Selective depression of nociceptive responses of dorsal horn neurones by SNC 80 in a perfused hindquarter preparation of adult mouse

Detailed electrophysiological characterisation of spinal opioid receptors i n the mouse has been limited due to various technical difficulties. In this study, extracellular single unit recordings were made from dorsal horn neu rones in a perfused spinal cord with attached trunk-hindquarter to investig ate the role of delta -opioid receptor in mediating nociceptive and non-noc iceptive transmission in mouse. Noxious electrical shock, pinch and heat st imuli 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 sti mulus respectively. In 5 of 22 cells, repetitive noxious electrical stimuli applied to the hindpaw for 20 s produced a progressive increase in spike n umber, the phenomenon known as 'wind-up' and/or hyperactivity. When the sel ective delta -opioid receptor agonist (+)-4-[(alphaR)-alpha-((2S,5R)-4-ally l-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC 80 ) was perfused for 8-10 min, these evoked nociceptive responses were revers ibly depressed. SNC 80 (2 muM) depressed the nociceptive responses evoked b y 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) respec tively. The maximum depression by 5 muM SNC 80 was 92.6 +/- 6.8% (n = 3). S NC 80 at 5 muM also completely abolished the wind-up and/or hypersensitivit y (n = 5), The depressant effects of SNC 80 on the nociceptive responses we re completely blocked by 10 muM naloxone (n = 5) and 3 muM 17-(cyclopropylm ethyl)-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 h ighly selective delta -opioid receptor antagonist. Interestingly, HS 378 (3 muM) itself potentiated the background activity and evoked responses to pi nch 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 neurotics were not inhibited by S NC 80 at a dose of up to 10 muM (n = 5). These data demonstrate that delta -opioid receptor modulate nociceptive, bu t not non-nociceptive, transmission in spinal dorsal horn neurones of the a dult mouse. The potentiation of neuronal activity by HS 378 may reflect an autoregulatory role of the endogenous delta -opioid in nociceptive transmis sion in mouse. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.