Changes in Spinal Cord Expression of Fractalkine and its Receptor in a Rat Model of Disc Herniation by Autologous Nucleus Pulposus

Park, Hea-Woon; Ahn, Sungjin; Kim, Su-Jeong; Seo, Jeong-Min; Cho, Yun-Woo; Jang, Sung-Ho; Hwang, Se Jin; Kwak, Soyoung

doi:10.1097/brs.0b013e3181ef610b

Cited by 28 publications

(26 citation statements)

References 51 publications

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“…Recently, we reported that autologous implantation of NP on a nerve root in a rat caused upregulation of fractalkine in the spinal dorsal horn, which suggests that fractalkine is associated with radicular pain. 33 Our results are consistent with the notion that inflammatory responses, rather than mechanical compression, caused by NP are responsible for pain and suggest that some cellular changes occur after PRF administration to the DRG in a rat model of lumbar disc herniation.…”

Section: Discussionsupporting

confidence: 81%

“…Transplantation of autologous NP near a spinal nerve root is frequently used in animal models of lumbar intervertebral disc herniation, 17,19,29,31,33,34,41 and NP application without compression of the nerve root and DRG produces morphologic and functional changes and blood flow impairment, 18,30,51 enhances responses of secondary neurons to noxious stimuli, 3 and causes allodynia in the hindlimb. Recently, we reported that autologous implantation of NP on a nerve root in a rat caused upregulation of fractalkine in the spinal dorsal horn, which suggests that fractalkine is associated with radicular pain.…”

Section: Discussionmentioning

confidence: 99%

“…The sham procedure was performed in an identical manner and included autologous NP harvesting and nerve root exposure but not autologous NP implantation. 19,33,34,41 To determine microglia and astrocyte activity and pERK expression, we euthanized 3 NP-exposed rats at 10 days after surgery. The remaining 20 NP-exposed rats were divided into 2 groups of 10 each: NP-exposed with sham stimulation (NP+sham stimulation) and NPexposed with PRF (NP+PRF).…”

Section: Lumbar Disc Herniation and Prf Administration Proceduresmentioning

confidence: 99%

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Changes in pain behavior and glial activation in the spinal dorsal horn after pulsed radiofrequency current administration to the dorsal root ganglion in a rat model of lumbar disc herniation

Cho

Kim

et al. 2013

SPI

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Object Herniated discs can induce sciatica by mechanical compression and/or chemical irritation caused by proinflammatory cytokines. Using immunohistochemistry methods in the dorsal horn of a rat model of lumbar disc herniation, the authors investigated the effects of pulsed radiofrequency (PRF) current administration to the dorsal root ganglion (DRG) on pain-related behavior and activation of microglia, astrocytes, and mitogen-activated protein kinase. Methods A total of 33 Sprague-Dawley rats were randomly assigned to either a sham-operated group (n = 10) or a nucleus pulposus (NP)–exposed group (n = 23). Rats in the NP-exposed group were further subdivided into NP exposed with sham stimulation (NP+sham stimulation, n = 10), NP exposed with PRF (NP+PRF, n = 10), or euthanasia 10 days after NP exposure (n = 3). The DRGs in the NP+PRF rats were exposed to PRF waves (2 Hz) for 120 seconds at 45 V on postoperative Day 10. Rats were tested for mechanical allodynia 10 days after surgery and at 8 hours, 1 day, 3 days, 10 days, 20 days, and 40 days after PRF administration. Immunohistochemical staining of astrocytes (glial fibrillary acidic protein), microglia (OX-42), and phosphorylated extracellular signal–regulated kinases (pERKs) in the spinal dorsal horn was performed at 41 days after PRF administration. Results Starting at 8 hours after PRF administration, mechanical withdrawal thresholds dramatically increased; this response persisted for 40 days (p < 0.05). After PRF administration, immunohistochemical expressions of OX-42 and pERK in the spinal dorsal horn were quantitatively reduced (p < 0.05). Conclusions Pulsed radiofrequency administration to the DRG reduced mechanical allodynia and downregulated microglia activity and pERK expression in the spinal dorsal horn of a rat model of lumbar disc herniation.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Lumbar Disc Herniation and Prf Administration Proceduresmentioning

confidence: 99%

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Changes in pain behavior and glial activation in the spinal dorsal horn after pulsed radiofrequency current administration to the dorsal root ganglion in a rat model of lumbar disc herniation

Cho

Kim

et al. 2013

SPI

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“…Park et al19 found that CX3CL1 immunoreactivity gradually increased in laminae II and III of the ipsilateral dorsal horn by using a nucleus pulposus (NP) implantation-induced model of LDH. One recent study showed that CCL2/CCR2 signaling in the dorsal root ganglion and spinal cord plays a significant role in the maintenance of neuropathic pain in a rat model of LDH 20…”

Section: Introductionmentioning

confidence: 99%

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

Peng¹,

Chen²,

Fang³

et al. 2017

JPR

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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.

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“…For instance, previous data show that soluble fractalkine (CX3CL1) activates glia and leukocytes through its receptor CX3CR1 [11, 12]. Furthermore, spinal upregulation of CX3CL1 may be associated with mechanical allodynia and thermal hyperalgesia [13]. Thus, one important inflammatory molecule possibly influencing the sensory pathways may be CX3CL1.…”

Section: Introductionmentioning

confidence: 99%

Hyperexcitability in Spinal WDR Neurons following Experimental Disc Herniation Is Associated with Upregulation of Fractalkine and Its Receptor in Nucleus Pulposus and the Dorsal Root Ganglion

Jacobsen

Møen

Haugen

et al. 2016

International Journal of Inflammation

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Introduction. Lumbar radicular pain following intervertebral disc herniation may be associated with a local inflammatory response induced by nucleus pulposus (NP) cells. Methods. In anaesthetized Lewis rats, extracellular single unit recordings of wide dynamic range (WDR) neurons in the dorsal horn and qPCR were used to explore the effect of NP application onto the dorsal nerve roots (L3–L5). Results. A clear increase in C-fiber response was observed following NP conditioning. In the NP tissue, the expression of interleukin-1β (IL-1β), colony stimulating factor 1 (Csf1), fractalkine (CX3CL1), and the fractalkine receptor CX3CR1 was increased. Minocycline, an inhibitor of microglial activation, inhibited the increase in neuronal activity and attenuated the increase in IL-1β, Csf1, CX3L1, and CX3CR1 expression in NP tissue. In addition, the results demonstrated an increase in the expression of TNF, CX3CL1, and CX3CR1 in the dorsal root ganglions (DRGs). Conclusion. Hyperexcitability in the pain pathways and the local inflammation after disc herniation may involve upregulation of CX3CL1 signaling in both the NP and the DRG.

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Changes in Spinal Cord Expression of Fractalkine and its Receptor in a Rat Model of Disc Herniation by Autologous Nucleus Pulposus

Abstract: Our results indicate that autologous implantation of NP induces thermal hyperalgesia and mechanical allodynia, and leads to an upregulation of fractalkine and its receptor in spinal neurons and glia, implicating fractalkine in association with radicular pain.

Cited by 28 publications

References 51 publications

Changes in pain behavior and glial activation in the spinal dorsal horn after pulsed radiofrequency current administration to the dorsal root ganglion in a rat model of lumbar disc herniation

Changes in pain behavior and glial activation in the spinal dorsal horn after pulsed radiofrequency current administration to the dorsal root ganglion in a rat model of lumbar disc herniation

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

Hyperexcitability in Spinal WDR Neurons following Experimental Disc Herniation Is Associated with Upregulation of Fractalkine and Its Receptor in Nucleus Pulposus and the Dorsal Root Ganglion

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