Electrophysiological evidence that TRPM3 is a candidate in latent spinal sensitization of chronic low back pain

Latent spinal sensitization is one key mechanism developing at the early stage of chronic low back pain (LBP). TRPM3-mediated calcium transients of dorsal root ganglia (DRG) neurons are considered critical presynaptic signals involved in this latent sensitization. However, postsynaptic consequences in input laminae of the spinal cord have not been addressed so far. Here, by electrophysiological recordings in acute spinal cord slices from adult rats, we show that perfusion of the TRPM3 agonist pregnenolone sulfate (PregS) induced a significant increase in the frequency but not amplitude of spontaneous postsynaptic currents in lamina I and II neurons. This frequency increase started slowly during PregS perfusion but was reversible following washout. This result is consistent with a presynaptic action of the neurosteroid PregS, indicating the presynaptic expression of functional TRPM3 in the superficial dorsal horn of adult rats. Thus, PregS-induced TRPM3 activation enhances spinal synaptic strength, implying a mediating role of TRPM3 between neuroendocrine and nociceptive signaling, which might as well exist in chronic LBP primed by chronic stress that promotes the biosynthesis of PregS.

Automated summary

This study demonstrates that neurosteroid pregnenolone sulfate (PregS) enhances spinal synaptic strength by activating TRPM3, which is functionally expressed in the superficial dorsal horn of adult rats. This finding provides insight into the key mechanism of chronic low back pain development and suggests a potential role of TRPM3 in mediating the interactions between neuroendocrine and nociceptive signaling.