RNA-Protein Interactions in Nociception

This five-year R01 project funded by the National Institute of Neurological Disorders and Stroke (NINDS) to investigates a gene vector therapy approach for chronic pain. The project addresses the limitations and risks of current treatments—surgery and opioid medications—by probing cellular mechanisms within nociceptors, the neurons responsible for transmitting pain signals. Harrison and his team have identified CELF4, an RNA-binding protein present in nociceptors, which they hypothesize acts to inhibit production of pro-nociceptive cellular components.

The central aim is to limit synthesis of ion channels, receptors, and other molecules that sensitize nociceptors and thereby reduce their excitability. To test this, the researchers will explore local delivery of CELF4 into pain neurons using an adeno-associated virus (AAV) gene vector. This locally administered vector approach seeks to stimulate production of CELF4 specifically in targeted regions, reducing peripheral neuronal sensitization without systemic side effects associated with opioids or the irreversible consequences of some surgical interventions. The project will examine whether the AAV-driven expression of CELF4 can diminish molecular drivers of nociceptor hyperexcitability and translate into measurable reductions in pain at treated sites.

Researchers emphasize that the approach could offer a less invasive option for individuals with chronic pain who prefer to avoid major surgeries or long-term opioid therapy. The research is positioned to generate mechanistic insights into RNA–protein interactions in nociception by elucidating how CELF4 regulates translation of pro-nociceptive factors within pain-sensing neurons. Work under this grant will integrate biochemical and cellular studies of CELF4 function in nociceptors with preclinical evaluation of AAV-mediated delivery strategies. If successful, the study could lay the groundwork for clinical collaborations and future trials with clinicians to evaluate safety and efficacy in patients with chronic pain conditions.

The program reflects UNE’s broader research emphasis on translational biomedical work and the Center for Pain Research, leveraging molecular discovery to develop targeted, non-opioid therapeutic alternatives. The team aim to validate CELF4 as a modulatory factor in nociceptor biology and advance gene vector approaches that selectively reduce neuronal sensitization, potentially offering new therapeutic avenues for people living with chronic, treatment-resistant pain.