Differential gene expression of cytokines and neurotrophic factors in nerve and skin of patients with peripheral neuropathies

Abstract

Pathophysiologically relevant alterations in cytokine and neurotrophic factor levels have been reported in neuropathy subtypes. We characterized gene expression profiles of pro- and anti-inflammatory cytokines and neurotrophic factors in nerve and skin samples of patients with neuropathies of different etiologies. We prospectively studied 133 patients with neuropathies and compared data between subtypes and with healthy controls. All patients underwent sural nerve and/or skin punch biopsy at the lateral thigh and lower leg; controls received skin punch biopsies. Gene expression of pro- and anti-inflammatory cytokines (IL-1β, IL-2, IL-6, TNF, IL-10), neurotrophic factors (BDNF, NGF, NT3, TrkA), and erythropoietin with the erythropoietin receptor (Epo, EpoR) was analyzed. Sural nerve gene expression of the investigated cytokines and neurotrophic factors did not differ between neuropathies of different etiologies; however, IL-6 (p < 0.01) and IL-10 (p < 0.05) expression was higher in painful compared to painless neuropathies. Skin IL-6 and IL-10 gene expression was increased in patients compared to controls (p < 0.05), and IL-10 expression was higher in lower leg skin of patients with non-inflammatory neuropathies compared to inflammatory neuropathies (p < 0.05). Proximal and distal skin neurotrophic factor and Epo gene expression of patients with neuropathies was reduced compared to controls (NGF, NT3, Epo; p < 0.05). Neuropathies are associated with an increase in cytokine expression and a decrease in neurotrophic factor expression including nerve and skin.

Long‐term regulation of local cytokine production following immunization in mice

“…Through a systematic review, the involvement of higher levels of inflammatory cytokines (IL‐1β, IL‐6, and IL‐8) was reported, but their pathophysiological role in chronic pain has not been clearly elucidated . The study group also investigated the local expression of cytokines in skin punch biopsy, and gene expressions of IL‐6 and IL‐10 were higher in the painful group compared with that of painless neuropathies . There are no reports on CRPS after vaccination, but increased levels of inflammatory cytokine of IL‐6 may be responsible for local pain.…”

Cellular infiltrates in skin and sural nerve of patients with polyneuropathies

“…How these resident cells may be activated by nerve degeneration has yet to be defined. Peripheral neuropathies apparently may induce inflammatory signals in the skin and lead to an increase in pro‐ and anti‐inflammatory cytokines and a decrease in neurotrophic factors . In turn, alterations in skin cytokine expression may result in accumulation of cutaneous T‐cells and macrophages, regardless of whether or not the neuropathy is immune‐mediated.…”

Increased miR-132-3p expression is associated with chronic neuropathic pain

“…Neuropathies were classified as painful if the patients reported pain with an intensity of 3 or more on a numeric rating scale (NRS) ranging from 0 to 10 (0 meaning “no pain” and 10 “worst pain imaginable”), as previously reported (Üçeyler et al, 2015; Üçeyler et al, 2007). The Graded Chronic Pain Scale (GCPS) (Von Korff et al, 1992) for 4 week recall and the Neuropathic Pain Symptom Inventory (NPSI) (Bouhassira et al, 2004) for the last 24 h recall were also used to assess pain.…”