Effects of morphine administration on the rat neuropathic pain model

2004 Fiscal Year Final Research Report Summary

• Project/Area Number: 14571436
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: Shimane University (2004); Shimane Medical University (2002-2003)
• Principal Investigator: KIRIHARA Yumiko Shimane University, Experimental Animals, Technical Official, 医学部, 教務職員 (90234400)
• Co-Investigator(Kenkyū-buntansha): SAITO Yoji Shimane University, Anesthesiology, Professor, 医学部, 教授 (50162243) ; DOI Katsushi Shimane University, Anesthesiology, Associate Professor, 医学部, 助教授 (20304272)
• Project Period (FY): 2002 – 2004
• Keywords: neuropathic pain / opioid / intrathecal administration / hyperalgesia / noxious stimulus / non-noxious stimulus

Research Abstract

Opioids have been used for the treatment of patients suffering from neuropathic pain. However, their effects on neuropathic pain are still controversial. Clinical studies have shown inconsistent results. The present study was designed to investigate the characteristics of the modulation of opioids on the hypersensitive state in the rat neuropathic pain model.
With approval of the animal research and use committee of Shimane University, neuropathic pain model was created by placing four loosely tied ligatures around the left sciatic nerve in male Sprague-Dawley rats. To measure the response to noxious heat or mechanical stimulus, radiant heating(RH) test or paw pressure(PP) test was performed. The threshold to non-noxious stimulus was measured using Semmes-Weinstein monofilament(SWM). Measurements were performed on 5,7,9,12, and 14 days after the ligation.
Responses to both noxious and non-noxious stimuli increased 5 days after the sciatic nerve ligation in the rats. A bolus injection of morphine produced antinociceptive effects in both nerve ligated and non-nerve ligated paws in the rats. The hypersensitive state of nerve ligated rats did not change after the morphine antinociceptive effects disappeared.
The results of PP test showed that rats given repeated morphine increased hypersensitive state in non-ligated paw from day 7 to day 12 but in ligated paw on only day 9 compared to rats given repeated saline. Repeated morphine produced stronger morphine tolerance on non-ligated paw than on ligated paw. Chronic morphine treatment increased hypersensitive state and decreased antinociceptive effects in both ligated and non-ligated paws. However, it is less effective on ligated paws than non-ligated paws.
The coadministration of morphine and gabapentin reduced hypersensitive state and strongly inhibited the morphine tolerance on ligated paw than on non-ligated paw. The coadministration of morphine and gabapentin may become an effective clinical treatment for patients suffering from neuropathic pain.