Pain Behavior Changes Following Disc Puncture Relate to Nucleus Pulposus Rather than to the Disc Injury Per Se: An Experimental Study in Rats

Nilsson, Elin; Nakamae, Toshio; Olmarker, Kjell

doi:10.2174/1874325001105010072

Cited by 15 publications

(16 citation statements)

References 23 publications

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“…It was previously shown that posterior lumbar AF puncture could induce pain behavior changes in rats . A recent study further suggested that pain behavior changes might be related to the epidural presence of oozed nucleus pulposus (NP) in the posterior puncture model . In this study, anterior disc puncture did not significantly change spontaneous pain behavior.…”

mentioning

confidence: 45%

Both expression of cytokines and posterior annulus fibrosus rupture are essential for pain behavior changes induced by degenerative intervertebral disc: An experimental study in rats

Liu

Yang

et al. 2013

Journal Orthopaedic Research

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The aim of this study was to analyze the relationship between intervertebral disc degeneration and low back pain (LBP). Rat L4/5 disc degeneration model was established by annular puncture using a 0.4 mm needle anteriorly or posteriorly. In both anterior and posterior puncture models, magnetic resonance imaging (MRI) and histological analyses revealed marked disc degeneration 2 weeks after puncture. Cytokine expression was up-regulated in different level in nucleus pulposus (NP) from 3 days after puncture. Pain behavioral tests indicated that the anterior disc puncture did not induce pain behavior changes, whereas the posterior disc puncture resulted in mechanical allodynia from 1 day to 21 days after injury. Besides, cytokine expression was significantly increased in dorsal root ganglion (DRG) at 1 and 2 weeks after posterior puncture, but not after the anterior puncture. These findings indicate the NP of the degenerative disc expresses different levels of inflammatory cytokines, and posterior disc puncture produced mechanical allodynia. Keywords: intervertebral disc degeneration; low back pain; animal model; annulus fibrosus rupture; cytokine Low back pain (LBP) is a significant source of morbidity. Approximately 70% of the population experience LBP during their lives. 1 Although the exact cause of LBP is unclear, degeneration of intervertebral disc (IVD) is thought to drive LBP. 2,3 However, the relationship between intervertebral disc degeneration (IVDD) and LBP remains incompletely understood. Many patients with IVDD do not suffer from LBP. 4 Further investigation is needed to elucidate the relationship between IVDD and LBP.Inflammatory response plays an important role in the process of disc degeneration and LBP. Cytokines, such as tumor necrosis factor alpha (TNF-a), interleukin (IL)-1, and IL-6 are key factors associated with disc degeneration and LBP in human discs. [5][6][7] These inflammatory cytokines are involved in catabolic programs, angiogenesis, and nerve ingrowth in human discs. 8,9 However, the direct relationship between cytokine expression and pain symptoms is still unclear.Animal models are widely used to investigate the mechanisms underlying LBP and develop potential therapies. 10,11 IVD puncture models are popular among researchers, particularly posterior annulus fibrosus (AF) puncture and anterior AF puncture. It was previously shown that posterior lumbar AF puncture could induce pain behavior changes in rats. 12 A recent study further suggested that pain behavior changes might be related to the epidural presence of oozed nucleus pulposus (NP) in the posterior puncture model. 13 In this study, anterior disc puncture did not significantly change spontaneous pain behavior. The essential difference between posterior and anterior disc puncture is the location of the AF rupture. It seems that posterior AF rupture plays an important role in pain behavior changes in the rat disc puncture model.In the current study, we hypothesize that both expression of cytokines and posterior AF ruptu...

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mentioning

confidence: 45%

Both expression of cytokines and posterior annulus fibrosus rupture are essential for pain behavior changes induced by degenerative intervertebral disc: An experimental study in rats

Liu

Yang

et al. 2013

Journal Orthopaedic Research

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“…Behavior analysis demonstrated that application of nucleus pulposus is more likely to induce changes in grooming and "wet dog shakes" than the disc injury alone. 31 These findings suggest that the behavioral changes observed in rats with disc puncture are more likely related to the epidural presence of NP than the disc injury. This study also showed that ventral disc puncture did not induce any behavioral changes as compared with the sham exposure.…”

Section: Discogenic Pain Modelsmentioning

confidence: 92%

“…Olmarker et al 30,31 are the first to use spontaneous behavior analysis to assess pain discomfort in LBP models. In their studies, the behavioral test was conducted using a home cage monitoring for abnormal behaviors, including altered locomotor activity, rearing, grooming, bending, or “wet dog shaking” behaviors.…”

Section: Pain Assessments In Lbp Modelsmentioning

confidence: 99%

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Animal models for studying the etiology and treatment of low back pain

Shi

Qiu

Riester

et al. 2018

Journal Orthopaedic Research

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Chronic low back pain is a major cause of disability and health care costs. Effective treatments are inadequate for many patients. Animal models are essential to further understanding of the pain mechanism and testing potential therapies. Currently, a number of preclinical models have been developed attempting to mimic aspects of clinical conditions that contribute to low back pain (LBP). This review focused on describing these animal models and the main behavioral tests for assessing pain in each model. Animal models of LBP can be divided into the following five categories: Discogenic LBP, radicular back pain, facet joint osteoarthritis back pain, muscle-induced LBP, and spontaneous occurring LBP models. These models are important not only for enhancing our knowledge of how LBP is generated, but also for the development of novel therapeutic regimens to treat LBP in patients. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1305-1312, 2018.

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“…discussion Disc puncture, without deformation of spinal nervous tissue, can result in pain. [13][14][15] Microarrays have been used to profile expression of genes in the peripheral nervous system of rodents following a variety of neuropathic and inflammatory pain states. 16 In our study, RT-qPCR with TLDA was used to detect significant changes in expression of inflammationand pain-related genes: CYSLTR1, IL2RG, PLCB3, NOS1, and HTR2A.…”

Section: Figurementioning

confidence: 99%

Expression of Inflammation/Pain-Related Genes in the Dorsal Root Ganglion following Disc Puncture in Rats

Fujioka

Ståhlberg

Ochi

et al. 2016

J Orthop Surg (Hong Kong)

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Purpose.To determine the expression of inflammation-and pain-related genes at days 1 and 3 in the dorsal root ganglion (DRG) of rats with or without disc puncture, using real-time quantitative polymerase chain reaction (RT-qPCR) with the TaqMan low-density array (TLDA). Methods. 53 female Sprague-Dawley rats were used. The left facet joint between L4 and L5 was removed, and the DRG and intervertebral disc between the vertebrae were exposed. The L4-5 intervertebral disc was punctured using a 0.4-mm diameter injection needle (disc puncture group) or left unpunctured (sham group). After one or 3 days, the 53 DRGs were harvested, frozen, and assessed for expression of inflammation-related genes. Total RNA was isolated from the DRGs. Expression of 119 genes related to inflammation and pain in the DRG after disc puncture were analysed using RT-qPCR with the TLDA. Results. Of the 95 inflammation-related genes, 78 genes were reliably detected. Two genes were Expression of inflammation/pain-related genes in the dorsal root ganglion following disc puncture in rats significantly up-regulated: cysteinyl leukotriene receptor 1 (CYSLTR1) at day 3 and interleukin 2 receptor gamma (IL2RG) at day 1, and one gene was significantly down-regulated: phospholipase C beta 3 (PLCB3) at day 1. Of the 24 pain-related genes, 18 genes were reliably detected. Two genes were significantly up-regulated: nitric oxide synthase 1 (NOS1) at days 1 and 3 and 5-HT2A receptor (HTR2A) at day 1. Conclusion. Disc puncture may elicit changes in the expression of a variety of genes. Gene expression profiling is a useful tool for detecting new potential pharmaceutical targets for spinal pain syndromes.

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Pain Behavior Changes Following Disc Puncture Relate to Nucleus Pulposus Rather than to the Disc Injury Per Se: An Experimental Study in Rats

Cited by 15 publications

References 23 publications

Both expression of cytokines and posterior annulus fibrosus rupture are essential for pain behavior changes induced by degenerative intervertebral disc: An experimental study in rats

Both expression of cytokines and posterior annulus fibrosus rupture are essential for pain behavior changes induced by degenerative intervertebral disc: An experimental study in rats

Animal models for studying the etiology and treatment of low back pain

Expression of Inflammation/Pain-Related Genes in the Dorsal Root Ganglion following Disc Puncture in Rats

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