Increased somatosensory amplification is associated with decreased pressure pain thresholds at both trigeminal and extra-trigeminal locations in healthy individuals.

BACKGROUND: The diagnosis of temporomandibular disorders (TMD) is based on patient history and physical examination, and may require medical imaging. Masticatory muscle palpation is essential to make a diagnosis of TMD. However, the response of masticatory muscles to mechanical pressure stimuli depends on many physical and psychological factors. OBJECTIVE: This study aimed at determining the impact of somatosensory amplification (SSA)-an estimate of somatic awareness and bodily hypervigilance-on pressure pain thresholds (PPTs) measured at both trigeminal and extra-trigeminal locations in healthy individuals. METHODS: PPTs were measured at the right anterior temporalis and superficial masseter, and the thenar eminence of the right hand in one hundred healhty individuals (69F, 31M), divided in three groups based on their SSA scores: low (N = 32), intermediate (N = 34) and high (N = 34). General linear models were used to test between-group differences in PPTs including sex as a covariate. The level of significance was set at P < .05. RESULTS: Individuals with high SSA had lower PPTs at the anterior temporalis than individuals with low (P = .006) and intermediate (P = .001) SSA. No significant between-group differences were found in PPTs measured at the masseter (P = .372). PPTs measured at the thenar eminence were significantly lower in the high than the low SSA group (P = .009). Females had lower PPTs at the masseter than males (P = .021) but not at other muscle locations (all P > .05). CONCLUSION: Increased somatosensory amplification is associated with decreased pressure pain thresholds at both trigeminal and extra-trigeminal locations in healthy individuals. SSA could be a potential confounder while diagnosing TMD and evaluating treatment outcomes.

Autophagy is associated with chemoresistance in neuroblastoma.

BACKGROUND: Neuroblastoma (NB) is a frequent pediatric tumor characterized by a poor prognosis where a majority of tumors progress despite intensive multimodality treatments. Autophagy, a self-degradative process in cells, could be induced by chemotherapy and be associated with chemoresistance. The aim of this study was to determine whether: 1) autophagy is present in NB, 2) chemotherapy modified its levels, and 3) its inhibition decreased chemoresistance. METHODS: Immunohistochemical stainings were performed on samples from 184 NB patients in order to verify the expression of LC3B, a specific marker for autophagy, and Beclin 1, a positive regulator of autophagy. In addition, we performed an in vitro study with six NB cell lines and six drugs (vincristine, doxorubicin, cisplatin temozolomide, LY294002 and syrolimus). Inhibition of autophagy was performed using ATG5 knockdown cells or hydroxychloroquine (HCQ). Cell survival was measured using the MTT cell proliferation assay. Autophagy was detected by monodansylcadaverine, confocal microscopy and Western blot. In vivo study with tumor xenografts in NSG mice was performed. RESULTS: Our results have indicated that autophagy was present at low levels in NB and was not a prognostic factor, while Beclin 1 was highly expressed in children with poor NB prognosis. However, autophagy levels increased after chemotherapy in vitro and in vivo. Tumor progression was significantly decreased in mice treated with a combination of HCQ and vincristine. CONCLUSIONS: Taken together, autophagy is present in NB, induced by chemotherapy and associated with chemoresistance, which is significantly reduced by its inhibition. Therefore, targeting autophagy represents a very attractive approach to develop new therapeutic strategies in NB.