Analgesia with 5' extracellular nucleotidase-mediated electroacupuncture for neuropathic pain

ABSTRACT

Background: Acupuncture is a treatment for neuropathic pain, but its mechanism remains unclear. Previous studies showed that analgesia was induced in rats with neuropathic pain when their spinal cord adenosine content increased after electroacupuncture (EA); however, the mechanism behind this electroacupuncture-induced increase has not been clarified. Objective: This study aimed to determine the role that ecto-5’-nucleotidase plays in EA-induced analgesia for neuropathic pain. Methods: We performed electroacupuncture at the Zusanli acupoint on the seventh day after establishing a rat model of neuropathic pain induced through chronic constriction injuries. We observed the mechanical withdrawal threshold and thermal pain threshold and detected the expression of ecto-5’-nucleotidase in the spinal cord using Western blot. Chronic constriction injury rat models were intraperitoneally injected with α,β-methyleneadenosine 5'-diphosphate, an ecto-5’-nucleotidase inhibitor, 30 min before electroacupuncture. The adenosine content of the spinal cord was detected using high-performance liquid chromatography. Lastly, the adenosine A1 receptor agonist N6-cyclopentyladenosine was intrathecally injected into the lumbar swelling of the rats, and the mechanical withdrawal and thermal pain thresholds were reevaluated. Results: Analgesia and increased ecto-5’-nucleotidase expression and adenosine content in the spinal cord were observed 1 h after electroacupuncture. α,β-methyleneadenosine 5'-diphosphate was able to inhibit upregulation of adenosine content and electroacupuncture-induced analgesia. After administration of N6-cyclopentyladenosine, electroacupuncture-induced analgesia was restored. Conclusions: Our results suggest that electroacupuncture at Zusanli can produce analgesia in chronic constriction injury rat models, possibly via the increased ecto-5’-nucleotidase expression induced through electroacupuncture, thus leading to increased adenosine expression in the spinal cord.

RESUMO

Antecedentes: A acupuntura é um tratamento para a dor neuropática, mas seu mecanismo permanece obscuro. Estudos anteriores mostraram que a analgesia foi induzida em ratos com dor neuropática quando o conteúdo de adenosina da medula espinhal aumentou após a eletroacupuntura (EA); no entanto, o mecanismo por trás desse aumento induzido por eletroacupuntura não foi esclarecido. Objetivo: Este estudo teve como objetivo determinar o papel que a ecto-5'-nucleotidase desempenha na analgesia induzida por EA para dor neuropática. Métodos: Realizamos eletroacupuntura no ponto de acupuntura de Zusanli no sétimo dia após estabelecer um modelo de rato de dor neuropática induzida por lesão de constrição crônica. Observamos o limiar de retirada mecânica e o limiar de dor térmica, e detectamos a expressão de ecto-5'-nucleotidase na medula espinhal usando Western blot. Modelos de ratos com lesão de constrição crônica foram injetados intraperitonealmente com α, β-metilenadenosina 5'-difosfato, um inibidor de ecto-5'-nucleotidase, 30 min antes da eletroacupuntura. O conteúdo de adenosina da medula espinhal foi detectado por meio de cromatografia líquida de alta eficiência. Por último, o agonista do receptor de adenosina A1 N6-ciclopentiladenosina foi injetado por via intratecal no edema lombar dos ratos, e a retirada mecânica e os limiares de dor térmica foram reavaliados. Resultados: Analgesia e aumento da expressão de ecto-5'-nucleotidase e conteúdo de adenosina na medula espinhal foram observados 1 h após a eletroacupuntura. α, β-metilenadenosina 5'-difosfato foi capaz de inibir a sobrerregulação do conteúdo de adenosina e analgesia induzida por eletroacupuntura. Após administração de N6-ciclopentiladenosina, a analgesia induzida por eletroacupuntura foi restaurada. Conclusões: Nossos resultados sugerem que a eletroacupuntura em Zusanli pode produzir analgesia em modelos de ratos com lesão de constrição crônica, possivelmente por meio do aumento da expressão de ecto-5'-nucleotidase induzida por eletroacupuntura, levando ao aumento da expressão de adenosina na medula espinhal.

Keywords:

Electroacupuncture - Analgesia - 5'-nucleotidase - Neuralgia

Palavras-chave:

Eletroacupuntura - Analgesia - 5’-Nucleotidase - Neuralgia

Authors’ contributions:

QD: writing-original draft and writing-review & editing; SL: formal analysis and methodology; MR and XW: software; XY: validation and visualization; LF: investigation and validation; XN: data curation and formal analysis; YM: data curation and investigation; JW: resources and writing-review & editing.

Support

This work was supported by the Natural Science Foundation of Zhejiang Province of China, No. LY19H290008.

Publication History

Received: 16 April 2021

Accepted: 03 June 2021

Article published online:
30 January 2023

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