Managing debilitating pain, a hallmark of tissue injury and neuropathy, is an unmet clinical challenge and developing effective, non-addictive analgesics is critical to addressing both the chronic pain and the opioid epidemic. Through a multidisciplinary collaboration, we demonstrated the therapeutic potential by targeting the neuroimmune interaction between nociceptors and tissue immune cells, which contributes to neuropathic conditions including pain and itch. Most recently, in studying rare monogenetic diseases associated with neuropathic pain with an aim at identifying novel therapeutic targets, our laboratory has revealed that adult patients with Fibrodysplasia Ossificans Progressiva (FOP) carrying a gain-of-function point mutation (R206H) in the type I BMP receptor Activin A Receptor Type 1 (ACVR1), also known as Activin receptor-like kinase 2(ALK2), have ongoing mechanical and heat pain hypersensitivity. Supported by the NIH, foundation grants, intramural funding, and patients, our subsequent efforts utilizing both preclinical animal models and novel patient induced pluripotent stem cell (iPSC) derived disease model further demonstrate the potential targetability of ACVR1/ALK2 for common neuropathic pain conditions.
Activated nociceptors are also critical contributors to the host response after injury of the innervated tissues including skin, joint, bone and muscle. Heterotopic ossification (HO) can occur following orthopedic surgery and traumatic injuries, manifests with pathological bone formation in muscle and connective tissues. However, little progress has been made in developing effective treatments. Our group is actively studying sensory neuronal contribution to HO, with an aim at developing new strategies to manage pathological HO.
