1 Scientific RepoRts | 5:11894 | DOi: 10.1038/srep11894 www.nature.com/scientificreports protein alterations in women with chronic widespread pain – An explorative proteomic study of the trapezius muscle patrik olausson, Björn Gerdle, Nazdar Ghafouri, Dick sjöström, emelie Blixt & Bijar Ghafouri Chronic widespread pain (CWp) has a high prevalence in the population and is associated with prominent negative individual and societal consequences. there is no clear consensus concerning the etiology behind CWp although alterations in the central processing of nociception maintained by peripheral nociceptive input has been suggested. Here, we use proteomics to study protein changes in trapezius muscle from 18 female patients diagnosed with CWp compared to 19 healthy female subjects. the 2-dimensional gel electrophoresis (2-De) in combination with multivariate statistical analyses revealed 17 proteins to be diferently expressed between the two groups. Proteins were identiied by mass spectrometry. Many of the proteins are important enzymes in metabolic pathways like the glycolysis and gluconeogenesis. other proteins are associated with muscle damage, muscle recovery, stress and inlammation. The altered expressed levels of these proteins suggest abnormalities and metabolic changes in the myalgic trapezius muscle in CWp. taken together, this study gives further support that peripheral factors may be of importance in maintaining CWp. he prevalence of chronic widespread pain (CWP) approximates up to and around 10% of the general population 1-4 of which 10–20% are also diagnosed with ibromyalgia syndrome (FMS) 5–7 . he clinical pictures of CWP and FMS are dominated by the widespread pain but generally also include other somatic and psychological symptoms e.g. depressive symptoms, tiredness, unrefreshing sleep, reduced cognitive capacity. he risk factors for the transition from a local pain condition to CWP are largely unknown but according to a recent systematic review 8 some studies claim increasing age, female gen- der, low physical activity, obesity and depression as risk factors 3,4 . here is a mutual agreement that CWP/FMS is characterized by signs of central hyperexcitability and alterations in the pain matrix in the brain 5,9–12 . Other possibly related characteristics are disturbances in neuroendocrine and autonomic nervous system 13,14 . here is a debate concerning whether peripheral factors are of importance or not for maintaining the central alterations. Hence, there are reports indicating peripheral alterations 15–17 , which may act as pain generators in CWP/FMS, such as mitochondrial disturbances in type-I muscle ibres, increased DNA fragmentation of muscle nuclei, alterations in the mitochondrial respiration chain, reduced capillarization and altered microcirculation, and greater thickness of the endothelium of the capillaries 18–23 . Recently three research groups have reported alterations of the peripheral nociceptors in FMS 16,24,25 . Various treatment studies also indicate an important role of peripheral input in maintaining pain and central alterations in CWP/FMS 26–28 . hese studies give further support to the hypothesis that peripheral factors contribute to the maintenance of pain in CWP/FMS. Division of community Medicine, Department of Medical and Health Sciences, faculty of Health Sciences, Linköping University and Pain and Rehabilitation center, Anaesthetics, Operations and Specialty Surgery center, Region Östergötland. correspondence and requests for materials should be addressed to P.O. (email: patrik. olausson@liu.se) Received: 11 January 2015 Accepted: 09 June 2015 Published: 07 July 2015 opeN