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In the version of this article initially published online, the affiliations for Bertram Muller-Myhsok and Patricia Pozo-Rosich were incorrect or incomplete. These errors have been corrected for the print, PDF and HTML versions of this article.

Background: Fibromyalgia is characterised by chronic pain and a heterogeneous presentation of other symptoms (e.g., fatigue and depression) [1]. It is widely accepted that pain is promoted by both genetic susceptibility and environmental factors such as people’s behaviours [2]. In addition to genotype individual associations and gene-gene interactions, when considering complex phenotypes such as pain, gene-environmental interactions are likely present and can help to better understand the disease (i.e. by unravelling underlying mechanisms [3]). Objectives: To test the individual association of 64 polymorphisms (34 candidate-genes) and the gene-gene, gene-physical activity, and gene-sedentary behaviour interactions with pain and pain-related cognitions in fibromyalgia. Methods: In 274 women with fibromyalgia, saliva samples were collected for extracting DNA. We measured physical activity and sedentary behaviour by accelerometers for a week, pain with algometry and questionnaires, and pain cognitions with questionnaires. Age, body fat, and analgesics and antidepressants consumption were included as covariates. Significance was set at P-values lower than the Bonferroni’s correction or P- and false discovery rate values lower than 0.05. Results: The rs6311 and rs6313 polymorphisms were individually related to algometer scores. The interaction of rs4818 and rs1799971 polymorphisms was related to pain catastrophizing. Five gene-behaviour interactions were significant: the interactions of sedentary behaviour with rs1383914, rs6860, rs4680, rs165599, and rs12994338 polymorphisms were associated with the bodily pain subscale of the SF-36. Conclusion: The HTR2A gene (individually), COMT and OPRM1 gene-gene interaction, and the interactions of sedentary behaviour with ADRA1A, CHMP1A, COMT, and SCN9A genes were associated with pain-related outcomes in fibromyalgia females. Besides indicating the relevance of genetic background for pain and pain-catastrophizing, the observed genotype-behaviour interactions suggest that the effects of sedentary behaviour on pain may depend on the genotype of women with fibromyalgia. Future clinical experimental research should examine whether reducing sedentary behaviour is particularly beneficial for reducing pain in women with specific genotypes. References [1] Estevez-Lopez F, et al. Rheumatology (Oxford). 2017Nov;56(11):2015-2024 [2] Nielsen CS, et al. Pain. 2008May;136(1-2):21-9 [3] Hunter DJ. Nat Rev Genet. 2005Apr;6(4):287-98 Acknowledgement: This work was supported by the Spanish Ministry of Economy and Competitiveness [I+D+i DEP2010-15639, I+D+i DEP2013-40908-R to M.D.-F.; BES-2014-067612 to F.E.-L.], the Spanish Ministry of Education [FPU13/03410 to D.S.-T.; FPU15/0002 to B.G.-C.], the Consejeria de Turismo, Comercio y Deporte, Junta de Andalucia [CTCD-201000019242-TRA to MD-F], the Consejeria de Salud, Junta de Andalucia [PI-0520-2016 to M.D.-F.], and the University of Granada, Plan Propio de Investigacion 2016, Excellence actions: Units of Excellence; Unit of Excellence on Exercise and Health (UCEES). Disclosure of Interests: None declared

The papers of this thesis are not available in Munin:Paper I. Persistent postsurgical pain in a general population: Prevalence and predictors in the Tromsø study. Johansen A, Romundstad L, Nielsen CN, Schirmer H, Stubhaug A. Available in PAIN®, vol. 153, issue 7, 2012, pp. 1390–1396Paper II. Persistent post-surgical pain and experimental pain sensitivity in the Tromsø study: Comorbid pain matters. Johansen A, Schirmer H, Stubhaug A, Nielsen CS. Available in PAIN®, vol. 155, issue 2, 2014, pp. 341-348Paper III. Persistent post-surgical pain and signs of nerve injury. The Tromsø Study. (Manuscript). Persistent pain is reported to be a frequent complication from surgery. Among the proposed risk factors are perioperative nerve injury and individual differences in pain sensitivity. The 6th Tromsø Study, a cross-sectional survey and medical examination, provided questionnaire data on persistent pain in general and persistent pain following surgery in particular. Participants performed tests of sensitivity to experimental pain stimuli. A sample of participants who had performed surgery 3-36 months before the survey, were re-assessed with questionnaires and quantitative assessments of sensory function 15-32 months after Tromsø 6. In accordance with previous research, we found that persistent pain after surgery was common. Moderate or severe pain in the area of surgery 3-36 months after the procedure was reported by 18.3 %. Most cases were coexistent with other chronic pain. Only in a small minority of cases did the patients themselves attribute persistent pain to surgery alone. In a general surgical sample, we could not identify specific associations between persistent post-surgical pain and sensitivity to experimental pain stimuli when comorbid pain was adjusted for. Persistent post-surgical pain was strongly associated with self-reported sensory disturbances, indicating possible nerve injury as a contributing factor. Sensory aberrations were confirmed with sensory testing in a majority of individuals with persistent pain in the surgical area. However, nerve injury does not appear sufficient for development of such pain, as signs of nerve injury, confirmed with quantitative sensory testing, were just as common among individuals without persistent post-surgical pain.

Es konnte bereits in mehreren Veroffentlichungen gezeigt werden, dass Tranexamsaure zur Reduktion des Blutverlustes nach Knieendoprothetik beitragt. Zur intravenosen Applikation der Tranexamsaure liegen etwa 19 randomisierte Studien vor, die diesen Effekt bestatigen. Ziel der vorliegenden Untersuchung war es, die Wirksamkeit der kombinierten intravenosen/intraartikularen Tranexamsaure-Applikation im Vergleich zur alleinigen intravenosen Gabe zu evaluieren. Nielsen CS, Jans O, Orsnes T et al. Combined intra-articular and intravenous tranexamic acid reduces blood loss in total knee arthroplasty. A randomized, double-blind, placebo-controlled trial. J Bone Joint Surg Am. 2016; 98: 835–841