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1 Anesthesiology, Duke University, Durham, NC, USA; Anesthesiology, Duke University, Durham, NC, USA
2 Cell and Molecular Physiology, Univesity of North Carolina, Chapel Hill, NC, USA
3 Medicine, Duke University, Durham, NC, USA
4 Neurobiology, Duke University, Durham, NC, USA
* To whom correspondence should be addressed. E-mail: sas{at}neuro.duke.edu.
Nicotine is an alkaloid that is used by large numbers of people. When taken into the body it produces a myriad of physiological actions that occur primarily through the activation of neuronal nicotinic acetylcholine receptors (nAChRs). We have explored its ability to modulate TRPV1 receptors and voltage-gated sodium channels. The reason for investigating nicotines effect on sodium channels is to obtain a better understanding of its anti-nociceptive properties. The reasons for investigating its effects on capsaicin-activated TRPV1 channels are to understand how it may modulate this channel that is involved in pain, inflammation, and gustatory physiology. In whole-cell patch clamp recordings from rat trigeminal ganglion (TG) nociceptors nicotine exhibits anesthetic properties by decreasing the number of evoked action potentials and by inhibiting tetrodotoxin-resistant sodium currents. This anesthetic property can be produced without the necessity of activating nAChRs. Nicotine also modulates TRPV1 receptors inducing a several-fold increase in capsaicin-activated currents in both TG neurons and in cells with heterologously expressed TRPV1 receptors. This sensitizing effect does not require the activation of nAChRs. Nicotine did not alter the threshold temperature (~ 41°C) of heat-activated currents in TG neurons that were attributed to arise from the activation of TRPV1 receptors. In this regard, its effect on TRPV1 receptors differs from those of ethanol that has been shown to increase the capsaicin-activated current but decrease the threshold temperature. These studies document several new effects of nicotine on channels involved in nociception and indicate how they may impact physiological processes involving pain and gustation.
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