{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T20:30:54Z","timestamp":1791145854778,"version":"4.1.0"},"reference-count":69,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2007,9,19]],"date-time":"2007-09-19T00:00:00Z","timestamp":1190160000000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2007,9]]},"abstract":"<jats:p>Analgesic neurosteroids such as 5\u03b1\u2010pregnan\u20103\u03b1\u2010ol\u201020\u2010one (5\u03b13\u03b1) are potent selective endogenous modulators of the GABA<jats:sub>A<\/jats:sub>receptor (GABA<jats:sub>A<\/jats:sub>R) while certain synthetic derivatives (i.e. minaxolone) additionally enhance the function of recombinant glycine receptors (GlyR). Inhibitory transmission within the superficial dorsal horn has been implicated in mediating the analgesic actions of neurosteroids. However, the relative contribution played by synaptic and extrasynaptic receptors is unknown. In this study, we have compared the actions of 5\u03b13\u03b1 and minaxolone upon inhibitory transmission mediated by both GABA<jats:sub>A<\/jats:sub>and strychnine\u2010sensitive GlyRs in lamina II neurones of juvenile (P15\u201321) rats. At the near physiological temperature of 35\u00b0C and at a holding potential of \u221260 mV we recorded three kinetically distinct populations of miniature IPSCs (mIPSCs): GlyR\u2010mediated, GABA<jats:sub>A<\/jats:sub>R\u2010mediated and mixed GABA<jats:sub>A<\/jats:sub>R\u2010GlyR mIPSCs, arising from the corelease of both inhibitory neurotransmitters. In addition, sequential application of strychnine and bicuculline revealed a small (5.2 \u00b1 1.0 pA) GlyR\u2010 but not a GABA<jats:sub>A<\/jats:sub>R\u2010mediated tonic conductance. 5\u03b13\u03b1 (1\u201310 \u03bc<jats:sc>m<\/jats:sc>) prolonged GABA<jats:sub>A<\/jats:sub>R and mixed mIPSCs in a concentration\u2010dependent manner but was without effect upon GlyR mIPSCs. In contrast, minaxolone (1\u201310 \u03bc<jats:sc>m<\/jats:sc>) prolonged the decay of GlyR mIPSCs and, additionally, was \u223c10\u2010fold more potent than 5\u03b13\u03b1 upon GABA<jats:sub>A<\/jats:sub>R mIPSCs. However, 5\u03b13\u03b1 and minaxolone (1 \u03bc<jats:sc>m<\/jats:sc>) evoked a similar bicuculline\u2010sensitive inhibitory conductance, indicating that the extrasynaptic GABA<jats:sub>A<\/jats:sub>Rs do not discriminate between these two steroids. Furthermore, \u223c92% of the effect of 1 \u03bc<jats:sc>m<\/jats:sc>5\u03b13\u03b1 upon GABAergic inhibition could be accounted for by its action upon the extrasynaptic conductance. These findings are relevant to modulation of inhibitory circuits within spinally mediated pain pathways and suggest that extrasynaptic GABA<jats:sub>A<\/jats:sub>Rs may represent a relevant molecular target for the analgesic actions of neurosteroids.<\/jats:p>","DOI":"10.1113\/jphysiol.2007.134445","type":"journal-article","created":{"date-parts":[[2007,7,27]],"date-time":"2007-07-27T00:30:00Z","timestamp":1185496200000},"page":"1021-1040","source":"Crossref","is-referenced-by-count":73,"title":["GABA<sub>A<\/sub>and glycine receptor\u2010mediated transmission in rat lamina II neurones: relevance to the analgesic actions of neuroactive steroids"],"prefix":"10.1113","volume":"583","author":[{"given":"Elizabeth A.","family":"Mitchell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc J.","family":"Gentet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Dempster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delia","family":"Belelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,9,19]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0270(94)00204-T"},{"issue":"3","key":"e_1_2_5_3_1","article-title":"Guide to Receptors and Channels.","volume":"147","author":"Alexander SPH","year":"2006","journal-title":"Br J Pharmacol"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-2-36"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1044-7431(03)00236-7"},{"key":"e_1_2_5_6_1","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/S0031-6997(24)01363-2","article-title":"International Union of Pharmacology. 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