Pflügers Archiv - European Journal of Physiology

, Volume 470, Issue 12, pp 1815–1827 | Cite as

Electroacupuncture induces antihyperalgesic effect through endothelin-B receptor in the chronic phase of a mouse model of complex regional pain syndrome type I

  • Leidiane Mazzardo-Martins
  • Daiana Cristina Salm
  • Elisa C. Winkelmann-Duarte
  • Júlia Koerich Ferreira
  • Daniela Dero Lüdtke
  • Kamilla Pamplona Frech
  • Luiz Augusto Oliveira Belmonte
  • Verônica Vargas Horewicz
  • Anna Paula Piovezan
  • Francisco José Cidral-Filho
  • Ari Ojeda Ocampo Moré
  • Daniel Fernandes MartinsEmail author
Part of the following topical collections:
  1. Neuroscience


Complex regional pain syndrome (CRPS) is a disorder that involves abnormal inflammation and nerve dysfunction frequently resistant to a broad range of treatments. Peripheral nerve stimulation with electroacupuncture (EA) has been widely used in different clinical conditions to control pain and inflammation; however, the use of EA in the treatment of CRPS is under investigation. In this study, we explore the effects of EA on hyperalgesia and edema induced in an animal model of chronic post-ischemia pain (CPIP model) and the possible involvement of endothelin receptor type B (ETB) in this effect. Female Swiss mice were subjected to 3 h hind paw ischemia/reperfusion CPIP model. EA treatment produced time-dependent inhibition of mechanical and cold hyperalgesia, as well as edema in CPIP mice. Peripheral administration ( of BQ-788 (10 nmol), an ETB antagonist, prevented EA-induced antihyperalgesia while intrathecal administration prolonged EA’s effect. Additionally, peripheral pre-treatment with sarafotoxin (SRTX S6c, 30 pmol, ETB agonist) increased EA anti-hyperalgesic effect. Furthermore, the expression of peripheral ETB receptors was increased after EA treatments, as measured by western blot. These results may suggest that EA’s analgesic effect is synergic with ETB receptor activation in the periphery, as well as central (spinal cord) ETB receptor blockade. These data support the use of EA as a nonpharmacological approach for the management of CRPS-I, in an adjuvant manner to ETB receptor targeting drugs.


Chronic pain Chronic post-ischemia pain Neuropathic pain Sanyinjiao (SP6) Zusanli (ST36) 


Sources of funding

The present study was supported by grants from Universidade do Sul de Santa Catarina—Curso de Medicina and Programa Unisul de Iniciação Científica (PUIC), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq - 476454/2013-1), and Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina (FAPESC-3414/2012), Brazil.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

424_2018_2192_MOESM1_ESM.jpg (120 kb)
Figure S1 EA does not affect locomotive activity. Effect of cumulative treatment with EA from day 7 to 14 after IR upon locomotive activity. Data were expressed as mean ± standard deviation (SD) (n = 8 animals). EA: electroacupuncture; IR: ischemia and reperfusion. (JPG 120 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018
corrected publication September/2018

Authors and Affiliations

  • Leidiane Mazzardo-Martins
    • 1
    • 2
  • Daiana Cristina Salm
    • 1
    • 2
  • Elisa C. Winkelmann-Duarte
    • 1
  • Júlia Koerich Ferreira
    • 2
  • Daniela Dero Lüdtke
    • 2
    • 3
  • Kamilla Pamplona Frech
    • 1
  • Luiz Augusto Oliveira Belmonte
    • 2
    • 3
  • Verônica Vargas Horewicz
    • 2
    • 3
  • Anna Paula Piovezan
    • 2
    • 3
  • Francisco José Cidral-Filho
    • 2
    • 3
  • Ari Ojeda Ocampo Moré
    • 4
  • Daniel Fernandes Martins
    • 2
    • 3
    Email author
  1. 1.Postgraduate Program in Neuroscience, Center of Biological SciencesFederal University of Santa CatarinaFlorianópolisBrazil
  2. 2.Experimental Neuroscience Laboratory (LaNEx)University of Southern Santa CatarinaPalhoçaBrazil
  3. 3.Postgraduate Program in Health SciencesUniversity of Southern Santa CatarinaPalhoçaBrazil
  4. 4.Integrative Medicine and Acupuncture DivisionUniversity Hospital, Federal University of Santa CatarinaFlorianópolisBrazil

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