Peripheral effects of opioid drugs on capsaicin-sensitive neurones of the guinea-pig bronchus and rabbit ear

Abstract

The effect of a potent opioid agonist, [d-Met², Pro⁵]-enkephalinamide was investigated on two responses involving capsaicin-sensitive afferent neurones, namely, atropine-resistant contractions of the guinea-pig bronchus evoked by electrical field stimulation and the nociceptor stimulation to intraarterial injections of acetylcholine or capsaicin into the vascularly isolated rabbit ear. The hypotheses to be tested were whether (a) opioid receptor activation may inhibit mediator release from primary afferent neurones and (b) the opioid could exert an analgesic effect at a peripheral site of action. Non-cholinergic contractions of the guinea-pig isolated main bronchi due to electrical stimulation were concentration-dependently inhibited by [d-Met², Pro⁵]-enkephalinamide (10 nM–1 μM). This effect was abolished by naloxone (1 μM). Naloxone alone induced no change in the stimulation-evoked contractions of the bronchus, indicating that no endogenous opioid control was present. Substance P and neurokinin A induced bronchial contractions that were not influenced by [d-Met², Pro⁵]-enkephalinamide. This indicates that [d-Met², Pro⁵]-enkephalinamide inhibits electrically-evoked bronchial contractions by reduced mediator release from capsaicin-sensitive sensory nerve endings, since these contractions are most probably brought about by tachykinins, released from afferent neurones. Capsaicin-induced bronchial contractions were in contrast to electrical stimulation not influenced by [d-Met², Pro⁵]-enkephalinamide which suggests a different site of action. The activation of sensory neurones in the rabbit ear by i. a. injection of acetylcholine and capsaicin was not reduced under infusion of [d-Met², Pro⁵]-enkephalinamide (1 and 10 μM) or lofentanil (1 and 10 μM). The enhancement of the effect of acetylcholine by infusion of prostaglandin E₂ (0.15 μM) also remained unchanged under infusion of 10 μM [d-Met², Pro⁵]-enkephalinamide. A peripheral analgesic action of the two opioid agonists studied is therefore not indicated.