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

A new model of chronic hypersensitivity was developed in the rat by daily intraplantar administration of either prostaglandin E2 dopamine or isoprenaline, for a period of 2 weeks. Like other hyperalgesic mediators, dibutyryl-cAMP, when applied to the paws, caused an acute effect but did not produce persistent hypersensitivity. The persistent hypersensitive state was not affected by a typical non-steroidal anti-inflammatory drug (indomethacin), was temporarily inhibited by a centrally acting analgesic (morphine), was partially inhibited by a protein synthesis inhibitor (cycloheximide) and abolished by a single dose of peripherally acting analgesics such as dipyrone or N-methyl morphine. Once the residual hypersensitivity had been abolished with dipyrone or N-methyl morphine, a small dose of prostaglandin E2, dopamine or Interleukin-1 beta, which in normal animals causes a mild and short lived effect, restored the persistent hypersensitive state. This ability to restore the persistent effect was not observed with intraplantar administration of dibutyryl-cAMP. Our results suggest the existence of a peripheral trace of inflammatory pain, a phenomenon which may be associated with stimulation of neuronal adenylate cyclase and protein synthesis. This concept may explain part of the puzzle of chronic inflammatory pain and lead to the development of new analgesics.
Pain 1990 Sep
PMID:Induction, blockade and restoration of a persistent hypersensitive state. 217 28

Processes occurring within the immune system can alter neural function. Cytokines released by cells of the immune system during illness are key messengers in immune-to-brain communication. Interleukin-1 beta (IL-1 beta) is particularly important in this regard and is known to stimulate a myriad of illness-related outcomes such as fever, sickness behavior, aphagia, adipsia, hypothalamic-pituitary-adrenal activation, and changes in pain reactivity. Thus peripherally released IL-1 beta has potent neural effects and is a critical mediator of the impact of immune processes on brain. There is, however, uncertainty concerning the communication pathways involved. We provide evidence that a primary route of peripheral cytokine signalling is through stimulation of peripheral vagal afferents rather than or in addition to direct cytokine access to brain. Subdiaphragmatic, but not hepatic vagotomy, blocked rhIL-1 beta-induced hypothalamic norepinephrine depletion and attenuated rhIL-1 beta-induced increases in serum corticosterone. These data suggest that rhIL-1 beta activates the hypothalamic-pituitary-adrenal axis via stimulation of peripheral vagal afferents and further support the hypothesis that peripheral cytokine signalling to the CNS is mediated primarily by stimulation of peripheral afferents.
 ...
PMID:Interleukin-1 beta induced corticosterone elevation and hypothalamic NE depletion is vagally mediated. 767 Aug 84

Agents which induce symptoms of illness, such as lipopolysaccharide (LPS), cause diverse effects including hyperalgesia. While previous studies have examined central pathways mediating LPS hyperalgesia, the initial steps in activating this system remain unknown. Since LPS induces the release of various cytokines and eicosinoids from immune cells, the present series of experiments examined the potential involvement of these substances in LPS hyperalgesia. This work demonstrates that: (a) Interleukin-1 beta (IL-1 beta) can produce hyperalgesia following either intraperitoneal or intracerebroventricular injection. In contrast, IL-1 beta delivered intrathecally did not affect pain responsivity. (b) Liver macrophages (Kupffer cells) appear to be critically involved, and relay signals to the brain via hepatic vagal afferents. (c) Both IL-1 beta and tumor necrosis factor appear to be critical mediators of LPS hyperalgesia. In contrast, prostaglandins do not appear to be involved. Taken together, these studies suggest that substances classically thought of as products of the immune system may dynamically enhance pain responsivity via actions either on the hepatic vagus or at central sites.
 ...
PMID:Characterization of cytokine-induced hyperalgesia. 798 88

Interleukin-1 beta (IL-1 beta) and Tumour Necrosis Factor-alpha (TNF-alpha) exert their multifunctional biological effect by promoting and increasing the molecular events of cellular inflammation. The aim of this study was to find out whether the cytokine pattern of cervicogenic headache (CH) patients tends, like that seen in cluster headache, towards an inflammatory status. Fifteen CH patients, diagnosed according to the 1998 CHISG criteria, were analysed for serum IL-beta (ELISA) and TNF-alpha (bioassay and ELISA) both during the natural course of a painful attack and during a phase of mechanically worsened pain. The control groups consisted of 15 migraine without aura (MWA) patients and 15 historically healthy subjects. The MWA patients were studied both during (MWA-IN) and outside (MWA-OUT) a migraine attack. Higher levels of both IL-1 beta and TNF-alpha were detected in the sera of CH patients than in that of MWA-IN and MWA-OUT and C subjects. A difference also emerged in CH between spontaneous and mechanically worsened pain phases. We conclude that the degree of cytokine production may depend on the different pathophysiological mechanisms at work in MWA and CH.
 ...
PMID:Proinflammatory cytokines in cervicogenic headache. 1056 17

Cervicogenic headache (CEH) is a relatively common form of headache arising from the neck structures. The pathophysiology probably results from various local pain-producing factors such as intervertebral dysfunction, with a no less important role played by the frequent coexistence of a history of head traumas. This report represents a series of pathophysiological studies in CEH patients and the results achieved by pharmacological treatment of the disease. Interleukin-1 beta (IL-1 beta) and Tumour Necrosis Factor alpha (TNF-alpha) exert their multifunctional biological effects by promoting and increasing the molecular events of cellular inflammation. We found that the cytokine pattern of CEH patients is--similar to cluster headache--biased towards an inflammatory status. Higher levels of both IL-1 beta and TNF-alpha were detected in the sera of CEH patients than the levels in patients with migraine without aura and in healthy subjects. There were also differences between the spontaneous and mechanically worsened pain phases of CEH. Nitric oxide (NO) synthase is also activated in cervicogenic headache. No change in NO metabolites levels has been observed after NO donor administration. This behaviour is clearly different from that observed in migraine and tension headache patients. We conclude that the high degree of cytokine and NO production in CH may depend on the differing pathophysiological mechanisms at work in CEH than in other forms of headache.
 ...
PMID:Proinflammatory pathways in cervicogenic headache. 1082 85

Inflammation in the subacromial bursa causes pain in patients suffering from rotator cuff tear, with this long-lasting inflammation leading to fibrosis and thickening of the subacromial bursa. Both inflammatory cytokines and mechanical stress, and impingement in the subacromial space, might induce and worsen this inflammation. However, little is known of the mechanism of this inflammation. In this study, we used immunohistological staining to demonstrate the expression of Interleukin-1 beta (IL-1 beta), Tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta), and basic fibroblast growth factor (bFGF) in subacromial bursa derived from the patients suffering from rotator cuff tear. On the other hand the expression of these inflammatory cytokines and growth factors were little detected only to a small degree in patients with anterior shoulder instability who did not have severe shoulder pain and impingement in the subacromial space. Our findings suggest that those inflammatory cytokines and growth factors may play an important role in inflammation of the subacromial bursa. Controlling the expression of these cytokines and growth factors might be important for treating patients suffering from shoulder pain due to rotator cuff tear.
 ...
PMID:Immunolocalization of cytokines and growth factors in subacromial bursa of rotator cuff tear patients. 1156 92

Orofacial pain frequently originates from pathologic conditions in the masticatory muscles or temporomandibular joints (TMJs). The mediators and mechanisms that monitor pain and inflammation, centrally or peripherally, are of great interest in the search for new treatment modalities. The neuropeptides substance P (SP), calcitonin gene-related peptide (CGRP), and neuropeptide Y (NPY) have all been found at high levels in the synovial fluid of arthritic TMJs in association with spontaneous pain, while serotonin (5-HT) has been found in association with hyperalgesia/allodynia of the TMJ. Interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) have been found in arthritic TMJs, but not in healthy TMJs, in association with hyperalgesia/allodynia of the TMJ as well as spontaneous pain. Anterior open bite, which may be a clinical sign of TMJ destruction, has been found in association with high levels of CGRP, NPY, and IL-1 beta in the synovial fluid of the TMJ. Interleukin-1 beta has also been related to radiographic signs of joint destruction. Prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) are both present in the arthritic TMJ, and PGE2 has been shown to be associated with hyperalgesia/allodynia of the TMJ. Very little is known about pain and inflammatory mediators in muscles. However, we know that 5-HT and PGE2 are involved in the development of pain and hyperalgesia/allodynia of the masseter muscle in patients with fibromyalgia, whereas local myalgia (myofascial pain) seems to be modulated by other, as yet unknown mediators. Interaction between the peripheral nervous system (sensory and sympathetic nerves), the immune system, and local cells is probably of great importance for the modulation of pain and inflammation in the TMJ and orofacial musculature.
J Orofac Pain 2001
PMID:Neuroendocrine, immune, and local responses related to temporomandibular disorders. 1188 48

Intervertebral disc disease (IDD) characterized by sciatica is a common disorder affecting about 5% of individuals. Environmental factors can predispose to this disease, but IDD has a strong genetic background. Recent evidence suggests that inflammation is one of the key factors in the etiology of IDD. Here, a possible role of the inflammatory mediator genes was studied in 155 patients with IDD-related sciatica and 179 controls. Forty-eight patients were analyzed for mutations in the IL1A, IL1B, IL6 and TNFA genes, and 16 polymorphisms in 10 candidate cytokine genes (IL1A, IL1B, IL1RN, TNFA, IL2, IL4, IL4R, IL6, IL10, IFNG) were genotyped from all subjects. No disease-causing mutations were identified in IL1A, IL1B, IL6 or TNFA. Allele frequencies were, however, significantly different between the two groups for IL6 SNP, T15A in exon 5 (P=0.007). Furthermore, the genotypes AA and AT of the exon 5 SNP were more common in the patients (P=0.011; OR=4.4, 95% CI=1.2-15.7; AR=7.5%, 1.6-13.1%). Haplotypes were then generated for four IL6 SNPs, G-597A, G-572C, G-174C, and T15A in exon 5. Haplotype GGGA was more common in the patients (P=0.011; OR=4.8, 95% CI=1.6-14.5). To evaluate attributable risk, haplotype pairs were assigned for the individuals. The presence of GGGA/GGGA or GGGA/other genotypes had an OR of 5.4 (95% CI=1.5-19.2). Association of GGGA with disease was highly significant (P=0.0033), and the associated AR was 6.8% (1.9-11.5%). These findings support the role of IL-6 genetic variations in discogenic pain.
Pain 2005 Mar
PMID:Genetic variations in IL6 associate with intervertebral disc disease characterized by sciatica. 1573 44

Interleukin-1 beta (IL-1beta) and its endogenous IL-1 receptor antagonist (IL-1Ra) play an important role in inflammatory response and in pain modulation. It has recently been shown that polymorphism of the IL-1beta and IL-1Ra genes may account for variation in the production of these cytokines. The present study examined the hypothesis that polymorphism of IL-1beta and IL-1Ra genes is involved in pain sensitivity and morphine consumption in the immediate postoperative period. Genetic polymorphism was determined in 76 women undergoing transabdominal hysterectomy. The genotype of IL-1Ra was determined using PCR amplification of the variable number of tandem repeats (VNTR) of 86 base pair (bp) in intron 2, while for IL-1beta the cytosine to thymine transition at codon -511 of the promoter was determined by PCR. Morphine consumption and pain scores were evaluated in the first postoperative 24 h. The study group was divided based on morphine consumption to three sub-groups: low morphine consumers (LMC) (<28 mg/24 h), medium morphine consumers (MMC) (28-38 mg/24 h), and high morphine consumers (HMC) (>38 mg/24 h). Patients consuming the least amount of morphine postoperatively showed significant lower pain scores. IL-1Ra genetic polymorphism of the MMC group was significantly different compared to the other two groups. No difference in IL-1beta gene polymorphism was found among the three sub-groups. Since IL-1Ra polymorphism is known to affect the levels of both IL-1Ra and IL-1, cytokines associated with modulation of pain sensitivity and morphine analgesia, it is suggested that IL-1Ra genetic polymorphism may contribute to the variation in postoperative morphine consumption.
 ...
PMID:Postoperative pain, morphine consumption, and genetic polymorphism of IL-1beta and IL-1 receptor antagonist. 1677 24

Interleukin-1 beta (IL1) and tumor necrosis factor alpha (TNF) promote non-rapid eye movement sleep under physiological and inflammatory conditions. Additional cytokines are also likely involved but evidence is insufficient to conclude that they are sleep regulatory substances. Many of the symptoms induced by sleep loss, e.g. sleepiness, fatigue, poor cognition, enhanced sensitivity to pain, can be elicited by injection of exogenous IL1 or TNF. We propose that ATP, released during neurotransmission, acting via purine P2 receptors on glia releases IL1 and TNF. This mechanism may provide the means by which the brain keeps track of prior usage history. IL1 and TNF in turn act on neurons to change their intrinsic properties and thereby change input-output properties (i.e. state shift) of the local network involved. Direct evidence indicates that cortical columns oscillate between states, one of which shares properties with organism sleep. We conclude that sleep is a local use-dependent process influenced by cytokines and their effector molecules such as nitric oxide, prostaglandins and adenosine.
 ...
PMID:The role of cytokines in sleep regulation. 1907 17


1 2 3 Next >>