MrgprdCre lineage neurons mediate optogenetic allodynia through an emergent polysynaptic circuit

Warwick, C. et al. (2021) MrgprdCre lineage neurons mediate optogenetic allodynia through an emergent polysynaptic circuit. Pain, 162(7), pp. 2120-2131. (doi: 10.1097/j.pain.0000000000002227) (PMID:34130311) (PMCID:PMC8206522)

[img] Text
245060.pdf - Published Version
Available under License Creative Commons Attribution Non-commercial No Derivatives.



Most cutaneous C fibers, including both peptidergic and nonpeptidergic subtypes, are presumed to be nociceptors and respond to noxious input in a graded manner. However, mechanically sensitive, nonpeptidergic C fibers also respond to mechanical input in the innocuous range, so the degree to which they contribute to nociception remains unclear. To address this gap, we investigated the function of nonpeptidergic afferents using the MrgprdCre allele. In real-time place aversion studies, we found that low-frequency optogenetic activation of MrgrpdCre lineage neurons was not aversive in naive mice but became aversive after spared nerve injury (SNI). To address the underlying mechanisms of this allodynia, we recorded responses from lamina I spinoparabrachial (SPB) neurons using the semi-intact ex vivo preparation. After SNI, innocuous brushing of the skin gave rise to abnormal activity in lamina I SPB neurons, consisting of an increase in the proportion of recorded neurons that responded with excitatory postsynaptic potentials or action potentials. This increase was likely due, at least in part, to an increase in the proportion of lamina I SPB neurons that received input on optogenetic activation of MrgprdCre lineage neurons. Intriguingly, in SPB neurons, there was a significant increase in the excitatory postsynaptic current latency from MrgprdCre lineage input after SNI, consistent with the possibility that the greater activation post-SNI could be due to the recruitment of a new polysynaptic circuit. Together, our findings suggest that MrgprdCre lineage neurons can provide mechanical input to the dorsal horn that is nonnoxious before injury but becomes noxious afterwards because of the engagement of a previously silent polysynaptic circuit in the dorsal horn.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Hachisuka, Dr Junichi
Authors: Warwick, C., Cassidy, C., Hachisuka, J., Wright, M. C., Baumbauer, K. M., Adelman, P. C., Lee, K. H., Smith, K. M., Sheahan, T. D., Ross, S. E., and Koerber, H. R.
College/School:College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
Journal Name:Pain
Publisher:Lippincott, Williams & Wilkins
ISSN (Online):1872-6623
Published Online:04 February 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Pain 162(7): 2120-2131
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record