Maresin-2 inhibits inflammatory and neuropathic trigeminal pain and reduces neuronal activation in the trigeminal ganglion

Lopes, Raphael Vieira; Baggio, Darciane Favero; Ferraz, Camila R.; Bertozzi, Mariana M.; Saraiva-Santos, Telma; Verri, Waldiceu A.; Chichorro, Juliana Geremias

doi:10.1016/j.crneur.2023.100093

Cited by 8 publications

(8 citation statements)

References 44 publications

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“…Here, we show that homeostatic regulatory processes occur in medullary dorsal horn PNs during acute but not chronic pain. Although both types of injury lead to increased activity of the primary afferent 31,[33][34][35] (also see Supplementary Fig. 2), the excitability of medullary dorsal horn PNs reversibly decreases during acute inflammation but non-reversibly increases during chronic neuropathic nerve injury.…”

Section: Discussionmentioning

confidence: 96%

“…We examined the excitable properties of PNs in a model of chronic neuropathic pain, 2 -4 weeks after inducing a chronic constriction to the distal infraorbital branch of the trigeminal nerve (CCI-dION) when mice exhibited substantial ongoing pain and mechanical allodynia (Fig. 3b,c) accompanied with increased activity of TG neurons [33][34][35] . Unlike acute pain conditions, PNs of CCI-dION mice significantly increase their intrinsic excitability (Fig.…”

Section: The Excitability Of Pns Is Enhanced In Chronic Painmentioning

confidence: 99%

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Adaptation of pain-related projection neurons in acute but not chronic pain

Title,

Velasco,

Engelmayer

et al. 2024

Preprint

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Pain hypersensitivity is associated with increased activity of peripheral and central neurons along the pain neuroaxis. On the other hand, in other neuronal systems, increased activity leads to adaptive reduction of neuronal excitability to maintain homeostasis. Projection neurons (PNs) of spinal and medullary dorsal horns summate the activity of primary nociceptive and local central interneurons and convey it to higher centers. We show that at the peak of acute inflammatory pain, PNs reduce their intrinsic excitability and, consequently, action potential firing. When pain resolves, the excitability of PNs returns to baseline. Using electrophysiological and computational approaches, we found that an increase in potassium A-current (IA) underlies the decrease in the excitability of PNs in acute pain conditions. We hypothesized that an IA-induced decrease in PNs firing may restrain the output from the dorsal horn to prevent sensitization and pain chronification. Indeed, no changes of IA in PNs were observed in chronic pain conditions, and PNs exhibit increased intrinsic excitability and firing. Our results reveal an adaptive mechanism in acute pain conditions for regulating the output from the dorsal horn network, which, if interrupted, could trigger pain chronification.

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Section: Discussionmentioning

confidence: 96%

Section: The Excitability Of Pns Is Enhanced In Chronic Painmentioning

confidence: 99%

Adaptation of pain-related projection neurons in acute but not chronic pain

Title,

Velasco,

Engelmayer

et al. 2024

Preprint

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“…Functional analysis revealed that MaR2 promotes mucosal wound repair by driving intestinal epithelial migration through the activation of focal cell–matrix adhesion signaling in primary human intestinal epithelial cells [ 87 ]. In various orofacial pain models, MaR2 delivered via medullary subarachnoid injection significantly reduced phases I and II of orofacial formalin test in rats [ 129 ]. MaR2 also prevented the development of facial heat and mechanical hyperalgesia in post-operative rats [ 129 ].…”

Section: Maresinsmentioning

confidence: 99%

“…In various orofacial pain models, MaR2 delivered via medullary subarachnoid injection significantly reduced phases I and II of orofacial formalin test in rats [ 129 ]. MaR2 also prevented the development of facial heat and mechanical hyperalgesia in post-operative rats [ 129 ]. Additionally, in models of trigeminal neuropathic pain (CCI-ION), repeated MaR2 injections reversed facial heat and mechanical hyperalgesia while increasing both c-Fos + and CGRP + activated (nuclear pNF-κB) neurons in the trigeminal ganglion.…”

Section: Maresinsmentioning

confidence: 99%

“…Additionally, in models of trigeminal neuropathic pain (CCI-ION), repeated MaR2 injections reversed facial heat and mechanical hyperalgesia while increasing both c-Fos + and CGRP + activated (nuclear pNF-κB) neurons in the trigeminal ganglion. This study shows MaR2′s potent and long-lasting analgesic effects in inflammatory and neuropathic pain of orofacial origin [ 129 ].…”

Section: Maresinsmentioning

confidence: 99%

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Is Lipid Metabolism of Value in Cancer Research and Treatment? Part II: Role of Specialized Pro-Resolving Mediators in Inflammation, Infections, and Cancer

Babar,

Nassar,

Nie

et al. 2024

Metabolites

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Acute inflammation is the body’s first defense in response to pathogens or injury that is partially governed by a novel genus of endogenous lipid mediators that orchestrate the resolution of inflammation, coined specialized pro-resolving mediators (SPMs). SPMs, derived from omega-3-polyunstaturated fatty acids (PUFAs), include the eicosapentaenoic acid-derived and docosahexaenoic acid-derived Resolvins, Protectins, and Maresins. Herein, we review their biosynthesis, structural characteristics, and therapeutic effectiveness in various diseases such as ischemia, viral infections, periodontitis, neuroinflammatory diseases, cystic fibrosis, lung inflammation, herpes virus, and cancer, especially focusing on therapeutic effectiveness in respiratory inflammation and ischemia-related injuries. Resolvins are sub-nanomolar potent agonists that accelerate the resolution of inflammation by reducing excessive neutrophil infiltration, stimulating macrophage functions including phagocytosis, efferocytosis, and tissue repair. In addition to regulating neutrophils and macrophages, Resolvins control dendritic cell migration and T cell responses, and they also reduce the pro-inflammatory cytokines, proliferation, and metastasis of cancer cells. Importantly, several lines of evidence have demonstrated that Resolvins reduce tumor progression in melanoma, oral squamous cell carcinoma, lung cancer, and liver cancer. In addition, Resolvins enhance tumor cell debris clearance by macrophages in the tumor’s microenvironment. Resolvins, with their unique stereochemical structure, receptors, and biosynthetic pathways, provide a novel therapeutical approach to activating resolution mechanisms during cancer progression.

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Pro-resolving lipid mediators and therapeutic innovations in resolution of inflammation

Peh,

Chen

2025

Pharmacology & Therapeutics

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Maresin-2 inhibits inflammatory and neuropathic trigeminal pain and reduces neuronal activation in the trigeminal ganglion

Cited by 8 publications

References 44 publications

Adaptation of pain-related projection neurons in acute but not chronic pain

Adaptation of pain-related projection neurons in acute but not chronic pain

Is Lipid Metabolism of Value in Cancer Research and Treatment? Part II: Role of Specialized Pro-Resolving Mediators in Inflammation, Infections, and Cancer

Pro-resolving lipid mediators and therapeutic innovations in resolution of inflammation

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