Endogenous anandamide and self-reported pain are significantly reduced after a 2-week multimodal treatment with and without radon therapy in patients with knee osteoarthritis: a pilot study.
Anandamide
Endocannabinoid
Osteoarthritis
Radon
Journal
International journal of biometeorology
ISSN: 1432-1254
Titre abrégé: Int J Biometeorol
Pays: United States
ID NLM: 0374716
Informations de publication
Date de publication:
Jul 2021
Jul 2021
Historique:
received:
30
09
2020
accepted:
10
02
2021
revised:
10
02
2021
pubmed:
3
3
2021
medline:
23
6
2021
entrez:
2
3
2021
Statut:
ppublish
Résumé
Multimodal therapies comprising spa applications are widely used as non-pharmaceutical treatment options for musculoskeletal diseases. The purpose of this randomized, controlled, open pilot study was to elucidate the involvement of the endocannabinoid system in a multimodal therapy approach. Twenty-five elderly patients with knee osteoarthritis (OA) received a 2-week spa therapy with or without combination of low-dose radon therapy in the Bad Gastein radon gallery. A 10-point numerical rating scale (pain in motion and at rest), WOMAC questionnaire, and the EuroQol-5D (EQ-5D) questionnaire were recorded at baseline, and during treatment period at weeks one and two, and at 3-month and 6-month follow-ups. Plasma levels of the endocannabinoid anandamide (AEA) were determined at baseline and at 2 weeks, and serum levels of several cartilage metabolism markers at all five time-points. A significant and sustained reduction of self-reported knee pain was observed in the study population, but no further significant effect of the additional radon therapy up and above base therapy. This pain reduction was accompanied by a significant reduction of AEA plasma levels during treatment in both groups. No significant differences were seen in serum marker concentrations between the groups treated with or without radon, but a small reduction of serum cartilage degradation markers was observed during treatment in both groups. This is the first study investigating AEA levels in the context of a non-pharmacological OA treatment. Since the endocannabinoid system represents a potential target for the development of new therapeutics, further studies will have to elucidate its involvement in OA pain.
Identifiants
pubmed: 33649972
doi: 10.1007/s00484-021-02095-z
pii: 10.1007/s00484-021-02095-z
pmc: PMC8213596
doi:
Substances chimiques
Arachidonic Acids
0
Endocannabinoids
0
Polyunsaturated Alkamides
0
Radon
Q74S4N8N1G
anandamide
UR5G69TJKH
Types de publication
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
1151-1160Subventions
Organisme : Paracelsus Medizinische Privatuniversität
ID : PMU-FFF: R-16/01/076-DOB
Références
Annegret F, Thomas F (2013) Long-term benefits of radon spa therapy in rheumatic diseases: results of the randomised, multi-centre IMuRa trial. Rheumatol Int 33(11):2839–2850. https://doi.org/10.1007/s00296-013-2819-8
doi: 10.1007/s00296-013-2819-8
Antonelli M, Donelli D, Fioravanti A (2018) Effects of balneotherapy and spa therapy on quality of life of patients with knee osteoarthritis: a systematic review and meta-analysis. Rheumatol Int 38(10):1807–1824. https://doi.org/10.1007/s00296-018-4081-6
doi: 10.1007/s00296-018-4081-6
Bannuru RR, Osani MC, Vaysbrot EE, Arden NK, Bennell K, Bierma-Zeinstra SMA, Kraus VB, Lohmander LS, Abbott JH, Bhandari M, Blanco FJ, Espinosa R, Haugen IK, Lin J, Mandl LA, Moilanen E, Nakamura N, Snyder-Mackler L, Trojian T, Underwood M, McAlindon TE (2019) OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthr Cartil 27(11):1578–1589. https://doi.org/10.1016/j.joca.2019.06.011
doi: 10.1016/j.joca.2019.06.011
Becker K (2003) Health effects of high radon environments in Central Europe: another test for the LNT hypothesis? Nonlinearity Biol Toxicol Med 1(1):3–35. https://doi.org/10.1080/15401420390844447
doi: 10.1080/15401420390844447
Bender T, Nagy G, Barna I, Tefner I, Kadas E, Geher P (2007) The effect of physical therapy on beta-endorphin levels. Eur J Appl Physiol 100(4):371–382. https://doi.org/10.1007/s00421-007-0469-9
doi: 10.1007/s00421-007-0469-9
Bruehl S, Burns JW, Morgan A, Koltyn K, Gupta R, Buvanendran A, Edwards D, Chont M, Kingsley PJ, Marnett L, Stone A, Patel S (2019) The association between endogenous opioid function and morphine responsiveness: a moderating role for endocannabinoids. Pain 160(3):676–687. https://doi.org/10.1097/j.pain.0000000000001447
doi: 10.1097/j.pain.0000000000001447
Crombie KM, Brellenthin AG, Hillard CJ, Koltyn KF (2018) Endocannabinoid and opioid system interactions in exercise-induced hypoalgesia. Pain Med 19(1):118–123. https://doi.org/10.1093/pm/pnx058
doi: 10.1093/pm/pnx058
Cuttler JM (2020) Application of low doses of ionizing radiation in medical therapies. Dose-Response 18(1):1559325819895739. https://doi.org/10.1177/1559325819895739
doi: 10.1177/1559325819895739
Da Silva Santos R, Galdino G (2018) Endogenous systems involved in exercise-induced analgesia. J Physiol Pharmacol 69(1):3–13. https://doi.org/10.26402/jpp.2018.1.01
doi: 10.26402/jpp.2018.1.01
Daghestani HN, Jordan JM, Renner JB, Doherty M, Wilson AG, Kraus VB (2017) Serum N-propeptide of collagen IIA (PIIANP) as a marker of radiographic osteoarthritis burden. PLoS One 12(12):e0190251. https://doi.org/10.1371/journal.pone.0190251
doi: 10.1371/journal.pone.0190251
Dam EB, Loog M, Christiansen C, Byrjalsen I, Folkesson J, Nielsen M, Qazi AA, Pettersen PC, Garnero P, Karsdal MA (2009) Identification of progressors in osteoarthritis by combining biochemical and MRI-based markers. Arthritis Res Ther 11(4):R115. https://doi.org/10.1186/ar2774
doi: 10.1186/ar2774
Desroches J, Beaulieu P (2010) Opioids and cannabinoids interactions: involvement in pain management. Curr Drug Targets 11(4):462–473. https://doi.org/10.2174/138945010790980303
doi: 10.2174/138945010790980303
Donvito G, Nass SR, Wilkerson JL, Curry ZA, Schurman LD, Kinsey SG, Lichtman AH (2018) The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain. Neuropsychopharmacology 43(1):52–79. https://doi.org/10.1038/npp.2017.204
doi: 10.1038/npp.2017.204
Dorner TE, Stein KV (2013) Prevalence and status quo of osteoarthritis in Austria. Analysis of epidemiological and social determinants of health in a representative cross-sectional survey. Wien Med Wochenschr 163:206–211
doi: 10.1007/s10354-013-0174-8
Falkenbach A, Kovacs J, Franke A, Jorgens K, Ammer K (2005) Radon therapy for the treatment of rheumatic diseases--review and meta-analysis of controlled clinical trials. Rheumatol Int 25(3):205–210. https://doi.org/10.1007/s00296-003-0419-8
doi: 10.1007/s00296-003-0419-8
Fioravanti A, Iacoponi F, Bellisai B, Cantarini L, Galeazzi M (2010) Short- and long-term effects of spa therapy in knee osteoarthritis. Am J Phys Med Rehabil 89(2):125–132. https://doi.org/10.1097/PHM.0b013e3181c1eb81
doi: 10.1097/PHM.0b013e3181c1eb81
Fitzgerald GK, Hinman RS, Zeni J Jr, Risberg MA, Snyder-Mackler L, Bennell KL (2015) OARSI clinical trials recommendations: design and conduct of clinical trials of rehabilitation interventions for osteoarthritis. Osteoarthr Cartil 23(5):803–814. https://doi.org/10.1016/j.joca.2015.03.013
doi: 10.1016/j.joca.2015.03.013
Forestier R, Desfour H, Tessier JM, Francon A, Foote AM, Genty C, Rolland C, Roques CF, Bosson JL (2010) Spa therapy in the treatment of knee osteoarthritis: a large randomised multicentre trial. Ann Rheum Dis 69(4):660–665. https://doi.org/10.1136/ard.2009.113209
doi: 10.1136/ard.2009.113209
Franke A, Reiner L, Resch KL (2007) Long-term benefit of radon spa therapy in the rehabilitation of rheumatoid arthritis: a randomised, double-blinded trial. Rheumatol Int 27(8):703–713. https://doi.org/10.1007/s00296-006-0293-2
doi: 10.1007/s00296-006-0293-2
Galvez I, Torres-Piles S, Ortega-Rincon E (2018) Balneotherapy, immune system, and stress response: a hormetic strategy? Int J Mol Sci 19(6). https://doi.org/10.3390/ijms19061687
Harirforoosh S, Asghar W, Jamali F (2013) Adverse effects of nonsteroidal antiinflammatory drugs: an update of gastrointestinal, cardiovascular and renal complications. J Pharm Pharm Sci 16(5):821–847. https://doi.org/10.18433/j3vw2f
doi: 10.18433/j3vw2f
Hawker GA (2019) Osteoarthritis is a serious disease. Clin Exp Rheumatol 37(Suppl 120 (5)):3–6
Kojima S, Thukimoto M, Cuttler JM, Inoguchi K, Ootaki T, Shimura N, Koga H, Murata A (2018) Recovery from rheumatoid arthritis following 15 months of therapy with low doses of ionizing radiation: a case report. Dose-Response 16(3):1559325818784719. https://doi.org/10.1177/1559325818784719
doi: 10.1177/1559325818784719
Kuciel-Lewandowska J, Gnus J, Pawlik-Sobecka L, Placzkowska S, Kokot I, Kasperczak M, Paprocka-Borowicz M (2018) The assessment of the integrated antioxidant system of the body in the course of radon therapy: a pilot study. Biomed Res Int 2018:6038106–6038107. https://doi.org/10.1155/2018/6038106
doi: 10.1155/2018/6038106
Kuciel-Lewandowska J, Kasperczak M, Pawlik-Sobecka L, Paprocka-Borowicz M, Gnus J (2020) Assessment of changes in concentration of total antioxidant status, acute-phase protein, and prolactin in patients with osteoarthritis subjected to a complex spa treatment with radon water: preliminary results. PPAR Res 2020:9459418–9459419. https://doi.org/10.1155/2020/9459418
doi: 10.1155/2020/9459418
La Porta C, Bura SA, Llorente-Onaindia J, Pastor A, Navarrete F, Garcia-Gutierrez MS, De la Torre R, Manzanares J, Monfort J, Maldonado R (2015) Role of the endocannabinoid system in the emotional manifestations of osteoarthritis pain. Pain 156(10):2001–2012. https://doi.org/10.1097/j.pain.0000000000000260
doi: 10.1097/j.pain.0000000000000260
La Porta C, Bura SA, Negrete R, Maldonado R (2014) Involvement of the endocannabinoid system in osteoarthritis pain. Eur J Neurosci 39(3):485–500. https://doi.org/10.1111/ejn.12468
doi: 10.1111/ejn.12468
Lambova SN, Muller-Ladner U (2018) Osteoarthritis - current insights in pathogenesis, diagnosis and treatment. Curr Rheumatol Rev 14(2):91–97. https://doi.org/10.2174/157339711402180706144757
doi: 10.2174/157339711402180706144757
Lange U, Dischereit G, Tarner I, Frommer K, Neumann E, Muller-Ladner U, Kurten B (2016) The impact of serial radon and hyperthermia exposure in a therapeutic adit on pivotal cytokines of bone metabolism in rheumatoid arthritis and osteoarthritis. Clin Rheumatol 35(11):2783–2788. https://doi.org/10.1007/s10067-016-3236-7
doi: 10.1007/s10067-016-3236-7
Lotz M, Martel-Pelletier J, Christiansen C, Brandi ML, Bruyere O, Chapurlat R, Collette J, Cooper C, Giacovelli G, Kanis JA, Karsdal MA, Kraus V, Lems WF, Meulenbelt I, Pelletier JP, Raynauld JP, Reiter-Niesert S, Rizzoli R, Sandell LJ, Van Spil WE, Reginster JY (2014) Republished: Value of biomarkers in osteoarthritis: current status and perspectives. Postgrad Med J 90(1061):171–178. https://doi.org/10.1136/postgradmedj-2013-203726rep
doi: 10.1136/postgradmedj-2013-203726rep
Man GS, Mologhianu G (2014) Osteoarthritis pathogenesis - a complex process that involves the entire joint. J Med Life 7(1):37–41
Maniar KH, Jones IA, Gopalakrishna R, Vangsness CT Jr (2018) Lowering side effects of NSAID usage in osteoarthritis: recent attempts at minimizing dosage. Expert Opin Pharmacother 19(2):93–102. https://doi.org/10.1080/14656566.2017.1414802
doi: 10.1080/14656566.2017.1414802
McAlindon TE, Bannuru RR, Sullivan MC, Arden NK, Berenbaum F, Bierma-Zeinstra SM, Hawker GA, Henrotin Y, Hunter DJ, Kawaguchi H, Kwoh K, Lohmander S, Rannou F, Roos EM, Underwood M (2014) OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthr Cartil 22(3):363–388. https://doi.org/10.1016/j.joca.2014.01.003
doi: 10.1016/j.joca.2014.01.003
Nagy K, Berhes I, Kovacs T, Kavasi N, Somlai J, Bender T (2009) Does balneotherapy with low radon concentration in water influence the endocrine system? A controlled non-randomized pilot study. Radiat Environ Biophys 48(3):311–315. https://doi.org/10.1007/s00411-009-0222-3
doi: 10.1007/s00411-009-0222-3
Parolaro D, Rubino T, Vigano D, Massi P, Guidali C, Realini N (2010) Cellular mechanisms underlying the interaction between cannabinoid and opioid system. Curr Drug Targets 11(4):393–405. https://doi.org/10.2174/138945010790980367
doi: 10.2174/138945010790980367
Richardson D, Pearson RG, Kurian N, Latif ML, Garle MJ, Barrett DA, Kendall DA, Scammell BE, Reeve AJ, Chapman V (2008) Characterisation of the cannabinoid receptor system in synovial tissue and fluid in patients with osteoarthritis and rheumatoid arthritis. Arthritis Res Ther 10(2):R43. https://doi.org/10.1186/ar2401
doi: 10.1186/ar2401
Ruhle PF, Klein G, Rung T, Tiep Phan H, Fournier C, Fietkau R, Gaipl US, Frey B (2019) Impact of radon and combinatory radon/carbon dioxide spa on pain and hypertension: results from the explorative RAD-ON01 study. Mod Rheumatol 29(1):165–172. https://doi.org/10.1080/14397595.2018.1442640
doi: 10.1080/14397595.2018.1442640
Ruhle PF, Wunderlich R, Deloch L, Fournier C, Maier A, Klein G, Fietkau R, Gaipl US, Frey B (2017) Modulation of the peripheral immune system after low-dose radon spa therapy: detailed longitudinal immune monitoring of patients within the RAD-ON01 study. Autoimmunity 50(2):133–140. https://doi.org/10.1080/08916934.2017.1284819
doi: 10.1080/08916934.2017.1284819
Shehata M, Schwarzmeier JD, Hilgarth M, Demirtas D, Richter D, Hubmann R, Boeck P, Leiner G, Falkenbach A (2006) Effect of combined spa-exercise therapy on circulating TGF-beta1 levels in patients with ankylosing spondylitis. Wien Klin Wochenschr 118(9-10):266–272. https://doi.org/10.1007/s00508-006-0560-y
doi: 10.1007/s00508-006-0560-y
van Spil WE, Szilagyi IA (2020) Osteoarthritis year in review 2019: biomarkers (biochemical markers). Osteoarthr Cartil 28(3):296–315. https://doi.org/10.1016/j.joca.2019.11.007
doi: 10.1016/j.joca.2019.11.007
van Tubergen A, Landewe R, van der Heijde D, Hidding A, Wolter N, Asscher M, Falkenbach A, Genth E, The HG, van der Linden S (2001) Combined spa-exercise therapy is effective in patients with ankylosing spondylitis: a randomized controlled trial. Arthritis Rheum 45(5):430–438. https://doi.org/10.1002/1529-0131(200110)45:5<430::aid-art362>3.0.co;2-f
doi: 10.1002/1529-0131(200110)45:5<430::aid-art362>3.0.co;2-f
van Tubergen A, van der Linden S (2002) A brief history of spa therapy. Ann Rheum Dis 61(3):273–275. https://doi.org/10.1136/ard.61.3.273
doi: 10.1136/ard.61.3.273
Verhagen AP, Bierma-Zeinstra SM, Boers M, Cardoso JR, Lambeck J, de Bie R, de Vet HC (2015) Balneotherapy (or spa therapy) for rheumatoid arthritis. Cochrane Database Syst Rev 4:CD000518. https://doi.org/10.1002/14651858.CD000518.pub2
doi: 10.1002/14651858.CD000518.pub2
World Health Organisation (2020) Chronic diseases and health promotion. https://www.who.int/chp/topics/rheumatic/en/ . Accessed April 27, 2020 2020
Wunderlich R, Ruhle PF, Deloch L, Rodel F, Fietkau R, Gaipl US, Frey B (2019) Ionizing radiation reduces the capacity of activated macrophages to induce T-cell proliferation, but does not trigger dendritic cell-mediated non-targeted effects. Int J Radiat Biol 95(1):33–43. https://doi.org/10.1080/09553002.2018.1490037
doi: 10.1080/09553002.2018.1490037
Yamaoka K, Mitsunobu F, Hanamoto K, Mori S, Tanizaki Y, Sugita K (2004a) Study on biologic effects of radon and thermal therapy on osteoarthritis. J Pain 5(1):20–25. https://doi.org/10.1016/j.jpain.2003.09.005
doi: 10.1016/j.jpain.2003.09.005
Yamaoka K, Mitsunobu F, Hanamoto K, Shibuya K, Mori S, Tanizaki Y, Sugita K (2004b) Biochemical comparison between radon effects and thermal effects on humans in radon hot spring therapy. J Radiat Res 45(1):83–88. https://doi.org/10.1269/jrr.45.83
doi: 10.1269/jrr.45.83
Yamaoka K, Mitsunobu F, Kojima S, Shibakura M, Kataoka T, Hanamoto K, Tanizaki Y (2005) The elevation of p53 protein level and SOD activity in the resident blood of the Misasa radon hot spring district. J Radiat Res 46(1):21–24. https://doi.org/10.1269/jrr.46.21
doi: 10.1269/jrr.46.21
Zubrzycki M, Stasiolek M, Zubrzycka M (2019) Opioid and endocannabinoid system in orofacial pain. Physiol Res 68(5):705–715. https://doi.org/10.33549/physiolres.934159
doi: 10.33549/physiolres.934159