Transcriptomic analyses of dorsal spinal cord after surgical incision.

Background: Peripheral nociceptors expressing the ion channel TRPV1 play an important role in mediating post-operative pain. Signaling from these nociceptors in the peri- and post-operative period can lead to plastic changes in the spinal cord and, when controlled, can yield analgesia. The transcriptomic changes in the dorsal spinal cord after surgery, and potential coupling to TRPV1+ nociceptor signaling, remain poorly studied.Methods: Resiniferatoxin was injected subcutaneously into rat hindpaw several minutes prior to surgical incision to inactivate TRPV1+ nerve terminals. The effects of resiniferatoxin on post-incisional measures of pain were assessed through post-operative day 10 (n=51). Transcriptomic changes in the dorsal spinal cord, with and without peripheral TRPV1+ nerve terminal inactivation, were assessed by RNA-Sequencing (n=22).Results: Peripherally administered resiniferatoxin increased thermal withdrawal latency by at least 2-fold through post-operative day 4, increased mechanical withdrawal threshold by at least 7-fold through post-operative day 2, and decreased guarding score by 90% relative to vehicle control (p<0.05). Surgical incision induced 70 genes in the dorsal horn and these changes were specific to the ipsilateral dorsal horn. Gene induction with surgical incision persisted despite robust analgesia from resiniferatoxin pre-treatment. Many of the genes induced were related to microglial activation, such as Cd11b and Iba1.Conclusions: A single subcutaneous injection of resiniferatoxin prior to incision attenuated both evoked and non-evoked measures of post-operative pain. Surgical incision induced transcriptomic changes in the dorsal horn that persisted despite analgesia with resiniferatoxin, suggesting that post-surgical pain signals can be blocked without preventing transcription changes in the dorsal horn.