Abstract
Bradykinin is a major inflammatory mediator that produces peripheral pain hypersensitivity by acting on nociceptor peripheral terminals. We show that central sensitization, an activity-dependent increase in synaptic efficacy in the spinal cord, also requires bradykinin B2 receptor activation. B2 receptors are expressed in dorsal horn neurons and B2 agonists substantially augment AMPA and NMDA receptor mediated currents in lamina II neurons, acting pre- and postsynaptically. Augmentation of these currents by bradykinin requires co-activation of protein kinase C (PKC) and A (PKA), the latter via cyclooxygenase-1 (COX1). Administration of an intrathecal B2-selective antagonist to the spinal cord suppresses behavioral manifestations of central sensitization. Bradykinin is a central synaptic neuromodulator that potentiates glutamatergic synaptic transmission in the spinal cord by activating ampersand kinases, producing pain hypersensitivity.
