Articles: hyperalgesia.
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Levetiracetam, a novel antiepileptic drug, has recently been shown to have antinociceptive effects in various animal models of pain. The purpose of this study was to investigate the antihyperalgesic effect of levetiracetam and its mechanism of action, by examining the involvement of GABAergic, opioidergic, 5-hydroxytryptaminergic (5-HTergic) and adrenergic systems in its effect, in a rat model of inflammatory pain. ⋯ These results show that levetiracetam produced antihyperalgesia which is at least in part mediated by GABA(A), opioid, 5-HT and alpha(2)-adrenergic receptors, in an inflammatory model of pain. The efficacy of levetiracetam in this animal model of inflammatory pain suggests that it could be a potentially important agent for treating inflammatory pain conditions in humans.
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Eccentric muscle exercise is a common cause of acute and chronic (lasting days to weeks) musculoskeletal pain. To evaluate the mechanisms involved, we have employed a model in the rat, in which eccentric hind limb exercise produces both acute mechanical hyperalgesia as well as long-term changes characterized by enhanced hyperalgesia to subsequent exposure to an inflammatory mediator. Eccentric exercise of the hind limb produced mechanical hyperalgesia, measured in the gastrocnemius muscle, which returned to baseline at 120 h post-exercise. ⋯ This marked prolongation of PGE(2) hyperalgesia induced by eccentric exercise was prevented by the spinal intrathecal injection of oligodeoxynucleotide antisense to protein kinase Cε, a second messenger in nociceptors implicated in the induction of chronic pain. Exercise-induced hyperalgesia and prolongation of PGE(2) hyperalgesia were inhibited by the spinal intrathecal administration of antisense for the interleukin-6 but not the tumor necrosis factor α type 1 receptor. These findings provide further insight into the mechanism underlying exercise-induced chronic muscle pain, and suggest novel approaches for the prevention and treatment of exercise- or work-related chronic musculoskeletal pain syndromes.
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Activation of sodium channels is essential to action potential generation and propagation. Recent genetic and pharmacological evidence indicates that activation of Na(v)1.8 channels contributes to chronic pain. Herein, we describe the identification of a novel series of structurally related pyridine derivatives as potent Na(v)1.8 channel blockers. ⋯ Further characterization of TTX-R current block in rat DRG neurons demonstrated that A-887826 (100nM) shifted the mid-point of voltage-dependent inactivation of TTX-R currents by approximately 4mV without affecting voltage-dependent activation and did not exhibit frequency-dependent inhibition. The present data demonstrate that A-887826 is a structurally novel and potent Na(v)1.8 blocker that inhibits rat DRG TTX-R currents in a voltage-, but not frequency-dependent fashion. The ability of this structurally novel Na(v)1.8 blocker to effectively reduce tactile allodynia in neuropathic rats further supports the role of Na(v)1.8 sodium channels in pathological pain states.
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Randomized Controlled Trial
Botulinum toxin A for treatment of allodynia of complex regional pain syndrome: a pilot study.
To investigate the efficacy and tolerability of Botulinum toxin A (BoNT-A) in allodynia of patients with complex regional pain syndrome. ⋯ Intrademal and subcutaneous administration of BoNT-A into the allodynic skin of the patients with complex regional pain syndrome (CRPS) failed to improve pain and was poorly tolerated.
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J. Pharmacol. Exp. Ther. · Sep 2010
Monoamine-dependent, opioid-independent antihypersensitivity effects of intrathecally administered milnacipran, a serotonin noradrenaline reuptake inhibitor, in a postoperative pain model in rats.
The neurotransmitters serotonin (5-HT) and noradrenaline (NA) have important roles in suppressing nociceptive transmission in the spinal cord. In the present study, we determined the efficacy and nature of the antihypersensitivity effects of milnacipran, a 5-HT and NA reuptake inhibitor (SNRI), in the spinal cord in a rat model of postoperative pain. Sprague-Dawley rats were used in all experiments. ⋯ Microdialysis studies revealed that milnacipran increased both 5-HT and NA levels in the spinal dorsal horn. These findings suggest that the antihypersensitivity effect of intrathecal milnacipran in the postoperative pain model is monoamine-mediated. Combined administration of an SNRI with morphine might be a promising treatment to suppress postoperative hypersensitivity.