Electrical Stimulation of the Auricular Branch Vagus Nerve Using Random and Alternating Frequencies Triggers a Rapid Onset and Pronounced Antihyperalgesia via Peripheral Annexin A1-Formyl Peptide Receptor 2/ALX Pathway in a Mouse Model of Persistent Inflammatory Pain

Salm, Daiana Cristina; Horewicz, Verônica Vargas; Tanaka, Fernanda; Ferreira, Júlia Koerich; Oliveira, Bruna Hoffmann de; Maio, Júlia Maria Batista; Donatello, Nathalia Nahas; Lüdtke, Daniela Dero; Mazzardo-Martins, Leidiane; Dutra, Aline Raulino; Mack, Josiel Mileno; Kunzler, Deborah de Camargo Hizume; Cargnin-Ferreira, Eduardo; Salgado, Afonso Shiguemi Inoue; Bittencourt, Edsel B.; Bianco, Gianluca; Piovezan, Anna Paula; Bobinski, Franciane; Moré, Ari Ojeda Ocampo; Martins, Daniel Fernandes

doi:10.1007/s12035-023-03237-7

Cited by 7 publications

(5 citation statements)

References 111 publications

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“…To induce the peripheral inflammation model, the animals received an intraplantar injection of CFA (Complete Freund Adjuvant; Sigma-Aldrich, St. Louis, MO, USA) in a 50% solution, dissolved in saline solution and Tween ® 80. Each animal received 20 μl of this solution in the right hind paw 1 day before starting the treatment ( Salm et al, 2023 ).…”

Section: Methodsmentioning

confidence: 99%

“…The treatment times were 10, 20, and 30 min (min) and the intensity of 0.8 mA. The treatment was carried out for four consecutive days ( Salm et al, 2023 ).…”

Section: Methodsmentioning

confidence: 99%

“…Values were estimated by interpolating data using a standard curve for each cytokine by a colorimetric assay, which was measured at 450 nm (correction at 540 nm) in a spectrophotometer (Perlong DNM-9602, Nanjing Perlove Medical Equipment Co., Nanjing, China). Values obtained were expressed in picograms per milligram ( Salm et al, 2023 ).…”

Section: Methodsmentioning

confidence: 99%

“…Interestingly, these two therapies also contribute to pain relief ( Vina and Kwoh, 2018 ), inflammation reduction ( Nesbitt et al, 2015 ; Frangos and Komisaruk, 2017 ), and inflammation resolution ( Rosas-Ballina and Tracey, 2009 ). Our research group has previously shown that both the physical exercise of swimming and pVNS reduce the mechanical hyperalgesia caused by CFA alone ( Salm et al, 2023 ). However, the effect of combining the two vagal activation therapies, as has been done in clinical practice, has yet to be investigated.…”

Section: Introductionmentioning

confidence: 99%

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Electrical stimulation of the auricular branch of the vagus nerve potentiates analgesia induced by physical exercise in mice with peripheral inflammation

Dutra,

Salm,

da Silva

et al. 2023

Front. Integr. Neurosci.

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ObjectiveThis study evaluated the antihyperalgesic and anti-inflammatory effects of percutaneous vagus nerve electrical stimulation (pVNS) associated with physical exercise, i.e., swimming, in mice with peripheral inflammation.MethodsThe pain model was induced by intraplantar (i.pl.) injection of Freund’s complete adjuvant (CFA). Sixty-four male Swiss mice (35–40 g) received an i.pl. of CFA and underwent behavioral tests, i.e., mechanical hyperalgesia, edema, and paw temperature tests. Additionally, cytokine levels, specifically interleukin-6 (IL-6) and interleukin-10 (IL-10), were determined by enzyme-linked immunosorbent assay. Mice were treated with swimming exercise for 30 min alone or associated with different time protocols (10, 20, or 30 min) of stimulation in the left ear with random frequency during four consecutive days.ResultspVNS for 20 min prolonged the antihyperalgesic effect for up to 2 h, 24 h after CFA injection. pVNS for 30 min prolonged the antihyperalgesic effect for up to 7 h, 96 h after CFA injection. However, it did not alter the edema or temperature at both analyzed times (24 and 96 h). Furthermore, the combination of pVNS plus swimming exercise, but not swimming exercise alone, reduced IL-6 levels in the paw and spinal cord, as well as IL-10 levels in the spinal cord.ConclusionpVNS potentiates the analgesic effect induced by swimming, which may be, at least in part, mediated by the modulation of inflammatory cytokines in the periphery (paw) and central nervous system (spinal cord). Therefore, the combination of these therapies may serve as an important adjunctive treatment for persistent inflammatory pain.

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Section: Methodsmentioning

confidence: 99%

“…The treatment times were 10, 20, and 30 min (min) and the intensity of 0.8 mA. The treatment was carried out for four consecutive days ( Salm et al, 2023 ).…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Electrical stimulation of the auricular branch of the vagus nerve potentiates analgesia induced by physical exercise in mice with peripheral inflammation

Dutra,

Salm,

da Silva

et al. 2023

Front. Integr. Neurosci.

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“…In addition to sympathetic nerves, parasympathetic nerves are also involved in inflammatory pain. Transcutaneous vagus nerve electrical stimulation (tVNS) of the left ear for 10 min has a significant analgesic effect, and FPR2/ALX receptors participate in this effect [126] . By activating the sciatic and vagus nerves, electroacupuncture can reduce the release of joint neutrophils and systemic inflammatory factors and relieve inflammation and pain in mice with Lyme joint [109] .…”

Section: Animal Experiments Of Acupuncture Analgesia In the Autonomic...mentioning

confidence: 99%

Research Progress of Acupuncture Analgesia Based on Autonomic Nerve Regulation Pathway

Pang,

Chen,

Lan

et al. 2023

Acupuncture and Herbal Medicine

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The autonomic nervous system (ANS) includes the sympathetic, parasympathetic, and enteric nervous systems, and its senior regulatory center includes the brainstem, cingulate gyrus, and hypothalamus. Acupuncture can affect visceral, vascular, and glandular functions via the autonomic nervous regulatory pathway. In this paper, the relationship between pain and autonomic nervous function, the application of acupuncture guided by the autonomic nervous system, and the basis and clinical research on acupuncture analgesia are reviewed.

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Vía catecolaminérgica antiinflamatoria en pulpa dental y su relación con el control del dolor durante el manejo complementario con electroacupuntura: un estudio de cohorte

Castro-Gutiérrez

Argueta-Figueroa

Bautista-Hernández

et al. 2023

Revista Internacional de Acupuntura

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Electrical Stimulation of the Auricular Branch Vagus Nerve Using Random and Alternating Frequencies Triggers a Rapid Onset and Pronounced Antihyperalgesia via Peripheral Annexin A1-Formyl Peptide Receptor 2/ALX Pathway in a Mouse Model of Persistent Inflammatory Pain

Cited by 7 publications

References 111 publications

Electrical stimulation of the auricular branch of the vagus nerve potentiates analgesia induced by physical exercise in mice with peripheral inflammation

Electrical stimulation of the auricular branch of the vagus nerve potentiates analgesia induced by physical exercise in mice with peripheral inflammation

Research Progress of Acupuncture Analgesia Based on Autonomic Nerve Regulation Pathway

Vía catecolaminérgica antiinflamatoria en pulpa dental y su relación con el control del dolor durante el manejo complementario con electroacupuntura: un estudio de cohorte

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