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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

In the endotoxin-induced inflammation, interleukin-10 reduced significantly, and in a dose-dependent manner, the inflammatory pain as assessed by mechanical and thermal tests. The levels of Tumour Necrosis Factor (TNF)alpha and NGF were upregulated at 1.5 h whereas those of IL-1beta at 6 h after ET injection. IL-10 downregulated the levels of TNFalpha (from 4974.75 +/- 875.78 to 1008 +/- 350 pg/hind paw), NGF (from 352.9 +/- 46.7 to 33.9 +/- 2.4 pg/hind paw) and IL-1beta (from 2773.88 +/- 423.96 to 1108 +/- 399.56 pg/hind paw). These data suggest that IL-10 inhibits ET-induced hyperalgesia by downregulation of TNFalpha, IL-1beta and NGF production.
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PMID:Interleukin-10 reduces the endotoxin-induced hyperalgesia in mice. 966 59

Thalidomide reduces thermal hyperalgesia and mechanical allodynia in chronic constrictive sciatic nerve injury (CCI). Since thalidomide mainly inhibits tumor necrosis factor alpha (TNF-alpha) synthesis with less well defined effects on other cytokines, we investigated the effect of the drug on the expression of the proinflammatory cytokines TNF-alpha, interleukin-1beta (IL-1beta) and interleukin 6 (IL-6), and of the anti-inflammatory cytokine interleukin-10 (IL-10) in the lesioned rat sciatic nerve. The increase of endoneurial TNF-alpha during the first week after CCI was reduced after thalidomide treatment, as shown with immunohistochemistry and enzyme-linked-immunosorbent assay. In contrast, endoneurial IL-1beta-immunoreactivity (IR) and IL-6-IR were not altered by thalidomide treatment, nor was macrophage influx. Recruitment of epineurial IL-10 immunoreactive macrophages as well as the recovery of injury-induced depletion of endoneurial IL-10-IR was enhanced by thalidomide treatment. To control for central plasticity as another factor for the effects of thalidomide, the spinal cord was analyzed for changes in neurotransmitters. The decrease in CGRP-IR and SP-IR in the dorsal horn of operated animals was not influenced by treatment. In contrast, the increase in met-enkephalin observed in the dorsal horn of operated animals was further enhanced in the thalidomide-treated animals. The study elucidates some of the complex alterations in CCI and its modulation by thalidomide, and provides further evidence for a possible therapeutic benefit of cytokine-modulating substances in the treatment of neuropathic pain.
Pain 2000 Dec 01
PMID:Thalidomide treatment in chronic constrictive neuropathy decreases endoneurial tumor necrosis factor-alpha, increases interleukin-10 and has long-term effects on spinal cord dorsal horn met-enkephalin. 1106 14

Intraspinal injection of quisqualic acid (QUIS) produces excitotoxic injury with pathophysiological characteristics similar to those associated with ischemic and traumatic spinal cord injury (SCI). Responses to QUIS-induced injury include an inflammatory component, as well as the development of spontaneous and evoked pain behaviors. We hypothesized that QUIS-induced inflammation and subsequent gene expression contribute to the development and progression of pain-related behaviors and that blockade of inflammation-related gene expression leads to the amelioration of these behaviors. Using the QUIS model of spinal cord injury, we examined whether interleukin-10 (IL-10), a potent anti-inflammatory cytokine, is able to reduce mRNA levels of inflammatory and cell death-related genes leading to a reduction of pain behaviors. The results demonstrate that animals receiving systemic injection of IL-10, 30 minutes following QUIS-induced SCI, showed a significant delay in the onset of excessive grooming behavior, a significant reduction in grooming severity, and a significant reduction in the longitudinal extent of a pattern of neuronal loss within the spinal cord characterized as "grooming-type damage." QUIS injections also resulted in an increase in mRNA levels of interleukin-1 beta (IL-1 beta), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), CD95 ligand (CD95-L, also called FAS-L/APO-1L), and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Results of QUIS injury plus IL-10 treatment resulted in a significant downregulation of IL1-beta and iNOS mRNA and these results were supported by Western blot analysis of protein levels following IL-10 treatment. These data suggest that IL-10 reduces inflammation and that targeting injury-induced inflammation is an effective strategy for limiting the extent of neuronal damage following excitotoxic SCI and thus the onset and progression of injury-induced pain behaviors.
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PMID:Effects of interleukin-10 (IL-10) on pain behavior and gene expression following excitotoxic spinal cord injury in the rat. 1117 Jul 29

Traditional acupuncture has been used for treating a variety of health conditions. In contrast, Western physicians limited acupuncture to the alleviation of pain. Concomitant with a recent view that not all kinds of pain are within the reach of acupuncture-induced relief, it has been suggested that some conditions other than pain can be effectively treated by this method. Increased release of the neuropeptide beta-endorphin was proposed to explain the antinociceptive function of acupuncture. Even if correct beta-endorphin cannot account for the effect of acupuncture in other conditions. Endorphins might be interacting with cytokines, some of which (e.g. interleukin-10) downregulate the inflammatory component of disorders in which acupuncture may be useful. We present a speculative notion of the view that acupuncture may amplify the interaction between neuropeptides and cytokines. A non-invasive approach, such as immune-committed cells harvested from blood of acupuncture-treated patients, could be used to examine this hypothesis. Inclusion of a placebo group might support the credibility of acupuncture.
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PMID:Acupuncture beyond the endorphin concept? 1201 73

Cytokines such as IL-1beta, IL-6 and tumor necrosis factor-alpha (TNF-alpha) have been shown to contribute directly to central and peripheral neuropathic pain. Recently, exogenous interleukin-10 (IL-10) was shown to impede development of dynorphin-induced allodynia presumably by inhibiting IL-1beta. We therefore wanted to determine whether endogenous IL-10 had a role in pain perception. By measuring the latency of the paw licking response, we show in IL-10 knockout mice and in normal mice treated with anti-IL-10 that latency times are increased, suggesting that endogenous IL-10 increases nociception. This does not appear to be directly correlated with IL-10's regulation of DREAM, a transcriptional regulator of prodynorphin synthesis.
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PMID:Evidence for endogenous interleukin-10 during nociception. 1279 32

An adhesion of the subacromial bursa in the shoulder causes pain during joint motion and restricts the range of motion of the glenohumeral joint. To understand the biologic features of an adhesion, the gene expressions in adhesive subacromial bursa were analyzed by quantitative real-time reverse transcriptase-polymerase chain reaction. The gene expressions in adhesive subacromial bursae were approximately threefold to fourfold greater than those in nonadhesive bursae for the genes for Type I and Type III procollagens, CD34 antigen in vascular endothelium, hyaluronan synthase-3, and interferon-gamma. The gene expression of interleukin-8 was predominant in adhesive bursa. The gene expressions of hyaluronan synthase-1, hyaluronan synthase-2, and interleukin-10 which is an antiadhesive cytokine were predominant in nonadhesive bursae. Chromatography analysis revealed that a hyaluronan, of which molecular weight was more than 100 kDa, was present in the cavity of nonadhesive subacromial bursae. It is suggested that pathologic fibrosis and vascularization are maintained by the presence of interferon-gamma and interleukin-8 in adhesive subacromial bursae and that high molecular weight hyaluronan or interleukin-10 plays a role for antiadhesion.
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PMID:Pathologic gene expression in adhesive subacromial bursae of human shoulder. 1283 53

Intraspinal injection of the AMPA/metabotropic receptor agonist quisqualic acid (QUIS) results in a pathophysiology that leads to excessive grooming behavior, which has been proposed as a model of spontaneous at-level pain after spinal cord injury (SCI). To further characterize the onset and progression of this behavior we evaluated the effects of 3 drugs, agmatine (Agm), interleukin-10 (IL-10), and cyclosporin A (CsA), on different characteristics of this behavior. In these experiments rats were given saline, Agm, CsA10, or CsA20 once daily for 14 days (or a single injection of IL-10) starting either 30 minutes post-QUIS (group 1) or 10 to 18 days post-QUIS when excessive grooming behavior had been established (group 2). In the first group of animals agmatine, IL-10, CsA10, or CsA20 reduced the longitudinal extent of neuronal loss in the spinal cord compared to QUIS-injected animals treated with saline. The behavioral consequences of this effect included the delayed onset of excessive grooming behavior, reduction in the area of skin targeted for excessive grooming, and reduced grooming severity. Animals treated at the time of excessive grooming onset showed significantly reduced grooming area, grooming severity, and neuronal loss in the spinal cord compared to QUIS animals treated with saline. In conclusion, systemic administration of Agm, IL-10, or CsA significantly delayed the onset and reduced the severity of a spontaneous pain-like behavior. These effects are believed to be due, in part, to the neuroprotective properties of these drugs against QUIS-induced excitotoxicity. The effective treatment of excessive grooming behavior suggests that Agm, IL-10, and CsA modulate ongoing cellular events responsible for the progression of this behavior.
J Pain 2003 Apr
PMID:Effects of agmatine, interleukin-10, and cyclosporin on spontaneous pain behavior after excitotoxic spinal cord injury in rats. 1462 10

Snakebites constitute a serious public health problem in Central and South America, where species of the lancehead pit vipers (genus Bothrops) cause the majority of accidents. Bothrops envenomations are very painful, and this effect is not neutralized by antivenom treatment. Two variants of secretory phospholipases A2 (sPLA2), corresponding to Asp49 and Lys49 PLA2s, have been isolated from Bothrops asper venom. These sPLA2s induce hyperalgesia in rats following subcutaneous injection. However, venom in natural Bothrops bites is frequently delivered intramuscularly, thereby potentially reaching peripheral nerve bundles. Thus, the present series of experiments tested whether these sPLA2s could exert pain-enhancing effects following administration around healthy sciatic nerve. Both were found to produce mechanical allodynia ipsilateral to the injection site; no thermal hyperalgesia was observed. As no prior study has examined potential spinal mechanisms underlying sPLA2 actions, a series of anatomical and pharmacological studies were performed. These demonstrated that both sPLA2s produce activation of dorsal horn astrocytes and microglia that is more prominent ipsilateral to the site of injection. As proinflammatory cytokines and nitric oxide have each been previously implicated in spinally mediated pain facilitation, the effect of pharmacological blockade of these substances was tested. The results demonstrate that mechanical allodynia induced by both sPLA2s is blocked by interleukin-1 receptor antagonist, anti-rat interleukin-6 neutralizing antibody, the anti-inflammatory cytokine interleukin-10, and a nitric oxide synthesis inhibitor (L-NAME). As a variety of immune cells also produce and release sPLA2s during inflammatory states, the data may have general implications for the understanding of inflammatory pain.
Pain 2004 Mar
PMID:Snake venom phospholipase A2s (Asp49 and Lys49) induce mechanical allodynia upon peri-sciatic administration: involvement of spinal cord glia, proinflammatory cytokines and nitric oxide. 1510 22

Despite many decades of drug development, effective therapies for neuropathic pain remain elusive. The recent recognition of spinal cord glia and glial pro-inflammatory cytokines as important contributors to neuropathic pain suggests an alternative therapeutic strategy; that is, targeting glial activation or its downstream consequences. While several glial-selective drugs have been successful in controlling neuropathic pain in animal models, none are optimal for human use. Thus the aim of the present studies was to explore a novel approach for controlling neuropathic pain. Here, an adeno-associated viral (serotype II; AAV2) vector was created that encodes the anti-inflammatory cytokine, interleukin-10 (IL-10). This anti-inflammatory cytokine is known to suppress the production of pro-inflammatory cytokines. Upon intrathecal administration, this novel AAV2-IL-10 vector was successful in transiently preventing and reversing neuropathic pain. Intrathecal administration of an AAV2 vector encoding beta-galactosidase revealed that AAV2 preferentially infects meningeal cells surrounding the CSF space. Taken together, these data provide initial support that intrathecal gene therapy to drive the production of IL-10 may prove to be an efficacious treatment for neuropathic pain.
Mol Pain 2005 Feb 25
PMID:Controlling neuropathic pain by adeno-associated virus driven production of the anti-inflammatory cytokine, interleukin-10. 1581 97


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