Changes in Expression of mRNA for Interleukin-8 and Effects of Interleukin-8 Receptor Inhibitor in the Spinal Dorsal Horn in a Rat Model of Lumbar Disc Herniation

Kim, Su-Jeong; Park, Sung Min; Cho, Yun-Woo; Jung, Yong-Jae; Lee, Dong Gyu; Park, Hea-Woon; Hwang, Se Jin; Ahn, Sungjin

doi:10.1097/brs.0b013e31821945a3

Cited by 49 publications

(34 citation statements)

References 63 publications

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“…Among the chemokines family, IL-8 and its receptors CXCR1/2 have been emerging as one of the most promising target for the pharmacological management of CIPN due to its implication in sympathetic components of inflammatory hypernociception and in neuropathic nociceptive response [46–47]. Interestingly, a recent controlled clinical study showed a significant upregulation of IL8 gene expression in the skin biopsies of patients affected by CIPN [23].…”

Section: Discussionmentioning

confidence: 99%

CXCR1/2 pathways in paclitaxel-induced neuropathic pain

et al. 2017

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Chemotherapy-induced peripheral neuropathy (CIPN) is a type of neuropathic pain that represents a frequent and serious consequence of chemotherapy agents. Over the last years, significant progress has been achieved in elucidating the underlying pathogenesis of CIPN. The interference of taxanes with microtubule has been proposed as a mechanism that leads to altered axonal transport and to permanent neurological damages. The inflammatory process activated by chemotherapeutic agents has been considered as a potential trigger of nociceptive process in CIPN.In this study we investigated the effect of reparixin, an inhibitor of CXCR1/CXCR2, in suppressing the development of paclitaxel-induced nociception in rats. Moreover, reparixin activity in reversing the neurotoxic effects induced by paclitaxel or GRO/KC in F11 cells was also analyzed.Reparixin administered by continuous infusion ameliorated paclitaxel-induced mechanical and cold allodynia in rats. In F11 cells, reparixin was able to inhibit the increase of acetyladed α-tubulin induced both by paclitaxel and GRO/KC. The subsequent experiments were performed in order to dissect the signal transduction pathways under GRO/KC control, eventually modulated by paclitaxel and/or reparixin. To this aim we found that reparixin significantly counteracted p-FAK, p-JAK2/p-STAT3, and PI3K-p-cortactin activation induced either by paclitaxel or GRO/KC.Overall the present results have identified IL-8/CXCR1/2 pathway as a mechanism involved in paclitaxel-induced peripheral neuropathy. In particular, the obtained data suggest that the inhibition of CXCR1/2 combined with standard taxane therapy, in addition to potentiating the taxane anti-tumor activity can reduce chemotherapy-induced neurotoxicity, thus giving some insight for the development of novel treatments.

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Section: Discussionmentioning

confidence: 99%

CXCR1/2 pathways in paclitaxel-induced neuropathic pain

et al. 2017

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“…20 In the study reported here, immunohistochemical examination of the spinal cord for GFAP, OX-42, and pERK at Day 41 after PRF administration revealed reactive astrocytes with thickened processes in the dorsal horn, ipsilateral and contralateral to disc herniation in the NP+sham-stimulation group; this astrocyte activation was not affected by PRF administration. In contrast, the numbers of microglia increased in the dorsal horn ipsilateral to disc herniation in the NP+sham-stimulation group (mean gray value 29 …”

Section: Microglia Astrocytes and Perkmentioning

confidence: 91%

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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“…In experimental studies, autologous nucleus pulposus (NP) implantation in the dorsal root ganglion (DRG) is used to initiate LDH in rats. Recent studies have reported that several chemokines were involved in the NP-induced neuropathic pain [5][6] . For example, it has been reported that IL-8 mRNA expression was increased in the DRG after NP exposure while IL-8 inhibition could attenuated NP-induced allodynia in the spinal cord 6 .…”

Section: ■ Introductionmentioning

confidence: 99%

NF-kB mediated CX3CL1 activation in the dorsal root ganglion contributes to the maintenance of neuropathic pain induced in adult male Sprague Dawley rats

et al. 2018

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Changes in Expression of mRNA for Interleukin-8 and Effects of Interleukin-8 Receptor Inhibitor in the Spinal Dorsal Horn in a Rat Model of Lumbar Disc Herniation

Abstract: IL-8 might be a potential therapeutic target in chronic radicular neuropathic pain because of disc herniation, CXCL8 inhibitor could be one of its promising therapeutic agents.

Cited by 49 publications

References 63 publications

CXCR1/2 pathways in paclitaxel-induced neuropathic pain

CXCR1/2 pathways in paclitaxel-induced neuropathic pain

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

NF-kB mediated CX3CL1 activation in the dorsal root ganglion contributes to the maintenance of neuropathic pain induced in adult male Sprague Dawley rats

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