Modulation of persistent nociceptive inputs in the anterior pretectal nucleus of the rat

The anterior pretectal nucleus (APtN) participates in nociceptive and antinociceptive mechanisms. Drugs were injected into the ventral APtN to evaluate how intrinsic mechanisms interact in the nucleus during persistent allodynia produced by a surgical incision in a rat hind paw. Naloxone (1 and 10 ng/0.08 microl), methysergide (0.037 and 3.7 ng/0.08 microl) or atropine (0.1 and 10 ng/0.08 microl) increased the allodynia. The effect of methysergide was intensified by naloxone or atropine, the effect of atropine was intensified by naloxone or methysergide, but the effect of naloxone was not changed by methysergide or atropine. DAMGO (1.5 microg/0.08 microl), oxotremorine (5 microg/0.08 microl) or serotonin (5 microg/0.08 microl) reduced the allodynia. The effect of DAMGO was less intense in methysergide-treated rats but was not changed in atropine-treated rats, the effect of serotonin was not changed by naloxone or atropine, and the effect of oxotremorine was not changed by naloxone or methysergide. Baclofen (150 ng/0.08 microl) increased, whereas phaclofen (300 ng/0.1 microl) reduced the allodynia. Bicuculline (50 ng/0.08 microl) increased the incision pain, while muscimol (50 ng/0.08 microl) did not change it. Phaclofen was inhibited by methysergide but was unchanged by atropine. The effect of DAMGO was reduced by phaclofen (100 ng/0.1 microl). We interpret these results as indicative that noxious inputs utilize cholinergic and serotonergic pathways in the vAPtN for the activation of descending pain control mechanisms, the serotonergic pathway being under the control of GABAergic neurons which, in turn, are modulated negatively by opioid nerve terminals.