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Papers of the Week


Papers: 15 Jul 2023 - 21 Jul 2023

RESEARCH TYPE:
Basic Science


Genetics, Human Studies, Molecular/Cellular, Neurobiology

PAIN TYPE:
Cancer Pain, Orofacial/Head Pain


2023 Jun 21


Cells


37443709


12


13

Calcitonin Related Polypeptide Alpha Mediates Oral Cancer Pain.

Authors

Tu NH, Inoue K, Lewis PK, Khan A, Hwang JH, Chokshi V, Dabovic BB, Selvaraj S, Bhattacharya A, Dubeykovskaya Z, Pinkerton NM, Bunnett NW, Loomis CA, Albertson DG, Schmidt BL

Abstract

Oral cancer patients suffer pain at the site of the cancer. Calcitonin gene related polypeptide (CGRP), a neuropeptide expressed by a subset of primary afferent neurons, promotes oral cancer growth. CGRP also mediates trigeminal pain (migraine) and neurogenic inflammation. The contribution of CGRP to oral cancer pain is investigated in the present study. The findings demonstrate that CGRP-immunoreactive (-ir) neurons and neurites innervate orthotopic oral cancer xenograft tumors in mice. Cancer increases anterograde transport of CGRP in axons innervating the tumor, supporting neurogenic secretion as the source of CGRP in the oral cancer microenvironment. CGRP antagonism reverses oral cancer nociception in preclinical oral cancer pain models. Single-cell RNA-sequencing is used to identify cell types in the cancer microenvironment expressing the CGRP receptor components, receptor activity modifying protein 1 and calcitonin receptor like receptor (CLR, encoded by ). and transcripts are detected in cells expressing marker genes for Schwann cells, endothelial cells, fibroblasts and immune cells. and transcripts are more frequently detected in cells expressing fibroblast and immune cell markers. This work identifies CGRP as mediator of oral cancer pain and suggests the antagonism of CGRP to alleviate oral cancer pain.