Detailed electrophysiological characterisation of spinal
opioid receptors in the mouse has been limited due to various technical difficulties. In this study, extracellular single unit recordings were made from dorsal horn neurones in a perfused spinal cord with attached trunk-hindquarter to investigate the role of
delta-opioid receptor in mediating nociceptive and non-nociceptive transmission in mouse. Noxious electrical
shock, pinch and heat stimuli evoked a mean response of 20.8+/-2.5 (n=10, P<0.005), 30.1+/-5.4 (n=58, P<0.005) and 40.9+/-6.3 (n=29, P<0.005) spikes per stimulus respectively. In 5 of 22 cells, repetitive noxious electrical stimuli applied to the hindpaw for 20 s produced a progressive increase in spike number, the phenomenon known as 'wind-up' and/or hyperactivity. When the selective
delta-opioid receptor agonist (+)-4-[(alpha R)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-
N,N-diethylbenzamide (
SNC 80) was perfused for 8-10 min, these evoked nociceptive responses were reversibly depressed.
SNC 80 (2 microM) depressed the nociceptive responses evoked by electrical
shock, pinch and heat by 74.0+/-13.7% (n=8, P<0.01), 66.5+/-16.6% (n=10, P<0.01) and 74.1+/-17.0% (n=10, P<0.01) respectively. The maximum depression by 5 microM
SNC 80 was 92.6+/-6.8% (n=3).
SNC 80 at 5 microM also completely abolished the wind-up and/or
hypersensitivity (n=5). The depressant effects of
SNC 80 on the nociceptive responses were completely blocked by 10 microM
naloxone (n=5) and 3 microM 17-(cyclopropylmethyl)-6,7-dehydro-4,5 alpha-epoxy-14 beta-ethoxy-5 beta-methylindolo [2',3':6',7'] morphinan-3-ol hydrochloride (
HS 378, n=8), a novel highly selective
delta-opioid receptor antagonist. Interestingly,
HS 378 (3 microM) itself potentiated the background activity and evoked responses to pinch and heat by 151.8+/-38.4% (P<0.05, n=8), 34.2+/-6.1% (P<0.01, n=7) and 45.5+/-11.8% (P<0.05, n=5) respectively. In contrast, the responses of non-nociceptive dorsal horn neurones were not inhibited by
SNC 80 at a dose of up to 10 microM (n=5). These data demonstrate that
delta-opioid receptor modulate nociceptive, but not non-nociceptive, transmission in spinal dorsal horn neurones of the adult mouse. The potentiation of neuronal activity by
HS 378 may reflect an autoregulatory role of the endogenous delta-
opioid in nociceptive transmission in mouse.