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

Complex regional pain syndrome (CRPS) is a disabling disease characterized by the classic symptoms and signs of inflammation. In this study we investigated the innate cytokine profile in patients with CRPS to determine a possible role of the immune system in the pathophysiology of CRPS. The cytokine profile before and after lipopolysaccharide and thrombin stimulation was determined in 26 severely affected CRPS patients and 20 healthy controls. No difference in the production of pro- and anti- inflammatory cytokines between patients and controls was found. Hence, our results do not support a role of genetic factors responsible for the cytokine profile in the pathophysiology of CRPS. These findings encourage further investigations of mechanisms responsible for neurogenic-induced inflammation.
Pain 2001 Apr
PMID:Innate cytokine profile in patients with complex regional pain syndrome is normal. 1127 82

Perispinal (intrathecal) injection of the human immunodeficiency virus-1 (HIV-1) envelope glycoprotein gp120 creates exaggerated pain states. Decreases in response thresholds to both heat stimuli (thermal hyperalgesia) and light tactile stimuli (mechanical allodynia) are rapidly induced after gp120 administration. gp120 is the portion of HIV-1 that binds to and activates microglia and astrocytes. These glial cells have been proposed to be key mediators of gp120-induced hyperalgesia and allodynia because these pain changes are blocked by drugs thought to affect glial function preferentially. The aim of the present series of studies was to determine whether gp120-induced pain changes involve proinflammatory cytokines [interleukin-1beta (IL-1) and tumor necrosis factor-alpha (TNF-alpha)], substances released from activated glia. IL-1 and TNF antagonists each prevented gp120-induced pain changes. Intrathecal gp120 produced time-dependent, site-specific increases in TNF and IL-1 protein release into lumbosacral CSF; parallel cytokine increases in lumbar dorsal spinal cord were also observed. Intrathecal administration of fluorocitrate (a glial metabolic inhibitor), TNF antagonist, and IL-1 antagonist each blocked gp120-induced increases in spinal IL-1 protein. These results support the concept that activated glia in dorsal spinal cord can create exaggerated pain states via the release of proinflammatory cytokines.
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PMID:Intrathecal HIV-1 envelope glycoprotein gp120 induces enhanced pain states mediated by spinal cord proinflammatory cytokines. 1130 33

In a preliminary study the hypothesis was tested that cytokine profiles in peripheral blood were higher in women with deep infiltrating endometriosis and cytokine profiles in peritoneal fluid were higher in women with superficial endometriosis. Thirteen women of reproductive age having laparoscopy for infertility (n=9), pain (n=3) or combined pain and infertility (n=1). Peripheral blood and peritoneal fluid were obtained and analyzed for Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-alpha), Interleukin-10 (IL-10), Transforming Growth Factor-betal (TGFbeta1), and Interferon-gamma (IFN-gamma). No significant cytokine differences were observed in either peritoneal fluid or peripheral blood between IL-6, TGFbeta1, IFNgamma, TNF-alpha and IL-10 of women with superficial endometriosis (n=7) and women with deeply infiltrating endometriosis (n=6). The results of this preliminary study do not show significant differences in peripheral blood and peritoneal fluid cytokine levels between women with deep infiltrating endometriosis compared to women with superficial disease. Future studies with increased sample size are required to either confirm or refute these preliminary findings.
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PMID:Cytokine profiles in autologous peritoneal fluid and peripheral blood of women with deep and superficial endometriosis. 1132 93

The concept suggesting the involvement of the proinflammatory cytokine tumor necrosis factor (TNF)-alpha in the pathogenesis of rheumatoid arthritis (RA) has been demonstrated by several clinical trials targeting TNF-alpha. In addition to reduction of pain and swelling, a dramatic effect of TNF blocking therapies on the progression of joint destruction was shown. Nevertheless, complete remissions of the disease are rare even with these powerful therapeutic agents, and the optimal doses and dosage intervals of TNF blockers remain to be determined. Some insights into the pathogenesis of RA are provided by studying the effects of therapeutic TNF blockade on the biology of the disease. The fact that inflammation is not completely halted and destruction is ongoing in some patients suggests that other mechanisms may also be involved, including other cytokines such as interleukin-1 and interleukin-6. In addition to the necessity of understanding the pathogenic events proximal to TNF-alpha induction, pharmacologic intervention with small molecules in the TNF signaling pathways may constitute a promising strategy.
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PMID:One-year inhibition of tumor necrosis factor-alpha: a major success or a larger puzzle? 1133 50

It is known that prostaglandins (PGs) modify the inflammatory reaction in concert with other biologically active mediators. However, characteristics of these interactions or modulating actions have not yet been clarified well. Recently, the production of mice with specific receptor deficiencies by using the gene targeting procedure for PG receptors has accelerated elucidation of the roles of PGs through correlation of their phenotypes and experimental features. Here I discuss roles of PGs in experimental paw edema, the writhing reaction of a pain model, and regulation of cytokine production, as determined using some PG-receptor-deficient mice. From the experiment of carrageenin-induced paw edema in IP receptor-deficient mice, with an indomethacin or bradykinin antagonist, we conclude that bradykinin initially induces paw swelling and then stimulates the release PGI2, which in turn enhances the swelling with bradykinin. By comparing the writhing responses in IP-deficient and wild-type mice, we found that PGI2 is a main mediator for this pain reaction. However, in the LPS-pretreated mice, not only PGI2 but also other PGs produced by COX-2 may be involved in pain induction. Production of TNF alpha and IL-10 was modified with PGI2 or PGE2; the production of TNF alpha was down-regulated by the stimulation via IP-, EP2- or EP4 receptor, but that of IL-10 was up-regulated by these receptors, resulting in an anti-inflammatory effect.
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PMID:[Inflammation-allergy and prostanoids. (1). Prostanoids in experimental inflammatory reaction]. 1133 74

As the article in the current issue by Shinoda and colleagues shows, during the last two decades, there has been a dramatic increase in the understanding of basic biology behind chronic temporomandibular joint (TMJ) pain, inflammation and destruction. The involvement and contribution of cytokines to TMJ pain and inflammation must now be considered as established, evident and fundamental. Based on the present knowledge, it is now possible to design and investigate novel therapeutic strategies. These new and very encouraging approaches include manipulation of cytokine function, immune reactivity and the behaviour of inflammatory cells while maintaining the integrity of the affected tissue.
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PMID:Cytokines in temporomandibular joint arthritis. 1135 71

Cytokines may be pathophysiologically involved in hyperalgesia. Uncertainty exists about the types of cytokines and their site of action. To study the role of key pro- and anti-inflammatory cytokines in a chronic constriction model of neuropathic pain, mRNA expression of TNF, IL-1beta, IL-6, and IL-10 was quantified using competitive RT-PCR. Each cytokine mRNA in rat sciatic nerve was examined at days 3, 7, 14, and 45 after chronic constriction injury (CCI). We also undertook behavioral testing of these rats. Thermal warming and touch thresholds were significantly reduced at days 3, 7, and 14 in the CCI group, compared with the sham-operated group. Cytokine gene expression in sciatic nerve was significantly increased at day 7 for IL-1beta and IL-6 and at day 14 for TNF. Expression of IL-10 underwent a gradual and progressive increase, reaching statistical significance at day 45.
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PMID:Pro- and anti-inflammatory cytokine gene expression in rat sciatic nerve chronic constriction injury model of neuropathic pain. 1135 51

Aspirin is known to cause gastric injury and to delay ulcer healing. The effects of aspirin on gastric epithelial cell function are heterogeneous; in contrast to injuring the mucosa, aspirin may also act beneficially by inducing adaptation; a mechanism that is poorly understood. We aimed to document the effects of different doses of aspirin on gastric epithelial cell function defined as proliferation, and secretion as well as mRNA expression of cytokines. Furthermore, we studied the effects of aspirin pretreatment on cytokine secretion as a potential element of gastric adaptation. The proliferative activity of three different gastric epithelial cell lines (AGS, KATO III, RGM-1) was assessed by (3)H-thymidine incorporation; secretion of growth factors PDGF-AB and VEGF into culture supernatant was documented by ELISA. mRNA transcripts of both cytokines were quantified by real time RT-PCR. Low doses of aspirin did not alter the proliferative dynamics in two of the three studied cell lines; high doses abolished proliferation. Secretion of PDGF-AB and VEGF increased during the first days of low dose aspirin exposition; higher concentrations led to a depletion of cytokines after an initial liberation in the case of VEGF, mRNA of which was also dose-dependently increased by aspirin. Seven-day pretreatment with low amounts of aspirin did not alter the secretory response of the epithelia caused by higher doses of this drug. The secretion of cytokines and proliferation of gastric epithelial cells are adversely effected by aspirin in a similarly dose-dependent fashion as the intended effects of this drug on platelet function and pain relief.
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PMID:Aspirin effects on gastric epithelial cell proliferation and cytokine expression. 1137 96

We hypothesize that antigenic stimuli in susceptible persons during key developmental life stages alters neuroendocrine-immune organization and leads to the development of aberrant immune and neuroendocrine responses to subsequent environmental stressors, with longterm physical and psychological consequences. The release of interleukin-1beta (IL-1beta) and other proinflammatory cytokines associated with the immune response during times when individuals are most vulnerable to the effects of environmental influences activates the hypothalamic-pituitary-adrenal (HPA) axis and leads to maladaptive responses to subsequent stressors. The primed HPA axis is reactivated by proinflammatory cytokines, resulting in the secretion of corticotropin-releasing hormone (CRH) and cortisol, followed by physical and psychological effects that feedback on the HPA axis to produce an array of outcomes affecting general wellbeing. Through the release of histamine and other mediators and their effects on the mast cell-leukocyte cytokine cascade, immune stimuli in susceptible persons increase allergic inflammation and magnify stressors' effects through the release of HPA-axis-activating cytokines, such as IL-1beta, that drive the axis and reinforce the physiological and behavioral effects. Thus, specific proinflammatory cytokines and allergic reactions initiate, promote, and maintain immune-stimulus-associated HPA axis activity, and with CRH and cortisol, participate in a positive feedback loop, resulting in aberrant, maladaptive responses to physical or psychological stressors, with outcomes such as depression, hyperalgesia, and pain-related behavior.
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PMID:Immediate and longterm effects of immune stimulation: hypothesis linking the immune response to subsequent physical and psychological wellbeing. 1139 9

Pro-inflammatory cytokines have been shown to be involved in the genesis, persistence, and severity of neuropathic pain following nerve injury. The transcription factor, nuclear factor-kappa B (NF-kappaB), plays a pivotal role in regulating pro-inflammatory cytokine gene expression. To elucidate the role of NF-kappaB in the pathogenesis of neuropathic pain, using a gene-based approach of NF-kappaB decoy, we tested whether the activated NF-kappaB affected pain behavior via the expression of inflammatory mediators. Single endoneurial injections of NF-kappaB decoy, at the site of nerve lesion, significantly alleviated thermal hyperalgesia for up to 2 weeks and suppressed the expression of mRNA of the inflammatory cytokines, iNOS, and adhesion molecules at the site of nerve injury. This finding suggests that a perineural inflammatory cascade, that involves NF-kappaB, is involved in the pathogenesis of neuropathic pain.
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PMID:NF-kappa B decoy suppresses cytokine expression and thermal hyperalgesia in a rat neuropathic pain model. 1144 11


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