Mechanical allodynia and thermal hyperalgesia induced by experimental squamous cell carcinoma of the lower gingiva in rats.
We developed a rat model of oral cancer pain by inoculating cancer cells into the lower gingiva. A squamous cell carcinoma (SCC) derived from Fisher rats, SCC-158, was inoculated into the subperiosteal tissue on the lateral side of the lower gingiva in male Fisher rats. Inoculation of cancer cells induced marked mechanical allodynia and thermal hyperalgesia in the ipsilateral maxillary and mandibular nerve area. Infiltration of the tumor cells into the mandible and the completely encompassed inferior alveolar nerve was observed. Calcitonin gene-related peptide (CGRP)-, substance P (SP)-, ATP receptor (P2X(3))-, and capsaicin receptor (TRPV1)-immunoreactive cells strikingly increased in the small-cell group of trigeminal ganglia (TGs) after tumor cell inoculation. The TRPV1-immunoreactive cells also increased in the medium- and large-cell groups. Retrograde tracing combined with immunofluorescence techniques revealed the increased expression of peptides and the receptors in maxillary nerve afferent neurons. These results suggest that inoculation of SCC cells into the lower gingiva produces mechanical allodynia and thermal hyperalgesia, indicating the establishment of a novel rat model of oral cancer pain. Increased expression of CGRP, SP, P2X(3), and TRPV1 in the TG may be involved in the behavioral changes in this model.


CONCLUSIONS
To clarify the mechanisms of oral cancer pain, we examined the expression of calcitonin gene-related peptide, substance P, ATP receptor P2X(3), and capsaicin receptor TRPV1 in trigeminal ganglia. Characterizations of these molecular systems which mediate pain perception are important to develop novel clinical tools for promoting relief of oral cancer pain.
Nagamine
Kenjiro
K
Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Ozaki
Noriyuki
N
Shinoda
Masamichi
M
Asai
Hideaki
H
Nishiguchi
Hiroaki
H
Mitsudo
Kenji
K
Tohnai
Iwai
I
Ueda
Minoru
M
Sugiura
Yasuo
Y
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000150:complications* / Q000503:physiopathology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005881:Gingiva / Q000294:innervation / Q000473:pathology / Q000503:physiopathology*; D006358:Hot Temperature / Q000009:adverse effects; D006930:Hyperalgesia / Q000209:etiology* / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D009061:Mouth Mucosa / Q000294:innervation / Q000473:pathology / Q000503:physiopathology; D009062:Mouth Neoplasms / Q000150:complications* / Q000503:physiopathology; D009475:Neurons, Afferent / Q000378:metabolism; D009619:Nociceptors / Q000378:metabolism; D010812:Physical Stimulation / Q000009:adverse effects; D051381:Rats; D011916:Rats, Inbred F344; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D058477:Receptors, Purinergic P2X3; D013373:Substance P / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism; D012668:Trigeminal Ganglion / Q000166:cytology / Q000378:metabolism; D014276:Trigeminal Nerve / Q000378:metabolism
C546410:P2rx3 protein, rat; D018048:Receptors, Purinergic P2; D058477:Receptors, Purinergic P2X3; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D013373:Substance P; D015740:Calcitonin Gene-Related Peptide