AMPK is a regulator of TRPA1

AMPK is a widely expressed intracellular energy sensor that monitors and modulates energy expenditure (1).

AMPK activation is impaired in muscle cell cultures derived from ME patients (2).

Transient receptor potential ankyrin 1 (TRPA1) channel is a widely recognized chemical and thermal sensor that plays vital roles in pain transduction (1).

Some ME patients have single nucleotide polymorphism in TRPA1 (3).

Wang et al discovered a functional link between AMPK and TRPA1 in dorsal root ganglion (DRG) neurons, in which AMPK activation rapidly resulted in downregulation of membrane-associated TRPA1 and its channel activity within minutes. Treatment with two AMPK activators, metformin or AICAR, inhibited TRPA1 activity in DRG neurons by decreasing the amount of membrane-associated TRPA1. Metformin induced a dose-dependent inhibition of TRPA1-mediated calcium influx (1).

Further reading:

A role for TRPs in ME/CFS/POTS/MCS/pain/endothelial dysfunction...?

TRP blogposts - an overview

A curcumin derivative J147 ameliorates diabetic peripheral neuropathy in streptozotocin (STZ)-induced DPN rat models through negative regulation AMPK on TRPA1

Ingestion of transient receptor potential channel agonists attenuates exercise-induced muscle cramps

Proteinase-Activated Receptor-2 Sensitivity of Amplified TRPA1 Activity in Skeletal Muscle Afferent Nerves and Exercise Pressor Reflex in Rats with Femoral Artery Occlusion

Role of TNF-α in Regulating the Exercise Pressor Reflex in Rats With Femoral Artery Occlusion


Referencer

1) Diabetes. 2018 Jan;67(1):98-109. doi: 10.2337/db17-0503. Epub 2017 Oct 12.
Negative Regulation of TRPA1 by AMPK in Primary Sensory Neurons as a Potential Mechanism of Painful Diabetic Neuropathy.
Wang S1,2, Kobayashi K3, Kogure Y1, Yamanaka H3, Yamamoto S1, Yagi H4, Noguchi K5, Dai Y6,2,3. https://www.ncbi.nlm.nih.gov/pubmed/29025860

2) Biosci Rep. 2018 May 8;38(3). pii: BSR20180242. doi: 10.1042/BSR20180242. Print 2018 Jun 29. Pharmacological activation of AMPK and glucose uptake in cultured human skeletal muscle cells from patients with ME/CFS. Brown AE1, Dibnah B1, Fisher E1, Newton JL1,2, Walker M3,2. https://www.ncbi.nlm.nih.gov/pubmed/29654166

3) Marshall-Gradisnk et al. Examination of Single Nucleotide Polymorphisms (SNPs) in Transient Receptor Potential (TRP) Ion Channels in Chronic Fatigue Syndrome Patients https://journals.sagepub.com/doi/10.4137/III.S25147