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

In inflammatory neuropathy, immune activation near intact peripheral nerves induces mechanical allodynia. The identity of the peripheral immune product(s) that lead to these changes in pain behavior is unknown. The present series of studies utilized the sciatic inflammatory neuropathy (SIN) model to examine this question. Here, inflammatory neuropathy is created by injecting an immune activator (zymosan) around one sciatic nerve via an indwelling catheter. Our prior studies demonstrated that peri-sciatic zymosan activated macrophages and neutrophils to release proinflammatory cytokines and reactive oxygen species (ROS). In addition, zymosan is a classical activator of the complement cascade. Thus the present series of experiments examined whether any of these inflammatory mediators are involved in the initial induction of SIN-induced ipsilateral or bilateral allodynias. Peri-sciatic injection of selective inhibitors/antagonists revealed that a number of immune products are early mediators of the resultant allodynias, including proinflammatory cytokines (tumor necrosis factor, interleukin-1, and interleukin-6), ROS, and complement. Thus these immune-derived substances can markedly alter sensory nerve function at mid-axon.
Pain 2004 Jul
PMID:Peri-sciatic proinflammatory cytokines, reactive oxygen species, and complement induce mirror-image neuropathic pain in rats. 1527 80

It has become clear that spinal cord glia (microglia and astrocytes) importantly contribute to the creation of exaggerated pain responses. One model used to study this is peri-spinal (intrathecal, i.t.) administration of gp120, an envelope protein of HIV-1 known to activate glia. Previous studies demonstrated that i.t. gp120 produces pain facilitation via the release of glial proinflammatory cytokines. The present series of studies tested whether spinal nitric oxide (NO) contributes to i.t. gp120-induced mechanical allodynia and, if so, what effect NO has on spinal proinflammatory cytokines. gp120 stimulation of acutely isolated lumbar dorsal spinal cords released NO as well as proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta (IL1), interleukin-6 (IL6)), thus identifying NO as a candidate mediator of gp120-induced behavioral effects. Behaviorally, identical effects were observed when gp120-induced mechanical allodynia was challenged by i.t. pre-treatment with either a broad-spectrum nitric oxide synthase (NOS) inhibitor (L-NAME) or 7-NINA, a selective inhibitor of NOS type-I (nNOS). Both abolished gp120-induced mechanical allodynia. While the literature pre-dominantly documents that proinflammatory cytokines stimulate the production of NO rather than the reverse, here we show that gp120-induced NO increases proinflammatory cytokine mRNA levels (RT-PCR) and both protein expression and protein release (serial ELISA). Furthermore, gp120 increases mRNA for IL1 converting enzyme and matrix metalloproteinase-9, enzymes responsible for activation and release of proinflammatory cytokines.
Pain 2004 Aug
PMID:HIV-1 gp120 stimulates proinflammatory cytokine-mediated pain facilitation via activation of nitric oxide synthase-I (nNOS). 1528 92

Herniation of the nucleus pulposus (NP) from lumbar intervertebral discs commonly results in radiculopathic pain and paresthesia (sciatica). While traditionally considered the result of mechanical compression of the dorsal root ganglion (DRG) and/or spinal nerve root, recent studies implicate pro-inflammatory mediators released from or evoked by NP, a possibility that was presently investigated. Single-unit recordings were made from L5 wide dynamic range dorsal horn neurons in pentobarbital-anesthetized rats. Autologous NP was harvested from a coccygeal disc and placed onto the exposed L5 DRG. A control group had subcutaneous adipose tissue or saline placed similarly. To test involvement of tumor necrosis factor-alpha (TNF-alpha), a third group received autologous NP plus local soluble TNF-alpha receptor type 1 (0.013 microg) which binds TNF-alpha to prevent its action. In each group, neuronal responses to graded heat (38-50 degrees C) and mechanical (von Frey filaments 4-76 g) stimuli were recorded prior to and at three successive hourly intervals following each treatment. Responses to noxious heat and mechanical stimuli were significantly enhanced 1 h post-NP and remained elevated thereafter. Thermally and mechanically evoked responses were not significantly affected in control rats or those treated with NP + soluble TNF-alpha receptor type 1. These results indicate that sensitization of nociceptive spinal neuronal responses develops quickly following exposure of the DRG to NP, and that TNF-alpha is involved. This electrophysiological model of herniated NP may prove useful in further characterizing the role of inflammatory mediators in hyperalgesia and allodynia resulting from lumbar disc herniation.
Pain 2004 Aug
PMID:Role of TNF-alpha in sensitization of nociceptive dorsal horn neurons induced by application of nucleus pulposus to L5 dorsal root ganglion in rats. 1528 98

Snakebites are a relevant public health problem in Central and South America. Snake bite envenomations cause intense pain, not relieved by anti-venom. The fangs of many species are short, causing subcutaneous injection. Fangs of larger species inflict subcutaneous or intramuscular envenomation. To understand pain induced by subcutaneous venom, this study examined spinal mechanisms involved in pain-enhancing effects of subcutaneous Lys49 and Asp49 secretory phospholipase-A(2) (sPLA2), two components of Bothrops asper snake venom showing highly different enzymatic activities. Unilateral intraplantar sPLA2-Lys49 (catalytically inactive) or sPLA2-Asp49 (catalytically active) into rat hindpaws each induced mechanical hyperalgesia (Randall-Selitto test), whereas only catalytically active sPLA2-Asp49 caused mechanical allodynia (von Frey test). Effects induced by both sPLA2s were inhibited by intrathecal fluorocitrate, a reversible glial metabolic inhibitor. In support, immunohistochemical analysis revealed activation of dorsal horn astrocytes and microglia after intraplantar injection of either sPLA2. Spinal proinflammatory cytokines, nitric oxide, and prostanoids each appear to be involved in the pain-enhancing effects of these sPLA2s. Blockade of interleukin-1 (IL1) inhibited hyperalgesia induced by both sPLA2s, while leaving allodynia unaffected. Blockade of tumor necrosis factor reduced responses to sPLA2-Asp49. An inhibitor of neuronal nitric oxide synthase, 7-nitroindazole (7-NI), inhibited hyperalgesia induced by both sPLA2s, without interfering with allodynia induced by sPLA2-Asp49. On the other hand, L-N(6)-(1-iminoethyl)lysine (L-NI), an inhibitor of the inducible nitric oxide synthase, did not alter any sPLA2-induced effect. Lastly, celecoxib, an inhibitor of cyclooxygenase-2, attenuated sPLA2 actions. These data provide the first evidence of spinal mediators involved in pain facilitation induced by subcutaneous venoms.
Pain 2004 Sep
PMID:Snake venom components enhance pain upon subcutaneous injection: an initial examination of spinal cord mediators. 1532 10

Dioscoreae Rhizoma (MDR), the root of Dioscorea tokoro MAKINO, has been used for the treatment of arthritis, muscular pain and urinary diseases in oriental medicine. The present work evaluates a methanol extract of Dioscoreae Rhizoma (MDR). MDR did not show any cytotoxic effect on mouse lung fibroblast cells (mLFCs) or human fibroblast-like synovial cells (hFLSCs). However, it significantly reduced the proliferation of hFLSCs stimulated by interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha). MDR significantly inhibited the production of TNF-alpha and IL-1beta as well as down-regulating the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in IL-1beta- and TNF-alpha-stimulated hFLSCs. MDR also effectively reduced the level of reactive oxygen species (ROS) in these cells. Taken together, these findings provide evidence that MDR may be a candidate for the treatment of rheumatoid arthritis (RA).
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PMID:Methanol extract of Dioscoreae Rhizoma inhibits pro-inflammatory cytokines and mediators in the synoviocytes of rheumatoid arthritis. 1535 18

BACKGROUND: Past studies suggested that tumor necrosis factor (TNF) assisted anti-tumor treatment and intensified the sensitivity of chemotherapy. However its clinical application has been curbed because of its low purity, high dosage, and strong toxicity. This research, through perspective random clinical control experiment, observed the therapeutic effect of the treatment of late malignant tumor through the injection of recombinant mutant human tumor necrosis factor (rmhTNF) combined with general chemotherapy and its adverse reactions. METHODS: 105 patients with advanced malignant tumor were randomly divided into trial group, 69 patients, and control group, 36 patients. Injection of rmhTNF 4 x 106u/m2 was given to the trial group, from the 1st to 7th days, the 11th to 17th days combined with chemotherapy course. The chemotherapy plan was as follows: CAP for patients with the NSCLC; FAM for patients with gastric cancer; FC for patients with colorectal cancer. One treatment cycle lasted for 21 days and two cycles were scheduled. The control group was given only the same chemotherapy as the trial group. RESULTS: In the trial group there was 1 CR case and 12 PR cases, and the response rate is 13/69 (18.84%); in the control group 1 PR case, the response rate 1/36 (2.78%). The response rate of the trial group was significantly higher than that of the control group (P = 0.022). The response rate for NSCLC in the trial group was 8/17 (47.06%), and 1/6 (16.67%) in the control group. The response rates for gastric cancer and colorectal cancer in the trial groups also were higher than those of the control groups. After the treatment the KPS is 89.00 +/- 9.92 in the trial group, and 84.17 +/- 8.84 in the control group, with a significant difference between the two groups (P = 0.028). The adverse reactions of rmhTNF injection included: pain in the injection area, chill, hardening and swelling and redness in the injection area, fever, ostealgia and myosalgia, and cold-like symptoms. All these adverse reactions were mild and bearable. CONCLUSIONS: The administration of rmhTNF injection in combination with general chemotherapy is an effective and secure means in treating advanced malignant tumor.
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PMID:The effect of chemotherapy combined with recombination mutant human tumor necrosis factor on advanced cancer. 1548 73

Cytokine release during surgery can produce a long-lasting hyperalgesia. Thus, preoperatively-administered cytokine inhibitors might reduce the production of cytokines, decreasing central nervous system sensitization and improving the quality of postoperative pain relief. We investigated the hypothesis that preincisional IV pentoxifylline (PTX) treatment could attenuate the release of proinflammatory (tumor necrosis factor, interleukin (IL)-1beta, IL-6, and IL-8) and antiinflammatory (IL-1 receptor antagonist) cytokines in patients who underwent elective colorectal cancer surgery. Forty patients were randomly assigned to 1 of 2 groups of 20 each: the PTX group received a PTX 5 mg/kg IV infusion before the induction of anesthesia, whereas the control group received an equal volume of normal saline. Venous blood samples were obtained at frequent intervals. After surgery, all patients received patient-controlled analgesia (PCA) morphine for postoperative pain relief. Patients in the PTX group exhibited longer PCA trigger times, less morphine consumption, and a faster return of bowel function compared with patients in the control group. Moreover, the plasma levels of IL-6, IL-8, and IL-1 receptor antagonist were less in the treatment group, and there was no significant difference in wound infections, tumor recurrence, or metastatic rates between groups during a 2-yr follow-up.
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PMID:Preincisional intravenous pentoxifylline attenuating perioperative cytokine response, reducing morphine consumption, and improving recovery of bowel function in patients undergoing colorectal cancer surgery. 1550 50

The pro-inflammatory cytokine tumor necrosis factor-alpha (TNF) contributes to injury-induced peripheral nerve pathology and to the development of neuropathic pain. Here, we investigated whether TNF protein is altered at the site of crush injury of rat sciatic nerve using enzyme-linked immunoassay (ELISA) and immunohistochemistry (IHC). TNF protein levels determined by ELISA were low in nerve homogenates from naive rats. After crush injury, local TNF increased rapidly with a two-fold increase on day 0.5. TNF content remained elevated on day 3 and returned to baseline levels again by day 14 after crush. IHC revealed prominent TNF-immunoreactivity in many epineurial macrophages on days 0.5 to 3 after crush injury. These data indicate that TNF protein is early and transiently upregulated at the site of peripheral nerve trauma.
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PMID:Wallerian degeneration after crush injury of rat sciatic nerve increases endo- and epineurial tumor necrosis factor-alpha protein. 1554 43

Venular microvascular circulation in patients with sickle cell anemia exhibits reduced and episodic blood flow. Sickle erythrocyte adhesion to postcapillary venule endothelium is postulated to initiate and propagate episodes of vasoocclusive pain. Hemodynamics likely mediate the adherence of sickle cells to endothelium, controlling delivery of potentially adherent erythrocytes and removal of loosely adherent erythrocytes on the endothelium. This study found a high dependence on shear stress of sickle erythrocyte adhesion to vascular cell adhesion molecule-1 (VCAM-1) on endothelium stimulated by tumor necrosis factor-alpha (TNF-alpha). Shear stress varied from 1.0 dyne/cm 2 (microvascular venular flow), in which VCAM-1 ligand interactions induced by TNF-alpha primarily controlled adherence, to 0.1 dyne/cm 2 (low flow), in which stimulation had little effect on adherence. At shear stresses analogous to in vivo velocities from laser Doppler ultrasound studies (0.8 and 0.6 dyne/cm 2 ), TNF-alpha promoted 1.9- and 2.7-fold increases in adhesion compared with unstimulated (baseline) adherence. These findings suggest a dynamic vasoocclusive process that depends on both receptor expression and shear stress. These results indicate that, in the microvasculature, slightly reduced inflow rate, increased receptor expression, or both may result in large increases in sickle erythrocyte adhesion.
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PMID:Sickle cell adhesion depends on hemodynamics and endothelial activation. 1557 Feb 44

Proinflammatory mediators, such as tumor necrosis factor (TNF) alpha, interleukin (IL)-1beta and IL-6 have been found to play a key role in the propagation of persistent pain states. We investigated the temporal expressions of the mRNAs and the receptor mRNAs of TNFalpha, IL-1beta and IL-6 in rat dorsal root ganglia and spinal cord in a chronic constriction injury model of neuropathic pain. Our results show that the maximal induction of IL-6 mRNA occurred later and was more sustained than those of TNFalpha and IL-1beta mRNAs in the dorsal root ganglia and spinal cord following chronic injury. Receptors mRNAs, except TNF receptor 2 and gp130 mRNAs, showed temporal profiles that were similar to those of their cytokine mRNAs. Additionally, the induction of the mRNAs of cytokines and of their receptors in the dorsal root ganglia was more rapid than in the spinal cord.
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PMID:Temporal expression of cytokines and their receptors mRNAs in a neuropathic pain model. 1559 59


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