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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The chronic constriction injury model of mononeuropathy is a direct, partial nerve injury yielding thermal hyperalgesia. The inflammation that results from this injury is believed to contribute importantly to both the neuropathological and behavioral sequelae. This study involved administering a single dose (250 ng) of interleukin-10 (IL-10), an endogenous anti-inflammatory peptide, at the site and time of a chronic constriction injury (CCI) lesion to determine if IL-10 administration could attenuate the inflammatory response of the nerve to CCI and resulting thermal hyperalgesia. In IL-10-treated animals, thermal hyperalgesia was significantly reduced following CCI (days 3, 5 and 9). Histological sections from the peripheral nerve injury site of those animals had decreased cell profiles immunoreactive for ED-1, a marker of recruited macrophages, at both times studied (2 and 5 days post-CCI). IL-10 treatment also decreased cell profiles immunoreactive for the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) at day 2, but not day 5. Qualitative light microscopic assessment of neuropathology at the lesion site did not suggest substantial differences between IL-10 and vehicle-treated sections. The authors propose that initial production of TNF-alpha and perhaps other proinflammatory cytokines at the peripheral nerve lesion site importantly influences the long-term behavioral outcome of nerve injury, and that IL-10 therapy may accomplish this by downregulating the inflammatory response of the nerve to injury.
Pain 1998 Jan
PMID:Anti-inflammatory interleukin-10 therapy in CCI neuropathy decreases thermal hyperalgesia, macrophage recruitment, and endoneurial TNF-alpha expression. 951 58

Wallerian degeneration with macrophage influx and production of proinflammatory cytokines is a critical factor in the development of hyperalgesia in animal models of neuropathic pain. We hypothesized that in the mouse strain with delayed Wallerian degeneration, the C57BL/Wld mouse, the temporal course of mechanical allodynia and thermal hyperalgesia as well as the temporal profile of cytokine expression after nerve injury would differ from normal mice. Here we used the model of chronic constriction injury of the sciatic nerve (CCI) to study the correlation of pain related behavior with peripheral nerve de- and regeneration and concomitant cytokine production. Indeed, after CCI, C57BL/Wld mice showed markedly reduced thermal hyperalgesia compared to normal C57BL/6 mice, temporally related to the delayed recruitment of hematogeneous macrophages to the injured nerve. Endoneurial tumor necrosis factor-alpha (TNF)-like immunoreactivity increased rapidly in normal mice but did so with a delayed time course in C57BL/Wld mice. In addition, the duration of mechanical allodynia was significantly prolonged in C57BL/Wld mice as compared to C57BL/6 mice, in accordance with the delay in regeneration of sensory nerve fibers in these mice. These results suggest that macrophage invasion and production of TNF may influence the development of thermal hyperalgesia and that regenerative activity is linked to mechanical allodynia in peripheral mononeuropathy.
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PMID:Painful mononeuropathy in C57BL/Wld mice with delayed wallerian degeneration: differential effects of cytokine production and nerve regeneration on thermal and mechanical hypersensitivity. 951 88

Neuropathic pain responds poorly to opioids. We now report that combination of systemic morphine (2 mg/kg) and dextromethorphan (45 mg/kg), a clinically available antitussive with NMDA-antagonist properties, markedly alleviated mechanical and cold allodynia-like behavior in a rat model of peripheral mononeuropathy. Neither drug produced a significant effect on its own at these doses. The anti-allodynic effect of morphine plus dextromethorphan was reversed by naloxone. The present results suggest that a combination of NMDA-antagonist and opiates might be effective in treating neuropathic pain. Furthermore, the effect of this drug combination is mainly mediated via opioid receptors.
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PMID:Dextromethorphan potentiates the effect of morphine in rats with peripheral neuropathy. 960 69

Interleukin-6 (IL-6) is a multifunctional cytokine whose actions include modulation of proliferation, differentiation, and maturation of hemapoietic progenitors and other cell lineages; growth regulation of certain carcinoma cell lines; and control of cellular metabolic activities. Initially described in terms of its activities in the immune system and inflammation, accumulating evidence supports an essential role of IL-6 in the development, differentiation, regeneration and degeneration of neurons in the peripheral and central nervous system. We have previously demonstrated that immunoreactive-like IL-6 protein is significantly elevated in the spinal cord in response to peripheral nerve injury that results in neuropathic pain behaviors in the rat. In the current study, our objective was to determine if the source of IL-6 protein was endogenous to the central nervous system by measuring any detectable increases in spinal IL-6 mRNA expression following established mononeuropathy procedures associated with neuropathic pain: spinal nerve cryoneurolysis (SPCN) or spinal nerve tight ligation (SPTL). Using in situ hybridization and a digoxigenin-labeled oligonucleotide, IL-6 mRNA in neurons was significantly elevated at 3 and 7 days post SPCN and 7 days post SPTL in both dorsal and ventral horns. The cellular localization of the IL-6 mRNA expression was predominately neuronal as confirmed by NeuN serial staining. For example, in the SPCN 7 day group, IL-6 mRNA cell profiles in the ipsilateral dorsal horn were significantly different from the normal group (38.7+/-12.8 vs. 4.89+/-1.6, p<0.001). These data demonstrate the central, spinal production of a proinflammatory cytokine in response to a peripheral nerve injury. In addition, these results add to the growing body of literature implicating these immune products, cytokines, as potential neuromodulators/neurotransmitters and provides further evidence for their role in the nociceptive processing which leads to chronic pain.
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PMID:Increase of interleukin-6 mRNA in the spinal cord following peripheral nerve injury in the rat: potential role of IL-6 in neuropathic pain. 981 45

The past 10 years have brought several new experimental models with which to study chronic neuropathic pain in animals. Consequently, our knowledge about the mechanisms subserving neuropathic pain in humans has improved. However, the first animal model that was used for studying this type of chronic pain was the autotomy-model which can still be considered as a useful tool for pain studies. The present review assesses some of the similarities and differences between autotomy-model and more recent models of experimental traumatic mononeuropathy. In addition, it considers some of the similarities between the results obtained in clinical studies and in autotomy studies.
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PMID:Correlation between autotomy-behavior and current theories of neuropathic pain. 986 16

The objective of this study was to investigate the central processing of dynamic mechanical allodynia in patients with mononeuropathy. Regional cerebral blood flow, as an indicator of neuronal activity, was measured with positron emission tomography. Paired comparisons were made between three different states; rest, allodynia during brushing the painful skin area, and brushing of the homologous contralateral area. Bilateral activations were observed in the primary somatosensory cortex (S1) and the secondary somatosensory cortex (S2) during allodynia compared to rest. The S1 activation contralateral to the site of the stimulus was more expressed during allodynia than during innocuous touch. Significant activations of the contralateral posterior parietal cortex, the periaqueductal gray (PAG), the thalamus bilaterally and motor areas were also observed in the allodynic state compared to both non-allodynic states. In the anterior cingulate cortex (ACC) there was only a suggested activation when the allodynic state was compared with the non-allodynic states. In order to account for the individual variability in the intensity of allodynia and ongoing spontaneous pain, rCBF was regressed on the individually reported pain intensity, and significant covariations were observed in the ACC and the right anterior insula. Significantly decreased regional blood flow was observed bilaterally in the medial and lateral temporal lobe as well as in the occipital and posterior cingulate cortices when the allodynic state was compared to the non-painful conditions. This finding is consistent with previous studies suggesting attentional modulation and a central coping strategy for known and expected painful stimuli. Involvement of the medial pain system has previously been reported in patients with mononeuropathy during ongoing spontaneous pain. This study reveals a bilateral activation of the lateral pain system as well as involvement of the medial pain system during dynamic mechanical allodynia in patients with mononeuropathy.
Pain 1999 Dec
PMID:A PET activation study of dynamic mechanical allodynia in patients with mononeuropathy. 1056 54

Wallerian degeneration, induced after injury to a peripheral nerve, is associated with upregulation of proinflammatory cytokines, which are suggested to contribute to the development of lesion-induced neuropathic pain. In chronic constrictive injury (CCI), an animal model of injury-induced painful mononeuropathy, inhibition of synthesis, release, or function of the cytokine tumor necrosis factor-alpha (TNF) results in reduced pain-associated behavior. Here, changes of TNF content in rat sciatic nerves after CCI (days 0, 0.5, 1, 3, 7 and 14) were investigated by enzyme-linked-immunoassay. Low levels of TNF were already detectable in control nerves. Concentrations increased rapidly after CCI, with a maximum (2.7-fold) at 12 h, and remained elevated on a lower level until day 3. Baseline levels were reached again at day 14. These results indicate that TNF is produced at an early time point in the cascade of events resulting in Wallerian degeneration and hyperalgesia following peripheral nerve injury. Given that only prophylactic treatment with TNF inhibitors efficiently reduces hyperalgesia in CCI, TNF seems to contribute to the initiation of neuropathic pain in this model.
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PMID:Serial determination of tumor necrosis factor-alpha content in rat sciatic nerve after chronic constriction injury. 1063 Jan 97

NMDA-type glutamate receptors are involved in the generation and maintenance of altered pain states. In the present study, we examined the effect of an NMDA-glycine site antagonist, GV196771A [E-4, 6-dichloro-3-(2-oxo-1-phenyl-pyrrolidin-3-ylidenemethyl)-1H- indole-2- carboxylic acid sodium salt], on responses to noxious stimuli both in normal rats and during peripheral mononeuropathy induced by chronic constriction injury (CCI) of the sciatic nerve. In one series of experiments, activity of nociceptive neurons in the ventroposterolateral (VPL) nucleus of the thalamus was recorded in response to pressure stimuli to the contralateral hindpaw. Intravenous injection (iv) of the glycine antagonist had no effect on these cells in normal rats. When tested in rats with CCI induced 2-3 weeks previously, however, GV196771A (0.125, 0.5 and 2.0mg/kg) blocked responses to noxious stimulation in a dose-dependent and reversible manner. Morphine (0.5mg/kg, iv) and the NMDA channel blocker MK801 (0.1mg/kg, iv) suppressed noxious stimulus-evoked activity of VPL neurons in both normal and CCI-treated rats. MK801 also decreased the responses of non-nociceptive neurons to brush stimulation in both sets of animals, in contrast to the glycine antagonist which did not alter the responses of these cells. Similar results were obtained from a series of behavior experiments in which the latency for paw withdrawal from heat stimulation was measured in normal and CCI-treated rats. GV196771A (3 and 10mg/kg) injected orally, reduced the hyperalgesic response in the treated rats but did not change the withdrawal latency in normal rats. Taken together, these findings suggest that block of the NMDA receptor decreases nociceptive transmission in the thalamus and can modulate hyperalgesic states. GV196771A and glycine antagonists in general may represent innovative and safe agents for the treatment of neuropathic pain.
Pain 2000 Feb
PMID:Modulation of nociceptive transmission by NMDA/glycine site receptor in the ventroposterolateral nucleus of the thalamus. 1066 26

Recent functional brain imaging studies with positron emission tomography (PET), in painful peripheral mononeuropathy and nitroglycerin-provoked cluster headache attacks, suggest a preference of the right hemisphere, especially the anterior cingulate cortex (ACC) and the medial prefrontal cortex (MPFC), in attributing emotional valence and attention to the pain suffering. We have investigated the central processing of painful trigeminal neuropathy (PTN) in patients treated with electric extradural precentral gyrus stimulation (PCGS). Increased regional cerebral blood flow (rCBF) was detected in the right caudal ACC [Brodmann area (BA) 24] and anterior limbic thalamus, while a decreased activity was observed in the right MPFC (BA 9/32) during the habitual-pain state, in comparison with the pain-alleviated state regardless of the inflicted side of PTN. The involvement of BA 9/32 and the anterior limbic thalamus spatially extended to the left hemisphere, but the local maxima and a significant negative correlation between the rCBF changes in the two structures were found only in the right hemisphere. The activation of the caudal BA24 further supports the theory that ACC is crucial for the suffering in chronic pain. Our study not only verifies the preferential role of the right hemisphere in the appreciation of pain suffering, but further supports that sustained chronic pain, being devoid of the motivational component of an escape response, targets the right hemisphere, particularly the BA24 of the ACC. Copyright 1999 European Federation of Chapters of the International Association for the Study of Pain.
Eur J Pain 1999 Mar
PMID:PET study on central processing of pain in trigeminal neuropathy. 1070 Mar 37

It is well recognized that gender differences play a major role in pain sensitivity, pain report, analgesic efficacy and prevalence of certain chronic pain disorders. In the present study we sought to determine whether male or female rats of two different outbred strains (Sprague-Dawley and Holtzman) experienced differential pain sensitivity after the same mononeuropathy lesion. Following baseline mechanical allodynia testing, rats of each sex and strain underwent an L5 spinal nerve transection. Mechanical allodynia using 2 and 12 g von Frey filaments was assessed at days 1, 3, 5, 7, and 10 post surgery. There were no statistically significant differences in allodynia between gender in the Holtzman strain or between strains. However, mechanical allodynia was significantly greater in female Sprague-Dawley rats as compared with males following a spinal nerve transection. These data suggest that the choice of rat gender and strain should be considered in experimental neuropathic pain studies, especially in the assessment of potential analgesics.
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PMID:Gender differences in rat neuropathic pain sensitivity is dependent on strain. 1071 25


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