Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Subacromial bursal tissue was studied in 12 patients operated on for painful (10 patients with constant pain and 2 patients with pain on motion) rotator cuff tendinitis/impingement syndrome. The Neer acromioplasty technique was used. Six patients had moderate inflammatory changes and one had a slight inflammation. In three of the five remaining patients, the subacromial bursa did not show any signs of inflammatory involvement, but patients experienced pain at rest and at night, reflecting clinical inflammation in tissues other than the bursa. The two patients with pain only on strain did not show inflammation of the bursa. Immunohistochemical typing of the bursal tissue disclosed a typical chronic mononuclear cell infiltrate consisting mainly of CD2-positive T lymphocytes (50-80% of all inflammatory cells), accompanied by less frequent CD11b (C3bi receptor)-positive monocyte/macrophages (10-40%). The relative paucity of plasmablasts/plasma cells expressing PCA-1 suggests this to be an inflammatory rather than an immune response. Active involvement of some of the local cells is suggested to be the source of algogenic and hyperalgesic substances contributing to pain in chronic shoulder pain syndromes.
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PMID:Inflammation of the subacromial bursa in chronic shoulder pain. 136 Feb 27

In the present study we investigated the modulation of the polymorphonuclear neutrophil (PMN)-endothelial cell adhesion process by the two main proteinases released from activated PMN during their adhesion to endothelium. Our results showed that, in contrast with elastase, cathepsin G was a powerful inhibitor of PAIN adhesion to interleukin-1 (IL-1)-treated human umbilical vein endothelial cells. This inhibitory effect was linked to the enzymatic activity of the proteinase and was selectively directed against PMN. Because the viability and the reactivity of PMN were not modified by cathepsin G, we looked for a possible effect on adhesion molecules. L-selectin was not cleaved by cathepsin G, whereas it was by chymotrypsin, a closely related proteinase. Cathepsin G blocked PMN adhesion to activated endothelial cells, but also to serum- or fibrinogen-coated plates, three adhesion processes mediated by CD11b/CD18. However, by FACScan analysis or by immunoprecipitation, we failed to find evidence of modifications of CD11b/CD18 expression. Although the precise molecular target(s) of cathepsin G remain(s) to be defined, these data indicate that this proteinase, which is known as an inflammatory mediator, can also be considered as a potential down-regulator of adhesion reactions involved in the inflammatory process.
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PMID:Inhibition of neutrophil-endothelial cell adhension by a neutrophil product, cathepsin G. 869 Oct 71

The effect of recombinant bovine somatotropin (bST) on the chemiluminescence, diapedesis, and expression of adhesion receptors (CD11a, CD11b, CD18) of isolated polymorphonuclear leukocytes was studied. The plasma concentrations of insulin-like growth factor-I (IGF-I), bST, cortisol, and alpha-lactalbumin were also monitored. In addition, general and local clinical symptoms and the differentiation of circulating leukocytes were also studied during experimentally induced Streptococcus uberis mastitis in cows. Ten cows were infected with 500 cfu of S. uberis O140J in both left quarters. Five cows were subcutaneously treated with 500 mg of recombinant bST 7 d before and after infection, and 5 control cows received the excipient. General (fever, tachycardia, inappetance, and depression) and local symptoms (swelling, pain, firmness, and flecks in milk) were more acute, severe, and longer-lasting in control cows. Treatment with bST had no effect on chemiluminescence and diapedesis of circulating polymorphonuclear leukocytes and no effect on the expression of adhesion receptors. Recombinant bST induced significantly higher IGF-I and bST concentrations in plasma. The leukopenia observed after infection was less pronounced in the bST-treated cows, and the number of circulating band neutrophils and metamyelocytes was significantly lower in the treated group. The concentration of cortisol did not differ between both groups, but the blood concentration of alpha-lactalbumin significantly increased in both groups from 6 d after infection. These results showed that treatment with recombinant bST improves animal welfare by protecting the cows from severe local and general clinical symptoms during subsequent S. uberis mastitis, but that it has no effect on chemiluminescence, diapedesis, and the expression of adhesion receptors of circulating polymorphonuclear leukocytes.
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PMID:Effect of bovine somatotropin on neutrophil functions and clinical symptoms during Streptococcus uberis mastitis. 1041 62

Nerve root deformation magnitude affects behavioral sensitivity and spinal cytokine expression in a lumbar radiculopathy model. Despite evidence suggesting spinal glia play a role in persistent pain, no study has examined the relationship between injury severity in painful radiculopathy and spinal glial activation. This study quantified local in vivo biomechanics for nerve root injury, describing effects on temporal glial activation. Sham rats had only nerve root exposure; ligation rats received a tight L5 nerve root ligation with silk suture. Using image analysis, the magnitude of nerve root compressive strain was calculated at the time of injury. Mechanical allodynia was assessed from days 1 to 14 following injury and spinal microglial and astrocytic expression were evaluated using immunohistochemistry on days 1, 3, 7, and 14. More severe ligations produced greater microglial activation, indicating injury severity modulates spinal microglial activation. However, astrocytic activation levels did not demonstrate any relationship with the degree of initial injury severity. While allodynia decreased slightly over time following injury, the temporal changes in mechanical allodynia were not significant. Microglial activation levels were maintained temporally, and in some cases increased over time; whereas, changes in astrocytic activation levels were not temporally or injury-related. While initial nerve root injury severity likely modulates spinal OX-42 (CR3/CD11b) expression, OX-42 staining does not directly correlate with nerve root injury-induced mechanical allodynia.
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PMID:Nerve root injury severity differentially modulates spinal glial activation in a rat lumbar radiculopathy model: considerations for persistent pain. 1244 98

Activated spinal glial cells have been strongly implicated in the development and maintenance of persistent pain states following a variety of stimuli including traumatic nerve injury. The present study was conducted to characterize the time course of surface markers indicative of microglial and astrocytic activation at the transcriptional level following an L5 nerve transection that results in behavioral hypersensitivity. Male Sprague-Dawley rats were divided into a normal group, a sham surgery group with an L5 spinal nerve exposure and an L5 spinal nerve transected group. Mechanical allodynia (heightened response to a non-noxious stimulus) of the ipsilateral hind paw was assessed throughout the study. Spinal lumbar mRNA levels of glial fibrillary acidic protein (GFAP), integrin alpha M (ITGAM), toll-like receptor 4 (TLR4) and cluster determinant 14 (CD14) were assayed using real-time reverse transcription polymerase chain reaction (RT-PCR) at 4 h, 1, 4, 7, 14 and 28 days post surgery. The spinal lumbar mRNA expression of ITGAM, TLR4, and CD14 was upregulated at 4 h post surgery, CD14 peaked 4 days after spinal nerve transection while ITGAM and TLR4 continued to increase until day 14 and returned to almost normal levels by postoperative day 28. In contrast, spinal GFAP mRNA did not significantly increase until postoperative day 4 and then continued to increase over the duration of the study. Our optimized real-time RT-PCR method was highly sensitive, specific and reproducible at a wide dynamic range. This study demonstrates that peripheral nerve injury induces an early spinal microglial activation that precedes astrocytic activation using mRNA for surface marker expression; the delayed but sustained expression of mRNA coding for GFAP implicates astrocytes in the maintenance phase of persistent pain states. In summary, these data demonstrate a distinct spinal glial response following nerve injury using real-time RT-PCR.
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PMID:Quantitative real-time RT-PCR assessment of spinal microglial and astrocytic activation markers in a rat model of neuropathic pain. 1514 54

Glial cells function in maintenance of homeostasis as well as in pathophysiology. In this study, we determined the time course of spinal glial cell activation during the development of morphine analgesic tolerance in an L5 spinal nerve transection rodent model of neuropathic pain. We also sought to assess whether the method of morphine administration affected neuroimmune activation at the levels of transcription and translation. Rats received L5 spinal nerve transection or no surgery on day 0. On day 6 post-transection, osmotic minipumps were implanted to deliver saline or morphine s.c. (1 or 10 mg/kg) or i.t. (5 or 20 nmol/h). Mechanical allodynia developed immediately after spinal nerve transection; this hypersensitivity was reversed with both low- and high-dose morphine by either route. Tolerance to antiallodynia developed after 3 days of i.t. morphine and after 6 days of s.c. morphine, indicating hastened tolerance following i.t. delivery. Analysis of mRNA revealed that s.c. morphine treatment did not lead to increases in glial activation markers. In contrast, i.t. morphine caused a biphasic alteration in glial fibrillary acidic protein (GFAP) and integrin alpha M mRNA. Protein levels for GFAP were elevated after s.c. and i.t. administration of morphine; however, induction was further enhanced in the latter group. Here, we show for the first time that there is differential recruitment of transcriptional and translational mechanisms of glial activation by systemic and i.t. morphine. Furthermore, we suggest that enhanced neuroimmune activation after i.t. dosing contributes to the hastened development of analgesic tolerance seen in these animals.
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PMID:Transcriptional and translational regulation of glial activation by morphine in a rodent model of neuropathic pain. 1574 26

Tick saliva contains molecules that modulate the haemostasis, pain/itch responses, wound healing and immune defences of the host. Using BALB/c mice that were each infested with 10 nymphs of Dermacentor andersoni Stiles (Acari: Ixodidae), an attempt has now been made to determine the influence of tick infestation on the expression of leucocyte adhesion molecules in the host. The ticks became fully engorged by the fourth to sixth day of infestation. On the fourth day of infestation, the results of flow cytometry indicated that 2% of the host's splenocytes were expressing high levels of CD49 (alpha4 integrin of VLA-4) and low levels of CD11a (alphaL subunit of the integrin LFA-1). By the eighth day of infestation, 30% of the hosts' splenocytes had this phenotype and were negative for the lineage markers CD3e (T-lymphocytes), DX5 (natural-killer cells of a BALB/c lineage), B220 (B-lymphocytes), CD11b (monocytes/macrophages, granulocytes, natural-killer cells, activated T-lymphocytes, and B-1 cells) and CD11c (myeloid and splenic dendritic cells). Histological examination of the spleens from infested mice revealed disruption of the white-pulp/red-pulp demarcations and the presence of a large number of basophilic normoblasts. The CD11a(lo) population of splenocytes from the tick-infested mice was positive for TER-119 but negative for CD3, B220, CD11b and Gr, confirming that the splenocytes were members of the erythroid lineage. These results indicate that, within 8 days of their initiation, the tick infestations induced extramedullary erythropoiesis in the spleens of their murine hosts.
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PMID:Murine extramedullary erythropoiesis induced by tick infestation. 1600 11

Polymorphonuclear cells (PMN) are recruited in early inflammation and are believed to contribute to inflammatory pain. However, studies demonstrating a hyperalgesic role of PMN did not examine selective PMN recruitment or did not document effective PMN recruitment. We hypothesized that hyperalgesia does not develop after chemokine-induced PMN selective recruitment and is independent of PMN infiltration in complete Freund's adjuvant (CFA)-induced, local inflammation. PMN were recruited by intraplantar injection of CXC chemokine ligand 1 (CXCL1; keratinocyte-derived chemokine), CXCL2/3 (macrophage inflammatory protein-2), or CFA, with or without preceding systemic PMN depletion. Chemokine inoculation resulted in dose (0-30 microg)- and time (0-12 h)-dependent, selective recruitment of PMN as quantified by flow cytometry. CXCL2/3, but not CXCL1, was less effective at high doses, probably as a result of significant down-regulation of CXC chemokine receptor 2 expression on blood PMN. Neither chemokine caused mechanical or thermal hyperalgesia as determined by the Randall-Selitto and Hargreaves test, respectively, despite comparable expression of activation markers (i.e., CD11b, CD18, and L-selectin) on infiltrating PMN. In contrast, CFA injection induced hyperalgesia, independent of PMN recruitment. c-Fos mRNA and immunoreactivity in the spinal cord were increased significantly after inoculation of CFA-independent of PMN-migration but not of CXCL2/3. Measurement of potential hyperalgesic mediators showed that hyperalgesia correlated with local prostaglandin E2 (PGE2) but not with interleukin-1beta production. In summary, hyperalgesia, local PGE2 production, and spinal c-Fos expression occur after CFA-induced inflammation but not after CXCL1- or CXCL2/3-induced, selective PMN recruitment. Thus, PMN seem to be less important in inflammatory hyperalgesia than previously thought.
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PMID:Selective local PMN recruitment by CXCL1 or CXCL2/3 injection does not cause inflammatory pain. 1689 80

Increasing evidence points to a role for spinal neuroimmune dysregulation (glial cell activation and cytokine expression) in the pathogenesis of chronic pain. Suppression of astrocytic and microglial activation with the methylxanthine derivative, propentofylline, pre-emptively attenuates the development of nerve injury-induced allodynia. Currently, we investigated the ability of systemic propentofylline to reverse existing, long-term allodynia after nerve injury--a clinically relevant paradigm. Rats received L5 spinal nerve transection or sham surgery and the development of mechanical allodynia was assessed daily for 2 weeks, at which time injured rats exhibited robust responses to non-noxious von Frey filaments. On days 14-27, rats received either saline or 101 mg/kg propentofylline by intraperitoneal (i.p.) injection. On day 28 or 42 (after a 14-day drug washout period), lumbar spinal cord sections were processed for assessment of astrocytic glial fibrillary acidic protein (GFAP) and microglial OX-42 (antibody against CR3/CD11b). Propentofylline treatment to nerve injured rats resulted in significant reversal of allodynia that lasted throughout the 14-day washout period. Spinal microglial activation was observed at days 28 and 42 post-injury at the protein level, in the absence of mRNA level changes. Less robust increases in GFAP immunoreactivity were observed at days 28 and 42 post-transection. Interestingly, propentofylline treatment suppressed microglial activation at both time points in this paradigm. Taken together, our results highlight the clinical potential of the glial modulating agent, propentofylline, for the treatment of neuropathic pain as well as a role for microglia in the long-term maintenance of allodynia.
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PMID:Efficacy of propentofylline, a glial modulating agent, on existing mechanical allodynia following peripheral nerve injury. 1694 51

Paclitaxel is a commonly used cancer chemotherapy drug that frequently causes painful peripheral neuropathies. The mechanisms underlying this dose-limiting side effect are poorly understood. Growing evidence supports that proinflammatory cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor (TNF), released by activated spinal glial cells and within the dorsal root ganglia (DRG) are critical in enhancing pain in various animal models of neuropathic pain. Whether these cytokines are involved in paclitaxel-induced neuropathy is unknown. Here, using a rat neuropathic pain model induced by repeated systemic paclitaxel injections, we examined whether paclitaxel upregulates proinflammatory cytokine gene expression, and whether these changes and paclitaxel-induced mechanical allodynia can be attenuated by intrathecal IL-1 receptor antagonist (IL-1ra) or intrathecal delivery of plasmid DNA encoding the anti-inflammatory cytokine, interleukin-10 (IL-10). The data show that paclitaxel treatment induces mRNA expression of IL-1, TNF, and immune cell markers in lumbar DRG. Intrathecal IL-1ra reversed paclitaxel-induced allodynia and intrathecal IL-10 gene therapy both prevented, and progressively reversed, this allodynic state. Moreover, IL-10 gene therapy resulted in increased IL-10 mRNA levels in lumbar DRG and meninges, measured 2 weeks after initiation of therapy, whereas paclitaxel-induced expression of IL-1, TNF, and CD11b mRNA in lumbar DRG was markedly decreased. Taken together, these data support that paclitaxel-induced neuropathic pain is mediated by proinflammatory cytokines, possibly released by activated immune cells in the DRG. We propose that targeting the production of proinflammatory cytokines by intrathecal IL-10 gene therapy may be a promising therapeutic strategy for the relief of paclitaxel-induced neuropathic pain.
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PMID:Intrathecal interleukin-10 gene therapy attenuates paclitaxel-induced mechanical allodynia and proinflammatory cytokine expression in dorsal root ganglia in rats. 1717 26


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