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BEHAVIORAL PHARMACOLOGY

Continuous Administration of the 5-Hydroxytryptamine_1A Agonist (3-Chloro-4-fluoro-phenyl)-[4-fluoro-4-{[(5-methyl-pyridin-2-ylmethyl) -amino]-methyl}piperidin-1-yl]-methadone (F 13640) Attenuates Allodynia-Like Behavior in a Rat Model of Trigeminal Neuropathic Pain

Laboratory of Anesthesiology, University of Antwerp, Antwerp, Belgium (K.D., H.A.); and Centre de Recherche Pierre Fabre, Castres Cédex, France (W.K., F.C.C.)

(3-Chloro-4-fluoro-phenyl)-[4-fluoro-4-{[(5-methyl-pyridin-2-ylmethyl)-amino]-methyl}piperidin-1-yl]-methadone (F 13640) is a recently discovered high-efficacy 5-hydroxytryptamine (HT)_1A receptor agonist that produces central analgesia through the neuroadaptive mechanisms of inverse tolerance and cooperation. In a rat model of trigeminal neuropathic pain, the chronic constriction injury of the infraorbital nerve causes allodynia-like behavior that develops within 2 weeks and remains stable thereafter. We report that early after surgery, during which time allodynia develops, the continuous 2-week infusion of 0.63 mg/day F 13640 inhibited the allodynia-like behavior, whereas 5 mg/day morphine showed no significant effect. When F 13640 infusion was initiated late after surgery, when allodynia was well established, it produced an antiallodynic effect that was apparent during the entire infusion period. In contrast, morphine infusion caused an initially marked antiallodynic effect to which tolerance developed within the 2-week infusion period. The GABA-B receptor agonist baclofen (1.06 mg/day) that has a recognized usefulness in the treatment of trigeminal neuralgia, demonstrated effectiveness in both conditions. The data are consistent with a theory of nociceptive signal transduction, as well as with previous data, in demonstrating the neuroadaptive mechanisms of inverse tolerance and cooperation. That is, in contrast with morphine, the antiallodynic effect induced by 5-HT_1A receptor activation does not decay, but, if anything, grows with chronicity. Also, 5-HT_1A receptor activation seemed to cooperate with nociceptive stimulation in, paradoxically, inducing an antiallodynic effect. The data presented here suggest that F 13640 may perhaps offer a lasting treatment of trigeminal neuralgia.

Address correspondence to: Dr. Kristof Deseure, Universiteit Antwerpen, Labo Anesthesiologie S4, Universiteitsplein 1, B-2610 Antwerpen, Belgium. E-mail: kristof.deseure{at}ua.ac.be

This article has been cited by other articles:

				F. C. Colpaert, K. Deseure, L. Stinus, and H. Adriaensen High-Efficacy 5-Hydroxytryptamine 1A Receptor Activation Counteracts Opioid Hyperallodynia and Affective Conditioning J. Pharmacol. Exp. Ther., February 1, 2006; 316(2): 892 - 899. [Abstract] [Full Text] [PDF]

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