Effects of TRPV1 and TRPA1 activators on the cramp threshold frequency: a randomized, double-blind placebo-controlled trial

Eur J Appl Physiol. 2017 Aug;117(8):1641-1647. doi: 10.1007/s00421-017-3653-6. Epub 2017 Jun 1.


Purpose: Previous data indicate that a strong sensory input from orally administered TRPV1 and TRPA1 activators alleviates muscle cramps in foot muscles by reducing the α-motor neuron hyperexcitability. We investigated if TRP activators increase the cramp threshold frequency of the medial gastrocnemius.

Methods: We randomly assigned 22 healthy male participants to an intervention (IG) and a control group (CG). While participants of the IG ingested a mixture of TRPV1 and TRPA1 activators, the CG received a placebo. We tested the cramp threshold frequency (CTF), the cramp intensity (EMG activity), and the perceived pain of electrically induced muscle cramps before (pre), and 15 min, 4, 8, and 24 h after either treatment. We further measured the maximal isometric force of knee extensors at pre, 4, and 24 h to assess potential side-effects on the force output.

Results: When we included all measurement time points, no group-by-time interaction was observed for the CTF. However, when only pre and 15 min values were incorporated, a significant interaction, with a slightly greater CTF increase in IG (3.1 ± 1.5) compared to the CG (2.0 ± 1.5), was observed. No significant group by time interaction was found for the cramp intensity, the perceived pain, and the maximal isometric force.

Conclusion: Our data indicate that orally administered TRPV1 and TRPA1 activators exert a small short-term effect on the CTF, but not on the other parameters tested. Future studies need to investigate whether such small CTF increments are sufficient to prevent exercise-associated muscle cramps.

Keywords: Muscle cramp; Muscle, skeletal; TRPA1 protein; TRPV1 protein.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Double-Blind Method
  • Electric Stimulation
  • Electromyography
  • Exercise / physiology
  • Humans
  • Isometric Contraction / drug effects*
  • Isometric Contraction / physiology
  • Male
  • Muscle Cramp / physiopathology*
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / physiopathology
  • TRPA1 Cation Channel / agonists*
  • TRPV Cation Channels / agonists*
  • Young Adult


  • TRPA1 Cation Channel
  • TRPV Cation Channels