THE MEDIATION OF FORMALIN PAIN BY THE FOREBRAIN MEDIAL SEPTUM

Abstract

Behavioral, electrophysiological, immunocytochemical and pharmacological investigations were performed to identify the role of medial septum (MS) in nociception (pain) about which little is known. Experiments were performed using formalin model of persistent inflammatory pain. Interestingly, formalin induces a biphasic pattern of hippocampal theta activation which is in parallel with biphasic pattern of nociceptive licking and flinching, and biphasic increase in ambulation (agitation). Hippocampal theta is MS-mediated large extracellular rhythmic sinusoidal activity that reflects intracellular membrane potential oscillations during processing of information. Experiments were performed using intraseptal injection of the following: muscimol, a GABA agonist, zolpidem, a positive allosteric modulator of GABAA receptors, and bicuculline, an antagonist at GABAA receptors. The results showed that MS facilitates nociception, and that pain-induced agitation is sensitive to perturbation of theta-linked GABAergic mechanisms in MS as compared to licking and flinching. The effect on agitation is consistent with the sensorimotor integrative function of theta.