Accepted

Schwann cells (SC) are essential to the growth, maintenance and regeneration of peripheral nerves, but the proteome of normal human SC is poorly defined. Here, we performed a proteomic analysis by liquid chromatography tandem mass spectrometry (LC-MS/MS) to define the protein expression profile of primary human SC. A total of 19,557 unique peptides corresponding to 1,553 individual proteins were identified. Ingenuity Pathway Analysis (IPA), Gene Ontology (GO) and Database for Annotation, Visualization and Integrated Discovery (DAVID) were used to assign protein localization and function, and to define enriched pathways. EIF2, mTOR and integrin signalling were among the most enriched pathways and the most enriched biological function was cell-cell adhesion, which is in agreement with the supportive role of SC in peripheral nerves. In addition, several nociceptors and synaptic proteins have been identified and may contribute to the recently discovered role of SC in pain sensation and cancer progression. This proteome analysis of normal human SC constitutes a reference for future molecular explorations of physiological and pathological processes where SC are involved. This article is protected by copyright. All rights reserved.

Epidemiological studies have to a little extent addressed the potential fluctuations of chronic pain over time, and there is a lack of information about the long-term course of pain using repeated measurements. We wanted to identify different trajectories of pain during eight waves of follow-up over four years among individuals in the general population reporting pain lasting at least six months at baseline. Secondarily, we wanted to investigate whether biopsychosocial factors at baseline were associated with the different pain trajectories. Longitudinal Latent Class Analysis (LLCA) was performed to classify 1905 random participants from a larger population-based study (HUNT3) into groups based on their longitudinal pain severity reporting. A five-class solution gave the best fit. The terms chosen to describe the pain trajectories were: "fluctuating" (n = 586 [31 %]), "persistent mild" (n = 449 [24 %]), "persistent moderate" (n = 414 [22 %]), "persistent severe" (n = 251 [13 %]), and "gradual improvement" (n = 205 [11 %]). In a multinomial logistic regression model using "gradual improvement" as the reference category, the "persistent moderate", "persistent severe", and "fluctuating" pain groups were associated with chronic widespread pain (CWP), elevated levels of catastrophizing, and poorer mental health. The "persistent mild" group was associated with sleep difficulties only. This study finds that although most individuals have a stable pain course, individuals in the largest distinct trajectory reports pain that fluctuate between mild and moderate levels, thus fluctuating under and above the chronic pain definition using moderate pain or more as a criterion. Perspective: When examining the long-term course of chronic pain in the general population, five trajectories emerge. Although most individuals have stable pain, the largest distinct trajectory fluctuated under and above the chronic pain cut-off, using moderate pain or more as a criterion. A dichotomous categorization of chronic pain may be overly simplistic.