PHARMACOLOGICAL TREATMENT OF CHEMOTHERAPY-INDUCED NEUROPATHIC PAIN: PPAR AGONISTS AS A PROMISING TOOL.
- 1Universidade do Vale do Itajaí, Brazil
- 2Federal University of Rio de Janeiro, Brazil
Chemotherapy-induced neuropathic pain (CINP) is one of the most severe side effects of anticancer agents, such as platinum- and taxanes-derived drugs (oxaliplatin, cisplatin, carboplatin and paclitaxel). CINP may even be a factor of interruption of treatment and consequently increasing the risk of death. Besides that, it is important to take into consideration that the incidence of cancer is increasing worldwide, including colorectal, gastric, lung, cervical, ovary and breast cancers, all treated with the aforementioned drugs, justifying the concern for medical community and issues regarding quality of live. Several physiopathological mechanisms have already been described for CINP, such as changes in axonal transport, mitochondrial damage, increased ion channel activity and inflammation in the central nervous system (CNS). Another less frequent event that may occur after chemotherapy, particularly under oxaliplatin treatment, is the central neurotoxicity leading to disorders such as mental confusion, catatonia, hyporeflexia, etc. To date, no pharmacological therapy has shown satisfactory effect in these cases. In this scenario, duloxetine is the only drug currently in clinical use. Peroxisome proliferator-activated receptors (PPAR) belong to the class of nuclear receptors and are present in several tissues, mainly participating in lipid and glucose metabolism and inflammatory response. There are 3 PPAR isoforms: α, β/δ and . PPAR, the protagonist of this review, is expressed in adipose tissue, large intestine, spleen and neutrophils. This subtype also plays important role in energy balance, lipid biosynthesis and adipogenesis. The effects of PPARy agonists, known for their positive activity on type II diabetes mellitus, have been explored and present promising effects in the control of neuropathic pain, including CINP, and also cancer. This review focuses largely on the mechanisms involved in chemotherapy-induced neuropathy and the effects of the activation of PPAR to treat CINP. It is the aim of this review to help understanding and developing novel CINP therapeutic strategies integrating PPAR signalling.
Keywords: chemotherapy, Platinum, Taxane, nuclear receptor, Neuropathy, Chronic Pain, side effects, Quality of Life
Received: 29 May 2019;
Accepted: 14 Aug 2019.
Edited by:Michael Costigan, Boston Children's Hospital, Harvard Medical School, United States
Reviewed by:Lorenzo Di Cesare Mannelli, University of Florence, Italy
Nasiara Karim, University of Malakand, Pakistan
Copyright: © 2019 Quintão, Santin, Stoeberl, Corrêa, Melato and Costa. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Prof. Nara L. Quintão, Universidade do Vale do Itajaí, Itajai, Brazil, email@example.com