Central mechanisms of peripheral nerve stimulation in headache disorders

The effect of peripheral neurostimulation has traditionally been attributed to the activation of non-noxious afferent nerve fibers (Aβ-fibers) thought to modulate Aδ and C-fiber-mediated nociceptive transmission in the spinal cord, compatible with the 'gate control theory of pain'. The concept has been extended since its initial description and more recent experimental evidence suggests that the analgesic effects of peripheral nerve stimulation in pain states such as in chronic headache require an interplay of multiple influences. Besides segmental pain-modulating mechanisms in the spinal cord involving various transmitter systems, experimental evidence suggests also a contribution of descending pain modulating pathways in mediating the analgesic effect of peripheral nerve stimulation. Beyond the concept of neuromodulation--decreasing excitation or increasing inhibition--a prerequisite of this arrangement is the convergence of different types of afferent activity and an intact descending modulatory network. In this review, we focus on the functional anatomy, pathophysiological mechanisms and neurophysiological and pharmacological findings elucidating the central mechanisms of peripheral nerve stimulation.