The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Naringenin modulates GABA mediated response in a sex-dependent manner in substantia gelatinosa neurons of trigeminal subnucleus caudalis in immature mice

  • Seon Ah Park (Department of Oral Physiology, School of Dentistry & Institute of Oral Bioscience, Jeonbuk National University) ;
  • Thao Thi Phuong Nguyen (Faculty of Odonto – Stomatology, Hue University of Medicine and Pharmacy, Hue University) ;
  • Soo Joung Park (Department of Oral Physiology, School of Dentistry & Institute of Oral Bioscience, Jeonbuk National University) ;
  • Seong Kyu Han (Department of Oral Physiology, School of Dentistry & Institute of Oral Bioscience, Jeonbuk National University)
  • Received : 2023.10.20
  • Accepted : 2023.12.13
  • Published : 2024.01.01
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Abstract

The substantia gelatinosa (SG) within the trigeminal subnucleus caudalis (Vc) is recognized as a pivotal site of integrating and modulating afferent fibers carrying orofacial nociceptive information. Although naringenin (4',5,7-thrihydroxyflavanone), a natural bioflavonoid, has been proven to possess various biological effects in the central nervous system (CNS), the activity of naringenin at the orofacial nociceptive site has not been reported yet. In this study, we explored the influence of naringenin on GABA response in SG neurons of Vc using whole-cell patch-clamp technique. The application of GABA in a bath induced two forms of GABA responses: slow and fast. Naringenin enhanced both amplitude and area under curve (AUC) of GABA-mediated responses in 57% (12/21) of tested neurons while decreasing both parameters in 33% (7/21) of neurons. The enhancing or suppressing effect of naringenin on GABA response have been observed, with enhancement occurring when the GABA response was slow, and suppression when it was fast. Furthermore, both the enhancement of slower GABA responses and the suppression of faster GABA responses by naringenin were concentration dependent. Interestingly, the nature of GABA response was also found to be sex-dependent. A majority of SG neurons from juvenile female mice exhibited slower GABA responses, whereas those from juvenile males predominantly displayed faster GABA responses. Taken together, this study indicates that naringenin plays a partial role in modulating orofacial nociception and may hold promise as a therapeutic target for treating orofacial pain, with effects that vary according to sex.

Keywords

Acknowledgement

This research was supported by National University Development Project at Jeonbuk National University in 2021.

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