The Capsaicin Sensitive Afferent Neuron Innervating Skeletal Muscle is Abnormal in the Mdx Mouse

Duchenne muscular dystrophy (DMD) is a severe type of muscular dystrophy caused by a mutation of the dystrophin gene at locus Xp21, located on the short arm of the X chromosome. Muscle wasting and weakness are common in DMD and in the murine mdx model. We previously demonstrated Group III and IV afferent neurons, which innervate skeletal muscle and control blood pressure and heart rate in response to exercise, are abnormal in settings of ischemia and atrophy; such as cardiomyopathy. We hypothesized that these afferent neurons would also display abnormalities in the mdx mouse. To test this hypothesis, we developed a decerebrate mouse model using 10 wk and 6 mo old male BL10 WT and MDX mice to test mean arterial pressure (MAP) responses to intra-arterial capsaicin (IA-Cap; a specific stimulant of group IV afferent neurons). Mice were anesthetized and MAP was continuously recorded with a pressure transducer in the left carotid artery after which the animal was rendered decerebrate. Following decerebration, anesthesia was discontinued and IA-Cap (0,003-1ug/100ul) was delivered via the left common iliac artery. In rats, we have demonstrated this to be a valid model for evaluating MAP responses to activation of metabolically active afferent neurons. We observed that MAP increased in a dose-related fashion in both 10wk and 6 mo old WT and MDX, while 10 wk old MDX mouse had a normal response, the 6 months MDX mouse response was significantly blunted when compared to WT. To test whether these abnormalities are related to the onset of cardiomyopathy, Echocardiography was performed using 6 months old BL10 WT and MDX mice, no abnormality was found in terms of LV dimensions and function in MDX mice comparing with WT mice. Further studies will be performed to determine whether these abnormalities are inherent to changes in the skeletal muscle of the mdx mouse. We conclude that this murine model displays pressor responses to IA-Cap, similar to the rat and that MDX mice have a blunted blood pressure response to IA-Cap. These results indicate that abnormalities exist within the skeletal muscle afferent neurons in the mdx model.