Peripheral nerve injury increases contribution of L-type calcium channels to synaptic transmission in spinal lamina II: Role of α2δ–1 subunits

Alles, Sascha R.A.; Garcı́a, Esperanza; Balasubramanyan, Sridhar; Jones, Karen L.; Tyson, John R.; Joy, Twinkle; Snutch, Terrance P.; Smith, Peter A.

doi:10.1177/1744806918765806

Cited by 17 publications

(15 citation statements)

References 51 publications

(75 reference statements)

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“…KEGG pathway analyses show that these differential mRNAs enriched into 32 KEGG pathways, including TNF, cytokine–cytokine receptor interaction, calcium signaling, and FoxO pathway. The TNF,44,45 cytokine,8,43,46 and calcium-related pathway47,48 contribute to neuropathic pain development in the dorsal spinal cord. Although FoxO has not been confirmed to take part in the neuropathic pain, bioinformatics predicted that FoxO pathway in the dorsal spinal cord37 or dorsal root ganglion49 was related to neuropathic pain.…”

Section: Discussionmentioning

confidence: 99%

<p>Transcriptome Changes In Dorsal Spinal Cord Of Rats With Neuropathic Pain</p>

Cao

Yuan

Zhang

et al. 2019

JPR

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BackgroundMechanisms of neuropathic pain are not fully understood. Molecular changes in spinal dorsal horn take part in the initiation and development of neuropathic pain.MethodsTo detect the transcriptome changes in the dorsal spinal cord of neuropathic pain rat, sciatic nerve chronic constriction injury (CCI) rats were used. Then, the CCI ipsilateral dorsal spinal cords of lumbar L3-L5 segments were collected at 14th day post-CCI and subjected to microRNA and long non-coding RNA (lncRNA)/mRNA microarray. To evaluate functions of differential mRNAs, bioinformatics methods including gene ontology (GO) and KEGG pathway analysis were conducted for significantly up- and downregulated mRNAs.ResultsMicroRNA microarrays showed that 13 microRNAs were differently expressed between CCI and sham-operated rats (fold change ≥ 2.0). Six of them were upregulated, and the other seven were downregulated in CCI group. MicroRNA-1b overexpressed 18.7 times after CCI. LncRNA/mRNA microarray detected 876 lncRNAs with significant differential expression (fold change ≥ 2.0). Among them, 339 were significantly upregulated, and 537 were downregulated in CCI group. Sixteen of them differentially expressed more than 10 times and the lncRNA XR_356687 overexpressed as high as 53 times. In addition, 950 mRNAs were differentially expressed (fold change ≥ 2.0), including 405 upregulated and 545 downregulated in CCI group. Ten of these mRNAs with changed expressions of more than 10 times. The Hspa1b (encodes heat shock protein 70) overexpressed 24 times in CCI rats. Gene ontology analysis revealed that hundreds of differentially expressed mRNAs involved in the biological processes, cellular component, and molecular function. In addition, these genes significantly enriched into 32 KEGG pathways, including the TNF, FoxO, cytokine–cytokine receptor interaction, and calcium signaling pathways.ConclusionNeuropathic pain induced comprehensive changes of transcription profile in the dorsal spinal cord. These differentially expressed transcripts in spinal cord could be potential targets in defeating neuropathic pain.

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Section: Discussionmentioning

confidence: 99%

<p>Transcriptome Changes In Dorsal Spinal Cord Of Rats With Neuropathic Pain</p>

Cao

Yuan

Zhang

et al. 2019

JPR

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“…As L-type channels are widely distributed in cells that participate in the pain pathway, previous studies have also examined the role of these channels [1, 38, 41]. Increased L-type channels in spinal cord lamina II mediate hyperalgesia in rats in a chronic constriction injury (CCI) model [1]. Lack expression of L-type channels in the anterior cingulate cortex of mice correlates with pain relief [23].…”

Section: Discussionmentioning

confidence: 99%

“…For example, in one animal model of chronic pain, the chronic constriction injury (CCI) model, up-regulation of L-type channels markedly decreases the pain threshold in rats. Moreover, use of L-type calcium channel blockers reduces the frequency of spontaneous excitatory postsynaptic currents, thereby providing relief from pain [1]. Thus, if we overexpressed the L-type channels in the DRG, the rats would likely remain in a constant state of hyperalgesia, and this could be difficult to distinguish from postsurgical pain.…”

Section: Discussionmentioning

confidence: 99%

Sleep deprivation of rats increases postsurgical expression and activity of L-type calcium channel in the dorsal root ganglion and slows recovery from postsurgical pain

Zhu

et al. 2019

acta neuropathol commun

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Perioperative sleep disturbance is a risk factor for persistent pain after surgery. Clinical studies have shown that patients with insufficient sleep before and after surgery experience more intense and long-lasting postoperative pain. We hypothesize that sleep deprivation alters L-type calcium channels in the dorsal root ganglia (DRG), thus delaying the recovery from post-surgical pain. To verify this hypothesis, and to identify new predictors and therapeutic targets for persistent postoperative pain, we first established a model of postsurgical pain with perioperative sleep deprivation (SD) by administering hind paw plantar incision to sleep deprivation rats. Then we conducted behavioral tests, including tests with von Frey filaments and a laser heat test, to verify sensory pain, measured the expression of L-type calcium channels using western blotting and immunofluorescence of dorsal root ganglia (an important neural target for peripheral nociception), and examined the activity of L-type calcium channels and neuron excitability using electrophysiological measurements. We validated the findings by performing intraperitoneal injections of calcium channel blockers and microinjections of dorsal root ganglion cells with adeno-associated virus. We found that short-term sleep deprivation before and after surgery increased expression and activity of L-type calcium channels in the lumbar dorsal root ganglia, and delayed recovery from postsurgical pain. Blocking these channels reduced impact of sleep deprivation. We conclude that the increased expression and activity of L-type calcium channels is associated with the sleep deprivation-mediated prolongation of postoperative pain. L-type calcium channels are thus a potential target for management of postoperative pain.

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“…Cytosolic calcium overload causes mitochondrial oxidative stress (Dryanovski et al, 2013) and subsequent redox modification of ATP-sensitive potassium channels (K-ATP) (Knowlton et al, 2018) that control the spontaneous tonic pacemaker activity (Liss et al, 2001, 2005; Schiemann et al, 2012), which may lead into a vicious cycle. Although nociceptive neurons are not spontaneously active, L-, N- and T-type voltage-gated calcium channels and K-ATP essentially contribute to the enhancement (calcium channels) (Alles et al, 2018; Candelas et al, 2019; Choi et al, 2016; Neugebauer et al, 1996) or lowering (K-ATP) of nociceptive neuron excitability (Kawano et al, 2009; Rodrigues and Duarte, 2000).…”

Section: Nociceptive Neurons In Pdmentioning

confidence: 99%

Sensory neuropathy and nociception in rodent models of Parkinson's disease

Valek

Auburger

Tegeder

2019

Disease Models &Amp; Mechanisms

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Parkinson's disease (PD) often manifests with prodromal pain and sensory losses whose etiologies are not well understood. Multiple genetic and toxicity-based rodent models of PD partly recapitulate the histopathology and motor function deficits. Although far less studied, there is some evidence that rodents, similar to humans, develop sensory manifestations of the disease, which may precede motor disturbances and help to elucidate the underlying mechanisms of PD-associated pain at the molecular and neuron circuit levels. The present Review summarizes nociception and other sensory functions in frequently used rodent PD models within the context of the complex phenotypes. In terms of mechanisms, it appears that the acute loss of dopaminergic neurons in systemic toxicity models (MPTP, rotenone) primarily causes nociceptive hyperexcitability, presumably owing to a loss of inhibitory control, whereas genetic models primarily result in a progressive loss of heat perception, reflecting sensory fiber neuropathies. At the molecular level, neither α-synuclein deposits alone nor failure of mitophagy alone appear to be strong enough to result in axonal or synaptic pathology of nociceptive neurons that manifest at the behavioral level, and peripheral sensory loss may mask central ‘pain’ in behavioral tests. Hence, allostatic combinations or additional challenges and novel behavioral assessments are needed to better evaluate PD-associated sensory neuropathies and pain in rodents.

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Peripheral nerve injury increases contribution of L-type calcium channels to synaptic transmission in spinal lamina II: Role of α2δ–1 subunits

Cited by 17 publications

References 51 publications

<p>Transcriptome Changes In Dorsal Spinal Cord Of Rats With Neuropathic Pain</p>

<p>Transcriptome Changes In Dorsal Spinal Cord Of Rats With Neuropathic Pain</p>

Sleep deprivation of rats increases postsurgical expression and activity of L-type calcium channel in the dorsal root ganglion and slows recovery from postsurgical pain

Sensory neuropathy and nociception in rodent models of Parkinson's disease

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