Inhibition of acute nociceptive responses in rat spinal cord by a bradykinin B1 receptor antagonist

Rachel K Conley; Alan Wheeldon; Janine K Webb; Robert M DiPardo; Carl F Homnick; Mark G Bock; Tsing-Bau Chen; Raymond S L Chang; Douglas J Pettibone; Susan Boyce

doi:10.1016/j.ejphar.2005.06.057

Inhibition of acute nociceptive responses in rat spinal cord by a bradykinin B1 receptor antagonist

Eur J Pharmacol. 2005 Dec 19;527(1-3):44-51. doi: 10.1016/j.ejphar.2005.06.057. Epub 2005 Nov 28.

Authors

Rachel K Conley¹, Alan Wheeldon, Janine K Webb, Robert M DiPardo, Carl F Homnick, Mark G Bock, Tsing-Bau Chen, Raymond S L Chang, Douglas J Pettibone, Susan Boyce

Affiliation

¹ Merck Sharp and Dohme, In Vivo Neuroscience Department, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex, CM20 2QR, UK. [email protected]

PMID: 16310181
DOI: 10.1016/j.ejphar.2005.06.057

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.

Publication types

Comparative Study

MeSH terms

Amides / administration & dosage
Amides / pharmacokinetics*
Animals
Bradykinin B1 Receptor Antagonists*
Carrageenan / administration & dosage
Carrageenan / toxicity
Disease Models, Animal
Dose-Response Relationship, Drug
Electrophysiology / methods
Foot
Hindlimb
Hot Temperature / adverse effects
Hyperalgesia / etiology
Hyperalgesia / physiopathology
Hyperalgesia / prevention & control
Hypersensitivity / etiology
Hypersensitivity / physiopathology
Injections, Intravenous
Injections, Spinal
Male
Morphine / pharmacology
Naphthalenes / administration & dosage
Naphthalenes / pharmacokinetics*
Nociceptors / drug effects
Nociceptors / physiology
Pain Measurement / methods*
Psychomotor Performance / drug effects
Pyrrolidines / administration & dosage
Pyrrolidines / pharmacokinetics*
Rats
Rats, Sprague-Dawley
Spinal Cord / drug effects*
Spinal Cord / physiology

Substances

(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
Amides
Bradykinin B1 Receptor Antagonists
Naphthalenes
Pyrrolidines
Morphine
Carrageenan