Methysergide and spinal inhibition from electrical stimulation in the periaqueductal grey

In barbiturate anaesthetized cats, electrical stimulation in the periaqueductal grey (PAG) selectively inhibited the excitation of multireceptive dorsal horn neurons by noxious heating of the skin or by electrical stimulation of unmyelinated primary afferents. Intravenous methysergide (0.2-1.0 mg/kg) had opposing effects on uninhibited responses, increasing excitation by noxious heat but reducing responses to C fibre stimulation. Evidence was obtained that the increases to noxious heat resulted from increased firing of peripheral nociceptors secondary to decreased cutaneous blood flow. Intravenous methysergide reduced inhibition from PAG stimulation. When administered electrophoretically from micropipettes however, methysergide did not reduce such inhibition. The mechanism whereby systemic methysergide reduces PAG spinal inhibition is unknown and cannot necessarily be related to a blockade of spinally released 5-hydroxytryptamine.