title: In vivo potency of different ligands on voltage-gated sodium channels.
abstract: The Ranvier nodes of thick myelinated nerve fibers contain almost exclusively voltage-gated sodium channels (Navs), while the unmyelinated fibers have several receptors (e.g., cannabinoid, transient receptor potential vanilloid receptor 1), too. Therefore, a nerve which contains only motor fibers can be an appropriate in vivo model for selective influence of Navs. The goals were to evaluate the potency of local anesthetic drugs on such a nerve in vivo; furthermore, to investigate the effects of ligands with different structures (arachidonic acid, anandamide, capsaicin and nisoxetine) that were proved to inhibit Navs in vitro with antinociceptive properties. The marginal mandibular branch of the facial nerve was explored in anesthetized Wistar rats; after its stimulation, the electrical activity of the vibrissae muscles was registered following the perineural injection of different drugs. Lidocaine, bupivacaine and ropivacaine evoked dose-dependent decrease in electromyographic activity, i.e., lidocaine had lower potency than bupivacaine or ropivacaine. QX-314 did not cause any effect by itself, but its co-application with lidocaine produced a prolonged inhibition. Nisoxetine had a very low potency. While anandamide and capsaicin in high doses caused about 50% decrease in the amplitude of action potential, arachidonic acid did not influence the responses. We proved that the classical local anesthetics have high potency on motor nerves, suggesting that this method might be a reliable model for selective targeting of Navs in vivo circumstances. It is proposed that the effects of these endogenous lipids and capsaicin on sensory fibers are not primarily mediated by Navs.
authors.affiliation: Department of Orthodontics and Pediatric Dentistry, Faculty of Dentistry, University of Szeged, Tisza L. krt. 64, H-6720 Szeged, Hungary. Electronic address: safrany.arpad@stoma.szote.u-szeged.hu.
authors.forename: Arpad
authors.initials: A
authors.lastname: Safrany-Fark
authors.affiliation: Institute of Physical Education and Sport Science, Juhász Gyula Faculty of Education, University of Szeged, Hattyas sor 10, H-6725 Szeged, Hungary. Electronic address: petrovszki.zita@med.u-szeged.hu.
authors.forename: Zita
authors.initials: Z
authors.lastname: Petrovszki
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Szeged, Dóm tér 10, H-6720 Szeged, Hungary. Electronic address: kekesi.gabriella@med.u-szeged.hu.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Kekesi
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Szeged, Dóm tér 10, H-6720 Szeged, Hungary. Electronic address: lp@med.u-szeged.hu.
authors.forename: Peter
authors.initials: P
authors.lastname: Liszli
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Szeged, Dóm tér 10, H-6720 Szeged, Hungary. Electronic address: benedek.gyorgy@med.u-szeged.hu.
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Benedek
authors.affiliation: Department of Medical Communication and Translation, Faculty of Medicine, University of Szeged, Szentháromság u. 5, H-6720 Szeged, Hungary. Electronic address: keresztes.csilla@med.u-szeged.hu.
authors.forename: Csilla
authors.initials: C
authors.lastname: Keresztes
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Szeged, Dóm tér 10, H-6720 Szeged, Hungary. Electronic address: horvath.gyongyi@med.u-szeged.hu.
authors.forename: Gyongyi
authors.initials: G
authors.lastname: Horvath
mesh_terms: D000700:Analgesics / Q000378:metabolism / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005154:Facial Nerve / Q000187:drug effects / Q000502:physiology; D008024:Ligands; D051381:Rats; D017208:Rats, Wistar; D061567:Voltage-Gated Sodium Channel Blockers / Q000378:metabolism / Q000494:pharmacology*; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism*
chemical_list: D000700:Analgesics; D000779:Anesthetics, Local; D008024:Ligands; D061567:Voltage-Gated Sodium Channel Blockers; D061566:Voltage-Gated Sodium Channels
keywords: Anandamide; Anandamide (PubChem CID: 5281969); Arachidonic acid (PubChem CID: 444899); Bupivacaine (PubChem CID: 2474); Capsaicin; Capsaicin (PubChem CID: 1548943); Ketamine (PubChem CID: 3821); Lidocaine (PubChem CID: 3676); Local anesthetic drugs; Motor nerves; Nisoxetine; Nisoxetine (PubChem CID: 134453); QX-314 (PubChem CID: 3925); Ropivacaine (PubChem CID: 175805); Voltage-gated sodium channels; Xylazin (PubChem CID: 5707)