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Licensed Unlicensed Requires Authentication Published by De Gruyter February 23, 2019

Decline of substance P levels after stress management with cognitive behaviour therapy in women with the fibromyalgia syndrome

  • Bo Karlsson ORCID logo EMAIL logo , Gunilla Burell , Per Kristiansson , Karin Björkegren , Fred Nyberg and Kurt Svärdsudd


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.


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.


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”.


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.

Corresponding author: Bo Karlsson, MD, Department of Public Health and Caring Sciences, Uppsala University, Uppsala SE-751 22, Sweden, Phone: +46 70 227 81 26

Funding source: Swedish Research Council

Award Identifier / Grant number: 9459

Award Identifier / Grant number: 2003-139

Award Identifier / Grant number: 51/04

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.


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.

  1. Authors’ statements

  2. Conflict of interest: The authors declare they have no competing interests.

  3. Informed consent: All participants gave oral informed consent to participation, which was standard procedure at the time.

  4. Ethical approval: The Research Ethics Committee at Uppsala University approved the study [registration number Ups 00-010]. The trial is registered with NCT01004458. The trial was performed in accordance with the Helsinki declaration.


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Supplementary Material

The online version of this article offers supplementary material (

Received: 2018-10-16
Revised: 2019-01-21
Accepted: 2019-01-22
Published Online: 2019-02-23
Published in Print: 2019-07-26

©2019 Scandinavian Association for the Study of Pain. Published by Walter de Gruyter GmbH, Berlin/Boston. All rights reserved.

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