Thyrotropin-releasing hormone facilitates spinal nociceptive responses by potentiating NMDA receptor-mediated transmission

Abstract

The interaction of thyrotropin-releasing hormone (TRH) with NMDA receptor-mediated responses has been investigated in α-chloralose-anaesthetized spinalized rats with respect to its relevance to spinal nociceptive transmission. The effects of TRH and of the uncompetitive NMDA antagonist ketamine were tested on responses of dorsal horn wide dynamic range neurones to noxious pinch, heat and electrical stimuli in parallel with those to iontophoretically applied N-methyl- d-aspartate (NMDA) and AMPA (α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid). Tests with NMDA blocking doses of ketamine (4 mg/kg i.v.) demonstrated a variable NMDA receptor-mediated component of all synaptic responses. TRH (0.5–1 mg/kg i.v.) enhanced the responses to NMDA (but not AMPA) in parallel with an increase of responses to all noxious stimuli and the ‘wind-up’ component of the responses to repeated electrical stimulation. This potentiation was completely reversed by a subsequent administration of ketamine (4 mg/kg i.v.). The results indicate that TRH facilitates nociceptive transmission in the spinal dorsal horn via a selective positive modulation of NMDA receptor-mediated transmission.