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See detailGenome-wide analysis of single nucleotide polymorphisms and copy number variants in fibromyalgia suggest a role for the central nervous system.
Docampo Martinez, Elisa ULg; Escaramis, Georgia; Gratacos, Monica et al

in Pain (2014), 155(6), 1102-9

Fibromyalgia (FM) is a highly disabling syndrome defined by a low pain threshold and a permanent state of pain. The mechanisms explaining this complex disorder remain unclear, and its genetic factors have ... [more ▼]

Fibromyalgia (FM) is a highly disabling syndrome defined by a low pain threshold and a permanent state of pain. The mechanisms explaining this complex disorder remain unclear, and its genetic factors have not yet been identified. With the aim of elucidating FM genetic susceptibility factors, we selected 313 FM cases having low comorbidities, and we genotyped them on the Illumina 1 million duo array. Genotypic data from 220 control women (Illumina 610k array) was obtained for genome-wide association scan (GWAS) analysis. Copy number variants in FM susceptibility were analyzed by array comparative genomic hybridization (aCGH) experiments on pooled samples using the Agilent 2x400K platform. No single nucleotide polymorphism (SNP) reached GWAS association threshold, but 21 of the most associated SNPs were chosen for replication in 952 cases and 644 controls. Four of the SNPs selected for replication showed a nominal association in the joint analysis, and rs11127292 (MYT1L) was found to be associated to FM with low comorbidities (P=4.28x10(-5), odds ratio [95% confidence interval]=0.58 [0.44-0.75]). aCGH detected 5 differentially hybridized regions. They were followed up, and an intronic deletion in NRXN3 was demonstrated to be associated to female cases of FM with low levels of comorbidities (P=.021, odds ratio [95% confidence interval]=1.46 [1.05-2.04]). Both GWAS and aCGH results point to a role for the central nervous system in FM genetic susceptibility. If the proposed FM candidate genes were further validated in replication studies, this would highlight a neurocognitive involvement in agreement with latest reports. [less ▲]

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See detailPalliative sedation: Why we should be more concerned about the risks that patients experience an uncomfortable death
Deschepper, R; Laureys, Steven ULg; Hachimi-Idrissi, S et al

in Pain (2013), Vol 154

[No abstract available]

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See detailIs chronic migraine a never-ending migraine attack?
Schoenen, Jean ULg

in Pain (2011), 152(2), 239-40

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See detailThe nociception coma scale: A new tool to assess nociception in disorders of consciousness.
Schnakers, Caroline ULg; Chatelle, Camille ULg; Vanhaudenhuyse, Audrey ULg et al

in Pain (2010), 148

Assessing behavioral responses to nociception is difficult in severely brain-injured patients recovering from coma. We here propose a new scale developed for assessing nociception in vegetative (VS) and ... [more ▼]

Assessing behavioral responses to nociception is difficult in severely brain-injured patients recovering from coma. We here propose a new scale developed for assessing nociception in vegetative (VS) and minimally conscious (MCS) coma survivors, the Nociception Coma Scale (NCS), and explore its concurrent validity, inter-rater agreement and sensitivity. Concurrent validity was assessed by analyzing behavioral responses of 48 post-comatose patients to a noxious stimulation (pressure applied to the fingernail) (28 VS and 20 MCS; age range 20-82years; 17 of traumatic etiology). Patients' were assessed using the NCS and four other scales employed in non-communicative patients: the 'Neonatal Infant Pain Scale' (NIPS) and the 'Faces, Legs, Activity, Cry, Consolability' (FLACC) used in newborns; and the 'Pain Assessment In Advanced Dementia Scale' (PAINAD) and the 'Checklist of Non-verbal Pain Indicators' (CNPI) used in dementia. For the establishment of inter-rater agreement, fifteen patients were concurrently assessed by two examiners. Concurrent validity, assessed by Spearman rank order correlations between the NCS and the four other validated scales, was good. Cohen's kappa analyses revealed a good to excellent inter-rater agreement for the NCS total and subscore measures, indicating that the scale yields reproducible findings across examiners. Finally, a significant difference between NCS total scores was observed as a function of diagnosis (i.e., VS or MCS). The NCS constitutes a sensitive clinical tool for assessing nociception in severely brain-injured patients. This scale constitutes the first step to a better management of patients recovering from coma. [less ▲]

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See detailNitroglycerin sensitises in healthy subjects CNS structures involved in migraine pathophysiology: evidence from a study of nociceptive blink reflexes and visual evoked potentials.
Di Clemente, Laura; Coppola, Gianluca; Magis, Delphine ULg et al

in Pain (2009), 144(1-2), 156-61

Nitroglycerin (NTG), a NO donor, induces an attack in migraine patients approximately 4-6 h after administration. The causative mechanisms are not known, but the long delay leaves room for a central ... [more ▼]

Nitroglycerin (NTG), a NO donor, induces an attack in migraine patients approximately 4-6 h after administration. The causative mechanisms are not known, but the long delay leaves room for a central effect, such as a change in neuronal excitability and synaptic transmission of various CNS areas involved in pain and behaviour including trigeminal nucleus caudalis and monoaminergic brain stem nuclei. To explore the central action of NTG, we have studied its effects on amplitude and habituation of the nociceptive blink reflex (nBR) and the visual evoked potential (VEP) before, 1 h and 4 h after administration of NTG (1.2 mg sublingual) or placebo (vehicle sublingual) in two groups of 10 healthy volunteers. We found a significant decrease in nBR pain and reflex thresholds both 1 and 4 h post-NTG. At the 4 h time point R2 latency was shorter (p=0.04) and R2 response area increased (p<0.01) after NTG but not after placebo. Habituation tended to become more pronounced after both NTG and placebo administration. There was a significant amplitude increase in the 5th VEP block (p=0.03) at 1h after NTG and in the 1st block (p=0.04) at 4 h. VEP habituation was replaced by potentiation at both delays after NTG; the change in habituation slope was significant at 1h (p=0.02). There were no significant VEP changes in subjects who received sublingual placebo. In conclusion, we found that in healthy subjects sublingual NTG, but not its vehicle, induces changes in a trigeminal nociceptive reflex and an evoked cortical response which are comparable to those found immediately before and during an attack of migraine. These changes could be relevant for the attack-triggering effect of NTG in migraineurs. [less ▲]

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See detailThe relation between catastrophizing and facial responsiveness to pain.
Kunz, Miriam; Chatelle, Camille ULg; Lautenbacher, Stefan et al

in Pain (2008), 140(1), 127-34

Pain catastrophizing has recently been suggested to have a social function based on a positive association observed with facial responsiveness to noxious stimulation. However, this assumption is based on ... [more ▼]

Pain catastrophizing has recently been suggested to have a social function based on a positive association observed with facial responsiveness to noxious stimulation. However, this assumption is based on studies applying nociceptive stimuli of fixed intensity, such that high catastrophizers not only displayed increased pain behavior but also rated the stimulation as being more painful. The aim of this study was to investigate the relation between catastrophizing and facial responsiveness while controlling for individual differences in pain sensitivity. The facial expression of pain was investigated in 44 young and pain-free individuals in response to painful and non-painful phasic heat stimuli. Painful temperatures were tailored to the individual sensitivity to produce moderate pain. Facial responses were videotaped and objectively examined using the Facial Action Coding System. We also assessed skin conductance activity as an autonomic indicator of pain-related responses. Catastrophizing was assessed using the Pain Catastrophizing Scale (PCS). In accordance with previous findings, subjects scoring higher on pain catastrophizing required lower thermal intensities to induce a moderately painful sensation (r=-0.40, p=0.007). However, catastrophizing did not correlate with facial responsiveness to perceptually controlled painful stimulation (r=-0.02, p=0.88). Moreover, correlation analyses revealed no significant associations between catastrophizing and skin conductance responses. The present findings provide further support for the impact of pain catastophizing on pain sensitivity. However, our finding of no relation between catastrophizing and facial responsiveness when participants are experiencing comparable psychophysical pain intensities, challenges previous assumptions that high catastrophizers display amplified pain behavior; at least in young and pain-free individuals. [less ▲]

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See detailSuboccipital injection with a mixture of rapid- and long-acting steroids in cluster headache: A double-blind placebo-controlled study
Ambrosini, A.; Vandenheede, Michel; Gathot, P. et al

in Pain (2005), 118(1-2), 92-96

Oral steroids can interrupt bouts of cluster headache (CH) attacks, but recurrence is frequent and may lead to steroid-dependency. Suboccipital steroid injection may be an effective 'single shot ... [more ▼]

Oral steroids can interrupt bouts of cluster headache (CH) attacks, but recurrence is frequent and may lead to steroid-dependency. Suboccipital steroid injection may be an effective 'single shot' alternative, but no placebo-controlled trial is available. The aim of our study was to assess in a double-blind placebo-controlled trial the preventative effect on CH attacks of an ipsilateral steroid injection in the region of the greater occipital nerve. Sixteen episodic (ECH) and seven chronic (CCH) CH outpatients were included. ECH patients were in a new bout since no more than I week. After a one-week run-in period, patients were allocated by randomization to the placebo or verurn arms and received on the side of attacks a suboccipital injection of a mixture of long- and rapid-acting betamethasone (n=13; Verum-group) or physiological saline (n=10; Plac-group). Acute treatment was allowed at any time, additional preventative therapy if attacks persisted after I week. Three investigators performed the injections, while four others, blinded to group allocation, followed the patients. Follow-up visits were after I and 4 weeks, whereafter patients were followed routinely. Eleven Verum-group patients (3 CCH) (85%) became attack-free in the first week after the injection compared to none in the Plac-group (P=0.0001). Among them eight remained attack-free for 4 weeks (P=0.0026). Remission lasted between 4 and 26 months in five patients. A single suboccipital steroid injection completely suppresses attacks in more than 80% of CH patients. This effect is maintained for at least 4 weeks in the majority of them. (c) 2005 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. [less ▲]

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See detailLack of estrogen increases pain in the trigeminal formalin model: a behavioural and immunocytochemical study of transgenic ArKO mice
Multon, Sylvie ULg; Pardutz, A.; Mosen, Jeanine ULg et al

in Pain (2005), 114(1-2), 257-265

In order to examine the effect of estrogen on facial pain, we first compared the face-rubbing evoked by a formalin injection in the lip of aromatase-knockout (ArKO) mice, lacking endogenous estrogen ... [more ▼]

In order to examine the effect of estrogen on facial pain, we first compared the face-rubbing evoked by a formalin injection in the lip of aromatase-knockout (ArKO) mice, lacking endogenous estrogen production, 17 beta-estradiol-treated ArKO mice (ArKO-E2) and wild-type (WT) littermates. During the 'acute' phase of pain the time spent rubbing was similar in the three groups, whereas during the following 'interphase' and the second phase of pain, grooming was increased ill ArKO mice. Estradiol-treatment restored a behaviour similar to WT group. To better understand estrogens modulation on pain processes, we examined changes in 5-HT and CGRP innervations of trigeminal nucleus caudalis (TNC) in ArKO, ArKO-E2 and WT groups sacrified during the interphase. Whereas serotonin and CGRP immunoreactivities were comparable in WT and ArKO non-injected control groups, our data showed that 9 min after formalin injection, the density of serotoninergic terminals increased significantly in WT, but not in ArKO mice, while that of CGRP-immunoreactive fibers was lower in WT than in ArKO mice on the injected side. Estradiol-treatment only partially reversed these changes in ArKO-E2 mice. We conclude that estrogen deprivation in ArKO mice can be responsible for increased nociceptive response and that it is accompanied by transmitter changes favouring pro- over anti-nociceptive mechanisms in TNC during interphase of the formalin model. That estradiol-treatment completely reverses the behavioural abnormality Suggests that estrogens absence produces chiefly functional activation-dependent changes. However, the fact that the immunohistochemical abnormalities were not totally normalized by estradiol-treatment suggested that some permanent developmental alterations may occur in ArKO mice. (c) 2005 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. [less ▲]

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See detailDepression in tension-type headache sufferers: bystander or villain?
Schoenen, Jean ULg

in Pain (2004), 111(3), 225-225

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See detailVagus nerve stimulation in awake rats reduces formalin-induced nociceptive behaviour and fos-immunoreactivity in trigeminal nucleus caudalis
Bohotin, C.; Scholsem, M.; Multon, Sylvie ULg et al

in Pain (2003), 101(1-2), 3-12

Besides its well-established efficacy in epilepsy, vagus nerve stimulation (VNS) may be of potential interest in pain treatment. It has, however, not yet been assessed in animal pain models with the ... [more ▼]

Besides its well-established efficacy in epilepsy, vagus nerve stimulation (VNS) may be of potential interest in pain treatment. It has, however, not yet been assessed in animal pain models with the devices and stimulation protocols used in humans. We have therefore studied in awake rats the effects of left cervical VNS on trigeminal nociception using an implantable electrode and stimulator (NCP-Cyberonics((R)). VNS was applied for 24 h at 2 mA intensity, 20 Hz frequency, 0.5 ms pulse width and a duty cycle of 20 s ON/18 s OFF. As a nociceptive stimulus, we injected formalin into the left mystacial vibrissae, assessed behaviour for 45 min and sacrificed the animals 45 min later. Fos-immunoreactive (Fos-Ir) neurons were counted in laminae I-II of trigeminal nucleus caudalis (TNC on both sides. We used three groups of control animals: VNS without formalin, formalin without VNS and sham VNS (implanted without stimulation or formalin). Whereas sham VNS had no significant effect, VNS alone increased Fos expression in ipsilateral TNC in addition to the expected increase in nucleus tractus solitarius. It also significantly attenuated the increase of Fos-Ir neurons observed in ipsilateral TNC laminae I-II after formalin injection. If the proper VNS effect on Fos-expression was subtracted, the reduction of formalin-induced nociceptor activation was 55%. VNS also reduced nociceptive behaviour on average by 96.1% during the early phase (0-6 min) and by 60.7% during the late phase (6-45 min) after the formalin injection. These results suggest that VNS applied with a device used in human therapy may have in awake rats a significant antinociceptive effect in a model of trigeminal pain. (C) 2002 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved. [less ▲]

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See detailAuditory evoked potentials and multiple personality measures in migraine and post-traumatic headaches.
Wang, W.; Wang, Y.-H.; Fu, X. M. et al

in Pain (1999), 79(2-3), 235-42

Migraine sufferers have abnormal cerebral information processing and personality disorders, post-traumatic headache sufferers also have some personality changes. We therefore, studied intensity dependence ... [more ▼]

Migraine sufferers have abnormal cerebral information processing and personality disorders, post-traumatic headache sufferers also have some personality changes. We therefore, studied intensity dependence of auditory evoked potentials, Plutchik-van Praag's depression inventory, Zuckerman's sensation seeking scales and Zuckerman-Kuhlman's personality questionnaire in patients suffering from migraine without aura (n = 26) and chronic post-traumatic headaches (n = 26) as well as in healthy volunteers (n = 30). The migraine group showed significantly increased neuroticism-anxiety than controls, increased intensity dependence of N1-P2, and decreased thrill and adventure score compared with the controls and post-traumatic headaches. The post-traumatic headache had significantly increased depression compared with the controls, and increased disinhibition compared with the controls and migraines. This study demonstrates that the two headache types have different neurophysiological and personality traits. The pronounced intensity dependence of N1-P2 suggests a cortical potentiation response, together with a decreased thrill and adventure seeking, favor a lower serotonergic innervation in migraine. While the elevated disinhibition and depression, as consequences, may be linked with the wide cortical neuronal/axonal degeneration in post-traumatic headache. [less ▲]

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See detailPsychological Approaches During Conscious Sedation. Hypnosis Versus Stress Reducing Strategies: A Prospective Randomized Study
Faymonville, Marie-Elisabeth ULg; Mambourg, P. H.; Joris, Jean ULg et al

in Pain (1997), 73(3), 361-7

Stress reducing strategies are useful in patients undergoing surgery. Hypnosis is also known to alleviate acute and chronic pain. We therefore compared the effectiveness of these two psychological ... [more ▼]

Stress reducing strategies are useful in patients undergoing surgery. Hypnosis is also known to alleviate acute and chronic pain. We therefore compared the effectiveness of these two psychological approaches for reducing perioperative discomfort during conscious sedation for plastic surgery. Sixty patients scheduled for elective plastic surgery under local anesthesia and intravenous sedation (midazolam and alfentanil upon request) were included in the study after providing informed consent. They were randomly allocated to either stress reducing strategies (control: CONT) or hypnosis (HYP) during the entire surgical procedure. Both techniques were performed by the same anesthesiologist (MEF). Patient behavior was noted during surgery by a psychologist, the patient noted anxiety, pain, perceived control before, during and after surgery, and postoperative nausea and vomiting (PONV). Patient satisfaction and surgical conditions were also recorded. Peri- and postoperative anxiety and pain were significantly lower in the HYP group. This reduction in anxiety and pain were achieved despite a significant reduction in intraoperative requirements for midazolam and alfentanil in the HYP group (alfentanil: 8.7 +/- 0.9 microg kg(-1)/h(-1) vs. 19.4 +/- 2 microg kg(-1)/h(-1), P < 0.001; midazolam: 0.04 +/- 0.003 mg kg(-1)/h(-1) vs. 0.09 +/- 0.01 mg kg(-1)/h(-1), P < 0.001). Patients in the HYP group reported an impression of more intraoperative control than those in the CONT group (P < 0.01). PONV were significantly reduced in the HYP group (6.5% vs. 30.8%, P < 0.001). Surgical conditions were better in the HYP group. Less signs of patient discomfort and pain were observed by the psychologist in the HYP group (P < 0.001). Vital signs were significantly more stable in the HYP group. Patient satisfaction score was significantly higher in the HYP group (P < 0.004). This study suggests that hypnosis provides better perioperative pain and anxiety relief, allows for significant reductions in alfentanil and midazolam requirements, and improves patient satisfaction and surgical conditions as compared with conventional stress reducing strategies support in patients receiving conscious sedation for plastic surgery. [less ▲]

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See detailInhibition of the Blink Reflex R2 Component after Supraorbital and Index Finger Stimulations Is Reduced in Cluster Headache: An Indication for Both Segmental and Suprasegmental Dysfunction?
Lozza, A.; Schoenen, Jean ULg; Delwaide, P. J.

in Pain (1997), 71(1), 81-8

Peripheral as well as central mechanisms are thought to play a role in cluster headache pathogenesis. We have studied recovery curves of the R2 component of the blink reflex after conditioning by ... [more ▼]

Peripheral as well as central mechanisms are thought to play a role in cluster headache pathogenesis. We have studied recovery curves of the R2 component of the blink reflex after conditioning by supraorbital or index finger stimuli in 10 episodic cluster headache (CH) patients during a cluster period and in 10 healthy controls. There was no significant change of R2 threshold, latency or area in CH patients. After paired supraorbital stimuli, R2 recovered more rapidly in patients on the symptomatic side. After index stimulations, R2 recovery was more rapid on both symptomatic and non-symptomatic sides in patients compared to controls. Naloxone (0.4 mg) i.v. in two subjects partially reversed the R2 suppression induced by index finger stimuli. The unilateral decrease of R2 inhibition after a segmental supraorbital stimulus most likely reflects sensitisation in the spinal trigeminal nucleus. Whether the latter is due to irritation of the ophthalmic nerve within the cavernous sinus region, which is thought to be pivotal in CH pathogenesis, remains to be proven. In addition, we propose that the bilateral deficit of R2 inhibition after an extrasegmental exteroceptive stimulus might reflect hypoactivity of reticular nuclei, possibly because of reduced central opioid activity. [less ▲]

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See detailReduction of Temporalis Exteroceptive Suppression by Peripheral Electrical Stimulation in Migraine and Tension-Type Headaches
Wang, W.; Schoenen, Jean ULg

in Pain (1994), 59(3), 327-34

Inhibition of the second exteroceptive suppression of temporalis muscle activity (ES2) produced by a preceding electrical stimulus applied at the index was studied in patients suffering from migraine ... [more ▼]

Inhibition of the second exteroceptive suppression of temporalis muscle activity (ES2) produced by a preceding electrical stimulus applied at the index was studied in patients suffering from migraine without aura (MO), chronic (CTH) or episodic (ETH) tension-type headache. Each patient group comprised of 12 subjects was compared to a group of healthy controls. Mean duration of unconditioned ES2, measured on 10 averaged rectified responses after labial stimulation at a 0.1 Hz frequency, was reduced in CTH only. From stimulation intensities of 20 mA onward, peripheral-induced inhibition of temporalis ES2 was significantly more pronounced in both subtypes of tension-type headache compared to migraineurs or controls. After an index finger stimulus of 20 mA, temporalis ES2 was abolished in 83% of CTH, 67% of ETH, 25% of MO patients and 8% of controls, whereas unconditioned ES2 was present in all patients. Among 9 ETH patients with normal (> or = 32 msec) unconditioned ES2, 5 had total disappearance of ES2 after a 20 mA index stimulation. These results demonstrate that peripheral conditioning at 20 mA increases the diagnostic sensitivity of ES2 studies. They suggest that the changes observed in tension-type headache are due to hyperexcitability of the reticular nuclei which inhibit the medullary inhibitory interneurons mediating ES2. [less ▲]

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See detailCephalic and extracephalic pressure pain thresholds in chronic tension-type headache.
Schoenen, Jean ULg; Bottin, D.; Hardy, F. et al

in Pain (1991), 47(2), 145-9

Pressure pain thresholds were assessed with an algometer (Somedic Inc.), over the forehead, temple and suboccipital region as well as over the Achilles tendon. A group of 32 patients suffering from ... [more ▼]

Pressure pain thresholds were assessed with an algometer (Somedic Inc.), over the forehead, temple and suboccipital region as well as over the Achilles tendon. A group of 32 patients suffering from chronic tension-type headache was compared to 20 healthy controls and to 10 migraineurs without aura. Although individual values were widely scattered, pressure pain thresholds were on average significantly lower in chronic tension-type headache, not only at pericranial sites but also over the Achilles tendon. Only 50% of these patients had one or more pericranial thresholds 1.5 S.D. below the mean of controls. After muscular biofeedback therapy, all pain thresholds were on average increased. Along with results obtained previously, the present data support the hypothesis that diffuse disruption of central pain-modulating systems, possibly due to a modified limbic input to the brain-stem, is pivotal in the pathophysiology of chronic tension-type headache. [less ▲]

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See detailOpiates suppress carrageenan-induced edema and hyperthermia at doses that inhibit hyperalgesia
Joris, Jean ULg; Costello, A.; Dubner et al

in Pain (1990), 43

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See detailA new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia.
Hargreaves, K.; Dubner, R.; Brown, F. et al

in Pain (1988), 32(1), 77-88

A method to measure cutaneous hyperalgesia to thermal stimulation in unrestrained animals is described. The testing paradigm uses an automated detection of the behavioral end-point; repeated testing does ... [more ▼]

A method to measure cutaneous hyperalgesia to thermal stimulation in unrestrained animals is described. The testing paradigm uses an automated detection of the behavioral end-point; repeated testing does not contribute to the development of the observed hyperalgesia. Carrageenan-induced inflammation resulted in significantly shorter paw withdrawal latencies as compared to saline-treated paws and these latency changes corresponded to a decreased thermal nociceptive threshold. Both the thermal method and the Randall-Selitto mechanical method detected dose-related hyperalgesia and its blockade by either morphine or indomethacin. However, the thermal method showed greater bioassay sensitivity and allowed for the measurement of other behavioral parameters in addition to the nociceptive threshold. [less ▲]

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