Fig. 1.

Pathobiology of peripheral neuropathy induced by several chemotherapeutic agents: peripheral nerve damage associated with taxanes, vinca alkaloids and bortezomib is characterized by various mechanisms like microtubular damage, mitochondrial dysfunction, neuronal apoptosis etc. [24]. Damage to the microtubules causes impairment in axonal transmission and mitochondrial dysfunction. The mitochondrial dysfunction is due to opening of mitochondrial permeability transition pore (mPTP), swollen and vacuolated mitochondria which brings Ca²⁺ deregulation and activation of caspases thus driving the neuronal cell towards apoptosis [34]. These changes consequently stimulate microglia cells which releases the proinflammatory mediators and growth factors to the damaged areas leading to peripheral sensitization thus causing spontaneous discharge and hyper excitability [3]. Further proinflammatory mediators are also capable of damaging myelin sheath [35]. Platinum compounds like cisplatin and oxaliplatin can affect mitochondrial DNA, leading to mitochondrial dysfunction and also induces neuronal apoptosis through activation of mitogen activated protein kinase (MAPK) pathway. These chemotherapeutic agents are also reported to cause peripheral sensitization by the up regulation of N-methyl D-aspartate (NMDA) receptors, transient receptor potential vanilloid (TRPV) channels, and protein kinase C (PKC) [34].Oxaliplatin also alters the Na⁺ channel conductance through chelation of Ca²⁺[36]. All these effects can damage the sensory neurons such as Aδ and C fibers, which leads to neuropathic pain characterized by hyperalgesia and allodynia.