Involvement of TRPV1 in nociceptive behavior in a rat model of cancer pain.
To investigate the mechanisms underlying cancer pain, we developed a rat model of cancer pain by inoculating SCC-158 into the rat hind paw, resulting in squamous cell carcinoma, and determined the time course of thermal, mechanical sensitivity, and spontaneous nocifensive behavior in this model. In addition, pharmacological and immunohistochemical studies were performed to examine the role played by transient receptor potential vanilloid (TRPV)1 and TRPV2 expressed in the dorsal root ganglia. Inoculation of SCC-158 induced marked mechanical allodynia, thermal hyperalgesia, and signs of spontaneous nocifensive behavior, which were diminished by systemic morphine administration. Intraplantar administration of the TRPV1 antagonist capsazepine or TRP channels antagonist ruthenium red did not inhibit spontaneous nocifensive behavior at all. However, intraplantar administration of capsazepine or ruthenium red completely inhibited mechanical allodynia and thermal hyperalgesia produced by SCC-158 inoculation. Immunohistochemically, the number of TRPV1-positive, large-sized neurons increased, whereas there was no change in small-sized neurons in the dorsal root ganglia. Our results suggest that TRPV1 play an important role in the mechanical allodynia and thermal hyperalgesia caused by SCC-158 inoculation.


CONCLUSIONS
We describe a cancer pain model that induced marked mechanical allodynia, thermal hyperalgesia, signs of spontaneous nocifensive behavior, and upregulation of TRPV1. Mechanical allodynia and thermal hyperalgesia were inhibited by TRP channel antagonists. The results suggest that TRPV1 plays an important role in the model of cancer pain.
Shinoda
Masamichi
M
Department of Functional Anatomy and Neuroscience, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Ogino
Akina
A
Ozaki
Noriyuki
N
Urano
Hiroko
H
Hironaka
Katsunori
K
Yasui
Masaya
M
Sugiura
Yasuo
Y
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002211:Capsaicin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D005534:Foot Diseases / Q000150:complications / Q000378:metabolism / Q000473:pathology; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology; D009374:Neoplasms, Experimental / Q000150:complications / Q000378:metabolism / Q000473:pathology; D009619:Nociceptors / Q000187:drug effects / Q000503:physiopathology*; D010146:Pain / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold; D051381:Rats; D011916:Rats, Inbred F344; D012430:Ruthenium Red / Q000008:administration & dosage / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*
D000701:Analgesics, Opioid; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D012430:Ruthenium Red; D009020:Morphine; C071423:capsazepine; D002211:Capsaicin