Excrescence of neurotransmitter glutamate from disc material has nociceptive qualities: evidence from a rat model

Osgood, Doreen; Kenney, Elizabeth V.; Harrington, William F.; Harrington, J. Frederick

doi:10.1016/j.spinee.2010.07.390

Cited by 6 publications

(4 citation statements)

References 45 publications

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“…Herein, gabapentin produced partial relief of primary and secondary mechanical hyperalgesia in the lumbar axial deep tissues at L1 and L4/L5 in LBP-10X rats. In work by others using a rat model of IVD injury, the extracellular glutamate concentration was markedly increased due to enzymatic breakdown of aggrecan in the disk cartilage extracellular matrix, and slow clearance of glutamate due the avascular nature of IVDs and their low rates of cellular metabolism (Osgood et al, 2010). A pronociceptive role for this IVD glutamate ‘reservoir’ may be underpinned by upregulated expression levels of glutamate receptors (NMDA and AMPA) in the lumbar DRGs (Osgood et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…In work by others using a rat model of IVD injury, the extracellular glutamate concentration was markedly increased due to enzymatic breakdown of aggrecan in the disk cartilage extracellular matrix, and slow clearance of glutamate due the avascular nature of IVDs and their low rates of cellular metabolism (Osgood et al, 2010). A pronociceptive role for this IVD glutamate ‘reservoir’ may be underpinned by upregulated expression levels of glutamate receptors (NMDA and AMPA) in the lumbar DRGs (Osgood et al, 2010). Whether expression levels of the α 2 δ 1 subunit of voltage-gated calcium channels in the lumbar DRGs and/or the spinal dorsal horn are also increased (Kim et al, 2011), remains for future investigation in our new model.…”

Section: Discussionmentioning

confidence: 99%

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Establishment and Characterization of a Novel Rat Model of Mechanical Low Back Pain Using Behavioral, Pharmacologic and Histologic Methods

et al. 2017

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Chronic low back pain (LBP), the leading cause of disability globally, is notoriously difficult to treat. Most rodent models of LBP mimic lumbar radicular pain rather than mechanical LBP. Here, we describe establishment of a new rat model of mechanical LBP that is devoid of a neuropathic component. Groups of adult male Sprague Dawley rats were anesthetized and their lumbar L4/L5 and L5/L6 intervertebral disks (IVDs) were punctured (0.5 mm outer diameter, 2mm-deep) 5 (LPB-5X), or 10 (LBP-10X) times per disk. Sham-rats underwent similar surgery, but without disk puncture. Baseline noxious pressure hyperalgesia of lumbar axial deep tissues, mechanical allodynia in the hindpaws and gait were assessed prior to surgery and once-weekly until study completion on day 49. The model was also characterized using pharmacologic and histologic methods. Good animal health was maintained for ≥ 49 days post-surgery. For LBP- but not sham-rats, there was temporal development of noxious pressure hyperalgesia in lumbar axial deep tissues at days 14–49 post-surgery. Importantly, there were no between-group differences in von Frey paw withdrawal thresholds or gait parameters until study completion. On day 49, significant histologic changes were observed in the L4/L5 and L5/L6 IVDs for LBP-10X rats, but not sham-rats. In LBP-10X rats, single bolus doses of morphine produced dose-dependent relief of primary and secondary mechanical hyperalgesia in lumbar axial deep tissues at L4/L5 and L1, respectively. In conclusion, our new rat model has considerable potential for providing novel insight on the pathobiology of mechanical LBP and for analgesic efficacy assessment of novel compounds.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Establishment and Characterization of a Novel Rat Model of Mechanical Low Back Pain Using Behavioral, Pharmacologic and Histologic Methods

et al. 2017

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“…Glutamic acid is an excitatory neurotransmitter, which on excess stimulation is known to cause seizures and many neuropsychic disorders [32]. Multiple studies have demonstrated their excrescence from herniated disc material and ability to have nociceptive effect on dorsal root ganglion of nerves [33]. Excessive glutamic acid production in CSF has been found in patients with bacterial infection.…”

Section: Ubiquitin Mediated Proteasome Degradation In Modic Changesmentioning

confidence: 99%

Modic changes are associated with activation of intense inflammatory and host defense response pathways – molecular insights from proteomic analysis of human intervertebral discs

et al. 2022

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“…Ionotropic kainate, N -Methyl-4-isoxazoleproionic acid (NMDA) and a-amino-3-hydroxy-5-methyl-4-isoxaleprionic acid (AMPA) have receptors implicated in peripheral nociception, and are present in the dorsal root ganglion cell bodies. [9102125] We have performed animal experiments to determine if blocking dorsal root ganglion (DRG) glutamate receptors with epidural ionotropic glutamate receptor antagonists could reduce glutamate induced focal nociception in the lower extremity.…”

Section: Introductionmentioning

confidence: 99%

The utility of ionotropic glutamate receptor antagonists in the treatment of nociception induced by epidural glutamate infusion in rats

Osgood

Harrington²,

Kenney³

et al. 2013

Surg Neurol Int

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Background:The authors have previously demonstrated that human herniated disc material contains high concentrations of free glutamate. In an experimental model, elevated epidural glutamate concentrations in the lumbar spine can cause a focal hyperesthetic state.Methods:Rats underwent epidural glutamate infusion in the lumbar spine by a miniosmotic pump over a 72-hour period. Some rats underwent coinfusion with glutamate and ionotropic glutamate antagonists. Nociception was assessed by von Frey fibers and by assessment of glutamate receptor expression in the corresponding dorsal horn of the spinal cord.Results:The kainic acid antagonist, UBP 301, decreased epidural glutamate-based hyperesthesia in a dose dependent manner. Concordant with these findings, there was significant decrease in kainate receptor expression in the dorsal horn. The N-Methyl-4-isoxazoleproionic acid (NMDA) antagonist Norketamine also significantly diminished hyperesthesia and decreased receptor expression in the dorsal horn.Conclusions:Both UBP 301, the kainic acid receptor antagonist and Norketamine, an NMDA receptor antagonist, dampened epidural glutamate-based nociception. Focal epidural injections of Kainate or NMDA receptor antagonists could be effective treatments for disc herniation-based lumbar radiculopathy.

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Excrescence of neurotransmitter glutamate from disc material has nociceptive qualities: evidence from a rat model

Cited by 6 publications

References 45 publications

Establishment and Characterization of a Novel Rat Model of Mechanical Low Back Pain Using Behavioral, Pharmacologic and Histologic Methods

Establishment and Characterization of a Novel Rat Model of Mechanical Low Back Pain Using Behavioral, Pharmacologic and Histologic Methods

Modic changes are associated with activation of intense inflammatory and host defense response pathways – molecular insights from proteomic analysis of human intervertebral discs

The utility of ionotropic glutamate receptor antagonists in the treatment of nociception induced by epidural glutamate infusion in rats

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