Continuous administration of the 5-HT 1A agonist, F 13640 attenuates allodynia-like behavior in a rat model of trigeminal neuropathic pain

F 13640 is a recently discovered high-efficacy 5-HT 1A receptor agonist that produces central analgesia through the neuroadaptive mechanisms of inverse tolerance and co-operation. In a rat model of trigeminal neuropathic pain, the chronic constriction injury of the infraorbital nerve causes allodynia-like behavior that develops within two weeks and remains stable thereafter. We report that, early after surgery during which time allodynia develops, the continuous two-week infusion of 0.63 mg/day of F 13640, inhibited the allodynia-like behavior, whereas 5 mg/day of morphine showed no significant effect. When F 13640 infusion was initiated late after surgery, when allodynia was well established, it produced an anti-allodynic effect that was apparent during the entire infusion period. In contrast, morphine infusion caused an initially marked anti-allodynic effect to which tolerance developed within the two-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 earlier data, in demonstrating the neuroadaptive mechanisms of inverse tolerance and cooperation. That is, in contrast with morphine, the anti-allodynic effect induced by 5-HT 1A receptor activation does not decay, but, if anything, grows with chronicity. Also, 5-HT 1A receptor activation appeared to co-operate with nociceptive stimulation in, paradoxically, inducing an anti-allodynic effect. The data presented here suggest that F 13640 may perhaps offer a lasting treatment of trigeminal neuralgia.