• Masami Suzuki, Minoru Narita, Minami Hasegawa, Sadayoshi Furuta, Tomoyuki Kawamata, Maho Ashikawa, Kanako Miyano, Kazuyoshi Yanagihara, Fumiko Chiwaki, Takahiro Ochiya, Tsutomu Suzuki, Motohiro Matoba, Hiroki Sasaki, and Yasuhito Uezono.
• Division of Cancer Pathophysiology, Department of Palliative Medicine, National Cancer Center Research Institute, Tokyo, Japan.
• Anesthesiology. 2012 Oct 1;117(4):847-56.

BackgroundPatients with peritoneal carcinomatosis often report abdominal pain, which is relatively refractory to morphine. It has been considered that a new animal model is required to investigate the mechanism of abdominal pain for the development of optimal treatments for this type of pain.MethodsTo prepare a peritoneal carcinomatosis model, highly peritoneal-seeding gastric cancer cells, 60As6, were implanted into the abdominal cavity. The nociceptive modality for pain-related behavior was assessed in terms of withdrawal behavior in response to mechanical stimuli and hunching behavior. Tissue samples from mouse dorsal root ganglia and spinal cord were subject to immunohistochemistry and real-time reverse transcription polymerase chain reaction.ResultsMice with peritoneal dissemination showed significant hypersensitivity of the abdomen to mechanical stimulation and spontaneous visceral pain-related behavior. There was a significant increase in c-Fos-positive cells in the spinal cord in tumor-bearing mice. Those mice exhibited a remarkable increase in substance P-positive neurons in the dorsal root ganglia (control vs. tumor, 15.4 ± 1.1 vs. 24.2 ± 3.6, P < 0.05, n = 3). A significant decreases in μ-opioid receptor expression mainly in substance P-positive neurons was observed in tumor-bearing mice (69.3 ± 4.9 vs. 38.7 ± 0.9, P < 0.05, n = 3), and a relatively higher dose of morphine was required to significantly reverse the abdominal hypersensitivity.ConclusionBoth the up-regulation of substance P and down-regulation of μ-opioid receptor seen in the dorsal root ganglia may be, at least in part, responsible for the abdominal pain-like state associated with peritoneal carcinomatosis.

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