Increased local expressions of CX3CL1 and CCL2 are related to clinical severity in lumbar disk herniation patients with sciatic pain

Abstract

BackgroundChemokines have been identified to be involved in the modulation of pain through both peripheral and central mechanisms. However, the role of chemokines in lumbar disk herniation (LDH) with sciatic pain remains unknown.ObjectiveThe current study was performed to explore the expression of two most commonly studied chemokines CX3CL1 and CCL2 and assess their associations with clinical severity in LDH patients with sciatic pain.MethodsThe soft tissues around nerve root (STANR), annulus fibrosus (AF), and nucleus pulposus (NP) biopsies were obtained from 36 LDH patients with chronic sciatic pain and 10 scoliosis patients (painless controls). The serum and local expressions of CX3CL1 and CCL2 were determined using enzyme-linked immunosorbent assay and Western blot analysis, respectively. The visual analog scale (VAS) scores for low back pain and lower extremity pain and Japanese Orthopaedic Association (JOA) scores were recorded on the day of hospital admission to evaluate the clinical severity. LDH patients with sciatic pain were divided into severe pain (SP) group (VAS ≥7; n=18) and mild-to-moderate pain (M-MP) group (VAS <7; n=18) for lower extremity pain.ResultsLocal expressions instead of CX3CL1 and CCL2 in STANR, AF, and NP were significantly higher in the SP group than in M-MP compared with scoliosis painless group. Expressions of both CX3CL1 and CCL2 in STANR and AF were positively correlated with VAS scores for lower extremity and for low back pain, respectively. In addition, CX3CL1 and CCL2 expressions in STANR were negatively associated with JOA scores. There were no significant differences of serum CX3CL1 and CCL2 levels among SP group, M-MP group, and scoliosis painless group.ConclusionBoth CX3CL1 and CCL2 may play important roles in maintaining pain in LDH patients. Local blockade of CX3CL1 and CCL2 in LDH patients with persistent pain deserves further intensive study.

The Role of Spinal Cord CX3CL1/CX3CR1 Signalling in Chronic Pain

“…For instance, in fibromyalgia patients, high levels of FKN are measured in the CSF compared to controls [48••]. There is also isolated evidence to suggest that fractalkine expression is elevated at a tissue level in patients with chronic sciatic pain [49]. Specifically, the expression of FKN is elevated in the soft tissues of the nerve root and intervertebral disc in patients with severe chronic pain caused by lumbar disk herniation compared to those reporting milder pain.…”

The relationship of the shear wave elastography findings of patients with unilateral lumbar disc herniation and clinical characteristics

“…In LDH, nucleus pulposus(NP) material exits the disk space area through the annulus fibrosus(AF), causing mild compression on the spinal nerves and resulting in neurological dysfunction including pain, sensory deficits, and weakness in the low back and leg [12].There are several changes in the biology of the intervertebral disc which is thought to contribute to LDH. These include increased percent of type I collagen within the NP and inner AF [13] , reduced water retention in the NP [14,15,16],degradation of collagen and extracellular matrix materials (ECM) [17], and upregulation of systems of degradation such as apoptosis, matrix metalloproteinase (MMP) expression,and inflammatory pathways [18].Increased expression of chemokines are associated to clinical severity of sciatic pain in lumbar disk herniation patients [19] .Mechanical compression and accompanying chemical stimulation may cause severe nerve root damage, which in turn affects the axonal transport, affecting the circulation of nerve roots and the metabolism of neurotransmitters [21]. Thereby causes neurilemma edema, fibroblast infiltration, and nerve fiber deformation.These changes can lead to demyelination of the nerve and can alter the nerve connective tissue [20], causing the proliferation of scar tissue and the acceleration of the transverse wave in the nerve.SWE is an imaging technique that emits transverse waves to tissue through a transducer.According to E=3ρc∧2 (E is the Young's modulus, c is the shear wave propagation velocity, and ρ is the tissue density), the machine displays the E value,The faster the shear wave propagation speed, the higher the E value.SWE can 8 quantitatively calculate the E value according to the shear wave propagation velocity in the region of interest, and evaluate the elastic properties of tissues qualitatively by the E value.The tissue stiffness is displayed by color coding.The harder the tissue, the faster the shear wave travels, the higher the E value, and the image appears red.…”

The relationship of the shear wave elastography findings of patients with unilateral lumbar disc herniation and clinical characteristics

“…In LDH, nucleus pulposus(NP) material exits the disk space area through the annulus fibrosus(AF), causing mild compression on the spinal nerves and resulting in neurological dysfunction including pain, sensory deficits, and weakness in the low back and leg [12].There are several changes in the biology of the intervertebral disc which is thought to contribute to LDH. These include increased percent of type I collagen within the NP and inner AF [13] , reduced water retention in the NP [14,15,16],degradation of collagen and extracellular matrix materials (ECM) [17], and upregulation of systems of degradation such as apoptosis, matrix metalloproteinase (MMP) expression,and inflammatory pathways [18].Increased expression of chemokines are associated to clinical severity of sciatic pain in lumbar disk herniation patients [19] .Mechanical compression and accompanying chemical stimulation may cause severe nerve root damage, which in turn affects the axonal transport, affecting the circulation of nerve roots and the metabolism of neurotransmitters [21]. Thereby causes neurilemma edema, fibroblast infiltration, and nerve fiber deformation.These changes can lead to demyelination of the nerve and can alter the nerve connective tissue [20], causing the proliferation of scar tissue and the acceleration of the transverse wave in the nerve.SWE is an imaging technique that emits transverse waves to tissue through a transducer.According to E=3ρc∧2 (E is the Young's modulus, c is the shear wave propagation velocity, and ρ is the tissue density), the machine displays the E value,The faster the shear wave propagation speed, the higher the E value.SWE can quantitatively calculate the E value according to the shear wave propagation velocity in the region of interest, and evaluate the elastic properties of tissues qualitatively by the E value.The tissue stiffness is displayed by color coding.The harder the tissue, the faster the shear wave travels, the higher the E value, and the image appears red.…”