Elevated Production of Nociceptive CC Chemokines and sE-Selectin in Patients With Low Back Pain and the Effects of Spinal Manipulation: A Nonrandomized Clinical Trial

Clin J Pain. 2018 Jan;34(1):68-75. doi: 10.1097/AJP.0000000000000507.


Background: The involvement of inflammatory components in the pathophysiology of low back pain (LBP) is poorly understood. It has been suggested that spinal manipulative therapy (SMT) may exert anti-inflammatory effects.

Purpose: The purpose of this study was to determine the involvement of inflammation-associated chemokines (CC series) in the pathogenesis of nonspecific LBP and to evaluate the effect of SMT on that process.

Methods: Patients presenting with nonradicular, nonspecific LBP (minimum pain score 3 on 10-point visual analog scale) were recruited according to stringent inclusion criteria. They were evaluated for appropriateness to treat using a high velocity low amplitude manipulative thrust in the lumbar-lumbosacral region. Blood samples were obtained at baseline and following the administration of a series of 6 high velocity low amplitude manipulative thrusts on alternate days over the period of 2 weeks. The in vitro levels of CC chemokine ligands (CCL2, CCL3, and CCL4) production and plasma levels of an inflammatory biomarker, soluble E-selectin (sE-selectin), were determined at baseline and at the termination of treatments 2 weeks later.

Results: Compared with asymptomatic controls baseline production of all chemokines was significantly elevated in acute (P=0.004 to <0.0001), and that of CCL2 and CCL4 in chronic LBP patients (P<0.0001). Furthermore, CCL4 production was significantly higher (P<0.0001) in the acute versus chronic LBP group. sE-selectin levels were significantly higher (P=0.003) in chronic but not in acute LBP patients. Following SMT, patient-reported outcomes showed significant (P<0.0001) improvements in visual analog scale and Oswestry Disability Index scores. This was accompanied by a significant decline in CCL3 production (P<0.0001) in both groups of patients. Change scores for CCL4 production differed significantly (P<0.0001) only for the acute LBP cohort, and no effect on the production of CCL2 or plasma sE-selectin levels was noted in either group.

Conclusions: The production of chemotactic cytokines is significantly and protractedly elevated in LBP patients. Changes in chemokine production levels, which might be related to SMT, differ in the acute and chronic LBP patient cohorts.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Chemokines, CC / blood*
  • Chi-Square Distribution
  • Disability Evaluation
  • Female
  • Humans
  • Low Back Pain / blood*
  • Low Back Pain / rehabilitation*
  • Male
  • Manipulation, Spinal / methods*
  • Middle Aged
  • Pain Measurement
  • Selectins / blood*
  • Statistics, Nonparametric
  • Young Adult


  • Chemokines, CC
  • Selectins