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A 'toothache tree' alkylamide inhibits Aδ mechanonociceptors to alleviate mechanical pain. J Physiol 2013 Jul 01;591(13):3325-40

Date

05/09/2013

Pubmed ID

23652591

Pubmed Central ID

PMC3717230

DOI

10.1113/jphysiol.2013.252106

Scopus ID

2-s2.0-84879845629 (requires institutional sign-in at Scopus site)   67 Citations

Abstract

In traditional medicine, the 'toothache tree' and other plants of the Zanthoxylum genus have been used to treat inflammatory pain conditions, such as toothache and rheumatoid arthritis. Here we examined the cellular and molecular mechanisms underlying the analgesic properties of hydroxy-α-sanshool, the active alkylamide produced by Zanthoxylum plants. Consistent with its analgesic effects in humans, sanshool treatment in mice caused a selective attenuation of mechanical sensitivity under naïve and inflammatory conditions, with no effect on thermal sensitivity. To elucidate the molecular mechanisms by which sanshool attenuates mechanical pain, we performed single fibre recordings, calcium imaging and whole-cell electrophysiology of cultured sensory neurons. We found that: (1) sanshool potently inhibits Aδ mechanonociceptors that mediate both sharp acute pain and inflammatory pain; (2) sanshool inhibits action potential firing by blocking voltage-gated sodium currents in a subset of somatosensory neurons, which express a unique combination of voltage-gated sodium channels; and (3) heterologously expressed Nav1.7 is most strongly inhibited by sanshool as compared to other sodium channels expressed in sensory neurons. These results suggest that sanshool targets voltage-gated sodium channels on Aδ mechanosensory nociceptors to dampen excitability and thus induce 'fast pain' analgesia.

Author List

Tsunozaki M, Lennertz RC, Vilceanu D, Katta S, Stucky CL, Bautista DM

Author

Cheryl L. Stucky PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Amides
Animals
CHO Cells
Cells, Cultured
Cricetulus
Ganglia, Spinal
Hot Temperature
Male
Mechanoreceptors
Mice
Mice, Inbred C57BL
Neurons
Pain
Sodium Channel Blockers
Voltage-Gated Sodium Channels
Zanthoxylum