A review of topical high-concentration L-menthol as a translational model of cold allodynia and hyperalgesia
European Journal of Pain
Abstract
Background
Cold
allodynia and cold hyperalgesia are both elusive features of
neuropathic pain, particularly in patients with various
polyneuropathies. Numerous studies have suggested that topical
application of L-menthol causes temporary cold hypersensitivity and thus
acts as a proxy for associated symptoms. This review summarizes studies
on L-menthol-induced nociception, cold allodynia and cold hyperalgesia in vitro, in animals and in humans.
Methods
A
comprehensive literature search was performed using the PubMed and
Google Scholar databases until February 2013. Obtained manuscripts were
reviewed for relevancy and reference lists of the retrieved articles
were cross-checked for additional important studies. Solely the
literature regarding topical application of L-menthol in humans was
attained systematically. Of the total identified studies (96), 10 met
the inclusion criteria being controlled studies applying L-menthol at a
concentration of ≥30%.
Results
The
extracted data are meticulously compared and presented with emphasis on
clarity and transparency. In seven animal studies, cold allodynia or
hyperalgesia was successfully established utilizing various methods.
Eight studies in healthy volunteers unanimously reported a significant
increase in cold pain threshold, representing cold allodynia and
increased supra-threshold cold pain sensitivity, thus demonstrating cold
hyperalgesia.
Conclusions
Topical
high-concentration L-menthol consistently induces cold hypersensitivity
in animals and humans, thus constituting a predictable surrogate model
of cold allodynia and hyperalgesia. Understanding translational features
of this model and its underlying mechanisms could be valuable in
preclinical and human phases of drug development and in improving
current treatment of patients with polyneuropathy.
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