title: Low dose alpha-2 antagonist paradoxically enhances rat norepinephrine and clonidine analgesia.
abstract: Ultralow-dose opioid antagonists prolong opioid antinociception and block tolerance. In this study we determined whether low doses of the α-2 adrenergic receptor (A2-R) antagonist, atipamezole, similarly influenced A2-R-induced antinociception and tolerance. In rats, intrathecal norepinephrine (NE) or clonidine in combination with atipamezole was tested using tail-flick and paw pressure tests. Acute tolerance to NE was induced by serial injections. Low-dose atipamezole significantly prolonged NE and clonidine-induced antinociception. Coadministration of atipamezole with A2-R agonists also prevented loss of agonist potency in the acute tolerance model. This study demonstrates paradoxical effects of low-dose A2-R antagonists augmenting A2-R agonist-induced analgesia.
authors.affiliation: Department of Anesthesiology & Perioperative Medicine, Queen's University, Kingston, Ontario, Canada.
authors.forename: Brian
authors.initials: B
authors.lastname: Milne
authors.forename: Maaja
authors.initials: M
authors.lastname: Sutak
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Cahill
authors.forename: Khem
authors.initials: K
authors.lastname: Jhamandas
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000008:administration & dosage*; D000698:Analgesia / Q000379:methods*; D000700:Analgesics / Q000008:administration & dosage; D000818:Animals; D003000:Clonidine / Q000008:administration & dosage; D004357:Drug Synergism; D007093:Imidazoles / Q000008:administration & dosage; D008297:Male; D009638:Norepinephrine / Q000008:administration & dosage*; D010146:Pain / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000700:Analgesics; D007093:Imidazoles; C050701:atipamezole; D003000:Clonidine; D009638:Norepinephrine