Antinociception after intrathecal biphalin application in rats: a reevaluation and novel, rapid method to confirm correct catheter tip position.
The opioid peptide dimmer biphalin [(Tyr-D-Ala-Gly-Phe-NH-)(2)] has high potency both in vivo and in vitro. Its antinociceptive activity depends on the route of administration: the lowest potency is after subcutaneous, and the highest after intrathecal or inracerebroventricular administration. We tested the analgesic activity of biphalin in a wide range of doses after intrathecal administration to rats. Doses as low as 0.005 nmol produced significant analgesia. Increasing the dose up to 2 nmol elevated and prolonged antinociception without any evident side effects, indicating that biphalin is an extremely potent opioid after intrathecal application with a wide therapeutic window. The highest dose tested (20 nmol) produced full analgesia and body rigidity lasting 2-3 h. After muscle tone returned to normal, antinociception lasted for several more hours. During these studies we observed a correlation between responses to biphalin and catheter placement. Postmortem verification of catheter placement revealed that in those rats in which high-dose biphalin did not produce analgesia or muscle rigidity, the catheter was positioned incorrectly or the flow of drug solution was obstructed. Therefore, a secondary conclusion is that assessment of transient rigidity after administration of a high dose of biphalin may be used as an easy method to confirm intrathecal placement of the catheter.
Kosson
Dariusz
D
Medical Research Centre, Polish Academy of Sciences, Warszawa, Poland. andrzej@lipkowski.org
Bonney
Iwona
I
Carr
Daniel B
DB
Mayzner-Zawadzka
Ewa
E
Lipkowski
Andrzej W
AW
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D002405:Catheterization, Central Venous / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004745:Enkephalins / Q000494:pharmacology*; D007278:Injections, Spinal; D008297:Male; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley
D000701:Analgesics, Opioid; D004745:Enkephalins; C053673:biphalin