Involvement of ventromedial medulla "multimodal, multireceptive" neurons in opiate spinal descending control system: a single-unit study of the effect of morphine in the awake, freely moving rat

Abstract

In the present work, we have studied the effects of systemic morphine on the electrophysiological properties of ventromedial medulla (VMM) neurons in the awake, freely moving rat. By means of a chronically implanted single-unit recording device, a drug delivery catheter, and the use of controlled innocuous and noxious cutaneous stimuli, we were able to study precisely the spontaneous and evoked VMM neuronal activities. We have particularly focused our attention upon the VMM "multimodal, multireceptive" units, excited by non-noxious and noxious stimuli (VMM MULT ON), which we have already determined as the neuronal class potentially involved in nociceptive processes at VMM level. We found that morphine (3 mg/kg, i.v.) does not affect the spontaneous activity of these neurons whereas their responses to noxious heat are strongly attenuated (70%), over a prolonged period (about 2 hr) associated with an increase in the response latency. This action of morphine appears to be pharmacologically specific since it is dose dependent to some extent, and is reversed by 0.3 mg/kg of naloxone. In parallel with this pharmacological specificity, we have also demonstrated a preferential physiological effect since the response of the VMM MULT ON neurons to light touch application is not affected by morphine. This specificity is emphasized by the fact that morphine does not modify the activity of the other VMM neuronal groups such as the units unresponsive to any kind of peripheral stimuli, and does not reveal "new" neuronal classes such as those we have found in previous studies after barbiturate administration. The differential effect upon the noxious versus innocuous inputs of these units produced by the opiate reinforces their participation in nociceptive processing since similar effects have been reported in well-known nociceptive somatosensory structures such as the dorsal horn of the spinal cord. Furthermore, although the precise mechanisms of action have not yet been determined, the spinal projection of the VMM MULT ON neurons, previously demonstrated by our group, suggests their involvement in an opiate descending spinal control system of nociception. Although speculative, one can imagine either a direct facilitatory MULT ON spinal effect being attenuated by morphine (disfacilitation), or a morphine-induced disinhibition of inhibitory GABAergic neurons acting upon the MULT ON neurons.