Articles: hyperalgesia.
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Randomized Controlled Trial
Ondansetron, a 5HT3-antagonist, does not alter dynamic mechanical allodynia or spontaneous ongoing pain in peripheral neuropathy.
The aim of this study was to examine whether the intensity of dynamic mechanical allodynia and spontaneous ongoing pain in patients with neuropathic pain associated with peripheral neuropathy was influenced by an intravenous infusion of the 5HT3-antagonist, ondansetron. ⋯ No influence from 8 mg of ondansetron could be shown on the intensity of brush-evoked or spontaneous ongoing pain in patients with peripheral neuropathy, indicating the lack of involvement of 5HT3-receptors in an earlier proposed spinobulbospinal loop with descending facilitation acting on spinal mechanisms related to dynamic mechanical allodynia.
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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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Pharmacol. Biochem. Behav. · May 2011
Formalin-induced long-term secondary allodynia and hyperalgesia are maintained by descending facilitation.
This work analyzes the role of cholecystokinin (CCK) receptors, dynorphin A₁₋₁₇ and descending facilitation originated in the rostral ventromedial medulla (RVM) on secondary allodynia and hyperalgesia in formalin-injected rats. Formalin injection (50 μL, 1%, s.c.) produced acute nociception (lasting 1 h) and long-term secondary allodynia and hyperalgesia in ipsilateral and contralateral hind paws (lasting 1-12 days). Once established, intra-RVM administration of lidocaine at day 6, but not at 2, reversed secondary allodynia and hyperalgesia in rats. ⋯ Moreover, intrathecal administration of dynorphin antiserum reversed, but was unable to prevent, secondary allodynia and hyperalgesia in both hind paws. These results suggest that formalin-induced secondary allodynia and hyperalgesia are maintained by activation of descending facilitatory mechanisms which are dependent on CCK₂ receptors located in the RVM and spinal cord. In addition, data suggest that spinal dynorphin A₁₋₁₇ and CCK play an important role in formalin-induced secondary allodynia and 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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Neuron glia biology · May 2011
Involvement of calcitonin gene-related peptide and CCL2 production in CD40-mediated behavioral hypersensitivity in a model of neuropathic pain.
The neuropeptide calcitonin gene-related peptide (CGRP) is known to play a pro-nociceptive role after peripheral nerve injury upon its release from primary afferent neurons in preclinical models of neuropathic pain. We previously demonstrated a critical role for spinal cord microglial CD40 in the development of spinal nerve L5 transection (L5Tx)-induced mechanical hypersensitivity. Herein, we investigated whether CGRP is involved in the CD40-mediated behavioral hypersensitivity. ⋯ Further, there was decreased CCL2 production in CD40 KO mice compared to WT mice 21 days post-L5Tx. However, CGRP8-37 did not significantly affect spinal cord CCL2 production following L5Tx in WT mice. Altogether, these data suggest that CD40 contributes to the maintenance of behavioral hypersensitivity following peripheral nerve injury in part through two distinct pathways, the enhancement of CGRP expression and spinal cord CCL2 production.