Abstract
Problem statement: Chemotherapy-induced peripheral neuropathy (CIPN) is a widespread and potentially disabling side effect of various anticancer drugs. In spite of the intensive research focused on obtaining therapies capable to treat or prevent CIPN, the medical demand remains very high. Microtubule-stabilizing agents, among which taxanes, are effective chemotherapeutic agents for the therapy of several oncologic diseases. The inflammatory process activated by chemotherapeutic agents has been interpreted as a potential trigger of the nociceptive process in CIPN. The chemotherapy-driven release of proinflammatory and chemokines has been recognized as one of the principal mechanisms controlling the establishment of CIPN. Several reports have indicated that probiotics are capable to regulate the balance of anti-inflammatory and pro-inflammatory cytokines. Accordingly, it has been suggested that some probiotic formulations, may have an effective role in the management of inflammatory pain symptoms. Experimental approaches used: we tested the hypothesis that paclitaxel-induced neuropathic pain can be counteracted by the probiotic DSF by using an in vitro model of sensitive neuron, the F11 cells. On this model, the biomolecular pathways involved in chemotherapy induced peripheral neuropathy depending on inflammatory cytokines were investigated by Real-time PCR, Western blotting and confocal microscopy. General conclusions: the results obtained, i.e. the increase of acetylated tubulin, the increase of the active forms of proteins involved in the establishment of neuropathic pain, point towards the use of this probiotic formulation as a possible adjuvant agent for counteracting CINP symptoms.
Highlights
Chemotherapy-induced peripheral neuropathy (CIPN) is a widespread and potentially disabling side effect of various anticancer drugs [1]
Peripheral nerve degeneration or small fiber neuropathy is associated with the main mechanism in the development of CIPN [6,7] but numerous studies underline that the occurrence of neuropathic pain, induced by anticancer drugs, may arise early after the first infusion showing no injury in intraepidermal nerve fibers or axonal degeneration in peripheral nerves [8,9]
Neurotoxicity caused by Paclitaxel is attributed to alteration of microtubule structure leading to increased microtubule stability by increasing acetylated α-tubulin causing neuropathic pain, but it has been recently indicated that Paclitaxel triggers the activation of IL-8 signaling in dorsal root ganglion (DRG) neurons in culture [21]
Summary
Chemotherapy-induced peripheral neuropathy (CIPN) is a widespread and potentially disabling side effect of various anticancer drugs [1]. Peripheral nerve degeneration or small fiber neuropathy is associated with the main mechanism in the development of CIPN [6,7] but numerous studies underline that the occurrence of neuropathic pain, induced by anticancer drugs, may arise early after the first infusion showing no injury in intraepidermal nerve fibers or axonal degeneration in peripheral nerves [8,9]. The inflammatory process activated by chemotherapeutic agents has been interpreted as a potential trigger of the nociceptive process in CIPN [11,12] and the chemotherapy-driven release of proinflammatory and chemokines (chemotactic cytokines) has been recognized as one of the principal mechanisms controlling the neuroimmune communication. Paclitaxel-induced neuropathic pain typically represents sensory neuropathy with the most common symptoms such as numbness, tingling in the hands, feet and burning pain. Neurotoxicity caused by Paclitaxel is attributed to alteration of microtubule structure leading to increased microtubule stability by increasing acetylated α-tubulin causing neuropathic pain, but it has been recently indicated that Paclitaxel triggers the activation of IL-8 signaling in DRG neurons in culture [21]
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