Cannabinoids consistently produced antinociceptive effects in preclinical models, whereas they heterogeneously influenced the perception of experimentally induced pain in humans and did not provide robust clinical analgesia, which jeopardizes the translation of preclinical research on cannabinoid-mediated antinociception into the human setting.

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Muscle morphology in LOPD patients shows a high variability with, in most cases, moderate pathology.Increased pathology is associated with more fibrosis and autophagy.

Background: Transient receptor potential ion channels play a role in thermal hyperalgesia and are among targets of novel analgesics. However, a role of TRPA1 in either heat or cold hyperalgesia is controversial. In this study, changes in thermal sensitivity were assessed following topical application of a specific sensitizer of TRPA1 and compared with the effects of sensitizers of TRPV1 and TRPM8. Methods: Employing a randomized cross-over design, thermal thresholds were assessed in 16 pain-free volunteers before and at 20 minutes after topical application of cinnamaldehyde, capsaicin or menthol stimulating TRPA1, TRPV1, or TRPM8, respectively. Cold or warm detection thresholds and cold or heat pain thresholds were assessed according to the standardized quantitative sensory testing protocol proposed by the German Research Network on Neuropathic Pain. Results: The effects of different irritants displayed a cluster structure. Hyperalgesia was induced by capsaicin and cinnamaldehyde on heat pain thresholds and by menthol on cold pain thresholds (Cohen d=2.2035, 0.9932, and 1.256, respectively). A second cluster comprised large effects directed toward hyposensitization, such as cold hyposensitization induced by capsaicin and cinnamaldehyde, or small or absent hyposensitizing effects. Conclusions: The observation that the TRPA1 irritant cinnamaldehyde induced heat hyperalgesia at an effect sizes comparable with that of capsaicin attributes TRPA1 a role in human heat-induced pain. Results suggest the inclusion of heat pain as a major efficacy measure in human experimental studies of the effects of TRPA1 antagonists and the development of TRPA1 antagonists for clinical pain settings involving heat hyperalgesia.

Sensitivity to pain is heterogeneous. Data-driven computational research approaches allow the identification of subgroups of subjects with a distinct pattern of sensitivity to cold stimuli. The subgroups are reproducible with different types of noxious cold stimuli. Subgroups show pattern that hints at distinct and inter-individually different types of the underlying molecular background.