Pain, emotion, and fear

Min Zhuo

Department of Physiology

University of Toronto Center for the Study for Pain

Neurons and synapses in the central nervous systems are plastic, and can undergo long-term changes throughout life.Studies of molecular and cellular mechanisms of such changes not only provide important insight into how we learn and store new knowledge in our brains, but also reveal the mechanisms of pathological changes occurring following an injury such as chronic pain and fear memory.We investigate the molecular and cellular mechanisms of synaptic transmission and plasticity in the central nervous system and functional implications of such plastic changes. We have used integrative approaches, a combination of genetic, electrophysiological, pharmacological and behavioral methods, to study physiological and pathological mechanisms for pain and emotional fear.At the single neuron level, whole-cell patch clamp recordings of synaptic responses are made from single neurons in brain and spinal cord slices.At the system level, neuronal evoked responses in intact or freely moving animals are performed to study neuronal plasticity in emotional learning, persistent pain and anxiety.At the behavioral level, a combination of pharmacological and genetic approaches in mice (genetic mutant mice) allows us to study molecular mechanisms of behaviors.

Pathological pain is likely a result of long-term plastic changes along somatosensory pathways, from the periphery to cortex.Due to long-term plastic changes in central regions, pain specificity is lost in the somatosensory pathway, at least from areas where allodynia was reported.Thus, drugs developed based on physiological pain mechanism may not be used for treating pathological pain.Understanding pathological pain requires understanding of plastic changes in somatosensory pathways, mainly the central nervous systems.We hope that our research activities including translational drug investigations will help to develop novel drugs/medicines for treating chronic pain, anxiety, fear and other psychiatric disorders.