Brandi Butler¹, Andrew Bell^1,2, Paula Ledesma Fernandez²

¹University of Glasgow School of Biodiversity, One Health and Veterinary Medicine, Glasgow, United Kingdom. ²University of Glasgow, Spinal Cord Group, School of Psychology and Neuroscience, Glasgow, United Kingdom

Objectives

The sodium channel Nav 1.8 is an emerging analgesic target in humans, as it can specifically modulate nociceptors. Nociceptors are small diameter sensory neurons that express the receptor TRPV1 and have cell bodies in the dorsal root ganglion (DRG) adjacent to the spinal cord. This aimed to quantify Nav1.8 expression in canine DRG, with a focus on nociceptors, as it his has not been fully characterised, limiting translational insight.

To achieve this, we conducted fluorescent in situ hybridisation (FISH) to detect the transcripts SCN10A (the gene encoding Nav1.8) and TRPV1 in DRG tissue. We quantified SCN10A expression in nociceptors - identified by both small diameter neuronal size and TRPV1 expression - with the hypothesis that, as in humans, canine DRG nociceptors express SCN10A.

Methods

Observational study. DRGs were collected from six dogs (equal sex distribution) and flash frozen within 2 hours post–mortem. DRGs were cryosectioned, slide mounted non-sequentially, processed using FISH and imaged using confocal microscopy. Neurons were profiled by diameter (<40mm, small; 40 – 60mm, medium; >60mm, large) and signal intensity for each probe (negative, positive, double positive) in Qupath. Data analysed and graphs generated in R.

Results

SCN10A and TRPV1 are expressed in 86.4% and 97.1%  of small diameter neurons, respectively.  88.7% of small neurons co-express SCN10A and TRPV1.

Statement: Impact/ Clinical Significance

Expression of SCN10A in a high proportion of nociceptors in the canine DRG supports Nav 1.8 targeting as a promising analgesic strategy in veterinary medicine. With further clinical validation, this could broaden treatment options for pain management in dogs.

This work was supported by a student research project grant from BSAVA Petsavers.