Contribution of diacylglycerol lipase β to pain after surgery

• DOI: 10.2147/jpr.s157208
• Publication Date: 2018-03-04T20:54:16Z
• Authors: Jennifer Luk; Yong Lu; Amanda Ackermann; Xiaoxue Peng; Diane Bogdan; Michelino Puopolo; David Komatsu; Simon Tong; Iwao Ojima; Mario Rebecchi; Martin Kaczocha
• Keywords: Diacylglycerol lipase; 2-Arachidonoylglycerol

Metabolism of the endocannabinoid 2-arachidonoylglycerol (2-AG) yields arachidonic acid (AA), precursor to proalgesic eicosanoids including prostaglandin E2 (PGE2). Diacylglycerol lipase β (DAGLβ) is an enzyme that synthesizes 2-AG and its inhibition reduces eicosanoid levels produces antinociceptive effects in models inflammatory pain. Here we test whether DAGLβ a model postoperative pain.Rats were administered selective inhibitor KT109 or vehicle underwent plantar incision. Postsurgical pain/disability was examined using evoked (mechanical hyperalgesia), functional (incapacitance/weight bearing), functional/spontaneous (locomotion) modalities.Activity-based protein profiling confirmed inhibited lumbar spinal cord (LSC) brain, confirming it systemically active inhibitor. Treatment with reduced basal 2-AG, AA, PGE2 liver but not indicating activity does significantly contribute production within central nervous system. Plantar incision elevated LSC. Although did alter postsurgical LSC, slightly levels. In contrast, clinically efficacious cyclooxygenase ketoprofen completely suppressed Similarly, had no significant effect upon at site, while abolished this location. reversed weight bearing imbalance induced by incision, yet neither nor any on mechanical hyperalgesia. partially rescued locomotor deficit without effect.DAGLβ principal controls derived AA after surgery, inhibitors targeting are unlikely be analgesics superior those already approved treat acute