Articles: hyperalgesia.
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To investigate mechanisms by which diabetes alters sensory processing, we measured levels of amino acid neurotransmitters in spinal dialysates from awake, unrestrained control and diabetic rats under resting conditions and following hind paw formalin injection. Under resting conditions, glutamate concentrations in spinal dialysates were significantly (P<0.05) decreased in diabetic rats compared to those of control rats whereas aspartate, taurine, glycine and citrulline remained unchanged and GABA was significantly (P<0.05) increased. Noxious stimulation of the hind paw by subcutaneous injection of 0.5% formalin into the dorsum caused a defined flinching behavior in the afflicted paw, and the amount of flinching was significantly (P<0.05) greater in diabetic rats than in controls. ⋯ Formalin injection did not alter dialysate GABA concentrations in control rats, whereas in diabetic rats there was an increase of 151+/-15% above basal levels. These findings indicate that the selective depression of basal and stimulus-evoked glutamate levels in the spinal cord of diabetic rats occurs in parallel with elevated spinal GABA levels. Because increased pain-associated behavior is accompanied by an attenuated spinal glutamate spike following paw formalin injection, hyperalgesia in diabetic rats does not appear to be secondary to enhanced glutamatergic input to the spinal cord.
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Chronic fibromyalgia (FM) pain is prevalent (estimated as high as 13%), predominantly affects women, and is associated with a variety of focal pain conditions. Ongoing FM pain is referred to deep tissues and is described as widespread but usually is maximally located within a restricted region such as the shoulders. Palpation of deep tissues reveals an enhanced nociceptive sensitivity that is not restricted to regions of clinical pain. ⋯ Thus, it appears that central mechanisms of FM pain are dependent on abnormal peripheral input(s) for development and maintenance of this condition. A substantial literature defines peripheral-CNS-peripheral interactions that are integral to FM pain. These reciprocal actions and related phenomena of relevance to FM pain are reviewed here, leading to suggestions for testing of therapeutic approaches.
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Osteoarthr. Cartil. · Oct 2006
Surgically induced osteoarthritis in the rat results in the development of both osteoarthritis-like joint pain and secondary hyperalgesia.
In the present study, we sought to develop/characterize the pain profile of a rat model of surgically induced osteoarthritis (OA). ⋯ The rat medial meniscal tear (MMT) model mimics both nociceptive and neuropathic OA pain and is responsive to both a selective cylooxygenase-2 (COX-2) inhibitor commonly utilized for OA pain (rofecoxib) and a widely prescribed drug for neuropathic pain (gabapentin). The rat MMT model may therefore represent a predictive tool for the development of pharmacologic interventions for the treatment of the symptoms associated with OA.
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Incisional pain remains underevaluated and undermanaged while evidence is growing that perioperative treatments strongly influence patients' outcome. The present review examines the recent developments in mechanisms underlying perioperative pain and questions current understanding of incisional pain features observed in patients. ⋯ Experimental studies and recent clinical trials using objective measures of sensory processing sensitization induced by surgical incision have shown the importance of hyperalgesia in perioperative pain. Effective perioperative block of nociceptive inputs from the wound as well as use of antihyperalgesic and analgesic drugs in combination seem the best way to control postoperative pain and specifically to prevent central sensitization.
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Spinal glial activation and consequent interleukin-1 (IL-1) release are implicated in pain facilitation induced by inflammation/damage to skin and peripheral nerves. It is unclear whether pain facilitation induced at deep tissue sites also depends on these. We investigated whether spinal IL-1 and/or glial activation mediates bilateral allodynia induced by repeated unilateral intramuscular injections of acidic saline to rats. Given the prominent role of spinal IL-1 in various bilateral pain models, we predicted that intrathecal IL-1 receptor antagonist (IL-1ra) would suppress bilateral allodynia in this model as well. Surprisingly, neither single nor repeated intrathecal injections of IL-1ra affected allodynia, measured by the von Frey test, induced by prior intramuscular acidic saline compared with vehicle-injected controls. In addition, we tested the effect of 2 additional intrathecal manipulations that are broadly efficacious in suppressing glially mediated pain facilitation: (1) a glial metabolic inhibitor (fluorocitrate) and (2) the anti-inflammatory cytokine, interleukin-10 (IL-10). Like IL-1ra, fluorocitrate and IL-10 each failed to reverse allodynia. Finally, we observed no significant activation of glial cells, as assessed by immunohistochemistry of glial activation markers, in the lumbar spinal cord in response to intramuscular acidic saline. Taken together, the present data suggest that acidic saline-induced bilateral allodynia is created independently of glial activation. ⋯ From converging lines of evidence, the current studies suggest that persistent bilateral allodynia induced by repeated intramuscular acidic saline is not mediated by spinal IL-1 and/or spinal glial activation. As such, this might represent the first evidence for pain facilitation occurring in the absence of glial involvement.