Electrophysiological properties of spinal wide dynamic range neurons in neuropathic pain rats following spinal nerve ligation

Liu, Fengyu; Qu, Xiao-Xiu; Cai, Jie; Wang, Fa-Tian; Xing, Guo-Gang; Wan, You

doi:10.1007/s12264-011-1039-z

Cited by 18 publications

(14 citation statements)

References 37 publications

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“…As we observed (Figure 8b), an increase in WDR neurons is accompanied by a decrease in LTM neurons for cases of chronic allodynia after spinal cord injury (Hao et al, 2004). This supports the growing evidence that WDR neurons mediate neuropathic pain (Hao et al, 2004;Nishigami et al, 2009;Quinn et al, 2010;Liu et al, 2011). An increase in the percentage of WDR neurons in the superficial laminae indicates a potential increase in the number of neurons in that region of the dorsal horn that respond to noxious stimuli, which may augment afferent signaling and facilitate nociception (Hains et al, 2003;Quinn et al, 2010).…”

Section: Discussionsupporting

confidence: 85%

The Roles of Mechanical Compression and Chemical Irritation in Regulating Spinal Neuronal Signaling in Painful Cervical Nerve Root Injury

Zhang

Nicholson

Smith

et al. 2013

SAE Technical Paper Series

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Both traumatic and slow-onset disc herniation can directly compress and/or chemically irritate cervical nerve roots, and both types of root injury elicit pain in animal models of radiculopathy. This study investigated the relative contributions of mechanical compression and chemical irritation of the nerve root to spinal regulation of neuronal activity using several outcomes. Modifications of two proteins known to regulate neurotransmission in the spinal cord, the neuropeptide calcitonin gene-related peptide (CGRP) and glutamate transporter 1 (GLT-1), were assessed in a rat model after painful cervical nerve root injuries using a mechanical compression, chemical irritation or their combination of injury. Only injuries with compression induced sustained behavioral hypersensitivity (p≤0.05) for two weeks and significant decreases (p<0.037) in CGRP and GLT-1 immunoreactivity to nearly half that of sham levels in the superficial dorsal horn. Because modification of spinal CGRP and GLT-1 is associated with enhanced excitatory signaling in the spinal cord, a second study evaluated the electrophysiological properties of neurons in the superficial and deeper dorsal horn at day 7 after a painful root compression. The evoked firing rate was significantly increased (p=0.045) after compression and only in the deeper lamina. The painful compression also induced a significant (p=0.002) shift in the percentage of neurons in the superficial lamina classified as lowthreshold mechanoreceptive (sham 38%; compression 10%) to those classified as wide dynamic range neurons (sham 43%; compression 74%). Together, these studies highlight mechanical compression as a key modulator of spinal neuronal signaling in the context of radicular injury and pain.

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Section: Discussionsupporting

confidence: 85%

The Roles of Mechanical Compression and Chemical Irritation in Regulating Spinal Neuronal Signaling in Painful Cervical Nerve Root Injury

Zhang

Nicholson

Smith

et al. 2013

SAE Technical Paper Series

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“…7,14,28,48,51 Therefore, the elevated expression of CGRP in the deep dorsal horn after a painful nerve root compression likely contributed to the neuronal hyperexcitability and the shift in the phenotypic properties observed in this same region (Figs. 3, 5, and 6).…”

Section: Discussionmentioning

confidence: 99%

“…33,36,41,51 Sensitization of wide dynamic range (WDR) neurons, in particular, is thought to drive neuronal hyperexcitability and behavioral sensitivity after spinal cord ischemia and spinal nerve ligation. 28,48 Although increased calcitonin gene-related peptide (CGRP) and associated signaling contribute to neuronal hyperexcitability after painful neural trauma, 7,51 painful root compression decreases CGRP in the superficial dorsal horn. 32,40 No study has evaluated CGRP expression in the deep laminae, despite the known involvement of neurons in that region of the dorsal horn in pain from peripheral nerve injuries.…”

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confidence: 99%

Riluzole effects on behavioral sensitivity and the development of axonal damage and spinal modifications that occur after painful nerve root compression

Nicholson

Zhang

Gilliland

et al. 2014

SPI

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Object Cervical radiculopathy is often attributed to cervical nerve root injury, which induces extensive degeneration and reduced axonal flow in primary afferents. Riluzole inhibits neuro-excitotoxicity in animal models of neural injury. The authors undertook this study to evaluate the antinociceptive and neuroprotective properties of riluzole in a rat model of painful nerve root compression. Methods A single dose of riluzole (3 mg/kg) was administered intraperitoneally at Day 1 after a painful nerve root injury. Mechanical allodynia and thermal hyperalgesia were evaluated for 7 days after injury. At Day 7, the spinal cord at the C-7 level and the adjacent nerve roots were harvested from a subgroup of rats for immunohistochemical evaluation. Nerve roots were labeled for NF200, CGRP, and IB4 to assess the morphology of myelinated, peptidergic, and nonpeptidergic axons, respectively. Spinal cord sections were labeled for the neuropeptide CGRP and the glutamate transporter GLT-1 to evaluate their expression in the dorsal horn. In a separate group of rats, electrophysiological recordings were made in the dorsal horn. Evoked action potentials were identified by recording extracellular potentials while applying mechanical stimuli to the forepaw. Results Even though riluzole was administered after the onset of behavioral sensitivity at Day 1, its administration resulted in immediate resolution of mechanical allodynia and thermal hyperalgesia (p < 0.045), and these effects were maintained for the study duration. At Day 7, axons labeled for NF200, CGRP, and IB4 in the compressed roots of animals that received riluzole treatment exhibited fewer axonal swellings than those from untreated animals. Riluzole also mitigated changes in the spinal distribution of CGRP and GLT-1 expression that is induced by a painful root compression, returning the spinal expression of both to sham levels. Riluzole also reduced neuronal excitability in the dorsal horn that normally develops by Day 7. The frequency of neuronal firing significantly increased (p < 0.045) after painful root compression, but riluzole treatment maintained neuronal firing at sham levels. Conclusions These findings suggest that early administration of riluzole is sufficient to mitigate nerve root–mediated pain by preventing development of neuronal dysfunction in the nerve root and the spinal cord.

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“…Von Frey filaments (0.41-15.1 g; North Coast, Gilroy, CA) were applied to the lateral plantar surface of the hind paws (i.e., to the receptive field of the sural nerve). The 50% PWT was calculated by the ''up and down'' method as described by Chaplan et al [26][27][28][29]. These behavioral tests were designed and carried out single-blindly.…”

Section: Mechanical Allodynia Measured As 50% Paw Withdrawal Thresholmentioning

confidence: 99%

Elevated Neurosteroids in the Lateral Thalamus Relieve Neuropathic Pain in Rats with Spared Nerve Injury

et al. 2016

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Neurosteroids are synthesized in the nervous system from cholesterol or steroidal precursors imported from peripheral sources. These compounds are important allosteric modulators of c-aminobutyric acid A receptors (GABA A Rs), which play a vital role in pain modulation in the lateral thalamus, a main gate where somatosensory information enters the cerebral cortex. Using high-performance liquid chromatography/tandem mass spectrometry, we found increased levels of neurosteroids (pregnenolone, progesterone, deoxycorticosterone, allopregnanolone, and tetrahydrodeoxycorticosterone) in the chronic stage of neuropathic pain (28 days after spared nerve injury) in rats.The expression of the translocator protein TSPO, the upstream steroidogenesis rate-limiting enzyme, increased at the same time. In vivo stereotaxic microinjection of neurosteroids or the TSPO activator AC-5216 into the lateral thalamus (AP -3.0 mm, ML ±3.0 mm, DV 6.0 mm) alleviated the mechanical allodynia in neuropathic pain, while the TSPO inhibitor PK 11195 exacerbated it. The analgesic effects of AC-5216 and neurosteroids were significantly attenuated by the GABA A R antagonist bicuculline. These results suggested that elevated neurosteroids in the lateral thalamus play a protective role in the chronic stage of neuropathic pain.

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Electrophysiological properties of spinal wide dynamic range neurons in neuropathic pain rats following spinal nerve ligation

Cited by 18 publications

References 37 publications

The Roles of Mechanical Compression and Chemical Irritation in Regulating Spinal Neuronal Signaling in Painful Cervical Nerve Root Injury

The Roles of Mechanical Compression and Chemical Irritation in Regulating Spinal Neuronal Signaling in Painful Cervical Nerve Root Injury

Riluzole effects on behavioral sensitivity and the development of axonal damage and spinal modifications that occur after painful nerve root compression

Elevated Neurosteroids in the Lateral Thalamus Relieve Neuropathic Pain in Rats with Spared Nerve Injury

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