Grant: Project Grant

Touch perception has two components: a sensory component that provides information about the physical properties of a tactile stimulus and an affective component relating to the emotional perception of touch. The affective component of touch contributes to social bonds and emotional regulation. Despite the importance of gentle touch for both physical and mental health, there is little understanding of the neural circuity underlying positive gentle touch. Gentle stroking touch is detected by specialized nerves in our skin and both animal and human research has shown that stimuli that selectively activates these nerves is perceived as the most pleasant or rewarding. However, gentle touch is not always pleasant and can be perceived negatively in many disorders including chronic pain. Furthermore, this plasticity in the perception of gentle touch is not unidirectional, as use of recreational drugs such as MDMA is associated with increased touch pleasantness. Here we propose that the affective quality of gentle touch can be bidirectionally modulated by differential recruitment of neurons at both the spinal cord and brain level and this recruitment is altered in chronic pain. To study the neural processing of gentle touch we will use specialized mouse lines that selectively express light-sensitive proteins in nerves that are activated by gentle touch. Shining light on these nerves will create a sensation like stroking gentle touch in the mice. We will assess whether chronic pain can decrease the pleasantness associated with this touch and whether administration of the 'touch-enhancing' drug MDMA can augment this pleasantness. We will use biological assays to detect activity in neurons in the spinal cords and brains of mice that have undergone these various interventions followed by light mediated activation of the gentle touch nerves. These experiments will elucidate the factors that influence gentle touch perception and how this is altered in chronic pain.