title: Antinociception after intrathecal biphalin application in rats: a reevaluation and novel, rapid method to confirm correct catheter tip position.
abstract: 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.
authors.affiliation: Medical Research Centre, Polish Academy of Sciences, Warszawa, Poland. andrzej@lipkowski.org
authors.forename: Dariusz
authors.initials: D
authors.lastname: Kosson
authors.forename: Iwona
authors.initials: I
authors.lastname: Bonney
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Carr
authors.forename: Ewa
authors.initials: E
authors.lastname: Mayzner-Zawadzka
authors.forename: Andrzej W
authors.initials: AW
authors.lastname: Lipkowski
mesh_terms: 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
chemical_list: D000701:Analgesics, Opioid; D004745:Enkephalins; C053673:biphalin