Neuropathic (nerve-related) pain is a devastating condition that affects 6 million people in the UK, commonly caused by diabetic neuropathy and entrapment neuropathies such as sciatica and Morton’s neuroma. The currently available pharmacological treatments, e.g., opioids and gabapentin, provide only limited benefits and come with addictive side effects. The limitations of current treatments are partly due to a lack of understanding of the pathophysiology of human neuropathic pain and the challenges in translating findings from preclinical murine models to humans. As a result, there is an increasing demand for the use of human nerve tissues and humanized in vitro model systems to better understand disease pathology at various stages of drug development. In November 2024, I published my findings on a ‘pain-associated’ glucocorticoid-induced macrophage (MGC) from patients with painful entrapment neuropathy, specifically Morton’s neuroma, in the journal PAIN. My fellowship research project aims to further investigate the specific role of MGC in the development of human neuropathic pain with using a humanised coculture model system and human injured nerves. The results of my research will deepen our understanding of the underlying neuro-immune interactions involved in human neuropathic pain, potentially paving the way for the development of macrophage-specific pain treatments within the next decade.

There are four objectives of my fellowship research project:

1. Characterize the effects of human MGC on the excitability of injured human induced pluripotent stem cell-derived sensory neurons (hiPSCdSN) in vitro
2. Assess the phenotypic changes of macrophage subpopulations after interacting with injured hiPSCdSN in vitro
3. Decipher the transcriptomic signatures and cell-cell interactions within Morton’s neuroma and control nerves at single-cell level
4. Extend the applicability of my findings to other human peripheral neuropathies, such as painful diabetic neuropathy

Relevant publications:

Chang, P.-S., Sandy-Hindmarch, O. P., Scheuren, P. S., De Schoenmacker, I., Hubli, M., Loizou, C., Wirth, S., Mahadevan, D., Wiberg, A., Furniss, D., Calvo, M., Bennett, D. L. H., Denk, F., Baskozos, G., & Schmid, A. B. (2024). The local molecular signature of human peripheral neuropathic pain. Pain. https://doi.org/10.1097/j.pain.0000000000003472