Abstract
Background and aims
Substance P (CSF-SP) is known to be elevated in females with fibromyalgia syndrome (FMS). The aims of this study were to evaluate the effect of cognitive behaviour therapy (CBT) on plasma SP levels in women with FMS and to find possible clinical behavioural correlates to plasma SP level changes.
Methods
Forty-eight women with FMS were randomly allocated into two groups. Group 1 received the CBT treatment intervention over the course of 6 months while group 2 was waitlisted. CBT was given with a protocol developed to diminish stress and pain. After 6 months, group 2 was given the same CBT treatment as well. All were followed up 1 year after the start of CBT treatment. This approach allowed for two analytical designs – a randomised controlled trial (RCT) (n=24 vs. n=24) and a before-and-after treatment design (n=48). All women were repeatedly evaluated by the West Haven-Yale Multidimensional Pain Inventory (MPI) and three other psychometric questionnaires and plasma SP was analysed.
Results
In the RCT design, the plasma SP level was 8.79 fmol/mL in both groups at the start of the trial, after adjustment for initial differences. At the end of the RCT, the plasma SP level was 5.25 fmol/mL in the CBT intervention group compared to 8.39 fmol/mL in the control group (p=0.02). In the before-and-after design, the plasma SP was reduced by 33% (p<0.01) after CBT, but returned to the pre-treatment level at follow-up 1 year after the start of CBT treatment. Plasma SP was associated with the MPI dimensions experienced “support from spouses or significant others” and “life control”.
Conclusions
Plasma SP might be a marker of the effect of CBT in FMS associated with better coping strategies and reduced stress rather than a biochemical marker of pain.
Funding source: Swedish Research Council
Award Identifier / Grant number: 9459
Funding source: Söderström-König Foundation
Award Identifier / Grant number: 2003-139
Funding source: Swedish Rheumatism Association
Award Identifier / Grant number: 51/04
Funding source: Swedish Social Insurance Agency
Award Identifier / Grant number: 11124
Funding source: Uppsala County Council
Award Identifier / Grant number: K2003-0036
Funding source: Uppsala University
Award Identifier / Grant number: UVF2003/39
Funding statement: This study was supported by grants from Swedish Research Council (9459), the Söderström-König Foundation (2003-139), the Swedish Rheumatism Association (51/04), the Swedish Social Insurance Agency (11124), Uppsala County Council (K2003-0036) and Uppsala University (UVF2003/39). The funding authorities had no influence on the design and performance of the study.
Acknowledgements
Thanks are due to Ulla Maria Anderberg MD PhD, Department of Public Health and Caring Sciences, Uppsala University who took part in the initial planning of the study. The authors would also like to thank Charlotta Marhold, psychologist and PhD, and Jenny Koertge, psychologist and PhD, who performed the cognitive behaviour therapy sessions. Finally, the authors extended their appreciation to Christina Holmgren, biomedical analyst, and Ingrid Hällsten, physiotherapist, for their valuable help in examining the participants in the study.
Authors’ statements
Conflict of interest: The authors declare they have no competing interests.
Informed consent: All participants gave oral informed consent to participation, which was standard procedure at the time.
Ethical approval: The Research Ethics Committee at Uppsala University approved the study [registration number Ups 00-010]. The trial is registered with Clinicaltrials.gov: NCT01004458. The trial was performed in accordance with the Helsinki declaration.
References
[1] Anderberg UM. Fibromyalgia – probably a result of prolonged stress syndrome. Lakartidningen 2000;97:2641–2.Search in Google Scholar
[2] Anderberg UM. Fibromyalgia syndrom in women-a stress disorder? Neurobiological and hormonal aspects. [Thesis] 1999.10.1080/080394899427908Search in Google Scholar
[3] Van Houdenhove B, Egle UT. Fibromyalgia: a stress disorder? Piecing the biopsychosocial puzzle together. Psychother Psychosom 2004;73:267–75.10.1159/000078843Search in Google Scholar
[4] Griep EN, Boersma JW, de Kloet ER. Altered reactivity of the hypothalamic-pituitary-adrenal axis in the primary fibromyalgia syndrome. J Rheumatol 1993;20:469–74.Search in Google Scholar
[5] Wingenfeld K, Nutzinger D, Kauth J, Hellhammer DH, Lautenbacher S. Salivary cortisol release and hypothalamic pituitary adrenal axis feedback sensitivity in fibromyalgia is associated with depression but not with pain. J Pain 2010;11:1195–202.10.1016/j.jpain.2010.02.011Search in Google Scholar
[6] Russell IJ, Vaeroy H, Javors M, Nyberg F. Cerebrospinal fluid biogenic amine metabolites in fibromyalgia/fibrositis syndrome and rheumatoid arthritis. Arthritis Rheum 1992;35:550–6.10.1002/art.1780350509Search in Google Scholar
[7] Lyon P, Cohen M, Quintner J. An evolutionary stress-response hypothesis for chronic widespread pain [fibromyalgia syndrome]. Pain Med 2011;12:1167–78.10.1111/j.1526-4637.2011.01168.xSearch in Google Scholar
[8] Liu Z, Welin M, Bragee B, Nyberg F. A high-recovery extraction procedure for quantitative analysis of substance P and opioid peptides in human cerebrospinal fluid. Peptides 2000;21:853–60.10.1016/S0196-9781(00)00219-9Search in Google Scholar
[9] Zieglgänsberger W. Substance P and pain chronicity. Cell Tissue Res 2019;375:227–41.10.1007/s00441-018-2922-ySearch in Google Scholar
[10] Ablin JN, Buskila D. Fibromyalgia syndrome – novel therapeutic targets. Maturitas 2013;75:335–40.10.1016/j.maturitas.2013.05.004Search in Google Scholar
[11] Hill R. NK1 (substance P) receptor antagonists – why are they not analgesic in humans? Trends Pharmacol Sci 2000;21:244–6.10.1016/S0165-6147(00)01502-9Search in Google Scholar
[12] Available at: URL: http://clinicaltrials.com/ct/show/NCT00264628.Search in Google Scholar
[13] Russell IJ, Orr MD, Littman B, Vipraio GA, Alboukrek D, Michalek JE, Lopez Y, MacKillip F. Elevated cerebrospinal fluid levels of substance P in patients with the fibromyalgia syndrome. Arthritis Rheum 1994;37:1593–601.10.1002/art.1780371106Search in Google Scholar PubMed
[14] De Stefano R, Selvi E, Villanova M, Frati E, Manganelli S, Franceschini E, Biasi G, Marcolongo R. Image analysis quantification of substance P immunoreactivity in the trapezius muscle of patients with fibromyalgia and myofascial pain syndrome. J Rheumatol 2000;27:2906–10.Search in Google Scholar
[15] Karlsson B, Burell G, Anderberg U, Svärdsudd K. Cognitive behaviour therapy in women with fibromyalgia. A ranomized clinical trial. Scand J Pain 2015;9:11–21.10.1016/j.sjpain.2015.04.027Search in Google Scholar
[16] Wicksell RK, Kemani M, Jensen K, Kosek E, Kadetoff D, Sorjonen K, Ingvar M, Olsson GL. Acceptance and commitment therapy for fibromyalgia: a randomized controlled trial. Eur J Pain 2013;17:599–611.10.1002/j.1532-2149.2012.00224.xSearch in Google Scholar
[17] Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenberg DL, Tugwell P, Campbell SM, Abeles M, Clark P, Fam AG, Farber SJ, Fiechtner JJ, Franklin CM, Gatter RA, Hamaty D, Lessard J, Lightbroun AS, Masi AT, McCain GA, et al. The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum 1990;33:160–72.10.1002/art.1780330203Search in Google Scholar
[18] Kerns RD, Turk DC, Rudy TE. The West Haven-Yale Multidimensional Pain Inventory [WHYMPI]. Pain 1985;23:345–56.10.1016/0304-3959(85)90004-1Search in Google Scholar
[19] Bergstrom G, Jensen IB, Bodin L, Linton SJ, Nygren AL, Carlsson SG. Reliability and factor structure of the Multidimensional Pain Inventory – Swedish Language Version [MPI-S]. Pain 1998;75:101–10.10.1016/S0304-3959(97)00210-8Search in Google Scholar
[20] Appels A, Hoppener P, Mulder P. A questionnaire to assess premonitory symptoms of myocardial infarction. Int J Cardiol 1987;17:15–24.10.1016/0167-5273(87)90029-5Search in Google Scholar
[21] Appels A, Falger PR, Schouten EG. Vital exhaustion as risk indicator for myocardial infarction in women. J Psychosom Res 1993;37:881–90.10.1016/0022-3999(93)90177-HSearch in Google Scholar
[22] Gulliksson M, Burell G, Lundin L, Toss H, Svardsudd K. Psychosocial factors during the first year after a coronary heart disease event in cases and referents. Secondary Prevention in Uppsala Primary Health Care Project [SUPRIM]. BMC Cardiovasc Disord 2007;7:36.10.1186/1471-2261-7-36Search in Google Scholar PubMed PubMed Central
[23] Orth-Gomer K, Unden AL, Edwards ME. Social isolation and mortality in ischemic heart disease. A 10-year follow-up study of 150 middle-aged men. Acta Med Scand 1988;224:205–15.10.1111/j.0954-6820.1988.tb19363.xSearch in Google Scholar
[24] Koertge J, Janszky I, Sundin O, Blom M, Georgiades A, László KD, Alinaghizadeh H, Ahnve S. Effects of a stress management program on vital exhaustion and depression in women with coronary heart disease: a randomized controlled intervention study. J Intern Med 2008;263:281–93.10.1111/j.1365-2796.2007.01887.xSearch in Google Scholar PubMed
[25] Claesson M, Burell G, Birgander LS, Lindahl B, Asplund K. Psychosocial distress and impaired quality of life – targets neglected in the secondary prevention in women with ischaemic heart disease. Eur J Cardiovasc Prev Rehabil 2003;10:258–66.10.1097/00149831-200308000-00007Search in Google Scholar
[26] Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry 1979;134:382–9.10.1192/bjp.134.4.382Search in Google Scholar
[27] Svanborg P, Asberg M. A comparison between the Beck Depression Inventory [BDI] and the self-rating version of the Montgomery Asberg Depression Rating Scale [MADRS]. J Affect Disord 2001;64:203–16.10.1016/S0165-0327(00)00242-1Search in Google Scholar
[28] Fantino B, Moore N. The self-reported Montgomery-Asberg Depression Rating Scale is a useful evaluative tool in Major Depressive Disorder. BMC Psychiatry 2009;9:26.10.1186/1471-244X-9-26Search in Google Scholar PubMed PubMed Central
[29] Lindh C, Liu Z, Lyrenas S, Ordeberg G, Nyberg F. Elevated cerebrospinal fluid substance P-like immunoreactivity in patients with painful osteoarthritis, but not in patients with rhizopatic pain from a herniated lumbar disc. Scand J Rheumatol 1997;26:468–72.10.3109/03009749709065721Search in Google Scholar PubMed
[30] Burell G, Granlund B. Women’s hearts need special treatment. Int J Behav Med 2002;9:228–42.10.1207/S15327558IJBM0903_05Search in Google Scholar
[31] Jacobson EJ. Progressive relaxation, 2nd ed. Oxford, England: University Chicago Press, 1938:498.Search in Google Scholar
[32] Statistical Analysis System. SAS Institute, Cary, North Carolina, USA.Search in Google Scholar
[33] Clauw DJ. Fibromyalgia: an overview. Am J Med 2009;122(12 Suppl):S3–13.10.1016/j.amjmed.2009.09.006Search in Google Scholar PubMed
[34] Field T, Diego M, Cullen C, Hernandez-Reif M, Sunshine W, Douglas S. Fibromyalgia pain and substance P decrease and sleep improves after massage therapy. J Clin Rheumatol 2002;8:72–6.10.1097/00124743-200204000-00002Search in Google Scholar PubMed
[35] Cho S, Zunin ID, Chao PJ, Heiby EM, McKoy J. Effects of pain controllability and discrepancy in social support on depressed mood among patients with chronic pain. Int J Behav Med 2012;19:270–9.10.1007/s12529-011-9175-4Search in Google Scholar PubMed
[36] Panksepp J, Biven L. The archaeology of mind, 1st ed. New York, London: W.W.Norton & Company, 2012:313–8.10.4324/9781315668505-26Search in Google Scholar
[37] Hellstrom B, Anderberg UM. Pain perception across the menstrual cycle phases in women with chronic pain. Percept Mot Skills 2003;96:201–11.10.2466/pms.2003.96.1.201Search in Google Scholar PubMed
[38] Chalastras T, Nicolopoulou-Stamati P, Patsouris E, Eleftheriadou A, Kandiloros D, Yiotakis I, Gonidi M, Athanassiadou P. Expression of substance P, vasoactive intestinal peptide and heat shock protein 70 in nasal mucosa smears of patients with allergic rhinitis: investigation using a liquid-based method. J Laryngol Otol 2008;122:700–6.10.1017/S0022215107001454Search in Google Scholar PubMed
[39] Li L, Gao X, Zhao J, Ji X, Wei H, Luo Y. Plasma and cerebrospinal fluid substance P in post-stroke patients with depression. Psychiatry Clin Neurosci 2009;63:298–308.10.1111/j.1440-1819.2009.01936.xSearch in Google Scholar PubMed
Supplementary Material
The online version of this article offers supplementary material (https://doi.org/10.1515/sjpain-2018-0324).
©2019 Scandinavian Association for the Study of Pain. Published by Walter de Gruyter GmbH, Berlin/Boston. All rights reserved.
