Reactive oxygen species increase neuronal excitability via activation of nonspecific cation channel in rat medullary dorsal horn neurons.
10.4196/kjpp.2017.21.4.371
- Author:
Hae In LEE
1
;
Byung Rim PARK
;
Sang Woo CHUN
Author Information
1. Department of Dental Hygiene, Gwangyang Health Science University, Gwangyang 57764, Korea.
- Publication Type:Original Article
- Keywords:
Nonspecific cation channel;
Orofacial pain;
Reactive oxygen species;
Xanthine oxidase
- MeSH:
Animals;
Catalase;
Facial Pain;
Fluorescence;
Ions;
Membranes;
Neurons*;
Oxidoreductases;
Posterior Horn Cells*;
Rats*;
Reactive Oxygen Species*;
Sodium;
Spinal Cord Dorsal Horn*;
Superoxide Dismutase;
Superoxides;
Trigeminal Nucleus, Spinal;
Xanthine Oxidase
- From:The Korean Journal of Physiology and Pharmacology
2017;21(4):371-376
- CountryRepublic of Korea
- Language:English
-
Abstract:
The caudal subnucleus of the spinal trigeminal nucleus (medullary dorsal horn; MDH) receives direct inputs from small diameter primary afferent fibers that predominantly transmit nociceptive information in the orofacial region. Recent studies indicate that reactive oxygen species (ROS) is involved in persistent pain, primarily through spinal mechanisms. In this study, we aimed to investigate the role of xanthine/xanthine oxidase (X/XO) system, a known generator of superoxide anion (O₂(·−)), on membrane excitability in the rat MDH neurons. For this, we used patch clamp recording and confocal imaging. An application of X/XO (300 µM/30 mU) induced membrane depolarization and inward currents. When slices were pretreated with ROS scavengers, such as phenyl N-tert-butylnitrone (PBN), superoxide dismutase (SOD), and catalase, X/XO-induced responses decreased. Fluorescence intensity in the DCF-DA and DHE-loaded MDH cells increased on the application of X/XO. An anion channel blocker, 4,4-diisothiocyanatostilbene-2,2-disulfonic acid (DIDS), significantly decreased X/XO-induced depolarization. X/XO elicited an inward current associated with a linear current-voltage relationship that reversed near −40 mV. X/XO-induced depolarization reduced in the presence of La³⁺, a nonselective cation channel (NSCC) blocker, and by lowering the external sodium concentration, indicating that membrane depolarization and inward current are induced by influx of Na⁺ ions. In conclusion, X/XO-induced ROS modulate the membrane excitability of MDH neurons, which was related to the activation of NSCC.
