Epidural Application of Nucleus Pulposus Enhances Nociresponses of Rat Dorsal Horn Neurons

Anzai, Hitomi; Hamba, Michiko; Onda, Akira; Konno, Satoshi; Kikuchi, Shinichi

doi:10.1097/00007632-200202010-00003

Cited by 69 publications

(36 citation statements)

References 33 publications

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“…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%

“…30 Previous studies have suggested that the signs of lumbar disc herniation are caused by chemical factors from the nucleus pulposus and by mechanical compression of the lumbar nerve root 3,18,27,28,30,51 and that they are mediated by proinflammmatory cytokines derived from the herniated intervertebral disc. 13,16,37 Also implicated in NP-induced nerve root injury and associated radicular pain is expression of cytokines such as IL-1, IL-6, IL-8, tumor necrosis factor-a, and cyclooxygenase-2.…”

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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: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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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“…It has been known for some time that peripheral inflammatory conditions resulting in heightened pain sensitivity are characterized by an early release of TNFa at the site of inflammation. 1 Direct application of TNFa to peripheral nerve induces spontaneous electrophysiologic activity in neurons of the dorsal root ganglion (DRG), [2][3][4] and subcutaneous or epineurial application of TNFa produces nocisponsive behaviors. 5,6 A substantial body of evidence suggests that neuroimmune activation of glial cells in the dorsal horn of spinal cord results in the release of proinflammatory cytokines and plays an important role in facilitation of nociceptive neurotransmission and the development of chronic pain.…”

Section: Introductionmentioning

confidence: 99%

HSV-mediated transfer of interleukin-10 reduces inflammatory pain through modulation of membrane tumor necrosis factor α in spinal cord microglia

et al. 2007

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To dissect the molecular basis of the neuroimmune response associated with the genesis of inflammatory (nociceptive) pain, we constructed a herpes simplex virus-based gene transfer vector to express the antiinflammatory cytokine interleukin-10 (IL-10), and used it to examine the effect of IL-10 expression in activated microglial cells in vitro, and in inflammatory pain in vivo. IL-10 reduced the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and decreased the expression of full-length membrane spanning tumor necrosis factor-a (mTNFa) following lipopolysaccharide stimulation of microglia in vitro. IL-10 also reduced intracellular cleavage of mTNFa and release of the soluble cleavage product sTNFa. Similar effects on TNFa expression were observed when the cells were pretreated with a p38 MAPK inhibitor. In animals, injection of a dilute solution of formalin in the skin resulted in an increase in mTNFa in spinal dorsal horn, without detectable sTNFa. Local release of IL-10 achieved by gene transfer reduced the number of spontaneous flinches in the early and delayed phases of the formalin test of inflammatory pain. The effect of IL-10 on nocisponsive behavior correlated with a block in phosphorylation of p38 and reduced expression of 26 kDa mTNFa in spinal microglia. The results emphasize the key role played by membrane TNFa in the spinal neuroimmune response in pain caused by peripheral inflammation.

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“…NP application without compression of the nerve root and DRG produces morphologic/functional changes and blood flow impairment 2,6,9,31) , response of secondary neurons to noxious stimuli is enhanced 1) , and allodynia in the hind limb has been demonstrated 32) . The present study showed that allodynia was induced from post -operative day 1 in the NP and MC+NP groups.…”

Section: Discussionmentioning

confidence: 99%

A Comparison of Pain-Related Behavior Following Local Application of Nucleus Pulposus and/or Mechanical Compression on the Dorsal Root Ganglion

Sasaki

Sekiguchi

Shishido

et al. 2011

FJMS

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: Symptomatic induction of disc herniation involves both mechanical compression and chemical factors. Inhibitors of tumor necrosis factor -alpha (TNF -α) are known to reduce painrelated behavior in experimental models. Animals were divided into mechanical compression (MC) group ; a stainless steel rod was inserted on the dorsal root ganglion, nucleus pulposus (NP) group : NP was harvested from the coccygeal vertebral disc, MC and NP group ; rats were received stainless rod and NP, and sham group ; rats were received neither rod nor NP. Rats in the MC group received a TNF -α antibody (10 mg/kg) (antibody group) or were not treatment (untreated group). The withdrawal thresholds of the MC, NP and MC+NP groups decreased significantly compared with the sham group. In the antibody group, the threshold was significantly higher than that of the untreated group. An anti -TNF -α antibody reduced allodynia caused by DRG compression.

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Epidural Application of Nucleus Pulposus Enhances Nociresponses of Rat Dorsal Horn Neurons

Abstract: Results suggest that somewhat pathogenic factors in the nucleus pulposus may have a crucial role in the induction of hyperalgesia. This may help to elucidate the reason why a severe pain is sometimes induced without a visually identified protrusion.

Cited by 69 publications

References 33 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

HSV-mediated transfer of interleukin-10 reduces inflammatory pain through modulation of membrane tumor necrosis factor α in spinal cord microglia

A Comparison of Pain-Related Behavior Following Local Application of Nucleus Pulposus and/or Mechanical Compression on the Dorsal Root Ganglion

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