Table 1 |.
Key serum biomarker studies for CRPS
| Type of CRPS | Mean CRPS duration (range) In months | Mean pain intensity (range)a | Test target | Test type | Definition of test positivity | Controls | No. of patients/controls tested | Sensitivity and specificity | Clinical and prognostic associations |
|---|---|---|---|---|---|---|---|---|---|
| Early39 | 3.5 (0.2–15.8) | 6 (2–10) | Serum cytokines | Bead-based multiplex assay | Detection limits specified by manufacturer | Patients with upper-limb pain | 28/15 | No differences between patients and controls | None identified |
| Both early and persistent40 | 8 (2–21) | 3 (0–5) | Serum TNF | ELISA | Detection limit: <1.7 pg/ml | Patients after upper-limb fracture or with severe knee or hip osteoarthritis | 10/20 | No differences between patients with CRPS and patients with osteoarthritis; patients with fractures had lower levels than the other groups | In CRPS, temperature difference between limbs correlated with plasma TNF level (P < 0.02, ρ = 0.756) |
| Early41 | 3.0 (2.0–5.5) | 5 (IQR: 3–8) | Osteoprotegerin | ELISA | >90% CI of the control mean | Patients after limb trauma and patients undergoing three-phased bone scan for cancer staging | 23/31 | Sensitivity 74% and specificity 79%; AUC 0.8 (CI 0.68–0.91) | Carpal bone tracer uptake in three-phase bone scan correlated with serum osteoprotegerin (ρ = 0.391) |
| Early42 | 3.5 (0.5–19.0) | 4 (0–10) | β2‑Adrenergic receptor activation and M2 muscarinic receptor activation | Live-cell bioassay confirmed by ELISA | Healthy control mean + 2.5 × CI | Healthy individuals and patients with noninflammatory neuropathy or peripheral nerve lesion | 20/19 | Combined ELISA test results for the two targets: sensitivity 75% and specificity 100% versus all controls | None identified |
| Persistent43 | 17 (6–120) | 7.5 (6.0–10.0) | α1A‑Adrenergic receptor activation and muscarinic receptor activation | Live-cell bioassay | Healthy control mean ± 3 × s.d. | Healthy individuals and patients with neuropathic pain, fibromyalgia or myasthenia gravis | 18/57 | Combined test results for the two targets: sensitivity 61% and specificity 98% versus all controls | None identified |
ρ, Spearman’s rank correlation oefficient; AUC, area under the curve; CRPS, complex regional pain syndrome; ELISA, enzyme-linked immunosorbent assay; IQR, interquartile range; TNF, tumour necrosis factor.
a
Measured on an 11-point (0–10) pain-rating scale.