Lysophosphatidylcholine causes neuropathic pain via the increase of neuronal nitric oxide synthase in the dorsal root ganglion and cuneate nucleus

Wang, Hsin Ying; Tsai, Yi Ju; Chen, Seu Hwa; Lin, Chi Te; Lue, June‐Horng

doi:10.1016/j.pbb.2013.03.002

Cited by 25 publications

(17 citation statements)

References 47 publications

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“…Metabolites in Table 2 were input into Metaboanalyst and the metabolic networks were depicted (Figure 4B ). The result showed that paclitaxel primarily disturbed the LA metabolism (impact 1.0) and glycerophospholipid metabolism (impact 0.18), which was in accord with published literatures (Patwardhan et al, 2010 ; Wang et al, 2013 ; Sisignano et al, 2016 ). And LA metabolism was considered as a preferred target pathway of paclitaxel due to its significant impact score.…”

Section: Resultssupporting

confidence: 89%

Wen-Luo-Tong Decoction Attenuates Paclitaxel-Induced Peripheral Neuropathy by Regulating Linoleic Acid and Glycerophospholipid Metabolism Pathways

Deng

et al. 2018

Front. Pharmacol.

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Chemotherapy-induced peripheral neuropathy (CIPN) is a serious dose-limiting toxicity of many anti-neoplastic agents, especially paclitaxel, and oxaliplatin. Up to 62% of patients receiving paclitaxel regimens turn out to develop CIPN. Unfortunately, there are so few agents proved effective for prevention or management of CIPN. The reason for the current situation is that the mechanisms of CIPN are still not explicit. Traditional Chinese Medicine (TCM) has unique advantages for dealing with complex diseases. Wen-Luo-Tong (WLT) is a TCM ointment for topical application. It has been applied for prevention and management of CIPN clinically for more than 10 years. Previous animal experiments and clinical studies had manifested the availability of WLT. However, due to the unclear mechanisms of WLT, further transformation has been restricted. To investigate the therapeutic mechanisms of WLT, a metabolomic method on the basis of UPLC- MS was developed in this study. Multivariate analysis techniques, such as principal component analysis (PCA) and partial least squares discriminate analysis (PLS-DA), were applied to observe the disturbance in the metabolic state of the paclitaxel-induced peripheral neuropathy (PIPN) rat model, as well as the recovering tendency of WLT treatment. A total of 19 significant variations associated with PIPN were identified as biomarkers. Results of pathway analysis indicated that the metabolic disturbance of pathways of linoleic acid (LA) metabolism and glycerophospholipid metabolism. WLT attenuated mechanical allodynia and rebalanced the metabolic disturbances of PIPN by primarily regulating LA and glycerophospholipid metabolism pathway. Further molecular docking analysis showed some ingredients of WLT, such as hydroxysafflor yellow A (HSYA), icariin, epimedin B and 4-dihydroxybenzoic acid (DHBA), had high affinity to plenty of proteins within these two pathways.

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Section: Resultssupporting

confidence: 89%

Wen-Luo-Tong Decoction Attenuates Paclitaxel-Induced Peripheral Neuropathy by Regulating Linoleic Acid and Glycerophospholipid Metabolism Pathways

Deng

et al. 2018

Front. Pharmacol.

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“…Previous studies of neuropathic pain using lipidomic approach have mainly focused on PG which is rich in fatty acids and strongly contributes to the development of neuropathic pain [4]. Recently, phospholipids such as lysophosphatidylinositol and lysophosphatidylcholine were found to be also modulators of neuropathic pain [35, 36]. …”

Section: Discussionmentioning

confidence: 99%

Arachidonic acid containing phosphatidylcholine increases due to microglial activation in ipsilateral spinal dorsal horn following spared sciatic nerve injury

et al. 2017

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Peripheral nerve injury induces substantial molecular changes in the somatosensory system that leads to maladaptive plasticity and cause neuropathic pain. Understanding the molecular pathways responsible for the development of neuropathic pain is essential to the development of novel rationally designed therapeutics. Although lipids make up to half of the dry weight of the spinal cord, their relation with the development of neuropathic pain is poorly understood. We aimed to elucidate the regulation of spinal lipids in response to neuropathic peripheral nerve injury in mice by utilizing matrix-assisted laser desorption/ionization imaging mass spectrometry, which allows visualization of lipid distribution within the cord. We found that arachidonic acid (AA) containing

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“…In rats, NOS expression was higher than controls in DRG neurons after axotomy (Fiallos-Estrada et al, 1993;Shi et al, 1998;Verge, Xu, Xu, Wiesenfeld-Hallin, & Hokfelt, 1992) or visceral inflammation (Callsen-Cencic & Mense, 1997). It was proposed that NO can contribute to the excitation of sensory neurons and to pain (Cairns et al, 2014;Steel et al, 1994;Wang, Tsai, Chen, Lin, & Lue, 2013), but the underlying mechanisms have not been clarified. Afferent firing or excitatory transmitters such as calcitonin gene-related peptide (CGRP; Li, Vause, & Durham, 2008) or ATP (Borsani et al, 2010) raise intracellular Ca 2+ ([Ca 2+ ] in ) in sensory neurons, which in turn induces NOS activation and NO production.…”

Section: Introductionmentioning

confidence: 99%

Nitric oxide as a messenger between neurons and satellite glial cells in dorsal root ganglia

Belzer

Hanani

2019

Glia

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Abnormal neuronal activity in sensory ganglia contributes to chronic pain. There is evidence that signals can spread between cells in these ganglia, which may contribute to this activity. Satellite glial cells (SGCs) in sensory ganglia undergo activation following peripheral injury and participate in cellular communication via gap junctions and chemical signaling. Nitric oxide (NO) is released from neurons in dorsal root ganglia (DRG) and induces cyclic GMP (cGMP) production in SCGs, but its role in SGC activation and neuronal excitability has not been explored. It was previously reported that induction of intestinal inflammation with dinitrobenzoate sulfonate (DNBS) increased gap junctional communications among SGCs, which contributed to neuronal excitability and pain. Here we show that DNBS induced SGC activation in mouse DRG, as assayed by glial fibrillary acidic protein upregulation. DNBS also upregulated cGMP level in SGCs, consistent with NO production. In vitro studies on intact ganglia from DNBS‐treated mice showed that blocking NO synthesis inhibited both SGCs activation and cGMP upregulation, indicating an ongoing NO production. Application of NO donor in vitro induced SGC activation, augmented gap junctional communications, and raised neuronal excitability, as assessed by electrical recordings. The cGMP analog 8‐Br‐cGMP mimicked these actions, confirming the role of the NO‐cGMP pathway in intraganglionic communications. NO also augmented Ca2+ waves propagation in DRG cultures. It is proposed that NO synthesis in DRG neurons increases after peripheral inflammation and that NO induces SGC activation, which in turn contributes to neuronal hyperexcitability. Thus, NO plays a major role in neuron–SGC communication.

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Lysophosphatidylcholine causes neuropathic pain via the increase of neuronal nitric oxide synthase in the dorsal root ganglion and cuneate nucleus

Cited by 25 publications

References 47 publications

Wen-Luo-Tong Decoction Attenuates Paclitaxel-Induced Peripheral Neuropathy by Regulating Linoleic Acid and Glycerophospholipid Metabolism Pathways

Wen-Luo-Tong Decoction Attenuates Paclitaxel-Induced Peripheral Neuropathy by Regulating Linoleic Acid and Glycerophospholipid Metabolism Pathways

Arachidonic acid containing phosphatidylcholine increases due to microglial activation in ipsilateral spinal dorsal horn following spared sciatic nerve injury

Nitric oxide as a messenger between neurons and satellite glial cells in dorsal root ganglia

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