Cell, Molecular, and Systems Neuroscience applied to the challenge of reversing nerve-injury induced sensitization.

The problem. Chronic pain affects tens of millions of people in the United States and costs hundreds of billions of dollars each year. Our ability to treat neuropathic pain is limited. Opioids, unfortunately, have severe side effects and have contributed to the opioid epidemic.

The dorsal horn. The sensory landing point for signals from the body, and a key link between the body and the brain that does much more than mere relaying. It significantly filters, as many sensory systems do, signals that reach the central nervous system.

Why filtering matters. How incoming signals from nociceptors shouting damage damage damage are filtered in the dorsal horn is important. Without filtering, their messages are amplified and persistent. We aim to explain the fundamental biology of pain sensation that is long-lasting and not proportional to tissue damage.

What changes. After nerve injury the dorsal horn reorganizes. Neurons that once fired only to damage begin firing to light touch, and descending pathways that normally inhibit pain lose control.

What we do. We watch that reorganization happen — tracking the same circuit, in the same animal, across the weeks in which acute injury becomes chronic pain.

• In vivo calcium imaging
• Viral circuit tracing
• Light-sheet microscopy
• Automated behavioral scoring