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 formal in test. In Expt. I, two oxotremorine concentrations (0.1 and 0.2 mg/kg) an d two administration times (15 and 1 min before formalin injection) were ch osen. All spontaneous and formalin-evoked behavioral responses were conside red, 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 kil led 15, 30 or 60 min after formalin treatment. Blood was collected from the trunk to determine corticosterone plasma levels. Some brain areas (hypotha lamus, septum and periaqueductal gray matter) were dissected for determinat ion of the beta-endorphin content. Oxotremorine induced a dose- and time-de pendent reduction of all formalin-evoked responses: licking was decreased d uring both the first and second phases of the formalin test, flexing was de creased during the second phase by the higher concentration only and paw-je rk was decreased during the first phase by both concentrations. Rearing and line-crossing were significantly decreased by oxotremorine while explorato ry activity was only partially reduced; self-grooming was increased. These effects on exploratory activity and self-grooming were abolished by formali n treatment. beta-endorphin content in the septum was increased by oxotremo rine administered 15 min, but not 1 min, before formalin-treatment. beta-en dorphin in the hypothalamus increased in all formalin-treated groups indepe ndently of oxotremorine administration. These results confirm, and extend t o tonic pain, the analgesic effect exerted by oxotremorine on phasic respon ses. Because of the different effects on each formalin-induced response, th ey also indicate both spinal and supraspinal CNS sites of action. (C) 1999 Elsevier Science B.V. All rights reserved.