  Background: The spread of tumors through neural routes is common in several
types of cancer in which patients suffer from a moderate-to-severe neuropathy,
neural damage and a distorted quality of life. Here we aim to examine the
expression profiles of transient receptor potential vanilloid 1 (TRPV1) and of
transient receptor potential vanilloid 4 (TRPV4), toll-like receptor 4 (TLR4)
and extracellular signal-regulated kinase (ERK1/2), and to assess the possible
therapeutic strategies through blockade of transient receptor potential (TRP)
channels. Methods: Cancer was induced within the sciatic nerves of male
Copenhagen rats, and tissues from dorsal root ganglia (DRG) were collected and
used for measurements of immunofluorescence and Western blotting. The TRPV1
antagonist capsazepine, the selective TRPV4 antagonist HC-067047 and the
calcium ions inhibitor ruthenium red were used to treat thermal and/or
mechanical hyperalgesia. Results: Transient receptor potential vanilloid 1
showed a lower expression in DRGs on days 7 and 14. The expression of TRPV4,
TLR4 and ERK1/2 showed an increase on day 3 then a decrease on days 7 and 14.
TRPV1 and TLR4 as well as TRPV4 and ERK1/2 co-existed on the same neuronal
cells. The neuropathic pain was reversed in dose-dependent manners by using the
TRP antagonists and the calcium ions inhibitor. Conclusion: The decreased
expression of TRPV1 and TRPV4 is associated with high activation. The increased
expression of TLR4 and ERK1/2 reveals earlier immune response and tumor
progression, respectively, and their ultimate decrease is an indicator of nerve
damage. We studied the possible role of TRPV1 and TRPV4 in transducing
cancer-induced hyperalgesia. The possible treatment strategies of
cancer-induced thermal and/or mechanical hyperalgesia using capsazepine,
HC-067047 and ruthenium red are examined.
