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.

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