Effects of Sciatic Nerve Axotomy on Excitatory Synaptic Transmission in Rat Substantia Gelatinosa

Chen, Yishen; Balasubramanyan, Sridhar; Lai, Aaron Y.; Todd, Kathryn G.; Smith, Peter A.

doi:10.1152/jn.00296.2009

Cited by 47 publications

(48 citation statements)

References 70 publications

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“…The remaining 16 pairs (9 inhibitory and 7 excitatory connections) were not included in this report, because of insufficient morphological and/or electrophysiological details. The electrophysiological features (RMPs, AP patterns, and AP frequency) of Gly, PKCγ + , and TC neurons sampled from both L4 and L5 spinal segments of SNL rats did not differ from those sampled from naive rats (P > 0.05; Supplemental Table 1), suggesting that nerve injury has little effect on the intrinsic excitability of Gly, PKCγ + , and TC neurons, which is consistent with previous studies (35,36). Thus, it is unlikely that mechanical allodynia in animals with SNL is a result of changes in membrane excitability or discharge pattern of these neurons.…”

Section: Paired Patch-clamp Recordings Identify Synaptic Connections supporting

confidence: 89%

A feed-forward spinal cord glycinergic neural circuit gates mechanical allodynia

Lü

Dong²,

Gao³

et al. 2013

J. Clin. Invest.

251

302

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Neuropathic pain is characterized by mechanical allodynia induced by low-threshold myelinated Aβ-fiber activation. The original gate theory of pain proposes that inhibitory interneurons in the lamina II of the spinal dorsal horn (DH) act as "gate control" units for preventing the interaction between innocuous and nociceptive signals. However, our understanding of the neuronal circuits underlying pain signaling and modulation in the spinal DH is incomplete. Using a rat model, we have shown that the convergence of glycinergic inhibitory and excitatory Aβ-fiber inputs onto PKCγ + neurons in the superficial DH forms a feed-forward inhibitory circuit that prevents Aβ input from activating the nociceptive pathway. This feed-forward inhibition was suppressed following peripheral nerve injury or glycine blockage, leading to inappropriate induction of action potential outputs in the nociceptive pathway by Aβ-fiber stimulation. Furthermore, spinal blockage of glycinergic synaptic transmission in vivo induced marked mechanical allodynia. Our findings identify a glycinergic feed-forward inhibitory circuit that functions as a gate control to separate the innocuous mechanoreceptive pathway and the nociceptive pathway in the spinal DH. Disruption of this glycinergic inhibitory circuit after peripheral nerve injury has the potential to elicit mechanical allodynia, a cardinal symptom of neuropathic pain.

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Section: Paired Patch-clamp Recordings Identify Synaptic Connections supporting

confidence: 89%

A feed-forward spinal cord glycinergic neural circuit gates mechanical allodynia

Lü

Dong²,

Gao³

et al. 2013

J. Clin. Invest.

251

302

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show abstract

“…4A) and a decreased excitatory drive to putative inhibitory tonic-firing neurons ( Fig. 4B) (Bailey and Ribeiro-da-Silva, 2006;Balasubramanyan et al, 2006;Chen et al, 2009;Lu et al, 2009). Both of these changes would be expected to produce an overall increase in dorsal horn excitability.…”

Section: Increased Excitatory Drive To Excitatory Neurons and Decrmentioning

confidence: 99%

Etiology and Pharmacology of Neuropathic Pain

Alles¹,

Smith²

2018

Pharmacol Rev

Self Cite

311

251

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“…10 The excitability is associated with a series of synaptic plasticity such as long-term potentiation of spinal synaptic transmission, 36,37 which might be related to synthesis of more presynaptic vesicle protein, synaptophysin. 47 Several studies that used synaptophysin to quantify the number of terminals during neuroanatomical remodeling found that an increase within the ipsilateral dorsal horn of a CCI model highly correlated with the severity of neuropathic pain behaviors.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of neurobehavior associated with histomorphological alterations in a chronic constrictive nerve injury model through use of the CatWalk XT system

Chiang

Sheu

Cheng

et al. 2014

JNS

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Object Neuropathic pain is debilitating, and when chronic, it significantly affects the patient physically, psychologically, and socially. The neurobehavior of animals used as a model for chronic constriction injury seems analogous to the neurobehavior of humans with neuropathic pain. However, no data depicting the severity of histomorphological alterations of the nervous system associated with graded changes in neurobehavior are available. To determine the severity of histomorphological alteration related to neurobehavior, the authors created a model of chronic constrictive injury of varying intensity in rats and used the CatWalk XT system to evaluate neurobehavior. Methods A total of 60 Sprague-Dawley rats, weighing 250–300 g each, were randomly assigned to 1 of 5 groups that would receive sham surgery or 1, 2, 3, or 4 ligatures of 3-0 chromic gut loosely ligated around the left sciatic nerve. Neurobehavior was assessed by CatWalk XT, thermal hyperalgesia, and mechanic allodynia before injury and periodically after injury. The nerve tissue from skin to dorsal spinal cord was obtained for histomorphological analysis 1 week after injury, and brain evoked potentials were analyzed 4 weeks after injury. Results. Significant differences in expression of nerve growth factor existed in skin, and the differences were associated with the intensity of nerve injury. After injury, expression of cluster of differentiation 68 and tumor necrosis factor–α was increased, and expression of S100 protein in the middle of the injured nerve was decreased. Increased expression of synaptophysin in the dorsal root ganglion and dorsal spinal cord correlated with the intensity of injury. The amplitude of sensory evoked potential increased with greater severity of nerve damage. Mechanical allodynia and thermal hyperalgesia did not differ significantly among treatment groups at various time points. CatWalk XT gait analysis indicated significant differences for print areas, maximum contact maximum intensity, stand phase, swing phase, single stance, and regular index, with sham and/or intragroup comparisons. Conclusions. Histomorphological and electrophysiological alterations were associated with severity of nerve damage. Subtle neurobehavioral differences were detected by the CatWalk XT system but not by mechanical allodynia or thermal hyperalgesia. Thus, the CatWalk XT system should be a useful tool for monitoring changes in neuropathic pain, especially subtle alterations.

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Effects of Sciatic Nerve Axotomy on Excitatory Synaptic Transmission in Rat Substantia Gelatinosa

Abstract: Effects of sciatic nerve axotomy on excitatory synaptic transmission in rat substantia gelatinosa.

Cited by 47 publications

References 70 publications

A feed-forward spinal cord glycinergic neural circuit gates mechanical allodynia

A feed-forward spinal cord glycinergic neural circuit gates mechanical allodynia

Etiology and Pharmacology of Neuropathic Pain

Comprehensive analysis of neurobehavior associated with histomorphological alterations in a chronic constrictive nerve injury model through use of the CatWalk XT system

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