Articles: hyperalgesia.
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Brain Behav. Immun. · Nov 2014
Identification of a functional interaction of HMGB1 with Receptor for Advanced Glycation End-products in a model of neuropathic pain.
Recent studies indicate that the release of high mobility group box 1 (HMGB1) following nerve injury may play a central role in the pathogenesis of neuropathic pain. HMGB1 is known to influence cellular responses within the nervous system via two distinct receptor families; the Receptor for Advanced Glycation End-products (RAGE) and Toll-like receptors (TLRs). The degree to which HMGB1 activates a receptor is thought to be dependent upon the oxidative state of the ligand, resulting in the functional isoforms of all-thiol HMGB1 (at-HMGB1) acting through RAGE, and disufide HMGB1 (ds-HMGB1) interacting with TLR4. ⋯ Moreover, a single exposure to monoclonal antibody to RAGE (RAGE Ab) failed to abrogate pain behavior at PID 7, 14 and 21. However, RAGE Ab administration produced reversal of mechanical hyperalgesia on PID28. Thus, at-HMGB1 activation through RAGE may be responsible for sensory neuron sensitization and mechanical hyperalgesia associated with chronic neuropathic pain states.
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Yonsei medical journal · Nov 2014
Epidural dexamethasone decreased inflammatory hyperalgesia and spinal cPLA₂ expression in a rat formalin test.
The aim of this study was to investigate the effect of epidural dexamethasone on analgesia and cytosolic phospholipase A₂ (cPLA₂) expression in the spinal cord in a rat formalin test. ⋯ Taken together, these results suggest that 300 μg of epidural dexamethasone has an attenuating effect on the peripheral inflammatory tissue injury induced hyperalgesia and this effect is mediated through the inhibition of intraspinal cPLA₂ expression and the primary site of action is the laminae I-II of the spinal cord.
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Based upon studies using mechanical pin-prick, pressure, electrical or heat stimuli applied to painful and/or pain-free parts of the body, chronic low back pain (CLBP) has been shown to be associated with generalized and enhanced pain sensitivity and altered brain responses to noxious stimuli. To date, no study examined the processing of noxious laser heat pulses, which are known to selectively excite thermal nociceptors located in the superficial skin layers, in CLBP. ⋯ The results are in contrast to previous studies showing hypersensitivity to different experimental noxious stimuli (e.g., contact heat). We argue that these discrepancies may be due to low spatial and temporal summation within the central nervous system following laser heat stimulation. Our results indicate important methodological differences between laser heat and thermode stimulation that should be taken into account when interpreting results, such as from thermal quantitative sensory testing.
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Neuropathic pain is a debilitating condition caused by a lesion or disease of the somatosensory nervous system. Statins inhibit the rate-limiting step in cholesterol biosynthesis by blocking 3-hydroxy-3-methyl glutaryl coenzyme A reductase. Apart from the cholesterol-reducing actions of statins, recent studies have shown their pleiotropic actions; accordingly, their usefulness in attenuating different disease states has been described in preclinical studies. Studies in animals have also suggested their beneficial effects in attenuating neuropathic pain in various animal models of neuropathy. In these studies, their usefulness has been ascribed to cholesterol-independent actions, including anti-inflammatory, antioxidant, and neuromodulatory effects. On the contrary, clinical evidence suggests that statin administration in patients is associated with development of neuropathy, suggesting the dichotomous role of statins in neuropathic pain. The present review discusses the pain-attenuating as well as pain-inducing role of statins in preclinical and clinical studies, respectively. Furthermore, the review provides mechanistic insight to explain the paradoxical nature of this class of drugs in neuropathy in preclinical and clinical studies. ⋯ The article reviews the pain-inducing role of statins in clinical studies and its neuropathic pain-attenuating role in preclinical studies with possible mechanisms. Understanding key differences in mechanisms may help to attenuate pain induction in the clinical setting and may possibly project statins as neuropathic pain-attenuating agents.