Increased Interstitial Concentrations of Glutamate and Pyruvate in Vastus Lateralis of Women with Fibromyalgia Syndrome Are Normalized after an Exercise Intervention - A Case-Control Study.
BACKGROUND
Fibromyalgia syndrome (FMS) is associated with central alterations, but controversies exist regarding the presence and role of peripheral factors. Microdialysis (MD) can be used in vivo to study muscle alterations in FMS. Furthermore for chronic pain conditions such as FMS, the mechanisms for the positive effects of exercise are unclear. This study investigates the interstitial concentrations of algesics and metabolites in the vastus lateralis muscle of 29 women with FMS and 28 healthy women before and after an exercise intervention.


METHODS
All the participants went through a clinical examination and completed a questionnaire. In addition, their pressure pain thresholds (PPTs) in their upper and lower extremities were determined. For both groups, MD was conducted in the vastus lateralis muscle before and after a 15-week exercise intervention of mainly resistance training of the lower limbs. Muscle blood flow and interstitial muscle concentrations of lactate, pyruvate, glutamate, glucose, and glycerol were determined.


RESULTS
FMS was associated with significantly increased interstitial concentrations of glutamate, pyruvate, and lactate. After the exercise intervention, the FMS group exhibited significant decreases in pain intensity and in mean interstitial concentrations of glutamate, pyruvate, and glucose. The decrease in pain intensity in FMS correlated significantly with the decreases in pyruvate and glucose. In addition, the FMS group increased their strength and endurance.


CONCLUSIONS
This study supports the suggestion that peripheral metabolic and algesic muscle alterations are present in FMS patients and that these alterations contribute to pain. After an exercise intervention, alterations normalized, pain intensity decreased (but not abolished), and strength and endurance improved, all findings that suggest the effects of exercise are partially peripheral.
Pain and Rehabilitation Centre, and Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
Björn
B
Gerdle
Karolinska Institute, Department of Dental Medicine, Section of Orofacial Pain and Jaw Function and Scandinavian Centre for Orofacial Neuroscience (SCON), Stockholm, Sweden.
Malin
M
Ernberg
Section of Physiotherapy, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.|University of Gothenburg Centre for Person-Centred Care (GPCC), Sahlgrenska Academy, Gothenburg, Sweden.
Kaisa
K
Mannerkorpi
Pain and Rehabilitation Centre, and Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
Britt
B
Larsson
Department of Clinical Neuroscience and Osher Centre for Integrative Medicine, Karolinska Institute, Stockholm, Sweden.
Eva
E
Kosek
Karolinska Institute, Department of Dental Medicine, Section of Orofacial Pain and Jaw Function and Scandinavian Centre for Orofacial Neuroscience (SCON), Stockholm, Sweden.
Nikolaos
N
Christidis
Pain and Rehabilitation Centre, and Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
Bijar
B
Ghafouri
D016022:Case-Control Studies; D005081:Exercise Therapy / Q000379:methods; D045604:Extracellular Fluid / Q000737:chemistry; D005260:Female; D005356:Fibromyalgia / Q000628:therapy*; D018698:Glutamic Acid / Q000032:analysis*; D006801:Humans; D008875:Middle Aged; D019289:Pyruvic Acid / Q000032:analysis*; D052097:Quadriceps Muscle / Q000737:chemistry*
D018698:Glutamic Acid; D019289:Pyruvic Acid
Pain Res Manag. 2005 Autumn;10(3):145-52
16175250
Eur J Appl Physiol. 2010 Mar;108(4):657-69
19894061
Cochrane Database Syst Rev. 2007 Oct 17;(4):CD003786
17943797
Eur J Pain. 2015 Sep;19(8):1075-85
25430591
Pain. 2013 Nov;154(11):2310-2316
23748113
Diabetes. 2008 Nov;57(11):2933-42
18716044
Pain. 2009 Jul;144(1-2):95-100
19410366
J Physiol. 2009 Dec 1;587(Pt 23):5591-600
19805739
Exp Physiol. 2014 Feb;99(2):368-80
24142455
Brain. 2013 Jun;136(Pt 6):1857-67
23474848
Arthritis Care Res. 1999 Jun;12(3):193-9
10513509
Rheumatology (Oxford). 2002 Jul;41(7):721-4
12096218
Pharmacol Ther. 2013 Mar;137(3):309-17
23146925
Curr Pain Headache Rep. 2013 Dec;17(12):379
24190863
Eur J Pain. 2004 Apr;8(2):163-71
14987626
J Rehabil Med. 2010 Jul;42(7):679-87
20603699
Scand J Immunol. 2006 Sep;64(3):345-52
16918704
Pharmacol Ther. 2010 Dec;128(3):549-58
20807551
Neurosci Lett. 2012 Jun 29;520(2):156-64
22445888
J Neurosci Methods. 1991 Nov;40(1):31-8
1795551
Nutrition. 2006 Sep;22(9):965-72
16814517
Pain Physician. 2011 Mar-Apr;14(2):E217-45
21412381
Neuron. 2010 Nov 18;68(4):739-49
21092862
J Comp Neurol. 1998 Feb 2;391(1):78-86
9527543
Clin Physiol Funct Imaging. 2013 Mar;33(2):83-91
23383685
Scand J Urol Nephrol. 2008;42(3):293-300
18432536
Metabolomics. 2012 Jun;8(3):422-432
22661919
BMC Musculoskelet Disord. 2010 Mar 05;11:42
20205731
Arthritis Rheum. 1998 Mar;41(3):406-13
9506567
Nitric Oxide. 2012 Jan 1;26(1):32-7
22138296
J Rehabil Med. 2009 Sep;41(9):751-60
19774310
Pain Med. 2004 Dec;5(4):366-76
15563322
Pflugers Arch. 2011 Apr;461(4):401-21
21279380
Eur J Pain. 2006 Feb;10(2):137-44
16310717
Biochem Pharmacol. 2010 Jul 15;80(2):151-9
20230800
Best Pract Res Clin Rheumatol. 2011 Apr;25(2):155-64
22094192
PLoS One. 2012;7(12):e52560
23300707
Nitric Oxide. 2011 Oct 30;25(3):243-54
21723953
Pain Med. 2014 Aug;15(8):1379-89
24995488
J Signal Transduct. 2012;2012:982794
22175016
BMC Musculoskelet Disord. 2011 Oct 12;12:230
21992460
Pain. 2008 Jul;137(1):34-40
17869422
Soc Sci Med. 1995 Nov;41(10):1349-58
8560302
Clin Sci (Lond). 1994 Jan;86(1):15-25
8306547
BMC Musculoskelet Disord. 2009 Apr 15;10:36
19368705
Scand J Rheumatol. 1986;15(1):1-6
2421398
Eur J Pain. 2013 Sep;17(8):1205-15
23364928
Arthritis Rheum. 2006 Apr;54(4):1334-9
16575859
J Headache Pain. 2014 Dec 17;15:89
25519464
Arthritis Rheum. 1990 Feb;33(2):160-72
2306288
Ann Neurol. 2014 Feb;75(2):196-208
24243538
Clin J Pain. 2014 May;30(5):409-20
23887335
Pain. 2009 Sep;145(1-2):96-104
19540671
Pflugers Arch. 2010 Jan;459(2):277-89
19756719
Pain. 2010 Oct;151(1):77-86
20621420
J Psychosom Res. 2002 Feb;52(2):69-77
11832252
ScientificWorldJournal. 2012;2012:420984
22593684
Acta Psychiatr Scand. 1983 Jun;67(6):361-70
6880820
Eur Spine J. 2009 Nov;18(11):1604-9
19418074
J Neurosci Res. 2011 Jan;89(1):29-34
20936697
J Pain. 2010 Dec;11(12):1376-83
20451465
BMC Musculoskelet Disord. 2010 Feb 09;11:29
20144214
Rheumatology (Oxford). 2008 Aug;47(8):1235-8
18550637
J Exp Biol. 2005 Dec;208(Pt 24):4561-75
16326938
Inflamm Res. 2002 Aug;51(8):393-402
12234056
J Rehabil Med. 2007 Apr;39(3):260-8
17468796
J Neurol Neurosurg Psychiatry. 1994 Sep;57(9):1106-11
8089679
Pain. 2013 Sep;154(9):1649-1658
23707281
Arthritis Res Ther. 2015 Jun 18;17:161
26084281
J Rheumatol. 2001 Jun;28(6):1361-8
11409132
Life Sci. 1999;65(3):313-25
10447217
Br J Sports Med. 2012 Aug;46(10):719-26
21791457
J Appl Physiol (1985). 1999 Mar;86(3):1054-61
10066723
J Pain. 2007 Jan;8(1):59-66
16949881
Pain. 2006 Jan;120(1-2):161-169
16376018
Acta Physiol (Oxf). 2010 Aug;199(4):499-508
20345411
Neurology. 2011 Oct 18;77(16):1568-76
22006889
Eur Spine J. 2012 Apr;21(4):575-98
22072093
Best Pract Res Clin Rheumatol. 2011 Apr;25(2):299-309
22094203
Cochrane Database Syst Rev. 2013 Dec 20;(12):CD010884
24362925
Am J Med. 2009 Dec;122(12 Suppl):S22-30
19962493
Arthritis Res Ther. 2012 Nov 01;14(6):R236
23116302
Acta Physiol (Oxf). 2011 Aug;202(4):641-8
21624100
J Shoulder Elbow Surg. 1996 Jan-Feb;5(1):18-24
8919438
J Rehabil Med. 2014 Sep;46(8):773-80
25074026
J Pain Res. 2014 Jun 12;7:313-26
24966693
J Orthop Res. 2001 Sep;19(5):881-6
11562137
Phys Ther. 2014 Dec;94(12):1816-25
25035267
Mol Cells. 2005 Dec 31;20(3):315-24
16404144
J Proteome Res. 2007 Jun;6(6):2113-20
17428078
Neurology. 2000 Oct 24;55(8):1213-5
11071503
Arthritis Res Ther. 2011 Apr 28;13(2):210
21542894
ScientificWorldJournal. 2001 Oct 5;1:510-2
12805843
Pain. 1996 Mar;64(3):415-423
8783304
J Intern Med. 2007 Apr;261(4):349-62
17391109
Scand J Rheumatol. 1986;15(2):165-73
3462905
Eur Heart J. 1997 Jun;18(6):971-80
9183589
Pharmacol Ther. 2011 Jun;130(3):283-309
21276816
Am J Physiol Regul Integr Comp Physiol. 2004 Sep;287(3):R502-16
15308499
Exerc Immunol Rev. 2009;15:42-65
19957871
Am J Clin Nutr. 2009 Jan;89(1):467S-71S
19056588
Mayo Clin Proc. 1999 Apr;74(4):385-98
10221469
J Physiol. 2010 Dec 1;588(Pt 23):4785-94
20876199
Clin J Pain. 2012 Jul;28(6):519-26
22673485
J Physiol. 2004 Jul 1;558(Pt 1):5-30
15131240
Dis Model Mech. 2011 Nov;4(6):727-32
22065843
Pediatr Crit Care Med. 2011 Jul;12(4 Suppl):S43-9
22129549
Sports Med. 2011 Apr 1;41(4):289-306
21425888
J Electromyogr Kinesiol. 2010 Jun;20(3):457-64
19682926
Nat Rev Rheumatol. 2011 Jul 19;7(9):518-27
21769128
Eur J Pain. 2013 Apr;17(4):539-50
23132643
Pain Med. 2013 Sep;14(9):1291-300
23742198