Intraoperative Spinal Cord Stimulation Mitigates Pain after Spine Surgery in Mice

Abstract

Background: Managing postoperative pain after spine surgery is challenging, and up to 40% of operated patients develop failed back surgery syndrome (FBSS) resulting in intractable back and/or leg pain. While spinal cord stimulation (SCS) has been shown to effectively alleviate such chronic pain, it is unknown if intraoperative SCS can mitigate the development of central sensitization that potentially causes intense postoperative pain and FBSS after spine surgery. Methods: As an experimental spine surgery, unilateral T13 laminectomy was performed in mice to expose the dorsal part of L4-5 spinal segments that receive sensory inputs from the hind limb. After the laminectomy, a group of mice received intraoperative SCS epidurally applied to the exposed side of the dorsal part of the spinal cord for an hour under anesthesia before closing the surgical wounds. Secondary mechanical hypersensitivity, a behavioral manifestation of central sensitization, was measured in hind paws using von Frey assay one day before and at predetermined times after surgery. In addition, because von Frey assay is a nocifensive reflex-based analysis that primarily assesses the sensory-discriminative domain of pain, we also performed a conflict avoidance test to capture the affective-motivational domain of pain at selected timepoints post-laminectomy. Results: Mice that underwent unilateral T13 laminectomy developed mechanical hypersensitivity in both hind paws, which gradually resolved in 1-2 weeks. The extent of the hypersensitivity was significantly less in the contralateral hind paw (relative to the laminectomy) than in the ipsilateral hind paw only in females. Intraoperative SCS applied to the exposed side of the dorsal -spinal cord significantly inhibited the development of hind paw mechanical hypersensitivity only in the SCS-applied side. When paws were mechanically stimulated in their preferred place to present a conflict between pain/discomfort and natural preference, mice avoided the conflict after laminectomy, spending less time in the place than before the surgery. However, mice treated with intraoperative SCS after laminectomy did not avoid the conflict. Conclusion: These results demonstrate that spine surgery for unilateral laminectomy induces central sensitization that results in postoperative pain hypersensitivity. Intraoperative SCS after laminectomy can mitigate the development of this hypersensitivity on the SCS-applied side.