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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

Journal Article


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Abstract


  • 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 B 2 receptors, PLC, and release of calcium from intracellular stores, robustly inhibits M-type K + channels and opens Ca 2+-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.

Authors


  •   Liu, Boyi (external author)
  •   Linley, John (external author)
  •   Du, Xiaona (external author)
  •   Zhang, Xuan (external author)
  •   Ooi, Lezanne
  •   Zhang, Hailin (external author)
  •   Gamper, Nikita (external author)

Publication Date


  • 2010

Citation


  • Liu, B., Linley, J. E., Du, X., Zhang, X., Ooi, L., Zhang, H. & Gamper, N. (2010). 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. Journal of Clinical Investigation, 120 (4), 1240-1252.

Scopus Eid


  • 2-s2.0-77951183327

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=7999&context=scipapers

Ro Metadata Url


  • http://ro.uow.edu.au/scipapers/4656

Has Global Citation Frequency


Number Of Pages


  • 12

Start Page


  • 1240

End Page


  • 1252

Volume


  • 120

Issue


  • 4

Place Of Publication


  • United States

Abstract


  • 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 B 2 receptors, PLC, and release of calcium from intracellular stores, robustly inhibits M-type K + channels and opens Ca 2+-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.

Authors


  •   Liu, Boyi (external author)
  •   Linley, John (external author)
  •   Du, Xiaona (external author)
  •   Zhang, Xuan (external author)
  •   Ooi, Lezanne
  •   Zhang, Hailin (external author)
  •   Gamper, Nikita (external author)

Publication Date


  • 2010

Citation


  • Liu, B., Linley, J. E., Du, X., Zhang, X., Ooi, L., Zhang, H. & Gamper, N. (2010). 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. Journal of Clinical Investigation, 120 (4), 1240-1252.

Scopus Eid


  • 2-s2.0-77951183327

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=7999&context=scipapers

Ro Metadata Url


  • http://ro.uow.edu.au/scipapers/4656

Has Global Citation Frequency


Number Of Pages


  • 12

Start Page


  • 1240

End Page


  • 1252

Volume


  • 120

Issue


  • 4

Place Of Publication


  • United States