Neuropathic pain: role for presynaptic T-type channels in nociceptive signaling

Pain is an important clinical problem and, in its chronic form, may be a disabling condition. Most currently available therapies are insufficient and/or accompanied by serious side effects. Recent studies have implicated the CaV3.2 isoform of T-type Ca channels in nociceptive signaling. CaV3.2 channels are located in the somas of dorsal root ganglion cells and in the central endings of these cells in the dorsal horn of the spinal cord. These channels can support the development and maintenance of both physiological (nociceptive) and pathological (neuropathic) pain. In this review, we summarize the most recent evidence linking the presynaptic CaV3.2 channels to the etiology of neuropathic pain disorders. In particular, we focus on data linking plasticity of CaV3.2 channels with neuropathic pain disorders associated with mechanical peripheral nerve injury and with diabetic peripheral neuropathy. We also discuss the development of potential pain therapies aimed at these channels.