| The pathogenesis of idiopathic trigeminal neuralgia (TN) is unclear, and there are scarcely satisfactory therapies. At present, carbamazepine is thought to be the first line of treatment as the drug therapy, which mechanism is not completely known, but it is sure that it is a blocker of sodium channels and could prevent the generation and propagation of action potentials. Unfortunately, it lacks specificity and affects other excitable membranes. Therefore, it has side effects on the central nervous system and heart with long-term use, which limits its utility in the treatment of TN.Recently, many foreign researchers found that the tetrodotoxin-resistant (TTX-R) voltage-gated sodium channel, Nav1.8, which is expressed only by unmyelinated small-diameter sensory neurons associated with nociception in dorsal root ganglion(DRG) and trigeminal ganglion(TG), is involved in pain pathways and play a key role. Thus it provides a new idea in pain research.At present, the studies of Nav1.8 focus on animal models, especially on spinal nerve injury and inflammatory pain. And there is a little in the studies about Nav1 .8 in trigeminal nerve systerm and the relationship between Nav1.8 and clinical pain diseases. At the same time, because of the fact that carbamazepine , the blocker of sodium channels, has clinical effectiveness in TN patients, learning the relationship between TTX-R sodium channel Nav1.8 and TN turns to be an important problem we must encounter and resolve to understand further the pathogenesis of TN. Therefore, we have studied, for the first time, the presence of hNav1.8 (human Nav1.8) in the affected trigeminal nerves of TN patients in order to explain the molecular physiology mechanism in part and establish foundation for further investigation in mechanisms and therapies of TN to a certain extent.Our studies are as follows:1 . Five affected trigeminal divisions obtained from patients with idiopathic TN, to whom the drug therapy is not effective, were studied. As the normal nerve control and negative tissue control, one great auricular nerve and one muscle sample were also obtained from patients who underwent the combined radical neck dissection withglossectomy and hemimandibulectomy. Using reverse transcription polymerase chain reaction (RT-PCR) technique, we have determined qualitatively the expression of hNav1.8 mRNA with β-actin as an internal control. The expression of hNav1.8 mRNA could be found in all of the specimens of the affected nerves of TN patients, but none in the great auricular nerve and the muscle sample.2. Furthermore, we have studied the affected trigeminal divisions(inferior alveolar nerves) and non-affected divisions( lingual nerves ) of six patients with TN to whom the drug therapy was not effective.As negative controls, one great auricular nerve (from a patient who underwent the combined radical neck dissection with glossectomy and hemimandibulectomy) and one infraorbital nerve (from a patient who underwent subtotal resection of maxilla) were also obtained . Using semi-quantitative RT-PCR technique, we have determined the expression of hNav1.8 mRNA with β-actin as an internal control in the affected trigeminal divisions and non-affected divisions. We found that the relative amount of hNav1.8 mRNA from the affected trigeminal divisions( 1.233 ±0.324) was much higher than that from the non-affected divisions (1.018±0.249) ,t=3.919,P=0.011. It suggests that hNav1.8 increased significantly in affected trigeminal divisions of TN patients at mRNA level.Through our experiments, we think that hNav1.8 plays an important role in the pathogenesis of TN thus builds the molecular base of TN, Nowadays, effective therapies are lacking for TN, while various surgical treatments still have different proportional recurrence rate and lead to the loss of nomal senses. Thus, drug therapy is the crucial research field in long views. As Nav1.8 and pain have a close relation and hNav1.8 expression is restricted to sensory neurons, it sheds an encouraging light on t...
|
PDF Full Text Request