Circuit Basis of Pain & Itch

How do the circuits constituting our nervous system sense, perceive, and respond to stimuli causing pain and itch? How do pathological pain and itch alter these neural circuits? What are the molecular and cellular mechanisms that are involved in these processes?

We strive to answer the above questions and many more, leveraging genetic, optical, and behavioral techniques in mice.

In the long run, we hope our work will lead to novel therapeutic strategies to address clinical challenges in the treatment of chronic pain and itch.

How do our emotional states interact with pain and itch in the brain?

How we perceive pain and itch are often modulated by our emotional states, such as stress and anxiety. Although it is known that these interactions occur in the brain, the underlying neural mechanisms remain poorly understood. In our studies, we find that the lateral hypothalamic area, in the mid-brain, plays an important role in stress-mediated modulation of pain and itch. The lateral hypothalamus, through its downstream circuits in the brainstem and, thereby, the spinal cord, translates emotional information into modulation of pain or itch. These studies will be critical to understand how chronic stress and anxiety exacerbate pathological pain and itch, and vice versa.

What are the maladaptive mechanisms underlying chronic pain and itch?

Pain and itch are fundamentally protective. However, these useful protective mechanisms can become a burden when they become chronic or outlast the stimulus. When and where these otherwise beneficial mechanisms become pathological remains poorly understood. Our laboratory studies how these conditions might be linked to alterations in specific brain areas regarding their connectivity, molecular composition, and activity. We are particularly focused on how classical synaptic plasticity mechanisms might be involved in rewiring the neural circuits in our brains in an irreversible fashion, thereby causing long-lasting pain and itch that are difficult to treat.

How do neuropeptides and neuromodulators drive plasticity in pain and itch circuits?

The neural circuits for pain and itch are incredibly plastic. Repeated exposure to stimuli that cause pain and itch can alter the long-term activity of these circuits. These long-term changes often result in pathological chronic pain and itch. Neuropeptides and neuromodulators released by neurons in these circuits are the major players in neural plasticity. In our laboratory, we use recently developed in vivo fluorescence sensors for specific neuromodulators and peptides, such as serotonin, dopamine, norepinephrine, and substance P, to determine how the dynamics of these molecules change in circuits for chronic pain and itch.

Funders

Perception. Emotion. Modulation