Oxotremorine-induced modifications of the behavioral and neuroendocrine responses to formalin pain in male rats.

In the present investigation, the antinociceptive effects of the muscarinic cholinergic agonist, oxotremorine, were evaluated in rats using the formalin test. In Expt. I, two oxotremorine concentrations (0.1 and 0.2 mg/kg) and two administration times (15 and 1 min before formalin injection) were chosen. All spontaneous and formalin-evoked behavioral responses were considered, In Expt. 2, only the higher concentration of oxotremorine (0.2 mg/kg) was administered 15 or 1 min before the formalin test. The animals were killed 15, 30 or 60 min after formalin treatment. Blood was collected from the trunk to determine corticosterone plasma levels. Some brain areas (hypothalamus, septum and periaqueductal gray matter) were dissected for determination of the beta-endorphin content. Oxotremorine induced a dose- and time-dependent reduction of all formalin-evoked responses: licking was decreased during both the first and second phases of the formalin test, flexing was decreased during the second phase by the higher concentration only and paw-jerk was decreased during the first phase by both concentrations. Rearing and line-crossing were significantly decreased by oxotremorine while exploratory activity was only partially reduced; self-grooming was increased. These effects on exploratory activity and self-grooming were abolished by formalin treatment. beta-endorphin content in the septum was increased by oxotremorine administered 15 min, but not 1 min, before formalin-treatment. beta-endorphin in the hypothalamus increased in all formalin-treated groups independently of oxotremorine administration. These results confirm, and extend to tonic pain, the analgesic effect exerted by oxotremorine on phasic responses. Because of the different effects on each formalin-induced response, they also indicate both spinal and supraspinal CNS sites of action.