Opiate and clonidine receptors on spinal sympathetic neurons inhibit adenylate cyclase to produce neuronal depression

EFFECT OF MORPHINE-INDUCED CORTICAL EXCITATION ON SPINAL SENSORY TRANSMISSION. A. Hernandez and R. Soto-Moyano, Lab. of Neurophysiology, INTA, University of Chile, Cas. 15138 Santiago 11, Chile. Topical administration of morphine to the rat primary somatosensory cortex (SI) Increases the amplitude of evoked responses and generates rhythmic spike activity in this cortical area. Besides, it has been found that cortically applied morphine produces marked analgesia to tonic pain, As these observations suggest involvement of the cerebral cortex in the mechanisms of opiate pain control, this study was designed to examine whethermorphineinduced cortical excitation influences the afferent transmission of oain at the ventrolateral funiculus of the spinal cord (VLF). Experiments were carried out on ten Wistar rats under a-chloralose anesthesia. Prior and after topical application of 1% morphine solution to the SI cortical area, somatosensory evoked responses elicited by peripheral electrical stimulation were recorded simultaneously from the contralateral VLF and SI. After morphine, a typical pattern was observed in the ECoG, characterized by the appearance of spike activity with a frequency of 0.5 to 2.0 Hz. Time-related with each cortical spike a significant reduction in amplitude of VLF responses was observed. Since cortical administration of morphine generates descending influences having the ability to inhibit spinal sensory transmission, it is suggested that the cerebral cortex plays a role in opiate pain control.

OPIATE AND CLONIDINE RECEPTORS ON SPINAL SYMPATHETIC NEURONS INHIBIT ADENYLATE CYCLASE TO PRODUCE NEURONAL DEPRESSION. B.D. Hare and D.N. Franz,*DepartmentSof Anesthesiology and Pharmacology, University of Utah School of Medicine, Salt Lake City, UT 84132, USA Aim of Investigation: Both opiates and clonidine depress sympathetic preganglionic neurons (SPGNs) by activating their respective receptors. This study examined the possibility that activation of either opiate or clonidine receptors depresses SPGNs by inhibiting adenylate cyclase and thereby reducing cyclic AMP levels. Methods: Sympathetic discharges recorded from upper thoracic preganglionic rami were evoked at 0.1 Hz by stimulation of descending excitatory pathways in the cervical dorsolateral funiculus of unanesthetized, spinal cats. Drugs were administered intravenously. Results: Inhibition of cyclic AMP hosphodiesterase (PDE) by amimne (50 mg/kg), 1BMX (lmg/kgP or RO 20-1724 (1 mg/kg) enhanced intraspinal transmission to 175% of conirol values within 10 minutes. Both clonidine (25 ug/kg) and opiates (morphine, 2 mg/kg, and methadone, 1 mg/kg) almost completely prevented enhancement by the PDE inhibitors. The alpha-2 receptor antagonist, yohimbine (0.5 mg/kg), or the opiate antagonist, naloxone (20 ug/kg), rapidly reversed the respective depressant effects of the agonists and restored the ability of the PDE inhibitors to enhance transmission. Conclusions: These results support the proposal that clonidine and opiates depress SPGNs by respectively activating alpha-2 and opiate receptors, both of which are negatively coupled to adenylate cyclase. A similar mechanism may operate on spinal sensory systems to produce analgesia. (Supported by NIH grants RR-0528 and HL-24085)