Lessons learned in translating pain knowledge into practice.

Area of Science:

• Pain research
• Pharmacology
• Clinical trials

Background:

• Decades of research aimed to develop novel analgesics beyond opioids and NSAIDs.
• Limited success has been achieved, with few new drugs reaching clinicians.

Purpose of the Study:

• To review evidence for three drug targets for novel pain treatments.
• To explore reasons for clinical trial failures in pain management.

Main Methods:

• Selective review of best available evidence and practice.
• Focus on clinical updates aligned with the IASP Global Year.
• Analysis of three representative target molecules: nerve growth factor, NaV1.7, and neurokinin receptors.

Main Results:

• Nerve growth factor antibodies showed efficacy but led to joint replacement needs.
• NaV1.7 blockers lacked sufficient efficacy, potentially due to lack of patient stratification.
• Neurokinin receptor blockers also proved insufficiently effective.
• Primary reasons for failure were lack of efficacy and, less commonly, severe side effects.

Conclusions:

• Clinical trial failures highlight the need for improved preclinical models and patient stratification.
• Enhanced molecular phenotyping and patient stratification are crucial for future drug development.
• Collaboration among stakeholders, including better preclinical studies and patient participation, is vital for advancing analgesic discovery.