Upregulation of cerebrospinal fluid and peripheral prostaglandin E2 in a rat postoperative pain model

Analgesic management of postoperative pain associated with thoracic surgery remains a difficult clinical challenge. In the present study we used a thoracic muscle incision model to characterize pain-related behavior and changes in prostaglandin E-2 (PGE(2)) in both thoracic cerebrospinal fluid (CSF) and incision site tissues. A deep muscle incision was made in the left thoracic region of rats anesthetized with isoflurane, propofol, or spinal bupivacaine. Thoracic CSF and incision site tissue concentrations of PGE(2) were monitored for 6 h using microdialysis loop catheters. Postoperative pain-related behavior was assessed by recording exploratory locomotive activity. Thoracic muscle surgery decreased rearing and ambulation. Oral ketorolac or rofecoxib 3 mg/kg restored normal rearing and ambulation. Postoperative CSF PGE(2) concentration increased most (threefold) with spinal anesthesia, and not at all with propofol. With surgery under isoflurane or spinal bupivacaine, presurgical oral administration of ketorolac or rofecoxib 3 mg/kg reduced postsurgical CSF PGE(2) levels and tissue PGE(2) levels. Intrathecal ketorolac (4 mu g) reduced CSF PGE2 after surgery without affecting tissue PGE(2) levels, whereas intrathecal L-745,337 (80 mu g) did not reduce CSF PGE(2) Thoracic surgical wounds increase pain-related behavior and CSF and tissue PGE(2) levels, all of which can be attenuated by oral cyclooxygenase inhibitors.