Articles: hyperalgesia.
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Serotonin (5-hydroxtryptamine, 5-HT) is an important molecule in pain processing and modulation. Whether 5-HT has an analgesic or hyperalgesic action depends on the cell type and type of receptor it acts on. ⋯ Furthermore, genetic alterations in the 5-HT system may influence the susceptibility to migraine. In the central nervous system, 5-HT is involved in descending inhibition, but facilitatory serotonergic pathways may be functionally more important.
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This study investigated whether carbamazepine could produce local peripheral antinociception in a rat model of inflammatory mechanical hyperalgesia, and whether adenosine receptors are involved. Carbamazepine (100-1000 nmol/paw) co-administrated with a pro-inflammatory compound, concanavalin A, into the hind paw caused a significant dose- and time-dependent anti-hyperalgesia. ⋯ Drugs injected into the contralateral hind paw did not produce significant effects. These results suggest that carbamazepine produces local peripheral anti-hyperalgesia via peripheral adenosine A(1) receptors.
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Br J Clin Pharmacol · Apr 2006
Randomized Controlled TrialHyperalgesia induced by cutaneous freeze injury for testing analgesics in healthy volunteers.
The early phases of the clinical development of new analgesic agents are severely hindered by a lack of reliable sensitive tests based on experimental pain models. The aim of this study was to assess the ability of a localized hyperalgesia model induced by cutaneous freeze injury to evaluate the pharmacodynamic profile of weak analgesic agents in healthy volunteers. ⋯ Cutaneous freeze injury coupled with a von Frey electronic device to assess the mechanical pain threshold is a convenient model that causes no discomfort. The improved sensitivity and stability of this experimental model of hyperalgesia over three consecutive days make it a useful tool for evaluating the efficacy and detecting the potential sites of action of analgesic agents such as nonsteroidal anti-inflammatory drugs in healthy human subjects.
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Optimal management of neuropathic pain is a major clinical challenge. We investigated the involvement of c-Jun N-terminal kinase (JNK) in neuropathic pain produced by spinal nerve ligation (SNL) (L5). SNL induced a slow (>3 d) and persistent (>21 d) activation of JNK, in particular JNK1, in GFAP-expressing astrocytes in the spinal cord. ⋯ Finally, intrathecal administration of an astroglial toxin, l-alpha-aminoadipate, reversed mechanical allodynia. Our data suggest that JNK activation in the DRG and spinal cord play distinct roles in regulating the development and maintenance of neuropathic pain, respectively, and that spinal astrocytes contribute importantly to the persistence of mechanical allodynia. Targeting the JNK pathway in spinal astroglia may present a new and efficient way to treat neuropathic pain symptoms.
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Comparative Study
Involvement of nociceptin/orphanin FQ and its receptor in electroacupuncture-produced anti-hyperalgesia in rats with peripheral inflammation.
The neuropeptide nociceptin/orphanin FQ (N/OFQ), the endogenous agonist of the N/OFQ peptide receptor (NOP receptor), has been demonstrated to be involved in many physiological and pathological functions including pain regulation. In the present study, the involvement of N/OFQ-NOP receptor system in electroacupuncture (EA)-produced anti-hyperalgesia was investigated in rats with peripheral inflammation. ⋯ Additionally, the combination of N/OFQ injection with EA treatment could enhance anti-hyperalgesia compared to that produced by each component alone. These findings suggested that the spinal N/OFQ-NOP system might be involved in EA analgesia, which may be one of the mechanisms underlying the anti-nociceptive effect of EA in rat's peripheral inflammatory pain.