Effects of Chronic Oral Probiotic Treatment in Paclitaxel-Induced Neuropathic Pain

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) represents one of the most prevalent and potentially disabling side effects due to the use of anticancer drugs, one of the primary neuropathies detected is peripheral neuropathy induced by administration of taxanes, including paclitaxel. It has been demonstrated that gut microbiota is crucial for the therapeutic effect of chemotherapeutic drugs for inhibiting tumor growth and contributed to the pathogenesis of the CIPN. The use of nutraceuticals has receiving growing attention from the research community due to their phytochemical, biological, and pharmacological properties. It has been demonstrated that probiotic formulations may both reduce inflammation and modulate the expression of pain receptors. Our studies tested the efficacy of a probiotic formulation, SLAB51, in preventing paclitaxel-induced neuropathy. Interestingly, our probiotic formulation was able to keep the gut integrity, preserving its functionality, in CIPN-mice, moreover, it prevented the mechanical and cold hypersensitivity induced in paclitaxel-mice. Additionally, ex-vivo analysis showed that in CIPN-mice the pro-biotic treatment increased the expression of opioid and cannabinoid receptors in spinal cord, it prevented in the reduction in nerve fiber damage in the paws and modulated the serum proinflammatory cytokines concentration. On basis of these data, the use of this specific probiotic formulation may represent a valid adjuvant agent to paclitaxel, useful and not toxic for long-lasting therapies.

Nuclear PPAR-γ Activation Modulates Inflammation and Oxidative Stress in Attenuating Chemotherapy-Induced Neuropathic Pain in Vivo

“…A recent study showed decreased transcription factor in parallel with reduced expression of PPAR-γ in spinal cords after paclitaxel administration. In the same study, it is also observed that administration of probiotic formulation, SLAB51 reduced serum cytokine levels and increased PPAR- protein levels in spinal cord [36]. In accordance with previous studies, it seems activation of PPAR- relieved neuropathic pain state, possibly through an inhibitory action on neuro-immune glial activation and subsequent TNF-α release in spinal cord.…”

Gut Microbiome and Plasma Metabolome Signatures in Middle-Aged Mice With Cognitive Dysfunction Induced by Chronic Neuropathic Pain

“…Recent evidence suggests that dysbiosis exists in several types of CNP and cognitive impairments (Jiang et al, 2017 ; Lin et al, 2020 ; Marttinen et al, 2020 ) . Moreover, the interventions of gut microbiota, such as probiotics and fecal microbiota transplantation (FMT), showed beneficial effects on the two disorders (Van Laar et al, 2019 ; Bonomo et al, 2020 ; Cuozzo et al, 2021 ). Studies have also revealed that gut microbiota regulates the development of CNP or cognitive impairment through the vagus nerve, endocrine, and metabolic as well as immune communications (Sampson and Mazmanian, 2015 ; Sun et al, 2020 ; Chen et al, 2021 ).…”

A role for gut microbiota in early-life stress-induced widespread muscle pain in the adult rat

“…However, altering the gut microbiome population by administration of locally-acting antibiotics or by probiotics has been shown in preclinical and clinical studies to attenuate stress-induced visceral hyperalgesia, 22 , 23 , 30 , 41 as well as attenuate neuropathic cutaneous mechanical allodynia and thermal hyperalgesia. 42 , 43 How probiotic and antibiotic administration can ameliorate hyperalgesia, which is currently unknown, may depend on more than one mechanism. One mechanism may depend on modifying stress-induced gut dysbiosis.…”