Enkephalins and Dorsal Horn Neurones of the Cat: Effects on Responses to Noxious and Innocuous Skin Stimuli

Abstract

1In spinal cats anaesthetized with a-chloralose, a study was made of the effects of methionine enkephalin and methionine enkephalin amide on the responses of neurones of spinal laminae IV and V to noxious and innocuous skin stimuli. The enkephalins were ejected from micropipettes either in the region of cell bodies or in the substantia gelatinosa. 2 Administered near cell bodies the enkephalins reduced spontaneous firing and cell responses to both types of skin stimuli. These effects were antagonized by naloxone when administered near cell bodies but not when given intravenously in doses (0.3-0.6 mg/kg) more than adequate to antagonize analgesic doses of morphine. 3 Administered in the substantia gelatinosa the enkephalins were more selective in their action. The predominant effect was a reduction in nociceptive responses with little effect on non-nociceptive responses although spontaneous firing was commonly reduced. Naloxone administered either in the substantia gelatinosa or intravenously (0.1-0.3 mg/kg) reversed these effects of the enkephalins.

Naloxone enhancement of spinal reflexes in the rabbit.

“…However, in the reflexes we have studied it is clear that naloxone in small doses enhanced reflex drive from large as well as small afferents, an observation indicating that endogenous opioids are not concerned exclusively with the suppression of nociceptive responses. It is interesting that Duggan, Hall & Headley (1977) report that iontophoretic application ofenkephalins into laminae II and III of the cat dorsal horn caused a selective depression of the responses of neurones in laminae IV and V to high-threshold input, but that placing the opioids directly into the deeper laminae reduced responses to both large and small diameter afferents. This suggests that in our experiments naloxone exerts its action in laminae IV and V. The ipsilateral extension reflexes described here are probably manifestations of 'local sign' in withdrawal reflexes (Creed & Sherrington, 1926).…”

Actions of opioids on primate spinothalamic tract neurons

“…be inhibitory or excitatory, although the usual effect is inhibition (Davies and Dray, 1978;Duggan et al, 1977bDuggan et al, , 1981RandiC and MiletiC, 1978;Sastry and Goh, 1983;Satoh et al, 1979;Zieglgtinsberger and Sutor, 1983;Zieglgansberger and Tulloch, 1979).…”

Selective antinociceptive effects of tizanidine (DS 103–282), a centrally acting muscle relaxant, on dorsal horn neurones in the feline spinal cord

“…However, this seems unlikely in view of the 300-850 pm distance between ejecting and recording sites and because the duration of action of all three drugs used was at least twice as long when ejected into laminae II-III compared with ejections near laminae IV and V cell bodies (Tables 1 and 3). However, slightly higher ejecting currents of tizanidine (and noradrenaline and (-)-baclofen) may have been required to depress responses to noxious stimuli on administration into laminae II -III compared with that into laminae IV and V, simply because it is necessary to affect structures distributed through a greater volume of tissue surrounding the microelectrode tip at the former site (Duggan et al, 1977b). It is unlikely that the selective effects of tizanidine observed on ejection into laminae II-III resulted from depression of excitatory interneurones or excitation of inhibitory interneurones located in this region since the potent depressant isoguvacine, a GABA agonist (Krogsgaard-Larsen et al, 1977), and the excitant kainate ejected into laminae II-III both produced non-selective effects on responses of laminae IV and V neurones to cutaneous stimuli.…”