Studies on pain. Effects of morphine on a spinal nociceptive flexion reflex and related pain sensation in man

The nociceptive flexion reflex and the corresponding subjective pain score elicited by sural nerve stimulation were studied in 6 healthy volunteers. A significant correlation was found between the respective recruitment curves of the reflex and of the pain score as a function of stimulus intensity. Consequently, the reflex (Tr) and the pain (Tp) thresholds were found to be almost identical (mean: 10.6 and 10.3 mA, respectively). Similarly, the threshold of the maximal reflex response (Tmr) was very close to that of intolerable pain (Tip): 37.1 and 38.8 mA, respectively. These four parameters were studied before and after intravenous administration of morphine chlorhydrate (0.05, 0.1, 0.2 and 0.3 mg/kg) and subsequent administration of naloxone hydrochloride (0.02 mg/kg; i.v.). While 0.05 mg/kg morphine remained without any effect, higher doses produced an increase in the four thresholds (Tr, Tp, Tmr, Tip). Furthermore, a very significant linear relationship was found between the importance of the increase and the dose of morphine. Morphine also depressed in a dose-dependent fashion, the nociceptive reflexes elicited by a constant stimulation intensity (1.2-1.3 Tr). All these effects were immediately reversed by subsequent naloxone. During all the pharmacological situations, variations in Tr and Tp as well as in Tmr and Tip were found to be very significantly linearly related, indicating a close relationship between the effects of morphine on the nociceptive reflex and on the related pain sensation. These results suggest that, in our model involving a brief 'epicritic' nociceptive stimulus, the mechanisms of morphine-induced analgesia in man can be explained by a depressive effect on the nociceptive transmission directly at a spinal level.