Why opioids can make pain worse and stop working

Signaling Mechanisms of Opioid-Induced Hyperalgesia and Tolerance

['FUNDING_R01'] · UNIVERSITY OF TX MD ANDERSON CAN CTR · NIH-11323086

This research looks for the spinal-cord signals that make some people’s pain worsen or make opioids less effective after repeated use.

Quick facts

Phase['FUNDING_R01']
Study typeNih_funding
SexAll
SponsorUNIVERSITY OF TX MD ANDERSON CAN CTR (nih funded)
Locations1 site (HOUSTON, UNITED STATES)
Trial IDNIH-11323086 on ClinicalTrials.gov

What this research studies

Researchers will study how repeated opioid use changes proteins and signaling pathways in the spinal cord—especially BRAF, ERK, and NMDA receptors—to understand why pain can get worse and drugs stop working. They will use laboratory experiments and animal models to trace the molecular chain of events and test whether blocking specific signals prevents opioid-induced hyperalgesia and tolerance. The team aims to identify drug targets that could be given with opioids to keep them effective and safer. Most of the work is lab-based at a university medical center, so any patient involvement would be limited and specific.

Who could benefit from this research

Good fit: People taking opioid pain medications who are noticing worsening pain despite treatment or who require steadily higher opioid doses would be the most likely candidates for related future trials.

Not a fit: People who are not using opioids or whose pain is unrelated to opioid-induced hyperalgesia or tolerance are unlikely to benefit directly from this project.

Why it matters

Potential benefit: If successful, this work could lead to treatments that prevent opioids from increasing pain and reduce the need to raise opioid doses.

How similar studies have performed: Some approaches that block NMDA receptors (for example ketamine) have helped opioid-related increased pain, but targeting BRAF and upstream signaling is a newer and largely untested strategy.

Where this research is happening

HOUSTON, UNITED STATES

Researchers

About this research

  1. This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
  2. Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
  3. For full project details, budget, and progress reports, visit the official NIH RePORTER page below.

View on NIH RePORTER →

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.