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

Recent studies demonstrate that activation of proinflammatory cytokines following injury intensifies the process of nociception. The present investigation assessed the influence of pre-injury pentoxifiline (PTFL, a non-specific cytokine inhibitor) on the development of post-injury nociception in animals and patients. It was established that intrathecal or intraperitoneal PTFL, elevated the nociceptive threshold for mechanical stimuli in the formalin test in rats. Pre-injury PTFL also inhibited pain-related behaviour. These findings correlate with a lower TNFalpha level in the serum of animals receiving pre-injury PTFL. In clinical investigations PTFL was administered intravenously before elective cholecystectomy. Patients who received preoperative PTFL had lower opioid requirements in the early postoperative period than control. At the same time, serum levels of TNFalpha and IL6 were lower in the PTFL group. Our results confirm the hypothesis as to the possibility of modulating of nociception through preemptive administration of a cytokine inhibitor.
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PMID:The effect of pentoxifiline on post-injury hyperalgesia in rats and postoperative pain in patients. 1073 66

Inflammation or injury often lead to chronic pain states such as hyperalgesia where the perception of a normally painful stimulus is significantly exaggerated. Interleukin-1beta (IL-1beta) is a cytokine that is an important mediator of the inflammatory response. In addition, IL-1beta has been implicated in the modulation of pain transmission in both the peripheral and central nervous systems. We evaluated the spinal effect of this cytokine in the presence and absence of a peripheral carrageenan inflammation in rats since the spinal cord is a major region of the central nervous system in which nociceptive input is processed and modulated. Our results indicate that intrathecal IL-1beta has no effect on the latency of paw withdrawal in response to a noxious thermal stimuluation in normal rats. In contrast, we have observed that IL-1beta produces significant antinociception when administered intrathecally in rats with peripheral inflammation (carrageenan model). The IL-1beta effect appears to be selective as it is reversed when IL-1beta is administered in the presence of an IL-1beta neutralizing antibody. We evaluated some putative mechanisms of this IL-1beta-mediated antinociception and found it to be non-opioid-dependent. Collectively, these data indicate that intrathecal IL-1beta has no effect on the processing of thermal nociceptive information in the absence of a peripheral inflammation. Therefore, the response to acute pain remains normal in these rats. In contrast, IL-1beta is antinociceptive when applied spinally during inflammation. These results indicate that IL-1beta reduces inflammatory hyperalgesia while sparing the protective functions of acute pain. This study offers new insights into the role of IL-1beta and nociceptive processing at the level of the spinal cord and suggests that development of IL-1beta agonists may be an alternative to opiate based therapies in the treatment of inflammatory pain.
Pain 2000 May
PMID:Spinal interleukin-1beta reduces inflammatory pain. 1077 61

Adrenal medullary tissue including chromaffin cells was grafted intrathecally in cancer patients to relieve intractable pain. The central nervous system (CNS) is considered an immune privileged site. Therefore, non-HLA-matched and unencapsulated tissue was grafted in 15 patients and 1 sham control in a series of at least 20 grafts. We observed an increase in CSF lymphocyte counts in 15/20 allografts (75%). In contrast to peripheral blood, CD4 T cells predominated in the CSF, but failed to exhibit an activated phenotype (CD25+ CD45RO+ HLA-DR+). The positive effect of graft on pain, the high met-enkephalin levels, the absence of any increase in CSF cytokine levels particularly for IFN-gamma or IL-2 (but not IL-10 and IL-6), indirectly indicated that the graft was tolerated despite the presence of CSF lymphocytes. The single treatment failure and three of four cases of partial efficacy occurred in grafts where CSF lymphocytes were present. Moreover, when assayed (n = 7), the CD4+ CSF lymphocytes still retained the capacity to exhibit ex vivo a normal or enhanced frequency of T CD4 cells producing IFN-gamma and IL-2. Taken together, our observations indicate that impairment of the local immunosuppressive balance can lead to activation of those CSF CD4 T cells and drive a rejection process. This study suggests further work on the purification and/or the immunoisolation of tissues grafted in the CNS will be necessary, particularly when the possibility of long-term and repeated grafting is considered.
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PMID:Intrathecal grafting of unencapsulated adrenal medullary tissue can bring CD4 T lymphocytes into CSF: a potentially deleterious event for the graft. 1078 70

Evidence for the role of the cannabimimetic fatty acid derivatives (CFADs), i.e. anandamide (arachidonoylethanolamide, AEA), 2-arachidonoylglycerol (2-AG) and palmitoylethanolamide (PEA), in the control of inflammation and of the proliferation of tumor cells is reviewed here. The biosynthesis of AEA, PEA, or 2-AG can be induced by stimulation with either Ca(2+) ionophores, lipopolysaccharide, or platelet activating factor in macrophages, and by ionomycin or antigen challenge in rat basophilic leukemia (RBL-2H3) cells (a widely used model for mast cells). These cells also inactivate CFADs through re-uptake and/or hydrolysis and/or esterification processes. AEA and PEA modulate cytokine and/or arachidonate release from macrophages in vitro, regulate serotonin secretion from RBL-2H3 cells, and are analgesic in some animal models of inflammatory pain. However, the involvement of endogenous CFADs and cannabinoid CB(1) and CB(2) receptors in these effects is still controversial. In human breast and prostate cancer cells, AEA and 2-AG, but not PEA, potently inhibit prolactin and/or nerve growth factor (NGF)-induced cell proliferation. Vanillyl-derivatives of anandamide, such as olvanil and arvanil, exhibit even higher anti-proliferative activity. These effects are due to suppression of the levels of the 100 kDa prolactin receptor or of the high affinity NGF receptors (trk), are mediated by CB(1)-like cannabinoid receptors, and are enhanced by other CFADs. Inhibition of adenylyl cyclase and activation of mitogen-activated protein kinase underlie the anti-mitogenic actions of AEA. The possibility that CFADs act as local inhibitors of the proliferation of human breast cancer is discussed here.
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PMID:Cannabimimetic fatty acid derivatives in cancer and inflammation. 1078 41

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.
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PMID:Proinflammatory pathways in cervicogenic headache. 1082 85

Inflammatory signs, such as heat, redness, swelling and pain, have been described from the Greek era. In these phenomena various endogenous active substances, i.e., inflammatory mediators, could cause and manifest vascular dilatation, a vascular permeability increase and sensitization of pain receptors, etc. In order to evaluate the roles of inflammatory mediators, we have studied the time courses of inflammatory reaction along with detection of various active substances directly or indirectly in the experimental animal model of pleurisy, such as rat carrageenin-induced, and zymosan-induced pleurisy. These pleurisies showed almost similar time courses of pleural exudate accumulation and neutrophil migration. However, mediators detected in the exudates of such pleurisies were different; in carrageenin-induced pleurisy bradykinin and prostacyclin (PGI2) caused exudate formation, while zymosan-induced pleurisy showed early degradation of mast cells and activation of complements, followed by an increase in platelet activating factor (PAF). In both pleurisies TNF alpha, IL-1, IL-6 and CINC (cytokine-induced neutrophil chemoattractant) appeared similarly in the exudates to cause chemoattractant for neutrophils. TNF alpha and IL-1 could stimulate to produce IL-6 and IL-8. While prostaglandins may regulate cytokine production via a cellular cAMP-dependent mechanism. Thus one should consider the time for application of anti-inflammatory drugs, such as cyclooxygenase inhibitor, indomethacin, since it causes increases in TNF alpha and IL-1 production by reducing PGI2 and prostaglandin E2 (PGE2) levels. In conclusion, inflammatory reaction has its own automatic regulation mechanism through complex cross talks between inflammatory mediators.
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PMID:[Evaluation of time course and inter-relationship of inflammatory mediators in experimental inflammatory reaction]. 1082 9

The assessment of overall health status of a child with juvenile rheumatoid arthritis (JRA) is complex and multi-dimensional. The general physical examination is complemented by a rheumatological evaluation that includes determination of articular indices of inflammation and duration of inactivity stiffness. Laboratory assessment plays a critical role in monitoring side effects of pharmacologic management, but is limited in its ability to portray accurately the degree of active inflammation. Newly measureable indicators of inflammatory activity, such as serum cytokine and soluble cytokine receptors will likely become part of routine laboratory assessment in the future. Radiographs remain a useful tool for assessing disease progression, but may be replaced in the future by magnetic resonance imaging. In recent years, rheumatologists have realized that measurement of overall physical and psycho-social functional ability, quality of life, and pain are major descriptors to consider during routine follow-up. They are also critical in the assessment of long-term clinical effectiveness. The importance of nutritional assessment has also been realized. This section seeks to describe some of the methodologic approaches currently used to assess the variables mentioned above, and includes a brief discussion of the evolving instrumentation which attempts to measure variables of a more cognitive or subjective aspect.
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PMID:Juvenile rheumatoid arthritis--assessment. 1083 3

Objective: The objective of this single-center, open-label trial was to evaluate the percutaneous penetration of Aldara (imiquimod) cream, 5% when applied topically to patients with anogenital warts using a more frequent/aggressive dosing regimen.Methods: Ten otherwise healthy males and six otherwise healthy, nonpregnant, nonlactating females with histology results suggestive of, or diagnostic of, human papilloma virus/condyloma acuminata were enrolled. Females were required to be practicing an acceptable form of contraception control. Patients applied cream daily (8 +/- 2 hours) until complete wart clearance, or for a maximum of 16 weeks. Following the initial dose, at approximately week 4, and at the end-of-treatment, patients were confined for 42 hours in order to obtain a series of blood and urine samples. These samples were analyzed for levels of imiquimod and two metabolites, S-26704 and S-27700. Biological marker levels were not included as a part of this trial.Results: No quantifiable (>/=5 ng/mL) levels of imiquimod or the two metabolites were observed in any of the serum samples collected. Five patients had quantifiable (>/=10 ng/mL) imiquimod, S-26704, or both in urine. No quantifiable levels of S-27700 were observed. Complete clearance of warts occurred in 40% of male patients and 83% of female patients. Erythema was the most frequently observed local skin reaction and was moderate in intensity, although 6 of 16 patients reported a severe erythema reaction at some point in the study. Application site reactions (itching, burning and pain) were the most frequently reported adverse events.Conclusion: The lack of quantifiable levels of imiquimod or metabolites in serum, together with sporadically occurring quantifiable but low levels in urine, indicate that systemic exposure, after daily application of Aldara cream to genital/perianal skin, may occur but is minimal; however, pharmacological (immune marker) effects were not evaluated because cytokine measurements were not obtained. A future trial assessing cytokine levels after topical Aldara therapy with minimal systemic levels of imiquimod would help assess systemic drug and pharmacological effects and utility of this product in pregnant women.
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PMID:Percutaneous penetration of Aldara cream, 5% during the topical treatment of genital and perianal warts. 1083 79

Several independent pathophysiological mechanisms in both the peripheral and central nervous system are responsible for sensory symptoms as well as spontaneous and evoked pains in peripheral neuropathies: (1) Pathologic active or sensitized nociceptors can induce secondary changes in central processing, leading to spinal cord hyperexcitability that causes input from mechanoreceptive Abeta-fibers (light touching) to be perceived as pain. These patients characteristically have spontaneous pain, heat hyperalgesia, static mechanical allodynia, and and severe dynamic mechanical allodynia. (2) Nociceptor function may be selectively impaired within the allodynic skin. Pain and temperature sensation are profoundly impaired but light moving mechanical stimuli can often produce severe pain (dynamic mechanical allodynia). Anatomic reorganization in the dorsal horn resulting from C-fiber degeneration may lead to Abeta-fiber-mediated allodynia. (3) Persistent inflammatory reactions of the nerve trunk can induce ectopic activity in primary afferent nociceptors and thus is a potential cause of spontaneous pain and allodynia. This effect is mediated by the cytokine tumor necrosis factor-alpha produced by activated macrophages. (4) After nerve lesion the sympathetic nervous system might interact with afferent neurons. Activity in sympathetic fibers can induce further activity in sensitized nociceptors and, therefore, enhance pain and allodynia (sympathetically maintained pain). This pathologic interaction acts via noradrenaline released from sympathetic terminals and newly expressed receptors on the afferent neuron membrane. These mechanisms can operate in concert in a single disease entity (e.g., postherpetic neuralgia) and also in a single patient. Distinct pathophysiological mechanisms lead to specific sensory symptoms (e.g., dynamic mechanical allodynia, cold hyperalgesia). It is also possible that the pain-generating mechanism and the symptoms change during the course of the disease. A thorough analysis of sensory symptoms may, reveal the underlying mechanisms that are mainly active in a particular patient. The treatment of neuropathic pain is currently unsatisfactory. In the future, drugs will be developed that address specifically the relevant combination of mechanisms.
Clin J Pain 2000 Jun
PMID:Peripheral neuropathic pain: from mechanisms to symptoms. 1087 Jul 35

Interleukin-1 (IL-1) beta is a proinflammatory cytokine that is produced by a large variety of cells, including macrophages, fibroblasts, mesangial cells and endothelial cells, and is believed to play important roles in the inflammatory responses, including hyperalgesia. Hyperalgesia is characterized by intensified pain with a reduced threshold to somatic stimulation, and it is involved in chronic inflammatory disease. Substance P (SP), an undecapeptide, has been shown to relay noxious signals as a neurotransmitter in primary afferent neurons. Thus it is expected that the change of neuropeptide activities in primary afferent neurons is attributed to inflammatory hyperalgesia by IL-1 beta. In our recent studies, IL-1 beta was found to stimulate SP release from cultured dorsal root ganglion cells via the cyclooxygenase system. These studies provide a new insight in the neural-immune intercommunication involved in the pain-regulation system observed in inflammation-induced hyperalgesia.
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PMID:[Neural-immune interactions in dorsal root ganglia]. 1087 6


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