Fibromyalgia vs small fiber neuropathy: diverse keratinocyte transcriptome signature. Issue 10 (October 2021)

• Record Type: Journal Article
• Authors: Karl, Franziska; Bischler, Thorsten; Egenolf, Nadine; Evdokimov, Dimitar; Heckel, Tobias; Üçeyler, Nurcan
• Is Part Of: Pain. Volume 162:Issue 10(2021)
• Publication Date: 2021-10
• Subjects: Fibromyalgia -- Small fiber neuropathy -- Keratinocytes -- Cutaneous nociception; Pain -- Periodicals; Douleur -- Périodiques; Anesthésie -- Périodiques; Pain; Electronic journals; Periodicals; Electronic journals; 616.0472
• DOI: 10.1097/j.pain.0000000000002249
• Languages: English
• ISSNs: 0304-3959

Abstract

Abstract : Abstract: Damage to thinly myelinated and unmyelinated nerve fibers causes small fiber pathology, which is increasingly found in pain syndromes such as small fiber neuropathy (SFN) and fibromyalgia syndrome (FMS). The peripheral nerve endings of the small nerve fibers terminate within the epidermis, where they are surrounded by keratinocytes that may act as primary nociceptive transducers. We performed RNA sequencing of keratinocytes obtained from patients with SFN, FMS, and healthy controls. We found 141 deregulated protein coding genes between SFN patients and healthy controls and no differentially expressed genes between patients with FMS and healthy controls. When comparing patients with SFN with patients with FMS, we detected 167 differentially expressed protein coding genes (129 upregulated and 38 downregulated). Further analysis revealed enriched inflammatory pathways. Validation of selected candidates in an independent cohort confirmed higher expression of the proinflammatory mediators interleukin-8, C-X-C motif chemokine 3, endothelin receptor type A, and the voltage-gated sodium channel 1.7 in SFN compared with patients with FMS. We provide a diverse keratinocyte transcriptome signature between patients with SFN and patients with FMS, which may hint toward distinct pathomechanisms of small fiber sensitization in both entities and lay the basis for advanced diagnostics. Abstract : Supplemental Digital Content is Available in the Text.We provide a diverse keratinocyte transcriptome signature between patients with small fiber neuropathy and patients with fibromyalgia syndrome, which sheds light on the potential contribution of skin cells to neuropathic pain.