DESCRIPTION (provided by applicant): Chronic neuropathic pain can be a devastating disease and the management is often inadequate. A recent focus of pain research is examining changes in the expression of sodium channels that follow nerve injury since these changes may contribute to neuronal hyperexcitability and the development of neuropathic pain. This proposal will investigate the distributions of Nav1.1, Nav1.2, Nav1.3, Nav1.6, Nav1.7, Nav1.8 and Nav1.9 sodium channel isoforms at both the light and electron microscopic levels in normal rat trigeminal primary afferents (infraorbital nerve, trigeminal ganglion/root entry zone and trigeminal sensory nucleus) and in intrinsic neurons in the trigeminal sensory nucleus. Once the normal expression is determined for each isoform, then changes in this expression will be evaluated in the same regions following a chromic suture injury to; 1) infraorbital nerve, or 2) trigeminal root entry zone, combined with behavioral testing for altered nociception. The hypothesis is that there will be a change in the normal distribution of the sodium channel isoforms following injury that correlates with behavioral evidence for altered nociception, the changes may depend on the site of the injury (peripheral vs. central), these changes contribute to neuronal hyperactivity of both primary afferents and intrinsic neurons seen following lesions, and the reduction of hyperexcitability with sodium channel blocking drugs. The trigeminal system represents an excellent model system to evaluate differences in sodium channel expression following either peripheral nerve or central root injury since distinct clinical entities are seen in humans following these different injuries. Trigeminal neuralgia may result from a root entry zone injury, while peripheral trigeminal neuropathy follows damage to peripheral nerves. There may be a difference in the expression of sodium channels following peripheral and central injury, since patients with trigeminal neuralgia usually respond to carbamazepine, while patients with peripheral trigeminal neuropathy rarely obtain significant relief with only carbamazepine. A differential expression of sodium channels in different fiber types may also be responsible for the different clinical characteristics of pain seen following peripheral and central injury. Identification of specific sodium channel alterations after injury may help develop more selective treatments for neuropathic pain.
|Effective start/end date||8/1/02 → 7/31/08|
- National Institutes of Health: $267,636.00
- National Institutes of Health: $228,116.00
- National Institutes of Health: $264,124.00
- National Institutes of Health: $180,278.00
- National Institutes of Health: $268,919.00
- National Institutes of Health: $40,319.00