Cannabinoids and agmatine as potential therapeutic alternatives for cisplatin-induced peripheral neuropathy

Abstract

Cisplatin is a widely used antineoplastic agent in the treatment of various cancers. Peripheral neuropathy is a well-known side effect of cisplatin and has the potential to result in limiting and/or reducing the dose, decreasing the quality of life. Unfortunately, the mechanism for cisplatin-induced neuropathy has not been completely elucidated. Currently, available treatments for neuropathic pain (NP) are mostly symptomatic, insufficient and are often linked with several detrimental side effects; thus, effective treatments are needed. Cannabinoids and agmatine are endogenous modulators that are implicated in painful states. This review explains the cisplatin-induced neuropathy and antinociceptive effects of cannabinoids and agmatine in animal models of NP and their putative therapeutic potential in cisplatin-induced neuropathy.

Pathogenesis and Treatment of Pancreatic Cancer Related Pain

“…In pancreatic cancer specifically, cisplatin treatment is associated with axonal neuropathy in the dorsal root ganglion, although other large sensory fibers can be affected. Similar results have been observed in response to treatment with oxaliplatin (55,63,64). Gemcitabine and taxanes are also associated with a spectrum of neuropathies.…”

“…Cannabinoids, such as dronabinol and nabilone, are approved drugs for the symptomatic treatment of cancerrelated side effects (82). Cannabinoids reduce pain symptoms through supraspinal, spinal, and peripheral modes of action and can be used to alleviate both caner-and treatment-induced pain states (63,83,84). Additionally, cannabinoid treatment can address the cause of pain by reducing the release of inflammatory signals and increasing endogenous opioid release through the CB2 receptors, affecting mast cell receptors and keratinocytes (83,84).…”

Resveratrol Enhances Inhibition Effects of Cisplatin on Cell Migration and Invasion and Tumor Growth in Breast Cancer MDA-MB-231 Cell Models In Vivo and In Vitro

“…In clinic, the addition of platinum drugs can significantly improve the pathological complete response rate in the neoadjuvant therapy of TNBC. However, cisplatin, one of the most active cytotoxic drugs at present, has a therapeutic effect on a variety of malignant tumors [ 21 ], and also produces serious side effects such as severe toxicity including nephrotoxicity [ 22 ], neurotoxicity [ 23 ], gastrointestinal toxicity [ 24 ], peripheral neuropathy [ 25 ], ototoxicity [ 26 ], and hematological toxicity [ 27 ]. Therefore, it is particularly necessary to find drugs that can reduce the side effects of cisplatin and enhance the therapeutic effects.…”

Effects of agmatine and red wine concentrate, enriched with polyphenolic compounds, on L-arginine / nitrogen oxide system in the brain of rats with experimental diabetes mellitus

“…In the brain, agmatine plays a role of a neurotransmitter/neuromodulator as it binds to a2-adrenergic and imidazoline (I1) receptors. In addition, agmatine antagonizes N-methyl-D aspartate receptors (NMDAR), inhibits all isoforms of NO synthase, and modulates polyamine metabolism [6,8,18]. Agmatine possesses mild hypoglycemic effects, inhibits advanced glycation end product (AGE) formation [19], influences protein ADP-ribosylation and hence signaling pathways [21].…”