title: Knockdown of spinal opioid receptors by antisense targeting beta-arrestin reduces morphine tolerance and allodynia in rat.
abstract: The development of morphine tolerance and sciatic nerve injury-induced allodynia after functional knockdown of spinal opioid receptors using antisense oligonucleotides targeting beta-arrestin was investigated. Ineffectiveness of morphine in neuropathic pain suggests an implication of the same mechanism in these two processes. The development of morphine tolerance (10 microg intrathecally (i.th.), every 12 h) was significantly inhibited in rats, which received i.th. beta-arrestin antisenses (2 nM). Acute and chronic (6 days) i.th. administration of antisenses antagonized the allodynia in the rat model of neuropathic pain. Our results demonstrated that i.th. administration of beta-arrestin antisenses delayed development of tolerance to morphine and nerve injury-induced cold allodynia, which suggest that both of the investigated phenomena may be mediated by a similar mechanism, e.g. receptor desensitization. Moreover, the antisense oligonucleotides targeting beta-arrestin may constitute a new approach to the therapy of neuropathic pain.
authors.affiliation: Department of Molecular Neuropharmacology, Institute of Pharmacology, 12 Smetna Street, 31-343, Kraków, Poland. przebar@if-pan.krawkow.pl
authors.forename: Barbara
authors.initials: B
authors.lastname: Przewlocka
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Sieja
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Starowicz
authors.forename: Marcin
authors.initials: M
authors.lastname: Maj
authors.forename: Wiktor
authors.initials: W
authors.lastname: Bilecki
authors.forename: Ryszard
authors.initials: R
authors.lastname: Przewlocki
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D019390:Arrestins / Q000235:genetics*; D003080:Cold Temperature; D004361:Drug Tolerance; D006941:Hyperesthesia / Q000209:etiology / Q000503:physiopathology*; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009292:Narcotic Antagonists; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000293:injuries; D013116:Spinal Cord / Q000378:metabolism*; D014947:Wounds and Injuries / Q000150:complications; D000071557:beta-Arrestins
chemical_list: D000701:Analgesics, Opioid; D019390:Arrestins; D009292:Narcotic Antagonists; D016376:Oligonucleotides, Antisense; D000071557:beta-Arrestins; D009020:Morphine