Osteoarthritis pain mechanisms: basic studies in animal models.

Area of Science:

• Orthopedics
• Pain Research
• Neuroscience

Background:

• Osteoarthritis (OA) is a debilitating joint disease with significant unmet treatment needs.
• Current treatments for OA pain are often unsatisfactory, highlighting the need for better understanding and novel therapeutic strategies.

Purpose of the Study:

• To review and synthesize preclinical evidence on the mechanisms underlying osteoarthritis (OA) development and associated pain.
• To provide insights into OA pain mechanisms for improved therapeutic development.

Main Methods:

• Systematic review of preclinical research on osteoarthritis (OA) pain models.
• Analysis of rodent knee OA models induced by mono-iodoacetate (MIA), surgery, or spontaneous development.
• Examination of biochemical and electrophysiological studies in peripheral, spinal, and supraspinal pathways.

Main Results:

• OA pain mechanisms involve sensitization of knee nociceptors by peripheral pro-inflammatory mediators and neuropeptides.
• Spinal cytokines and neuropeptides exacerbate OA pain, while cannabinoids (CB1, CB1/CB2) offer inhibition.
• TRPV1, metalloproteinases, and 5-hydroxytryptamine (5-HT)/5-HT3 receptors in descending pathways contribute to OA pain.

Conclusions:

• Preclinical models confirm that peripheral and central sensitization, involving inflammatory mediators and neuropeptides, drives OA pain.
• Descending facilitation from the brainstem via 5-HT/5-HT3 receptors is a significant factor in OA pain.
• Further research is needed to clarify the role of altered brain functional connectivity in OA pain.