GABAA receptor-mediated effects of naringenin on substantia gelatinosa neurons in the medullary dorsal horn in juvenile mice
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Naringenin (5,7,4’-trihydroxyflavanone) is a natural bioflavonoid with numerous documented bioactivities in the central nervous system. The substantia gelatinosa (SG) of the trigeminal subnucleus caudalis (Vc; medullary dorsal horn) is recognized as a pivotal site for integration and modulation of orofacial nociceptive inputs. However, the potential effects of naringenin on orofacial pain responses and the contributions of GABAA receptor modulation have not yet been examined. In this study, whole-cell patch-clamp technique was applied to evaluate the effects of naringenin on the GABAA receptor responses on SG neurons in the Vc, and to assess potential sex-related differences. The GABAA receptor agonist muscimol was applied alone or with naringenin on SG neurons in the Vc that were patch-clamped with high chloride pipette solution to augment GABAA potentials. Naringenin increased both the amplitude and the area under the curve of muscimol-mediated responses in the majority (64.7%) of neurons tested (n = 17), and these effects differed by sex, suggesting that naringenin may modulate orofacial pain in a sex-dependent manner by enhancing GABAA potentials on SG neurons in the Vc. Naringenin may thus be a promising prototype compound for developing therapeutic agents against orofacial pain.
Abstract
Naringenin (5,7,4’-trihydroxyflavanone) is a natural bioflavonoid with numerous documented bioactivities in the central nervous system. The substantia gelatinosa (SG) of the trigeminal subnucleus caudalis (Vc; medullary dorsal horn) is recognized as a pivotal site for integration and modulation of orofacial nociceptive inputs. However, the potential effects of naringenin on orofacial pain responses and the contributions of GABAA receptor modulation have not yet been examined. In this study, whole-cell patch-clamp technique was applied to evaluate the effects of naringenin on the GABAA receptor responses on SG neurons in the Vc, and to assess potential sex-related differences. The GABAA receptor agonist muscimol was applied alone or with naringenin on SG neurons in the Vc that were patch-clamped with high chloride pipette solution to augment GABAA potentials. Naringenin increased both the amplitude and the area under the curve of muscimol-mediated responses in the majority (64.7%) of neurons tested (n = 17), and these effects differed by sex, suggesting that naringenin may modulate orofacial pain in a sex-dependent manner by enhancing GABAA potentials on SG neurons in the Vc. Naringenin may thus be a promising prototype compound for developing therapeutic agents against orofacial pain.