Role of prostaglandins and nitric oxide in the spinal plasticity

1998 Fiscal Year Final Research Report Summary

• Project/Area Number: 08457408
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: Shimane Medical University
• Principal Investigator: SAITO Yoji Shimane Medical University, Anesthesiology, Associate Professor, 医学部, 助教授 (50162243)
• Co-Investigator(Kenkyū-buntansha): KIRIHARA Yumiko Shimane Medical University, Anesthesiology, Technical Official, 医学部, 教務職員 (90234400) ; UCHIDA Hiroshi Shimane Medical University, Anesthesiology, Assistant Professor, 医学部, 講師 (70176692) ; YAMAMORI Yuji Shimane Medical University, Intensive care unit, Assistant Professor, 医学部, 講師 (80230598)
• Project Period (FY): 1996 – 1998
• Keywords: prostaglandin / nitric oxide / hypersensitivity / spinal cord

Research Abstract

This study was designed to investigate the role of prostaglandin (PG) _<2 alpha> on the spinal plasticity in rats. To examine the effects of intrathecally administered PGF_<2 alpha> on the different types of sensory processing, the tail flick (TE) test and the colorectal distension (CD) test were employed to measure responses to noxious stimuli, and the withdrawal response to mechanical pressure produced by Semmes-Weinstein-filaments (SWM) was measured. TF latencies and CD thresholds slightly decreased following the administration of PGF_<2 alpha> Those decreases were reversed by the posttreatment with nitric oxide synthase (NOS) inhibitor, NG-monomethyI-L-arginine (L-NMMA). Agitation scores (ASs) produced by SWM were increased after administration of P0, and the increase in ASs lasted for 7 days. Posttreatment with L-NMMA, NMDA antagonist, MK-801, and GABA agonist, baclofen, decreased in ASs for the first 60 mm. Pretreatment with L-NMMA and baclofen inhibited the increase in ASs during the subsequent 7 days. The number of NOS- immunoreactive neurons after the treatment with PGF_<2 alpha> was increased, especially in lamina III and V compared with saline treatment. Electrophysiological studies were used to examine PGF_<2 alpha> evoked changes in electrical activity of spinal cord neurons. PGF_2 increased spontaneous activity. Receptive field areas (RF) in spinal dorsal horn neurons increased dose-dependently following the treatment with PGF_2 a .The enlarged RF was reduced by the treatment with L-NMMA.These results suggest that hyperactivity of spinal dorsal horn neurons plays an important role in trigger a hypersensitive state in sensory processing pathways at the spinal level and that nitric oxide system including GABA and NMDA receptor systems may be involved the initiation and the maintenance of alpha induced hypersensitive state.