Peripheral Mechanisms for the Initiation of Pain Following Trigeminal Nerve Injury

Injury to a branch of the trigeminal nerve may lead to the develop-ment of chronic pain in the affected area. The etiology of this con-dition is not clear, but there is strong evidence to suggest that spontaneous and mechanically induced neural discharge from the injury site plays a crucial role. In laboratory studies, we have char-acterized this discharge following injury to the inferior alveolar or lingual nerves and have shown a temporal association with the accumulation of neuropeptides in the damaged axons. Substance P, calcitonin gene–related peptide, and vasoactive intestinal polypeptide were all found to be capable of increasing the dis-charge when applied systemically, and enkephalin caused a decrease. There were also changes in the expression of specific sodium channels and nitric oxide synthase, both at the injury site and in the trigeminal ganglion. Studies on lingual nerve neuromas taken from patients undergoing nerve repair also revealed accumu-lation of peptides, as well as inflammatory and structural changes, but the presence of these features did not correlate directly with the reported symptoms. The application of corticosteroids to an experimental injury site decreased the mechanically induced dis-charge, and the anticonvulsant carbamazepine reduced the sponta-neous discharge in some axons. Some of the responses that result from damage to a branch of the trigeminal nerve appear to differ from those that follow damage to other peripheral nerves. These differences will need to be taken into account when developing new therapeutic approaches for the management of injury-induced trigeminal pain.

ectopic discharge; nerve injury; neuropeptides; sodium channels; trigeminal nerve

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