The nociception impairment in diabetic patients is considered as one of the main predisposing factors for developing pressure ulcers. In addition to impairing nociception, alteration of skin nerve fibers may impede the inflammatory response and, so, affect the physiological skin response to injury. In this study, we aimed to determine the consequence of a specific sensory small fiber neuropathy (SFN) on cutaneous inflammatory biomarkers by a transcriptomic analysis.
SFN was induced in mice by a single intraperitoneal injection of resiniferatoxin (RTX), a capsaicin analog that specifically affects sensory small fibers that expressed the transient receptor potential vanilloid 1 (TRPV1). The back skin was removed 24h after the RTX administration. The transcriptome of the skin was investigated using the Agilent array Sureprint G3 mouse.
RTX mice develop a thermal hypoalgesia (hot plate test) and a tactile allodynia (von Frey). Transcriptomic analysis yielded a list of 1947 genes whose expression in the skin was dysregulated by RTX-induced neuropathy (fold change FC > 1.5, p < 0.05). The PCRq analysis validated the microarray results for 7 genes; camk2d (FC = +1.6, p = 0.018), card9 (FC = -2.2, p = 0.005), ccl5 (FC = -2.9, p = 0.010), ccr5 (FC = -2.8, p = 0.014), epng (FC = +2.7, p = 0.029), gzmb (FC = -2.9, p = 0.002) and socs2 (FC = +2.3, p = 0.015).
Card9, granzyme B and socs2 are key players of the inflammatory phase of the cutaneous wound healing. The interaction between CCL5 and CCR5 improve neovascularization in skin injuries. CCR5, EPNG (epigen) and Camk2d are implied in the generation of neuropathic pain.
Our results encourage further investigations into pathways implied by the dysregulation of these 7 genes to find news targets for the management of wounds and of neuropathic pain associated to small fiber neuropathy. Moreover, our data suggest that the skin inflammatory state is dysregulated by SFN, which can lead to abnormal inflammatory response responsible for an increased
risk of pressure ulcer and wound healing delay observed in diabetic conditions.