Remote Photoplethysmography for Evaluation of Cutaneous Sensory Nerve Fiber Function

About 2% of the world’s population suffers from small nerve fiber dysfunction, neuropathy, which can result in severe pain. This condition is caused by damage to the small nerve fibers and its assessment is challenging, due to the lack of simple and objective diagnostic techniques. The present study aimed to develop a contactless photoplethysmography system using simple instrumentation, for objective and non-invasive assessment of small cutaneous sensory nerve fiber function. The approach is based on the use of contactless photoplethysmography for the characterization of skin flowmotions and topical heating evoked vasomotor responses. The feasibility of the technique was evaluated on volunteers (n = 14) using skin topical anesthesia, which is able to produce temporary alterations of cutaneous nerve fibers function. In the treated skin region in comparison to intact skin: neurogenic and endothelial component of flowmotions decreased by ~61% and 41%, the local heating evoked flare area decreased by ~44%, vasomotor response trend peak and nadir were substantially reduced. The results indicate for the potential of the remote photoplethysmography in the assessment of the cutaneous nerve fiber function. It is believed that in the future this technique could be used in the clinics as an affordable alternative to laser Doppler imaging technique.

Prenylated quinolinecarboxylic acid compound-18 prevents sensory nerve fiber outgrowth through inhibition of the interleukin-31 pathway

Interleukin-31 (IL-31) is involved in excessive development of cutaneous sensory nerves in atopic dermatitis (AD), leading to severe pruritus. We previously reported that PQA-18, a prenylated quinolinecarboxylic acid (PQA) derivative, is an immunosuppressant with inhibition of p21-activated kinase 2 (PAK2) and improves skin lesions in Nc/Nga mice as an AD model. In the present study, we investigate the effect of PQA-18 on sensory nerves in lesional skin. PQA-18 alleviates cutaneous nerve fiber density in the skin of Nc/Nga mice. PQA-18 also inhibits IL-31-induced sensory nerve fiber outgrowth in dorsal root ganglion cultures. Signaling analysis reveals that PQA-18 suppresses phosphorylation of PAK2, Janus kinase 2, and signal transducer and activator of transcription 3 (STAT3), activated by IL-31 receptor (IL-31R), resulting in inhibition of neurite outgrowth in Neuro2A cells. Gene silencing analysis for PAK2 confirms the requirement for STAT3 phosphorylation and neurite outgrowth elicited by IL-31R activation. LC/MS/MS analysis reveals that PQA-18 prevents the formation of PAK2 activation complexes induced by IL-31R activation. These results suggest that PQA-18 inhibits the IL-31 pathway through suppressing PAK2 activity, which suppresses sensory nerve outgrowth. PQA-18 may be a valuable lead for the development of a novel drug for pruritus of AD.