Mas-related gene (Mrg) C receptors inhibit mechanical allodynia and spinal microglia activation in the early phase of neuropathic pain in rats

Wang, Dongmei; Xue, Ya‐Ping; Chen, Yajuan; Ruan, Liqin; Yu, Hong

doi:10.1016/j.neulet.2016.03.004

Cited by 9 publications

(1 citation statement)

References 43 publications

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“…Our results showed that nNOS protein was increased in DRG whether in the early or late stage of pathological pain following SNL. This is similar to previous reports [34][35][36]. Innovatively, single administration of AM 22−52 produced an immediate attenuation the expression of nNOS protein, suggesting that AM receptor signaling can recruit nNOS.…”

Section: Discussionsupporting

confidence: 92%

Adrenomedullin is an Important Pathological Mediator in Progression of Chronic Neuropathic Pain

Wang¹,

Xue²,

Lu³

et al. 2022

Front. Biosci. (Landmark Ed)

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Background:The characterization of neuropathic pain is maladaptive plasticity within the nociceptive system. Multiple alterations contribute to complex pain phenotypes. Adrenomedullin (AM) has been documented to be a pain mediator. However, its involvement in pathological pain is poorly understood. We studied the contribution of AM to chronic neuropathic pain in the spinal nerve ligation (SNL) model. Methods: Daily injection of the AM receptor antagonist AM22−52 (10 nmol) via an intrathecal (i.t.) route after SNL inhibited mechanical allodynia starting on day 6. Single administration of AM22−52 produced an immediate attenuation on pain hypersensitivity on day 2 or 10 post-SNL. Protein and mRNA levels were assayed by immunofluorescent staining and qRT-PCR, respectively, on days 1, 3, 7 and 15 post-SNL. Results: The results showed that AM at both protein and mRNA levels was increased in both injured (L5) and adjacent uninjured (L4) nerves starting on day 3 post-SNL. In dorsal root ganglion (DRG) at L5, AM was increase on days 1-7 at mRNA level but only on day 7 at protein level. However, AM was increase at mRNA level on days 1-7 and at protein level on days 3-15 in L4 DRG. AM mRNA expression was upregulated on days 1-7 in the spinal cord. Expression of receptor activity-modifying protein 2 (RAMP2), an essential AM1 receptor component, was upregulated in small and medium-diameter neurons on days 1-15 in both L5 and L4 DRG. Furthermore, single administration of AM22−52 suppressed the increase of nNOS in DRG induced by SNL and daily injection of AM22−52 for 7 days inhibited SNL-induced increase of CGRP mRNA in the spinal dorsal horn. Conclusions: This study indicates that the increased AM bioactivity in injured and uninjured peripheral nerves, uninjured adjacent DRG and the spinal dorsal horn play a critical role mainly in the late-phase development of neuropathic pain. The mechanism may involve the recruitment of nNOS and CGRP.

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Section: Discussionsupporting

confidence: 92%

Adrenomedullin is an Important Pathological Mediator in Progression of Chronic Neuropathic Pain

Wang¹,

Xue²,

Lu³

et al. 2022

Front. Biosci. (Landmark Ed)

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E3 Ubiquitin Ligase c-cbl Inhibits Microglia Activation After Chronic Constriction Injury

et al. 2018

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E3 ubiquitin ligase c-Caritas B cell lymphoma (c-cbl) is associated with negative regulation of receptor tyrosine kinases, signal transduction of antigens and cytokine receptors, and immune response. However, the expression and function of c-cbl in the regulation of neuropathic pain after chronic constriction injury (CCI) are unknown. In rat CCI model, c-cbl inhibited the activation of spinal cord microglia and the release of pro-inflammatory factors including tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β) and interleukin 6 (IL-6), which alleviated mechanical and heat pain through down-regulating extracellular signal-regulated kinase (ERK) pathway. Additionally, exogenous TNF-α inhibited c-cbl protein level vice versa. In the primary microglia transfected with c-cbl siRNA, when treated with TNF-α or TNF-α inhibitor, the corresponding secretion of IL-1β and IL-6 did not change. In summary, CCI down-regulated c-cbl expression and induced the activation of microglia, then activated microglia released inflammatory factors via ERK signaling to cause pain. Our data might supply a novel molecular target for the therapy of CCI-induced neuropathic pain.

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A Novel Mechanism of BAM8-22 Inhibiting Microglia Activation: Represses CX3CR1 Expression via Upregulating miR-184

et al. 2019

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Mas-related gene (Mrg) C receptors inhibit mechanical allodynia and spinal microglia activation in the early phase of neuropathic pain in rats

Cited by 9 publications

References 43 publications

Adrenomedullin is an Important Pathological Mediator in Progression of Chronic Neuropathic Pain

Adrenomedullin is an Important Pathological Mediator in Progression of Chronic Neuropathic Pain

E3 Ubiquitin Ligase c-cbl Inhibits Microglia Activation After Chronic Constriction Injury

A Novel Mechanism of BAM8-22 Inhibiting Microglia Activation: Represses CX3CR1 Expression via Upregulating miR-184

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