(-)-menthol increases excitatory transmission by activating both TRPM8 and TRPA1 channels in mouse spinal lamina II

Yuhui Luo1, Wuping Sun1, Xiaojin Feng2

  • 1Department of Pain Medicine and Shenzhen Municipal Key Laboratory for Pain Medicine, Shenzhen Nanshan People's Hospital and the 6th Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen, 518060, China.

Insights

(-)-menthol enhances excitatory synaptic transmission in the spinal cord. This effect involves activating transient receptor potential melastatin 8 (TRPM8) and transient receptor potential ankyrin 1 (TRPA1) channels in lamina II neurons.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Pain Research

Background:

  • (-)-menthol is widely used and known for peripheral analgesic effects mediated by TRPM8.
  • Central mechanisms of (-)-menthol's action, particularly in pain modulation, are not fully understood.
  • Spinal lamina II is crucial for processing nociceptive signals.

Purpose of the Study:

  • To investigate the central effects of (-)-menthol on excitatory synaptic transmission.
  • To elucidate the specific ion channels involved in (-)-menthol's action in the spinal cord.

Main Methods:

  • Patch-clamp recordings were used to measure synaptic activity in mice spinal cord lamina II.
  • Experiments involved dose-response analysis, genetic knockout, and pharmacological inhibition of TRPM8 and TRPA1 channels.

Main Results:

  • (-)-menthol dose-dependently increased the frequency of miniature excitatory postsynaptic currents (mEPSCs).
  • TRPM8 knockout or inhibition did not completely block the effect.
  • TRPA1 antagonism partially impaired the effect, while combined TRPM8 and TRPA1 antagonism abolished it.

Conclusions:

  • (-)-menthol enhances excitatory synaptic transmission in the spinal lamina II.
  • This action is mediated by the activation of both TRPM8 and TRPA1 channels.
  • These findings reveal a novel central mechanism for (-)-menthol's neuromodulatory effects.

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