Articles: hyperalgesia.
-
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.
-
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.
-
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.
-
We have all encountered the following postanesthesia care unit dilemma a myriad of times. As the attending covering the postanesthesia care unit, the anesthesiologist will be confronted not infrequently with the following clinical scenario: "He needed 500 μg fentanyl in the operating room for a toe amputation and has received 20 mg morphine, and he's still complaining of severe pain…. ⋯ When assessing a patient experiencing exaggerated postoperative or chronic pain, several questions should come to mind. First, is this patient experiencing tolerance or hyperalgesia induced by opiate therapy? Second, does the management differ for the two etiologies? Third, what underlying mechanisms, both at the neuroanatomic and molecular/chemical levels, underlie the two processes? Fourth, how does the recent literature on opiate-induced hyperalgesia influence previously accepted views of pre-emptive analgesia? Fifth, what treatment modalities exist for opiate-induced hyperalgesia? Most importantly, sixth, how can opiate-induced hyperalgesia be prevented? In this literature review, we aim to address these questions and to hopefully change the current perception and management of perioperative and chronic pain states with opiates.
-
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.