Deoxy-sphingolipids, oxidative stress, and vitamin C correlate with qualitative and quantitative patterns of small fiber dysfunction and degeneration

Abstract

Defined by dysfunction or degeneration of Ad and C fibers, small fiber neuropathies (SFNs) entail a relevant health burden. In 50% of cases, the underlying cause cannot be identified or treated. In 100 individuals (70% female individuals; mean age: 44.8 years) with an idiopathic, skin biopsy-confirmed SFN, we characterized the symptomatic spectrum and measured markers of oxidative stress (vitamin C, selenium, and glutathione) and inflammation (transforming growth factor beta, tumor necrosis factor alpha), as well as neurotoxic 1-deoxysphingolipids. Neuropathic pain was the most abundant symptom (95%) and cause of daily life impairment (72%). Despite the common use of pain killers (64%), the painDETECT questionnaire revealed scores above 13 points in 80% of patients. In the quantitative sensory testing (QST), a dysfunction of Ad fibers was observed in 70% and of C fibers in 44%, affecting the face, hands, or feet. Despite normal nerve conduction studies, QST revealed Ab fiber involvement in 46% of patients' test areas. Despite absence of diabetes mellitus or mutations in SPTLC1 or SPTLC2, plasma 1-deoxy-sphingolipids were significantly higher in the sensory loss patient cluster when compared with those in patients with thermal hyperalgesia (P , 0.01) or those in the healthy category (P , 0.1), correlating inversely with the intraepidermal nerve fiber density (1-deoxy-SA: P , 0.05, 1-deoxy-SO: P , 0.01). Patients with arterial hypertension, overweight (body mass index . 25 kg/m 2 ), or hyperlipidemia showed significantly lower L-serine (arterial hypertension: P , 0.01) and higher 1-deoxysphingolipid levels (arterial hypertension: P , 0.001, overweight: P , 0.001, hyperlipidemia: P , 0.01). Lower vitamin C levels correlated with functional Ab involvement (P , 0.05). Reduced glutathione was lower in patients with Ad dysfunction (P , 0.05). Idiopathic SFNs are heterogeneous. As a new pathomechanism, plasma 1-deoxy-sphingolipids might link the metabolic syndrome with small fiber degeneration.

Analysis of Ionomic Profiles of Spinal Cords in a Rat Model with Bone Cancer Pain

“…The third example is that Se is an important component of some enzymes in vivo, 56 and a biomarker of oxidative stress. 57 Previous findings revealed that Se mediated protective effects against docetaxel-induced adverse peripheral oxidative neurotoxicity and neuropathic pain in mice. 47 Yüksel et al reported that Se treatment significantly decreased fibromyalgia through modulating activities of TRPM2 and TRPV1 channels in rats.…”

Efficacy and safety of vixotrigine in idiopathic or diabetes-associated painful small fibre neuropathy (CONVEY): a phase 2 placebo-controlled enriched-enrolment randomised withdrawal study

“…Diabetes is one of the most common causes of SFN, and neuropathic pain is commonly the first and leading symptom in patients with SFN, having the most relevant patient-reported impact on quality of life. 20 , 21 However, patients with painful SFN have a significant unmet need due to a lack of specifically approved treatments. Current treatments for painful SFN are those approved for diabetic peripheral neuropathy 22 and are associated with significant safety and tolerability issues: gabapentinoids have adverse effects including sleepiness, dizziness, ataxia, oedema, and tremor; tricyclic antidepressants have anticholinergic effects and duloxetine often induces nausea and abdominal pain; and opioids and opiates may cause addiction.…”

Vitamins in neuropathy: pathophysiological and therapeutic roles

“…Adding vitamin C prophylactic supplementation could reduce the incidence of CRPS following stratifying fracture type surgeries [36]. Vitamin C deficiency is associated with Aβ-fiber dysfunction and sensory loss [37 ▪ ]. Deoxy-sphingolipids, oxidative stress, and vitamin C correlate with qualitative and quantitative patterns of small fiber dysfunction and degeneration [37 ▪ ].…”

“…Vitamin C deficiency is associated with Aβ-fiber dysfunction and sensory loss [37 ▪ ]. Deoxy-sphingolipids, oxidative stress, and vitamin C correlate with qualitative and quantitative patterns of small fiber dysfunction and degeneration [37 ▪ ].…”