Mechanistic Involvement of Inflammation in Bortezomib-induced Peripheral Neuropathy

Abstract

Aim: To establish the role of inflammation in bortezomib induced peripheral neuropathy (BIPN). Background: Peripheral neuropathy is the dose-limiting toxicity of bortezomib which can lead to discontinuation of the treatment. There are multiple mechanisms involved in the disposition of BIPN. However, the role of inflammatory mediators is still under investigation. The complete understanding of inflammatory markers in relation to BIPN can lead to the development of effective therapy for prophylaxis and treatment of peripheral neuropathy. Objective: Based on the available data, postulate the role of inflammatory mediators in the development of peripheral neuropathy due to bortezomib. Method: The “Pubmed” and “Google Scholar” were used as the search engines with terms like “peripheral neuropathy”, “bortezomib induced peripheral neuropathy” and “inflammation”. Original research, case reports and review articles were considered. Results: Bortezomib use is associated with the development of peripheral neuropathy. This effect is due to the damage to Schwann cells and dorsal root ganglion neurons; mitochondrial damage; increased ion channel susceptibility; and higher infiltration of macrophages in the spinal cord. All these factors collectively increase the secretion of inflammatory mediators and lead to the development of neuropathic pain. Conclusion: Targeting inflammatory mediators may be helpful in the treatment of bortezomib-induced peripheral neuropathy.

The nonlinear association between red blood cell distribution width (RDW) and bortezomib-related peripheral neurotoxicity (PN): A retrospective cohort study

“…[ 24 , 30 ]. Similarly, inflammation plays a significant role in the development of BIPN [ 31 ]. In animal experiments, bortezomib has been shown to enhance the expression of inflammatory cytokines and chemokines, most notably tumor necrosis factor alpha (TNF-α), CC chemokine ligand 2 (CCL2), interleukin-6 (IL-6), and prokineticin-2 [ [32] , [33] , [34] , [35] ].…”

“…In animal experiments, bortezomib has been shown to enhance the expression of inflammatory cytokines and chemokines, most notably tumor necrosis factor alpha (TNF-α), CC chemokine ligand 2 (CCL2), interleukin-6 (IL-6), and prokineticin-2 [ [32] , [33] , [34] , [35] ]. Furthermore, bortezomib causes direct damage to Schwann cells and dorsal root ganglion neurons, as well as increased ion channel sensitivity and significant macrophage infiltration in the spinal cord, all of which contribute to the advancement of neuropathic pain [ 31 ]. Therefore, based on the mechanisms described above, it is plausible that elevated RDW is associated with a high risk of BIPN.…”