Phosphorylation of extracellular signal-regulated kinase 1/2 in subepidermal nerve fibers mediates hyperalgesia following diabetic peripheral neuropathy.

Phosphorylation of extracellular signal-regulated kinase 1/2 in subepidermal nerve fibers mediates hyperalgesia following diabetic peripheral neuropathy. Neurotoxicology. 2018 Dec 21;: Authors: Liu CH, Lan CT, Chen LY, Liao WC, Ko MH, Tseng TJ Abstract Peripheral neuropathy, a chronic complication of diabetes mellitus (DM), is often accompanied by the onset of severe pain symptoms that affect quality of life. However, the underlying mechanisms remain elusive. In the present study, we used Sprague-Dawley rats to establish a rodent model of the human type 1 DM by a single intraperitoneal (i.p.) injection with streptozotocin (STZ) (60 mg/kg). Hypersensitivity, including hyperalgesia and allodynia, developed in the STZ-induced diabetic rats. Cutaneous innervation exhibited STZ-induced reductions of protein gene product 9.5-, peripherin-, and neurofilament 200-immunoreactivity (IR) subepidermal nerve fibers (SENFs). Moreover, the decreases of substance P (SP)- and calcitonin gene-related peptide (CGRP)-IR SENFs were distinct gathered from the results of extracellular signal-regulated kinase 1 and 2 (ERK1/2)- and phosphorylated ERK1/2 (pERK1/2)-IR SENFs in STZ-induced diabetic rats. Double immunofluorescence studies demonstrated that STZ-induced pERK1/2-IR was largely increased in SENFs where only a small portion was colocalized with SP- or CGRP-IR. By an intraplantar (i. pl.) injection with a MEK inhibitor, U0126 (1,4-Diamino-2,3-dicyan...
Source: Neurotoxicology - Category: Neurology Authors: Tags: Neurotoxicology Source Type: research