Does chronic nociceptive stimulation alter the development of morphine tolerance?
Conflicting results exist concerning the issues of whether chronic nociceptive stimulation (a) increases or decreases the effectiveness of morphine analgesia, and (b) facilitates or inhibits the development of narcotic tolerance. We carried out a series of experiments with appropriate controls in order to examine these two issues and their possible relationship. In experiment 1, rats received complete Freund's adjuvant (CFA), a chronic nociceptor, injected into a single hind paw or anesthesia without injection, together with morphine or placebo pellets in a 2 x 2 study design. The data indicate that the presence of the chronic nociceptive stimulus significantly facilitated the development of tolerance to morphine analgesia as measured using tail-flick latency (TFL) testing. Experiment 2 was designed to compare the analgetic effectiveness of an acute injection of morphine in rats experiencing chronic nociceptive stimulation and in controls. CFA was injected in the right hindpaw, and nine days later TFLs were tested after morphine doses of 1 and 2 mg/kg s.c. The data obtained showed that chronic nociceptive stimulation significantly reduced the effectiveness of morphine at the 1 mg/kg dose. However, baseline TFLs appeared to be shorter in rats treated with CFA, suggesting that the decrease in morphine effectiveness could be due to a general increase in pain sensitivity. Therefore, a third experiment was performed, using a less intense thermal stimulus to prolong baseline TFLs and accentuate any potential differences. Sixteen rats either received CFA or served as controls. TFLs were then measured at baseline and one hour after a 0.5 mg/kg dose of morphine.(ABSTRACT TRUNCATED AT 250 WORDS)
Gutstein
H B
HB
Department of Anesthesiology, University of Michigan, C.S. Mott Children's Hospital, Ann Arbor 48109-0211, USA.
Trujillo
K A
KA
Akil
H
H
D000818:Animals; D004361:Drug Tolerance; D005528:Foot; D005620:Freund's Adjuvant / Q000494:pharmacology; D007267:Injections; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009619:Nociceptors / Q000502:physiology*; D010146:Pain; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D012016:Reference Values; D013268:Stimulation, Chemical; D013997:Time Factors
D009020:Morphine; D005620:Freund's Adjuvant