The interaction of antinociceptive effects of morphine and GABA receptor agonists within the rat spinal cord.
Previous reports indicate that there may be an interaction between gamma-aminobutyric acid receptors and opioid receptors systems within the spinal cord, the antinociceptive effects of which have not been elucidated. We examined the effects of intrathecally coadministered morphine and muscimol or baclofen on somatic and visceral antinociception in rats. The tail flick (TF) test and colorectal distension (CD) test were used to assess somatic and visceral antinociceptive effects, respectively. Motor function was also assessed. The measurements were performed for 180 min after the intrathecal administration of morphine (0.1-10 micrograms), muscimol (0.2-10 micrograms), baclofen (0.03-1 microgram), combination of morphine and muscimol or baclofen, or saline. Morphine, muscimol, or baclofen increased both TF latency and CD threshold in a dose-dependent fashion. Although morphine 0.1 microgram, muscimol 0.2 microgram, or baclofen 0.03 microgram alone did not significantly increase TF latency and CD threshold, the combination of morphine 0.1 microgram and muscimol 0.2 microgram or baclofen 0.03 microgram significantly increased both TF latency and CD threshold. The coadministration of muscimol or baclofen increased the antinociceptive effects of morphine in intensity and duration. None of the rats showed motor dysfunction after the coadministration of morphine and muscimol 0.2 microgram, although muscimol produced motor paralysis of the lower limbs in a dose-dependent fashion. Those results suggest a clinical relevance of the coadministration of mu-opioids and GABA receptor agonists for pain control.


CONCLUSIONS
We examined the antinociceptive interaction between morphine and muscimol or baclofen at the spinal level in rats. Intrathecal muscimol or baclofen potentiated both somatic and visceral antinociceptive effects of morphine.
Hara
K
K
Department of Anesthesiology, Shimane Medical University, Japan.
Saito
Y
Y
Kirihara
Y
Y
Yamada
Y
Y
Sakura
S
S
Kosaka
Y
Y
D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000818:Animals; D001418:Baclofen / Q000008:administration & dosage; D003106:Colon; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004357:Drug Synergism; D018755:GABA Agonists / Q000008:administration & dosage*; D006358:Hot Temperature; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D009118:Muscimol / Q000008:administration & dosage; D010146:Pain / Q000517:prevention & control*; D017288:Pain Threshold; D051381:Rats; D017207:Rats, Sprague-Dawley
D000701:Analgesics, Opioid; D018755:GABA Agonists; D009118:Muscimol; D009020:Morphine; D001418:Baclofen