ArticlePloS one2015
Multimodal distribution of human cold pain thresholds.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9 citing papers in PubMed, 19 citations in OpenAlex.
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- Sensory dysfunction in SMA type 2 and 3 - adaptive mechanism or concomitant target of damage?Orphanet journal of rare diseases · 2024Article
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- The Use of Quantitative Sensation Testing to Identify the Physiological Differences Between the Median and Ulnar Nerves.Frontiers in human neuroscience · 2021Article
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- Sex differences in thermal detection and thermal pain threshold and the thermal grill illusion: a psychophysical study in young volunteers.Biology of sex differences · 2017Article
- Methods Used to Evaluate Pain Behaviors in Rodents.Frontiers in molecular neuroscience · 2017Article
- Identification of Molecular Fingerprints in Human Heat Pain Thresholds by Use of an Interactive Mixture Model R Toolbox (AdaptGauss).International journal of molecular sciences · 2015Article
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIt is assumed that different pain phenotypes are based on varying molecular pathomechanisms. Distinct ion channels seem to be associated with the perception of cold pain, in particular TRPM8 and TRPA1 have been highlighted previously. The present study analyzed the distribution of cold pain thresholds with focus at describing the multimodality based on the hypothesis that it reflects a contribution of distinct ion channels.
methodsCold pain thresholds (CPT) were available from 329 healthy volunteers (aged 18 - 37 years; 159 men) enrolled in previous studies. The distribution of the pooled and log-transformed threshold data was described using a kernel density estimation (Pareto Density Estimation (PDE)) and subsequently, the log data was modeled as a mixture of Gaussian distributions using the expectation maximization (EM) algorithm to optimize the fit.
resultsCPTs were clearly multi-modally distributed. Fitting a Gaussian Mixture Model (GMM) to the log-transformed threshold data revealed that the best fit is obtained when applying a three-model distribution pattern. The modes of the identified three Gaussian distributions, retransformed from the log domain to the mean stimulation temperatures at which the subjects had indicated pain thresholds, were obtained at 23.7 °C, 13.2 °C and 1.5 °C for Gaussian #1, #2 and #3, respectively.
conclusionsThe localization of the first and second Gaussians was interpreted as reflecting the contribution of two different cold sensors. From the calculated localization of the modes of the first two Gaussians, the hypothesis of an involvement of TRPM8, sensing temperatures from 25 - 24 °C, and TRPA1, sensing cold from 17 °C can be derived. In that case, subjects belonging to either Gaussian would possess a dominance of the one or the other receptor at the skin area where the cold stimuli had been applied. The findings therefore support a suitability of complex analytical approaches to detect mechanistically determined patterns from pain phenotype data.
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