Neurobiology of the Gustatory Zone of Nucleus Tractus Solitarius
I. Robin A. Barraco in Nucleus of the Solitary Tract, 2019
Inhibitory interactions can also occur independently of convergent input derived from the chorda tympani and glossopharyngeal nerve. The sodium channel blocker, amiloride, suppresses whole-nerve and single-fiber responses of the chorda tympani to NaCl.52-54 When responses of the second-order neurons in the NTS were examined after application of amiloride to the tongue, the responses of the central neurons were changed.55 A significant number of NTS neurons increased their firing rate after the application of amiloride, which indicates that removal of the amiloride-sensitive afferent input disinhibits these neurons.56 There is also indication of a descending inhibitory influence on neurons in the rNTS.57
Postherpetic Neuralgia
Gary W. Jay in Practical Guide to Chronic Pain Syndromes, 2016
A variety of other agents have been evaluated in the treatment of PHN or other neuropathic pain conditions. Other antiepileptic or antidepressants, besides those mentioned previously, may have potential efficacy but have not been shown to have convincing benefit as yet. NMDA antagonists, including ketamine, dextromethorphan, and memantine, have been studied but no conclusive evidence of their efficacy has been shown. Similarly, the sodium channel blocker mexiletine has not demonstrated convincing benefit. Furthermore, this particular agent is usually avoided given its high-toxicity profile. The use of these medications can be considered in select circumstances, when more conventional treatments have failed.
Complications after Spinal Cord Injury
Stephen M. Cohn, Matthew O. Dolich in Complications in Surgery and Trauma, 2014
Future advances in the science of SCI will provide this population of patients with the hope of an improved quality of life. The past decade has already seen an explosion of knowledge about the mechanisms that underlie primary and secondary SCI. Numerous drugs have shown promise in limiting nerve cell death from secondary injury in the laboratory setting. A randomized trial of the orally administered drug riluzole, a sodium channel blocker showing promise as a neuroprotectant, began in 2010 [32]. A starting dose of 50 mg by mouth given within 12 h of injury is continued every 12 h for 14 days and is intended to reduce secondary neuronal injury. The results of the study should be available in 2013.
The role of polytherapy in the management of epilepsy: suggestions for rational antiepileptic drug selection
Published in Expert Review of Neurotherapeutics, 2020
Alberto Verrotti, Renato Tambucci, Ludovica Di Francesco, Piero Pavone, Giulia Iapadre, Emma Altobelli, Sara Matricardi, Giovanni Farello, Vincenzo Belcastro
The aim of rational polytherapy is to identify AED combinations that maximize efficacy and minimize side effects [26]. Therapy should be always tailored to each patient, according to the seizure type, epilepsy type and epileptic syndrome [8]. There is evidence about the efficacy of certain AED associations on specific seizure types; for example, sodium valproate/ethosuximide for absence seizures [27], phenobarbital/phenytoin for tonic-clonic seizures [28], vigabatrin/tiagabine for refractory epilepsy [29], carbamazepine/valproate or vigabatrin for focal seizures [30] and lamotrigine/topiramate for a range of other epilepsy/seizure types [31]. Moreover, it is conceivable that the choice of AED association based on their mechanisms of action may augment the global effectiveness. In 2014, Margolis et al. conducted a large population-based study on patients with focal seizures and found that combinations of AEDs with different mechanisms of action produced better results, as in terms of reduced anticonvulsant treatment duration, and of lower risk for hospitalization and emergency department admission, with respect to combinations of AEDs with similar mechanisms of action [32]. Associations of AEDs with different mechanisms of action have been assessed in some human studies [27,33–36]. In particular, combining a sodium channel blocker with a drug enhancing GABA-ergic inhibition appears to be advantageous. This association has been proven to be more effective than the combination of two GABA-mimetic drugs, which in turn is better than the combination of two sodium channel blockers [10,37].
Neuropathic pain: preclinical and early clinical progress with voltage-gated sodium channel blockers
Published in Expert Opinion on Investigational Drugs, 2020
Mikhail Kushnarev, Iulia Paula Pirvulescu, Kenneth D. Candido, Nebojsa Nick Knezevic
The rationale for targeting a specific subtype of sodium-channel blocker for the treatment of chronic neuropathic pain is to avoid side effects associated with activity on other Nav subtypes, or possibly even other receptor classes. Most Nav blockers currently used for pain management are nonselective, such as local anesthetics (e.g. lidocaine), class I antiarrhythmics (e.g. mexiletine), antiepileptics (e.g. carbamazepine), and antidepressants (e.g. TCAs) [18]. These drugs are known for their narrow therapeutic index and multiple serious adverse effects due to their action on Nav subtypes in the CNS and the heart, such as dizziness, sedation, convulsions, and cardiotoxicity. Despite demonstration of efficacy of nonselective Nav channel blockers for specific neuropathic conditions in several small studies, these medications are not suggested in current guidelines for treatment of neuropathic pain, likely because their potential is hindered by their side effect profile (the exception being TCAs, which are not true sodium channel blockers, and act on multiple receptors and channels, including serotonergic, noradrenergic, dopaminergic, histaminergic, muscarinic, and calcium channels, along with neurotransmitter reuptake blockade) [5,10].
Translational issues in precision medicine in neuropathic pain
Published in Canadian Journal of Pain, 2020
Anthony H. Dickenson, Ryan Patel
To decipher a mechanism in a particular patient at any one time is next to impossible at present. An approach that would overcome this problem would be to reverse the process and work from the premise that the sensory signs and symptoms of the patient must reflect the underlying mechanisms at play and that drugs have a defined mode of action. Thus, attempting to align the sensory phenotype of the patient with a particular class of drug could be very fruitful. The overall aim would be to define patient subgroups and relate them to the efficacy of a particular drug. This has been achieved with the sodium channel blocker oxcarbazepine. In a randomized controlled trial with patients with neuropathic pain, the drug did not separate from placebo.13 However, when patients with a so-called irritable nociceptor who were suffering from evoked pain hypersensitivity were split off, the drug was effective. Thus, abnormal impulses in still-connected nerves in these patients appear to be driving the pain and thus blocking this activity through sodium channel modulation alleviates the pain.
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