Pain
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More than half of all cancer patients have significant pain during the course of their disease. The strategic localization of TMPRSS2, a membrane-bound serine protease, on the cancer cell surface may allow it to mediate signal transduction between the cancer cell and its extracellular environment. ⋯ Coculture of human cancer cells with murine trigeminal neurons demonstrated colocalization of TMPRSS2 with PAR2. These results point to a novel role for a cell membrane-anchored mediator in cancer pain, as well as pain in general.
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Accumulating evidence suggests an important contribution of reactive oxygen species (ROS) to pain and neuropsychiatric disorders, but their role in pain-related plasticity in the brain is largely unknown. Neuroplasticity in the central nucleus of the amygdala (CeA) correlates positively with pain behaviors in different models. Little is known, however, about mechanisms of visceral pain-related amygdala changes. ⋯ Whole-cell patch-clamp recordings of CeA neurons in brain slices from zymosan-treated rats showed that tempol decreased neuronal excitability and excitatory synaptic transmission of presumed nociceptive inputs from the brainstem (parabrachial area) through a combination of presynaptic and postsynaptic actions. Tempol had no effect in brain slices from sham controls. The results suggest that ROS contribute to visceral pain-related hyperactivity of amygdala neurons and amygdala-dependent behaviors through a mechanism that involves increased excitatory transmission and excitability of CeA neurons.