High-Efficacy 5-Hydroxytryptamine 1A Receptor Activation Counteracts Opioid Hyperallodynia and Affective Conditioning

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 316; no. 2; pp. 892 - 899
• Main Authors: Colpaert, Francis C, Deseure, Kristof, Stinus, Luis, Adriaensen, Hugo
• Format: Journal Article
• Language: English
• Published: United States American Society for Pharmacology and Experimental Therapeutics 01.02.2006
• Subjects: Analgesics, Opioid - adverse effects; Analgesics, Opioid - therapeutic use; Animals; Behavior, Animal - drug effects; Cranial Nerve Injuries - complications; Dose-Response Relationship, Drug; Drug Tolerance; Hyperalgesia - chemically induced; Hyperalgesia - prevention & control; Male; Orbit - innervation; Pain - drug therapy; Pain Measurement; Piperidines - therapeutic use; Pyridines - therapeutic use; Rats; Rats, Sprague-Dawley; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists - therapeutic use
• ISSN: 0022-3565; 1521-0103
• DOI: 10.1124/jpet.105.095109

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. Infusion of F 13640 (0.63 mg/day) prevented the development of opioid hyperallodynia and reversed opioid hyperallodynia once established. In studies of the affective/motivational quality of pain, F 13640 both prevented and reversed the conditioned place aversion induced by naloxone (0.04 mg/kg i.p.) in morphine-infused rats; F 13640 also prevented and reversed the conditioned place preference induced by morphine injections (7.5 mg/kg i.p.). 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.