Postoperative pain slows surgical recovery, impacting the return of normal function for weeks, months, or longer. Here we report the antihyperalgesic actions of a new compound, resolvin D1 (RvD1), known to reduce inflammation and to suppress pain after peripheral nerve injury, on the acute pain occurring after paw incision and the prolonged pain after skin-muscle retraction. Injection of RvD1 (20–40 ng) into the L5–L6 intrathecal space 30 minutes before surgery reduces the postincisional primary mechanical hypersensitivity, lowering the peak change by approximately 70% (with 40 ng) and reducing the area under the curve (AUC) for the entire 10-day postincisional course by approximately 60%. Intrathecal injection of RvD1 on postoperative day (POD) 1 reduces the hyperalgesia to the same level as that from preoperative injection within a few hours, an effect that persists for the remaining PODs. Tactile allodynia and hyperalgesia following the skin/muscle incision retraction procedure, measured at the maximum values 12 to 14 days, is totally prevented by intrathecal RvD1 (40 ng) given at POD 2. However, delaying the injection until POD 9 or POD 17 results in RvD1 causing only transient and incomplete reversal of hyperalgesia, lasting for <1 day. These findings demonstrate the potent, effective reduction of postoperative pain by intrathecal RvD1 given before or shortly after surgery. The much more limited effect of this compound on retraction-induced pain, when given 1 to 2 weeks later, suggests that the receptors or pathways for resolvins are more important in the early than the later stages of postoperative pain.
Single intrathecal injections of resolvin D1 in rats before or 1 to 2 days after surgery strongly reduce postoperative pain for several weeks.
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aPain Research Center, Department of Anesthesia, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA, USA
bCenter for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesia, Peri-operative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA, USA
cDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA
*Corresponding author at: Pain Research Center, MRB611, Brigham & Women’s Hospital, 75 Francis Street, Boston, MA 02115, USA. Tel.: +1 617 732 7802/8797; fax: +1 617 732 2801.
1Present address: Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
Submitted July 12, 2010; revised and accepted November 18, 2010.