Articles: hyperalgesia.
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J. Pharmacol. Exp. Ther. · Feb 2006
High-efficacy 5-hydroxytryptamine 1A receptor activation counteracts opioid hyperallodynia and affective conditioning.
Pain may become intractable as tolerance develops to opioids and the opioids, paradoxically, induce pain. We examined the hypothesis that the analgesia produced by the novel analgesic and high-efficacy 5-hydroxytryptamine (5-HT)(1A) receptor agonist (3-chloro-4-fluoro-phenyl)-[4-fluoro-4-[[(5-methyl-pyridin-2-ylmethyl)-amino]methyl]piperidin-1-yl]methanone, fumaric acid salt (F 13640) may counteract opioid-induced pain. In studies of the somatosensory quality of pain in infraorbital nerve-injured rats, morphine infusion (5 mg/day) by means of osmotic pumps initially caused analgesia (i.e., decreased the behavioral response to von Frey filament stimulation), followed by hyperallodynia and analgesic tolerance. ⋯ The data confirm that opioids produce bidirectional hypo- and proalgesic actions, and offer initial evidence that high-efficacy 5-HT(1A) receptor activation counteracts both the sensory and the affective/motivational qualities of opioid-induced pain. The data also indicate that F 13640 may be effective with opioid-resistant pain. It further is suggested that opioid addiction may represent self-therapy of opioid-induced pathological pain.
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Hyperalgesia following chronic morphine treatment is thought to be a response to opioid receptor activation and analgesia and contribute to the development of analgesic tolerance. Here, the relationship between these variables was studied in mice tested for nociceptive sensitivity on the tail-withdrawal test during chronic infusion of various morphine doses. Hyperalgesic onset was preceded by dose-dependent analgesia except for the lowest morphine dose, which caused hyperalgesia 6 h after the start of infusion. ⋯ In addition, acute injection of morphine-3beta-glucoronide (M3G) caused hyperalgesia that was cross-adaptive with the lower morphine dose only. The data demonstrate that morphine hyperalgesia is independent of prior or concurrent opioid receptor activity or analgesia and is unrelated to analgesic tolerance. Furthermore, the lack of hyperalgesic cross-adaptation between high and low morphine doses, and their differential cross-adaptation with M3G hyperalgesia, also suggests distinct morphine dose-dependent hyperalgesic systems.
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Comparative Study
Spontaneous pain, both neuropathic and inflammatory, is related to frequency of spontaneous firing in intact C-fiber nociceptors.
Spontaneous pain, a poorly understood aspect of human neuropathic pain, is indicated in animals by spontaneous foot lifting (SFL). To determine whether SFL is caused by spontaneous firing in nociceptive neurons, we studied the following groups of rats: (1) untreated; (2) spinal nerve axotomy (SNA), L5 SNA 1 week earlier; (3) mSNA (modified SNA), SNA plus loose ligation of the adjacent L4 spinal nerve with inflammation-inducing chromic gut; and (4) CFA (complete Freund's adjuvant), intradermal complete Freund's adjuvant-induced hindlimb inflammation 1 and 4 d earlier. In all groups, recordings of SFL and of spontaneous activity (SA) in ipsilateral dorsal root ganglion (DRG) neurons (intracellularly) were made. ⋯ Overall, SFL was related to SA rate in intact C-nociceptors. Both L5 degeneration and chromic gut cause inflammation. Therefore, both SA and SFL/spontaneous pain after nerve injury (mSNA) may result from cumulative neuroinflammation.