title: Clonidine as an adjuvant for propranolol enhances its effect on infiltrative cutaneous analgesia in rats.
abstract: Clonidine prolongs duration of analgesia when used as an adjunct to local anesthetics for infiltrative cutaneous analgesia, and propranolol produces local anesthesia. The purpose of the experiment was to evaluate clonidine as an adjuvant for propranolol on the quality and duration of cutaneous analgesia. A rat model of cutaneous trunci muscle reflex (CTMR) in response to local skin pinprick was employed to evaluate the cutaneous analgesic effect of propranolol combined with clonidine. The long-lasting local anesthetic bupivacaine was used as control. Cutaneous analgesia elicited by propranolol and bupivacaine was dose-dependent, and both propranolol (9.0μmol) and bupivacaine (1.8μmol) produced 100% nociceptive blockade. On an 50% effective dose (ED50) basis, the relative potency was bupivacaine [0.48 (0.42-0.55) μmol] greater than propranolol [2.27 (1.98-2.54) μmol] (p<0.01). Subcutaneous saline and clonidine (0.12μmol) did not produce cutaneous analgesia. The mixture of an ineffective-dose clonidine (0.12μmol) and a drug (propranolol or bupivacaine) at ED50 or ED95 increased the potency and extended the duration at producing cutaneous analgesia. The resulting data demonstrated that propranolol is less potent than bupivacaine as an infiltrative anesthetic. Clonidine as an adjuvant for propranolol or bupivacaine has a significant peripheral action in increasing the depth and duration of action on infiltrative cutaneous analgesia.
authors.affiliation: Department of Physical Therapy, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Ching-Hsia
authors.initials: CH
authors.lastname: Hung
authors.affiliation: Department of General Surgery, Chi Mei Medical Center, Tainan and Liouying, Taiwan; Department of Electrical Engineering, Southern Taiwan University of Science and Technology, Tainan, Taiwan.
authors.forename: Chong-Chi
authors.initials: CC
authors.lastname: Chiu
authors.affiliation: Department of Pharmacy, Chia Nan University of Pharmacy and Science, Tainan, Taiwan.
authors.forename: Kuo-Sheng
authors.initials: KS
authors.lastname: Liu
authors.affiliation: Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan.
authors.forename: Jhi-Joung
authors.initials: JJ
authors.lastname: Wang
authors.affiliation: Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan; Department of Physical Therapy, College of Health Care, China Medical University, Taichung, Taiwan. Electronic address: cywhwok@mail.cmu.edu.tw.
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Chen
mesh_terms: D000279:Administration, Cutaneous; D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use; D000779:Anesthetics, Local / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002045:Bupivacaine / Q000494:pharmacology / Q000627:therapeutic use; D003000:Clonidine / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D008297:Male; D011433:Propranolol / Q000494:pharmacology* / Q000627:therapeutic use; D017207:Rats, Sprague-Dawley
chemical_list: D000700:Analgesics; D000779:Anesthetics, Local; D011433:Propranolol; D003000:Clonidine; D002045:Bupivacaine
keywords: Adjuvant; Bupivacaine; Clonidine; Infiltrative cutaneous analgesia; Propranolol; Subcutaneous injection