Bradykinin produces pain hypersensitivity by potentiating spinal cord glutamatergic synaptic transmission.

Published

Journal Article

Bradykinin, an inflammatory mediator, sensitizes nociceptor peripheral terminals reducing pain threshold. We now show that the B2 kinin receptor is expressed in rat dorsal horn neurons and that bradykinin, a B2-specific agonist, augments AMPA- and NMDA-induced, and primary afferent-evoked EPSCs, and increases the frequency and amplitude of miniature EPSCs in superficial dorsal horn neurons in vitro. Administration of bradykinin to the spinal cord in vivo produces, moreover, an NMDA-dependent hyperalgesia. We also demonstrate that nociceptive inputs result in the production of bradykinin in the spinal cord and that an intrathecal B2-selective antagonist suppresses behavioral manifestations of central sensitization, an activity-dependent increase in glutamatergic synaptic efficacy. Primary afferent-evoked central sensitization is, in addition, reduced in B2 receptor knock-out mice. We conclude that bradykinin is released in the spinal cord in response to nociceptor inputs and acts as a synaptic neuromodulator, potentiating glutamatergic synaptic transmission to produce pain hypersensitivity.

Full Text

Duke Authors

Cited Authors

  • Wang, H; Kohno, T; Amaya, F; Brenner, GJ; Ito, N; Allchorne, A; Ji, R-R; Woolf, CJ

Published Date

  • August 31, 2005

Published In

Volume / Issue

  • 25 / 35

Start / End Page

  • 7986 - 7992

PubMed ID

  • 16135755

Pubmed Central ID

  • 16135755

Electronic International Standard Serial Number (EISSN)

  • 1529-2401

Digital Object Identifier (DOI)

  • 10.1523/JNEUROSCI.2393-05.2005

Language

  • eng

Conference Location

  • United States