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.
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.
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.
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.
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Analysis of variance
Average root mean square amplitude
Cramp threshold frequency
Exercise-associated muscle cramps
Transient receptor potential cation channel A1
Transient receptor potential cation channel V1
Visual analog scale
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Conflict of interest
The investigated mixture of TRP-activators was made available to us free of charge by Flex Pharma INC. (Boston, MA, USA). The manufacturer had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This research received no grant from any funding agency in the public, commercial, or not-for-profit sectors.
Communicated by Fabio Fischetti.
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Behringer, M., Nowak, S., Leyendecker, J. et al. Effects of TRPV1 and TRPA1 activators on the cramp threshold frequency: a randomized, double-blind placebo-controlled trial. Eur J Appl Physiol 117, 1641–1647 (2017). https://doi.org/10.1007/s00421-017-3653-6
- Muscle cramp
- Muscle, skeletal
- TRPV1 protein
- TRPA1 protein