new molecular+neuroadaptive mechanisms of pain relief: 5-HT(1A receptor acti

[Guest guest]

Curr Opin Investig Drugs. 2006 Jan;7(1):40-7.

5-HT(1A) receptor activation: new molecular and neuroadaptive

mechanisms of pain relief.

Colpaert FC.

Institut de Recherche Pierre Fabre, 3 rue des Satellites, BP 94244,

31432 Toulouse 4, France.

Guided by an understanding of signal transduction in pain-processing

systems, high-efficacy 5-hydroxytryptamine (5HT)1A receptor

activation, by means of F-13640, has been discovered as a new

molecular mechanism of pain relief in laboratory animals, inducing

two neuroadaptive phenomena. Firstly, this activation cooperates with

nociceptive stimulation, paradoxically causing analgesia, and

secondly, inverse tolerance develops so that the resulting analgesia

grows rather than decays. As an apparent result of these novel

neuroadaptive mechanisms, F-13640 exerts an analgesic action in rat

models of acute, tonic and chronic nociceptive pain that is rivaled

only by large doses of high-efficacy mu-opioid receptor agonists. In

models of neuropathic allodynia of peripheral or central origin,

chronic F-13640 administration causes an analgesia that surpasses

that observed with morphine or other agents exemplifying other

central nervous system drug mechanisms of pain relief (e.g.,

ketamine, imipramine and gabapentin).

Indeed, F-13640 produces long-lasting, preemptive and, most

remarkably, curative-like actions in neuropathic allodynia. Although

awaiting proof-of-concept evidence in humans, high-efficacy 5-HT(1A)

receptor activation may uniquely challenge the opioids for pain

therapy.