Chronic musculoskeletal pain: review of mechanisms and biochemical biomarkers as assessed by the microdialysis technique

Figures & data

Figure 1 Microdialysis catheter.

Notes: Perfusate is pumped from an infusion pump (A) to the microdialysis catheter (B1), and the dialysate is collected using a microvial (C). When the catheter has been inserted into the muscle tissue, the splittable introducer (with small blue handles, B2) is removed, and the catheter (B3) is implanted into the tissue during the microdialysis experiment. The catheter (B3) consists of a hollow cannula to which the tip (a semi-permeable dialysis membrane [shown in white]) is attached.

Table 1 Studies of chronic myalgia in humans sorted after muscle investigated

Study	Condition Number of subjects, % W	Substances investigated; flow rate
Masseter
Ernberg et al, 1999^Citation99	FMS (n=18), 100% W Localized myalgia of the temporomandibular system (n=17), 76% W Controls (n=10), 60% W	5-HT (corrected for S-5-HT); 7 μL/min
Hedenberg–Magnusson et al, 2001^Citation100	FMS (n=19), 89% W Localized myalgia of the temporomandibular system (n=19), 74% W Controls (n=11), 64% W	PGE2 and LTB4; 7 μL/min
Castrillon et al, 2010^Citation87	Myofascial temporomandibular disorder pain (n=13), 77% W Controls (n=10), 80% W	Glutamate; 2 μL/min
Trapezius
Flodgren et al, 2005^Citation88	Chronic shoulder pain (n=9), 100% W Controls (n=9), 100% W	Glutamate and PGE2; 0.3 μL/min
Flodgren et al, 2010^Citation96	Chronic trapezius myalgia (n=14), 100% W Controls (compared with controls [n=20] in^Citation97), 100% W	Lactate, pyruvate, glutamate, PGE2; 2 μL/min
Rosendal et al, 2004^Citation22	Chronic trapezius myalgia (n=19), 100% W Controls (n=20), 100% W	Lactate, pyruvate, glutamate, 5-HT; 5 μL/min
Rosendal et al, 2005^Citation95	Chronic trapezius myalgia (n=19), 100% W Controls (n=20), 100% W	K^+, LDH, IL-6, collagen turnover; 5 μL/min
Gerdle et al, 2008^Citation93	Chronic trapezius myalgia (n=19), 100% W Chronic whiplash-associated disorders (n=22), 100% W Controls (n=20), 100% W	BKN, KAL; 5 μL/min
Gerdle et al, 2008^Citation98	Chronic whiplash-associated disorders (n=22), 100% W Controls (n=20), 100% W	Lactate, pyruvate, glutamate, K^+, 5-HT, IL-6; 5 μL/min
Larsson et al, 2008^Citation89	Chronic trapezius myalgia (n=20), 100% W Controls (n=20), 100% W	Lactate, pyruvate, glutamate, 5-HT, K^+, BKN, GM-CSF, IL-1β, IL-6, IL-8, TNF-α, IL-2, IL-4, IL-5, IL-10; 5 μL/min
Ghafouri et al, 2010^Citation92	Chronic trapezius myalgia, (n=18), 100% W Controls (n=30), 100% W	5-HT; 5 μL/min
Ghafouri et al, 2011^Citation104	Chronic trapezius myalgia, (n=11), 100% W Controls (n=11), 100% W	PEA and SEA; 5 μL/min
Sjøgaard et al, 2010^Citation94	Chronic trapezius myalgia (n=43), 100% W Controls (n=19), 100% W	Lactate, pyruvate, glucose, K^+; 5 μL/min
Shah et al, 2005^Citation91	Myofascial trapezius pain with active trigger point (n=3) Controls with latent trigger point (n=3) Controls without trigger point (n=3)	BKN, CGRP, SP, IL-1β, TNF-α, 5-HT, norepinephrine, H^+; 1 and 2 μL/min
Shah et al, 2008^Citation90	Myofascial trapezius pain with active trigger point (n=3) Controls with latent trigger point (n=3) Controls without trigger point (n=3)	BKN, CGRP, SP, IL-1β, TNF-α, IL-6, IL-8, 5-HT, norepinephrine, H^+; 1 and 2 μL/min
Gerdle et al, 2010^Citation102	FMS (n=19), 100% W Controls (n=19), 100% W	Lactate, pyruvate, glutamate; 0.3 μL/min
Gerdle et al, 2014^Citation103	Chronic widespread pain (n=17), 100% W (15 of 17 had FMS) Controls (n=24), 100% W	Lactate, pyruvate, glutamate, glucose, glycerol; 5 μL/min
Ghafouri et al, 2011^Citation104	Chronic trapezius myalgia (n=11) 100% W Controls (n=11) 100% W	PEA and SEA; 5 μL/min
Ghafouri et al, 2013^Citation105	Chronic trapezius myalgia (n=34) 100% W Chronic widespread pain (n=18) 100% W Controls (n=24) 100% W	PEA and SEA; 5 μL/min
Vastus lateralis
McIver et al, 2006^Citation101	FMS (n=8), 100% W Controls (n=8), 100% W	Lactate; 2 μL/min

Note: *Low flow rate associated with 100% relative recovery was defined as 0.3 μL/minute.

Abbreviations: W, women; FMS, fibromyalgia syndrome; 5-HT, serotonin; PGE₂, prostaglandin E₂; LTB4, leukotriene B₄; K⁺, potassium; LDH, lactate dehydrogenase; BKN, bradykinin; KAL, kallidin; GM-CSF, granulocyte-macrophage colony-stimulating factor; IL-1β, interleukin 1β; IL-6, interleukin 6; IL-8, interleukin 8; TNF-α, tumor necrosis factor alpha; IL-2, interleukin 2; IL-4, interleukin 4; IL-5, interleukin 5; IL-10, interleukin 10; PEA, N-palmitoylethanolamine; SEA, N-stearoylethanolamine; CGRP, calcitonin gene-related peptide; SP, substance P; S-5-HT, Serum-5-HT.

ErnbergMHedenberg-MagnussonBAlstergrenPKoppSThe level of serotonin in the superficial masseter muscle in relation to local pain and allodyniaLife Sci199965331332510447217

 PubMed Web of Science ®Google Scholar

Hedenberg-MagnussonBErnbergMAlstergrenPKoppSPain mediation by prostaglandin E2 and leukotriene B4 in the human masseter muscleActa Odontol Scand200159634835511831483

 PubMed Web of Science ®Google Scholar

CastrillonEEErnbergMCairnsBEInterstitial glutamate concentration is elevated in the masseter muscle of myofascial temporomandibular disorder patientsJ Orofac Pain201024435036021197506

 PubMedGoogle Scholar

FlodgrenGMCrenshawAGAlfredsonHGlutamate and prostaglandin E2 in the trapezius muscle of female subjects with chronic muscle pain and controls determined by microdialysisEur J Pain20059551151516139179

 PubMed Web of Science ®Google Scholar

FlodgrenGMCrenshawAGHellströmFFahlströmMCombining microdialysis and near-infrared spectroscopy for studying effects of low-load repetitive work on the intramuscular chemistry in trapezius myalgiaJ Biomed Biotechnol2010201051380320625491

 PubMedGoogle Scholar

FlodgrenGMHellströmFBFahlströmMCrenshawAGEffects of 30 versus 60 min of low-load work on intramuscular lactate, pyruvate, glutamate, prostaglandin E(2) and oxygenation in the trapezius muscle of healthy femalesEur J Appl Physiol200697555756516767442

 PubMed Web of Science ®Google Scholar

RosendalLLarssonBKristiansenJIncrease in muscle nociceptive substances and anaerobic metabolism in patients with trapezius myalgia: microdialysis in rest and during exercisePain2004112332433415561388

 PubMed Web of Science ®Google Scholar

RosendalLKristiansenJGerdleBIncreased levels of interstitial potassium but normal levels of muscle IL-6 and LDH in patients with trapezius myalgiaPain20051191–320120916297553

 PubMed Web of Science ®Google Scholar

GerdleBHilgenfeldtULarssonBKristiansenJSøgaardKRosendalLBradykinin and kallidin levels in the trapezius muscle in patients with work-related trapezius myalgia, in patients with whiplash associated pain, and in healthy controls – A microdialysis study of womenPain2008139357858718657364

 PubMed Web of Science ®Google Scholar

GerdleBLemmingDKristiansenJLarssonBPeolssonMRosendalLBiochemical alterations in the trapezius muscle of patients with chronic whiplash associated disorders (WAD) – a microdialysis studyEur J Pain2008121829317459742

 PubMed Web of Science ®Google Scholar

LarssonBRosendalLKristiansenJResponses of algesic and metabolic substances to 8 h of repetitive manual work in myalgic human trapezius musclePain2008140347949019006649

 PubMed Web of Science ®Google Scholar

GhafouriBLarssonBKSjörsALeanderssonPGerdleBUInterstitial concentration of serotonin is increased in myalgic human trapezius muscle during rest, repetitive work and mental stress – an in vivo microdialysis studyScand J Clin Lab Invest201070747848620712520

 PubMed Web of Science ®Google Scholar

GhafouriNGhafouriBLarssonBHigh levels of N-palmitoylethanolamide and N-stearoylethanolamide in microdialysate samples from myalgic trapezius muscle in womenPLOS One2011611e2725722125609

 PubMed Web of Science ®Google Scholar

SjøgaardGRosendalLKristiansenJMuscle oxygenation and glycolysis in females with trapezius myalgia during stress and repetitive work using microdialysis and NIRSEur J Appl Physiol2010108465766919894061

 PubMed Web of Science ®Google Scholar

ShahJPPhillipsTMDanoffJVGerberLHAn in vivo microanalytical technique for measuring the local biochemical milieu of human skeletal muscleJ Appl Physiol (1985)20059951977198416037403

 PubMed Web of Science ®Google Scholar

ShahJPDanoffJVDesaiMJBiochemicals associated with pain and inflammation are elevated in sites near to and remote from active myofascial trigger pointsArch Phys Med Rehabil2008891162318164325

 PubMed Web of Science ®Google Scholar

GerdleBSoderbergKSalvador PuigvertLRosendalLLarssonBIncreased interstitial concentrations of pyruvate and lactate in the trapezius muscle of patients with fibromyalgia: a microdialysis studyJ Rehabil Med201042767968720603699

 PubMed Web of Science ®Google Scholar

GerdleBLarssonBForsbergFChronic widespread pain: increased glutamate and lactate concentrations in the trapezius muscle and plasmaClin J Pain201430540942023887335

 PubMed Web of Science ®Google Scholar

GhafouriNGhafouriBLarssonBStenssonNFowlerCJGerdleBPalmitoylethanolamide and stearoylethanolamide levels in the interstitium of the trapezius muscle of women with chronic widespread pain and chronic neck-shoulder pain correlate with pain intensity and sensitivityPain201315491649165823707281

 PubMed Web of Science ®Google Scholar

McIverKLEvansCKrausRMIspasLSciottiVMHicknerRCNO-mediated alterations in skeletal muscle nutritive blood flow and lactate metabolism in fibromyalgiaPain20061201–216116916376018

 PubMed Web of Science ®Google Scholar