-01

TRPA1 channels are non-selective cation channels that could be activated by plant-derived pungent products, including gingerol, a main active constituent of ginger. Ginger could improve the digestive function; however whether ginger improves the digestive function through activating TRPA1 receptor in gastrointestinal tract has not been investigated. In the present study, gingerol was used to stimulate cell lines (RIN14B or STC-1) while depletion of extracellular calcium. TRPA1 inhibitor (rethenium red) and TRPA1 gene silencing via TRPA1-specific siRNA were also used for mechanistic studies. The intracellular calcium and secretion of serotonin or cholecystokinin were measured by fura-2/AM and ELISA. Stimulation of those cells with gingerol increased intracellular calcium levels and the serotonin or cholecystokinin secretion. The gingerol-induced intracellular calcium increase and secretion (serotonin or cholecystokinin) release were completely blocked by ruthenium red, EGTA, and TRPA1-specific siRNA. In summary, our results suggested that gingerol derived from ginger might improve the digestive function through secretion releasing from endocrine cells of the gut by inducing TRPA1-mediated calcium influx. Copyright © 2016 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

The Tao of treating weeds: Reaching for restoration in the northern Rocky Mountains

Treesearch

Lisa-Natalie Anjozian

2008-01-01

Noxious weeds are a serious problem that is spreading across the West. Herbicides such as Picloram have proven to be powerful tools in reducing weed invaders, although use of this tool has often produced unintended consequences. Broadleaf herbicides kill forbs, such as the noxious knapweed, but also harm native forbs such as arrowleaf balsamroot. Removing weedy forbs...

Charting environmental pollution. [by noise measurements

NASA Technical Reports Server (NTRS)

Halpert, E.; Bizo, F.; Karacsonyi, Z.

1974-01-01

It is found that areas affected by different noxious agents are within the limits traced for high noise level areas; consequently, it is suggested that high noise pressure levels should be used as the primary indication of environmental pollution. A complex methodology is reported for charting environmental pollution due to physical, chemical and biological noxious agents on the scale of an industrial district.

Topical hindpaw application of L-menthol decreases responsiveness to heat with biphasic effects on cold sensitivity of rat lumbar dorsal horn neurons

PubMed Central

Klein, Amanda H.; Sawyer, Carolyn M.; Takechi, Kenichi; Davoodi, Auva; Ivanov, Margaret A.; Carstens, Mirela Iodi; Carstens, E

2012-01-01

Menthol is used in pharmaceutical applications because of its desired cooling and analgesic properties. The neural mechanism by which topical application of menthol decreases heat pain is not fully understood. We investigated the effects of topical menthol application on lumbar dorsal horn wide dynamic range and nociceptive-specific neuronal responses to noxious heat and cooling of glaborous hindpaw cutaneous receptive fields. Menthol increased thresholds for responses to noxious heat in a concentration-dependent manner. Menthol had a biphasic effect on cold-evoked responses, reducing the threshold (to warmer temperatures) at a low (1%) concentration and increasing threshold and reducing response magnitude at high (10, 40%) concentrations. Menthol had little effect on responses to innocuous or noxious mechanical stimuli, ruling out a local anesthetic action. Application of 40% menthol to the contralateral hindpaw tended to reduce responses to cooling and noxious heat, suggesting a weak heterosegmental inhibitory effect. These results indicate that menthol has an analgesic effect on heat sensitivity of nociceptive dorsal horn neurons, as well as biphasic effects on cold sensitivity, consistent with previous behavioral observations. PMID:22687951

Injections of Algesic Solutions into Muscle Activate the Lateral Reticular Formation: A Nociceptive Relay of the Spinoreticulothalamic Tract

PubMed Central

Panneton, W. Michael; Gan, Qi; Ariel, Michael

2015-01-01

Although musculoskeletal pain disorders are common clinically, the central processing of muscle pain is little understood. The present study reports on central neurons activated by injections of algesic solutions into the gastrocnemius muscle of the rat, and their subsequent localization by c-Fos immunohistochemistry in the spinal cord and brainstem. An injection (300μl) of an algesic solution (6% hypertonic saline, pH 4.0 acetate buffer, or 0.05% capsaicin) was made into the gastrocnemius muscle and the distribution of immunolabeled neurons compared to that obtained after control injections of phosphate buffered saline [pH 7.0]. Most labeled neurons in the spinal cord were found in laminae IV-V, VI, VII and X, comparing favorably with other studies, with fewer labeled neurons in laminae I and II. This finding is consistent with the diffuse pain perception due to noxious stimuli to muscles mediated by sensory fibers to deep spinal neurons as compared to more restricted pain localization during noxious stimuli to skin mediated by sensory fibers to superficial laminae. Numerous neurons were immunolabeled in the brainstem, predominantly in the lateral reticular formation (LRF). Labeled neurons were found bilaterally in the caudalmost ventrolateral medulla, where neurons responsive to noxious stimulation of cutaneous and visceral structures lie. Immunolabeled neurons in the LRF continued rostrally and dorsally along the intermediate reticular nucleus in the medulla, including the subnucleus reticularis dorsalis caudally and the parvicellular reticular nucleus more rostrally, and through the pons medial and lateral to the motor trigeminal nucleus, including the subcoerulear network. Immunolabeled neurons, many of them catecholaminergic, were found bilaterally in the nucleus tractus solitarii, the gracile nucleus, the A1 area, the CVLM and RVLM, the superior salivatory nucleus, the nucleus locus coeruleus, the A5 area, and the nucleus raphe magnus in the pons. The external lateral and superior lateral subnuclei of the parabrachial nuclear complex were consistently labeled in experimental data, but they also were labeled in many control cases. The internal lateral subnucleus of the parabrachial complex was labeled moderately. Few immunolabeled neurons were found in the medial reticular formation, however, but the rostroventromedial medulla was labeled consistently. These data are discussed in terms of an interoceptive, multisynaptic spinoreticulothalamic path, with its large receptive fields and role in the motivational-affective components of pain perceptions. PMID:26154308

Injections of Algesic Solutions into Muscle Activate the Lateral Reticular Formation: A Nociceptive Relay of the Spinoreticulothalamic Tract.

PubMed

Panneton, W Michael; Gan, Qi; Ariel, Michael

2015-01-01

Although musculoskeletal pain disorders are common clinically, the central processing of muscle pain is little understood. The present study reports on central neurons activated by injections of algesic solutions into the gastrocnemius muscle of the rat, and their subsequent localization by c-Fos immunohistochemistry in the spinal cord and brainstem. An injection (300 μl) of an algesic solution (6% hypertonic saline, pH 4.0 acetate buffer, or 0.05% capsaicin) was made into the gastrocnemius muscle and the distribution of immunolabeled neurons compared to that obtained after control injections of phosphate buffered saline [pH 7.0]. Most labeled neurons in the spinal cord were found in laminae IV-V, VI, VII and X, comparing favorably with other studies, with fewer labeled neurons in laminae I and II. This finding is consistent with the diffuse pain perception due to noxious stimuli to muscles mediated by sensory fibers to deep spinal neurons as compared to more restricted pain localization during noxious stimuli to skin mediated by sensory fibers to superficial laminae. Numerous neurons were immunolabeled in the brainstem, predominantly in the lateral reticular formation (LRF). Labeled neurons were found bilaterally in the caudalmost ventrolateral medulla, where neurons responsive to noxious stimulation of cutaneous and visceral structures lie. Immunolabeled neurons in the LRF continued rostrally and dorsally along the intermediate reticular nucleus in the medulla, including the subnucleus reticularis dorsalis caudally and the parvicellular reticular nucleus more rostrally, and through the pons medial and lateral to the motor trigeminal nucleus, including the subcoerulear network. Immunolabeled neurons, many of them catecholaminergic, were found bilaterally in the nucleus tractus solitarii, the gracile nucleus, the A1 area, the CVLM and RVLM, the superior salivatory nucleus, the nucleus locus coeruleus, the A5 area, and the nucleus raphe magnus in the pons. The external lateral and superior lateral subnuclei of the parabrachial nuclear complex were consistently labeled in experimental data, but they also were labeled in many control cases. The internal lateral subnucleus of the parabrachial complex was labeled moderately. Few immunolabeled neurons were found in the medial reticular formation, however, but the rostroventromedial medulla was labeled consistently. These data are discussed in terms of an interoceptive, multisynaptic spinoreticulothalamic path, with its large receptive fields and role in the motivational-affective components of pain perceptions.

Intracellular recordings of subnucleus reticularis dorsalis neurones revealed novel electrophysiological properties and windup mechanisms

PubMed Central

Soto, Cristina; Canedo, Antonio

2011-01-01

Abstract Aδ- and/or C-fibre nociceptive inputs drive subnucleus reticularis dorsalis (SRD) neurones projecting to a variety of regions including the spinal cord and the nucleus reticularis gigantocellularis (NRGc), but their electrophysiological properties are largely unknown. Here we intracellularly recorded the SRD neuronal responses to injection of polarising current pulses as well as to electrical stimulation of the cervical spinal posterior quadrant (PQ) and the NRGc. Three different classes of neurones with distinct electrophysiological properties were found: type I were characterised by the absence of a fast postspike hyperpolarisation, type II by the presence of a postspike hyperpolarisation followed by a depolarisation resembling low threshold calcium spikes (LTSs), and type III (lacking LTSs) had a fast postspike hyperpolarisation deinactivating A-like potassium channels leading to enlarged interspike intervals. All three classes generated depolarising sags to hyperpolarising current pulses and showed 3–4.5 Hz subthreshold oscillatory activity leading to windup when intracellularly injecting low-frequency repetitive depolarising pulses as well as in response to 0.5–2 Hz NRGc and PQ electrical stimulation. About half of the 132 sampled neurones responded antidromically to NRGc stimulation with more than 65% of the NRGc-antidromic cells, pertaining to all three types, also responding antidromically to PQ stimulation. NRGc stimulation induced exclusively excitatory first-synaptic-responses whilst PQ stimulation induced first-response excitation in most cases, but inhibitory postsynaptic potentials in a few type II and type III neurones not projecting to the spinal cord that also displayed cumulative inhibitory effects (inverse windup). The results show that SRD cells (i) can actively regulate different temporal firing patterns due to their intrinsic electrophysiological properties, (ii) generate windup upon gradual membrane depolarisation produced by low-frequency intracellular current injection and by C-fibre tonic input, both processes leading subthreshold oscillations to threshold, and (iii) collateralise to the NRGc and the spinal cord, potentially providing simultaneous regulation of ascending noxious information and motor reactions to pain. PMID:21746779

Intracellular recordings of subnucleus reticularis dorsalis neurones revealed novel electrophysiological properties and windup mechanisms.

PubMed

Soto, Cristina; Canedo, Antonio

2011-09-01

Aδ- and/or C-fibre nociceptive inputs drive subnucleus reticularis dorsalis (SRD) neurones projecting to a variety of regions including the spinal cord and the nucleus reticularis gigantocellularis (NRGc), but their electrophysiological properties are largely unknown. Here we intracellularly recorded the SRD neuronal responses to injection of polarising current pulses as well as to electrical stimulation of the cervical spinal posterior quadrant (PQ) and the NRGc. Three different classes of neurones with distinct electrophysiological properties were found: type I were characterised by the absence of a fast postspike hyperpolarisation, type II by the presence of a postspike hyperpolarisation followed by a depolarisation resembling low threshold calcium spikes (LTSs), and type III (lacking LTSs) had a fast postspike hyperpolarisation deinactivating A-like potassium channels leading to enlarged interspike intervals. All three classes generated depolarising sags to hyperpolarising current pulses and showed 3-4.5 Hz subthreshold oscillatory activity leading to windup when intracellularly injecting low-frequency repetitive depolarising pulses as well as in response to 0.5-2 Hz NRGc and PQ electrical stimulation. About half of the 132 sampled neurones responded antidromically to NRGc stimulation with more than 65% of the NRGc-antidromic cells, pertaining to all three types, also responding antidromically to PQ stimulation. NRGc stimulation induced exclusively excitatory first-synaptic-responses whilst PQ stimulation induced first-response excitation in most cases, but inhibitory postsynaptic potentials in a few type II and type III neurones not projecting to the spinal cord that also displayed cumulative inhibitory effects (inverse windup). The results show that SRD cells (i) can actively regulate different temporal firing patterns due to their intrinsic electrophysiological properties, (ii) generate windup upon gradual membrane depolarisation produced by low-frequency intracellular current injection and by C-fibre tonic input, both processes leading subthreshold oscillations to threshold, and (iii) collateralise to the NRGc and the spinal cord, potentially providing simultaneous regulation of ascending noxious information and motor reactions to pain.

Effect of systemic morphine on the responses of convergent neurons to noxious heat stimuli applied over graded surface areas.

PubMed

Gall, O; Bouhassira, D; Chitour, D; Le Bars, D

1999-04-01

Stimulus intensity is a major determinant of the antinociceptive activity of opiates. This study focused on the influence of the spatial characteristics of nociceptive stimuli, on opiate-induced depressions of nociceptive transmission at the level of the spinal cord. Anesthetized rats were prepared to allow extracellular recordings to be made from convergent neurons in the lumbar dorsal horn. The effects of systemic morphine (1 and 10 mg/kg) were compared with those of saline for thermal stimuli of constant intensity, applied to the area of skin surrounding the excitatory receptive field (1.9 cm2) or to a much larger adjacent area (18 cm2). The responses (mean +/- SD) elicited by the 1.9-cm2 stimulus were not modified by 1 mg/kg intravenous morphine, although they were decreased by the 10-mg/kg dose (to 11+/-4% of control values compared with saline; P < 0.05). In contrast, when the 18-cm2 stimulus was applied, 1 mg/kg intravenous morphine produced a paradoxical facilitation of the neuronal responses (159+/-36% of control values; P < 0.05) and 10 mg/kg intravenous morphine resulted in a weaker depression of the responses (to 42+/-24% of control values; P < 0.05) than was observed with the smaller stimulus. Doses of systemic morphine in the analgesic range for rats had dual effects on nociceptive transmission at the level of the spinal cord, depending on the surface area that was stimulated. Such effects are difficult to explain in terms of accepted pharmacodynamic concepts and may reflect an opioid-induced depression of descending inhibitory influences triggered by spatial summation.

Functional Neuroanatomy of the Noradrenergic Locus Coeruleus: Its Roles in the Regulation of Arousal and Autonomic Function Part II: Physiological and Pharmacological Manipulations and Pathological Alterations of Locus Coeruleus Activity in Humans

PubMed Central

Samuels, E. R; Szabadi, E

2008-01-01

The locus coeruleus (LC), the major noradrenergic nucleus of the brain, gives rise to fibres innervating most structures of the neuraxis. Recent advances in neuroscience have helped to unravel the neuronal circuitry controlling a number of physiological functions in which the LC plays a central role. Two such functions are the regulation of arousal and autonomic activity, which are inseparably linked largely via the involvement of the LC. Alterations in LC activity due to physiological or pharmacological manipulations or pathological processes can lead to distinct patterns of change in arousal and autonomic function. Physiological manipulations considered here include the presentation of noxious or anxiety-provoking stimuli and extremes in ambient temperature. The modification of LC-controlled functions by drug administration is discussed in detail, including drugs which directly modify the activity of LC neurones (e.g., via autoreceptors, storage, reuptake) or have an indirect effect through modulating excitatory or inhibitory inputs. The early vulnerability of the LC to the ageing process and to neurodegenerative disease (Parkinson’s and Alzheimer’s diseases) is of considerable clinical significance. In general, physiological manipulations and the administration of stimulant drugs, α2-adrenoceptor antagonists and noradrenaline uptake inhibitors increase LC activity and thus cause heightened arousal and activation of the sympathetic nervous system. In contrast, the administration of sedative drugs, including α2-adrenoceptor agonists, and pathological changes in LC function in neurodegenerative disorders and ageing reduce LC activity and result in sedation and activation of the parasympathetic nervous system. PMID:19506724

Gloves against mineral oils and mechanical hazards: composites of carboxylated acrylonitrile–butadiene rubber latex

PubMed Central

Krzemińska, Sylwia; Rzymski, Władysław M.; Malesa, Monika; Borkowska, Urszula; Oleksy, Mariusz

2016-01-01

Resistance to permeation of noxious chemical substances should be accompanied by resistance to mechanical factors because the glove material may be torn, cut or punctured in the workplace. This study reports on glove materials, protecting against mineral oils and mechanical hazards, made of carboxylated acrylonitrile–butadiene rubber (XNBR) latex. The obtained materials were characterized by a very high resistance of the produced materials to oil permeation (breakthrough time > 480 min). The mechanical properties, and especially tear resistance, of the studied materials were improved after the addition of modified bentonite (nanofiller) to the XNBR latex mixture. The nanocomposite meets the requirements in terms of parameters characterizing tear, abrasion, cut and puncture resistance. Therefore, the developed material may be used for the production of multifunctional protective gloves. PMID:26757889

Psychiatric therapeutic applications of virtual reality technology (VRT): research prospectus and phenomenological critique.

PubMed

Bloom, R W

1997-01-01

There is theoretical and empirical research supporting the hypothesis that virtual reality technology (VRT) can be efficaciously applied to attenuate the symptoms of mental disorders (Baer, 1996; Rothbaum et al, 1995a, 1995b; Rothbaum et al, 1996.) Yet there is also research suggesting psychiatric therapeutic applications of VRT may induce noxious or unexpected psychological consequences (Kolasinski, 1996; Muscott & Gifford, 1994; Regan & Price, 1994; Regan & Ramsey, 1996; Strickland, 1995.) A prudent conclusion would be to advocate ever more sophisticated studies on psychiatric therapeutic applications of VRT concerning (1) increasing the overall socioadaptiveness of patients, (2) the robustness of moderating, modifying, or other intermediary variables effecting or affecting VRT therapeutic efficacy, and (3) variables, processes, and hypotheses generated from VRT applications in non-psychiatric fields.

Neonatal capsaicin treatment in rats affects TRPV1-related noxious heat sensation and circadian body temperature rhythm.

PubMed

Jeong, Keun-Yeong; Seong, Jinsil

2014-06-15

The transient receptor potential vanilloid 1 (TRPV1) is a cation channel that serves as a polymodal detector of noxious stimuli such as capsaicin. Therefore, capsaicin treatment has been used to investigate the physiological function of TRPV1. Here, we report physiological changes induced by treating neonatal rats with capsaicin. Capsaicin (50mg/kg) (cap-treated) or vehicle (vehicle-treated) was systemically administered to newborn SD rat pups within 48 h after birth. TRPV1 expression, intake volume of capsaicin water, and noxious heat sensation were measured 6 weeks after capsaicin treatment. Circadian body temperature and locomotion were recorded by biotelemetry. Expression of Per1, Per2, Bmal1 and Hsf1 (clock genes) was also investigated. Neonatal capsaicin treatment not only decreased TRPV1 expression but also induced desensitization to noxious heat stimuli. Circadian body temperature of cap-treated rats increased significantly compared with that of vehicle-treated rats. Additionally, the amplitude of the circadian body temperature was reversed in cap-treated rats. Expression of the hypothalamic Hsf1 and liver Per2 clock genes followed a similar trend. Therefore, we suggest that these findings will be useful in studying various physiological mechanisms related to TRPV1. Copyright © 2014 Elsevier B.V. All rights reserved.

In vivo antinociceptive and anticonvulsant activity of extracts of Heliotropium strigosum.

PubMed

Khan, Haroon; Khan, Murad Ali; Hussain, Sajid; Gaffar, Rukhsana; Ashraf, Nadeem

2016-05-01

Natural healing agents are primarily focused to overcome unwanted side effects with synthetic drugs worldwide. In the proposed study, crude extracts and subsequent solvent fractions of Heliotropium strigosum were evaluated for antinociceptive and anticonvulsant activity in animal paradigms. In post acetic acid-induced writhing test, crude extract and fractions (hexane, ethyl acetate, and aqueous) demonstrated marked attenuation of nociception at test doses (50, 100, and 200 mg/kg i.p.). When challenged against thermally induced pain model, pretreatment of extracts exhibited prominent amelioration at test dose (50, 100, and 200 mg/kg i.p.). In both tests, inhibition of noxious stimulation was in a dose-dependent manner, and ethyl acetate fraction was most dominant. However, extracts did not antagonize the seizures and mortality induced by pentylenetetrazole. In conclusion, the extracts of H. strigosum illustrated significant antinociceptive effect in both centrally and peripherally acting pain models. © The Author(s) 2013.

Anterior Insula Activity Reflects the Effects of Intentionality on the Anticipation of Aversive Stimulation

PubMed Central

Dunne, Simon; O'Doherty, John P.

2014-01-01

If someone causes you harm, your affective reaction to that person might be profoundly influenced by your inferences about the intentionality of their actions. In the present study, we aimed to understand how affective responses to a biologically salient aversive outcome administered by others are modulated by the extent to which a given individual is judged to have deliberately or inadvertently delivered the outcome. Using fMRI, we examined how neural responses to anticipation and receipt of an aversive stimulus are modulated by this fundamental social judgment. We found that affective evaluations about an individual whose actions led to either noxious or neutral consequences for the subject did indeed depend on the perceived intentions of that individual. At the neural level, activity in the anterior insula correlated with the interaction between perceived intentionality and anticipated outcome valence, suggesting that this region reflects the influence of mental state attribution on aversive expectations PMID:25143614

Estrogen anti-inflammatory activity in brain: a therapeutic opportunity for menopause and neurodegenerative diseases

PubMed Central

Vegeto, Elisabetta; Benedusi, Valeria; Maggi, Adriana

2008-01-01

Recent studies highlight the prominent role played by estrogens in protecting the central nervous system (CNS) against the noxious consequences of a chronic inflammatory reaction. The neurodegenerative process of several CNS diseases, including Multiple Sclerosis, Alzheimer’s and Parkinson’s Diseases, is associated with the activation of microglia cells, which drive the resident inflammatory response. Chronically stimulated during neurodegeneration, microglia cells are thought to provide detrimental effects on surrounding neurons. The inhibitory activity of estrogens on neuroinflammation and specifically on microglia might thus be considered as a beneficial therapeutic opportunity for delaying the onset or progression of neurodegenerative diseases; in addition, understanding the peculiar activity of this female hormone on inflammatory signalling pathways will possibly lead to the development of selected anti-inflammatory molecules. This review summarises the evidence for the involvement of microglia in neuroinflammation and the anti-inflammatory activity played by estrogens specifically in microglia. PMID:18522863

Transcutaneous electrical nerve stimulation on Yongquan acupoint reduces CFA-induced thermal hyperalgesia of rats via down-regulation of ERK2 phosphorylation and c-Fos expression.

PubMed

Yang, Lin; Yang, Lianxue; Gao, Xiulai

2010-07-01

Activation of extracellular signal-regulated kinase-1/2 (ERK1/2) and its involvement in regulating gene expression in spinal dorsal horn, cortical and subcortical neurons by peripheral noxious stimulation contribute to pain hypersensitivity. Transcutaneous electrical nerve stimulation (TENS) is a treatment used in physiotherapy practice to promote analgesia in acute and chronic inflammatory conditions. In this study, a total number of 114 rats were used for three experiments. Effects of complete Freund's adjuvant (CFA)-induced inflammatory pain hypersensitivity and TENS analgesia on ERK1/2 phosphorylation and c-Fos protein expression were examined by using behavioral test, Western blot, and immunostaining methods. We found that CFA injection caused an area of localized swelling, erythema, hypersensitivity to thermal stimuli, the decreased response time of hind paw licking (HPL), as well as upregulation of c-Fos protein expression and ERK2 phosphorylation in the ipsilateral spinal dorsal horn and the contralateral primary somatosensory area of cortex and the amygdala of rats. TENS on Yongquan acupoint for 20 min produced obvious analgesic effects as demonstrated with increased HPL to thermal stimuli of CFA-treated rats. In addition, TENS application suppressed the CFA-induced ERK2 activation and c-Fos protein expression. These results suggest that down-regulation of ERK2 phosphorylation and c-Fos expression were involved in TENS inhibition on CFA-induced thermal hyperalgesia of rats.

Bilateral connectivity in the somatosensory region using near-infrared spectroscopy (NIRS) by wavelet coherence

NASA Astrophysics Data System (ADS)

Fernandez Rojas, Raul; Huang, Xu; Ou, Keng-Liang

2016-12-01

Near-infrared spectroscopy (NIRS) has been used in medical imaging to obtain oxygenation and hemodynamic response in the cerebral cortex. This technique has been applied in cortical activation detection and functional connectivity in brain research. Despite some advances in functional connectivity, most of the studies have focused on the prefrontal cortex and little has been done to study the somatosensory region (S1). For that reason, the aim of our present study is to assess bilateral connectivity in the somatosensory region by using NIRS and noxious stimulation. Eleven healthy subjects were investigated using near-infrared spectroscopy during an acupuncture stimulation procedure to safely induce pain in subjects. A multiscale analysis based on wavelet transform coherence (WTC) was designed to assess the functional connectivity of corresponding channel pairs within the left and right s1 region. The cortical activation in the somatosensory region was higher after the acupuncture stimulation, which was consistent with similar studies. The coherence in time-frequency domain between homologous signals generated by contralateral channel pairs revealed two main periods (3.2 s and 12.8 s) with high coherence. Based on the WTC analysis, it was also found that the coherence increase in these periods was task-related. This study contributes to the research field to investigate cerebral hemodynamic response of pain perception using NIRS and demonstrates the use of wavelet transform as a method to investigate functional lateralization in the cerebral cortex.

Thermally stimulated processes in samarium-modified lead titanate ferroelectric ceramics

NASA Astrophysics Data System (ADS)

Peláiz-Barranco, A.; García-Wong, A. C.; González-Abreu, Y.; Gagou, Y.; Saint-Grégoire, P.

2013-08-01

The thermally stimulated processes in a samarium-modified lead titanate ferroelectric system are analyzed from the thermally stimulated depolarization discharge current. The discharge due to the space charge injected during the poling process, the pyroelectric response and a conduction process related to oxygen vacancies are evaluated considering a theoretical decomposition by using a numerical method. The pyroelectric response is separated from other components to evaluate the polarization behavior and some pyroelectric parameters. High remanent polarization, pyroelectric coefficient and merit figure values are obtained at room temperature.

Explaining Entropy responses after a noxious stimulus, with or without neuromuscular blocking agents, by means of the raw electroencephalographic and electromyographic characteristics.

PubMed

Aho, A J; Lyytikäinen, L-P; Yli-Hankala, A; Kamata, K; Jäntti, V

2011-01-01

Entropy™, an anaesthetic EEG monitoring method, yields two parameters: State Entropy (SE) and Response Entropy (RE). SE reflects the hypnotic level of the patient. RE covers also the EMG-dominant part of the frequency spectrum, reflecting the upper facial EMG response to noxious stimulation. We studied the EEG, EMG, and Entropy values before and after skin incision, and the effect of rocuronium on Entropy and EMG at skin incision during sevoflurane-nitrous oxide (N₂O) anaesthesia. Thirty-eight patients were anaesthetized with sevoflurane-N₂O or sevoflurane-N₂O-rocuronium. The biosignal was stored and analysed off-line to detect EEG patterns, EMG, and artifacts. The signal, its power spectrum, SE, RE, and RE-SE values were analysed before and after skin incision. The EEG arousal was classified as β (increase in over 8 Hz activity and decrease in under 4 Hz activity with a typical β pattern) or δ (increase in under 4 Hz activity with the characteristic rhythmic δ pattern and a decrease in over 8 Hz activity). The EEG arousal appeared in 17 of 19 and 15 of 19 patients (NS), and the EMG arousal in 0 of 19 and 13 of 19 patients (P<0.01) with and without rocuronium, respectively. Both β (n=30) and EMG arousals increased SE and RE. The δ arousal (n=2) decreased both SE and RE. A significant increase in RE-SE values was only seen in patients without rocuronium. During sevoflurane-N₂O anaesthesia, both EEG and EMG arousals were seen. β and δ arousals had opposite effects on the Entropy values. The EMG arousal was abolished by rocuronium at the train of four level 0/4.

NMDA or non-NMDA receptor antagonism within the amygdaloid central nucleus suppresses the affective dimension of pain in rats: evidence for hemispheric synergy.

PubMed

Spuz, Catherine A; Borszcz, George S

2012-04-01

The amygdala contributes to generation of affective behaviors to threats. The prototypical threat to an individual is exposure to a noxious stimulus and the amygdaloid central nucleus (CeA) receives nociceptive input that is mediated by glutamatergic neurotransmission. The present study evaluated the contribution of glutamate receptors in CeA to generation of the affective response to acute pain in rats. Vocalizations that occur following a brief noxious tail shock (vocalization afterdischarges) are a validated rodent model of pain affect, and were preferentially suppressed by bilateral injection into CeA of the NMDA receptor antagonist D-2-amino-5-phosphonovalerate (AP5, 1 μg, 2 μg, or 4 μg) or the non-NMDA receptor antagonist 6-Cyano-7-nitroquinoxaline-2,3-dione disodium (CNQX, .25 μg, .5 μg, 1 μg, or 2 μg). Vocalizations that occur during tail shock were suppressed to a lesser degree, whereas spinal motor reflexes (tail flick and hind limb movements) were unaffected by injection of AP5 or CNQX into CeA. Unilateral administration of AP5 or CNQX into CeA of either hemisphere also selectively elevated vocalization thresholds. Bilateral administration of AP5 or CNQX produced greater increases in vocalization thresholds than the same doses of antagonists administered unilaterality into either hemisphere indicating synergistic hemispheric interactions. The amygdala contributes to production of emotional responses to environmental threats. Blocking glutamate neurotransmission within the central nucleus of the amygdala suppressed rats' emotional response to acute painful stimulation. Understanding the neurobiology underlying emotional responses to pain will provide insights into new treatments for pain and its associated affective disorders. Copyright © 2012 American Pain Society. Published by Elsevier Inc. All rights reserved.

Association of down-regulation of calcitonin gene-related peptide and substance P with increase of myocardial vulnerability in diabetic neuropathic rats.

PubMed

Li, Tu-Ping; Guo, Zheng; Liu, Chao-Jie; Sun, Tao; Chen, Lu; Zhao, Xin

2017-10-01

Diabetic patients present high co-morbidities of neuropathy and severer consequences of coronary heart disease. But the pathological mechanism is still unclear. Here we investigated a potential association of diabetic impairment of sensory nerves with increase of vulnerability of myocardium in acute myocardial ischemia/reperfusion. A rat model of diabetes mellitus was induced by high fat and sugar diet plus a small dose of streptozotocin. Impairment of sensory nerves was evaluated by measurement of changes in tail flick latency to noxious thermal stimulation and calcitonin gene-related peptide (CGRP) and substance P (SP) in the dorsal root ganglia (DRG) and the myocardium of the heart were examined. The myocardial injury was examined by infarct size, apoptosis ratio of cardiomyocytes and cardiac troponin I in the animals underwent acute myocardial ischemia (for 30min) and reperfusion (for 120min). The effects of CGRP and SP on cardiomyocyte injury induced by high glucose and hypoxia/reoxygenation were tested in cultured myocytes. The diabetic animals presented significant elevation of noxious thermal threshold with obvious reduction of the contents of CGRP and SP in the DRG and the myocardium. Importantly, the diabetic animals showed significant increases of infarct size, myocyte apoptosis and serum cardiac troponin I after acute myocardial ischemia/reperfusion, compared to the non-diabetic control. Furthermore, exogenously administered CGRP and SP attenuated the myocyte injury induced by the high concentration of glucose and hypoxia/reoxygenation. These findings suggested that impairment of sensory nerves with significant reduction of CGRP and SP in DRG, ventricular myocardium and serum may be associated with increase of myocardial vulnerability in acute myocardial ischemia/reperfusion in streptozotocin-induced diabetic rats. Copyright © 2017 Elsevier Inc. All rights reserved.

Peripheral KV7 channels regulate visceral sensory function in mouse and human colon

PubMed Central

Hockley, James RF; Reed, David E; Smith, Ewan St. John; Bulmer, David C; Blackshaw, L Ashley

2017-01-01

Background Chronic visceral pain is a defining symptom of many gastrointestinal disorders. The KV7 family (KV7.1–KV7.5) of voltage-gated potassium channels mediates the M current that regulates excitability in peripheral sensory nociceptors and central pain pathways. Here, we use a combination of immunohistochemistry, gut-nerve electrophysiological recordings in both mouse and human tissues, and single-cell qualitative real-time polymerase chain reaction of gut-projecting sensory neurons, to investigate the contribution of peripheral KV7 channels to visceral nociception. Results Immunohistochemical staining of mouse colon revealed labelling of KV7 subtypes (KV7.3 and KV7.5) with CGRP around intrinsic enteric neurons of the myenteric plexuses and within extrinsic sensory fibres along mesenteric blood vessels. Treatment with the KV7 opener retigabine almost completely abolished visceral afferent firing evoked by the algogen bradykinin, in agreement with significant co-expression of mRNA transcripts by single-cell qualitative real-time polymerase chain reaction for KCNQ subtypes and the B2 bradykinin receptor in retrogradely labelled extrinsic sensory neurons from the colon. Retigabine also attenuated responses to mechanical stimulation of the bowel following noxious distension (0–80 mmHg) in a concentration-dependent manner, whereas the KV7 blocker XE991 potentiated such responses. In human bowel tissues, KV7.3 and KV7.5 were expressed in neuronal varicosities co-labelled with synaptophysin and CGRP, and retigabine inhibited bradykinin-induced afferent activation in afferent recordings from human colon. Conclusions We show that KV7 channels contribute to the sensitivity of visceral sensory neurons to noxious chemical and mechanical stimuli in both mouse and human gut tissues. As such, peripherally restricted KV7 openers may represent a viable therapeutic modality for the treatment of gastrointestinal pathologies. PMID:28566000

Src family kinases mediate the inhibition of substance P release in the rat spinal cord by μ-opioid receptors and GABAB receptors, but not α2 adrenergic receptors

PubMed Central

Zhang, Guohua; Chen, Wenling; Marvizón, Juan Carlos G.

2010-01-01

GABAB, μ-opioid, and adrenergic α2 receptors inhibit substance P release from primary afferent terminals in the dorsal horn. Studies in cell expression systems suggest that μ-opioid and GABAB receptors inhibit transmitter release from primary afferents by activating Src family kinases (SFKs), which then phosphorylate and inhibit voltage-gated calcium channels. This study investigated whether SFKs mediate the inhibition of substance P release by these three receptors. Substance P release was measured as neurokinin 1 receptor (NK1R) internalization in spinal cord slices and in vivo. In slices, NK1R internalization induced by high frequency dorsal root stimulation was inhibited by the μ-opioid agonist DAMGO and the GABAB agonist baclofen. This inhibition was reversed by the SFK inhibitor PP1. NK1R internalization induced by low frequency stimulation was also inhibited by DAMGO, but PP1 did not reverse this effect. In vivo, NK1R internalization induced by noxious mechanical stimulation of the hind paw was inhibited by intrathecal DAMGO and baclofen. This inhibition was reversed by intrathecal PP1, but not by the inactive PP1 analog PP3. PP1 produced no effect by itself. The α2 adrenergic agonists medetomidine and guanfacine produced a small but statistically significant inhibition of NK1R internalization induced by low frequency dorsal root stimulation. PP1 did not reverse the inhibition by guanfacine. These results show that SFKs mediate the inhibition of substance P release by μ-opioid and GABAB receptors, but not by α2 receptors, which is probably mediated by the binding of G protein βγ subunits to calcium channels. PMID:20726886

Psychophysics, flare, and neurosecretory function in human pain models: capsaicin versus electrically evoked pain.

PubMed

Geber, Christian; Fondel, Ricarda; Krämer, Heidrun H; Rolke, Roman; Treede, Rolfe-Detlef; Sommer, Claudia; Birklein, Frank

2007-06-01

Intradermal capsaicin injection (CAP) and electrical current stimulation (ES) are analyzed in respect to patterns and test-retest reliability of pain as well as sensory and neurosecretory changes. In 10 healthy subjects, 2x CAP (50 microg) and 2x ES (5 to 30 mA) were applied to the volar forearm. The time period between 2 identical stimulations was about 4 months. Pain ratings, areas of mechanical hyperalgesia, and allodynia were assessed. The intensity of sensory changes was quantified by using quantitative sensory testing. Neurogenic flare was assessed by using laser Doppler imaging. Calcitonin gene-related peptide (CGRP) release was quantified by dermal microdialysis in combination with an enzyme immunoassay. Time course and peak pain ratings were different between CAP and ES. Test-retest correlation was high (r > or = 0.73). Both models induced primary heat hyperalgesia and primary plus secondary pin-prick hyperalgesia. Allodynia occurred in about half of the subjects. Maximum flare sizes did not differ between CAP and ES, but flare intensities were higher for ES. Test-retest correlation was higher for flare sizes than for flare intensity. A significant CGRP release could only be measured after CAP. The different time courses of pain stimulation (CAP: rapidly decaying pain versus ES: pain plateau) led to different peripheral neurosecretory effects but induced similar central plasticity and hyperalgesia. The present study gives a detailed overview of psychophysical and neurosecretory characteristics induced by noxious stimulation with capsaicin and electrical current. We describe differences, similarities, and reproducibility of these human pain models. These data might help to interpret past and future results of human pain studies using experimental pain.

[Oxytocin, a mediator of anti-stress, well-being, social interaction, growth and healing].

PubMed

Uvnas-Moberg, Kerstin; Petersson, Maria

2005-01-01

The neuroendocrine and physiological systems related to pain and stress have long been subjected to study. More recently, the corresponding systems promoting anti-stress and restoration have also come into focus. It is not only important to investigate the mechanisms underlying disease but also to examine the physiological and psychological mechanisms which protect and heal the body and soul. The nonapeptide oxytocin, originally known to stimulate labour and milk ejection, appears to play an important role in this regard. Oxytocin can induce anti-stress-like effects such as reduction of blood pressure and cortisol levels. It increases pain thresholds, exerts an anxiolytic-like effect and stimulates various types of positive social interaction. In addition, it promotes growth and healing. Repeated exposure to oxytocin causes long-lasting effects by influencing the activity of other transmitter systems, a pattern which makes oxytocin potentially clinically relevant. Oxytocin can be released by various types of non-noxious sensory stimulation, for example by touch and warmth. Ingestion of food triggers oxytocin release by activation of vagal afferents. Most likely, oxytocin can also be released by stimulation of other senses such as olfaction, as well as by certain types of sound and light. In addition, purely psychological mechanisms may trigger the release of oxytocin. This means that positive interaction involving touch and psychological support may be health-promoting. The social interaction of daily life, as well as a positive environment, continuously activate this system. In addition, various types of psychotherapy involving transfer of support, warmth and empathy are likely to induce similar effects, which thus contribute to the positive effects of these kinds of therapies.

Acute d-amphetamine pretreatment does not alter stimulant self-administration in humans.

PubMed

Stoops, William W; Vansickel, Andrea R; Lile, Joshua A; Rush, Craig R

2007-05-01

Recent clinical research indicates that d-amphetamine is effective in treating cocaine and methamphetamine dependence. There is concern, however, with the use of d-amphetamine as a pharmacotherapy because acute administration of d-amphetamine decreases inhibition in cocaine-using individuals and may increase drug-taking behavior. The purpose of the present experiment was to determine whether acute d-amphetamine pretreatment would alter the reinforcing, subject-rated, and cardiovascular effects of d-amphetamine. To this end, 7 human volunteers first sampled doses of oral d-amphetamine (0, 8, and 16 mg). These doses engender moderate drug taking and were selected to avoid a ceiling or floor effect. Volunteers were then allowed to self-administer these sampled doses using a modified progressive-ratio procedure in two sessions in which they received pretreatment with either 0 or 15 mg oral d-amphetamine 2 h prior to completing the modified progressive-ratio procedure. d-Amphetamine produced prototypical stimulant-like effects (e.g., increased ratings of stimulated, elevated blood pressure) and maintained responding on the modified progressive-ratio schedule. Pretreatment with 15 mg oral d-amphetamine also produced prototypical stimulant-like effects, but failed to alter break points for d-amphetamine on the modified progressive-ratio procedure relative to placebo pretreatment. These results indicate that acute d-amphetamine pretreatment does not increase stimulant self-administration.

Blood parameters and electroencephalographic responses of goats to slaughter without stunning.

PubMed

Sabow, A B; Goh, Y M; Zulkifli, I; Sazili, A Q; Kaka, U; Kadi, M Z A Ab; Ebrahimi, M; Nakyinsige, K; Adeyemi, K D

2016-11-01

The study compared changes in blood biochemistry, hormonal and electroencephalographic indices associated with possible noxious stimuli following neck cut slaughter in conscious, non-anaesthetized versus minimally-anaesthetized goats. Ten male Boer crossbreed goats were assigned into two groups and subjected to either slaughter conscious without stunning (SWS) or slaughter following minimal anaesthesia (SMA). Hormonal responses and changes in electroencephalographic (EEG) parameters were not influenced by slaughter method. The SWS goats had higher glucose and lactate than did SMA goats. It can be concluded that the noxious stimulus from the neck cut is present in both conscious and minimally anaesthetized goats. The application of slaughter without stunning causes changes in the EEG activities that are consistent with the presence of post slaughter noxious sensory input associated with tissue damage and would be expected to be experienced as pain in goats. Copyright © 2016. Published by Elsevier Ltd.

Pupillary Reflex for Evaluation of Thoracic Paravertebral Block: A Prospective Observational Feasibility Study.

PubMed

Duceau, Baptiste; Baubillier, Mélanie; Bouroche, Gaëlle; Albi-Feldzer, Aline; Jayr, Christian

2017-10-01

Although thoracic paravertebral block (TPVB) is recommended in major breast surgery, there is no gold standard to assess the success of TPVB. Pupillary dilation reflex (PDR) is the variation of the pupillary diameter after a noxious stimulus. The objective was to evaluate the feasibility of recording the PDR to assess analgesia in an anesthetized thoracic dermatome after TPVB. This prospective, observational, single-center study included 32 patients requiring breast surgery under general anesthesia and TPVB. TPVB was performed before surgery under ultrasound guidance with 20 mL of 0.75% ropivacaine. At the end of the surgery, remifentanil was stopped and the PDR was recorded after a 5-second tetanic stimulation (60 mA, 100 Hz) applied to the anterior chest wall. The PDR was defined as the maximal increase in pupil diameter after a standardized noxious stimulus, expressed as a percentage of the initial pupil diameter. The PDR was recorded twice in the same eye for each patient after a stimulus on both the TPVB and the control sides. Postoperative pain scores were recorded in a postanesthesia care unit. The primary outcome was the difference between the PDR on the TPVB and the control sides. The median (interquartile range) PDR was 9% (4%-13%) on the TPVB side and 41% (27%-66%) on the control side. There was a significant difference in the PDR between the TPVB and the control sides with a Hodges-Lehmann estimate of absolute difference of 37% points (95% confidence interval, 25-52, P < .001). Median postoperative pain scores (interquartile range) in the postanesthesia care unit were 1 (0-3) at rest and 1 (0-3) during mobilization, respectively. There was a linear correlation between maximal postoperative pain scores and the PDR on the TPVB side with a Pearson's correlation coefficient r = 0.40 (95% confidence interval, 0.06-0.66, P = .02). No correlation was found between the number of blocked dermatomes and maximal postoperative pain scores (P = .06) or between the number of blocked dermatomes and the PDR on the TPVB side (P = .15). This proof-of-concept trial suggests that the effect of TPVB could be monitored by measuring the PDR after anterior chest wall stimulation in the dermatome of interest.

Restoration of gait by functional electrical stimulation in paraplegic patients: a modified programme of treatment.

PubMed

Malezic, M; Hesse, S

1995-03-01

Restoration of standing and of gait by functional electrical stimulation in clinically complete paraplegic patients was modified in the course of treatment and in the stimulation parameters. By substituting an initial cyclic muscle strengthening with an active stimulated standing, four patients with T3-11 lesions started walking with electrical stimulation in 10-17 days. They walked without ankle-foot orthoses. With a satisfactory stride length of 0.75-0.97 m, their gait velocity ranged from very slow to that of a leisurely healthy gait. Already established stimulation of the quadriceps muscles for standing and of the peroneal nerves for lower limb flexion during the swing phase of gait was applied. Diminished limb flexion after several weeks was restored by an increase of the stimulation frequency of the peroneal nerve from 20 to 60 Hz. EMG and kinesiological measurements displayed an improved direct response of the ankle as well as of the reflex mediated hip, knee and ankle flexion response. At the same time stimulation frequency was reduced to 16 Hz for the quadriceps muscles in order to reduce fatigue.

Placing pain on the sensory map: classic papers by Ed Perl and colleagues.

PubMed

Mason, Peggy

2007-03-01

This essay looks at two papers published by Ed Perl and co-workers that identified specifically nociceptive neurons in the periphery and superficial dorsal horn. Bessou P and Perl ER. Response of cutaneous sensory units with unmyelinated fibers to noxious stimuli. J Neurophysiol 32: 1025-1043 1969. Christensen BN and Perl ER. Spinal neurons specifically excited by noxious or thermal stimuli: marginal zone of the dorsal horn. J Neurophysiol 33: 293-307 1970.

Blockade of Opioid Receptors in the Medullary Reticularis Nucleus Dorsalis, but not the Rostral Ventromedial Medulla, Prevents Analgesia Produced by Diffuse Noxious Inhibitory Control in Rats With Muscle Inflammation

PubMed Central

de Resende, Marcos A.; Silva, Luis Felipe S.; Sato, Karina; Arendt-Nielsen, Lars; Sluka, Kathleen A.

2014-01-01

Diffuse Noxious Inhibitory Controls (DNIC) involves application of a noxious stimulus outside the testing site to produce analgesia. In human subjects with a variety of chronic pain conditions, DNIC is less effective; however, in animal studies, DNIC is more effective after tissue injury. While opioids are involved in DNIC analgesia, the pathways involved in this opioid-induced analgesia are not clear. The aim of the present study was to test the effectiveness of DNIC in inflammatory muscle pain, and to study which brainstem sites mediate DNIC- analgesia. Rats were injected with 3% carrageenan into their gastrocnemius muscle and responses to cutaneous and muscle stimuli were assessed before and after inflammation, and before and after DNIC induced by noxious heat applied to the tail (45°C and 47°C). Naloxone was administered systemically, into rostral ventromedial medulla (RVM), or bilaterally into the medullary reticularis nucleus dorsalis (MdD) prior to the DNIC-conditioning stimuli. DNIC produced a similar analgesic effect in both acute and the chronic phases of inflammation reducing both cutaneous and muscle sensitivity in a dose-dependent manner. Naloxone systemically or microinjected into the MdD prevented DNIC-analgesia, while naloxone into the RVM had no effect on DNIC analgesia. Thus, DNIC analgesia involves activation of opioid receptors in the MdD. PMID:21330219

Commandant's international technical series. Volume 9. International regulations on the prevention of pollution from ships carrying hazardous chemicals in bulk. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1985-12-01

MARPOL was developed to minimize accidental and operational pollution from ships carrying noxious liquid substances in bulk. Accidental pollution could result from a collision, a grounding, or an overflow of a cargo tank. Operational pollution results from the disposal of cargo tank washings. Major amendments were made to the original Annex II by the International Maritime Organization. The United States and other States party to MARPOL will implement Annex II, as amended, on April 7, 1987. Implementation will affect seagoing ships transporting noxious liquid substances to and from such ships. The attached documents contain internationally agreed requirements, interpretations, and guidelinesmore » necessary for the implementation of Annex II. The documents attached include: (1) MARPOL Annex II as amended by amendments adopted by the twenty-second session of the IMO Marine Environment Protection Committee; (2) Unified Interpretations of Annex II; (3) Standards for the Procedures and Arrangements for the Discharge of Noxious Liquid Substances; (4) Ammendments to the Bulk Chemical Code and the International Bulk Chemical Code to include marine pollution concerns; (5) Guidelines on the Provision of Adequate Reception Facilities in Ports, Part II (Noxious Liquid Substances). The contents of these documents are being placed in regulations. The purpose of this document is to give members of the interested public advance notification of impending regulations.« less

Cross-modal and modality-specific expectancy effects between pain and disgust

PubMed Central

Sharvit, Gil; Vuilleumier, Patrik; Delplanque, Sylvain; Corradi-Dell’ Acqua, Corrado

2015-01-01

Pain sensitivity increases when a noxious stimulus is preceded by cues predicting higher intensity. However, it is unclear whether the modulation of nociception by expectancy is sensory-specific (“modality based”) or reflects the aversive-affective consequence of the upcoming event (“unpleasantness”), potentially common with other negative events. Here we compared expectancy effects for pain and disgust by using different, but equally unpleasant, nociceptive (thermal) and olfactory stimulations. Indeed both pain and disgust are aversive, associated with threat to the organism, and processed in partly overlapping brain networks. Participants saw cues predicting the unpleasantness (high/low) and the modality (pain/disgust) of upcoming thermal or olfactory stimulations, and rated the associated unpleasantness after stimuli delivery. Results showed that identical thermal stimuli were perceived as more unpleasant when preceded by cues threatening about high (as opposed to low) pain. A similar expectancy effect was found for olfactory disgust. Critically, cross-modal expectancy effects were observed on inconsistent trials when thermal stimuli were preceded by high-disgust cues or olfactory stimuli preceded by high-pain cues. However, these effects were stronger in consistent than inconsistent conditions. Taken together, our results suggest that expectation of an unpleasant event elicits representations of both its modality-specific properties and its aversive consequences. PMID:26631975

Acute heat-evoked temperature sensation is impaired but not abolished in mice lacking TRPV1 and TRPV3 channels.

PubMed

Marics, Irène; Malapert, Pascale; Reynders, Ana; Gaillard, Stéphane; Moqrich, Aziz

2014-01-01

The discovery of heat-sensitive Transient Receptor Potential Vanilloid ion channels (ThermoTRPVs) greatly advanced our molecular understanding of acute and injury-evoked heat temperature sensation. ThermoTRPV channels are activated by partially overlapping temperatures ranging from warm to supra-threshold noxious heat. TRPV1 is activated by noxious heat temperature whereas TRPV3 can be activated by warm as well as noxious heat temperatures. Loss-of-function studies in single TRPV1 and TRPV3 knock-out mice have shown that heat temperature sensation is not completely abolished suggesting functional redundancies among these two channels and highlighting the need of a detailed analysis of TRPV1::TRPV3 double knock-out mice (V1V3dKO) which is hampered by the close proximity of the loci expressing the two channels. Here we describe the generation of a novel mouse model in which trpv1 and trpv3 genes have been inactivated using bacterial artificial chromosome (BAC)-based homologous recombination in embryonic stem cells. In these mice, using classical thermosensory tests such hot plate, tail flick and the thermotaxis gradient paradigms, we confirm that TRPV1 is the master channel for sensing noxious heat temperatures and identify a cooperative role of TRPV1 and TRPV3 for sensing a well-defined window of acute moderate heat temperature. Using the dynamic hot plate assay, we unravel an intriguing and unexpected pronounced escape behavior in TRPV1 knock-out mice that was attenuated in the V1V3dKO. Together, and in agreement with the temperature activation overlap between TRPV1 and TRPV3 channels, our data provide in vivo evidence of a cooperative role between skin-derived TRPV3 and primary sensory neurons-enriched TRPV1 in modulation of moderate and noxious heat temperature sensation and suggest that other mechanisms are required for heat temperature sensation.

Cooperative interaction among the various regulatory sites within the NMDA receptor-channel complex in modulating the evoked responses to noxious thermal stimuli of spinal dorsal horn neurons in the cat.

PubMed

Song, X J; Zhao, Z Q

1998-05-01

Interactions among antagonists acting at different regulatory sites within the N-methyl-D-aspartate (NMDA) receptor-channel complex on the evoked responses to noxious thermal stimuli of wide dynamic range (WDR) neurons in spinal dorsal horn were studied on 21 adult anesthetized and spinalized cats. The responses of nociceptive spinal dorsal horn neurons to noxious heating (45-55 degrees C) of the glabrous skin of the unilateral hind paw were reduced markedly by iontophoretically applied antagonists. The specific recognition site antagonist, DL-2-amino-5-phosphonovaleratic acid (APV), the strychnine-insensitive glycine site antagonist 7-chlorokynurenic acid (7CKA), the polyamine site antagonist ifenprodil (IFEN), and the phencyclidine (PCP) site antagonists ketamine (KET) and MK-801 (40-100 nA) significantly reduced (t-tests, P < 0.01) the noxious thermal stimulus-evoked responses in about 70% of the neurons by (mean +/- SE) 54.1 +/- 5.8% (n = 19), 80.8 +/- 4.7% (n = 16), 51.1 +/- 6.4% (n = 10), 77 +/- 4.9% (n = 16) and 81.2 +/- 8.1% (n = 5), respectively. APV and IFEN were less effective in blocking noxious thermal stimuli-evoked responses than 7CKA, KET and MK-801 (ANOVA, P < 0.05). The responses were completely inhibited in some neurons. After co-administration of the antagonists, APV + 7CKA, APV + IFEN, 7CKA + IFEN, APV + KET and APV + MK-801, all at the subthreshold ejection current, the responses were reduced markedly in 13 of 16, 7 of 10, 5 of 10, 3 of 6 and 3 of 5 neurons, respectively. The present study suggests that blockage of any component of the NMDA receptor-channel complex antagonizes the NMDA receptor-mediated response, and that there are the cooperative interactions among the various regulatory sites within the NMDA receptor-channel complex in the transmission or modulation of spinal nociceptive thermal information.

Acute Heat-Evoked Temperature Sensation Is Impaired but Not Abolished in Mice Lacking TRPV1 and TRPV3 Channels

PubMed Central

Reynders, Ana; Gaillard, Stéphane; Moqrich, Aziz

2014-01-01

The discovery of heat-sensitive Transient Receptor Potential Vanilloid ion channels (ThermoTRPVs) greatly advanced our molecular understanding of acute and injury-evoked heat temperature sensation. ThermoTRPV channels are activated by partially overlapping temperatures ranging from warm to supra-threshold noxious heat. TRPV1 is activated by noxious heat temperature whereas TRPV3 can be activated by warm as well as noxious heat temperatures. Loss-of-function studies in single TRPV1 and TRPV3 knock-out mice have shown that heat temperature sensation is not completely abolished suggesting functional redundancies among these two channels and highlighting the need of a detailed analysis of TRPV1::TRPV3 double knock-out mice (V1V3dKO) which is hampered by the close proximity of the loci expressing the two channels. Here we describe the generation of a novel mouse model in which trpv1 and trpv3 genes have been inactivated using bacterial artificial chromosome (BAC)-based homologous recombination in embryonic stem cells. In these mice, using classical thermosensory tests such hot plate, tail flick and the thermotaxis gradient paradigms, we confirm that TRPV1 is the master channel for sensing noxious heat temperatures and identify a cooperative role of TRPV1 and TRPV3 for sensing a well-defined window of acute moderate heat temperature. Using the dynamic hot plate assay, we unravel an intriguing and unexpected pronounced escape behavior in TRPV1 knock-out mice that was attenuated in the V1V3dKO. Together, and in agreement with the temperature activation overlap between TRPV1 and TRPV3 channels, our data provide in vivo evidence of a cooperative role between skin-derived TRPV3 and primary sensory neurons-enriched TRPV1 in modulation of moderate and noxious heat temperature sensation and suggest that other mechanisms are required for heat temperature sensation. PMID:24925072

[Stings, bites and other adventures...].

PubMed

De Dobbeleer, G

2000-09-01

Most of us live in cities and nature seems beneficial. Unfortunately, invertebrates and vertebrates may be aggressive. We will try here a review of the diseases caused by arthropods and other noxious animals. Injuries caused by the following insects will be described: mosquitoes, flies, fleas, bees, wasps and ants, bugs, beetles, butterflies and caterpillars. In the class arachnida: spiders, scopions, ticks and mites. Among invertebrates: leeches, anemons, corals, sea urchins, sponges and mollusca. Noxious or venomous vertebrates will not be forgotten. Basic and practical attitudes are proposed.

Single Unit Recordings of Cells Responsive to Visual, Somatic, Acoustic, and Noxious Stimuli in the Superior Colliculus of the Golden Hamster.

DTIC Science & Technology

1978-08-01

Acoustic, and Noxious Stimuli Thesis in the Superior Colliculus of the Golden 6. PERFORMING OG. REPORT NUMBER Hamster -. _ // 7. AUTHOR( a ) S. CONTRACT...OR GRANT NUMBER(s) James P. Dixon I - "JV 9. PERF 7 MING ORGANIZATION NAME A D10. PROGRAM ELEMENT, PROJECT, TASK AFIT Student at: Virginia...studied in the superior colliculus of the golden hamster. A laminar organiza- tion was observed with cells in the superficial layers responding exclusively

A voltage-controlled capacitive discharge method for electrical activation of peripheral nerves.

PubMed

Rosellini, Will M; Yoo, Paul B; Engineer, Navzer; Armstrong, Scott; Weiner, Richard L; Burress, Chester; Cauller, Larry

2011-01-01

A voltage-controlled capacitive discharge (VCCD) method was investigated as an alternative to rectangular stimulus pulses currently used in peripheral nerve stimulation therapies.  In two anesthetized Gottingen mini pigs, the threshold (total charge per phase) for evoking a compound nerve action potential (CNAP) was compared between constant current (CC) and VCCD methods. Electrical pulses were applied to the tibial and posterior cutaneous femoralis nerves using standard and modified versions of the Medtronic 3778 Octad.  In contrast to CC stimulation, the combined application of VCCD pulses with a modified Octad resulted in a marked decrease (-73 ± 7.4%) in the stimulation threshold for evoking a CNAP. This was consistent for different myelinated fiber types and locations of stimulation.  The VCCD method provides a highly charge-efficient means of activating myelinated fibers that could potentially be used within a wireless peripheral nerve stimulator system. © 2011 International Neuromodulation Society.

Assessment of physiological noise modelling methods for functional imaging of the spinal cord.

PubMed

Kong, Yazhuo; Jenkinson, Mark; Andersson, Jesper; Tracey, Irene; Brooks, Jonathan C W

2012-04-02

The spinal cord is the main pathway for information between the central and the peripheral nervous systems. Non-invasive functional MRI offers the possibility of studying spinal cord function and central sensitisation processes. However, imaging neural activity in the spinal cord is more difficult than in the brain. A significant challenge when dealing with such data is the influence of physiological noise (primarily cardiac and respiratory), and currently there is no standard approach to account for these effects. We have previously studied the various sources of physiological noise for spinal cord fMRI at 1.5T and proposed a physiological noise model (PNM) (Brooks et al., 2008). An alternative de-noising strategy, selective averaging filter (SAF), was proposed by Deckers et al. (2006). In this study we reviewed and implemented published physiological noise correction methods at higher field (3T) and aimed to find the optimal models for gradient-echo-based BOLD acquisitions. Two general techniques were compared: physiological noise model (PNM) and selective averaging filter (SAF), along with regressors designed to account for specific signal compartments and physiological processes: cerebrospinal fluid (CSF), motion correction (MC) parameters, heart rate (HR), respiration volume per time (RVT), and the associated cardiac and respiratory response functions. Functional responses were recorded from the cervical spinal cord of 18 healthy subjects in response to noxious thermal and non-noxious punctate stimulation. The various combinations of models and regressors were compared in three ways: the model fit residuals, regression model F-tests and the number of activated voxels. The PNM was found to outperform SAF in all three tests. Furthermore, inclusion of the CSF regressor was crucial as it explained a significant amount of signal variance in the cord and increased the number of active cord voxels. Whilst HR, RVT and MC explained additional signal (noise) variance, they were also found (in particular HR and RVT) to have a negative impact on the parameter estimates (of interest)--as they may be correlated with task conditions e.g. noxious thermal stimuli. Convolution with previously published cardiac and respiratory impulse response functions was not found to be beneficial. The other novel aspect of current study is the investigation of the influence of pre-whitening together with PNM regressors on spinal fMRI data. Pre-whitening was found to reduce non-white noise, which was not accounted for by physiological noise correction, and decrease false positive detection rates. Copyright © 2011 Elsevier Inc. All rights reserved.

Neurophysiological measures of nociceptive brain activity in the newborn infant--the next steps.

PubMed

Hartley, Caroline; Slater, Rebeccah

2014-03-01

Infants within neonatal intensive care units can receive multiple medically essential painful procedures per day. How they respond to these events, how best to alleviate the negative effects, and the long-term consequences for the infant are all significant questions that have yet to be fully answered. In recent years, several studies have examined cortical responses to noxious stimuli in the neonate through the use of near-infrared spectroscopy (NIRS) and electroencephalography (EEG). These investigations dispel any notion that the newborn infant does not process noxious stimuli at a cortical level and open the way for future research. In this Viewpoint Article, we review these studies and discuss key clinical challenges which may be elucidated with the use of these techniques. Simultaneously measuring the changes that are evoked in behaviour, physiology and the cortex following noxious events will provide the best approach to understanding the neonate's experience of pain. © 2013 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Porter, Mark C.; Ketchum, Sarah

Noxious weeds threaten fish and wildlife habitat by contributing to increased sedimentation rates, diminishing riparian structure and function, and reducing forage quality and quantity. Wallowa Resources Wallowa Canyonlands Partnership (WCP) protects the unique ecological and economic values of the Hells Canyon grasslands along lower Joseph Creek, the lower Grande Ronde and Imnaha Rivers from invasion and degradation by noxious weeds using Integrated Weed Management techniques. Objectives of this grant were to inventory and map high priority weeds, coordinate treatment of those weeds, release and monitor bio-control agents, educate the public as to the dangers of noxious weeds and how tomore » deal with them, and restore lands to productive plant communities after treatment. With collaborative help from partners, WCP inventoried {approx} 215,000 upland acres and 52.2 miles of riparian habitat, released bio-controls at 23 sites, and educated the public through posters, weed profiles, newspaper articles, and radio advertisements. Additionally, WCP used other sources of funding to finance the treatment of 1,802 acres during the course of this grant.« less

Spinal cord processing of cardiac nociception: are there sex differences between male and proestrous female rats?

PubMed

Little, Janine M; Qin, Chao; Farber, Jay P; Foreman, Robert D

2011-09-21

Sex differences in the characteristics of cardiac pain have been reported from clinical studies. For example, women experience chest pain less frequently than men. Women describe their chest pain as sharp and stabbing, while men have chest pain that is felt as a pressure or heaviness. Pain is also referred to the back more often in women than men. The mechanisms underlying sex differences in cardiac pain are unknown. One possible mechanism for the observed differences could be related to plasma estradiol. This study investigated the actions of estradiol on the activity of T(3) spinal neurons that process cardiosomatic information in male and female rats. Extracellular potentials of T(3) spinal neurons were recorded in response to mechanical somatic stimulation and noxious chemical cardiac stimulation in pentobarbital-anesthetized male and proestrous female rats. Fifty one percent and fifty percent of neurons responded to intrapericardial algogenic chemicals (0.2 ml) in male and female rats, respectively. Somatic fields were located by applying brush, pressure, and pinch to the upper body. Of those neurons receiving cardiac input, 54% in female and 55% in male rats also received somatic input. In both male and female rats, 81% of neurons responding to somatic stimuli had somatic fields located on the side of the upper body, while 19% of neurons had somatic fields located on the chest. These results indicate there are no significant differences in the responses of T(3) spinal neurons to cardiosomatic stimulation between male and proestrous female rats, despite differences in estradiol levels. Published by Elsevier B.V.

Nociception and inflammatory hyperalgesia evaluated in rodents using infrared laser stimulation after Trpv1 gene knockout or resiniferatoxin lesion.

PubMed

Mitchell, Kendall; Lebovitz, Evan E; Keller, Jason M; Mannes, Andrew J; Nemenov, Michael I; Iadarola, Michael J

2014-04-01

TRPV1 is expressed in a subpopulation of myelinated Aδ and unmyelinated C-fibers. TRPV1+ fibers are essential for the transmission of nociceptive thermal stimuli and for the establishment and maintenance of inflammatory hyperalgesia. We have previously shown that high-power, short-duration pulses from an infrared diode laser are capable of predominantly activating cutaneous TRPV1+ Aδ-fibers. Here we show that stimulating either subtype of TRPV1+ fiber in the paw during carrageenan-induced inflammation or following hind-paw incision elicits pronounced hyperalgesic responses, including prolonged paw guarding. The ultrapotent TRPV1 agonist resiniferatoxin (RTX) dose-dependently deactivates TRPV1+ fibers and blocks thermal nociceptive responses in baseline or inflamed conditions. Injecting sufficient doses of RTX peripherally renders animals unresponsive to laser stimulation even at the point of acute thermal skin damage. In contrast, Trpv1-/- mice, which are generally unresponsive to noxious thermal stimuli at lower power settings, exhibit withdrawal responses and inflammation-induced sensitization using high-power, short duration Aδ stimuli. In rats, systemic morphine suppresses paw withdrawal, inflammatory guarding, and hyperalgesia in a dose-dependent fashion using the same Aδ stimuli. The qualitative intensity of Aδ responses, the leftward shift of the stimulus-response curve, the increased guarding behaviors during carrageenan inflammation or after incision, and the reduction of Aδ responses with morphine suggest multiple roles for TRPV1+ Aδ fibers in nociceptive processes and their modulation of pathological pain conditions. Copyright © 2014. Published by Elsevier B.V.

Eugenol and carvacrol excite first- and second-order trigeminal neurons and enhance their heat-evoked responses

PubMed Central

Klein, Amanda H.; Joe, Christopher L.; Davoodi, Auva; Takechi, Kenichi; Carstens, Mirela Iodi; Carstens, E

2014-01-01

Eugenol and carvacrol from clove and oregano, respectively, are agonists of the warmth-sensitive transient receptor potential channel TRPV3 and the irritant-sensitive TRPA1. Eugenol and carvacrol induce oral irritation that rapidly desensitizes, accompanied by brief enhancement of innocuous warmth and heat pain in humans. We presently investigated if eugenol and carvacrol activate nociceptive primary afferent and higher-order trigeminal neurons and enhance their heat-evoked responses, using calcium imaging of cultured trigeminal ganglion (TG) and dorsal root ganglion (DRG) neurons, and in vivo single-unit recordings in trigeminal subnucleus caudalis (Vc) of rats. Eugenol and carvacrol activated 20-30% of TG and 7-20% of DRG cells, the majority of which additionally responded to menthol, mustard oil and/or capsaicin. TG cell responses to innocuous (39°) and noxious (42°C) heating were enhanced by eugenol and carvacrol. We identified dorsomedial Vc neurons responsive to noxious heating of the tongue in pentobarbital-anesthetized rats. Eugenol and carvacrol dose-dependently elicited desensitizing responses in 55% and 73% of heat-sensitive units, respectively. Responses to noxious heat were briefly enhanced by eugenol and carvacrol. Many eugenol- and carvacrol-responsive units also responded to menthol, cinnamaldehyde and capsaicin. These data support a peripheral site for eugenol and carvacrol to enhance warmth- and noxious heat-evoked responses of trigeminal neurons, and are consistent with the observation that these agonists briefly enhance warmth and heat pain on the human tongue. PMID:24759772

Low dose native type II collagen prevents pain in a rat osteoarthritis model

PubMed Central

2013-01-01

Background Osteoarthritis is the most widespread joint-affecting disease. Patients with osteoarthritis experience pain and impaired mobility resulting in marked reduction of quality of life. A progressive cartilage loss is responsible of an evolving disease difficult to treat. The characteristic of chronicity determines the need of new active disease modifying drugs. Aim of the present research is to evaluate the role of low doses of native type II collagen in the rat model of osteoarthritis induced by sodium monoiodoacetate (MIA). Methods 1, 3 and 10 mg kg-1 porcine native type II collagen were daily per os administered for 13 days starting from the day of MIA intra-articular injection. Results On day 14, collagen-treated rats showed a significant prevention of pain threshold alterations induced by MIA. Evaluation were performed on paws using mechanical noxious (Paw pressure test) or non-noxious (Electronic Von Frey test) stimuli, and a decrease of articular pain was directly measured on the damaged joint (PAM test). The efficacy of collagen in reducing pain was as higher as the dose was lowered. Moreover, a reduced postural unbalance, measured as hind limb weight bearing alterations (Incapacitance test), and a general improvement of motor activity (Animex test) were observed. Finally, the decrease of plasma and urine levels of CTX-II (Cross Linked C-Telopeptide of Type II Collagen), a biomarker of cartilage degradation, suggests a collagen-dependent decrease of structural joint damage. Conclusions These results describe the preclinical efficacy of low dosages of native type II collagen as pain reliever by a mechanism that involves a protective effect on cartilage. PMID:23915264

Tissue response to intraperitoneal implants of polyethylene oxide-modified polyethylene terephthalate.

PubMed

Desai, N P; Hubbell, J A

1992-01-01

Polyethylene terephthalate films surface modified with polyethylene oxide of mol wt 18,500 g/mol (18.5 k) by a previously described technique, were implanted in the peritoneal cavity of mice, along with their respective untreated controls, for periods of 1-28 d. The implants were retrieved and examined for tissue reactivity and cellular adherence. The control polyethylene terephthalate surfaces showed an initial inflammatory reaction followed by an extensive fibrotic response with a mean thickness of 60 microns at 28 d. By contrast, polyethylene oxide-modified polyethylene terephthalate showed only a mild inflammatory response and no fibrotic encapsulation throughout the implantation period: at 28 d a cellular monolayer was observed. Apparently either the polyethylene oxide-modified surface was stimulating less inflammation, which was in turn stimulating less fibroblastic overgrowth, or the cellular adhesion to the polyethylene oxide-modified surface was too weak to support cellular multilayers.

Zika virus in Brazil and the danger of infestation by Aedes (Stegomyia) mosquitoes.

PubMed

Marcondes, Carlos Brisola; Ximenes, Maria de Fátima Freire de Melo

2016-02-01

Zika virus, already widely distributed in Africa and Asia, was recently reported in two Northeastern Brazilian: State of Bahia and State of Rio Grande do Norte, and one Southeastern: State of São Paulo. This finding adds a potentially noxious virus to a list of several other viruses that are widely transmitted by Aedes (Stegomyia) aegypti and Aedes (Stegomyia) albopictus in Brazil. The pathology and epidemiology, including the distribution and vectors associated with Zika virus, are reviewed. This review is focused on viruses transmitted by Aedes (Stegomyia) mosquitoes, including dengue, Chikungunya, Zika, Mayaro, and yellow fever virus, to emphasize the risks of occurrence for these arboviruses in Brazil and neighboring countries. Other species of Aedes (Stegomyia) are discussed, emphasizing their involvement in arbovirus transmission and the possibility of adaptation to environments modified by human activities and introduction in Brazil.

Race, ethnicity, and noxious facilities: Environmental racism re- examined

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nieves, A.L.; Nieves, L.A.

1992-10-01

The charge has been made that hazardous facilities tend to be located in proximity to minority populations. This study uses a facility density measure for three categories of noxious facilities to examine the relationship between facilities and minority population concentrations. County-level data are used in a correlation analysis for African Americans, Hispanics, and Asians in the four major regions of the US. Even controlling for income and housing value, and limiting the data set to urban areas, consistent patterns of moderate to strong association of facility densities with minority population percentages are found.

TRP channel functions in the gastrointestinal tract.

PubMed

Yu, Xiaoyun; Yu, Mingran; Liu, Yingzhe; Yu, Shaoyong

2016-05-01

Transient receptor potential (TRP) channels are predominantly distributed in both somatic and visceral sensory nervous systems and play a crucial role in sensory transduction. As the largest visceral organ system, the gastrointestinal (GI) tract frequently accommodates external inputs, which stimulate sensory nerves to initiate and coordinate sensory and motor functions in order to digest and absorb nutrients. Meanwhile, the sensory nerves in the GI tract are also able to detect potential tissue damage by responding to noxious irritants. This nocifensive function is mediated through specific ion channels and receptors expressed in a subpopulation of spinal and vagal afferent nerve called nociceptor. In the last 18 years, our understanding of TRP channel expression and function in GI sensory nervous system has been continuously improved. In this review, we focus on the expressions and functions of TRPV1, TRPA1, and TRPM8 in primary extrinsic afferent nerves innervated in the esophagus, stomach, intestine, and colon and briefly discuss their potential roles in relevant GI disorders.

Altered Neural Activity Associated with Mindfulness during Nociception: A Systematic Review of Functional MRI.

PubMed

Bilevicius, Elena; Kolesar, Tiffany A; Kornelsen, Jennifer

2016-04-19

To assess the neural activity associated with mindfulness-based alterations of pain perception. The Cochrane Central, EMBASE, Ovid Medline, PsycINFO, Scopus, and Web of Science databases were searched on 2 February 2016. Titles, abstracts, and full-text articles were independently screened by two reviewers. Data were independently extracted from records that included topics of functional neuroimaging, pain, and mindfulness interventions. The literature search produced 946 total records, of which five met the inclusion criteria. Records reported pain in terms of anticipation (n = 2), unpleasantness (n = 5), and intensity (n = 5), and how mindfulness conditions altered the neural activity during noxious stimulation accordingly. Although the studies were inconsistent in relating pain components to neural activity, in general, mindfulness was able to reduce pain anticipation and unpleasantness ratings, as well as alter the corresponding neural activity. The major neural underpinnings of mindfulness-based pain reduction consisted of altered activity in the anterior cingulate cortex, insula, and dorsolateral prefrontal cortex.

fMRI reveals neural activity overlap between adult and infant pain

PubMed Central

Goksan, Sezgi; Hartley, Caroline; Emery, Faith; Cockrill, Naomi; Poorun, Ravi; Moultrie, Fiona; Rogers, Richard; Campbell, Jon; Sanders, Michael; Adams, Eleri; Clare, Stuart; Jenkinson, Mark; Tracey, Irene; Slater, Rebeccah

2015-01-01

Limited understanding of infant pain has led to its lack of recognition in clinical practice. While the network of brain regions that encode the affective and sensory aspects of adult pain are well described, the brain structures involved in infant nociceptive processing are less well known, meaning little can be inferred about the nature of the infant pain experience. Using fMRI we identified the network of brain regions that are active following acute noxious stimulation in newborn infants, and compared the activity to that observed in adults. Significant infant brain activity was observed in 18 of the 20 active adult brain regions but not in the infant amygdala or orbitofrontal cortex. Brain regions that encode sensory and affective components of pain are active in infants, suggesting that the infant pain experience closely resembles that seen in adults. This highlights the importance of developing effective pain management strategies in this vulnerable population. DOI: http://dx.doi.org/10.7554/eLife.06356.001 PMID:25895592

Lateral Preoptic Control of the Lateral Habenula through Convergent Glutamate and GABA Transmission.

PubMed

Barker, David J; Miranda-Barrientos, Jorge; Zhang, Shiliang; Root, David H; Wang, Hui-Ling; Liu, Bing; Calipari, Erin S; Morales, Marisela

2017-11-14

The lateral habenula (LHb) is a brain structure that participates in cognitive and emotional processing and has been implicated in several mental disorders. Although one of the largest inputs to the LHb originates in the lateral preoptic area (LPO), little is known about how the LPO participates in the regulation of LHb function. Here, we provide evidence that the LPO exerts bivalent control over the LHb through the convergent transmission of LPO glutamate and γ-aminobutyric acid (GABA) onto single LHb neurons. In vivo, both LPO-glutamatergic and LPO-GABAergic inputs to the LHb are activated by aversive stimuli, and their predictive cues yet produce opposing behaviors when stimulated independently. These results support a model wherein the balanced response of converging LPO-glutamate and LPO-GABA are necessary for a normal response to noxious stimuli, and an imbalance in LPO→LHb glutamate or GABA results in the type of aberrant processing that may underlie mental disorders. Published by Elsevier Inc.

Proton spectral editing in the inhomogeneous radiofrequency field of a surface coil using modified stimulated echoes.

PubMed

Lahrech, H; Briguet, A

1990-11-01

It is shown that the modified stimulated echo sequence, [theta](+/- x +/- y)-t1-[theta](+ x)-t2/2-[2 theta](+ x)-t2/2- [theta](+ x)-t1-Acq(+/- x +/- y), denoted as MSTE[2 theta]x according to the exciter phase of the 2 theta pulse, is able to perform proton spectral editing without difference spectra. On the other hand, this sequence appears to be suitable for spatial localization. Sensitivity and spatial selectivity of MSTE and conventional stimulated echo sequence (STE) are briefly compared. MSTE is applied to editing lactate in the rat brain using the locally restricted excitation of a surface coil.

A novel multivariate STeady-state index during general ANesthesia (STAN).

PubMed

Castro, Ana; de Almeida, Fernando Gomes; Amorim, Pedro; Nunes, Catarina S

2017-08-01

The assessment of the adequacy of general anesthesia for surgery, namely the nociception/anti-nociception balance, has received wide attention from the scientific community. Monitoring systems based on the frontal EEG/EMG, or autonomic state reactions (e.g. heart rate and blood pressure) have been developed aiming to objectively assess this balance. In this study a new multivariate indicator of patients' steady-state during anesthesia (STAN) is proposed, based on wavelet analysis of signals linked to noxious activation. A clinical protocol was designed to analyze precise noxious stimuli (laryngoscopy/intubation, tetanic, and incision), under three different analgesic doses; patients were randomized to receive either remifentanil 2.0, 3.0 or 4.0 ng/ml. ECG, PPG, BP, BIS, EMG and [Formula: see text] were continuously recorded. ECG, PPG and BP were processed to extract beat-to-beat information, and [Formula: see text] curve used to estimate the respiration rate. A combined steady-state index based on wavelet analysis of these variables, was applied and compared between the three study groups and stimuli (Wilcoxon signed ranks, Kruskal-Wallis and Mann-Whitney tests). Following institutional approval and signing the informed consent thirty four patients were enrolled in this study (3 excluded due to signal loss during data collection). The BIS index of the EEG, frontal EMG, heart rate, BP, and PPG wave amplitude changed in response to different noxious stimuli. Laryngoscopy/intubation was the stimulus with the more pronounced response [Formula: see text]. These variables were used in the construction of the combined index STAN; STAN responded adequately to noxious stimuli, with a more pronounced response to laryngoscopy/intubation (18.5-43.1 %, [Formula: see text]), and the attenuation provided by the analgesic, detecting steady-state periods in the different physiological signals analyzed (approximately 50 % of the total study time). A new multivariate approach for the assessment of the patient steady-state during general anesthesia was developed. The proposed wavelet based multivariate index responds adequately to different noxious stimuli, and attenuation provided by the analgesic in a dose-dependent manner for each stimulus analyzed in this study.

A Tactile Stimulator for Studying Passive Shape Perception

PubMed Central

Lane, John W.; Fitzgerald, Paul J.; Yau, Jeffrey M.; Pembeci, Izzet; Hsiao, Steven S.

2009-01-01

We describe a computer-controlled tactile stimulator for use in human psychophysical and monkey neurophysiological studies of 3-D shape perception. The stimulator is constructed primarily of commercially available parts, as well as a few custom-built pieces for which we will supply diagrams upon request. There are two components to the stimulator: a tactile component and a hand positioner component. The tactile component consists of multiple stimulating units that move about in a Cartesian plane above the restrained hand. Each stimulating unit contains a servo-controlled linear motor with an attached small rotary stepper motor, allowing arbitrary stimulus shapes to contact the skin through vibration, static indentation, or scanning. The hand positioner component modifies the conformation of the restrained hand through a set of mechanical linkages under motorized control. The present design controls the amount of spread between digits two and three, the spread between digits four and three, and the degree to which digit three is flexed or extended, thereby simulating different conformations of the hand in contact with objects. This design is easily modified to suit the needs of the experimenter. Because the two components of the stimulator are independently controlled, the stimulator allows for parametric study of the mechanoreceptive and proprioceptive contributions to 3-D tactile shape perception. PMID:19800916

Effects of noxious stimuli on the electroencephalogram of anaesthetised chickens (Gallus gallus domesticus).

PubMed

McIlhone, Amanda E; Beausoleil, Ngaio J; Kells, Nikki J; Mellor, David J; Johnson, Craig B

2018-01-01

The reliable assessment and management of avian pain is important in the context of animal welfare. Overtly expressed signs of pain vary substantially between and within species, strains and individuals, limiting the use of behaviour in pain studies. Similarly, physiological indices of pain can also vary and may be confounded by influence from non-painful stimuli. In mammals, changes in the frequency spectrum of the electroencephalogram (EEG) recorded under light anaesthesia (the minimal anaesthesia model; MAM) have been shown to reliably indicate cerebral responses to noxious stimuli in a range of species. The aim of the current study was to determine whether the MAM can be applied to the study of nociception in birds. Ten chickens were lightly anaesthetised with halothane and their EEG recorded using surface electrodes during the application of supramaximal mechanical, thermal and electrical noxious stimuli. Spectral analysis revealed no EEG responses to any of these stimuli. Given that birds possess the neural apparatus to detect and process pain, and that the applied noxious stimuli elicit behavioural signs of pain in conscious chickens, this lack of response probably relates to methodological limitations. Anatomical differences between the avian and mammalian brains, along with a paucity of knowledge regarding specific sites of pain processing in the avian brain, could mean that EEG recorded from the head surface is insensitive to changes in neural activity in the pain processing regions of the avian brain. Future investigations should examine alternative electrode placement sites, based on avian homologues of the mammalian brain regions involved in pain processing.

Effects of noxious stimuli on the electroencephalogram of anaesthetised chickens (Gallus gallus domesticus)

PubMed Central

McIlhone, Amanda E.; Beausoleil, Ngaio J.; Mellor, David J.; Johnson, Craig B.

2018-01-01

The reliable assessment and management of avian pain is important in the context of animal welfare. Overtly expressed signs of pain vary substantially between and within species, strains and individuals, limiting the use of behaviour in pain studies. Similarly, physiological indices of pain can also vary and may be confounded by influence from non-painful stimuli. In mammals, changes in the frequency spectrum of the electroencephalogram (EEG) recorded under light anaesthesia (the minimal anaesthesia model; MAM) have been shown to reliably indicate cerebral responses to noxious stimuli in a range of species. The aim of the current study was to determine whether the MAM can be applied to the study of nociception in birds. Ten chickens were lightly anaesthetised with halothane and their EEG recorded using surface electrodes during the application of supramaximal mechanical, thermal and electrical noxious stimuli. Spectral analysis revealed no EEG responses to any of these stimuli. Given that birds possess the neural apparatus to detect and process pain, and that the applied noxious stimuli elicit behavioural signs of pain in conscious chickens, this lack of response probably relates to methodological limitations. Anatomical differences between the avian and mammalian brains, along with a paucity of knowledge regarding specific sites of pain processing in the avian brain, could mean that EEG recorded from the head surface is insensitive to changes in neural activity in the pain processing regions of the avian brain. Future investigations should examine alternative electrode placement sites, based on avian homologues of the mammalian brain regions involved in pain processing. PMID:29698446

Modulation of laser-evoked potentials and pain perception by transcutaneous electrical nerve stimulation (TENS): a placebo-controlled study in healthy volunteers.

PubMed

Vassal, François; Créac'h, C; Convers, Ph; Laurent, B; Garcia-Larrea, L; Peyron, R

2013-09-01

To investigate the effects of transcutaneous electrical nerve stimulation (TENS) on brain nociceptive responses (laser-evoked potentials, LEPs) and pain perception. Twenty healthy subjects were included. Nociceptive CO(2)-laser pulses were sequentially delivered to the dorsum of both feet. The amplitude of LEPs and nociceptive thresholds were collected in three consecutive conditions: T1: "sham" TENS (2 Hz/low-intensity) positioned heterotopically, over the left thigh; T2: "active" TENS (120 Hz/low-intensity) applied homotopically, over the left common peroneal nerve; and T3: "sham" TENS (replication of condition T1). Compared with "sham" TENS, "active" TENS significantly decreased the LEPs amplitude. This effect was observed exclusively when "active" TENS was applied ipsilaterally to the painful stimulus. Nociceptive thresholds increased with sessions in both limbs, but the increase observed during the "active" condition of TENS (T2) exceeded significantly that observed during the condition T3 only on the foot ipsilateral to TENS. Compared with a credible placebo TENS, high-frequency TENS induced a significant attenuation of both the acute pain and LEPs induced by noxious stimuli applied on the same dermatome. This modulation of subjective and objective concomitants of pain processing reflects a real neurophysiological TENS-related effect on nociceptive transmission. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

100-Hz Electroacupuncture but not 2-Hz Electroacupuncture is Preemptive Against Postincision Pain in Rats.

PubMed

Silva, Marcelo Lourenço; Silva, Josie Resende Torres; Prado, Wiliam Alves

2016-08-01

Preemptive analgesia involves introducing an analgesic before noxious stimulation. Electroacupuncture (EA) activates descending mechanisms that modulate nociceptive inputs into the spinal dorsal horn. This study evaluated whether preoperative EA is more effective than postoperative EA in reducing incision pain in rats. The nociceptive threshold to mechanical stimulation was utilized to examine the effects of an intraperitoneal injection of saline (0.1 mL/kg) or naloxone (1 mg/kg) on antinociception induced by a 20-minute period of 2-Hz or 100-Hz EA applied to the Zusanli (ST36) and Sanyinjiao (SP6) acupoints before surgical incision, or 10 minutes after or 100 minutes after surgical incision of the hind paw. The extent of mechanical hyperalgesia after the incision was significantly attenuated by the application of 100-Hz EA preoperatively, but not by its application at 10 minutes or 100 minutes postoperatively. By contrast, 2-Hz EA was effective against postoperative hyperalgesia when applied 10 minutes or 100 minutes after surgery but not when it was applied preoperatively. Only the effect of 2-Hz EA applied 10 minutes after surgery was sensitive to naloxone. The present study showed for the first time that 100-Hz EA, but not 2-Hz EA, exerts a nonopioidergic preemptive effect against postincision pain in rats. Copyright © 2016. Published by Elsevier B.V.

Cannabinoid-induced effects on the nociceptive system: a neurophysiological study in patients with secondary progressive multiple sclerosis.

PubMed

Conte, Antonella; Bettolo, Chiara Marini; Onesti, Emanuela; Frasca, Vittorio; Iacovelli, Elisa; Gilio, Francesca; Giacomelli, Elena; Gabriele, Maria; Aragona, Massimiliano; Tomassini, Valentina; Pantano, Patrizia; Pozzilli, Carlo; Inghilleri, Maurizio

2009-05-01

Although clinical studies show that cannabinoids improve central pain in patients with multiple sclerosis (MS) neurophysiological studies are lacking to investigate whether they also suppress these patients' electrophysiological responses to noxious stimulation. The flexion reflex (FR) in humans is a widely used technique for assessing the pain threshold and for studying spinal and supraspinal pain pathways and the neurotransmitter system involved in pain control. In a randomized, double-blind, placebo-controlled, cross-over study we investigated cannabinoid-induced changes in RIII reflex variables (threshold, latency and area) in a group of 18 patients with secondary progressive MS. To investigate whether cannabinoids act indirectly on the nociceptive reflex by modulating lower motoneuron excitability we also evaluated the H-reflex size after tibial nerve stimulation and calculated the H wave/M wave (H/M) ratio. Of the 18 patients recruited and randomized 17 completed the study. After patients used a commercial delta-9-tetrahydrocannabinol (THC) and cannabidiol mixture as an oromucosal spray the RIII reflex threshold increased and RIII reflex area decreased. The visual analogue scale score for pain also decreased, though not significantly. Conversely, the H/M ratio measured before patients received cannabinoids remained unchanged after therapy. In conclusion, the cannabinoid-induced changes in the RIII reflex threshold and area in patients with MS provide objective neurophysiological evidence that cannabinoids modulate the nociceptive system in patients with MS.

Zoning, equity, and public health.

PubMed

Maantay, J

2001-07-01

Zoning, the most prevalent land use planning tool in the United States, has substantial implications for equity and public health. Zoning determines where various categories of land use may go, thereby influencing the location of resulting environmental and health impacts. Industrially zoned areas permit noxious land uses and typically carry higher environmental burdens than other areas. Using New York City as a case study, the author shows that industrial zones have large residential populations within them or nearby. Noxious uses tend to be concentrated in poor and minority industrial neighborhoods because more affluent industrial areas and those with lower minority populations are rezoned for other uses, and industrial zones in poorer neighborhoods are expanded. Zoning policies, therefore, can have adverse impacts on public health and equity. The location of noxious uses and the pollution they generate have ramifications for global public health and equity; these uses have been concentrated in the world's poorer places as well as in poorer places within more affluent countries. Planners, policymakers, and public health professionals must collaborate on a worldwide basis to address these equity, health, and land use planning problems.

Zoning, equity, and public health.

PubMed Central

Maantay, J

2001-01-01

Zoning, the most prevalent land use planning tool in the United States, has substantial implications for equity and public health. Zoning determines where various categories of land use may go, thereby influencing the location of resulting environmental and health impacts. Industrially zoned areas permit noxious land uses and typically carry higher environmental burdens than other areas. Using New York City as a case study, the author shows that industrial zones have large residential populations within them or nearby. Noxious uses tend to be concentrated in poor and minority industrial neighborhoods because more affluent industrial areas and those with lower minority populations are rezoned for other uses, and industrial zones in poorer neighborhoods are expanded. Zoning policies, therefore, can have adverse impacts on public health and equity. The location of noxious uses and the pollution they generate have ramifications for global public health and equity; these uses have been concentrated in the world's poorer places as well as in poorer places within more affluent countries. Planners, policymakers, and public health professionals must collaborate on a worldwide basis to address these equity, health, and land use planning problems. PMID:11441726

Src family kinases mediate the inhibition of substance P release in the rat spinal cord by μ-opioid receptors and GABA(B) receptors, but not α2 adrenergic receptors.

PubMed

Zhang, Guohua; Chen, Wenling; Marvizón, Juan Carlos G

2010-09-01

GABA(B) , μ-opioid and adrenergic α(2) receptors inhibit substance P release from primary afferent terminals in the dorsal horn. Studies in cell expression systems suggest that μ-opioid and GABA(B) receptors inhibit transmitter release from primary afferents by activating Src family kinases (SFKs), which then phosphorylate and inhibit voltage-gated calcium channels. This study investigated whether SFKs mediate the inhibition of substance P release by these three receptors. Substance P release was measured as neurokinin 1 receptor (NK1R) internalization in spinal cord slices and in vivo. In slices, NK1R internalization induced by high-frequency dorsal root stimulation was inhibited by the μ-opioid agonist DAMGO and the GABA(B) agonist baclofen. This inhibition was reversed by the SFK inhibitor PP1. NK1R internalization induced by low-frequency stimulation was also inhibited by DAMGO, but PP1 did not reverse this effect. In vivo, NK1R internalization induced by noxious mechanical stimulation of the hind paw was inhibited by intrathecal DAMGO and baclofen. This inhibition was reversed by intrathecal PP1, but not by the inactive PP1 analog PP3. PP1 produced no effect by itself. The α(2) adrenergic agonists medetomidine and guanfacine produced a small but statistically significant inhibition of NK1R internalization induced by low-frequency dorsal root stimulation. PP1 did not reverse the inhibition by guanfacine. These results show that SFKs mediate the inhibition of substance P release by μ-opioid and GABA(B) receptors, but not by α(2) receptors, which is probably mediated by the binding of G protein βγ subunits to calcium channels. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd. No claim to original US government works.

Electrophysiological study of supraspinal input and spinal output of cat's subnucleus reticularis dorsalis (SRD) neurons.

PubMed

Velo, Patricia; Leiras, Roberto; Canedo, Antonio

2013-01-01

This work addressed the study of subnucleus reticularis dorsalis (SRD) neurons in relation to their supraspinal input and the spinal terminating sites of their descending axons. SRD extracellular unitary recordings from anesthetized cats aimed to specifically test, 1) the rostrocaudal segmental level reached by axons of spinally projecting (SPr) neurons collateralizing or not to or through the ipsilateral nucleus reticularis gigantocellularis (NRGc), 2) whether SPr fibers bifurcate to the thalamus, and 3) the effects exerted on SRD cells by electrically stimulating the locus coeruleus, the periaqueductal grey, the nucleus raphe magnus, and the mesencephalic locomotor region. From a total of 191 SPr fibers tested to cervical 2 (Ce2), thoracic 5 (Th5) and lumbar5 (Lu5) stimulation, 81 ended between Ce2 and Th5 with 39 of them branching to or through the NRGc; 21/49 terminating between Th5 and Lu5 collateralized to or through the same nucleus, as did 34/61 reaching Lu5. The mean antidromic conduction velocity of SPr fibers slowed in the more proximal segments and increased with terminating distance along the cord. None of the 110 axons tested sent collaterals to the thalamus; instead thalamic stimulation induced long-latency polysynaptic responses in most cells but also short-latency, presumed monosynaptic, in 7.9% of the tested neurons (18/227). Antidromic and orthodromic spikes were elicited from the locus coeruleus and nucleus raphe magnus, but exclusively orthodromic responses were observed following stimulation of the periaqueductal gray or mesencephalic locomotor region. The results suggest that information from pain-and-motor-related supraspinal structures converge on SRD cells that through SPr axons having conduction velocities tuned to their length may affect rostral and caudal spinal cord neurons at fixed delays, both directly and in parallel through different descending systems. The SRD will thus play a dual functional role by simultaneously regulating dorsal horn ascending noxious information and pain-related motor responses.

Electrophysiological Study of Supraspinal Input and Spinal Output of Cat's Subnucleus Reticularis Dorsalis (SRD) Neurons

PubMed Central

Canedo, Antonio

2013-01-01

This work addressed the study of subnucleus reticularis dorsalis (SRD) neurons in relation to their supraspinal input and the spinal terminating sites of their descending axons. SRD extracellular unitary recordings from anesthetized cats aimed to specifically test, 1) the rostrocaudal segmental level reached by axons of spinally projecting (SPr) neurons collateralizing or not to or through the ipsilateral nucleus reticularis gigantocellularis (NRGc), 2) whether SPr fibers bifurcate to the thalamus, and 3) the effects exerted on SRD cells by electrically stimulating the locus coeruleus, the periaqueductal grey, the nucleus raphe magnus, and the mesencephalic locomotor region. From a total of 191 SPr fibers tested to cervical 2 (Ce2), thoracic 5 (Th5) and lumbar5 (Lu5) stimulation, 81 ended between Ce2 and Th5 with 39 of them branching to or through the NRGc; 21/49 terminating between Th5 and Lu5 collateralized to or through the same nucleus, as did 34/61 reaching Lu5. The mean antidromic conduction velocity of SPr fibers slowed in the more proximal segments and increased with terminating distance along the cord. None of the 110 axons tested sent collaterals to the thalamus; instead thalamic stimulation induced long-latency polysynaptic responses in most cells but also short-latency, presumed monosynaptic, in 7.9% of the tested neurons (18/227). Antidromic and orthodromic spikes were elicited from the locus coeruleus and nucleus raphe magnus, but exclusively orthodromic responses were observed following stimulation of the periaqueductal gray or mesencephalic locomotor region. The results suggest that information from pain-and-motor-related supraspinal structures converge on SRD cells that through SPr axons having conduction velocities tuned to their length may affect rostral and caudal spinal cord neurons at fixed delays, both directly and in parallel through different descending systems. The SRD will thus play a dual functional role by simultaneously regulating dorsal horn ascending noxious information and pain-related motor responses. PMID:23544161

Activation of PAR(2) receptors sensitizes primary afferents and causes leukocyte rolling and adherence in the rat knee joint.

PubMed

Russell, F A; Schuelert, N; Veldhoen, V E; Hollenberg, M D; McDougall, J J

2012-12-01

The PAR(2) receptors are involved in chronic arthritis by mechanisms that are as yet unclear. Here, we examined PAR(2) activation in the rat knee joint. PAR(2) in rat knee joint dorsal root ganglia (DRG) cells at L3-L5, retrogradely labelled with Fluoro-gold (FG) were demonstrated immunohistochemically. Electrophysiological recordings from knee joint nerve fibres in urethane anaesthetized Wistar rats assessed the effects of stimulating joint PAR(2) with its activating peptide, 2-furoyl-LIGRLO-NH(2) (1-100 nmol·100 μL(-1) , via close intra-arterial injection). Fibre firing rate was recorded during joint rotations before and 15 min after administration of PAR(2) activating peptide or control peptide. Leukocyte kinetics in the synovial vasculature upon PAR(2) activation were followed by intravital microscopy for 60 min after perfusion of 2-furoyl-LIGRLO-NH(2) or control peptide. Roles for transient receptor potential vanilloid-1 (TRPV1) or neurokinin-1 (NK(1) ) receptors in the PAR(2) responses were assessed using the selective antagonists, SB366791 and RP67580 respectively. PAR(2) were expressed in 59 ± 5% of FG-positive DRG cells; 100 nmol 2-furoyl-LIGRLO-NH(2) increased joint fibre firing rate during normal and noxious rotation, maximal at 3 min (normal; 110 ± 43%, noxious; 90 ± 31%). 2-Furoyl-LIGRLO-NH(2) also significantly increased leukocyte rolling and adhesion over 60 min. All these effects were blocked by pre-treatment with SB366791 and RP67580 (P < 0.05 compared with 2-furoyl-LIGRLO-NH(2) alone). PAR(2) receptors play an acute inflammatory role in the knee joint via TRPV1- and NK(1) -dependent mechanisms involving both PAR(2) -mediated neuronal sensitization and leukocyte trafficking. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

Peripheral KV7 channels regulate visceral sensory function in mouse and human colon.

PubMed

Peiris, Madusha; Hockley, James Rf; Reed, David E; Smith, Ewan St John; Bulmer, David C; Blackshaw, L Ashley

2017-01-01

Background Chronic visceral pain is a defining symptom of many gastrointestinal disorders. The K V 7 family (K V 7.1-K V 7.5) of voltage-gated potassium channels mediates the M current that regulates excitability in peripheral sensory nociceptors and central pain pathways. Here, we use a combination of immunohistochemistry, gut-nerve electrophysiological recordings in both mouse and human tissues, and single-cell qualitative real-time polymerase chain reaction of gut-projecting sensory neurons, to investigate the contribution of peripheral K V 7 channels to visceral nociception. Results Immunohistochemical staining of mouse colon revealed labelling of K V 7 subtypes (K V 7.3 and K V 7.5) with CGRP around intrinsic enteric neurons of the myenteric plexuses and within extrinsic sensory fibres along mesenteric blood vessels. Treatment with the K V 7 opener retigabine almost completely abolished visceral afferent firing evoked by the algogen bradykinin, in agreement with significant co-expression of mRNA transcripts by single-cell qualitative real-time polymerase chain reaction for KCNQ subtypes and the B 2 bradykinin receptor in retrogradely labelled extrinsic sensory neurons from the colon. Retigabine also attenuated responses to mechanical stimulation of the bowel following noxious distension (0-80 mmHg) in a concentration-dependent manner, whereas the K V 7 blocker XE991 potentiated such responses. In human bowel tissues, K V 7.3 and K V 7.5 were expressed in neuronal varicosities co-labelled with synaptophysin and CGRP, and retigabine inhibited bradykinin-induced afferent activation in afferent recordings from human colon. Conclusions We show that K V 7 channels contribute to the sensitivity of visceral sensory neurons to noxious chemical and mechanical stimuli in both mouse and human gut tissues. As such, peripherally restricted K V 7 openers may represent a viable therapeutic modality for the treatment of gastrointestinal pathologies.

Association Between Genetic Polymorphisms and Pain Sensitivity in Patients with Hip Osteoarthritis.

PubMed

Olesen, Anne E; Nielsen, Lecia M; Feddersen, Søren; Erlenwein, Joachim; Petzke, Frank; Przemeck, Michael; Christrup, Lona L; Drewes, Asbjørn M

2018-06-01

Factors such as age, gender, and genetic polymorphisms may explain individual differences in pain phenotype. Genetic associations with pain sensitivity have previously been investigated in osteoarthritis patients, with a focus on the P2X7, TRPV1, and TACR1 genes. However, other genes may play a role as well. Osteoarthritis is a common joint disease, and many patients suffering from this disease are thought to have increased sensitivity to noxious stimuli resulting from sensitization in the nociceptive system. The aim of this study was to investigate if genetic variants of mu, kappa, and delta opioid receptor genes (OPRM1, OPRK1, and OPRD1) and the catechol-O-methyltransferase gene (COMT) influenced the pain phenotype in patients with osteoarthritis. The frequencies of 17 polymorphisms were examined. Pain sensitivity was assessed preoperatively by (1) hip rotation, (2) contact heat stimulation, (3) conditioned pain modulation effect, and (4) pressure stimulation at the tibia in both the affected and the unaffected leg. Ninety-two patients (mean age 66 years) with unilateral hip osteoarthritis were included in the study. Carriage of the OPRM1 rs589046T allele was found to be associated with increased pain ratings during hip rotation (P = 0.04) and increased conditioned pain modulation (P = 0.049). Carriage of the OPRD1 rs2234918C allele was found to be associated with an increased pain detection threshold to contact heat stimulation (P = 0.001). No other associations were found (all P > 0.05). Results from the present study suggest that, in patients with hip osteoarthritis, genetic variants in OPRM1 and OPRD1 may contribute to the pain phenotype. © 2017 World Institute of Pain.

Processing noxious information at the subnucleus reticularis dorsalis (SRD) of anesthetized cats: wind-up mechanisms.

PubMed

Soto, Cristina; Martín-Cora, Francisco J; Leiras, Roberto; Velo, Patricia; Canedo, Antonio

2008-11-15

With the exception of one monkey's study, where wind-up was not reported, electrophysiological data from SRD neurons were obtained in rodents where they show wind-up. This work was designed to examine the response properties of SRD neurons in anesthetized cats to study how general the data from rats may be. Since cat's SRD cells showed wind-up, its underlying mechanisms were approached, an issue not previously addressed at supraspinal level. Electrical stimulation, extracellular (combined with microiontophoresis) and intracellular techniques revealed that A delta information reaches the SRD via the ventrolateral cord, whereas C information preferentially follows a dorsal route. Wind-up was usually generated by spinal and peripheral stimulation, but it was also evoked either by stimulating the nucleus reticularis gigantocellularis (NRGc), even after spinal cord section and bilateral full thickness removal of the cerebral cortex, or by applying microiontophoretic pulses of l-glutamate at 0.3-1 Hz. Wind-up relied on afferent repetitive activity gradually depolarizing the SRD neurons leading 3-4.5 Hz subthreshold membrane rhythmic activity to threshold. Riluzole retarded wind-up generation and decreased the number of spikes per stimulus during wind-up. GABA or glycine abolished spontaneous and sensory-evoked activity and bicuculline, but not strychnine, increased spontaneous and stimulus-evoked activity. These results demonstrate that wind-up at the SRD is not merely the reflection of spinal wind-up, but (i) can be locally generated, (ii) is partially dependent upon persistent sodium currents, and (iii) is under the modulation of a tonic GABAa-dependent inhibition decreasing SRD excitability. Injury and/or inflammation producing tonic C-fiber activation will surpass tonic inhibition generating wind-up.

Maladaptive spinal plasticity opposes spinal learning and recovery in spinal cord injury

PubMed Central

Ferguson, Adam R.; Huie, J. Russell; Crown, Eric D.; Baumbauer, Kyle M.; Hook, Michelle A.; Garraway, Sandra M.; Lee, Kuan H.; Hoy, Kevin C.; Grau, James W.

2012-01-01

Synaptic plasticity within the spinal cord has great potential to facilitate recovery of function after spinal cord injury (SCI). Spinal plasticity can be induced in an activity-dependent manner even without input from the brain after complete SCI. A mechanistic basis for these effects is provided by research demonstrating that spinal synapses have many of the same plasticity mechanisms that are known to underlie learning and memory in the brain. In addition, the lumbar spinal cord can sustain several forms of learning and memory, including limb-position training. However, not all spinal plasticity promotes recovery of function. Central sensitization of nociceptive (pain) pathways in the spinal cord may emerge in response to various noxious inputs, demonstrating that plasticity within the spinal cord may contribute to maladaptive pain states. In this review we discuss interactions between adaptive and maladaptive forms of activity-dependent plasticity in the spinal cord below the level of SCI. The literature demonstrates that activity-dependent plasticity within the spinal cord must be carefully tuned to promote adaptive spinal training. Prior work from our group has shown that stimulation that is delivered in a limb position-dependent manner or on a fixed interval can induce adaptive plasticity that promotes future spinal cord learning and reduces nociceptive hyper-reactivity. On the other hand, stimulation that is delivered in an unsynchronized fashion, such as randomized electrical stimulation or peripheral skin injuries, can generate maladaptive spinal plasticity that undermines future spinal cord learning, reduces recovery of locomotor function, and promotes nociceptive hyper-reactivity after SCI. We review these basic phenomena, how these findings relate to the broader spinal plasticity literature, discuss the cellular and molecular mechanisms, and finally discuss implications of these and other findings for improved rehabilitative therapies after SCI. PMID:23087647

Characterization of p-phenylenediamine-albumin binding sites and T-cell responses to hapten-modified protein.

PubMed

Jenkinson, Claire; Jenkins, Rosalind E; Aleksic, Maja; Pirmohamed, Munir; Naisbitt, Dean J; Park, B Kevin

2010-03-01

Exposure to p-phenylenediamine (PPD) is associated with the development of T-cell-mediated allergic contact dermatitis. The purpose of this study was to define the nature of the interaction of PPD with the protein and the antigenic determinant that stimulates T cells. Mass spectrometry was employed to show that PPD oxidation products bind irreversibly to cysteine (Cys, position 34) in human serum albumin (HSA). A modified tryptic peptide was characterized with an increase in mass of 106 Da, corresponding to the addition of PPD and not to the secondary products of self conjugation. Lymphocytes from 10 PPD-allergic patients, but not tolerant/naive individuals, were stimulated with PPD and PPD-modified HSA. A total of 70 PPD-specific and 10 PPD-HSA-specific CD4+, CD8+, and CD4+CD8+, Th2-secreting T-cell clones were generated from three allergic patients. In total, 40 clones were stimulated with both PPD and PPD-modified HSA. PPD-modified HSA triggered T-cell responses through a classical hapten mechanism involving processing. Presentation of PPD to several clones was dependent on protein complex formation (42 out of 48) and processing (32 out of 68); however, 12% of clones were triggered with PPD directly. These data identify Cys as the single target for PPD-HSA binding, and show that PPD protein adducts are antigenic determinants in patients with contact dermatitis.

rFN/Cad-11-Modified Collagen Type II Biomimetic Interface Promotes the Adhesion and Chondrogenic Differentiation of Mesenchymal Stem Cells

PubMed Central

Guo, Hongfeng; Zhang, Yuan; Li, Zhengsheng; Kang, Fei; Yang, Bo; Kang, Xia; Wen, Can; Yan, Yanfei; Jiang, Bo; Fan, Yujiang

2013-01-01

Properties of the cell-material interface are determining factors in the successful function of cells for cartilage tissue engineering. Currently, cell adhesion is commonly promoted through the use of polypeptides; however, due to their lack of complementary or modulatory domains, polypeptides must be modified to improve their ability to promote adhesion. In this study, we utilized the principle of matrix-based biomimetic modification and a recombinant protein, which spans fragments 7–10 of fibronectin module III (heterophilic motif ) and extracellular domains 1–2 of cadherin-11 (rFN/Cad-11) (homophilic motif ), to modify the interface of collagen type II (Col II) sponges. We showed that the designed material was able to stimulate cell proliferation and promote better chondrogenic differentiation of rabbit mesenchymal stem cells (MSCs) in vitro than both the FN modified surfaces and the negative control. Further, the Col II/rFN/Cad-11-MSCs composite stimulated cartilage formation in vivo; the chondrogenic effect of Col II alone was much less significant. These results suggested that the rFN/Cad-11-modified collagen type II biomimetic interface has dual biological functions of promoting adhesion and stimulating chondrogenic differentiation. This substance, thus, may serve as an ideal scaffold material for cartilage tissue engineering, enhancing repair of injured cartilage in vivo. PMID:23919505

Transcranial magnetic stimulation: physics, electrophysiology, and applications.

PubMed

Fatemi-Ardekani, Ali

2008-01-01

Transcranial magnetic stimulation (TMS) is a noninvasive technique used to stimulate the brain. This review will examine the fundamental principles of physics upon which magnetic stimulation is based, the design considerations of the TMS device, and hypotheses about its electrophysiological effects resulting in neuromodulation. TMS is valuable in neurophysiology research and has significant therapeutic potential in clinical neurology and psychiatry. While TMS can modify neuronal currents in the brain, its underlying mechanism remains unknown. Salient applications are included and some suggestions are outlined for future development of magnetic stimulators that could lead to more effective neuronal stimulation and therefore better therapeutic and diagnostic applications.

The antiarrhythmic effect of vagal stimulation after acute coronary occlusion: Role of the heart rate.

PubMed

Manati, Waheed; Pineau, Julien; Doñate Puertas, Rosa; Morel, Elodie; Quadiri, Timour; Bui-Xuan, Bernard; Chevalier, Philippe

2018-01-03

Strong evidence suggests a causal link between autonomic disturbances and ventricular arrhythmias. However, the mechanisms underlying the antiarrhythmic effect of vagal stimulation are poorly understood. The vagal antiarrhythmic effect might be modulated by a decrease in heart rate. the proximal anterior interventricular artery was occluded in 16 pigs by clamping under general anaesthesia. Group 1: heart rates remained spontaneous (n = 6; 12 occlusions); Group 2: heart rates were fixed at 190 beats per minute (bpm) with atrial electrical stimulation (n = 10; 20 occlusions). Each pig received two occlusions, 30 min apart, one without and one with vagal stimulation (10 Hz, 2 ms, 5-20 mA). The antiarrhythmic effect of vagal activation was defined as the time to the appearance of ventricular fibrillation (VF) after occlusion. In Group 1, vagal stimulation triggered a significant decrease in basal heart rate (132 ± 4 vs. 110 ± 17 bpm, p < 0.05), and delayed the time to VF after coronary occlusion (1102 ± 85 vs. 925 ± 41 s, p < 0.05). In Group 2, vagal stimulation did not modify the time to VF (103 ± 39 vs. 91 ± 20 s). Analyses revealed that heart rate and the time to VF were positively linearly related. Maintaining a constant heart rate with atrial electrical stimulation in pigs prevented vagal stimulation from modifying the time to VF after acute coronary occlusion.

An investigation into the inhibitory function of serotonin in diffuse noxious inhibitory controls in the neuropathic rat.

PubMed

Bannister, K; Lockwood, S; Goncalves, L; Patel, R; Dickenson, A H

2017-04-01

Following neuropathy α2-adrenoceptor-mediated diffuse noxious inhibitory controls (DNIC), whereby a noxious conditioning stimulus inhibits the activity of spinal wide dynamic range (WDR) neurons, are abolished, and spinal 5-HT7 receptor densities are increased. Here, we manipulate spinal 5-HT content in spinal nerve ligated (SNL) animals and investigate which 5-HT receptor mediated actions predominate. Using in vivo electrophysiology we recorded WDR neuronal responses to von frey filaments applied to the hind paw before, and concurrent to, a noxious ear pinch (the conditioning stimulus) in isoflurane-anaesthetised rats. The expression of DNIC was quantified as a reduction in WDR neuronal firing in the presence of conditioning stimulus and was investigated in SNL rats following spinal application of (1) selective serotonin reuptake inhibitors (SSRIs) citalopram or fluoxetine, or dual application of (2) SSRI plus 5-HT7 receptor antagonist SB269970, or (3) SSRI plus α2 adrenoceptor antagonist atipamezole. DNIC were revealed in SNL animals following spinal application of SSRI, but this effect was abolished upon joint application of SSRI plus SB269970 or atipamezole. We propose that in SNL animals the inhibitory actions (quantified as the presence of DNIC) of excess spinal 5-HT (presumed present following application of SSRI) were mediated via 5-HT7 receptors. The anti-nociception depends upon an underlying tonic noradrenergic inhibitory tone via the α2-adrenoceptor. Following neuropathy enhanced spinal serotonin availability switches the predominant spinal 5-HT receptor-mediated actions but also alters noradrenergic signalling. We highlight the therapeutic complexity of SSRIs and monoamine modulators for the treatment of neuropathic pain. © 2016 European Pain Federation - EFIC®.

Diffuse noxious inhibitory controls and nerve injury: restoring an imbalance between descending monoamine inhibitions and facilitations.

PubMed

Bannister, Kirsty; Patel, Ryan; Goncalves, Leonor; Townson, Louisa; Dickenson, Anthony H

2015-09-01

Diffuse noxious inhibitory controls (DNICs) utilize descending inhibitory controls through poorly understood brain stem pathways. The human counterpart, conditioned pain modulation, is reduced in patients with neuropathy aligned with animal data showing a loss of descending inhibitory noradrenaline controls together with a gain of 5-HT3 receptor-mediated facilitations after neuropathy. We investigated the pharmacological basis of DNIC and whether it can be restored after neuropathy. Deep dorsal horn neurons were activated by von Frey filaments applied to the hind paw, and DNIC was induced by a pinch applied to the ear in isoflurane-anaesthetized animals. Spinal nerve ligation was the model of neuropathy. Diffuse noxious inhibitory control was present in control rats but abolished after neuropathy. α2 adrenoceptor mechanisms underlie DNIC because the antagonists, yohimbine and atipamezole, markedly attenuated this descending inhibition. We restored DNIC in spinal nerve ligated animals by blocking 5-HT3 descending facilitations with the antagonist ondansetron or by enhancing norepinephrine modulation through the use of reboxetine (a norepinephrine reuptake inhibitor, NRI) or tapentadol (μ-opioid receptor agonist and NRI). Additionally, ondansetron enhanced DNIC in normal animals. Diffuse noxious inhibitory controls are reduced after peripheral nerve injury illustrating the central impact of neuropathy, leading to an imbalance in descending excitations and inhibitions. Underlying noradrenergic mechanisms explain the relationship between conditioned pain modulation and the use of tapentadol and duloxetine (a serotonin, NRI) in patients. We suggest that pharmacological strategies through manipulation of the monoamine system could be used to enhance DNIC in patients by blocking descending facilitations with ondansetron or enhancing norepinephrine inhibitions, so possibly reducing chronic pain.

Blockade of opioid receptors in the medullary reticularis nucleus dorsalis, but not the rostral ventromedial medulla, prevents analgesia produced by diffuse noxious inhibitory control in rats with muscle inflammation.

PubMed

de Resende, Marcos A; Silva, Luis Felipe S; Sato, Karina; Arendt-Nielsen, Lars; Sluka, Kathleen A

2011-06-01

Diffuse Noxious Inhibitory Controls (DNIC) involves application of a noxious stimulus outside the testing site to produce analgesia. In human subjects with a variety of chronic pain conditions, DNIC is less effective; however, in animal studies, DNIC is more effective after tissue injury. While opioids are involved in DNIC analgesia, the pathways involved in this opioid-induced analgesia are not clear. The aim of the present study was to test the effectiveness of DNIC in inflammatory muscle pain, and to study which brainstem sites mediate DNIC- analgesia. Rats were injected with 3% carrageenan into their gastrocnemius muscle and responses to cutaneous and muscle stimuli were assessed before and after inflammation, and before and after DNIC induced by noxious heat applied to the tail (45 °C and 47 °C). Naloxone was administered systemically, into rostral ventromedial medulla (RVM), or bilaterally into the medullary reticularis nucleus dorsalis (MdD) prior to the DNIC-conditioning stimuli. DNIC produced a similar analgesic effect in both acute and the chronic phases of inflammation reducing both cutaneous and muscle sensitivity in a dose-dependent manner. Naloxone systemically or microinjected into the MdD prevented DNIC-analgesia, while naloxone into the RVM had no effect on DNIC analgesia. Thus, DNIC analgesia involves activation of opioid receptors in the MdD. The current study shows that DNIC activates opioid receptors in the MdD, but not the RVM, to produce analgesia. These data are important for understanding clinical studies on DNIC as well as for potential treatment of chronic pain patients. Copyright © 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.

Somatosensory spatial attention modulates amplitudes, latencies, and latency jitter of laser-evoked brain potentials.

PubMed

Franz, Marcel; Nickel, Moritz M; Ritter, Alexander; Miltner, Wolfgang H R; Weiss, Thomas

2015-04-01

Several studies provided evidence that the amplitudes of laser-evoked potentials (LEPs) are modulated by attention. However, previous reports were based on across-trial averaging of LEP responses at the expense of losing information about intertrial variability related to attentional modulation. The aim of this study was to investigate the effects of somatosensory spatial attention on single-trial parameters (i.e., amplitudes, latencies, and latency jitter) of LEP components (N2 and P2). Twelve subjects participated in a sustained spatial attention paradigm while noxious laser stimuli (left hand) and noxious electrical stimuli (right hand) were sequentially delivered to the dorsum of the respective hand with nonnoxious air puffs randomly interspersed within the sequence of noxious stimuli. Participants were instructed to mentally count all stimuli (i.e., noxious and nonnoxious) applied to the attended location. Laser stimuli, presented to the attended hand (ALS), elicited larger single-trial amplitudes of the N2 component compared with unattended laser stimuli (ULS). In contrast, single-trial amplitudes of the P2 component were not significantly affected by spatial attention. Single-trial latencies of the N2 and P2 were significantly smaller for ALS vs. ULS. Additionally, the across-trial latency jitter of the N2 component was reduced for ALS. Conversely, the latency jitter of the P2 component was smaller for ULS compared with ALS. With the use of single-trial analysis, the study provided new insights into brain dynamics of LEPs related to spatial attention. Our results indicate that single-trial parameters of LEP components are differentially modulated by spatial attention. Copyright © 2015 the American Physiological Society.

Prediction of chronic post-operative pain: pre-operative DNIC testing identifies patients at risk.

PubMed

Yarnitsky, David; Crispel, Yonathan; Eisenberg, Elon; Granovsky, Yelena; Ben-Nun, Alon; Sprecher, Elliot; Best, Lael-Anson; Granot, Michal

2008-08-15

Surgical and medical procedures, mainly those associated with nerve injuries, may lead to chronic persistent pain. Currently, one cannot predict which patients undergoing such procedures are 'at risk' to develop chronic pain. We hypothesized that the endogenous analgesia system is key to determining the pattern of handling noxious events, and therefore testing diffuse noxious inhibitory control (DNIC) will predict susceptibility to develop chronic post-thoracotomy pain (CPTP). Pre-operative psychophysical tests, including DNIC assessment (pain reduction during exposure to another noxious stimulus at remote body area), were conducted in 62 patients, who were followed 29.0+/-16.9 weeks after thoracotomy. Logistic regression revealed that pre-operatively assessed DNIC efficiency and acute post-operative pain intensity were two independent predictors for CPTP. Efficient DNIC predicted lower risk of CPTP, with OR 0.52 (0.33-0.77 95% CI, p=0.0024), i.e., a 10-point numerical pain scale (NPS) reduction halves the chance to develop chronic pain. Higher acute pain intensity indicated OR of 1.80 (1.28-2.77, p=0.0024) predicting nearly a double chance to develop chronic pain for each 10-point increase. The other psychophysical measures, pain thresholds and supra-threshold pain magnitudes, did not predict CPTP. For prediction of acute post-operative pain intensity, DNIC efficiency was not found significant. Effectiveness of the endogenous analgesia system obtained at a pain-free state, therefore, seems to reflect the individual's ability to tackle noxious events, identifying patients 'at risk' to develop post-intervention chronic pain. Applying this diagnostic approach before procedures that might generate pain may allow individually tailored pain prevention and management, which may substantially reduce suffering.

Sex-specific effects of intranasal oxytocin on thermal pain perception: A randomised, double-blind, placebo-controlled cross-over study.

PubMed

Tracy, Lincoln M; Labuschagne, Izelle; Georgiou-Karistianis, Nellie; Gibson, Stephen J; Giummarra, Melita J

2017-09-01

Chronic neck and shoulder pain (CNSP) is a common musculoskeletal disorder in adults, which is linked to hypersensitivity to noxious stimuli. The hormone oxytocin has been implicated as a potential therapeutic for the management of chronic pain disorders, and has been suggested to have sex-specific effects on the salience of threatening stimuli. This study investigated the influence of intranasal oxytocin on the perception of noxious thermal stimuli. Participants were 24 individuals with CNSP lasting >12months (eight women), and 24 age- and sex-matched healthy, pain-free controls. In a randomised double-blind, placebo-controlled, cross-over study, participants attended two sessions, self-administering intranasal oxytocin (24 IU) in one session, and placebo in another. Participants rated intensity and unpleasantness of thermal heat stimuli at three body sites: the cervical spine, deltoid, and tibialis anterior, on 11-point numerical rating scales. Compared with placebo, intranasal oxytocin increased the perceived intensity of noxious heat stimuli in women with CNSP (Cohen's d=0.71), but not in men with CNSP, or healthy, pain-free controls. Men and women displayed divergent sensitivity across target sites for ratings of pain intensity (partial eta squared=0.12) and pain unpleasantness (partial eta squared=0.24), irrespective of drug condition. Men were more sensitive at the cervical spine and deltoid, whereas women were more sensitive at the tibialis. These findings suggest that oxytocin and endogenous sex hormones may interact to influence the salience of noxious stimuli. The hyperalgesic effects of oxytocin in women suggest that caution should be taken when considering oxytocin in the management of chronic pain. CT-2016-CTN-01313-1; ACTRN12616000532404. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Opiates Modulate Noxious Chemical Nociception through a Complex Monoaminergic/Peptidergic Cascade

PubMed Central

Mills, Holly; Ortega, Amanda; Law, Wenjing; Hapiak, Vera; Summers, Philip; Clark, Tobias

2016-01-01

The ability to detect noxious stimuli, process the nociceptive signal, and elicit an appropriate behavioral response is essential for survival. In Caenorhabditis elegans, opioid receptor agonists, such as morphine, mimic serotonin, and suppress the overall withdrawal from noxious stimuli through a pathway requiring the opioid-like receptor, NPR-17. This serotonin- or morphine-dependent modulation can be rescued in npr-17-null animals by the expression of npr-17 or a human κ opioid receptor in the two ASI sensory neurons, with ASI opioid signaling selectively inhibiting ASI neuropeptide release. Serotonergic modulation requires peptides encoded by both nlp-3 and nlp-24, and either nlp-3 or nlp-24 overexpression mimics morphine and suppresses withdrawal. Peptides encoded by nlp-3 act differentially, with only NLP-3.3 mimicking morphine, whereas other nlp-3 peptides antagonize NLP-3.3 modulation. Together, these results demonstrate that opiates modulate nociception in Caenorhabditis elegans through a complex monoaminergic/peptidergic cascade, and suggest that this model may be useful for dissecting opiate signaling in mammals. SIGNIFICANCE STATEMENT Opiates are used extensively to treat chronic pain. In Caenorhabditis elegans, opioid receptor agonists suppress the overall withdrawal from noxious chemical stimuli through a pathway requiring an opioid-like receptor and two distinct neuropeptide-encoding genes, with individual peptides from the same gene functioning antagonistically to modulate nociception. Endogenous opioid signaling functions as part of a complex, monoaminergic/peptidergic signaling cascade and appears to selectively inhibit neuropeptide release, mediated by a α-adrenergic-like receptor, from two sensory neurons. Importantly, receptor null animals can be rescued by the expression of the human κ opioid receptor, and injection of human opioid receptor ligands mimics exogenous opiates, highlighting the utility of this model for dissecting opiate signaling in mammals. PMID:27194330

Neuromuscular Electrical Stimulation for Skeletal Muscle Function

PubMed Central

Doucet, Barbara M.; Lam, Amy; Griffin, Lisa

2012-01-01

Lack of neural innervation due to neurological damage renders muscle unable to produce force. Use of electrical stimulation is a medium in which investigators have tried to find a way to restore movement and the ability to perform activities of daily living. Different methods of applying electrical current to modify neuromuscular activity are electrical stimulation (ES), neuromuscular electrical stimulation (NMES), transcutaneous electrical nerve stimulation (TENS), and functional electrical stimulation (FES). This review covers the aspects of electrical stimulation used for rehabilitation and functional purposes. Discussed are the various parameters of electrical stimulation, including frequency, pulse width/duration, duty cycle, intensity/amplitude, ramp time, pulse pattern, program duration, program frequency, and muscle group activated, and how they affect fatigue in the stimulated muscle. PMID:22737049

Creation of X-Ray Transparency of Matter by Stimulated Elastic Forward Scattering.

PubMed

Stöhr, J; Scherz, A

2015-09-04

X-ray absorption by matter has long been described by the famous Beer-Lambert law. Here, we show how this fundamental law needs to be modified for high-intensity coherent x-ray pulses, now available at x-ray free electron lasers, due to the onset of stimulated elastic forward scattering. We present an analytical expression for the modified polarization-dependent Beer-Lambert law for the case of resonant core-to-valence electronic transitions and incident transform limited x-ray pulses. Upon transmission through a solid, the resonant absorption and dichroic contrasts are found to vanish with increasing x-ray intensity, with the stimulation threshold lowered by orders of magnitude through a resonant superradiantlike effect. Our results have broad implications for the study of matter with x-ray lasers.

Creation of X-Ray Transparency of Matter by Stimulated Elastic Forward Scattering

NASA Astrophysics Data System (ADS)

Stöhr, J.; Scherz, A.

2015-09-01

X-ray absorption by matter has long been described by the famous Beer-Lambert law. Here, we show how this fundamental law needs to be modified for high-intensity coherent x-ray pulses, now available at x-ray free electron lasers, due to the onset of stimulated elastic forward scattering. We present an analytical expression for the modified polarization-dependent Beer-Lambert law for the case of resonant core-to-valence electronic transitions and incident transform limited x-ray pulses. Upon transmission through a solid, the resonant absorption and dichroic contrasts are found to vanish with increasing x-ray intensity, with the stimulation threshold lowered by orders of magnitude through a resonant superradiantlike effect. Our results have broad implications for the study of matter with x-ray lasers.

Characterization of the functional near-infrared spectroscopy response to nociception in a pediatric population.

PubMed

Olbrecht, Vanessa A; Jiang, Yifei; Viola, Luigi; Walter, Charlotte M; Liu, Hanli; Kurth, Charles D

2018-02-01

Near-infrared spectroscopy can interrogate functional optical signal changes in regional brain oxygenation and blood volume to nociception analogous to functional magnetic resonance imaging. This exploratory study aimed to characterize the near-infrared spectroscopy signals for oxy-, deoxy-, and total hemoglobin from the brain in response to nociceptive stimulation of varying intensity and duration, and after analgesic and neuromuscular paralytic in a pediatric population. We enrolled children 6 months-21 years during propofol sedation before surgery. The near-infrared spectroscopy sensor was placed on the forehead and nociception was produced from an electrical current applied to the wrist. We determined the near-infrared spectroscopy signal response to increasing current intensity and duration, and after fentanyl, sevoflurane, and neuromuscular paralytic. Heart rate and arm movement during electrical stimulation was also recorded. The near-infrared spectroscopy signals for oxy-, deoxy-, and total hemoglobin were calculated as optical density*time (area under curve). During electrical stimulation, nociception was evident: tachycardia and arm withdrawal was observed that disappeared after fentanyl and sevoflurane, whereas after paralytic, tachycardia persisted while arm withdrawal disappeared. The near-infrared spectroscopy signals for oxy-, deoxy-, and total hemoglobin increased during stimulation and decreased after stimulation; the areas under the curves were greater for stimulations 30 mA vs 15 mA (13.9 [5.6-22.2], P = .0021; 5.6 [0.8-10.5], P = .0254, and 19.8 [10.5-29.1], P = .0002 for HbO 2 , Hb, and Hb T , respectively), 50 Hz vs 1 Hz (17.2 [5.8-28.6], P = .0046; 7.5 [0.7-14.3], P = .0314, and 21.9 [4.2-39.6], P = .0177 for HbO 2 , Hb, and Hb T , respectively) and 45 seconds vs 15 seconds (16.3 [3.4-29.2], P = .0188 and 22.0 [7.5-36.5], P = .0075 for HbO 2 and Hb T , respectively); the areas under the curves were attenuated by analgesics but not by paralytic. Near-infrared spectroscopy detected functional activation to nociception in a broad pediatric population. The near-infrared spectroscopy response appears to represent nociceptive processing because the signals increased with noxious stimulus intensity and duration, and were blocked by analgesics but not paralytics. © 2017 John Wiley & Sons Ltd.

Electrical Cerebral Stimulation Modifies Inhibitory Systems

NASA Astrophysics Data System (ADS)

Cuéllar-Herrera, M.; Rocha, L.

2003-09-01

Electrical stimulation of the nervous tissue has been proposed as a method to treat some neurological disorders, such as epilepsy. Epileptic seizures result from excessive, synchronous, abnormal firing patterns of neurons that are located predominantly in the cerebral cortex. Many people with epilepsy continue presenting seizures even though they are under regimens of antiepileptic medications. An alternative therapy for treatment resistant epilepsy is cerebral electrical stimulation. The present study is focused to review the effects of different types of electrical stimulation and specifically changes in amino acids.

The Postnatal Development of Spinal Sensory Processing

NASA Astrophysics Data System (ADS)

Fitzgerald, Maria; Jennings, Ernest

1999-07-01

The mechanisms by which infants and children process pain should be viewed within the context of a developing sensory nervous system. The study of the neurophysiological properties and connectivity of sensory neurons in the developing spinal cord dorsal horn of the intact postnatal rat has shed light on the way in which the newborn central nervous system analyzes cutaneous innocuous and noxious stimuli. The receptive field properties and evoked activity of newborn dorsal horn cells to single repetitive and persistent innocuous and noxious inputs are developmentally regulated and reflect the maturation of excitatory transmission within the spinal cord. These changes will have an important influence on pain processing in the postnatal period.

Forecasting system predicts presence of sea nettles in Chesapeake Bay

NASA Astrophysics Data System (ADS)

Brown, Christopher W.; Hood, Raleigh R.; Li, Zhen; Decker, Mary Beth; Gross, Thomas F.; Purcell, Jennifer E.; Wang, Harry V.

Outbreaks of noxious biota, which occur in both aquatic and terrestrial systems, can have considerable negative economic impacts. For example, an increasing frequency of harmful algal blooms worldwide has negatively affected the tourism industry in many regions. Such impacts could be mitigated if the conditions that give rise to these outbreaks were known and could be monitored. Recent advances in technology and communications allow us to continuously measure and model many environmental factors that are responsible for outbreaks of certain noxious organisms. A new prototype ecological forecasting system predicts the likelihood of occurrence of the sea nettle (Chrysaora quinquecirrha), a stinging jellyfish, in the Chesapeake Bay.

Federal Interagency Coordination for Invasive Plant Issues -- The Federal Interagency Committee for the Management of Noxious and Exotic Weeds (FICMNEW)

USGS Publications Warehouse

Westbrooks, Randy G.

2011-01-01

The U.S. Federal Interagency Committee for the Management of Noxious and Exotic Weeds (FICMNEW) is a formal partnership between 16 federal agencies that have invasive plant management and regulatory responsibilities for the United States and its territories. Efforts to develop a national level federal interagency committee to coordinate federal activities were initiated by national weed program managers with the USDA Forest Service and the Bureau of Land Management in 1989. FICMNEW was formally established through a Memorandum of Understanding that was signed by agency administrators of member agencies in August, 1994.

Sensing the heat with TRPM3.

PubMed

Vriens, Joris; Voets, Thomas

2018-05-01

Heat sensation, the ability to detect warm and noxious temperatures, is an ancient and indispensable sensory process. Noxious temperatures can have detrimental effects on the physiology and integrity of cells, and therefore, the detection of environmental hot temperatures is absolutely crucial for survival. Temperature-sensitive ion channels, which conduct ions in a highly temperature-dependent manner, have been put forward as molecular thermometers expressed at the endings of sensory neurons. In particular, several temperature-sensitive members of the transient receptor potential (TRP) superfamily of ion channels have been identified, and a multitude of in vivo studies have shown that the capsaicin-sensitive TRPV1 channel plays a key role as a noxious heat sensor. However, Trpv1-deficient mice display a residual heat sensitivity suggesting the existence of additional heat sensor(s). In this chapter, we provide evidence for the role of the non-selective calcium-permeable TRPM3 ion channel as an additional heat sensor that acts independently of TRPV1, and give an update of the modulation of this channel by various molecular mechanisms. Finally, we compare antagonists of TRPM3 to specific blockers of TRPV1 as potential analgesic drugs to treat pathological pain.

Flies dynamically anti-track, rather than ballistically escape, aversive odor during flight.

PubMed

Wasserman, Sara; Lu, Patrick; Aptekar, Jacob W; Frye, Mark A

2012-08-15

Tracking distant odor sources is crucial to foraging, courtship and reproductive success for many animals including fish, flies and birds. Upon encountering a chemical plume in flight, Drosophila melanogaster integrates the spatial intensity gradient and temporal fluctuations over the two antennae, while simultaneously reducing the amplitude and frequency of rapid steering maneuvers, stabilizing the flight vector. There are infinite escape vectors away from a noxious source, in contrast to a single best tracking vector towards an attractive source. Attractive and aversive odors are segregated into parallel neuronal pathways in flies; therefore, the behavioral algorithms for avoidance may be categorically different from tracking. Do flies plot random ballistic or otherwise variable escape vectors? Or do they instead make use of temporally dynamic mechanisms for continuously and directly avoiding noxious odors in a manner similar to tracking appetitive ones? We examine this question using a magnetic tether flight simulator that permits free yaw movements, such that flies can actively orient within spatially defined odor plumes. We show that in-flight aversive flight behavior shares all of the key features of attraction such that flies continuously 'anti-track' the noxious source.

Flies dynamically anti-track, rather than ballistically escape, aversive odor during flight

PubMed Central

Wasserman, Sara; Lu, Patrick; Aptekar, Jacob W.; Frye, Mark A.

2012-01-01

SUMMARY Tracking distant odor sources is crucial to foraging, courtship and reproductive success for many animals including fish, flies and birds. Upon encountering a chemical plume in flight, Drosophila melanogaster integrates the spatial intensity gradient and temporal fluctuations over the two antennae, while simultaneously reducing the amplitude and frequency of rapid steering maneuvers, stabilizing the flight vector. There are infinite escape vectors away from a noxious source, in contrast to a single best tracking vector towards an attractive source. Attractive and aversive odors are segregated into parallel neuronal pathways in flies; therefore, the behavioral algorithms for avoidance may be categorically different from tracking. Do flies plot random ballistic or otherwise variable escape vectors? Or do they instead make use of temporally dynamic mechanisms for continuously and directly avoiding noxious odors in a manner similar to tracking appetitive ones? We examine this question using a magnetic tether flight simulator that permits free yaw movements, such that flies can actively orient within spatially defined odor plumes. We show that in-flight aversive flight behavior shares all of the key features of attraction such that flies continuously ‘anti-track’ the noxious source. PMID:22837456

Transient receptor potential ankyrin 1 antagonists block the noxious effects of toxic industrial isocyanates and tear gases.

PubMed

Bessac, Bret F; Sivula, Michael; von Hehn, Christian A; Caceres, Ana I; Escalera, Jasmine; Jordt, Sven-Eric

2009-04-01

The release of methyl isocyanate in Bhopal, India, caused the worst industrial accident in history. Exposures to industrial isocyanates induce lacrimation, pain, airway irritation, and edema. Similar responses are elicited by chemicals used as tear gases. Despite frequent exposures, the biological targets of isocyanates and tear gases in vivo have not been identified, precluding the development of effective countermeasures. We use Ca(2+) imaging and electrophysiology to show that the noxious effects of isocyanates and those of all major tear gas agents are caused by activation of Ca(2+) influx and membrane currents in mustard oil-sensitive sensory neurons. These responses are mediated by transient receptor potential ankyrin 1 (TRPA1), an ion channel serving as a detector for reactive chemicals. In mice, genetic ablation or pharmacological inhibition of TRPA1 dramatically reduces isocyanate- and tear gas-induced nocifensive behavior after both ocular and cutaneous exposures. We conclude that isocyanates and tear gas agents target the same neuronal receptor, TRPA1. Treatment with TRPA1 antagonists may prevent and alleviate chemical irritation of the eyes, skin, and airways and reduce the adverse health effects of exposures to a wide range of toxic noxious chemicals.

Modified prenatal sensory stimulation influences postnatal behavioral and perceptual responsiveness in bobwhite quail chicks (Colinus virginianus).

PubMed

Reynolds, Greg D; Lickliter, Robert

2004-06-01

Asynchronous bimodal stimulation during prenatal development elicits higher levels of behavioral and physiological arousal in precocial avian embryos than does unimodal sensory stimulation. To investigate whether the increased arousal associated with prenatal bimodal stimulation has enduring effects into postnatal development, bobwhite quail (Colinus virginianus) embryos received no supplemental stimulation, unimodal auditory stimulation, or bimodal (audiovisual) stimulation prior to hatching. Embryos exposed to concurrent bimodal stimulation demonstrated greater levels of behavioral activity and failed to use maternal visual cues to successfully direct species-specific perceptual preferences following hatching. These results provide initial evidence that asynchronous bimodal sensory stimulation during prenatal development can have enduring effects on early postnatal behavioral arousal and perceptual responsiveness and suggest that developmental limitations on prenatal sensory stimulation play an important role in the emergence of species-typical behavior.

Practical use of the raw electroencephalogram waveform during general anesthesia: the art and science.

PubMed

Bennett, Cambell; Voss, Logan J; Barnard, John P M; Sleigh, James W

2009-08-01

Quantitative electroencephalogram (qEEG) monitors are often used to estimate depth of anesthesia and intraoperative recall during general anesthesia. As with any monitor, the processed numerical output is often misleading and has to be interpreted within a clinical context. For the safe clinical use of these monitors, a clear mental picture of the expected raw electroencephalogram (EEG) patterns, as well as a knowledge of the common EEG artifacts, is absolutely necessary. This has provided the motivation to write this tutorial. We describe, and give examples of, the typical EEG features of adequate general anesthesia, effects of noxious stimulation, and adjunctive drugs. Artifacts are commonly encountered and may be classified as arising from outside the head, from the head but outside the brain (commonly frontal electromyogram), or from within the brain (atypical or pathologic). We include real examples of clinical problem-solving processes. In particular, it is important to realize that an artifactually high qEEG index is relatively common and may result in dangerous anesthetic drug overdose. The anesthesiologist must be certain that the qEEG number is consistent with the apparent state of the patient, the doses of various anesthetic drugs, and the degree of surgical stimulation, and that the qEEG number is consistent with the appearance of the raw EEG signal. Any discrepancy must be a stimulus for the immediate critical examination of the patient's state using all the available information rather than reactive therapy to "treat" a number.

Near infrared spectroscopy for fibre based gas detection

NASA Astrophysics Data System (ADS)

Stewart, George; Johnstone, Walter; Thursby, Graham; Culshaw, Brian

2010-04-01

Gas sensing systems based on fibre optic linked near infra red absorption cells are potentially a flexible and effective tool for monitoring accumulations of hazardous and noxious gases in enclosed areas such as tunnels and mines. Additionally the same baseline technology is readily modified to measure concentrations of hydrocarbon fuels - notably but not exclusively methane, and monitoring emissions of greenhouse gases. Furthermore the system can be readily implemented to provide intrinsically safe monitoring over extensive areas at up to ~250 points from a single interrogation unit. In this paper we review our work on fibre coupled gas sensing systems. We outline the basic principles through which repeatable and accurate self calibrating gas measurements may be realised, including the recover of detailed line shapes for non contact temperature and / or pressure measurements in addition to concentration assessments in harsh environments. We also outline our experience in using these systems in extensive networks operating under inhospitable conditions over extended periods extending to several years.

Rab7-a novel redox target that modulates inflammatory pain processing.

PubMed

Kallenborn-Gerhardt, Wiebke; Möser, Christine V; Lorenz, Jana E; Steger, Mirco; Heidler, Juliana; Scheving, Reynir; Petersen, Jonas; Kennel, Lea; Flauaus, Cathrin; Lu, Ruirui; Edinger, Aimee L; Tegeder, Irmgard; Geisslinger, Gerd; Heide, Heinrich; Wittig, Ilka; Schmidtko, Achim

2017-07-01

Chronic pain is accompanied by production of reactive oxygen species (ROS) in various cells that are important for nociceptive processing. Recent data indicate that ROS can trigger specific redox-dependent signaling processes, but the molecular targets of ROS signaling in the nociceptive system remain largely elusive. Here, we performed a proteome screen for pain-dependent redox regulation using an OxICAT approach, thereby identifying the small GTPase Rab7 as a redox-modified target during inflammatory pain in mice. Prevention of Rab7 oxidation by replacement of the redox-sensing thiols modulates its GTPase activity. Immunofluorescence studies revealed Rab7 expression to be enriched in central terminals of sensory neurons. Knockout mice lacking Rab7 in sensory neurons showed normal responses to noxious thermal and mechanical stimuli; however, their pain behavior during inflammatory pain and in response to ROS donors was reduced. The data suggest that redox-dependent changes in Rab7 activity modulate inflammatory pain sensitivity.

Age-dependent effects of topiramate on the acquisition and the retention of rapid kindling.

PubMed

Mazarati, Andréy; Shin, Don; Auvin, Stéphane; Sankar, Raman

2007-04-01

To examine antiepileptogenic, disease modifying, and anticonvulsant effects of topiramate under conditions of rapid kindling at different stages of development. Afterdischarge threshold (ADT) and duration (ADD) were examined in 2-, 3-, and 5-week-old Wistar rats before and after administration of topiramate (200 mg/kg). Animals underwent a rapid kindling protocol (sixty 10-s trains, bipolar 20 Hz square wave pulses delivered every 5 min). The progression of behavioral and electrographic seizures, and responses to test stimulations 24 h after the protocol were compared between topiramate and vehicle-treated control rats. In addition, rats that were previously given vehicle only prior to kindling, were then given topiramate to examine the effect on established kindled seizures. In 2-week-old animals, topiramate affected neither the baseline afterdischarge, nor the progression of kindled seizures. In 3-week-old rats, topiramate did not modify the baseline afterdischarge, but significantly delayed the occurrence of full motor seizures in response to repeated stimulations. Topiramate treatment of 5-week-old rats increased baseline ADT, shortened ADD, and delayed the progression of kindled seizures. Twenty-four h after the last kindling stimulation, animals of all ages exhibited a decreased ADT, an increase ADD, and developed behavioral seizures in response to threshold stimulation. Vehicle-treated kindled rats that were then given topiramate displayed significantly attenuated behavioral seizures induced by the threshold stimulation. Topiramate exhibited age-dependent disease-modifying effects under conditions of rapid kindling, but failed to block epileptogenesis. Topiramate also inhibited kindled seizures with equal efficacy across the three ages.

Age-Dependent Effects of Topiramate on the Acquisition and the Retention of Rapid Kindling

PubMed Central

Mazarati, Andréy; Shin, Don; Auvin, Stéphane; Sankar, Raman

2008-01-01

Summary Purpose To examine antiepileptogenic, disease-modifying, and anticonvulsant effects of topiramate under conditions of rapid kindling at different stages of development. Methods Afterdischarge threshold (ADT) and duration (ADD) were examined in two-, three-, and five-week old Wistar rats before and after administration of topiramate (200 mg/kg). Animals underwent a rapid kindling protocol (sixty 10 second trains, bipolar 20 Hz square wave pulses delivered every five minutes). The progression of behavioral and electrographic seizures, and responses to test stimulations 24 hours after the protocol were compared between topiramate and vehicle treated control rats. In addition, rats that were previously given vehicle only prior to kindling, were then given topiramate to examine the effect on established kindled seizures. Results In two-week old animals, topiramate affected neither the baseline afterdischarge, nor the progression of kindled seizures. In three-week old rats, topiramate did not modify the baseline afterdischarge, but significantly delayed the occurrence of full motor seizures in response to repeated stimulations. Topiramate treatment of five-week old rats increased baseline ADT, shortened ADD, and delayed the progression of kindled seizures. Twenty four hours after the last kindling stimulation, animals of all ages exhibited a decreased ADT, an increase ADD, and developed behavioral seizures in response to threshold stimulation. Vehicle treated kindled rats that were then given topiramate displayed significantly attenuated behavioral seizures induced by the threshold stimulation. Conclusions Topiramate exhibited age-dependent disease-modifying effects under conditions of rapid kindling, but failed to block epileptogenesis. Topiramate also inhibited kindled seizures with equal efficacy across the three ages. PMID:17319916

The role of endogenous molecules in modulating pain through transient receptor potential vanilloid 1 (TRPV1)

PubMed Central

Morales-Lázaro, Sara L; Simon, Sidney A; Rosenbaum, Tamara

2013-01-01

Pain is a physiological response to a noxious stimulus that decreases the quality of life of those sufferring from it. Research aimed at finding new therapeutic targets for the treatment of several maladies, including pain, has led to the discovery of numerous molecular regulators of ion channels in primary afferent nociceptive neurons. Among these receptors is TRPV1 (transient receptor potential vanilloid 1), a member of the TRP family of ion channels. TRPV1 is a calcium-permeable channel, which is activated or modulated by diverse exogenous noxious stimuli such as high temperatures, changes in pH, and irritant and pungent compounds, and by selected molecules released during tissue damage and inflammatory processes. During the last decade the number of endogenous regulators of TRPV1's activity has increased to include lipids that can negatively regulate TRPV1, as is the case for cholesterol and PIP2 (phosphatidylinositol 4,5-biphosphate) while, in contrast, other lipids produced in response to tissue injury and ischaemic processes are known to positively regulate TRPV1. Among the latter, lysophosphatidic acid activates TRPV1 while amines such as N-acyl-ethanolamines and N-acyl-dopamines can sensitize or directly activate TRPV1. It has also been found that nucleotides such as ATP act as mediators of chemically induced nociception and pain and gases, such as hydrogen sulphide and nitric oxide, lead to TRPV1 activation. Finally, the products of lipoxygenases and omega-3 fatty acids among other molecules, such as divalent cations, have also been shown to endogenously regulate TRPV1 activity. Here we provide a comprehensive review of endogenous small molecules that regulate the function of TRPV1. Acting through mechanisms that lead to sensitization and desensitization of TRPV1, these molecules regulate pathways involved in pain and nociception. Understanding how these compounds modify TRPV1 activity will allow us to comprehend how some pathologies are associated with its deregulation. PMID:23613529

The role of endogenous molecules in modulating pain through transient receptor potential vanilloid 1 (TRPV1).

PubMed

Morales-Lázaro, Sara L; Simon, Sidney A; Rosenbaum, Tamara

2013-07-01

Pain is a physiological response to a noxious stimulus that decreases the quality of life of those sufferring from it. Research aimed at finding new therapeutic targets for the treatment of several maladies, including pain, has led to the discovery of numerous molecular regulators of ion channels in primary afferent nociceptive neurons. Among these receptors is TRPV1 (transient receptor potential vanilloid 1), a member of the TRP family of ion channels. TRPV1 is a calcium-permeable channel, which is activated or modulated by diverse exogenous noxious stimuli such as high temperatures, changes in pH, and irritant and pungent compounds, and by selected molecules released during tissue damage and inflammatory processes. During the last decade the number of endogenous regulators of TRPV1's activity has increased to include lipids that can negatively regulate TRPV1, as is the case for cholesterol and PIP2 (phosphatidylinositol 4,5-biphosphate) while, in contrast, other lipids produced in response to tissue injury and ischaemic processes are known to positively regulate TRPV1. Among the latter, lysophosphatidic acid activates TRPV1 while amines such as N-acyl-ethanolamines and N-acyl-dopamines can sensitize or directly activate TRPV1. It has also been found that nucleotides such as ATP act as mediators of chemically induced nociception and pain and gases, such as hydrogen sulphide and nitric oxide, lead to TRPV1 activation. Finally, the products of lipoxygenases and omega-3 fatty acids among other molecules, such as divalent cations, have also been shown to endogenously regulate TRPV1 activity. Here we provide a comprehensive review of endogenous small molecules that regulate the function of TRPV1. Acting through mechanisms that lead to sensitization and desensitization of TRPV1, these molecules regulate pathways involved in pain and nociception. Understanding how these compounds modify TRPV1 activity will allow us to comprehend how some pathologies are associated with its deregulation.

Comparison of results of cycles treated with modified mild protocol and short protocol for ovarian stimulation.

PubMed

Coelho, F; Aguiar, L F; Cunha, G S P; Cardinot, N; Lucena, E

2014-01-01

The ovarian stimulation has been applied in order to increase the number of oocytes to compensate for the poor results of in vitro fertilization, allowing the selection of one or more embryos to be transferred. Our aim is to compare the results obtained in IVF/ICSI cycles using the short protocol for controlled ovarian stimulation to the results from the modified mild protocol used in our department. A total of 240 cycles were conducted from January 2010 to December 2011. When comparing both protocols, it could be observed that there was a significant difference in the quantity of gonadotropins doses in the mild protocol and in the short protocol. No significant difference was observed regarding pregnancy rates per cycle, 22% and 26.2%, in short and mild protocols, respectively. The protocols of controlled ovarian stimulation are often associated with high risk of complications such as ovarian hyperstimulation syndrome, excessive emotional stress, high rates of treatment dropouts, and abdominal discomfort. With the data obtained in this study, one can conclude that there are less risks and complications for the patient when using the mild stimulation protocol. It was also observed that in this group there was a slightly higher rate.

Transcranial focal electrical stimulation via tripolar concentric ring electrodes does not modify the short- and long-term memory formation in rats evaluated in the novel object recognition test.

PubMed

Rogel-Salazar, G; Luna-Munguía, H; Stevens, K E; Besio, W G

2013-04-01

Noninvasive transcranial focal electrical stimulation (TFS) via tripolar concentric ring electrodes (TCREs) has been under development as an alternative/complementary therapy for seizure control. Transcranial focal electrical stimulation has shown efficacy in attenuating penicillin-, pilocarpine-, and pentylenetetrazole-induced acute seizures in rat models. This study evaluated the effects of TFS via TCREs on the memory formation of healthy rats as a safety test of TFS. Short- and long-term memory formation was tested after the application of TFS using the novel object recognition (NOR) test. The following independent groups were used: naïve, control (without TFS), and TFS (treated). The naïve, control, and stimulated groups spent more time investigating the new object than the familiar one during the test phase. Transcranial focal electrical stimulation via TCREs given once does not modify the short- and long-term memory formation in rats in the NOR test. Results provide an important step towards a better understanding for the safe usage of TFS via TCREs. Copyright © 2013 Elsevier Inc. All rights reserved.

Acetylation mediates Cx43 reduction caused by electrical stimulation

PubMed Central

Meraviglia, Viviana; Azzimato, Valerio; Colussi, Claudia; Florio, Maria Cristina; Binda, Anna; Panariti, Alice; Qanud, Khaled; Suffredini, Silvia; Gennaccaro, Laura; Miragoli, Michele; Barbuti, Andrea; Lampe, Paul D.; Gaetano, Carlo; Pramstaller, Peter P.; Capogrossi, Maurizio C.; Recchia, Fabio A.; Pompilio, Giulio; Rivolta, Ilaria; Rossini, Alessandra

2015-01-01

Communication between cardiomyocytes depends upon Gap Junctions (GJ). Previous studies have demonstrated that electrical stimulation induces GJ remodeling and modifies histone acetylases (HAT) and deacetylases (HDAC) activities, although these two results have not been linked. The aim of this work was to establish whether electrical stimulation modulates GJ-mediated cardiac cell-cell communication by acetylation-dependent mechanisms. Field stimulation of HL-1 cardiomyocytes at 0.5 Hz for 24 hours significantly reduced Connexin43 (Cx43) expression and cell-cell communication. HDAC activity was down-regulated whereas HAT activity was not modified resulting in increased acetylation of Cx43. Consistent with a post-translational mechanism, we did not observe a reduction in Cx43 mRNA in electrically stimulated cells, while the proteasomal inhibitor MG132 maintained Cx43 expression. Further, the treatment of paced cells with the HAT inhibitor Anacardic Acid maintained both the levels of Cx43 and cell-cell communication. Finally, we observed increased acetylation of Cx43 in the left ventricles of dogs subjected to chronic tachypacing as a model of abnormal ventricular activation. In conclusion, our findings suggest that altered electrical activity can regulate cardiomyocyte communication by influencing the acetylation status of Cx43. PMID:26264759

Do Decapod Crustaceans Have Nociceptors for Extreme pH?

PubMed Central

Puri, Sakshi; Faulkes, Zen

2010-01-01

Background Nociception is the physiological detection of noxious stimuli. Because of its obvious importance, nociception is expected to be widespread across animal taxa and to trigger robust behaviours reliably. Nociception in invertebrates, such as crustaceans, is poorly studied. Methodology/Principal Findings Three decapod crustacean species were tested for nociceptive behaviour: Louisiana red swamp crayfish (Procambarus clarkii), white shrimp (Litopenaeus setiferus), and grass shrimp (Palaemonetes sp.). Applying sodium hydroxide, hydrochloric acid, or benzocaine to the antennae caused no change in behaviour in the three species compared to controls. Animals did not groom the stimulated antenna, and there was no difference in movement of treated individuals and controls. Extracellular recordings of antennal nerves in P. clarkii revealed continual spontaneous activity, but no neurons that were reliably excited by the application of concentrated sodium hydroxide or hydrochloric acid. Conclusions/Significance Previously reported responses to extreme pH are either not consistently evoked across species or were mischaracterized as nociception. There was no behavioural or physiological evidence that the antennae contained specialized nociceptors that responded to pH. PMID:20422026

Effects of Cyberprogram 2.0 on "face-to-face" bullying, cyberbullying, and empathy.

PubMed

Garaigordobil, Maite; Martínez-Valderrey, Vanesa

2015-01-01

The considerable prevalence of cyberbullying and its noxious effects on all those concerned reveals the need for programs to prevent and/or intervene in this type of violence. The purpose of this study was to assess the effects of Cyberprogram 2.0 on "face-to-face" bullying, cyberbullying, and empathy. A sample of 176 adolescents of the Basque Country (Spain), aged between 13 and 15 years, who studied Compulsory Secondary Education, was used. Of them, 93 were randomly assigned to the experimental condition, and 83 to the control condition. The study used a pretest-posttest repeated measures design with a control group. Before and after the program, two assessment instruments were administered. The results confirmed that the program significantly stimulated: (a) a decrease in the amount of bullying and cyberbullying behaviors suffered and/or carried out (level of victimization, perpetration, aggressive-victimization); and (b) an increase in the capacity for empathy. The study provides evidence of the effectiveness of Cyberprogram 2.0 to prevent and reduce bullying and cyberbullying. The discussion analyzes aspects of the program that may account for the significant intervention effects.

Effect of morphine-induced antinociception is altered by AF64A-induced lesions on cholinergic neurons in rat nucleus raphe magnus.

PubMed

Abe, Kenji; Ishida, Kota; Kato, Masatoshi; Shigenaga, Toshiro; Taguchi, Kyoji; Miyatake, Tadashi

2002-11-01

To examine the role of cholinergic neurons in the nucleus raphe magnus (NRM) in noxious heat stimulation and in the effects of morphine-induced antinociception by rats. After the cholinergic neuron selective toxin, AF64A, was microinjected into the NRM, we examined changes in the antinociceptive threshold and effects of morphine (5 mg/kg, ip) using the hot-plate (HP) and tail-flick (TF) tests. Systemic administration of morphine inhibited HP and TF responses in control rats. Microinjection of AF64A (2 nmol/site) into the NRM significantly decreased the threshold of HP response after 14 d, whereas the TF response was not affected. Morphine-induced antinociception was significantly attenuated in rats administered AF64A. Extracellular acetylcholine was attenuated after 14 d to below detectable levels in rats given AF64A. Naloxone (1 microg/site) microinjected into control rat NRM also antagonized the antinociceptive effect of systemic morphine. These findings suggest that cholinergic neuron activation in the NRM modulates the antinociceptive effect of morphine simultaneously with the opiate system.

Corticostriatal Regulation of Acute Pain

PubMed Central

Martinez, Erik; Lin, Harvey H.; Zhou, Haocheng; Dale, Jahrane; Liu, Kevin; Wang, Jing

2017-01-01

The mechanisms for acute pain regulation in the brain are not well understood. The prefrontal cortex (PFC) provides top-down control of emotional processes, and it projects to the nucleus accumbens (NAc). This corticostriatal projection forms an important regulatory pathway within the brain’s reward system. Recently, this projection has been suggested to control both sensory and affective phenotypes specifically associated with chronic pain. As this projection is also known to play a role in the transition from acute to chronic pain, we hypothesized that this corticostriatal circuit can also exert a modulatory function in the acute pain state. Here, we used optogenetics to specifically target the projection from the PFC to the NAc. We tested sensory pain behaviors with Hargreaves’ test and mechanical allodynia, and aversive pain behaviors with conditioned place preference (CPP) test. We found that the activation of this corticostriatal circuit gave rise to bilateral relief from peripheral nociceptive inputs. Activation of this circuit also provided important control for the aversive response to transient noxious stimulations. Hence, our results support a novel role for corticostriatal circuitry in acute pain regulation. PMID:28603489

Functional significance of M-type potassium channels in nociceptive cutaneous sensory endings

PubMed Central

Passmore, Gayle M.; Reilly, Joanne M.; Thakur, Matthew; Keasberry, Vanessa N.; Marsh, Stephen J.; Dickenson, Anthony H.; Brown, David A.

2012-01-01

M-channels carry slowly activating potassium currents that regulate excitability in a variety of central and peripheral neurons. Functional M-channels and their Kv7 channel correlates are expressed throughout the somatosensory nervous system where they may play an important role in controlling sensory nerve activity. Here we show that Kv7.2 immunoreactivity is expressed in the peripheral terminals of nociceptive primary afferents. Electrophysiological recordings from single afferents in vitro showed that block of M-channels by 3 μM XE991 sensitized Aδ- but not C-fibers to noxious heat stimulation and induced spontaneous, ongoing activity at 32°C in many Aδ-fibers. These observations were extended in vivo: intraplantar injection of XE991 selectively enhanced the response of deep dorsal horn (DH) neurons to peripheral mid-range mechanical and higher range thermal stimuli, consistent with a selective effect on Aδ-fiber peripheral terminals. These results demonstrate an important physiological role of M-channels in controlling nociceptive Aδ-fiber responses and provide a rationale for the nocifensive behaviors that arise following intraplantar injection of the M-channel blocker XE991. PMID:22593734

Habituation as an adaptive shift in response strategy mediated by neuropeptides

NASA Astrophysics Data System (ADS)

Ardiel, Evan L.; Yu, Alex J.; Giles, Andrew C.; Rankin, Catharine H.

2017-08-01

Habituation is a non-associative form of learning characterized by a decremented response to repeated stimulation. It is typically framed as a process of selective attention, allowing animals to ignore irrelevant stimuli in order to free up limited cognitive resources. However, habituation can also occur to threatening and toxic stimuli, suggesting that habituation may serve other functions. Here we took advantage of a high-throughput Caenorhabditis elegans learning assay to investigate habituation to noxious stimuli. Using real-time computer vision software for automated behavioral tracking and optogenetics for controlled activation of a polymodal nociceptor, ASH, we found that neuropeptides mediated habituation and performed an RNAi screen to identify candidate receptors. Through subsequent mutant analysis and cell-type-specific gene expression, we found that pigment-dispersing factor (PDF) neuropeptides function redundantly to promote habituation via PDFR-1-mediated cAMP signaling in both neurons and muscles. Behavioral analysis during learning acquisition suggests that response habituation and sensitization of locomotion are parts of a shifting behavioral strategy orchestrated by pigment dispersing factor signaling to promote dispersal away from repeated aversive stimuli.

Functional Tooth Regeneration Using a Bioengineered Tooth Unit as a Mature Organ Replacement Regenerative Therapy

PubMed Central

Imamura, Aya; Ogawa, Miho; Yasukawa, Masato; Yamazaki, Hiromichi; Morita, Ritsuko; Ikeda, Etsuko; Nakao, Kazuhisa; Takano-Yamamoto, Teruko; Kasugai, Shohei; Saito, Masahiro; Tsuji, Takashi

2011-01-01

Donor organ transplantation is currently an essential therapeutic approach to the replacement of a dysfunctional organ as a result of disease, injury or aging in vivo. Recent progress in the area of regenerative therapy has the potential to lead to bioengineered mature organ replacement in the future. In this proof of concept study, we here report a further development in this regard in which a bioengineered tooth unit comprising mature tooth, periodontal ligament and alveolar bone, was successfully transplanted into a properly-sized bony hole in the alveolar bone through bone integration by recipient bone remodeling in a murine transplantation model system. The bioengineered tooth unit restored enough the alveolar bone in a vertical direction into an extensive bone defect of murine lower jaw. Engrafted bioengineered tooth displayed physiological tooth functions such as mastication, periodontal ligament function for bone remodeling and responsiveness to noxious stimulations. This study thus represents a substantial advance and demonstrates the real potential for bioengineered mature organ replacement as a next generation regenerative therapy. PMID:21765896

Changes in the nitric oxide system in the shore crab Hemigrapsus sanguineus (Crustacea, Decapoda) CNS induced by a nociceptive stimulus.

PubMed

Dyuizen, Inessa V; Kotsyuba, Elena P; Lamash, Nina E

2012-08-01

Using NADPH-diaphorase (NADPH-d) histochemistry, inducible nitric oxide synthase (iNOS)-immunohistochemistry and immunoblotting, we characterized the nitric oxide (NO)-producing neurons in the brain and thoracic ganglion of a shore crab subjected to a nociceptive chemical stimulus. Formalin injection into the cheliped evoked specific nociceptive behavior and neurochemical responses in the brain and thoracic ganglion of experimental animals. Within 5-10 min of injury, the NADPH-d activity increased mainly in the neuropils of the olfactory lobes and the lateral antenna I neuropil on the side of injury. Later, the noxious-induced expression of NADPH-d and iNOS was detected in neurons of the brain, as well as in segmental motoneurons and interneurons of the thoracic ganglion. Western blotting analysis showed that an iNOS antiserum recognized a band at 120 kDa, in agreement with the expected molecular mass of the protein. The increase in nitrergic activity induced by nociceptive stimulation suggests that the NO signaling system may modulate nociceptive behavior in crabs.

The association between chronic pain and obesity.

PubMed

Okifuji, Akiko; Hare, Bradford D

2015-01-01

Obesity and pain present serious public health concerns in our society. Evidence strongly suggests that comorbid obesity is common in chronic pain conditions, and pain complaints are common in obese individuals. In this paper, we review the association between obesity and pain in the general population as well as chronic pain patients. We also review the relationship between obesity and pain response to noxious stimulation in animals and humans. Based upon the existing research, we present several potential mechanisms that may link the two phenomena, including mechanical/structural factors, chemical mediators, depression, sleep, and lifestyle. We discuss the clinical implications of obesity and pain, focusing on the effect of weight loss, both surgical and noninvasive, on pain. The literature suggests that the two conditions are significant comorbidities, adversely impacting each other. The nature of the relationship however is not likely to be direct, but many interacting factors appear to contribute. Weight loss for obese pain patients appears to be an important aspect of overall pain rehabilitation, although more efforts are needed to determine strategies to maintain long-term benefit.

Inhibition of mammalian target of rapamycin activation in the rostral anterior cingulate cortex attenuates pain-related aversion in rats.

PubMed

Lu, Bo; Jiang, Jingyan; Sun, Jianliang; Xiao, Chun; Meng, Bo; Zheng, Jinwei; Li, Xiaoyu; Wang, Ruichun; Wu, Guorong; Chen, Junping

2016-09-01

Pain is a complex experience that comprises both sensory and affective dimensions. Mammalian target of rapamycin (mTOR) plays an important role in the modulation of neuronal plasticity associated with the pathogenesis of pain sensation. However, the role of mTOR in pain affect is unclear. Using a formalin-induced conditioned place avoidance (F-CPA) test, the current study investigated the effects of the mTOR specific inhibitor rapamycin on noxious stimulation induced aversion in the rostral anterior cingulate cortex (rACC). Intraplantar injection of 5% formalin was associated with significant activation of mTOR, as well as p70 ribosomal S6 protein (p70S6K), its downstream effector, in the rACC. The inhibition of mTOR activation with rapamycin disrupted pain-related aversion; however, this inhibition did not affect formalin-induced spontaneous nociceptive behaviors in rats. These findings demonstrated for the first time that mTOR and its downstream pathway in the rACC contribute to the induction of pain-related negative emotion. Copyright © 2016 Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

United States. Bonneville Power Administration, Portland, OR; Oregon Department of Agriculture Noxious Weed Control Program

During the 1996 season ODA executed the contract between BPA and ODA. Execution of this contract included the following activities: Survey for target noxious weeds, such as Gorse; collection and redistribution of biological control agents, for example, Apion seed weevils for Scotch broom, bioagents for diffuse and spotted knapweed, Gorse spider mite, and gall fly releases for control of Canada thistle and bull thistle; and control of isolated infestations of Gorse on BPA rights-of-way. Training was provided for line crews at the Chemawa, Alevy and North Bend districts. The purpose of the program is to assist BPA in the integratedmore » prevention and control of noxious weed species on BPA transmission line maintenance right-of-ways.« less

Anesthetic effects on fictive locomotion in the rat isolated spinal cord

PubMed Central

Jinks, Steven L.; Andrada, Jason; Satter, Omar

2011-01-01

General anesthetic mechanisms are poorly understood. Anesthetic immobilizing effects occur in the spinal ventral horn. However, a detailed analysis of anesthetic effects on ventral motor networks is lacking. We delivered isoflurane, desflurane, or propofol during NMDA/5-HT-induced, or noxious tail stimulus-evoked, fictive locomotion in neonatal rat isolated spinal cords. Anesthetics changed the frequency, amplitude, and regularity of fictive locomotion with little effect on phase-lag. Isoflurane abolished pharmacologically-induced vs noxious stimulus-induced motor output at similar concentrations. Propofol abolished pharmacologically-induced fictive locomotion via a GABAA-receptor mechanism. Anesthetic effects on pharmacologically-elicted fictive locomotion appear clinically-relevant, and support a ventral horn immobilizing effect on locomotor rhythm generation. PMID:21817927

Responsibility modulates pain-matrix activation elicited by the expressions of others in pain

PubMed Central

Cui, Fang; Abdelgabar, Abdel-Rahman; Keysers, Christian; Gazzola, Valeria

2015-01-01

Here we examine whether brain responses to dynamic facial expressions of pain are influenced by our responsibility for the observed pain. Participants played a flanker task with a confederate. Whenever either erred, the confederate was seen to receive a noxious shock. Using functional magnetic resonance imaging, we found that regions of the functionally localized pain-matrix of the participants (the anterior insula in particular) were activated most strongly when seeing the confederate receive a noxious shock when only the participant had erred (and hence had full responsibility). When both or only the confederate had erred (i.e. participant's shared or no responsibility), significantly weaker vicarious pain-matrix activations were measured. PMID:25800210

Benefits of gene transduction of granulocyte macrophage colony-stimulating factor in cancer vaccine using genetically modified dendritic cells.

PubMed

Ojima, Toshiyasu; Iwahashi, Makoto; Nakamura, Masaki; Matsuda, Kenji; Nakamori, Mikihito; Ueda, Kentaro; Naka, Teiji; Katsuda, Masahiro; Miyazawa, Motoki; Yamaue, Hiroki

2007-10-01

Granulocyte macrophage colony-stimulating factor (GM-CSF) is a key cytokine for the generation and stimulation of dendritic cells (DCs), and it may also play a pivotal role in promoting the survival of DCs. In this study, the feasibility of creating a cancer vaccine using DCs adenovirally transduced with the carcinoembryonic antigen (CEA) gene and the GM-CSF gene was examined. In addition, the effect of the co-transduction of GM-CSF gene on the lifespan of these genetically modified DCs was determined. A cytotoxic assay using peripheral blood mononuclear cell (PBMC)-derived cytotoxic T lymphocytes (CTLs) was performed in a 4-h 51Cr release assay. The apoptosis of DCs was examined by TdT-mediated dUTP-FITC nick end labeling (TUNEL) assay. CEA-specific CTLs were generated from PBMCs stimulated with genetically modified DCs expressing CEA. The cytotoxicity of these CTLs was augmented by co-transduction of DCs with the GM-CSF gene. Co-transduction of the GM-CSF gene into DCs inhibited apoptosis of these DCs themselves via up-regulation of Bcl-x(L) expression, leading to the extension of the lifespan of these DCs. Furthermore, the transduction of the GM-CSF gene into DCs also suppressed the incidence of apoptosis of DCs induced by transforming growth factor-beta1 (TGFbeta-1). Immunotherapy using these genetically modified DCs may therefore be useful with several advantages as follows: i) adenoviral toxicity to DCs can be reduced; ii) the lifespan of vaccinated DCs can be prolonged; and iii) GM-CSF may protect DCs from apoptosis induced by tumor-derived TGFbeta-1 in the regional lymph nodes.

Note: Automated optical focusing on encapsulated devices for scanning light stimulation systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bitzer, L. A.; Benson, N., E-mail: niels.benson@uni-due.de; Schmechel, R.

Recently, a scanning light stimulation system with an automated, adaptive focus correction during the measurement was introduced. Here, its application on encapsulated devices is discussed. This includes the changes an encapsulating optical medium introduces to the focusing process as well as to the subsequent light stimulation measurement. Further, the focusing method is modified to compensate for the influence of refraction and to maintain a minimum beam diameter on the sample surface.

Neural pathways from thalamus associated with regulation of aggressive behavior.

PubMed

Bandler, R J; Flynn, J P

1974-01-11

Small electrolytic lesions were made through electrodes in the thalamus of cats at sites where electrical stimulation elicited attack on a rat. Staining by modified Nauta reduced silver methods revealed that significant degeneration passed caudally from the lesions and entered the midbrain dorsal central gray region. Electrical stimulation of this dorsal midbrain region elicited attack on a rat, and destruction of this region suppressed the attack elicited by thalamic stimulation.

Application of microchip CGE for the analysis of PEG-modified recombinant human granulocyte-colony stimulating factors.

PubMed

Park, Eun Ji; Lee, Kyung Soo; Lee, Kang Choon; Na, Dong Hee

2010-11-01

The purpose of this study was to evaluate the microchip CGE (MCGE) for the analysis of PEG-modified granulocyte-colony stimulating factor (PEG-G-CSF) prepared with PEG-aldehydes. The unmodified and PEG-modified G-CSFs were analyzed by Protein 80 and 230 Labchips on the Agilent 2100 Bioanalyzer. The MCGE allowed size-based separation and quantitation of PEG-G-CSF. The Protein 80 Labchip was useful for PEG-5K-G-CSF, while the Protein 230 Labchip was more suitable for PEG-20K-G-CSF. The MCGE was also used to monitor a search for optimal PEG-modification (PEGylation) conditions to produce mono-PEG-G-CSF. This study demonstrates the usefulness of MCGE for monitoring and optimizing the PEGylation of G-CSF with the advantages of speed, minimal sample consumption, and automatic quantitation.

Absence of food alternatives promotes risk-prone feeding of unpalatable substances in honey bees

PubMed Central

Desmedt, Lucie; Hotier, Lucie; Giurfa, Martin; Velarde, Rodrigo; de Brito Sanchez, Maria Gabriela

2016-01-01

The question of why animals sometimes ingest noxious substances is crucial to understand unknown determinants of feeding behaviour. Research on risk-prone feeding behaviour has largely focused on energy budgets as animals with low energy budgets tend to ingest more aversive substances. A less explored possibility is that risk-prone feeding arises from the absence of alternative feeding options, irrespectively of energy budgets. Here we contrasted these two hypotheses in late-fall and winter honey bees. We determined the toxicity of various feeding treatments and showed that when bees can choose between sucrose solution and a mixture of this sucrose solution and a noxious/unpalatable substance, they prefer the pure sucrose solution and reject the mixtures, irrespective of their energy budget. Yet, when bees were presented with a single feeding option and their escape possibilities were reduced, they consumed unexpectedly some of the previously rejected mixtures, independently of their energy budget. These findings are interpreted as a case of feeding helplessness, in which bees behave as if it were utterly helpless to avoid the potentially noxious food and consume it. They suggest that depriving bees of variable natural food sources may have the undesired consequence of increasing their acceptance of food that would be otherwise rejected. PMID:27534586

Absence of food alternatives promotes risk-prone feeding of unpalatable substances in honey bees.

PubMed

Desmedt, Lucie; Hotier, Lucie; Giurfa, Martin; Velarde, Rodrigo; de Brito Sanchez, Maria Gabriela

2016-08-18

The question of why animals sometimes ingest noxious substances is crucial to understand unknown determinants of feeding behaviour. Research on risk-prone feeding behaviour has largely focused on energy budgets as animals with low energy budgets tend to ingest more aversive substances. A less explored possibility is that risk-prone feeding arises from the absence of alternative feeding options, irrespectively of energy budgets. Here we contrasted these two hypotheses in late-fall and winter honey bees. We determined the toxicity of various feeding treatments and showed that when bees can choose between sucrose solution and a mixture of this sucrose solution and a noxious/unpalatable substance, they prefer the pure sucrose solution and reject the mixtures, irrespective of their energy budget. Yet, when bees were presented with a single feeding option and their escape possibilities were reduced, they consumed unexpectedly some of the previously rejected mixtures, independently of their energy budget. These findings are interpreted as a case of feeding helplessness, in which bees behave as if it were utterly helpless to avoid the potentially noxious food and consume it. They suggest that depriving bees of variable natural food sources may have the undesired consequence of increasing their acceptance of food that would be otherwise rejected.

The noxious effects of electroimmobilization in adult Holstein cows: a pilot study.

PubMed Central

Pascoe, P J; McDonell, W N

1986-01-01

Ten adult Holstein cows were used in an experiment to determine whether the induction of electroimmobilization was a noxious event. The cows were halter trained and accustomed to being led into a set of stocks. The time taken for the cattle to walk the last ten metres into the stocks was recorded. The heart rate of the cow was recorded for a three minute period prior to a ten second exposure to a high pitched sound (the conditioning stimulus). Measurements were collected for three repetitions and then the cows were assigned to two groups of five. One group was immobilized for 30 seconds using a commercial electroimmobilizer, the other group was not treated. This procedure was repeated ten times over a period of eight days. The cows were then exposed to the conditioning stimulus and their response observed. The treated group took significantly (P less than 0.05) longer to get into the stocks and the regression slopes for heart rate were significantly different from the control group. The treated cows responded to the conditioning stimulus at five and nine months after the end of the conditioning period. Adult Holstein cows regarded electroimmobilization as a noxious event and were very strongly conditioned to this stimulus. PMID:3756681

Thulium fibre laser nerve stimulation and its application in human pain research

NASA Astrophysics Data System (ADS)

Warnaby, Catherine E.

Experimental pain induction, in combination with psychophysical and functional imaging techniques, allows the controlled study of the mechanisms, pathways and brain areas involved in the processing of noxious stimuli. Laser nerve stimulation provides an excellent stimulus that selectively activates the Adelta and C nociceptors with only low concurrent activity in the warmth system. Thulium fibre laser systems, operating near 2mum, offer several advantages over other pain stimulators including the CO[2] and Tm:YAG laser systems. These advantages include direct absorption at the location of the nociceptors, reduced likelihood of tissue damage, improved compatibility with fMRI, and wavelength tunability. The main aims of the thesis were to apply an initial thulium fibre laser system to pain activation studies in healthy subjects and confirm the potential advantages. A 1D finite difference photothermal model confirmed that thulium fibre laser radiation is absorbed throughout the expected location of the nociceptors and produces a lower surface temperature than CO[2] radiation. In order to produce a temperature rise of 9°C at 150mum, thulium radiation induces a surface temperature rise of 12°C compared to 21°C surface temperature rise using CO[2] radiation. The use of thulium fibre radiation greatly reduces the likelihood of tissue damage and first-degree burns when compared to CO[2] radiation. The spatial temperature gradient and the surface temperature rise were also found to be strongly dependent on the thulium fibre laser emission wavelength, which implies that wavelength tuning may be used to obtain the optimum stimulus wavelength in the 2mum region. The 5W initial fibre laser system was fully characterised before application to human pain studies and was shown to have excellent reproducibility of the stimulus parameters, with short-term and long-term deviations of the pulse energy of 5% and 8% of the mean respectively. The thulium fibre laser emits radiation over a 38nm wavelength range from 2.006-2.044mum. The initial system was used successfully to elicit painful sensations and laser evoked potentials (LEPs), which showed the expected dependence on the laser stimulus parameters. In agreement with the modelled results, beam diameters from 5-8mm for a 150ms pulse duration were found to elicit painful responses while minimising tissue damage. Psychophysical assessment of the pain threshold energy and energy density in ten volunteers, using the modified staircase technique and the method of constant stimuli, also showed the expected dependence on the laser beam diameter over this range. The topographical distribution of the LEPs elicited by the thulium fibre laser and a CO[2] pain stimulator were found to be very similar. However, statistically significant differences in the peak latencies of the LEP components were observed. The peak latency of the N2, P2 and P3 components elicited by the thulium fibre laser were found to be longer by 44ms, 52ms and 78ms respectively than those elicited by the CO[2] laser across five volunteers. These latency differences are believed to be due to the difference in beam diameter of the two stimuli, which produces an increase in local spatial summation for the CO[2] laser stimuli. The effectiveness of the thulium fibre laser as a controlled pain stimulator for human pain research has been confirmed. Using the current thulium fibre laser stimulation system, the optimum stimulus parameters are provided by a beam diameter of 6mm and a pulse duration of 150ms. However, further application of the current system to human pain research is limited by the available output power and the delivery of the thulium radiation to the subject. Suggestions are made for further work using an improved thulium fibre laser system with an increased output power of 20W, optical fibre delivery and wavelength tuning.

7 CFR 360.200 - Designation of noxious weeds.

Code of Federal Regulations, 2010 CFR

2010-01-01

... mantegazzianum Sommier & Levier (giant hogweed) Homeria spp. Imperata brasiliensis Trinius (Brazilian satintail) Imperata cylindrica (Linnaeus) Raeuschel (cogongrass) Ischaemum rugosum Salisbury (murainograss) Leptochloa...

Serotonin-1A Receptor Polymorphism (rs6295) Associated with Thermal Pain Perception

PubMed Central

Lindstedt, Fredrik; Karshikoff, Bianka; Schalling, Martin; Olgart Höglund, Caroline; Ingvar, Martin; Lekander, Mats; Kosek, Eva

2012-01-01

Background Serotonin (5-HT) is highly involved in pain regulation and serotonin-1A (5-HT1A) receptors are important in determining central 5-HT tone. Accordingly, variation in the 5-HT1A receptor gene (HTR1A) may contribute to inter-individual differences in human pain sensitivity. The minor G-allele of the HTR1A single nucleotide polymorphism (SNP) rs6295 attenuates firing of serotonergic neurons and reduces postsynaptic expression of the receptor. Experiments in rodents suggest that 5-HT1A-agonism modulates pain in opposite directions at mild compared to high noxious intensities. Based upon this and several other similar observations, we hypothesized that G-carriers would exhibit a relative hypoalgesia at mild thermal stimuli but tend towards hyperalgesia at higher noxious intensities. Methods Fourty-nine healthy individuals were selectively genotyped for rs6295. Heat- and cold-pain thresholds were assessed along with VAS-ratings of a range of suprathreshold noxious heat intensities (45°C–49°C). Nociceptive-flexion reflex (NFR) thresholds were also assessed. Results Volunteers did not deviate significantly from Hardy-Weinberg equilibrium. G-carriers were less sensitive to threshold-level thermal pain. This relative hypoalgesia was abolished at suprathreshold noxious intensities where G-carriers instead increased their ratings of heat-pain significantly more than C-homozygotes. No differences with regard to NFR-thresholds emerged. Conclusion/Significance To the best of our knowledge this is the first study of human pain perception on the basis of variation in HTR1A. The results illustrate the importance of including a range of stimulus intensities in assessments of pain sensitivity. In speculation, we propose that an attenuated serotonergic tone may be related to a ‘hypo- to hyperalgesic’ response-pattern. The involved mechanisms could be of clinical interest as variation in pain regulation is known to influence the risk of developing pain pathologies. Further investigations are therefore warranted. PMID:22952650

Ionic mechanisms of spinal neuronal cold hypersensitivity in ciguatera.

PubMed

Patel, Ryan; Brice, Nicola L; Lewis, Richard J; Dickenson, Anthony H

2015-12-01

Cold hypersensitivity is evident in a range of neuropathies and can evoke sensations of paradoxical burning cold pain. Ciguatoxin poisoning is known to induce a pain syndrome caused by consumption of contaminated tropical fish that can persist for months and include pruritus and cold allodynia; at present no suitable treatment is available. This study examined, for the first time, the neural substrates and molecular components of Pacific ciguatoxin-2-induced cold hypersensitivity. Electrophysiological recordings of dorsal horn lamina V/VI wide dynamic range neurones were made in non-sentient rats. Subcutaneous injection of 10 nm ciguatoxin-2 into the receptive field increased neuronal responses to innocuous and noxious cooling. In addition, neuronal responses to low-threshold but not noxious punctate mechanical stimuli were also elevated. The resultant cold hypersensitivity was not reversed by 6-({2-[2-fluoro-6-(trifluoromethyl)phenoxy]-2-methylpropyl}carbamoyl)pyridine-3-carboxylic acid, an antagonist of transient receptor potential melastatin 8 (TRPM8). Both mechanical and cold hypersensitivity were completely prevented by co-injection with the Nav 1.8 antagonist A803467, whereas the transient receptor potential ankyrin 1 (TRPA1) antagonist A967079 only prevented hypersensitivity to innocuous cooling and partially prevented hypersensitivity to noxious cooling. In naive rats, neither innocuous nor noxious cold-evoked neuronal responses were inhibited by antagonists of Nav 1.8, TRPA1 or TRPM8 alone. Ciguatoxins may confer cold sensitivity to a subpopulation of cold-insensitive Nav 1.8/TRPA1-positive primary afferents, which could underlie the cold allodynia reported in ciguatera. These data expand the understanding of central spinal cold sensitivity under normal conditions and the role of these ion channels in this translational rat model of ciguatoxin-induced hypersensitivity. © 2015 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Chromogranin A and cortisol at intraoperative repeated noxious stimuli: Surgical stress in a dog model

PubMed Central

Hagman, Ragnvi; Stridsberg, Mats

2015-01-01

Objectives: Biomarkers representing sympathetic tone and the surgical stress response are measured to objectively evaluate surgical techniques and anaesthetic protocols. If a part of the intraoperative procedure is repeated on the contralateral organ, one animal may potentially serve as its own control and, if so, may minimize the problem of individual differences of the stress response to anaesthesia and surgery. This study aimed to investigate the use of chromogranin A for measurement of the intraoperative sympathetic tone. Additional aims were to investigate chromogranin A and cortisol as indicators of the intraoperative surgical stress response caused by repeated noxious stimuli in dogs subjected to ovariohysterectomy and thereby to investigate the possibility of one dog serving as its own control. Methods: Experiments were carried out on 10 dogs subjected to ovariohysterectomy. Perioperative blood samples (0–6) were collected after premedication, immediately before induction of anaesthesia (0), after induction of anaesthesia and before incision (1), before (2) and after (3) removal of the first ovary, after a 15-min pause before removal of the second ovary (4), after removal of the second ovary (5) and after closing the abdomen (6). Plasma chromogranin A and cortisol were analysed. Results: Plasma chromogranin A did not change. Plasma cortisol concentration did not change between before anaesthesia and opening of the abdomen. Plasma cortisol increased at removal of the first ovary. Cortisol did not change at removal of the second ovary but remained increased compared to initial sample. Conclusion: The results suggest chromogranin A is a poor indicator of intraoperative sympathetic tone during elective surgery in dogs. Cortisol measurement was useful for assessment of intraoperative noxious stimuli. However, at these test conditions, neither plasma chromogranin A nor plasma cortisol was useful for assessment of repeated intraoperative noxious stimuli where one dog served as its own control. PMID:26770773

Locus coeruleus phasic discharge is essential for stimulus-induced gamma oscillations in the prefrontal cortex.

PubMed

Neves, Ricardo M; van Keulen, Silvia; Yang, Mingyu; Logothetis, Nikos K; Eschenko, Oxana

2018-03-01

The locus coeruleus (LC) noradrenergic (NE) neuromodulatory system is critically involved in regulation of neural excitability via its diffuse ascending projections. Tonic NE release in the forebrain is essential for maintenance of vigilant states and increases the signal-to-noise ratio of cortical sensory responses. The impact of phasic NE release on cortical activity and sensory processing is less explored. We previously reported that LC microstimulation caused a transient desynchronization of population activity in the medial prefrontal cortex (mPFC), similar to noxious somatosensory stimuli. The LC receives nociceptive information from the medulla and therefore may mediate sensory signaling to its forebrain targets. Here we performed extracellular recordings in LC and mPFC while presenting noxious stimuli in urethane-anesthetized rats. A brief train of foot shocks produced a robust phasic response in the LC and a transient change in the mPFC power spectrum, with the strongest modulation in the gamma (30-90 Hz) range. The LC phasic response preceded prefrontal gamma power increase, and cortical modulation was proportional to the LC excitation. We also quantitatively characterized distinct cortical states and showed that sensory responses in both LC and mPFC depend on the ongoing cortical state. Finally, cessation of the LC firing by bilateral local iontophoretic injection of clonidine, an α 2 -adrenoreceptor agonist, completely eliminated sensory responses in the mPFC without shifting cortex to a less excitable state. Together, our results suggest that the LC phasic response induces gamma power increase in the PFC and is essential for mediating sensory information along an ascending noxious pathway. NEW & NOTEWORTHY Our study shows linear relationships between locus coeruleus phasic excitation and the amplitude of gamma oscillations in the prefrontal cortex. Results suggest that the locus coeruleus phasic response is essential for mediating sensory information along an ascending noxious pathway.

Accumulation of stimulants of Toll-like receptor (TLR)-2 and TLR4 in meat products stored at 5 °C.

PubMed

Erridge, Clett

2011-03-01

Recent evidence suggests that exposure to stimulants of the innate immune receptors Toll-like receptor (TLR)-2 and TLR4 may contribute to the development of atherosclerosis and insulin resistance. We showed recently that common foodsuffs can contain TLR-stimulants, and that the greatest concentrations were present in meat-based products. Using a recently developed quantitative bioassay, we here examined the kinetics of accumulation of TLR2- and TLR4-stimulants in a variety of meat products held at 5 °C in air or under a modified atmosphere for up to 8 d. Meat content of TLR-stimulants increased with time in each meat examined and was paralleled by growth of pseudomonads and Enterobacteriaceae, suggesting that bacterial lipopeptides and lipopolysaccharides are the likely sources of TLR2- and TLR4-stimulants, respectively. TLR-stimulants reached the highest levels (approximately 80 μg lipopeptide-equivalents per gramme and approximately 7 μg lipopolysaccharide-equivalents per gram) in meat that was minced rather than intact, and when stored in air rather than under a modified atmosphere. TLR2- and TLR4-stimulants in meat products cooked for 1 h retained approximately 20% and approximately 40% of their bioactivity, respectively. In summary, storage conditions and microbial flora critically regulate the kinetics of TLR2- and TLR4-stimulant accumulation in meat products and these may retain biological activity after cooking. The novel assays presented in this work could be used to predict the potential of foodstuffs to promote inflammatory signaling in human subjects, which may be deleterious to health. These assays may also be used to monitor the historical microbial flora in food products after cooking or other forms of food processing may have rendered the original microflora nonviable.

Erratum: Creation of X-Ray Transparency of Matter by Stimulated Elastic Forward Scattering [Phys. Rev. Lett. 115 , 107402 (2015)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stöhr, J.; Scherz, A.

X-ray absorption by matter has long been described by the famous Beer-Lambert law. Here we show how this fundamental law needs to be modified for high-intensity coherent x-ray pulses, now available at x-ray free electron lasers, due to the onset of stimulated elastic forward scattering. We present an analytical expression for the modified polarization-dependent Beer-Lambert law for the case of resonant core-to-valence electronic transitions and incident transform limited x-ray pulses. Upon transmission through a solid, the absorption and dichroic contrasts are found to vanish with increasing x-ray intensity, with the stimulation threshold lowered by orders of magnitude through a super-radiativemore » coherent effect. Our results have broad implications for the study of matter with x-ray lasers.« less

The impact of adjunctive guanfacine extended release on stimulant adherence in children/adolescents with attention-deficit/hyperactivity disorder.

PubMed

Meyers, Juliana; Gajria, Kavita; Candrilli, Sean D; Fridman, Moshe; Sikirica, Vanja

2017-03-01

To assess stimulant adherence among children/adolescents with attention-deficit/hyperactivity disorder (ADHD) augmenting stimulants with guanfacine extended-release (GXR). Inclusion criteria: 6-17 years, ≥1 ADHD diagnosis, ≥1 long-acting and/or short-acting stimulant with GXR augmentation. Modified medication possession ratio (mMPR; days medication available/days in period, excluding medication holidays) was assessed; mMPR <0.80 nonadherent. Regression models assessed change in mMPR adjusting for demographic and clinical characteristics. Among patients nonadherent to stimulants pre-augmentation (n = 165), unadjusted mean (SD) pre- and post-stimulant mMPRs were 0.68 (0.11) and 0.87 (0.16). Adjusted mean change in mMPR was 0.20 for long-acting versus 0.18 for short-acting stimulants (p = 0.34). Among patients nonadherent to stimulants, GXR augmentation was associated with increased stimulant adherence.

The Antinociceptive and Antihyperalgesic Effects of Topical Propofol on Dorsal Horn Neurons in the Rat

PubMed Central

Takechi, Kenichi; Carstens, Mirela Iodi; Klein, Amanda H.; Carstens, E.

2013-01-01

Background Propofol (2,6-diisopropylphenol) is an IV anesthetic used for general anesthesia. Recent evidence suggests that propofol-anesthetized patients experience less postoperative pain, and that propofol has analgesic properties when applied topically. We presently investigated the antinociceptive effects of topical propofol using behavioral and single-unit electrophysiological methods in rats. Methods In behavioral experiments with rats, we assessed the effect of topical hindpaw application of propofol (1–25%) on heat and mechanically evoked paw withdrawals. In electrophysiology experiments we recorded from lumbar dorsal horn wide dynamic range (WDR)-type neurons in pentobarbital-anesthetized rats. We assessed the effect of topical application of propofol to the ipsilateral hindpaw on neuronal responses elicited by noxious heat, cold and mechanical stimuli. We additionally tested if propofol blocks heat sensitization of paw withdrawals and WDR neuronal responses induced by topical application of allyl isothiocyanate (AITC; mustard oil). Results Topical application of propofol (1–25%) significantly increased the mean latency of the thermally evoked hindpaw withdrawal reflex on the treated (but not opposite) side in a concentration-dependent manner, with no effect on mechanically evoked hindpaw withdrawal thresholds. Propofol also prevented shortening of paw withdrawal latency induced by AITC. In electrophysiological experiments, topical application of 10 and 25% propofol, but not 1% propofol or vehicle (10% intralipid), to the ipsilateral hindpaw significantly attenuated the magnitude of responses of WDR neurons to noxious heating of glabrous hindpaw skin with no significant change in thermal thresholds. Maximal suppression of noxious heat-evoked responses was achieved 15-min after application followed by recovery to the pre-propofol baseline by 30 min. Responses to skin cooling or graded mechanical stimuli were not significantly affected by any concentration of propofol. Topical application of AITC enhanced the noxious heat-evoked response of dorsal horn neurons. This enhancement of heat-evoked responses was attenuated when 10% propofol was applied topically after application of AITC. Conclusions The results indicate that topical propofol inhibits responses of WDR neurons to noxious heat consistent with analgesia, and reduced AITC sensitization of WDR neurons consistent with an antihyperalgesic effect. These results are consistent with clinical studies demonstrating reduced postoperative pain in surgical patients anesthetized with propofol. The mechanism of analgesic action of topical propofol is not clear, but may involve desensitization of TRPV1 or TRPA1 receptors expressed in peripheral nociceptive nerve endings, engagement of endocannabinoids, or activation of peripheral gamma-aminobutyric acid A receptors. PMID:23337417

A Short Term Therapy Approach to Processing Trauma: Art Therapy and Bilateral Stimulation

ERIC Educational Resources Information Center

Tripp, Tally

2007-01-01

This article describes a dynamic, short-term art therapy approach that has been developed for the treatment of trauma related disorders. Using a modified Eye Movement Desensitization and Reprocessing (EMDR) protocol with alternating tactile and auditory bilateral stimulation, associations are rapidly brought to conscious awareness and expressed in…

Modifying the Genetic Regulation of Bone and Cartilage Cells and Associated Tissue by EMF Stimulation Fields and Uses Thereof

NASA Technical Reports Server (NTRS)

Goodwin, Thomas J. (Inventor); Shackelford, Linda C. (Inventor)

2014-01-01

An apparatus and method to modify the genetic regulation of mammalian tissue, bone, or any combination. The method may be comprised of the steps of tuning at least one predetermined profile associated with at least one time-varying stimulation field thereby resulting in at least one tuned time-varying stimulation field comprised of at least one tuned predetermined profile, wherein said at least one tuned predetermined profile is comprised of a plurality of tuned predetermined figures of merit and is controllable through at least one of said plurality of tuned predetermined figures of merit, wherein said plurality of predetermined tuned figures of merit is comprised of a tuned B-Field magnitude, tuned rising slew rate, tuned rise time, tuned falling slew rate, tuned fall time, tuned frequency, tuned wavelength, and tuned duty cycle; and exposing mammalian chondrocytes, osteoblasts, osteocytes, osteoclasts, nucleus pulposus, associated tissue, or any combination to said at least one tuned time-varying stimulation field comprised of said at least one tuned predetermined profile for a predetermined tuned exposure time or plurality of tuned exposure time sequences.

LTP Induction Modifies Functional Relationship among Hippocampal Neurons

ERIC Educational Resources Information Center

Yun, Sung H.; Lee, Deok S.; Lee, Hyunjung; Baeg, Eun H.; Kim, Yun B.; Jung, Min W.

2007-01-01

To obtain evidence linking long-term potentiation (LTP) and memory, we examined whether LTP induction modifies functional relationship among neurons in the rat hippocampus. In contrast to neurons in low-frequency stimulated or AP5-treated slices, LTP induction altered "functional connectivity," as defined by the degree of synchronous firing, among…

7 CFR 361.6 - Noxious weed seeds.

Code of Federal Regulations, 2012 CFR

2012-01-01

... & Levier Hydrilla verticillata (Linnaeus f.) Royle Hygrophila polysperma T. Anderson Imperata brasiliensis Trinius Imperata cylindrica (Linnaeus) Palisot de Beauvois Inula britannica Linnaeus Ipomoea aquatica...

7 CFR 360.200 - Designation of noxious weeds.

Code of Federal Regulations, 2014 CFR

2014-01-01

... mantegazzianum Sommier & Levier (giant hogweed) Imperata brasiliensis Trinius (Brazilian satintail) Imperata cylindrica (Linnaeus) Palisot de Beauvois (cogongrass) Inula britannica Linnaeus (British elecampane, British...

7 CFR 361.6 - Noxious weed seeds.

Code of Federal Regulations, 2013 CFR

2013-01-01

... & Levier Hydrilla verticillata (Linnaeus f.) Royle Hygrophila polysperma T. Anderson Imperata brasiliensis Trinius Imperata cylindrica (Linnaeus) Palisot de Beauvois Inula britannica Linnaeus Ipomoea aquatica...

7 CFR 361.6 - Noxious weed seeds.

Code of Federal Regulations, 2014 CFR

2014-01-01

... & Levier Hydrilla verticillata (Linnaeus f.) Royle Hygrophila polysperma T. Anderson Imperata brasiliensis Trinius Imperata cylindrica (Linnaeus) Palisot de Beauvois Inula britannica Linnaeus Ipomoea aquatica...

7 CFR 360.200 - Designation of noxious weeds.

Code of Federal Regulations, 2013 CFR

2013-01-01

... mantegazzianum Sommier & Levier (giant hogweed) Imperata brasiliensis Trinius (Brazilian satintail) Imperata cylindrica (Linnaeus) Palisot de Beauvois (cogongrass) Inula britannica Linnaeus (British elecampane, British...

7 CFR 360.200 - Designation of noxious weeds.

Code of Federal Regulations, 2012 CFR

2012-01-01

... mantegazzianum Sommier & Levier (giant hogweed) Imperata brasiliensis Trinius (Brazilian satintail) Imperata cylindrica (Linnaeus) Palisot de Beauvois (cogongrass) Inula britannica Linnaeus (British elecampane, British...

Occupational hazards in hospitals: accidents, radiation, exposure to noxious chemicals, drug addiction and psychic problems, and assault.

PubMed Central

Gestal, J J

1987-01-01

Except for infectious diseases all the main occupational hazards affecting health workers are reviewed: accidents (explosions, fires, electrical accidents, and other sources of injury); radiation (stochastic and non-stochastic effects, protective measures, and personnel most at risk); exposure to noxious chemicals, whose effects may be either local (allergic eczema) or generalised (cancer, mutations), particular attention being paid to the hazards presented by formol, ethylene oxide, cytostatics, and anaesthetic gases; drug addiction (which is more common among health workers than the general population) and psychic problems associated with promotion, shift work, and emotional stress; and assault (various types of assault suffered by health workers, its causes, and the characterisation of the most aggressive patients). PMID:3307896