Presynaptic effects of morphine and methionine-enkephalin in feline spinal cord

Abstract

The effects of morphine (applied either iontophoretically in substantia gelatinosa or injected intravenously) and met-enkephalin (iontophoretically) were examined on the terminal excitabilities of single sural C, post-A δ and A δ afferents, in cats that were decerebrated and then spinalized. Small amounts of morphine (0.1–2.0 mg/kg or 15–80 nA) and met-enkephalin (15–80 nA) produced an increase in the threshold for antidromic activation of these sural fibres. In these doses, the opiate and the opioid peptide potentiated the enhancement of sural afferent terminal excitability produced by superficial peroneal (SP) nerve stimulation. The above effects of both agonists were antagonized by small doses of naloxone (0.05–0.15 mg/kg or 20–40 nA). In large amounts, morphine (3.2–6.4 mg/kg or 50–150 nA) and met-enkephalin (60–150 nA) increased the excitabilities of the sural afferent terminals and antagonized the enhancement of the terminal excitability produced by SP nerve stimulation. These actions by large doses of the agonists were not consistently antagonized by naloxone. In some experiments in which the peripheral nerves, except a few post-A δ fibres from which recordings were made, were left intact, intraarterially injected bradykinin (10 μg, to a hind limb) produced a decrease in threshold for antidromic activation of the post-A δ fibres and converted the increase in threshold produced by small amounts of morphine and met-enkephalin into a decrease in threshold. Morphine (0.8–6.4 mg/kg or 30–200 nA) did not consistently alter the excitabilities of muscle group I afferent terminals. The results of these studies indicate that morphine- and met-enkephalin-induced analgesia is, at least, partly due to the ability of the agents to potentiate “presynaptic inhibition” of nociceptive pathways in the spinal cord.