Bradykinin excites tetrodotoxin-resistant primary afferent fibers.

Bradykinin is a nonapeptide that plays a central role in the production of pain and inflammation. A horizontal spinal cord slice preparation with attached dorsal root and dorsal root ganglion was used to study the effect of bradykinin on afferent fibers. Intracellular recordings were made from dorsal root ganglion and dorsal horn neurons. Bath application of bradykinin (1 microM) to the dorsal root ganglion compartment produced a depolarization (5 +/+ 0.8 mV) and firing of action potentials in eight out of eighteen dorsal root ganglion neurons tested. Simultaneous intracellular recordings from dorsal horn neurons revealed that the application of bradykinin to dorsal root ganglion, peripheral nerve trunk or dorsal root resulted in the synaptic activation of dorsal horn neurons. The depolarizing effect of bradykinin on the dorsal root ganglion neurons and its synaptic excitatory effect on dorsal horn neurons was abolished by pretreatment of the same segment of sensory neurons by a B2 bradykinin receptor antagonist (D-Arg0,Hyp3,beta-Thi5,8,D-Phe7)-bradykinin (5 microM). Bath application of tetrodotoxin (TTX; 0.2-1 microM) to the sensory neurons blocked electrically-evoked action potentials in large dorsal root ganglion neurons and, consequently, excitatory postsynaptic potentials in dorsal horn neurons evoked by electrical activation of low threshold afferent fibers. However, the stimulatory effects, both depolarization and firing of action potentials, of bradykinin were resistant to TTX. Replacement of sodium ions with TRIS completely abolished the stimulatory effect of bradykinin on the sensory neurons. Bradykinin potentiated the postsynaptic potentials induced by electrical stimulation of TTX-resistant afferent fibers.(ABSTRACT TRUNCATED AT 250 WORDS)