Abstract
The widely used cancer treatment, chemotherapy, causes severe long-term neuropathic pain in 30–40% cases, the condition clinically known as chemotherapy-induced peripheral neuropathy (CIPN). Approved conventional analgesics are sometimes ineffective, while others like opioids have undesirable side effects like addiction, seizures, and respiratory malfunctioning. Tricyclic antidepressants and anticonvulsants, although exhibit anti-allodynic effects in neuropathy, also have unpleasant side effects. Thus, alternative medicines are being explored for CIPN treatment. Despite scattered reports on different extracts from different plants having potential anti-allodynic effects against CIPN, no established medicine or formulation of herbal origin exists. In this study, efficacy of an herbal decoction, formulated based on ancient medicinal principles and protocols for treating neuropathic pain, Divya-Peedantak-Kwath (DPK), has been evaluated in a paclitaxel (PTX)-induced peripheral neuropathic mouse model. We observed that DPK has prominent anti-allodynic and anti-hyperalgesic effects and acts as a nociceptive modulator for CIPN. With exhibited antioxidative effects, DPK restored the redox potential of the sciatic nerves to the normal. On histopathological evaluation, DPK prevented the PTX-induced lesions in the sciatic nerve, in a dose-dependent manner. It also prevented inflammation by modulating the levels of pro-inflammatory cytokines involved in CIPN pathogenesis. Our observations evinced that DPK can alleviate CIPN by attenuating oxidative stress and concomitant neuroinflammation through immune modulation.
Highlights
Chemotherapy-induced peripheral neuropathy (CIPN), one of the most common side effects of chemotherapeutic agents, has symptoms like pain, allodynia, loss of sensation, paresthesia, numbness, tingling, and gait disturbances (Miltenburg and Boogerd, 2014; Heuvel et al, 2017)
We report that DPK is a potent antiallodynic and an anti-hyperalgesic agent and a very efficient antioxidant that can effectively attenuate the neuroinflammation associated with PTX-induced neuropathy through cytokine modulation
Culture media RPMI-1640, fetal bovine serum, and antibiotic/ antimycotic mixture were obtained from Gibco, and cytokines interleukin IL-1β, IL-6, and tumor necrosis factor-α (TNF-α) ELISA kits were purchased from BD Biosciences
Summary
Chemotherapy-induced peripheral neuropathy (CIPN), one of the most common side effects of chemotherapeutic agents, has symptoms like pain, allodynia, loss of sensation, paresthesia, numbness, tingling, and gait disturbances (Miltenburg and Boogerd, 2014; Heuvel et al, 2017). CIPN quite often leads to reduction in the dose of the chemotherapeutic agent being administered or, in the worst case, discontinuation of the treatment altogether This affects the quality of life and puts the survival of the patient at stake (Miltenburg and Boogerd, 2014). Considering CIPN as neuropathic pain due to axonal degeneration, relevant pharmacologic treatments, involving tricyclic antidepressants and anticonvulsants, are administered These agents showed suboptimal efficacy against CIPN and, not to mention, have unacceptable aftereffects (Rao et al, 2007; Rao et al, 2008; Fukuda et al, 2017). Duloxetine has side effects like nausea, dry mouth, sleepiness, fatigue, constipation, loss of appetite, increased sweating, and dizziness (Hershman et al, 2014; Hou et al, 2018)
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