title: The effect of clonidine pretreatment on epidural resiniferatoxin in a neuropathic pain rat model.
abstract: Resiniferatoxin (RTX) is an ultrapotent synthetic TRPV1 (transient receptor potential vanilloid subtype 1) agonist with significant initial transient hyperalgesia followed by a prolonged analgesic effect in response to thermal stimulus. Using a rat model of neuropathic pain, we evaluated the effect of pretreatment with clonidine-which has been shown to relieve intradermal capsaicin-induced hyperalgesia-on the initial hyperalgesic response and the thermal analgesic property of RTX. Thirty-six male rats were divided into 6 treatment groups (n=6 each):RTX 500 ng, RTX 1 μg, clonidine 20 μg (Cl), Cl＋RTX 500 ng, Cl＋RTX 1 μg, or normal saline 20 μL (control). We evaluated the short-term (180 min) and long-term (20 days) analgesic effects of RTX after thermal stimulation and mechanical stimulation. RTX had significant initial transient hyperalgesia followed by a prolonged analgesic effect in response to the thermal stimulus, but the RTX 500 ng and RTX 1 μg groups showed no initial short-term thermal hyperalgesic responses when pretreated with clonidine. The Cl＋RTX 1 μg rats' behavior scores indicated that they were more calm and comfortable compared to the RTX 1 μg rats. Even though we cannot precisely confirm that pretreatment with clonidine potentiates or adds to the analgesic effect of RTX, clonidine pretreatment with epidural RTX eliminated the initial RTX-associated hyperalgesic response and systemic toxicity in this neuropathic pain rat model.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gachon University Gil Hospital, Incheon 405-760, Korea.
authors.forename: Mi Geum
authors.initials: MG
authors.lastname: Lee
authors.forename: Dong Kyu
authors.initials: DK
authors.lastname: Lee
authors.forename: Billy K
authors.initials: BK
authors.lastname: Huh
authors.forename: Sang Sik
authors.initials: SS
authors.lastname: Choi
authors.forename: Hee Zoo
authors.initials: HZ
authors.lastname: Kim
authors.forename: Byung Gun
authors.initials: BG
authors.lastname: Lim
authors.forename: Hong Soon
authors.initials: HS
authors.lastname: Kim
authors.forename: Yun Suk
authors.initials: YS
authors.lastname: Choi
authors.forename: Won Seok
authors.initials: WS
authors.lastname: Hur
authors.forename: Mi Kyoung
authors.initials: MK
authors.lastname: Lee
mesh_terms: D015360:Analgesia, Epidural / Q000379:methods; D000700:Analgesics / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D003000:Clonidine / Q000008:administration & dosage / Q000627:therapeutic use*; D004224:Diterpenes / Q000008:administration & dosage* / Q000627:therapeutic use*; D006930:Hyperalgesia / Q000150:complications; D007268:Injections, Epidural; D008297:Male; D023421:Models, Animal; D009437:Neuralgia / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000700:Analgesics; D004224:Diterpenes; C024353:resiniferatoxin; D003000:Clonidine