Ameliorative potential of standardized fruit extract of Pterodon pubescens Benth on neuropathic pain in mice: Evidence for the mechanisms of action

• Published in: Journal of ethnopharmacology 2015-12, Vol.175, p.273-286
• Main Authors: Nucci-Martins, Catharina, Martins, Daniel F., Nascimento, Leandro F., Venzke, Dalila, Oliveira, Aldo S., Frederico, Marisa J.S., Silva, Fátima R.M.B., Brighente, Inês M.C., Pizzolatti, Moacir G., Santos, Adair R.S.
• Format: Article
• Language: English
• Subjects: Analgesics - pharmacology; Analgesics - therapeutic use; Animals; Fabaceae; Female; Fruit; Glutamate; Hyperalgesia - drug therapy; Hyperalgesia - metabolism; Interleukin-1beta - metabolism; Mice; Neuralgia - drug therapy; Neuralgia - metabolism; Neuropathic pain; Phytotherapy; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Pterodon pubescens; Sciatic Nerve - injuries; Spinal Cord Dorsal Horn - drug effects; Spinal Cord Dorsal Horn - metabolism; Transient Receptor Potential Channels - metabolism; TRPA1; TRPA1 Cation Channel; TRPV Cation Channels - metabolism; TRPV1; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2015.09.005

The medicinal plant Pterodon pubescens Benth has been traditionally used for a long time to treat rheumatic diseases due to its anti-inflammatory and analgesic activities. The present study aims to evaluate the antinociceptive effect of ethanolic extract from P. pubescens fruits (EEPp) in a model of neuropathic pain in mice. The phytochemical analysis of EEPp was performed through GC–MS, HPLC and colorimetric analysis. The antinociceptive effects of EEPp (30–300mg/kg, i.g.) were evaluated on mechanical and thermal (cold or heat) hyperalgesia in neuropathic pain induced by partial sciatic nerve ligation (PSNL) in mice. We also investigated the effects of EEPp on the nociceptive response induced by intrathecal injection (i.t.) of ionotropic (AMPA, NMDA and kainate) and metabotropic (trans-ACPD) glutamate receptor agonists, proinflammatory cytokines such as IL-1β and TNF-α, as well as TRPV1 and TRPA1 agonists. In addition, we also investigated the safety profile of prolonged treatment with EEPp in mice. The phytochemical analysis showed a higher amount terpenes, being nine sesquiterpenes and seven diterpenes with vouacapan skeletons, as well as a small amount of phenols and flavonoids. The exact mechanism by which EEPp promotes its antinociceptive effect is not yet fully understood, but its oral administration causes significant inhibition of glutamate-, kainate-, NMDA-, trans-ACPD-induced biting responses, as well as of proinflammatory cytokines (TNF-α and IL-1β) and TRPV1 and TRPA1 channels activators (capsaicin and cinnamaldehyde, respectively). These results may indicate, at least in part, some of the mechanisms that are involved in this effect. In particular, EEPp decreases neuropathic pain and clearly shows, for the first time, a thermal and mechanical hyperalgesia reduction in the model of partial sciatic nerve ligation (PSNL), without inducing tolerance. Furthermore, the prolonged treatment with EEPp (300mg/kg, i.g.) showed a cumulative effect over 24h, in the 15th day, after last treatment. In addition, the open-field test showed that doses up to 300mg/kg in both treatments, acute and/or prolonged, did not affect the motor activity of mice. Also, EEPp showed no toxicity according to the serum levels of the renal and hepatic injury indicators or observed macroscopic organs, after PSNL. Taken together, these results provide the first experimental evidence of the significant antinociceptive effect of EEPp on neuropathic pain without causing side effects