scholarly journals Remote Photoplethysmography for Evaluation of Cutaneous Sensory Nerve Fiber Function

Sensors ◽  
2021 ◽  
Vol 21 (4) ◽  
pp. 1272
Author(s):  
Zbignevs Marcinkevics ◽  
Alise Aglinska ◽  
Uldis Rubins ◽  
Andris Grabovskis

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.

2000 ◽  
Vol 38 (4) ◽  
pp. 366-371 ◽  
Author(s):  
Norikuni TOIBANA ◽  
Hisataka SAKAKIBARA ◽  
Mamoru HIRATA ◽  
Takaaki KONDO ◽  
Hideaki TOYOSHIMA

2019 ◽  
Vol 48 (1) ◽  
pp. 59-70 ◽  
Author(s):  
Lisa M. Mangus ◽  
Deepa B. Rao ◽  
Gigi J. Ebenezer

Analysis of intraepidermal nerve fibers (IENFs) in skin biopsy samples has become a standard clinical tool for diagnosing peripheral neuropathies in human patients. Compared to sural nerve biopsy, skin biopsy is safer, less invasive, and can be performed repeatedly to facilitate longitudinal assessment. Intraepidermal nerve fiber analysis is also more sensitive than conventional nerve histology or electrophysiological tests for detecting damage to small-diameter sensory nerve fibers. The techniques used for IENF analysis in humans have been adapted for large and small animal models and successfully used in studies of diabetic neuropathy, chemotherapy-induced peripheral neuropathy, HIV-associated sensory neuropathy, among others. Although IENF analysis has yet to become a routine end point in nonclinical safety testing, it has the potential to serve as a highly relevant indicator of sensory nerve fiber status in neurotoxicity studies, as well as development of neuroprotective and neuroregenerative therapies. Recently, there is also interest in the evaluation of IENF via skin biopsy as a biomarker of small fiber neuropathy in the regulatory setting. This article provides an overview of the anatomic and pathophysiologic principles behind IENF analysis, its use as a diagnostic tool in humans, and applications in animal models with focus on comparative methodology and considerations for study design.


2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Francesca Magrinelli ◽  
Chiara Briani ◽  
Marcello Romano ◽  
Susanna Ruggero ◽  
Elisabetta Toffanin ◽  
...  

Diabetic peripheral neuropathy (DPN) is a frequent complication of type 2 diabetes mellitus (DM) and may involve small and large peripheral nerve fibers. Recent evidence suggests a role of cytokines in DPN. The paper is aimed at exploring whether the serum concentration of cytokines is associated with small and large nerve fiber function and with neuropathic pain (NP). We recruited a group of 32 type 2 DM patients who underwent serum cytokines (TNF-α, IL-2, IL-4, IL-6, and IL-10) dosage as well as electrodiagnostic and quantitative sensory testing (QST) assessment to explore damage to large and small nerve fibers. Raised serum levels of IL-6 and IL-10 correlated with markers of large nerve fiber sensory and motor axonal damage. Raised IL-10 serum level was associated with signs of motor nerve demyelination. No differences were found in pain characteristics and electrodiagnostic and QST markers of small nerve fiber function in relation to cytokines serum levels. IL-6 and IL-10 serum levels were associated with large nerve fiber damage but not to small fibers function or NP. IL-6 and IL-10 cytokines might play a role in the pathogenesis of nerve fiber damage or represent a compensatory or neuroprotective mechanism.


PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246630
Author(s):  
Masato Ogura ◽  
Kumiko Endo ◽  
Toshiyuki Suzuki ◽  
Yoshimi Homma

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.


2022 ◽  
Author(s):  
Xiuxiang Tan ◽  
Mika Rosin ◽  
Simone Appinger ◽  
Jan Bednarsch ◽  
Dong Liu ◽  
...  

Background & Aims: Perihilar cholangiocarcinoma (pCCA) is a hepatobiliary malignancy. Nerve fiber invasion (NFI) shows cancer invading the nerve and is considered an aggressive feature. Nerve fiber density (NFD) consists of small nerve fibers without cancer invasion and is divided into high NFD (high numbers of small nerve fibers) or low NFD (low numbers of small nerve fibers). We aim to explore differences in immune cell populations and survival. Approach & Results: We applied multiplex immunofluorescence (mIF) on 47 pCCA surgically resected patients and investigated immune cell composition in the tumor microenvironment (TME) of nerve fiber phenotypes (NFI, high and low NFD). Group comparison was performed and overall survival (OS) was assessed. The NFI Region of Interest (ROI) was measured with highest CD68+ macrophage levels among 3 ROIs (NFI compared to tumor free p= 0.016 and to tumor p=0.034) and PD1 expression on CD8 and were more abundant in the tumor rather than NFI ROI (p= 0.004 and p= 0.0029 respectively). NFD compared to NFI, demonstrated co-expression of CD8+PD1+ as well as CD68+PD1+ to be significantly higher in high NFD patients (p= 0.027 and p= 0.044, respectively). The high NFD OS was 92 months median OS (95% CI:41-142), for low NFD 20 months ((95% CI: 4-36) and for NFI 19 months (95% CI 7-33). High NFD OS was significantly better compared to low NFD (p= 0.046) and NFI (p= 0.032). Conclusions: PD1+ T-cells correlate with high NFD as a prognostic biomarker, the biological pathway behind this needs to be investigated.


2021 ◽  
Author(s):  
Si-Qi Chen ◽  
Xue-Yan Chen ◽  
Ying-Zhe Cui ◽  
Bing-Xi Yan ◽  
Yuan Zhou ◽  
...  

Abstract Recent studies have illustrated that psoriatic lesions are innervated by dense sensory nerve fibers. Psoriatic plaques appeared to improve after central or peripheral nerve injury. Therefore, the nervous system may play a vital role in psoriasis. We aimed to clarify the expression of nerve fibers in psoriasis and their relationship with immune cells and keratinocytes, and to explore the effect of skin nerve impairment. Our results illustrated that nerve fibers in psoriatic lesions increased and were closely innervated around immune cells and keratinocytes. RNA-seq analysis showed that peripheral sensory nerve-related genes were disrupted in psoriasis. In spinal cord hemi-section mice, sensory impairment improved psoriasiform dermatitis and inhibited the abnormal proliferation of keratinocytes. Botulinum toxin A alleviated psoriasiform dermatitis by inhibiting the secretion of calcitonin gene-related peptide. Collectively, cutaneous nerve fibers participate in the progression of psoriasis by linking epidermal keratinocytes and immunocytes. Neurological intervention may be a new treatment strategy for psoriasis.


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