Epitranscriptomic Regulation of NMDA Receptors Rears its Ugly Head in Chemotherapy-Induced Neuropathic Pain

Excerpt

A number of different cancer chemotherapy agents such as cisplatin, oxaliplatin, and paclitaxel can lead to nerve damage, thereby giving rise to neuropathic pain states that present with mechanical and cold allodynia [1]. Although these pain conditions often resolve after completion of the chemotherapy, a significant portion of patients exhibit long-lasting pain that can persist longer than 12 months with a negative impact on the quality of life of affected individuals [1]. Underlying cellular and molecular mechanisms have been studied extensively, and include dysregulation of ion channels such as HCN, potassium, and calcium channels [2‐4] in sensory neurons, and inhibitors of voltage-gated calcium channels can reverse the observed pain phenotype in preclinical models [5, 6]. The underlying mechanisms for this type of ion channel dysregulation remain incompletely explored but may include neuroimmune crosstalk [7]. An elegant study by Lu and colleagues in a recent issue of the Journal of Clinical Investigation implicates epigenetic regulation of presynaptic N-Methyl-D-Aspartate (NMDA) receptors in sensory neurons [8] as a key factor in paclitaxel-induced neuropathic pain. …