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Kaurenoic Acid Reduces Ongoing Chronic Constriction Injury-Induced Neuropathic Pain: Nitric Oxide Silencing of Dorsal Root Ganglia Neurons.
Zaninelli, Tiago H; Mizokami, Sandra S; Bertozzi, Mariana M; Saraiva-Santos, Telma; Pinho-Ribeiro, Felipe A; de Oliveira, Gabriele Inácio; Streck, Renata; Araújo, Eduardo J A; Arakawa, Nilton S; Borghi, Sergio M; Casagrande, Rubia; Verri, Waldiceu A.
  • Zaninelli TH; Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Center of Biological Sciences, Londrina State University, Londrina 86057-970, Paraná, Brazil.
  • Mizokami SS; Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Center of Biological Sciences, Londrina State University, Londrina 86057-970, Paraná, Brazil.
  • Bertozzi MM; Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Center of Biological Sciences, Londrina State University, Londrina 86057-970, Paraná, Brazil.
  • Saraiva-Santos T; Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Center of Biological Sciences, Londrina State University, Londrina 86057-970, Paraná, Brazil.
  • Pinho-Ribeiro FA; Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Center of Biological Sciences, Londrina State University, Londrina 86057-970, Paraná, Brazil.
  • de Oliveira GI; Department of Pharmaceutical Sciences, Center of Health Sciences, Londrina State University, Londrina 86039-440, Paraná, Brazil.
  • Streck R; Department of Histology, Londrina State University, Londrina 86057-970, Paraná, Brazil.
  • Araújo EJA; Department of Histology, Londrina State University, Londrina 86057-970, Paraná, Brazil.
  • Arakawa NS; Department of Pharmaceutical Sciences, Center of Health Sciences, Londrina State University, Londrina 86039-440, Paraná, Brazil.
  • Borghi SM; Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Center of Biological Sciences, Londrina State University, Londrina 86057-970, Paraná, Brazil.
  • Casagrande R; Department of Pharmaceutical Sciences, Center of Health Sciences, Londrina State University, Londrina 86039-440, Paraná, Brazil.
  • Verri WA; Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Center of Biological Sciences, Londrina State University, Londrina 86057-970, Paraná, Brazil.
Pharmaceuticals (Basel) ; 16(3)2023 Feb 23.
Article en En | MEDLINE | ID: mdl-36986443
Kaurenoic acid (KA) is a diterpene extracted from Sphagneticola trilobata (L.) Pruski. KA presents analgesic properties. However, the analgesic activity and mechanisms of action of KA in neuropathic pain have not been investigated so far; thus, we addressed these points in the present study. A mouse model of neuropathic pain was induced by chronic constriction injury (CCI) of the sciatic nerve. Acute (at the 7th-day post-CCI surgery) and prolonged (from 7-14th days post-CCI surgery) KA post-treatment inhibited CCI-induced mechanical hyperalgesia at all evaluated time points, as per the electronic version of von Frey filaments. The underlying mechanism of KA was dependent on activating the NO/cGMP/PKG/ATP-sensitive potassium channel signaling pathway since L-NAME, ODQ, KT5823, and glibenclamide abolished KA analgesia. KA reduced the activation of primary afferent sensory neurons, as observed by a reduction in CCI-triggered colocalization of pNF-κB and NeuN in DRG neurons. KA treatment also increased the expression of neuronal nitric oxide synthase (nNOS) at the protein level as well as the intracellular levels of NO in DRG neurons. Therefore, our results provide evidence that KA inhibits CCI neuropathic pain by activating a neuronal analgesic mechanism that depends on nNOS production of NO to silence the nociceptive signaling that generates analgesia.
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