Systemic Morphine Inhibits Dorsal Horn Projection Neurons through Spinal Cholinergic System Independent of Descending Pathways

Abstract

Cholinergic circuitry and muscarinic receptors within the spinal cord have been proposed to contribute to the analgesic effects of systemic morphine. In this study, we determined whether the descending pathways are involved in the inhibitory effect of systemic morphine on dorsal horn projection neurons mediated by activation of the spinal cholinergic system. Single-unit activity of dorsal horn projection neurons was recorded in anesthetized rats. The neuronal responses to mechanical stimuli applied to the receptive field were determined before and after intravenous injection of morphine. The inhibitory effect of intravenous morphine on dorsal horn neurons was also tested before and after topical spinal application of the muscarinic antagonist atropine in both intact and spinally transected rats. Intravenous injection of 2.5 mg/kg morphine significantly inhibited the evoked response of dorsal horn neurons in both intact and spinally transected rats. Spinal topical application of the mu opioid antagonist H-d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH(2) (CTAP) completely blocked the effect of morphine on dorsal horn neurons. In addition, spinal application of 10 microM atropine significantly attenuated the effect of systemic morphine. In rats subjected to cervical spinal transection, atropine produced a similar attenuation of the inhibitory effect of systemic morphine on dorsal horn neurons. Data from this electrophysiological study suggest that systemic morphine inhibits ascending dorsal horn neurons through stimulation of spinal mu opioid receptors. Furthermore, activation of the local spinal cholinergic circuitry and muscarinic receptors is involved in the inhibitory effect of systemic morphine on dorsal horn projection neurons independent of descending pathways.