Pain modulation research reagent

Pain & Analgesia

LSP investigators are developing novel non-opioid treatments for pain with greater long-term efficacy and lower potential for abuse.

Existing therapies for pain are often ineffective or liable to abuse, contributing to our current addiction and overdose crisis. Despite the interest in non-addictive alternatives, developing non-opioid analgesics remains one of the most challenging problems in contemporary drug discovery.

To help solve this problem, LSP investigators use diverse cutting-edge systems pharmacology tools, including iPSC-derived neuronal drug screening, mass spectrometry proteomics, protein structure prediction and docking, computation-assisted synthesis planning, and advanced AI-assisted behavioral assays. This approach is target agnostic, aiming to understand the complex cellular interactions that underlie pain sensation and identify cell-based phenotypes that indicate nociceptor silencing.

These efforts are part of an ambitious multi-institution project funded by DARPA (the Panacea Research Program), which aims to develop novel small molecules and biologics for treating chronic pain and inflammation while expanding computation-enabled methods for drug discovery.

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Featured Publications

Nociceptor-immune interactomes reveal insult-specific immune signatures of pain

Jain et al.

Nat Immunol. 2024 May 28. PMCID: PMC11224023

State-Dependent Inhibition of Nav1.8 Sodium Channels by VX-150 and VX-548

Vaelli et al.

Mol Pharmacol. 2024 Nov 18. PMCID: PMC11585256

Related Publications

• Barkai, O., Zhang, B., Turnes, B. L., Arab, M., Yarmolinsky, D. A., Zhang, Z., Barrett, L. B., & Woolf, C. J. (2025). A machine learning tool with light-based image analysis for automatic classification of 3D pain behaviors. Cell Reports Methods, 5(9), 101145.
• Ma, X. C., & Clardy, J. (2025). Spontaneous Generation of an Endogenous RORγt Agonist. Journal of the American Chemical Society, 147(14), 11688–11692.
• Vaelli, P., Fujita, A., Jo, S., Zhang, H.-X. B., Osorno, T., Ma, X., & Bean, B. P. (2024). State-Dependent Inhibition of Nav1.8 Sodium Channels by VX-150 and VX-548. Molecular Pharmacology, 106(6), 298–308.
• Jain, A., Gyori, B. M., Hakim, S., Jain, A., Sun, L., Petrova, V., Bhuiyan, S. A., Zhen, S., Wang, Q., Kawaguchi, R., Bunga, S., Taub, D. G., Ruiz-Cantero, M. C., Tong-Li, C., Andrews, N., Kotoda, M., Renthal, W., Sorger, P. K., & Woolf, C. J. (2024). Nociceptor-immune interactomes reveal insult-specific immune signatures of pain. Nature Immunology.
• Jayakar, S., Shim, J., Jo, S., Bean, B. P., Singeç, I., & Woolf, C. J. (2021). Developing nociceptor-selective treatments for acute and chronic pain. Science Translational Medicine, 13(619), eabj9837.
• Lee, S., Jo, S., Talbot, S., Zhang, H.-X. B., Kotoda, M., Andrews, N. A., Puopolo, M., Liu, P. W., Jacquemont, T., Pascal, M., Heckman, L. M., Jain, A., Lee, J., Woolf, C. J., & Bean, B. P. (2019). Novel charged sodium and calcium channel inhibitor active against neurogenic inflammation. eLife, 8.