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J Vet Sci. 2017 Sep 30;18(3):267-272. doi: 10.4142/jvs.2017.18.3.267.

Inoculation of Lewis lung carcinoma cells enhances formalin-induced pain behavior and spinal Fos expression in mice.

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Department of Physiology and Medical Science and Brain Research Institute, College of Medicine, Chungnam National University, Daejeon 35015, Korea.
KM Fundamental Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea.
Department of Meridian & Acupoint, College of Oriental Medicine, Wonkwang University, Iksan 54538, Korea.


The incidence of lung cancer has rapidly increased and cancer patients at a later cancer stage frequently suffer from unbearable cancer-associated pain. However, the pathophysiology of lung cancer pain has not been fully described due to a lack of appropriate animal models. This study was designed to determine the effect of Lewis lung carcinoma (LLC) cell inoculation on formalin-induced pain behavior and spinal Fos expression in C57BL/6 mice. LLC cells (1.5 × 105, 2.5 × 105, 3.0 × 105 or 5.0 × 105) were inoculated into back or peri-sciatic nerve areas. Back area inoculation was adopted to determine the effect of cancer cell circulating factors and the peri-sciatic nerve area was used to evaluate the possible effects of cancer cell contacting and circulating factors on formalin-induced pain. At postinoculation day 7, LLC cell (5.0 × 105) inoculations in both back and peri-sciatic nerve area significantly increased formalin-induced paw-licking time and spinal Fos expression over those in cell-media-inoculated (control) mice. Enhanced pain behavior and spinal Fos expression were significantly suppressed by ibuprofen pretreatment (250 mg/kg). The results of this study suggest that LLC cell circulating factors and inflammatory responses may be critical in enhancing pain sensation in the early stage of lung cancer cell inoculation.


Fos; Lewis lung carcinoma; formalin; lung neoplasms; pain

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