title: Spinal cord dynorphin expression increases, but does not drive microglial prostaglandin production or mechanical hypersensitivity after incisional surgery in rats.
abstract: Spinally released dynorphin contributes to hypersensitivity from nerve injury, inflammation, and sustained morphine treatment, but its role in post-operative pain has not been tested. Intrathecal injection of dynorphin activates cyclooxygenase (COX)-1 and -2 to induce hypersensitivity. Spinal COX-1 expression and activity increase following incisional paw surgery in rats, although the stimulus for this increase is not known. In the current study we tested whether spinal dynorphin expression increases after incisional surgery and induces hypersensitivity in this setting, and whether dynorphin stimulates COX-1 activity in spinal cord microglia. Paw incision resulted in increased prodynorphin immunoreactivity in laminae I, IIo, and V in the L4-L6 spinal cord dorsal horn ipsilateral to surgery. Change in prodynorphin expression did not parallel that of mechanical hypersensitivity. Repeated intrathecal dynorphin A antiserum injection failed to alter mechanical hypersensitivity after incisional surgery, although it was effective against mechanical hypersensitivity following spinal nerve ligation. Paw incision increased COX-1 immunoreactivity in the L4-L6 ipsilateral spinal cord, and these cells were confirmed to be microglia by co-localization with OX-42. Spinal cord microglia in culture expressed COX-1 immunoreactivity and released PGE2, but dynorphin A failed to increase release of PGE2 in these cultures. These results suggest that increased COX-1 expression occurs in spinal cord microglia following incisional surgery. Although prodynorphin immunoreactivity also increases, it likely does not drive COX-1 expression or mechanical hypersensitivity in this setting.
authors.affiliation: Department of Anesthesiology, Center for the Pharmacologic Plasticity in the Presence of Pain, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA.
authors.forename: Xiaying
authors.initials: X
authors.lastname: Zhu
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Vincler
authors.forename: Renee
authors.initials: R
authors.lastname: Parker
authors.forename: James C
authors.initials: JC
authors.lastname: Eisenach
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D051545:Cyclooxygenase 1 / Q000378:metabolism; D004399:Dynorphins / Q000378:metabolism*; D006930:Hyperalgesia / Q000503:physiopathology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D017628:Microglia / Q000378:metabolism*; D010149:Postoperative Pain / Q000503:physiopathology*; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000503:physiopathology*; D014110:Touch
chemical_list: D008565:Membrane Proteins; D011453:Prostaglandins; D004399:Dynorphins; D051545:Cyclooxygenase 1; C496513:Ptgs1 protein, rat