title: Epinephrine as adjuvant for propranolol produces a marked peripheral action in intensifying and prolonging analgesia in response to local dorsal cutaneous noxious pinprick in rats.
abstract: The aim of this study was to evaluate the effect of epinephrine as additive for propranolol as an infiltrative anesthetic. Using a rat model of cutaneous trunci muscle reflex (CTMR), we tested the effect of co-administration of epinephrine with propranolol on infiltrative cutaneous analgesia. Bupivacaine, a long-lasting local anesthetic, was used as control. Subcutaneous propranolol and bupivacaine elicited a dose-dependent local anesthetic effect on infiltrative cutaneous analgesia. On the 50% effective dose (ED50) basis, the relative potency was bupivacaine [2.05 (1.95-2.21) μmol/kg]>propranolol [9.21 (9.08-9.42) μmol/kg] (P<0.01 for each comparison). Subcutaneous epinephrine (0.012 μmol/kg) did not produce cutaneous analgesia. Mixtures of epinephrine (0.012 μmol/kg) with drugs (propranolol or bupivacaine) at ED50 or ED95, respectively, intensified and prolonged drug action on infiltrative cutaneous analgesia. Intraperitoneal injection of combined drugs (propranolol or bupivacaine) at ED95 with epinephrine (0.012 μmol/kg) exhibited no cutaneous analgesia. We concluded that propranolol was less potent but produced a similar duration of action when compared to bupivacaine on infiltrative cutaneous analgesia. Epinephrine as adjuvant for propranolol or bupivacaine enhanced the potency and extended the duration of action on infiltrative cutaneous analgesia.
authors: Department of Food Sciences and Technology, Chia Nan University of Pharmacy and Science, Jen-Te, Tainan City, Taiwan; Department of Anesthesiology, Chi-Mei Medical Center, Yong Kang, Tainan City, Taiwan.
authors: Jann-Inn
authors: JI
authors: Tzeng
authors: Department of Medical Research, Chi-Mei Medical Center, Tainan, Taiwan.
authors: He-Jia
authors: HJ
authors: Pan
authors: Department of Pharmacy, Chia Nan University of Pharmacy and Science, Tainan, Taiwan.
authors: Kuo-Sheng
authors: KS
authors: Liu
authors: Department of Medical Research, Chi-Mei Medical Center, Tainan, Taiwan; Department of Physical Therapy & Graduate Institute of Rehabilitation Science, China Medical University, Taichung, Taiwan. Electronic address: cywhwok@mail.cmu.edu.tw.
authors: Yu-Wen
authors: YW
authors: Chen
authors: Division of Physical Therapy, Department of Physical Medicine and Rehabilitation, Cheng Hsin General Hospital, Taipei, Taiwan.
authors: Yu-Chung
authors: YC
authors: Chen
authors: Department of Medical Research, Chi-Mei Medical Center, Tainan, Taiwan.
authors: Jhi-Joung
authors: JJ
authors: Wang
mesh_terms: D000277:Adjuvants, Pharmaceutic / Q000627:therapeutic use*; D000698:Analgesia; D000779:Anesthetics, Local / Q000627:therapeutic use*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004357:Drug Synergism; D004837:Epinephrine / Q000627:therapeutic use*; D008297:Male; D010146:Pain / Q000188:drug therapy*; D011433:Propranolol / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley
chemical_list: D000277:Adjuvants, Pharmaceutic; D000779:Anesthetics, Local; D011433:Propranolol; D004837:Epinephrine
keywords: (±)-Propranolol HCl (Pub Chem CID: 62882); Bupivacaine HCl (Pub Chem CID: 49852290); Co-administration; Cutaneous analgesia; Epinephrine HCl (Pub Chem CID: 5924); Subcutaneous injection