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A Procedure for Implanting a Spinal Chamber for Longitudinal In Vivo Imaging of the Mouse Spinal Cord
Published on: December 3, 2014
(-)-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.
Abstract:
(-)-menthol, a major form of menthol, is one of the most commonly used chemicals. Many studies have demonstrated that (-)-menthol produces analgesic action through peripheral mechanisms which are mainly mediated by activation of TRPM8. Moreover, intrathecal injection of menthol induces analgesia as well. However, the central actions and mechanisms of (-)-menthol remain unclear. Here, we have investigated the action of (-)-menthol on excitatory synaptic transmission in spinal lamina II layer which plays a pivotal role in modulating nociceptive transmission from the periphery by using patch-clamp technique in mice spinal cord. We found that (-)-menthol increased miniature excitatory postsynaptic current frequency. The frequency increases which (-)-menthol induced were in a dose-dependent manner (EC50: 0.1079 mM). However, neither genetic knockout nor pharmacological inhibition of TRPM8 could block (-)-menthol-induced effects entirely. Furthermore, this increase was also impaired by TRPA1 antagonist HC030031, but abolished utterly by co-application of TRPM8 and TRPA1 antagonist. Our results indicate that (-)-menthol increases the excitatory synaptic transmission by activating either TRPA1 or TRPM8 channels in spinal lamina II layer.
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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