Articles: hyperalgesia.
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Journal of neurochemistry · Mar 2007
A comparison of the glutamate release inhibition and anti-allodynic effects of gabapentin, lamotrigine, and riluzole in a model of neuropathic pain.
The effects of treatment with the anti-convulsant agents, lamotrigine and riluzole were compared with gabapentin in a rat experimental model of neuropathic pain. Rats were treated intraperitoneally, with gabapentin (30, 100 and 300 mg/kg), lamotrigine (2, 10 and 50 mg/kg) or riluzole (6 and 12 mg/kg) prior to, and every 12 h for 4 days following chronic constriction injury (CCI) of the sciatic nerve. Mechanical and cold sensitivity were assessed prior to surgery (baseline) and then at 4, 8 and 12 days following CCI. ⋯ Riluzole produced profound and prolonged reductions in the spinal levels of glutamate and aspartate both for basal and formalin-stimulated release. In conclusion, the results suggest that the anti-convulsant agents gabapentin, lamotrigine and riluzole may reduce the development of hyperalgesia in a rat model of neuropathic pain by reducing the spinal release of glutamate. Riluzole's pronounced suppressive effects on spinal EAA levels is attributed to its established role as a glutamate release inhibitor and an enhancer of glutamate transporter activity.
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Persistent herpes zoster-associated pain is a significant clinical problem and an area of largely unmet therapeutic need. Progress in elucidating the underlying pathophysiology of zoster-associated pain and related co-morbidity behavior, in addition to appropriately targeted drug development has been hindered by the lack of an appropriate animal model. This study further characterizes a recently developed rat model of zoster-associated hypersensitivity and investigates (a) response to different viral strains; (b) relationship between viral inoculum concentration ('dose') and mechanical hypersensitivity ('response'); (c) attenuation of virus-associated mechanical hypersensitivity by clinically useful analgesic drugs; and (d) measurement of pain co-morbidity (anxiety-like behavior) and pharmacological intervention in the open field paradigm (in parallel with models of traumatic peripheral nerve injury). ⋯ This may reflect pain-related co-morbidity. Further, anxiety-like behavior was attenuated by acute i.p. administration of gabapentin (30 mg/kg) in nerve-injured, but not virus-infected animals. This model will prove useful in elucidating the pathophysiology of zoster-associated pain and provide a tool for pre-clinical screening of analgesic drugs.
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Inflammatory conditions can lead to debilitating and persistent pain. This hyperalgesia reflects sensitization of peripheral terminals and facilitation of pain signaling at the spinal level. Studies of peripheral systems show that tissue injury triggers not only inflammation but also a well-orchestrated series of events that leads to reversal of the inflammatory state. ⋯ Furthermore, activation of extracellular signal-regulated kinase and c-Jun N-terminal kinase in astrocytes, which has been indicated to play an important role in spinal pain processing, was attenuated in the presence of lipoxins. This linkage opens the possibility that lipoxins regulate spinal nociceptive processing though their actions upon astrocytic activation. Targeting mechanisms that counterregulate the spinal consequences of persistent peripheral inflammation provide a novel endogenous mechanism by which chronic pain may be controlled.
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Neuroscience letters · Feb 2007
Pentoxifylline attenuates the development of hyperalgesia in a rat model of neuropathic pain.
Pentoxifylline, a non-specific cytokine inhibitor, has shown to be beneficial in inflammatory pain in both experimental and clinical studies. The present study demonstrates for the first time, to our knowledge, the antihyperalgesic effect of pentoxifylline in the neuropathic pain using L5 spinal nerve transection rat model. In a preventive paradigm, pentoxifylline (12.5, 25, 50, or 100mg/kg intraperitoneally) was administered systemically daily, beginning 1h prior to nerve transection. ⋯ Furthermore, we investigated the activity of nuclear factor kappa B (NF-kappaB) in the contralateral brain on days 7 after surgery. In accordance with the change of proinflammatory cytokines, Pentoxifylline (50 or 100mg/kg) significantly inhibited the activation of NF-kappaB in the brain. This research supports a growing body of literature emphasizing the importance of neuroinflammation and neuroimmune activation in the development of neuropathic pain states, and the potential preventive value of pentoxifylline in the treatment of neuropathic pain.
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Randomized Controlled Trial
Effects of oral pregabalin and aprepitant on pain and central sensitization in the electrical hyperalgesia model in human volunteers.
Central sensitization is an important mechanism of neuropathic pain; its human models could be useful for early detection of efficacy of novel treatments. The electrical hyperalgesia model invokes central sensitization by repetitive stimulation of the skin. To assess its predictive value, we have investigated pregabalin, a standard neuropathic pain treatment, and aprepitant, an NK(1) antagonist, as an example of a drug class active in animal models but not in neuropathic pain patients. Furthermore, we explored if combinations of either of these drugs with the COX-2 inhibitor parecoxib could improve its efficacy. ⋯ The model can serve to predict analgesic efficacy in early human development and investigate the mechanism of action. The model could also be used to explore efficacy of analgesic combinations to provide a rationale for patient studies.