Effects of adrenaline, an alpha 2-adrenoceptor agonist, the volume of injection, and the global pain state of the animal on the activity of epidural sufentanil.
A study was made of the effects of different volumes of injection product, adrenaline, the alpha 2-adrenoceptor-agonist medetomidine and Mycobacterium butyricum on epidural sufentanil in the rat. Increasing the volume of epidural sufentanil, and similarly decreasing the concentration of the injection product, resulted in a potentiation of the analgesic properties of epidural sufentanil without affecting the effects of the drug on the pinna and cornea reflexes and on muscle tonus. An analogue effect was observed if rats were tested for epidural analgesia during a chronic pain phase after inoculation with Mycobacterium butyricum. Adding adrenaline to epidural sufentanil also resulted in an increased analgesia but there was also a minor potentiation of all other behavioural parameters measured. The alpha 2-adrenoceptor-agonist medetomidine, clearly potentiated all behavioural effects induced by epidural sufentanil. As a consequence, there was no gain in specificity for epidural analgesia. Medetomidine, however, clearly reversed the normally observed skeletal muscle rigidity into a muscle hypotonia. Globally, these results thus indicate that manipulations of the volume of injection, the additional treatment with other drugs and the pain state of the animal can alter the activity of epidural sufentanil. Therefore, it might be concluded that the differences in the duration of analgesia observed with epidural sufentanil between human and animal studies can be partially explained in terms of differences between the experimental conditions.
Meert
T F
TF
Department of Neuropsychopharmacology, Janssen research Foundation, Beerse, Belgium.
Noorduin
H
H
Van Craenendonck
H
H
Vermote
P
P
Boersma
F P
FP
Janssen
P A
PA
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D015360:Analgesia, Epidural; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004357:Drug Synergism; D004837:Epinephrine / Q000494:pharmacology*; D005283:Fentanyl / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D020926:Medetomidine; D009170:Nontuberculous Mycobacteria; D051381:Rats; D011919:Rats, Inbred Strains; D017409:Sufentanil
D000316:Adrenergic alpha-Agonists; D000701:Analgesics, Opioid; D007093:Imidazoles; D017409:Sufentanil; D020926:Medetomidine; D005283:Fentanyl; D004837:Epinephrine