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Chemokine Signaling in Chemotherapy-Induced Neuropathic Pain.

ABSTRACT: Chemotherapy-induced peripheral neuropathy (CIPN) is a side effect of chemotherapics such as taxanes, vinca alkaloids, and platinum compounds. In recent years, several reports have indicated the involvement of different molecular mechanisms in CIPN. The pathways described so far are diverse and target various components of the peripheral Nervous System (PNS). Among the contributors to neuropathic pain, inflammation has been indicated as a powerful driver of CIPN. Several pieces of evidence have demonstrated a chemotherapy-induced increase in peripheral pro-inflammatory cytokines and a strong correlation with peripheral neuropathy. At present, there are not adequate strategies to prevent CIPN, although there are drugs for treating CIPN, such as duloxetine, that have displayed a moderate effect on CIPN. In this review, we focus on the players involved in CIPN with a particular emphasis on chemokine signaling.

SUBMITTER: Brandolini L

PROVIDER: S-EPMC6627296 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Chemokine Signaling in Chemotherapy-Induced Neuropathic Pain.

Brandolini Laura L d'Angelo Michele M Antonosante Andrea A Allegretti Marcello M Cimini Annamaria A

International journal of molecular sciences 20190614 12

Chemotherapy-induced peripheral neuropathy (CIPN) is a side effect of chemotherapics such as taxanes, vinca alkaloids, and platinum compounds. In recent years, several reports have indicated the involvement of different molecular mechanisms in CIPN. The pathways described so far are diverse and target various components of the peripheral Nervous System (PNS). Among the contributors to neuropathic pain, inflammation has been indicated as a powerful driver of CIPN. Several pieces of evidence have ...[more]

PMID: 31197114

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Project description: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 of the medical community about the patient's quality of life. 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 (PPARs) 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 three PPAR isoforms: ?, ?/? 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 PPAR? 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.

Dataset Information

Chemokine Signaling in Chemotherapy-Induced Neuropathic Pain.

Publications

Chemokine Signaling in Chemotherapy-Induced Neuropathic Pain.

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