Highlights
- •PAR2 contributes to mechanical hyperalgesia and cold hypersensitivity evoked by OXL.
- •TRPV1 contributes to mechanical hyperalgesia evoked by OXL.
- •TRPV1 is one of downstream pathways for PAR2 to play a role.
Abstract
Oxaliplatin (OXL) is a third-generation chemotherapeutic agent commonly used to treat
metastatic digestive tumors; however, neuropathic pain is one of the main limiting
complications of OXL. The purpose of this study was to examine the underlying mechanisms
by which neuropathic pain is induced by OXL in a rat model. Our results demonstrated
that blocking spinal proteinase-activated receptor 2 (PAR2) and transient receptor
potential vanilloid 1 (TRPV1) attenuated pain responses evoked by mechanical stimulation
and decreased the releases of substance P and CGRP in the superficial dorsal horn
of the spinal cord. The attenuating effect on mechanical pain was significantly smaller
in OXL-rats than that in control rats. Blocking PAR2 also attenuated a heightened
cold sensitivity evoked by OXL; whereas blocking TRPV1 had little effects on OXL-evoked
hypersensitive cold response. Our data also showed that OXL increased the protein
expressions of PAR2 and TRPV1 in the superficial dorsal horn. In addition, blocking
PAR2 decreased TRPV1 expression in OXL-rats. Overall, our data suggest that upregulated
expression of PAR2 in the superficial dorsal horn contributes to mechanical hyperalgesia
and cold hypersensitivity; whereas amplified TRPV1 plays a role in regulating mechanical
hyperalgesia, but not cold hypersensitivity after administration of OXL. We further
suggest that TRPV1 is likely one of the signaling pathways for PAR2 to play a role
in regulating OXL-induced neuropathic pain.
Keywords
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Article info
Publication history
Published online: March 26, 2015
Accepted:
March 17,
2015
Received in revised form:
March 11,
2015
Received:
February 10,
2015
Identification
Copyright
© 2015 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
