The present study demonstrates that a hindpaw plantar incision induces SFL behaviors in rats and that these behaviors have higher bioassay sensitivity to analgesic interventions with morphine and buprenorphine compared with mechanically evoked behaviors.
This study describes a modified Hargreaves’ method for assessing paw withdrawal threshold temperatures for heat (PWT-H) nociception in the rat hind paws. The method utilizes applications of radiant heat to maintain controlled lamp temperatures (CLT) on a glass floor beneath the rat hind paw. An ascending series of CLTs were each applied for 10-s, with 5–10 min intervals between applications, until a characteristic withdrawal behavior was observed, or a cutoff CLT was reached. Average plantar epicutaneous temperatures measured from anesthetized rats corresponding to CLTs and withdrawal latencies were used for determining PWT-H. The mean PWT-H in 2-months old (mo) naïve Sprague-Dawley rats (n=38) was 47.6±0.2°C, and is comparable to the noxious threshold temperature for human glabrous skin (46.5±0.5°C). The PWT-H is consistent between trials and daily assessments over four consecutive days. No significant differences were observed between the PWT-H in 2 mo, 6–8 mo, and >24 mo F344 rats, but the PWT-H in 1-mo rats was significantly decreased. Three hours following plantar incision, the PWT-H decreased to 37.5±0.2°C, which correlates with previous observations of C-fiber afferents from incised glabrous skin firing at 36.7±3.6°C. Parallel testing with the current method and an electronic von Frey device illustrated similar degrees of incision-induced hyperalgesia, improvement of hyperalgesia over time, and reversals induced by morphine and gabapentin. In conclusion, the present method allows us to compare PWT-H with electrophysiological and human psychophysical studies involving thermosensation and, as a behavioral assay identical to von Frey testing in measuring threshold for nociception.
Background
Spontaneous pain after surgical incision is a significant problem for most post‐operative patients. Pain management that relies on opioids is hindered by numerous side effects, fuelling interest in non‐opioid alternatives and multimodal approaches. Subcutaneous capsaicin infiltration has shown potential for reducing post‐operative pain, but there are unanswered questions about safety and possible side effects. In adult rats, we characterized the analgesic effects of pre‐operative capsaicin infiltration into the skin prior to plantar incision and assessed wound healing and epidermal innervation.
Methods
The surgical site on the plantar surface of the rat hind paw was infiltrated with 1% capsaicin or vehicle 30 min or 1 week prior to surgical incision. Spontaneous and evoked pain behaviours were assessed. Digital images of incised hind paws were used to quantify the surface area of the wound after suture removal. Epidermal nerve fibre quantification was performed on peri‐incisional tissue biopsies.
Results
Intraplantar administration of capsaicin 30 min before surgical incision attenuated spontaneous pain behaviours, heat hyperalgesia, epidermal innervation, but it did not alter the rate of wound healing. Incisional pain hypersensitivity returned to baseline 2 weeks post‐incision, at a time when no recovery of epidermal innervation is observed.
Conclusions
Subcutaneous infiltration of capsaicin prior to surgical incision attenuated incision‐induced pain behaviours and reduced epidermal innervation around the incision site. The long‐lasting epidermal denervation by capsaicin had no impact in the rate of wound healing and recovery from pain behaviours.
Significance
Pre‐operative capsaicin infiltration attenuated spontaneous pain‐like behaviour and prevented the development of heat hyperalgesia following plantar skin incision. While capsaicin caused long‐lasting and widespread loss of epidermal and dermal nerve fibres, there was no measurable impact on the rate of wound healing. Pre‐ or intra‐operative infiltration of capsaicin into surgical sites could act as a safe prophylactic for post‐operative pain and reduce the need for opioids during recovery.
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