Involvement of Endothelin Receptors in Peripheral Sensory Neuropathy Induced by Oxaliplatin in Mice

Area of Science:

• Neuroscience
• Pharmacology
• Oncology

Background:

• Oxaliplatin is a common chemotherapy agent.
• Oxaliplatin can cause peripheral sensory neuropathy (OIN), a debilitating side effect.
• The role of endothelin receptors in OIN is not fully understood.

Purpose of the Study:

• To investigate the involvement of endothelin ET_A and ET_B receptors in oxaliplatin-induced peripheral sensory neuropathy (OIN) in mice.
• To evaluate the therapeutic potential of bosentan, a non-selective endothelin receptor antagonist, in managing OIN.

Main Methods:

• Adult male Swiss mice were treated with oxaliplatin to induce OIN.
• Expression levels of endothelin ET_A and ET_B receptors in dorsal root ganglia (DRG) and spinal cords were analyzed.
• Selective and non-selective endothelin receptor antagonists were administered.
• Mechanical and thermal nociception tests were performed to assess hypersensitivity.

Main Results:

• Oxaliplatin induced mechanical and thermal hypersensitivity in mice.
• Endothelin ET_A receptor expression increased in DRG and spinal cord.
• Endothelin ET_B receptor expression increased in DRG.
• Selective antagonists for ET_A and ET_B receptors partially alleviated mechanical hyperalgesia.
• Bosentan effectively prevented both mechanical and thermal hypersensitivity.

Conclusions:

• Both endothelin ET_A and ET_B receptors play a significant role in the development of OIN in mice.
• Targeting endothelin receptors, particularly with agents like bosentan, shows promise for managing oxaliplatin-induced peripheral sensory neuropathy.