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

We investigated, in a well-established canine model of human sepsis, the effects of two different techniques of sympathetic blockade during bacterial peritonitis on pain relief, hemodynamics, and survival rate. Twenty-two purpose-bred beagles (12-28 months old, weighing 10-12 kg) were studied. Fourteen animals received an epidural infusion of bupivicaine and morphine, and the other eight received either a celiac plexus block (n = 4) or a sham block (n = 4). Eighteen of the 22 animals received an intraperitoneal challenge of Escherichia coli (1-10 x 10(9) CFU kg(-1) body weight). At comparable doses of intraperitoneal-implanted E. coli (2.5-5 x 10(9) CFU kg(-1) body weight), the addition of sympathetic blockade produced a synergistic decrease in survival times (P = 0.002) and mean left ventricular ejection fraction (P = 0.008), and increase in creatinine levels (P = 0.02). There was also a significant increase in tumor necrosis factor (TNF) levels (P = 0.004) and decrease in blood endotoxin clearance (P = 0.006) associated with sympathetic blockade during sepsis. The celiac plexus-blocked animals had no improvement in pain scores, and subjectively looked clinically worse than animals with sepsis without a celiac plexus block. In contrast, the epidural block was effective in blocking the pain and discomfort associated with low lethality doses of intraperitoneal bacteria reflected by no increase in pain scores compared with animals not receiving bacterial challenge. This study shows that during severe bacterial peritonitis, maintenance of sympathetic tone irrespective of pain relief provided is necessary for clearance of bacterial toxins, control of proinflammatory mediator release, hemodynamic stability, and survival.
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PMID:Sympathetic blockade in a canine model of gram-negative bacterial peritonitis. 1263 May 20

Recent advancements in the pain field have identified a central nervous system (CNS) neuroimmune response that may act as the driving force for neuronal hypersensitivity, the pathological correlate to chronic pain following peripheral nerve injury. Neuroimmune activation involves the activation of nonneuronal cells such as endothelial and glial cells, which when stimulated leads to enhanced production of a host of inflammatory mediators, such as cytokines. The central production of proinflammatory cytokines, such as interleukin-1beta (IL-1beta), IL-6 and tumor necrosis factor have been found to play a key role in the propagation of persistent pain states. In addition, chemotactic cytokines, chemokines, have also been recently identified in the CNS neuroimmune cascade that ensues after injury to a peripheral nerve. The extravasation of leukocytes from the blood to the site of perceived injury is defined as the neuroinflammatory aspect of this cascade. Chemokines directly control this leukocyte transmigration process. They are synthesized at the site of injury and establish a concentration gradient through which immune cells migrate. Recent studies have demonstrated leukocyte trafficking into the CNS following peripheral nerve or lumbar nerve root injury. With the use of selective cytokine inhibitors and neutralizing antibodies, tactile and thermal hypersensitivity is attenuated in animal models of neuropathy. A further understanding of the role of nonneuronal cells, the physiological mechanisms of CNS cytokines and chemokines, and their relevance to neuro- immune activation and neuroinflammatory processes may lead to the development of novel pharmacological agents for the treatment and prevention of chronic pain. (c) 2002 Prous Science. All rights reserved.
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PMID:The Role of Cytokines in the Initiation and Maintenance of Chronic Pain. 1267 47

Proinflammatory cytokines are supposed to play a major role in the pathophysiology of vasculitis and in the development of neuropathic pain. Here we studied the cytokine expression in sural nerve biopsy specimens from patients with vasculitic and other inflammatory and non-inflammatory neuropathies, and investigated whether an increased cytokine expression was correlated with the presence of neuropathic pain. We used immunohistochemistry including double labeling and morphometry to localize and quantify the expression of interleukin-1 beta (IL-1beta), IL-6, and tumor necrosis factor-alpha (TNF) in sural nerve biopsy samples of 41 patients with vasculitic neuropathy (VANP), chronic inflammatory demyelinating neuropathy (CIDP), non-inflammatory chronic axonal neuropathy (CANP), and 3 controls. Overall cytokine immunoreactivity was highest in VANP, less strong in CIDP and lowest in CANP. Cytokine immunoreactivity was directly correlated with the degree of axonal degeneration, endoneurial macrophages and epineurial T cells. In VANP and CANP, a higher cytokine content was associated with neuropathic pain.
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PMID:Cytokines in sural nerve biopsies from inflammatory and non-inflammatory neuropathies. 1273 66

Sepsis is the leading cause of death in non-coronary intensive care unit patients. Sepsis is caused by the immune response to infection and is manifest by pain, fever and edema as the result of the activation of coagulation and inflammatory responses. In severe cases, sepsis leads to organ dysfunction and failure. Sepsis affects more than 750,000 people each year in the US alone, with a mortality rate of over 35 percent making it one of the leading causes of death in developed countries. In addition many patients that die of other diseases have their hospital courses complicated by sepsis. Most patients with infection do not develop severe sepsis and septic shock and yet those that do have a significantly increased risk of death. Genetic and environmental variables may influence why one patient with infection gets sicker than the next. For example, people may be programmed to respond to infection in different ways; some with aggressive immune responses that may be able to wipe out infection before it manifests itself in physical symptoms, while others may have less aggressive immune systems that allow them to get sick more often. The discovery of various common genetic polymorphisms in genes that control the inflammatory response (e.g. tumor necrosis factor) has lent credence to this hypothesis. Yet discovery of the actual relationship between risks of infection / severe sepsis and individual genotypes will require larger, more rigorously designed studies.
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PMID:Genetic variation and risk of sepsis. 1276 15

Cytokines such as IL-1beta, IL-6 and tumor necrosis factor-alpha (TNF-alpha) have been shown to contribute directly to central and peripheral neuropathic pain. Recently, exogenous interleukin-10 (IL-10) was shown to impede development of dynorphin-induced allodynia presumably by inhibiting IL-1beta. We therefore wanted to determine whether endogenous IL-10 had a role in pain perception. By measuring the latency of the paw licking response, we show in IL-10 knockout mice and in normal mice treated with anti-IL-10 that latency times are increased, suggesting that endogenous IL-10 increases nociception. This does not appear to be directly correlated with IL-10's regulation of DREAM, a transcriptional regulator of prodynorphin synthesis.
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PMID:Evidence for endogenous interleukin-10 during nociception. 1279 32

When pain becomes chronic this is a process that takes place at several levels of the peripheral and central nervous systems. In recent years, proinflammatory substances like bradykinin, prostaglandins and signal molecules like cytokines have been identified as allogenic factors. In the present paper we examined whether cytokines play a role also in non-inflammatory peripheral nerve lesions, i.e. whether they are of importance in the causation of pain in general and whether their antagonists can be used therapeutically. The development of pain after peripheral nerve lesion in animal models follows the process of Wallerian degeneration. During Wallerian degeneration the expression of proinflammatory cytokines in the nerve is upregulated. Here we studied the temporal course of cytokine expression with several different analytical methods, analyzing tumor necrosis factor-alpha (TNF) and interleukin-beta (IL-beta) in the mouse model of chronic constrictive injury (CCI) of the sciatic nerve. This model is associated with reproducible pain related behavior in the animals. We found an early increase of TNF 12 hours after injury. Neutralizing antibodies to TNF were able to reduce the hyperalgesia that evolved due to the nerve injury. As TNF exerts its effects via two receptors, TNF receptor 1 (TNF-R1) and TNF receptor 2 (TNF R2), we also investigated, which of the receptors is relevant to the causation of pain in this model. It turned out that antibodies to TNF-R1, but not to TNF-R2 reduced hyperalgesia, indicating that TNF-R1 is the receptor concerned. Neutralizing antibodies to IL-1 receptor and to IL-6 receptor also reduced pain related behavior. These results lead to the conclusion that proinflammatory cytokines are involved not only in inflammatory pain but also in neuropathic pain. Therapeutic strategies involving cytokine inhibition have been tested experimentally and are already being used in preliminary clinical studies in immune-mediated diseases. In the future, they might be a useful addition to the range of treatments for patients with neuropathic pain.
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PMID:[Animal studies on neuropathic pain: the role of cytokines and cytokine receptors in pathogenesis and therapy]. 1279 19

The scientific review is devoted to an analysis of neuro-immune aspects of the pathological pain and to the role of disregulation between the central nervous system (CNS) and the immune system in triggering the mechanisms of such pain. The importance of anti-inflammatory cytokines (interleukins, and tumor necrosis factor) as well as of autoantibodies to neuro-mediators in the pathogenesis of different forms of hyperalgetic conditions is evaluated. New data are discussed, which are related with the possibility of modulating the antibodies to neuro-transmitters (serotonin and catecholamines) of experimental neuropathic pain syndromes.
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PMID:[Immunologic aspects of pathologic pain]. 1286 9

Evidence indicates a role for tumor necrosis factor-alpha (TNF) in neuropathic pain. We correlated pain behavior in response to mechanical stimulation with immunoreactivity for TNF receptor (TNFR) 1 and 2 at 6, 24, 76 and 120 h following L5 and L6 spinal nerve ligation (SNL). Allodynia began in both L4 and L5 dermatomes within 6 h following SNL, peaking by 24 h. In L5 (injured) dorsal root ganglia (DRG), TNFR1 and TNFR2 levels displayed a bimodal increase, peaking at 6 and 120 h after SNL. In L4 (uninjured) DRG, TNFR1 and TNFR2 immunoreactivity peaked at 24 h returning to basal levels by 120 h. TNFR upregulation in injured and adjacent uninjured DRG neurons may be essential for mediating enhanced TNF effects and thus contribute to the development of pain-related behavior.
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PMID:Spinal nerve ligation induces transient upregulation of tumor necrosis factor receptors 1 and 2 in injured and adjacent uninjured dorsal root ganglia in the rat. 1287 15

The role of proinflammatory cytokines in neuropathic and inflammatory pain is well established. Recent studies suggest that cytokines such as tumor necrosis factor-alpha (TNF) may also be involved in the development of muscle pain. To investigate the pathophysiology of intramuscular TNF, exogenous TNF (0.1-10 microg), formalin (9%) or vehicle was injected into the gastrocnemius or biceps brachii muscles of rats. To quantify muscle hyperalgesia, changes in forelimb grip force or withdrawal thresholds to increasing pressure applied to the gastrocnemius muscle were measured. TNF evoked a time- and dose-dependent muscle hyperalgesia within several hours after injection that was totally reversed by systemic treatment with the non-opioid analgesic metamizol. Paw withdrawal thresholds or latencies to mechanical and thermal stimuli, respectively, were unchanged after intramuscular injection of TNF or formalin. In contrast to formalin, which induced significant muscle tissue damage, macrophage infiltration, swelling and partial motor impairment demonstrated in rotarod tests, TNF induced neither histopathological tissue damage nor motor dysfunction. To investigate the effect of TNF and formalin on other potentially algesic mediators, muscles were analyzed for calcitonin-gene related peptide (CGRP), prostaglandin E2 (PGE2) and nerve growth factor (NGF) 1 day after injection. TNF and formalin evoked intramuscular upregulation of CGRP and NGF, whereas PGE2 was increased exclusively after TNF injection. These findings allow us to speculate that endogenous TNF may play a role in the development of muscle hyperalgesia. Targeting proinflammatory cytokines might be beneficial for the treatment of musculoskeletal pain syndromes.
Pain 2003 Aug
PMID:Intramuscular injection of tumor necrosis factor-alpha induces muscle hyperalgesia in rats. 1292 30

Opioids and their receptors are key players in a cross-talk between the nervous and immune systems. For example, the endogenous opioid system is activated during inflammation as a physiological feedback mechanism to attenuate inflammatory pain. Herein, we report that in primary human T lymphocytes, Raji B cells, U937 monocytes, primary human polymorphonuclear leukocytes, and mature dendritic cells, the proinflammatory cytokine tumor necrosis factor induced mu-opioid receptor gene transcription. Transcriptional induction of the gene in immune cells was mediated via tumor necrosis factor receptor type 2. Using selective in vivo disruption of possibly involved transcription factors with decoy oligonucleotides, nuclear factor-kappaB was identified as the factor responsible for induction of the gene in immune cells, whereas activator protein-1 was found to be uninvolved. Nuclear factor-kappaB also mediates up-regulation of mu-opioid receptors in neuronal cells stimulated with tumor necrosis factor. Among six putative nuclear factor-kappaB binding sites on the mu-opioid receptor gene promoter, three cis-active elements at nt -2174, -557, and -207 were identified using transfection experiments of reporter gene constructs, electrophoretic mobility shift assays, and in vivo binding studies with decoy oligonucleotides. An allelic variation within the -557 element significantly reduced its trans-activating potency, which may affect regulation of the mu-opioid receptor gene in persons carrying this mutation. This study suggests a regulatory function of tumor necrosis factor in opioid-mediated processes in neuronal and immune cells, with possible impact on the complex of inflammation-induced analgesia.
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PMID:The role of nuclear factor kappaB in tumor necrosis factor-regulated transcription of the human mu-opioid receptor gene. 1450 Jul 35


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