Table 2.
Main characteristics of studies included in qualitative analysis.
| First author (year) | No. of participants | Diagnostic criteria | ECS markers studied | Sampling/analytical method/s | Age, y | Male/female | BMI, kg/m2 | Cannabis use | Medication use | Comorbidities | Intensity of pain, depression and anxiety | Other blood markers | Main outcomes | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Baumeister (2018) | n = 89 (FMS) n = 36 (HC) |
ACR 1990 | Plasma AEA, 2-AG, PEA | Venepuncture/liquid chromatography/multiple reaction monitoring (LC/MRM) | FMS: 55.4 (9.5) HC: 61.4 (12.4) |
FMS: 7/82 HC: 20/16 |
FMS: 29.2 (6.5) HC: 26.9 (4.0) |
Cannabis users were excluded from the study | Antidepressants: FMS: 41.6% (38) HC: 0% (0), P = 0.001 Opiates: FMS: 5.6% (6) HC: 0% (0), P = 0.1 NSAIDs: FMS: 58.4% (53) HC: 13.9% (5), P = 0.001 Channel blockers: FMS: 15.7% (14) HC: 0% (0), P = 0.01 |
Diabetes mellitus: FMS: 11.2% (10) HC: 2.8% (1), P = 0.1 |
Average pain/4 wk (NRS 0–10): FMS: 6.2 (1.6) HC: 0.0 (0.0), P = 0.001 Depression (HADS): FMS: 8.1 (4.4) HC: 3.0 (3.2), P = 0.001 Anxiety (HADS): FMS: 9.2 (4.2) HC: 3.6 (2.5), P = 0.001 |
Not reported | FMS (pmol/L): AEA: 0.56 (0.31) 2AG: 2.18 (1.20) PEA: 5.92 (2.14) |
HC (pmol/L): AEA: 0.55 (0.28) 2AG: 2.13 (1.20) PEA: 5.80 (2.53) |
BF10: AEA: 0.22 2AG: 0.21 PEA: 0.24 |
|
| Kaufmann (2008) | n = 22 (FMS) n = 22 (HC) |
ACR 1990 | Plasma AEA | Venepuncture/high performance liquid chromatography-tandem mass spectrometry (HPLC/MS–MS) | FMS: 53.1 (2.1) HC: 48.1 (5.1) |
FMS: 5/17 HC: 5/17 |
Not reported | Not reported | Not reported Participants had abstained from their medication for at least 24 h before blood sampling. Subjects taking immunosuppressive or acetylsalicylic acid medication were excluded |
Not reported Subjects with inflammatory conditions, diabetes mellitus, endocrinologic disorders including thyroid disease, infections, hypertension, muscle or joint diseases, acute injury, pregnancy, major depressive disorder, addiction, general anxiety disorder, psychosis, major personality disorder, or current compensation claims were excluded |
Pain (0–10 cm VAS): FMS: 6.4 (1.4) HC: 0.0 (0.0), P < 0.0001 Stress (PTSS-10): FMS: 46.7 (3.5) HC: 19.0 (2.3), P < 0.001 |
Plasma epinephrine and norepinephrine, serum cortisol, white blood cell count, neutrophil function (H2O2 production, adhesion and phagocytosis capabilities) | AEA (μg/L): FMS vs HC: P < 0.0001 |
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| Stensson (2018) | n = 104 (FMS) n = 116 (HC) |
ACR 1990 | Plasma AEA, OEA, PEA, SEA, 2-AG | Venepuncture/liquid chromatography-tandem mass spectrometry (LC-MS/MS) |
FMS: 50.8 (9.7) HC: 48.1 (5.1) |
FMS: 0/104 HC: 0/116 |
FMS: 27.7 (5.1) HC: 24.0 (3.7) |
Not reported | Not reported Participants had to refrain from analgesics, NSAIDS, or hypnotics for 48 h before examinations |
Not reported Patients with FMS with high blood pressure, osteoarthritis (hip/knee), other severe somatic or psychiatric disorders, and primary causes of pain other than FMS were excluded from the study |
Pain (100-mm VAS): FMS: 51.2 (21.6) HC: 2.7 (6.6) Depression (HAD-D): FMS: 7.3 (3.6) HC: 1.8 (2.4) Anxiety (HAD-A): FMS: 8.7 (4.1) HC: 3.4 (3.2) |
Not reported | FMS (nM): AEA: 0.31 (0.15) OEA: 6.2 (2.3) PEA: 9.5 (2.4) SEA: 2.6 (1.0) 2AG: 14.5 (9.2) |
HC (nM): AEA: 0.31 (0.15) OEA: 5.4 (1.8) PEA: 8.6 (2.5) SEA: 2.1 (0.9) 2AG: 11.1 (5.1) |
P: AEA: 0.99 OEA: 0.006 PEA: 0.010 SEA: 0.001 2AG: 0.001 |
|
| Stensson (2020) | Primary cohort: n = 37 (FMS) n = 33 (HC) |
ACR 1990 | Plasma AEA, OEA, PEA, SEA, 2-AG | Venepuncture/liquid chromatography-tandem mass spectrometry (LC-MS/MS) |
FMS: 50.1 (10.5) HC: 50.3 (12.8) |
FMS: 0/37 HC: 0/33 |
FMS: 26.5 (4.7) HC: 24.4 (4.4) |
Not reported | Not reported Participants had to refrain from analgesics, NSAIDS, or hypnotics for 48 h before examinations |
Not reported Patients with FMS with high blood pressure, osteoarthritis (hip/knee), other severe somatic or psychiatric disorders, and primary causes of pain other than FMS were excluded from the study |
Pain (100-mm VAS): FMS: 48.7 (22.9) HC: 1.9 (5.9), P = 0.001 Depression (HAD-D): FMS: 7.7 (4.2) HC: 3.1 (3.0), P = 0.001 Anxiety (HAD-A): FMS: 8.8 (4.7) HC: 1.5 (1.8), P = 0.001 |
Not reported | FMS (nM): Pre-exercise: AEA: 0.26 (0.13) OEA: 5.66 (1.92) PEA: 8.51 (2.03) SEA: 2.56 (1.18) 2AG: 12.8 (8.49) Post-exercise: AEA: 0.34 (0.18) OEA: 5.33 (2.11) PEA: 7.96 (2.69) SEA: 2.05 (1.10) 2AG: 11.5 (8.03) |
HC (nM): Pre-exercise: AEA: 0.31 (0.16) OEA: 5.39 (1.29) PEA: 8.72 (1.63) SEA: 2.05 (0.83) 2AG: 12.5 (3.97) Post-exercise: AEA: 0.25 (0.14) OEA: 6.06 (1.96) PEA: 9.18 (2.54) SEA: 2.57 (1.06) 2AG: 12.6 (6.17) |
P: Pre-exercise: AEA: 0.12 OEA: 0.50 PEA: 0.63 SEA: 0.04 2AG: 0.83 Post-exercise: AEA: 0.03 OEA: 0.14 PEA: 0.06 SEA: 0.05 2AG: 0.51 |
|
|
Hellström (2016) |
Morning sample: n = 5 (CWP) n = 15 (HC) Afternoon sample: n = 9 (CWP) n = 12 (HC) |
ACR 1990 | Plasma 2-AG, AEA, PEA, SEA, OEA, LEA | Venepuncture/Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) |
CWP: 55.5 (6.0) HC: 47.5 (9.0) |
CWP: 0/14 HC: 0/27 |
FMS: 26.8 (4.3) HC: 24.0 (3.0) |
Not reported | Not reported All participants were asked not to use any pain medications except for paracetamol preparations 3 days before the blood sampling |
Not reported Subjects with rheumatoid arthritis, systemic lupus erythematosus, Bechterew disease, multiple sclerosis, epilepsy or Parkinson disease, type I diabetes, cardiovascular disease, or endocrine diseases were excluded |
Average pain/1 wk (NRS 0–10): CWP: 5.3 (1.3) HC: no pain Current pain (NRS 0–10): CWP: 3.8 (1.8) HC: no pain Depression/anxiety: Not reported |
9-HODE, 13-HODE, 9,10-DiHOME, 12,13-DiHOME, 9,10,13-TriHOME, 9,12,13-TriHOME, 13-oxo-ODE, 5-HETE, 8,9-DiHETrE |
CWP (nM) | HC (nM) | ||
|
AM: 2AG: 3.28 (2.12) AEA: 0.16 (0.16) PEA: 2.08 (1.12) SEA: 11.31 (8.34) OEA: 1.76 (1.01) LEA: 0.62 (0.60) |
PM: 8.30 (10.83) 0.22 (0.17) 2.96 (1.68) 10.69 (5.58) 1.29 (1.39) 0.71 (0.90) |
AM: 5.38 (3.22) 0.18 (0.05) 1.93 (0.53) 8.44 (3.74) 0.93 (1.25) 0.62 (0.14) |
PM: 6.39 (8.50) 0.19 (0.10) 2.73 (0.89) 11.22 (4.02) 1.77 (0.73) 0.95 (0.34) |
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| Stensson (2017) | n = 17 (CWP) n = 21 (HC) |
ACR 1990 | Plasma OEA, PEA, SEA | Venepuncture/Liquid chromatography-tandem mass spectrometry (LC-MS/MS) |
CWP: 41.7 (10) HC: 47.9 (9.6) |
CWP: 0/17 HC: 0/21 |
FMS: 24.2 (2.1) HC: 26.8 (5.3) |
Not reported | Not reported. | Not reported. Subjects with bursitis, disorders of the spine, tendonitis, capsulitis, postoperative conditions (neck/shoulder), prior neck trauma, neurological disease, rheumatoid arthritis or any other systemic disease, metabolic disease, malignancy, severe psychiatric illness, pregnancy were excluded. |
Pain (NRS 0–10): CWP: 5.3 (2.1) HC: 0.0 (0.0), P < 0.001 Depression/Anxiety: Not reported |
IL-6, IL-8, IL-10, TNF-α, IL-1β | CWP (nM): OEA: 11.1 (3.0) PEA: 18.1 (9.7) SEA: 38.6 (28.7) |
HC (nM): OEA: 7.5 (3.7) PEA: 10.5 (6.2) SEA: 27.2 (20.7) |
P: OEA: 0.003 PEA: 0.006 SEA: 0.164 |
|
| Ghafouri (2013) | n = 18 (CWP) n = 24 (HC) |
ACR 1990 | Interstitial PEA and SEA (trapezius muscle) | Microdialysis/liquid chromatography-tandem mass spectrometry (LC–MS/MS) | CWP: 47.6 (8.3) HC: 42.8 (7.3) |
CWP: 0/18 HC: 0/24 |
FMS: 27.5 (4.0) HC: 24.3 (2.8) |
Not reported | Not reported Participants were asked not to take nonsteroidal anti-inflammatory drugs for 7 d and/or paracetamol medication for 12 h before the experiment |
Not reported Subjects with bursitis, disorders of the spine, tendonitis, capsulitis, postoperative conditions (neck/shoulder), prior neck trauma, neurological disease, rheumatoid arthritis or any other systemic disease, metabolic disease, malignancy, severe psychiatric illness, and pregnancy were excluded |
Pain (NRS 0–10): CWP vs HC: P = 0.001 Depression/anxiety: Not reported |
Not reported | CWP (nM): Pre-exercise: PEA: 1.23 (0.55) SEA: 1.48 (0.93) Post-exercise: PEA 0.95 (0.58) SEA: 0.95 (0.70) |
HC (nM): Pre-exercise: PEA: 1.17 (0.84) SEA: 0.98 (0.68) Post-exercise: PEA: 0.85 (0.55) SEA: 0.75 (0.43) |
P: Pre-exercise: PEA: NS SEA: NS Post-exercise: PEA: NS SEA: NS |
|
| Stensson (2016) | n = 17 (CWP) n = 19 (HC) |
ACR 1990 | Interstitial OEA, PEA, and SEA (trapezius muscle) | Microdialysis/liquid chromatography-tandem mass spectrometry (LC-MS/MS) |
CWP: 48.8 (10.0) HC: 41.8 (10.7) |
CWP: 0/17 HC: 0/19 |
FMS: 27.5 (5.7) HC: 24.5 (2.9) |
Not reported | Not reported. | Not reported Subjects with bursitis, disorders of the spine, tendonitis, capsulitis, postoperative conditions (neck/shoulder), prior neck trauma, neurological disease, rheumatoid arthritis or any other systemic disease, metabolic disease, malignancy, severe psychiatric illness, and pregnancy were excluded |
Pain (NRS 0–10): CWP vs HC: P < 0.001 Depression/anxiety: Not reported |
Not reported | CWP (nM) 120 min: OEA: 2.22 (1.78) PEA: 0.93 (0.50) SEA: 3.67 (3.54) |
HC (nM) 120 min: OEA: 0.34 (0.48) PEA: 0.55 (0.95) SEA: 0.74 (0.69) |
P: OEA: 0.000 PEA: 0.148 SEA: 0.001 |
|
2-AG, 2-arachidonoylglycycerol; ACR, American College of Rheumatology; AEA, N-arachidonoylethanolamide, or anandamide; AM, morning sample; CWP, chronic widespread pain; FMS, fibromyalgia syndrome; HCs, healthy controls; IL, interleukin; LEA, linoleoylethanolamide; OEA, oleoylethanolamide; PEA, palmitoylethanolamide; PM, afternoon sample; SEA, stearoylethanolamide; TNF-α, tumor necrosis factor-α.