Mechanisms driving chronic pain-related hyperexcitability in nociceptive sensory neurons

After spinal cord injury, peripheral nerve damage, or chemotherapy, injury-detecting sensory neurons (primary nociceptors) switch from an electrically silent state to a hyperexcitable state that can result in the spontaneous firing of action potentials. This spontaneous activity has been shown to be correlated with chronic pain, and selective suppression of nociceptor hyperactivity by antisense knockdown of a sensory-neuron-specific Na+ channel (Nav1.8) proved to be sufficient to reduce neuropathic pain.

My research employs electrophysiological (patch-clamp) and behavioral approaches to define intracellular signaling pathways that induce and maintain the pain-related spontaneous activity in nociceptors. Of particular interest to my work are the roles of cyclic AMP dependent pathways and circulating cytokines on the generation and maintenance of this nociceptor hyperactive state.

Advances in the knowledge of the molecular signaling maintaining the nociceptor hyperexcitable state are fundamental as they provide new targets to develop efficient therapies, other than opioids, to alleviate chronic pain.