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

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 latenc...

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Bibliographic Details
Published in:European journal of pharmacology 2005-12, Vol.527 (1-3), p.44-51
Main Authors: CONLEY, Rachel K, WHEELDON, Alan, WEBB, Janine K, DIPARDO, Robert M, HOMNICK, Carl F, BOCK, Mark G, CHEN, Tsing-Bau, CHANG, Raymond S. L, PETTIBONE, Douglas J, BOYCE, Susan
Format: Article
Language:English
Subjects:
Amides - administration & dosage
Amides - pharmacokinetics
Animals
Biological and medical sciences
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
Medical sciences
Morphine - pharmacology
Naphthalenes - administration & dosage
Naphthalenes - pharmacokinetics
Nociceptors - drug effects
Nociceptors - physiology
Pain Measurement - methods
Pharmacology. Drug treatments
Psychomotor Performance - drug effects
Pyrrolidines - administration & dosage
Pyrrolidines - pharmacokinetics
Rats
Rats, Sprague-Dawley
Spinal Cord - drug effects
Spinal Cord - physiology
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Summary: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.
ISSN:0014-2999
1879-0712
DOI:10.1016/j.ejphar.2005.06.057