SEPARABLE YET INTERACTIVE COMPONENTS OF EXPERIMENTAL POST-INCISIONAL MECHANICAL HYPERESTHESIA

Abstract

Acute post-operative pain limits function and slows recovery. To better understand the mechanisms underlying acute pain we have further investigated a post-incisional pain model using tactile hypersensitivity as an index of pain. After 1 cm incision of the medial-dorsal skin of male rats, closed with one silk suture, there is a rapidly developing increase in the responsiveness to punctate stimulation using nylon monofilament von Frey hairs (VFH), appearing as the increased contraction of sub-cutaneous muscles, the graded cutaneous truncii muscle response (CTMR). Such hypersensitivity in rats represents both the perception of pain in response to previously non-painful stimuli (allodynia) and an enlargement of the responses to stimuli that were mildly painful in intact skin (hyperalgesia). We found the probability and vigor of CTMR increases with increasing VFH force, described by a complex Force vs Response (F-R) curve.  In intact/pre-incisional skin, such F-R data are well fitted by a single sigmoidal function that has one threshold (liminal force to produce a statistically “just-detectable” response), and one mid-point (force to produce half the maximum response). Four hours after incision, at the peak of post-incisional hypersensitivity, the F-R data are better fit by the sum of two such sigmoidal functions, with post-incisional allodynia accounted for by the emergence of a previously undetected response to VFH forces ten-fold lower than the threshold of intact skin. Interestingly, both the peak amplitude and the duration of these low-threshold, post-incisional allodynic responses are enhanced by “conditioning”, when the skin is also stimulated by strong force VFHs (that test hyperalgesia), a phenomenon that does not occur in intact skin. Actions of sub-incisional bupivacaine suggest that allodynia is initiated by local injury and inflammatory processes, while central sensitization accounts for the enhancement of allodynia by conditioning stimulation.