Articles: hyperalgesia.
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Opioid-induced hyperalgesia (OIH) and tolerance are challenging maladaptations associated with opioids in managing pain. Recent genetic studies and the existing literature suggest the 5-hydroxytryptamine type 3 (5-HT3) receptor participates in these phenomena. The location of the relevant receptor populations and the interactions between the 5-HT3 system and other systems controlling OIH and tolerance have not been explored, however. We hypothesized that 5-HT3 receptors modulate OIH and tolerance, and that this modulation involves the control of expression of multiple neurotransmitter and receptor systems. ⋯ Morphine acts via a 5-HT3-dependent mechanism to support multiple maladaptations to the chronic administration of morphine. Furthermore, the use of 5-HT3 receptor antagonists may provide a new avenue to prevent or reverse OIH and tolerance associated with chronic opioid use.
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Previous studies showed that triptans and other 5-HT(1B/1D)-receptor agonists attenuate hyper-responsiveness to mechanical stimulation of the face in a rat model of trigeminal neuropathic pain, probably by activating 5-HT(1B/1D)-receptors on primary afferent nociceptive fibers. We now tested whether blockade of post-synaptic receptors for the excitatory amino acid glutamate released by these fibers would increase this action. We thus evaluated whether (±)1-hydroxy-3-aminopyrrolidine-2-one (HA-966), an antagonist at the glycine/D-serine site of N-methyl-D-aspartate (NMDA)-receptors, would potentiate the anti-allodynic action of dihydroergotamine and zolmitriptan in rats with chronic constriction injury to the infraorbital nerve (CCI-ION). ⋯ HA-966 (2.5mg/kg, s.c.), inactive on its own, enhanced the anti-allodynic effects of dihydroergotamine (eightfold increase) and zolmitriptan (threefold increase) in CCI-ION rats, but these drugs exerted no effects in allodynic CCI-SN rats. NMDA-receptor blockade by memantine (5mg/kg, i.p.) also enhanced, whereas activation at glycine/NMDA site by D-cycloserine (3mg/kg, i.p.) reduced the anti-allodynic properties of zolmitriptan in CCI-ION rats. Combined administration of NMDA-receptor antagonist and 5-HT(1B/1D)-receptor agonist may be a promising approach for alleviating trigeminal neuropathic pain.
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The pathogenesis of widespread pain and increased tenderness in Fibromyalgia (FM) are still unknown. Recently, the role of central nervous system hyperexcitability is emphasized in pathogenesis of FM. The central sensitization was demonstrated with decrease in nociceptive flexion reflex (NFR) threshold in patients with FM. The NFR and cutaneous silent period (CuSP) are excitatory and inhibitory parts of the same spinal protective reflex, respectively. The aim of this study was to evaluate the changes in CuSP in FM. ⋯ The latency elongation of the CuSP shows that there is some delay in the development of the inhibitory part of the spinal protective reflex in patients with FM. The observed changes in CuSP of the patients with FM may suggest some abnormalities in the circuits of sensorimotor integration at spinal and supraspinal levels. The results regarding the changes observed in the CuSP in patients with FM should be confirmed by further studies.
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Gabapentin is an anticonvulsant and adjuvant analgesic. It is effective in several pain studies. Neuropathic pain is the most difficult type of pain to treat. In this study, we examined if intrathecal gabapentin could prevent nerve injury-induced pain. ⋯ We showed a preventative effect of intrathecal gabapentin on the development of nerve injury-induced mechanical allodynia and thermal hyperalgesia. Our data suggest that continuous intrathecal gabapentin may be considered as an alternative for the prevention of nerve injury-induced pain.