Background & Aims
Wound-related pain affects approximately 80% of individuals with chronic wounds (1). Currently, there are no well-characterised or translationally relevant in vivo models of wound-related pain. While some prior pain-related behavioural work has been carried out in the rat back hairy skin incision model, first developed by Duarte et al., 2005 (2), this research is limited in its translational application, as it has focused primarily on male rodents.
The endocannabinoid system (ECS) is involved in the maintenance of skin homeostasis and in the modulation of nociception. Recently, the ECS has been highlighted as a potential target for the management of wound-related pain (3).
The aims of this study were to 1) characterise the temporal profile of pain-related behaviour following dorsum incision in both male and female rats, 2) assess the affective component of pain, and 3) investigate potential alterations in the ECS.
Methods
Male and female Sprague-Dawley rats (150-200 g on arrival, n=9/group) were subjected to a brief period of isoflurane anaesthesia to allow for shaving of the dorsum and marking of the area for primary mechanical hypersensitivity testing. 7 days later, rats were subject to either dorsum incision surgery (HSBI) or sham procedure. HSBI surgery involves a 1.2 cm incision posterior to the L4 transverse process, closed via two sutures.
Pain-related behavioural testing was carried out at baseline (pre-surgery) and up to post-surgery day (PSD) 34 in the dorsum (primary mechanical hypersensitivity) via the ascending manual Von Frey method and in the hind paws (secondary mechanical hypersensitivity) via electronic Von Frey. The affective component of pain was assessed via the Place Escape Avoidance Paradigm (PEAP) on PSD 8. Rats were euthanized on PSD 35, and levels of endocannabinoids (2-AG and AEA) and related N-acylethanolamines (PEA and OEA) in key brain regions were assessed via LC-MS/MS.
Results
Incision-related primary mechanical hypersensitivity was observed in male and female rats at 1cm ipsilateral to the wound vs. sham counterparts (p<0.05), persisting to PSD 7 in females and PSD 14 in males. Both male and female rats displayed reduced paw withdrawal threshold (PWT) in the ipsilateral (left) hind paw vs. their sham counterparts, indicating the development of secondary hypersensitivity. There was no difference in the time spent in the light side of the arena in the PEAP at PSD 8 – although there was higher percent positive responses to suprathreshold ipsilateral paw stimulation in both male and female HSBI rats. LC-MS/MS indicated no significant difference in the levels of 2-AG, AEA, OEA, or PEA in the rostroventromedial medulla (RVM), periaqueductal grey (PAG) or thalamus between HSBI rats and sham.
Conclusions
Results from this study indicate the presence of robust primary hypersensitivity in the dorsum of both male and female Sprague-Dawley rats following incision. The results reveal the development of secondary hypersensitivity following dorsum incision in both male and female rats, as indicated by a reduced paw withdrawal threshold in the ipsilateral paw compared with the sham counterparts. Investigation into the affective component of pain, assessed via the PEAP, suggests that on PSD 8, there is no effect of incision on the affective component of pain in either male or female rats. Further investigation of the potential ECS alterations in other key regions related to nociception will facilitate the further characterization of this system following dorsum incision.
In conclusion, the results from this study indicate that the HSBI model is suitable for the translationally-relevant study of wound-related pain in both male and female Sprague Dawley rats.
References
1.Woo, K., Sibbald, G., Fogh, K., Glynn, C., Krasner, D., Leaper, D., Österbrink, J., Price, P. and Teot, L., 2008. Assessment and management of persistent (chronic) and total wound pain. International wound journal, 5(2), pp.205-215.
2.Duarte, A.M., Pospisilova, E., Reilly, E., Mujenda, F., Hamaya, Y. and Strichartz, G.R., 2005. Reduction of postincisional allodynia by subcutaneous bupivacaine: findings with a new model in the hairy skin of the rat. The Journal of the American Society of Anesthesiologists, 103(1), pp.113-125.
3.Healy, C.R., Gethin, G., Pandit, A. and Finn, D.P., 2023. Chronic wound-related pain, wound healing and the therapeutic potential of cannabinoids and endocannabinoid system modulation. Biomedicine & Pharmacotherapy, 168, p.115714.
Presenting Author
Catherine Healy
Poster Authors
Catherine Healy
BSc (Hons)
University of Galway
Lead Author
David Finn
University of Galway
Lead Author
Maria C. Redmond
BSc (Hons)
University of Galway
Lead Author
Georgina Gethin
PhD
University of Galway
Lead Author
Abhay Pandit,PhD
University of Galway
Lead Author
Topics
- Models: Transition to Chronic Pain