Bradykinin is a potent inflammatory mediator that causes hyperalgesia. The action
of bradykinin on the sensory system is well documented but its effects on motoneurons,
the final pathway of the motor system, are unknown. By a combination of patch-clamp
recordings and two-photon calcium imaging, we found that bradykinin strongly sensitizes
spinal motoneurons. Sensitization was characterized by an increased ability to generate
self-sustained spiking in response to excitatory inputs. Our pharmacological study
described a dual ionic mechanism to sensitize motoneurons, including inhibition of
a barium-sensitive resting K+ conductance and activation of a nonselective cationic
conductance primarily mediated by Na+. Examination of the upstream signaling pathways
provided evidence for postsynaptic activation of B2 receptors, G protein activation
of phospholipase C, InsP3 synthesis and calmodulin activation. This study questions
the influence of motoneurons in the assessment of hyperalgesia since the withdrawal
motor reflex is commonly used as a surrogate pain model.
