Re-organization of P2X3 receptor localization on epidermal nerve fibers in a murine model of cancer pain.
To determine whether ATP and P2X3 receptors contribute to bone-cancer pain in a mouse model, immunohistochemical techniques were used to identify whether changes in the labeling of P2X3 receptors on epidermal nerve fibers (ENFs) occurred during tumor development. C3H mice were injected with osteolytic fibrosarcoma cells in and around the calcaneus bone. These mice exhibited mechanical hyperalgesia by day 10 post-implantation as assessed using von Frey monofilaments. Biopsies of the plantar skin overlying the tumor were obtained at days 10, 14, and 18 post-implantation. Confocal images were analyzed for the number of PGP 9.5, P2X3, and CGRP immunoreactive (ir) ENFs. The overall ENF population (PGP-ir) decreased progressively over time, whereas the subsets of P2X3-ir fibers demonstrated a modest increase and CGRP-ir nerve fibers remained fairly constant. Importantly, the proportion of CGRP-ir fibers that labeled for P2X3 increased from approximately 6% in control animals to nearly 30% at day 14 following tumor cell implantation. These studies demonstrate increased expression of P2X3 receptors on CGRP-ir ENFs during tumor growth and suggest a role for ATP in cancer-related pain.
Gilchrist
Laura S
LS
Physical Therapy Program, College of St. Catherine, Minneapolis, MN 55454, USA.
Cain
David M
DM
Harding-Rose
Catherine
C
Kov
Anh N
AN
Wendelschafer-Crabb
Gwen
G
Kennedy
William R
WR
Simone
Donald A
DA
D000818:Animals; D001859:Bone Neoplasms / Q000150:complications / Q000378:metabolism*; D002111:Calcaneus / Q000473:pathology / Q000601:surgery; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005354:Fibrosarcoma / Q000150:complications / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation / Q000379:methods; D009412:Nerve Fibers / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D010146:Pain / Q000209:etiology / Q000378:metabolism*; D010147:Pain Measurement / Q000379:methods; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058477:Receptors, Purinergic P2X3; D012867:Skin / Q000294:innervation* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D043222:Ubiquitin Thiolesterase / Q000378:metabolism
C546409:P2rx3 protein, mouse; D018048:Receptors, Purinergic P2; D058477:Receptors, Purinergic P2X3; D043222:Ubiquitin Thiolesterase; C496976:Uchl1 protein, mouse; D015740:Calcitonin Gene-Related Peptide