Prevention And Treatment Of Chronic Pain Conditions Using Abeta Amyloid-Targeting Agents

Brief Description

A mechanistic discovery linking amyloid beta (Aβ)-associated neurodegeneration with chronic pain after peripheral nerve injury, revealing Aβ as a novel therapeutic target.

Full Description

Researcher at UC Irvine uncovered a novel mechanism linking neuronal amyloid beta (Aβ) production to chronic pain following peripheral nerve injury. The study revealed that post-injury disruptions in lipid metabolism and protein synthesis trigger the release of neurotoxic Aβ. Importantly, blocking Aβ production using inhibitors of NAAA (ARN19702), BACE1 (LY2811376, MK8931) or γ-secretase (NGP555) prevented the development of persistent pain hypersensitivity and associated anxiety-like behaviors in mice. This targeted approach offers a promising therapeutic pathway for chronic pain modification without affecting acute pain responses or cognitive functions.

Suggested uses

• Development of novel chronic pain therapeutics targeting Aβ pathways.
• Repositioning of existing Alzheimer’s drugs for chronic pain patients. 
• Pharmaceutical innovation in neurodegenerative and pain disorders. 
• Personalized medicine approaches for persistent pain management.

Advantages

• Identifies a direct mechanistic link between neurodegeneration and chronic pain. 
• Offers a novel target for disease-modifying therapies in chronic pain. 
• Enables repositioning of existing Alzheimer’s treatments for chronic pain management. 
• Provides a potential pathway to prevent or treat pain chronification.

Patent Status

Patent Pending

Related Materials

• Fotio, Y., et al. Piomelli, D. (2021). Antinociceptive Profile of ARN19702, (2-Ethylsulfonylphenyl)-[(2S)-4-(6-fluoro-1,3-benzothiazol-2-yl)-2-methylpiperazin-1-yl]methanone, a Novel Orally Active N-Acylethanolamine Acid Amidase Inhibitor, in Animal Models. The Journal of Pharmacology and Experimental Therapeutics, 378 (2).