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Papers of the Week

Papers: 10 Jun 2023 - 16 Jun 2023

Basic Science

Animal Studies, Molecular/Cellular, Neurobiology

Cancer Pain, Psychological/Comorbidities

2023 Jun 14

Mol Pharmacol


Inhibition of tumor-derived CCL2 expression attenuates tactile allodynia in NCTC 2472 fibrosarcoma-inoculated mice.


Taniguchi M, Yasukochi S, Yamakawa W, Tsurudome Y, Tsuruta A, Horiguchi M, Ushijima K, Yamashita T, Shindo N, Ojida A, Matsunaga N, Koyanagi S, Ohdo S


Neuropathic pain associated with cancers is caused by tumor growth compressing and damaging nerves, which would also be enhanced by inflammatory factors through sensitizing nociceptor neurons. One troublesome hallmark symptom of neuropathic pain is hypersensitivity to innocuous stimuli, a condition known as “tactile allodynia” which is often refractory to NSAIDs and opioids. The involvement of chemokine CCL2 (monocyte chemoattractant protein-1) in cancer-evoked neuropathic pain is well established, but opinions remain divided as to whether CCL2 is involved in the production of tactile allodynia with tumor growth. In this study, we constructed knockout NCTC2472 (-KO NCTC) fibrosarcoma cells and conducted pain behavioral test using -KO NCTC-implanted mice. Implantation of naïve NCTC cells around the sciatic nerves of mice produced tactile allodynia in the inoculated paw. Although the growth of KO NCTC-formed tumors was comparable to that of naïve NCTC-formed tumors, -KO NCTC-bearing mice failed to show tactile pain hypersensitivity, suggesting the involvement of CCL2 in cancer-induced allodynia. Subcutaneous administration of controlled-release nanoparticles containing CCL2 expression inhibitor NS-3-008 significantly attenuated tactile allodynia in naïve NCTC-bearing mice accompanied by a reduction of CCL2 content in tumor masses. Our present findings suggest that inhibition of CCL2 expression in cancer cells is useful strategy to attenuate tactile allodynia induced by tumor growth. Development of a controlled release system of CCL2 expression inhibitor may be a preventive option for the treatment of cancer-evoked neuropathic pain. The blockade of chemokine/receptor signaling, particularly for C-C motif chemokine ligands 2 (CCL2) and its high-affinity receptor CCR2, has been implicated to attenuate cancer-induced inflammatory and nociceptive pain. This study demonstrated that continuous inhibition of CCL2 production from cancer cells also prevents the development of tactile allodynia associated with tumor growth. Development of controlled release system of CCL2 expression inhibitor may be a preventative option for management of cancer-evoked tactile allodynia.