Lack of the development of antinociceptive tolerance to morphine and U-50,488H in neuropathic pain model mice following a partial sciatic nerve ligation

• Published in: Japanese Journal of Pharmacology Vol. 85; no. suppl.1; p. 225
• Main Authors: Sourisak Sounvoravong, Masakatsu Takahashi, Mihoko N. Nakashima, Ken-ichiro Nakashima
• Format: Journal Article
• Language: Japanese
• Published: The Japanese Pharmacological Society 2001
• ISSN: 0021-5198; 1347-3506

Based on the fact that repeated morphine produced the delay in the development of analgesic tolerance in formalin-treated mice, we have studied the alteration of the development of tolerance to morphine- and U-50,488Hinduced analgesia in neuropathic pain model mice. In mice suffered from partial ligation of the sciatic nerve, morphine, 10 mg/kg .s.c., produced a weak analgesic effect; however, both intracerebroventricular (i.c.v.) and intrathecal (i.t.) administration of morphine, 10 μg and 0.3-10 μg/mouse, respectively, and U-50,488H given 5 mg/kg s.c., 20 μg/mouse i.t., produced antinociceptive effect to the same extent of that in normal mice in the tail-pinch test. Neither repeated morphine, given i.c.v. and i.t., nor U-50,488H, given s.c. and i.t., resulted in the development of tolerance in the neuropathic pain model animals. These findings here that while s.c. morphine failed to produce antinociception, U-50,488H produced full antinociception and daily administration of the compound did not develop tolerance in the neuropathic animals support the activation of κ -opioid receptor system in pain state, and also suggest the potential advantage of κ -receptor agonist in relief of a certain neuropathic pain.