Abstract
Oxaliplatin is a chemotherapeutic drug widely used to treat various types of tumors. However, it can induce a serious peripheral neuropathy characterized by cold and mechanical allodynia that can even disrupt the treatment schedule. Since the approval of the agent, many laboratories, including ours, have focused their research on finding a drug or method to decrease this side effect. However, to date no drug that can effectively reduce the pain without causing any adverse events has been developed, and the mechanism of the action of oxaliplatin is not clearly understood. On the dorsal root ganglia (DRG) sensory neurons, oxaliplatin is reported to modify their functions, such as the propagation of the action potential and induction of neuropathic pain. Voltage-gated sodium channels in the DRG neurons are important, as they play a major role in the excitability of the cell by initiating the action potential. Thus, in this small review, eight studies that investigated the effect of oxaliplatin on sodium channels of peripheral neurons have been included. Its effects on the duration of the action potential, peak of the sodium current, voltage–response relationship, inactivation current, and sensitivity to tetrodotoxin (TTX) are discussed.
Highlights
Oxaliplatin is a third-generation platinum-based chemotherapeutic drug that is widely used to treat various types of cancer, such as breast, colorectal, and lung cancers [1]
By using in vivo spinal cord extracellular recording methods, we demonstrated that the activities of wide dynamic range (WDR) neurons, which are present in the spinal dorsal horn and encode the information received from both the innocuous and noxious signs that transmit peripheral neurons [20], are highly upregulated after oxaliplatin treatment compared to that after vehicle injection in rats [15,16,18]
The effect of oxaliplatin on voltage-gated sodium channels was observed based on the results obtained from eight studies
Summary
Oxaliplatin is a third-generation platinum-based chemotherapeutic drug that is widely used to treat various types of cancer, such as breast, colorectal, and lung cancers [1]. By using in vivo spinal cord extracellular recording methods, we demonstrated that the activities of wide dynamic range (WDR) neurons, which are present in the spinal dorsal horn and encode the information received from both the innocuous and noxious signs that transmit peripheral neurons [20], are highly upregulated after oxaliplatin treatment compared to that after vehicle injection in rats [15,16,18] These results let us focus on the role of peripheral sensory neurons in oxaliplatin-induced neuropathic pain [21]. Considering the importance of the peripheral sensory neurons and voltage-gated sodium channels in the development and maintenance of neuropathic pain, it appeared to be important to combine all studies published during the past 20 years, and report on them for a better understanding of the action of oxaliplatin and the development of an effective drug (Table 1)
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