IB4(+) and TRPV1(+) sensory neurons mediate pain but not proliferation in a mouse model of squamous cell carcinoma

Background: Cancer pain severely limits function and significantly reduces quality of life. Subtypes of sensory neurons involved in cancer pain and proliferation are not clear.Methods: We produced a cancer model by inoculating human oral squamous cell carcinoma (SCC) cells into the hind paw of athymic mice. We quantified mechanical and thermal nociception using the paw withdrawal assays. Neurotoxins isolectin B4-saporin (IB4-SAP), or capsaicin was injected intrathecally to selectively ablate IB4(+) neurons or TRPV1(+) neurons, respectively. JNJ-17203212, a TRPV1 antagonist, was also injected intrathecally. TRPV1 protein expression in the spinal cord was quantified with western blot. Paw volume was measured by a plethysmometer and was used as an index for tumor size. Ki-67 immunostaining in mouse paw sections was performed to evaluate cancer proliferation in situ.Results: We showed that mice with SCC exhibited both mechanical and thermal hypersensitivity. Selective ablation of IB4(+) neurons by IB4-SAP decreased mechanical allodynia in mice with SCC. Selective ablation of TRPV1(+) neurons by intrathecal capsaicin injection, or TRPV1 antagonism by JNJ-17203212 in the IB4-SAP treated mice completely reversed SCC-induced thermal hyperalgesia, without affecting mechanical allodynia. Furthermore, TRPV1 protein expression was increased in the spinal cord of SCC mice compared to normal mice. Neither removal of IB4(+) or TRPV1(+) neurons affected SCC proliferation.Conclusions: We show in a mouse model that IB4(+) neurons play an important role in cancer-induced mechanical allodynia, while TRPV1 mediates cancer-induced thermal hyperalgesia. Characterization of the sensory fiber subtypes responsible for cancer pain could lead to the development of targeted therapeutics.

Spontaneous osteonecrosis of the jaws in the maxilla of mice on antiresorptive treatment: A novel ONJ mouse model

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

A method using artificial neural networks to morphologically assess mouse blastocyst quality

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Disperse Red 1 (textile dye) induces cytotoxic and genotoxic effects in mouse germ cells

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

A comparison of mucosal surface area and villous histology in small intestines of the brazilian free-tailed bat (Tadarida brasiliensis) and the mouse (Mus musculus)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Optimal clearance of Sporothrix schenckii requires an intact Th17 response in a mouse model of systemic infection

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Lifetime reproductive efficiency of BALB/c mouse pairs after an environmental modification at 3 mating ages

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Chemopreventive effects of mate against mouse mammary and colon carcinogenesis

The present study evaluated the chemopreventive potential of mate tea-like intake on mammary and colon carcinogenesis initiated by 7,12-dimethylbenz(a)antracene (DMBA) and 1,2-dimethylhydrazine (DMH) in female Swiss mice. After the initiation period, the animals received basal diet and organic mate tea-like, conventional mate tea-like, or green tea (positive control) at 2.0% as the drinking fluid during 15 weeks. At week 20, colon and mammary gland were analyzed for preneoplastic and neoplastic lesions development. Colon and mammary gland complexes were processed for cell proliferation analysis, estimated by proliferating cell nuclear antigen labeling index (PCNA-LI%). Specially, organic mate tea-like reduced the values of PCNA-LI% in colonic crypts (p < .003) and in mammary glands (p < .05) in DMBA/DMH-initiated groups. A lower incidence of aberrant crypt foci (ACF) in colon (p = .03) and of hyperplastic and neoplastic lesions in mammary gland (p < .05 and p < .02, respectively) was observed in DMBA/DMH-initiated groups treated with organic mate tea-like. These results suggest that post-initiation treatment with organic mate tea-like inhibited the development of colon and mammary carcinogenesis in a two-step medium-term mouse carcinogenesis model.

Essential oil of Melaleuca alternifolia for the treatment of oral candidiasis induced in an immunosuppressed mouse model

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Single-cell expression profiling reveals a dynamic state of cardiac precursor cells in the early mouse embryo

In the early vertebrate embryo, cardiac progenitor/precursor cells (CPs) give rise to cardiac structures. Better understanding their biological character is critical to understand the heart development and to apply CPs for the clinical arena. However, our knowledge remains incomplete. With the use of single-cell expression profiling, we have now revealed rapid and dynamic changes in gene expression profiles of the embryonic CPs during the early phase after their segregation from the cardiac mesoderm. Progressively, the nascent mesodermal gene Mesp1 terminated, and Nkx2-5+/Tbx5+ population rapidly replaced the Tbx5low+ population as the expression of the cardiac genes Tbx5 and Nkx2-5 increased. At the Early Headfold stage, Tbx5-expressing CPs gradually showed a unique molecular signature with signs of cardiomyocyte differentiation. Lineage-tracing revealed a developmentally distinct characteristic of this population. They underwent progressive differentiation only towards the cardiomyocyte lineage corresponding to the first heart field rather than being maintained as a progenitor pool. More importantly, Tbx5 likely plays an important role in a transcriptional network to regulate the distinct character of the FHF via a positive feedback loop to activate the robust expression of Tbx5 in CPs. These data expands our knowledge on the behavior of CPs during the early phase of cardiac development, subsequently providing a platform for further study.