Xiaoying Zhu1, James C Eisenach. 1. Department of Anesthesiology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157, USA. xzhu@wfubmc.edu
Abstract
BACKGROUND: The mechanisms underlying neuropathic pain are incompletely understood and its treatment is often unsatisfactory. Spinal cyclooxygenase-2 (COX-2) expression is upregulated after peripheral inflammation, associated with spinal prostaglandin production leading to central sensitization, but the role of COX isoenzymes in sensitization after nerve injury is less well characterized. The current study was undertaken to determine whether COX-1 was altered in this model. METHODS: Male rats underwent partial sciatic nerve transsection (PSNT) or L5-L6 spinal nerve ligation (SNL). Four weeks after PSNT and 4 h, 4 days, or 2 weeks after SNL, COX-1 immunohistochemistry was performed on the L2-S2 spinal cord. RESULTS: COX-1 immunoreactivity (COX-1-IR) was unaffected 4 h after SNL. In contrast, 4 days after SNL, the number of COX-1-IR cells increased in the ipsilateral spinal cord. COX-1-IR increased in cells with glial morphology in the superficial laminae, but decreased in the rest of the ipsilateral spinal cord 4 weeks after PSNT and 2 weeks after SNL. These changes in immunostaining were greatest at the L5 level. CONCLUSION: These data suggest that COX-1 expression in the spinal cord is not static, but changes in a time- and laminar-dependent manner after nerve injury. These anatomic data are consistent with observations by others that spinally administered specific COX-1 inhibitors may be useful to prevent and treat neuropathic pain.
BACKGROUND: The mechanisms underlying neuropathic pain are incompletely understood and its treatment is often unsatisfactory. Spinal cyclooxygenase-2 (COX-2) expression is upregulated after peripheral inflammation, associated with spinal prostaglandin production leading to central sensitization, but the role of COX isoenzymes in sensitization after nerve injury is less well characterized. The current study was undertaken to determine whether COX-1 was altered in this model. METHODS: Male rats underwent partial sciatic nerve transsection (PSNT) or L5-L6 spinal nerve ligation (SNL). Four weeks after PSNT and 4 h, 4 days, or 2 weeks after SNL, COX-1 immunohistochemistry was performed on the L2-S2 spinal cord. RESULTS:COX-1 immunoreactivity (COX-1-IR) was unaffected 4 h after SNL. In contrast, 4 days after SNL, the number of COX-1-IR cells increased in the ipsilateral spinal cord. COX-1-IR increased in cells with glial morphology in the superficial laminae, but decreased in the rest of the ipsilateral spinal cord 4 weeks after PSNT and 2 weeks after SNL. These changes in immunostaining were greatest at the L5 level. CONCLUSION: These data suggest that COX-1 expression in the spinal cord is not static, but changes in a time- and laminar-dependent manner after nerve injury. These anatomic data are consistent with observations by others that spinally administered specific COX-1 inhibitors may be useful to prevent and treat neuropathic pain.