Contribution of bradykinin to heat-induced substance P release in the hind instep of rats

Life Sci. 1995;56(20):1679-88. doi: 10.1016/0024-3205(95)98574-y.


To investigate the possible contribution of the bradykinin (BK) system to heat-induced substance P (SP) release from the peripheral endings of primary afferent nerves, we used the high molecular weight (HMW) and low molecular weight (LMW) kininogen-deficient rat strain (Brown Norway-Katholiek, B/N-Ka) and the normal rat strain (Brown Norway-Kitasato, B/N-Ki). We found that immersion of the paw of B/N-Ki rats in water of 47 degrees C for 20 min led to significant increases of BK, SP and Evans blue extravasation in the s.c. perfusate, and that similar treatment resulted in significantly lower levels in B/N-Ka rats. Local application of BK (10(-4) M) to the s.c. perfusate and intra-arterial infusion of BK 10(-5) mol/kg) increased Evans blue extravasation and SP release evoked by heat stimulation, respectively, in B/N-Ka rats to similar levels to those in B/N-Ki rats after heat-stimulation without BK treatment. These results indicate that BK released into the extravascular space by noxious stimulation is involved in SP release from the peripheral endings of capsaicin-sensitive primary sensory neurons.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Bradykinin / physiology*
  • Evans Blue
  • Extravasation of Diagnostic and Therapeutic Materials
  • Hindlimb / innervation
  • Hot Temperature
  • Kininogens / deficiency
  • Nerve Endings / metabolism
  • Nerve Endings / physiology*
  • Neurons, Afferent / metabolism
  • Neurons, Afferent / physiology*
  • Perfusion
  • Rats
  • Rats, Inbred BN
  • Substance P / metabolism*


  • Kininogens
  • Substance P
  • Evans Blue
  • Bradykinin