192 IgG -saporin-induced selective cholinergic denervation modifies formalin pain in male rats.

Previous studies showed an involvement of ACh in pain processes. The aim of the present experiment was to investigate the role of central cholinergic pathways in formalin pain-induced responses. 192 IgG-saporin, a potent immunotoxin able to induce the loss of cholinergic neurons, was ICV injected into male rats for 3 consecutive days; vehicle was used as control. During the 3 weeks following treatment (saporin or vehicle), the pain threshold (plantar test) and spontaneous behaviors (hole board) were determined, then the animals were subjected to the formalin test (50 l, 5% SC in the dorsal hind paw). The formalin-evoked licking, flexing, and jerking of the injected paw were recorded for 60 min. No differences between groups were found in the plantar test and hole board determinations. None of the formalin-evoked responses showed a saporin-induced modification during the first 15 min (first phase). During the second phase (15–60 min), there was a difference in the first part (ascending) of the curve, with higher levels of licking and jerking in the saporin-treated animals than in controls, and in the second part (descending), with lower levels of licking and jerking in saporin-injected animals. The results show an involvement of the cholinergic system in the second, longer lasting phase of formalin pain. The cholinergic activation, known to be induced by pain mostly during the second phase, appears to delay the behavioral output due to the central processes involved in the maintenance of pain.