Heat and mechanical hyperalgesia in mice model of cancer pain.
We developed a mouse model of cancer pain to investigate its underlying mechanisms. SCC-7, squamous cell carcinoma (SCC) derived from C3H mice, was inoculated subcutaneously into either the plantar region or thigh in male C3H/Hej mice. Heat and mechanical sensitivity as well as spontaneous behavior were measured at the plantar surface of the ipsilateral hind paw after the inoculation. Inoculated sites were histologically examined, and the expression of capsaicin receptors (TRPV1) was examined in the dorsal root ganglia (DRG) to clarify their potential contribution to pain sensitivity. Inoculation of cancer cells induced marked heat hyperalgesia and mechanical allodynia in the ipsilateral hind paw for two weeks in both plantar- and thigh-inoculation models. Signs of spontaneous pain, such as lifting, licking and flinching of the paw were also observed. However, further growth of the tumor reversed the mechanical allodynia in both plantar- and thigh-inoculation models, and heat hyperalgesia in thigh-inoculation models. Histologically, no infiltration of the tumor cells into the nerve was observed. TRPV1 immunoreactive cells increased in the L5 DRG on day 7, but returned to the control level on day 15 post-inoculation. Intraperitoneal administration of the competitive TRPV1 antagonist capsazepine inhibited hyperalgesia induced by tumor cell-inoculation in either plantar- or thigh-inoculated animals. This study indicated that inoculation of SCC resulted in spontaneous pain, heat hyperalgesia and mechanical allodynia. The altered expression of TRPV1 in the DRG may be involved in behavioral changes in this model.
Asai
Hideaki
H
Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Ozaki
Noriyuki
N
Shinoda
Masamichi
M
Nagamine
Kenjiro
K
Tohnai
Iwai
I
Ueda
Minoru
M
Sugiura
Yasuo
Y
D000818:Animals; D001831:Body Temperature; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002452:Cell Count / Q000379:methods; D045744:Cell Line, Tumor; D048429:Cell Size; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000473:pathology / Q000601:surgery; D006801:Humans; D006930:Hyperalgesia / Q000503:physiopathology*; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation / Q000379:methods; D009369:Neoplasms / Q000150:complications* / Q000473:pathology; D010146:Pain / Q000209:etiology* / Q000473:pathology; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000502:physiology; D011930:Reaction Time / Q000187:drug effects; D013194:Staining and Labeling / Q000379:methods; D050916:TRPV Cation Channels / Q000378:metabolism; D013997:Time Factors
D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C071423:capsazepine; D002211:Capsaicin