Bisphenol A Regulates Sodium Ramp Currents in Mouse Dorsal Root Ganglion Neurons and Increases Nociception

Area of Science:

• Neuroscience
• Endocrinology
• Toxicology

Background:

• 17β-Estradiol influences pain perception and sex differences in nociception.
• Bisphenol A (BPA), an environmental chemical with estrogenic activity, has largely unknown effects on pain.
• Understanding BPA's impact on pain is crucial due to its widespread environmental presence.

Purpose of the Study:

• To investigate the effects of BPA exposure on pain sensitivity in male mice.
• To determine the cellular mechanisms underlying BPA's influence on nociceptors.
• To explore the role of estrogen receptors and signaling pathways in BPA-induced pain modulation.

Main Methods:

• Male mice were treated with BPA (50 µg/kg/day) for 8 days.
• Dissociated dorsal root ganglia (DRG) nociceptors were incubated with BPA (1 nM).
• Electrophysiological recordings assessed action potential firing and sodium channel currents (Na_v).
• Pharmacological agents and DRG from ERβ^-/- mice were used to identify involved pathways.

Main Results:

• BPA treatment decreased latency to pain behavior in response to heat, indicating increased pain sensitivity.
• BPA exposure increased action potential firing frequency in DRG nociceptors.
• BPA enhanced Na_v-mediated ramp currents, crucial for neuronal excitability.
• The effects of BPA involved estrogen receptor alpha (ERα) and phosphoinositide 3-kinase (PI3K).
• BPA did not alter mRNA expression or other biophysical properties of Na_v channels.

Conclusions:

• Environmentally relevant doses of BPA can increase pain sensitivity in male mice.
• BPA enhances neuronal excitability in nociceptors by modulating Na_v channel ramp currents.
• These findings highlight BPA as a potential factor in the etiology of pain conditions.