title: Inhibition of acute nociceptive responses in rat spinal cord by a bradykinin B1 receptor antagonist.
abstract: This study used behavioural and in vivo electrophysiological paradigms to examine the effects of systemic and spinal administration of a bradykinin B1 receptor antagonist, compound X, on acute nociceptive responses in the rat. In behavioural experiments, compound X significantly increased the latency to withdraw the hindpaw from a radiant heat source after both intravenous and intrathecal administration, without affecting motor performance on the rotarod. In electrophysiological experiments, both intravenous and direct spinal administration of compound X attenuated the responses of single dorsal horn neurones to noxious thermal stimulation of the hindpaw. These data show that the antinociceptive effects of a bradykinin B1 receptor antagonist are mediated, at least in part, at the level of the spinal cord and suggest a role for spinal bradykinin B1 receptors in acute nociception.
authors.affiliation: Merck Sharp and Dohme, In Vivo Neuroscience Department, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex, CM20 2QR, UK. rachel_conley@merck.com
authors.forename: Rachel K
authors.initials: RK
authors.lastname: Conley
authors.forename: Alan
authors.initials: A
authors.lastname: Wheeldon
authors.forename: Janine K
authors.initials: JK
authors.lastname: Webb
authors.forename: Robert M
authors.initials: RM
authors.lastname: DiPardo
authors.forename: Carl F
authors.initials: CF
authors.lastname: Homnick
authors.forename: Mark G
authors.initials: MG
authors.lastname: Bock
authors.forename: Tsing-Bau
authors.initials: TB
authors.lastname: Chen
authors.forename: Raymond S L
authors.initials: RS
authors.lastname: Chang
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Pettibone
authors.forename: Susan
authors.initials: S
authors.lastname: Boyce
mesh_terms: D000577:Amides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D065169:Bradykinin B1 Receptor Antagonists; D002351:Carrageenan / Q000008:administration & dosage / Q000633:toxicity; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology / Q000379:methods; D005528:Foot; D006614:Hindlimb; D006358:Hot Temperature / Q000009:adverse effects; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D006967:Hypersensitivity / Q000209:etiology / Q000503:physiopathology; D007275:Injections, Intravenous; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009281:Naphthalenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D010147:Pain Measurement / Q000379:methods*; D011597:Psychomotor Performance / Q000187:drug effects; D011759:Pyrrolidines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology
chemical_list: C507656:(3R)-3-(3,4-dichlorophenyl)-N-((1R)-1-(4-(4,5-dihydro-1H-imidazol-2-yl)benzyl)-(2-oxo-2-pyrrolidin-1-ylethyl)-3-(2-naphthylsulfonyl)amino)propanamide; D000577:Amides; D065169:Bradykinin B1 Receptor Antagonists; D009281:Naphthalenes; D011759:Pyrrolidines; D009020:Morphine; D002351:Carrageenan