Behavioural Characterisation and Pharmacological Validation of an Incisional Wound-Related Pain Model.

Abstract

BACKGROUND: Wound-related pain represents a significant unmet clinical need. To advance its understanding and treatment, there is a need for a validated preclinical model for the study of wound-related pain in both sexes. METHODS: A 1.2 cm incision was created on the hairy skin of the dorsum of male and female Sprague-Dawley rats posterior to L4. In the first study, mechanical withdrawal thresholds at the dorsum and hind paws were assessed for 34 days post-incision in both male and female rats to investigate the temporal profile of mechanical hypersensitivity following a dorsum incision. The second study investigated the effects of morphine (3 mg/kg s.c.) on mechanical hypersensitivity in the dorsum and hind paws on post-incision Day 8 in male Sprague-Dawley rats. RESULTS: Robust mechanical hypersensitivity was evident in the dorsum up to 14 days post-incision in males and 7 days post-incision in females, indicating sex differences in the temporal profile of mechanical hypersensitivity following incision. Secondary mechanical hypersensitivity was present in the hind paws of both sexes following a dorsum incision. Morphine (3 mg/kg s.c.) significantly attenuated dorsum and hind paw mechanical hypersensitivity on post-incision Day 8. CONCLUSIONS: These results suggest that the dorsum incision model is suitable for modelling incisional wound-related pain and exhibits sex differences in pain-related behaviour post-incision. SIGNIFICANCE: This paper extends the characterisation of an animal model of incisional wound-related pain, in both sexes. It represents an advancement in the ability to model this condition pre-clinically and will facilitate investigation of underlying mechanisms and novel therapeutics.