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J Cell Physiol. 2006, 207:767-74. 10.1002\/jcp.20623","journal-title":"J Cell Physiol"},{"key":"ref47","doi-asserted-by":"publisher","DOI":"10.1159\/000323875","article-title":"Sensory innervation of the nonspecialized connective tissues in the low back of the rat","volume":"194","author":"Corey SM","year":"2011","unstructured":"Corey SM, Vizzard MA, Badger GJ, Langevin HM. Sensory innervation of the nonspecialized connective tissues in the low back of the rat. Cells Tissues Organs. 2011, 194:521-30. 10.1159\/000323875","journal-title":"Cells Tissues Organs"},{"key":"ref48","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.6885.1","article-title":"Viscoelastic properties of hyaluronan in physiological conditions","volume":"4","author":"Cowman MK","year":"2015","unstructured":"Cowman MK, Schmidt TA, Raghavan P, Stecco A. Viscoelastic properties of hyaluronan in physiological conditions. 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Nat Rev Mol Cell Biol. 2014, 15:786-801. 10.1038\/nrm3904","journal-title":"Nat Rev Mol Cell Biol"},{"key":"ref51","doi-asserted-by":"publisher","DOI":"10.1177\/15598276211049345","article-title":"Gluten, inflammation, and neurodegeneration","volume":"16","author":"Philip A","year":"2022","unstructured":"Philip A, White ND. Gluten, inflammation, and neurodegeneration. Am J Lifestyle Med. 2022, 16:32-5. 10.1177\/15598276211049345","journal-title":"Am J Lifestyle Med"},{"key":"ref52","doi-asserted-by":"publisher","DOI":"10.1016\/j.bj.2022.12.002","article-title":"Grounding - the universal anti-inflammatory remedy","volume":"46","author":"Sinatra ST","year":"2023","unstructured":"Sinatra ST, Sinatra DS, Sinatra SW, Chevalier G. Grounding - the universal anti-inflammatory remedy. Biomed J. 2023, 46:11-16. 10.1016\/j.bj.2022.12.002","journal-title":"Biomed J"},{"key":"ref53","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgv038","article-title":"Environmental immune disruptors, inflammation and cancer risk","volume":"36","author":"Thompson PA","year":"2015","unstructured":"Thompson PA, Khatami M, Baglole CJ, et al.. Environmental immune disruptors, inflammation and cancer risk. Carcinogenesis. 2015, 36:S232-53. 10.1093\/carcin\/bgv038","journal-title":"Carcinogenesis"},{"key":"ref54","doi-asserted-by":"publisher","DOI":"10.1177\/1099800420941105","article-title":"The metabolomics of chronic pain conditions: a systematic review","volume":"22","author":"Aroke EN","year":"2020","unstructured":"Aroke EN, Powell-Roach KL. The metabolomics of chronic pain conditions: a systematic review. 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