• Atanaska N Velichkova, Sophie E Coleman, and Carole Torsney.
• Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, UK.
• Br J Anaesth. 2022 Apr 1; 128 (4): 718-733.

BackgroundPostoperative pain is a common clinical problem that, in preclinical studies, has almost exclusively been studied in males. Altered C-fibre activity-dependent slowing (ADS) is a potential underlying mechanism, given it is altered after tissue inflammation and nerve injury, but this has not been explored post-incision. We therefore investigated the effect of hind-paw incision on C-fibre ADS in both sexes and the involvement of voltage-gated sodium channels (NaV) as they contribute to ADS. We also assessed mechanical and thermal sensitivity post-incision in both sexes.MethodsDorsal roots were isolated from hind-paw incision (2-4 days post-surgery) or naive (control) juvenile rats of both sexes. Compound action potential recordings were made to assess C-fibre ADS in response to ×40 stimuli at 2 and 10 Hz and repeated in the presence of 20 nM tetrodotoxin/vehicle. Data were quantified by the normalised change in latency (negative peak) and width (positive-to-positive peak) of the triphasic C-fibre response. Hind-paw mechanical withdrawal thresholds and thermal withdrawal latencies were measured pre- and post-incision.ResultsIncision facilitates C-fibre ADS in both sexes, with more pronounced facilitation in females. Tetrodotoxin induces sex- and injury-dependent changes in C-fibre ADS that were distinct between latency and width measures. Hind-paw incision induced comparable mechanical hypersensitivity in both sexes but less peak heat hypersensitivity in females.ConclusionsHind-paw incision induces sex-dependent changes in C-fibre activity-dependent slowing, which likely contribute to the observed sex difference in peak thermal hypersensitivity. This may reflect sex- and incision-induced differences in functional expression of NaV channels that differs by C-fibre subtype.Copyright © 2021 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

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