The acute nociceptive signals induced by bradykinin in rat sensory neurons are mediated by inhibition of M-type K+ channels and activation of Ca2+-activated Cl- channels

Bradykinin (BK) is an inflammatory mediator and one of the most potent endogenous pain-inducing substances. When released at sites of tissue damage or inflammation, or applied exogenously, BK produces acute spontaneous pain and causes hyperalgesia (increased sensitivity to potentially painful stimul...

Full description

Saved in:
Bibliographic Details
Published inThe Journal of clinical investigation Vol. 120; no. 4; pp. 1240 - 1252
Main Authors Liu, Boyi, Linley, John E, Du, Xiaona, Zhang, Xuan, Ooi, Lezanne, Zhang, Hailin, Gamper, Nikita
Format Journal Article
LanguageEnglish
Published United States American Society for Clinical Investigation 01.04.2010
Subjects
Animals
Bradykinin - pharmacology
Calcium - metabolism
Chloride Channels - drug effects
Ganglia, Spinal - drug effects
Ganglia, Spinal - physiology
Nociceptors - physiology
Pain - chemically induced
Potassium Channel Blockers - pharmacology
Rats
Rats, Sprague-Dawley
Rats, Wistar
Receptor, Bradykinin B2 - physiology
Sensory Receptor Cells - drug effects
Sensory Receptor Cells - physiology
Signal Transduction
Online AccessGet full text

Cover

More Information
Summary:Bradykinin (BK) is an inflammatory mediator and one of the most potent endogenous pain-inducing substances. When released at sites of tissue damage or inflammation, or applied exogenously, BK produces acute spontaneous pain and causes hyperalgesia (increased sensitivity to potentially painful stimuli). The mechanisms underlying spontaneous pain induced by BK are poorly understood. Here we report that in small nociceptive neurons from rat dorsal root ganglia, BK, acting through its B2 receptors, PLC, and release of calcium from intracellular stores, robustly inhibits M-type K+ channels and opens Ca2+-activated Cl- channels (CaCCs) encoded by Tmem16a (also known as Ano1). Summation of these two effects accounted for the depolarization and increase in AP firing induced by BK in DRG neurons. Local injection of inhibitors of CaCC and specific M-channel openers both strongly attenuated the nociceptive effect of local injections of BK in rats. These results provide a framework for understanding spontaneous inflammatory pain and may suggest new drug targets for treatment of such pain.
Bibliography:Authorship note: Boyi Liu and John E. Linley contributed equally to this work.
ISSN:0021-9738
1558-8238
DOI:10.1172/jci41084