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The Role of Phospholipase A2 and Nitric Oxide in Pain-Related Behavior Produced by an Allograft of Intervertebral Disc Material to the Sciatic Nerve of the Rat

Kawakami, Mamoru, MD, PhD*; Tamaki, Tetsuya, MD, PhD*; Hashizume, Hiroshi, MD*; Weinstein, James N., DO, MS; Meller, Stephen T., PhD

Basic Science

Study Design. To elucidate the pathomechanisms of radicular pain secondary to lumbar disc herniation.

Objectives. To evaluate whether intervertebral disc material applied to the sciatic nerve produces hyperalgesia, and if the hyperalgesia is influenced by inhibitors of phospholipase A2 and nitric oxide synthase.

Summary of Background Data. Previously, the authors reported that application of nucleus pulposus and anulus fibrosus material to the lumbar epidural space produces different forms of hyperalgesia (mechanical versus thermal), with different and distinct histologic changes. Additional pharmacologic studies showed that phospholipase A2 and nitric oxide are involved in the mechanisms that produce the mechanical and thermal hyperalgesia, respectively. Nω-nitro-L-arginine methyl ester and mepacrine are relatively selective inhibitors of nitric oxide synthase and phospholipase A2, respectively. However, it is not known what the relation is between the hyperalgesia produced and the activation and involvement of phospholipase A2 and production of nitric oxide, or why the application of nucleus pulposus and nucleus pulposus with anulus fibrosus produces different types of hyperalgesia.

Methods. Experiments were performed in five groups of rats: The control group (no treatment), the sham group (exposure of the sciatic nerve only), the fat group (allografted fat on the sciatic nerve), the nucleus pulposus group (allografted nucleus pulposus) and the nucleus pulposus + anulus fibrosus group (allografted nucleus pulposus and anulus fibrosus). Withdrawal threshold and latency from mechanical pressure and a radiant heat to hind paws were measured preoperatively and postoperatively. After local sciatic nerve administration of Nϑ-nitro-L-arginine methyl ester or mepacrine into the operated site, sensitivities to noxious stimuli were reevaluated after treatment.

Results. Only rats in the nucleus pulposus group showed evidence of mechanical hyperalgesia. However, injection of Nϑ-nitro-L-arginine methyl ester resulted in evidence of mechanical hyperalgesia in the nucleus pulposus + anulus fibrosus group. Mechanical hyperalgesia was produced in the nucleus pulposus group and after injection of Nϑ-nitro-L-arginine methyl ester in the nucleus pulposus + anulus fibrosus group, both of which returned to normal after mepacrine injection. There were no significant changes in sensitivity to thermal stimuli in any of the experimental groups.

Conclusion. It appears that phospholipase A2 and nitric oxide play important but different roles in pathomechanisms of radicular pain in lumbar disc herniation.

From the *Department of Orthopedic Surgery, Wakayama Medical College, Wakayama, Japan, the †Department of Orthopedic Surgery, University of Iowa, Iowa City, Iowa, and the ‡OTC-Health Care Technology Division, The Procter & Gamble Company, Cincinnati, Ohio.

Supported in part by grants from Japan Orthopaedics and Traumatology Foundation, Inc. no. 0066, 1994, and the Japan Ministry of Education, Science and Culture grant-in-aid for scientific research no. 06671473, 1994-5.

Acknowledgment date: March 14, 1996.

Acceptance date: August 19, 1996.

Device status category: 1.

Address reprint requests to Mamoru Kawakami, MD, PhD; Department of Orthopedic Surgery; Wakayama Medical College; 27,7-Bancho; Wakayama City; Wakayama Japan 640.

© 1997 by Lippincott Williams & Wilkins