Pain-induced analgesia mediated by mesolimbic reward circuits

We tested the hypothesis that noxious stimuli induce pain modulation by act ivation of supraspinal structures. We found that intense noxious stimuli (i .e., subdermal injection of capsaicin or paw immersion in hot water) induce d profound attenuation of the jaw-opening reflex in the anesthetized rat; f orepaw subdermal capsaicin also elevated the mechanical hindpaw-withdrawal threshold in the awake rat. These antinociceptive effects were blocked by p revious injection of either a dopamine antagonist (flupentixol) or an opioi d antagonist (naloxone) into the nucleus accumbens. Additional experiments in anesthetized animals showed that the antinociceptive effect of noxious s timulation by either capsaicin (greater than or equal to 100 mu g) or hindp aw immersion in hot water (greater than or equal to 45 degrees C for 4 min) correlated with the intensity of the stimulus. The maximal antinociceptive effect of capsaicin was similar in magnitude to that of a high dose of mor phine (10 mg/kg) injected subcutaneously. Injection of the GABA(A)-receptor agonist muscimol, but not naloxone, into the rostroventral medulla, a majo r component of descending pain modulation systems, blocked capsaicin-induce d antinociception. Although it is widely thought that painful stimuli may i nduce analgesia by activating forebrain structures, this is the first demon stration that such a mechanism exists. Furthermore, this mechanism can be e ngaged by naturalistic stimuli in awake animals. These observations imply t hat painful stimuli might under certain conditions be rewarding.