Zachary T. Campbell

Credentials: Betty J. Bamforth Distinguished Chair in Anesthesiology, Vice Chair for Research (DoA), and Associate Professor, Departments of Biomolecular Chemistry and Anesthesiology

Email: zcampbell@wisc.edu

Website: Lab Website

Address:
8451 Wisconsin Institutes for Medical Research (WIMR)
1111 Highland Avenue, Madison, WI 53705

Education: B.S., University of Arizona; Ph.D., University of Arizona; Postdoctoral, University of Wisconsin-Madison
Areas of Expertise: Cell Structure & Signaling; Gene Expression & RNA Biology

Molecular mechanisms of pain signaling

Pain is pervasive and devastating. Poorly treated chronic pain is the largest source of disability in America with an estimated economic cost of more than 500 billion dollars per year. Moreover, existing strategies to disrupt pain (e.g. opiates) have well known and highly undesirable effects on reward circuits in the CNS. Better strategies for preventing chronic pain are desperately needed. In the vast majority of cases, pain originates in the periphery in a specialized type of sensory neuron called a nociceptor. Long-lived changes in their excitability – which are intimately linked to chronic pain – require de novo protein synthesis. Multiple groups have shown that peripheral inhibition of translation diminishes pain associated behaviors in pre-clinical rodent models. This suggests that translation, likely in nerve fibers, is critical for nociceptive plasticity. But what are the mRNAs that need to be locally translated and what governs the specificity of protein synthesis in nociceptors? To address these key questions, we make use of biochemistry, functional genomics, pharmacology, physiology, and genetic approaches.

The Dorsal Root Ganglion image with various pathways — Left: The Dorsal Root Ganglion (DRG) contains the cell bodies for a broad array of sensory neurons – including nociceptors – that innervate the body. Right Top – Anatomy of a eukaryotic transcript. Center – key mechanisms that have been demonstrated as analgesic in rodents. Below – a key pathway known as the integrated stress response that plays a key role in diabetic neuropathies.

Publication Highlights

Smith P, Garcia G, Meyer AR, Ryazanov AG, Ma T, Loerch S, and Campbell ZT. eEF2K regulates pain through translational control of BDNF. Molecular Cell. 2025. 85 (4) 756-769. DOI: 10.1016/j.molcel.2024.11.023

Srikanth KD … Campbell ZT, Paik R, Price TJ, Dalva MB. The synaptic ectokinase VLK triggers the EphB2–NMDAR interaction to drive injury-induced pain. Science. 2025. 20;390(6775):eadp1007. doi: 10.1126/science.adp1007

Mikesell AR, Meyer AR, Garcia G, Frietz L, Stucky CL, Pan T, Campbell ZT. GCN2 regulates paclitaxel-induced neuropathic pain. British Journal of Pharmacology. 2025. In press.

Meyer A, Garcia G, Mikesell A, O’Flanagan S, Campbell ZT. Translational control by GCN2 kinase regulates methylglyoxal-induced pain in mice. Pain. 2025. In press.

De la Peña JB, Garcia G, Campbell ZT. Ribosome profiling reveals that post-transcriptional control of Nalf1 by heterogeneous nuclear ribonucleoprotein L is required for paclitaxel-induced neuropathic pain. Pain. 2025. 2;166(9):2091-2102. DOI: 10.1097/j.pain.0000000000003577