Abstract
Chronic pain is very difficult to treat. Thus, novel analgesics are a critical area of research. Strong preclinical evidence supports the analgesic effects of α-conopeptides, Vc1.1 and RgIA, which block α9α10 nicotinic acetylcholine receptors (nAChRs). However, the analgesic mechanism is controversial. Some evidence supports the block of α9α10 nAChRs as an analgesic mechanism, while other evidence supports the inhibition of N-type CaV (CaV2.2) current via activation of GABAB receptors. Here, we reassess the effect of Vc1.1 and RgIA on CaV current in rat sensory neurons. Unlike the previous findings, we found highly variable effects among individual sensory neurons, but on average only minimal inhibition induced by Vc1.1, and no significant effect on the current by RgIA. We also investigated the potential involvement of GABAB receptors in the Vc1.1-induced inhibition, and found no correlation between the size of CaV current inhibition induced by baclofen (GABAB agonist) versus that induced by Vc1.1. Thus, GABAB receptors are unlikely to mediate the Vc1.1-induced CaV current inhibition. Based on the present findings, CaV current inhibition in dorsal root ganglia is unlikely to be the predominant mechanism by which either Vc1.1 or RgIA induce analgesia.
Footnotes
↵1 The authors declare no competing financial interests.
↵3 The funding for this work came from NIH Grants GM48677, GM103801 (J.M.M.), and AR59397 (K.S.E.). The University of Utah holds patents on α-conotoxin RgIA, of which J. Michael McIntosh is listed as an inventor. We thank Doju Yoshikami for critical reading of the manuscript.
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
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