Somatosensory and vasomotor manifestations of individual and combined stimulation of TRPM8 and TRPA1 using topical L‐menthol and trans‐cinnamaldehyde in healthy volunteers

@article{Olsen2014SomatosensoryAV,
  title={Somatosensory and vasomotor manifestations of individual and combined stimulation of TRPM8 and TRPA1 using topical L‐menthol and trans‐cinnamaldehyde in healthy volunteers},
  author={Rasmus Vinther Olsen and Hjalte Holm Andersen and Heidi Guldborg M{\o}ller and Peter Winther Eskelund and Lars Arendt-Nielsen},
  journal={European Journal of Pain},
  year={2014},
  volume={18}
}
Activation of TRPM8 and TRPA1 receptors generates cold and cold pain sensations, respectively, and is presumably important in clinical pain manifestations, such as cold hyperalgesia. This study investigated the interaction between TRPM8 and TRPA1 receptors through stimulation of glabrous human skin (volar forearm) by topical administration of 40% L‐menthol and 10% trans‐cinnamaldehyde (CA), individually and in combination. 
Anti-hyperalgesic effects of a novel TRPM8 agonist in neuropathic rats: A comparison with topical menthol
TLDR
The data suggest that menthol induced hyperalgesia is not consistently replicable in the rat and that the analgesic properties of TRPM8 agonists might be beneficial in neuropathy without affecting normal cold sensitivity.
TRPA1 Sensitization Produces Hyperalgesia to Heat but not to Cold Stimuli in Human Volunteers
TLDR
The observation that the TRPA1 irritant cinnamaldehyde induced heat hyperalgesia at an effect sizes comparable with that of capsaicin attributes TRPA 1 a role in human heat-induced pain suggests the inclusion of heat pain as a major efficacy measure in human experimental studies of the effects ofTRPA1 antagonists and the development of TRPA2 antagonists for clinical pain settings involving heat hyperAlgesia.
Psychophysical and vasomotor evidence for interdependency of TRPA1 and TRPV1-evoked nociceptive responses in human skin: an experimental study
TLDR
It is suggested that TRPA1 nociceptive responses in human skin strongly depend on intact capsaicin-sensitive, TRPV1+ fibers.
High-Concentration L-Menthol Exhibits Counter-Irritancy to Neurogenic Inflammation, Thermal and Mechanical Hyperalgesia Caused by Trans-cinnamaldehyde.
TLDR
It is shown that the frequently used topical counterirritant and TRPM8 agonist, L-menthol, decreased evoked pain, hyperalgesia, and inflammation, indicating direct and indirect antinociceptive mechanisms.
A human surrogate model of itch utilizing the TRPA1 agonist trans-cinnamaldehyde.
TLDR
Topical trans-cinnamaldehyde proved feasible as a human itch model with applicability in studying itch mechanisms or anti-pruritic drug profiling.
Conditioning pain stimulation does not affect itch induced by intra-epidermal histamine pricks but aggravates neurogenic inflammation in healthy volunteers
TLDR
CPM was found to aggravate histamine-induced neurogenic inflammation, likely facilitated by efferent sympathetic fibers, suggesting that pruriceptive signaling is not inhibited by pain-recruited endogenous modulation.
"Combining topical agonists with the recording of event-related brain potentials to probe the functional involvement of TRPM8, TRPA1 and TRPV1 in heat and cold transduction in the human skin".
TLDR
Findings are compatible with previous evidence indicating that TRPM8 is involved in innocuous cold transduction and that TRPV1 and TRPA1 are involved in noxious heat transduction in humans.
Cold and L-menthol-induced sensitization in healthy volunteers—a cold hypersensitivity analogue to the heat/capsaicin model
TLDR
It is proposed that cold/menthol enhances or prolong L-menthol-evoked sensitization, and this model may prove beneficial for testing analgesic compounds when a sufficient duration of time is needed to see drug effects on CPT or mechanical hypersensitivity.
Epidermal expression of human TRPM8, but not of TRPA1 ion channels, is associated with sensory responses to local skin cooling.
TLDR
The present observations demonstrating a lack of association of TRPA1 channel expression with cold sensitivity related measures reinforce doubts about involvement of this channel in cold pain in humans.
Antipruritic Effect of Cold-induced and Transient Receptor Potential-agonist-induced Counter-irritation on Histaminergic Itch in Humans.
TLDR
Cold-induced counter-irritation had an inhibitory effect on histaminergic itch, suggesting that agonists of cold transduction receptors could be of potential antipruritic value.
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