AI Article Synopsis
- Platinum-based chemotherapy agents like oxaliplatin can cause peripheral neuropathy and pain, including cold allodynia, which is a sensitivity to cold temperatures.
- The TRPM8 ion channel plays a key role in this pain but blocking it can lead to unwanted side effects like hypothermia.
- A newly designed cyclic peptide called DeC-1.2 selectively targets TRPM8 to inhibit cold allodynia in mice treated with oxaliplatin without affecting their body temperature, showing promise as a potential pain relief option.
Article Abstract
Platinum-based compounds in chemotherapy such as oxaliplatin often induce peripheral neuropathy and neuropathic pain such as cold allodynia in patients. Transient Receptor Potential Melastatin 8 (TRPM8) ion channel is a nociceptor critically involved in such pathological processes. Direct blockade of TRPM8 exhibits significant analgesic effects but also incurs severe side effects such as hypothermia. To selectively target TRPM8 channels against cold allodynia, a cyclic peptide DeC-1.2 is de novo designed with the optimized hot-spot centric approach. DeC-1.2 modality specifically inhibited the ligand activation of TRPM8 but not the cold activation as measured in single-channel patch clamp recordings. It is further demonstrated that DeC-1.2 abolishes cold allodynia in oxaliplatin treated mice without altering body temperature, indicating DeC-1.2 has the potential for further development as a novel analgesic against oxaliplatin-induced neuropathic pain.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8596132 | PMC |
| http://dx.doi.org/10.1002/advs.202101717 | DOI Listing |
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