Clinical Value of Serum Neuroplasticity Mediators in Identifying the Central Sensitivity Syndrome in Patients With Chronic Pain With and Without Structural Pathology

Clin J Pain. 2015 Nov;31(11):959-67. doi: 10.1097/AJP.0000000000000194.


Background and objectives: Central sensitivity syndrome (CSS) encompasses disorders with overlapping symptoms in a spectrum of structural pathology from persistent somatic nociception (eg, osteoarthritis) to absence of tissue injury such as in fibromyalgia, chronic tension-type headache, and myofascial pain syndrome. Likewise, the spectrum of the neuroplasticity mediators associated with CSS might present a pattern of clinical utility.

Methods: We studied the brain-derived neurotrophic factor (BDNF), tumor necrosis factor-α (TNF-α), and interleukins 6 (IL-6) and IL-10 in female patients with CSS absent of structural pathology (chronic tension-type headache [n=30], myofascial pain syndrome [n=29], fibromyalgia [n=22]); with CSS due to persistent somatic/visceral nociception (osteoarthritis [n=27] and endometriosis [n=32]); and in pain-free controls (n=37).

Results: Patients with CSS absent of structural pathology presented higher serum TNF-α (28.61±12.74 pg/mL) and BDNF (49.87±31.86 ng/mL) than those with persistent somatic/visceral nociception (TNF-α=17.35±7.38 pg/mL; BDNF=20.44±8.30 ng/mL) and controls (TNF-α=21.41±5.74 pg/mL, BDNF=14.09±11.80 ng/mL). Moreover, CSS patients absent of structural pathology presented lower IL levels. Receiver operator characteristics analysis showed the ability of BDNF to screen CSS (irrespective of the presence of structural pathology) from controls (cutoff=13.31 ng/mL, area under the curve [AUC]=0.86, sensitivity=95.06%, specificity=56.76%); and its ability to identify persistent nociception in CSS patients when experiencing moderate-severe depressive symptoms (AUC=0.81; cutoff=42.83 ng/mL, sensitivity=56.80%, specificity=100%). When the level of pain measured on the visual analog scale was <5 and moderate-severe depressive symptoms were observed TNF-α discriminated structural pathology in the chronic pain conditions (AUC=0.97; cutoff=22.11 pg/mL, sensitivity=90%, specificity=91.3%).

Conclusion: Neuroplasticity mediators could play a role as screening tools for pain clinicians, and as validation of the complex and diffuse symptoms of these patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brain-Derived Neurotrophic Factor / blood*
  • Chronic Pain / blood*
  • Chronic Pain / etiology*
  • Chronic Pain / psychology
  • Cross-Sectional Studies
  • Depression / blood
  • Endometriosis / blood
  • Female
  • Fibromyalgia / blood
  • Humans
  • Interleukin-10 / blood*
  • Interleukin-6 / blood*
  • Middle Aged
  • Myofascial Pain Syndromes / blood
  • Neuronal Plasticity
  • Osteoarthritis / blood
  • ROC Curve
  • Retrospective Studies
  • Sensitivity and Specificity
  • Tension-Type Headache / blood
  • Tumor Necrosis Factor-alpha / blood*


  • Brain-Derived Neurotrophic Factor
  • IL10 protein, human
  • IL6 protein, human
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • BDNF protein, human