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

Abstract

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.

A cross-sectional study: serum CCL3/MIP-1&alpha; levels may reflect lumbar intervertebral disk degeneration in Han Chinese people

“… 31 – 33 In addition, in nonspecific patients with LBP, improvements in VAS and ODI scores were closely accompanied by the obvious decline of CCL3 following spinal manipulation. 34 All these works implicate that systematic CCL3 levels may participate the pain production in various disease. In our study, we observed that increased CCL3 levels were related to pain determined by VAS scores and functional disability by ODI index, suggesting serum that CCL3 expression plays a major role in the pain formation of disk degeneration through potential mechanisms.…”

Szérumbiomarkerek akut lumbalis-lumbosacralis fájdalomban

“…A kemokinek elősegítik a gyulladást, a gyulladásos sejtek és a neuronok közötti kommunikációban, a fájdalom transzmissziójában játszanak szerepet. A fájdalom és a különböző kemokinek kapcsolatát eddig még kevés vizsgálat elemezte [36].…”

“…Akut és krónikus derékfájdalomban szenvedők szérummintáiban összehasonlítva a CCL2, CCL3, CCL4 kemokinek szintjeit egy kontrollcsoport mintáival, szignifikánsan emelkedett kemokinszinteket írtak le a fájdalomban szenvedők csoportjában (63 fő). Ezenfelül a CCL4 szintje jelentősen magasabb volt az akut derékfájdalomban szenvedők körében, mint a krónikus derékfájdalom miatt vizsgált egyénekben [36].…”

Effects of spinal manipulation and pain education on pain in patients with chronic low back pain: a protocol of randomized sham-controlled trial

“…Few studies have suggested possible pathophysiological mechanisms in LBP as the increase of the inflammatory biomarkers tumor necrosis factor-α (TNF-α), interleukins (IL)-1α, IL-1β, IL-6, IL-17, chemokines (CCL) 2 and 4, and a decrease of IL-10, anti-inflammatory cytokines. 4 , 5 , 6 , 7 , 8 , 9 These biomarkers (e.g., cytokines) are small secreted proteins released by immune cells populations, predominantly by T Helper and macrophages cells. They have a specific effect on the interactions and communication between cells.…”