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Breakthrough in Chronic Pain Treatment: PIANO-ITN Consortium Develops Innovative Therapies

Millions of people worldwide suffer from chronic neuropathic pain due to spinal cord injuries, nerve damage, or chemotherapy-induced neuropathy (CIPN). Current painkillers often provide limited relief and come with serious side effects, highlighting the urgent need for novel, targeted therapies. The PIANO-ITN consortium has made significant strides in addressing this challenge by developing innovative drug delivery systems and new pain treatments.

A New Approach to Chronic Pain Relief

A team of 10–15 Early Stage Researchers (ESRs) within PIANO-ITN has identified key mechanisms in pain pathways and developed groundbreaking therapeutic strategies targeting sensory neurons and macrophages in the dorsal root ganglia (DRG), a crucial site for pain processing. Their research focused on:

• Advanced Biomaterials – Development of controlled drug delivery systems and contrast agents for imaging.
• Neuroimmune Communication – Identifying how neurons interact with macrophages in the DRG to influence pain signaling.
• Targeted Pain Modulation – Investigating key neuronal receptors involved in nociceptive processing.

Innovative Drug Delivery and Targeted Therapies

PIANO-ITN researchers have successfully formulated drug-loaded nanoparticles to precisely target sensory neurons and macrophages in the DRG. Additional breakthroughs include:

• Hydrogel-Nanoparticle Patches – Designed for sustained pain relief.
• Novel Pain Channel Modulators – Developed to target TRPV1, TRPM8, and TRPA1, key receptors involved in chemotherapy-induced neuropathic pain (CINP).
• Next-Generation Pain Blockers – A total of 22 Nav1.7 blockers and 15 TRPV1 antagonists have been synthesized, with potential for patent applications and future topical formulations.

Decoding the Role of the Immune System in Pain

The research has also shed light on how proinflammatory macrophages release extracellular vesicles (EVs) carrying microRNA miR-155, which can influence neuronal activity and exacerbate pain. By leveraging GABA-A receptor activation and chemical technologies to selectively target pro-inflammatory macrophages, PIANO-ITN has introduced a novel therapeutic approach for pain relief.

One of the most promising advancements is the development of an injectable hydrogel formulation, allowing for the sustained release of a miR-155 antagomir at the site of spinal cord injury (SCI). This breakthrough has the potential to promote neuroregeneration and long-term pain relief.

Driving Innovation and Impact

The findings from PIANO-ITN have been widely shared through high-impact publications, international conferences (e.g., Society for Neuroscience), and social media engagement. This dissemination strategy has fostered interdisciplinary collaboration and heightened interest in nanoparticle technology and chronic pain treatment.

Beyond academia, these advancements hold potential for clinicians, researchers, and pharmaceutical companies developing next-generation analgesics. The exploitation of PIANO-ITN’s findings is expected to improve the quality of life for individuals suffering from chronic pain and contribute to healthcare innovation across Europe.

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This press release was authored by Roberta Censi, Saniya Salathia, and Stefan Jackson, coordinated by Lynda Zeboudj, and based on the final results document authored by Marzia Malcangio