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The importance of central sensitization for clinical trials of disease modifying osteoarthritis drugs (DMOADs)

David A Walsh1,2, Daniel F McWilliams1,3

  • 1Pain Centre Versus Arthritis & Academic Rheumatology, University of Nottingham, UK.

Osteoarthritis Imaging
|June 4, 2026
PubMed

Insights

Central sensitization, a condition affecting the central nervous system, can hinder pain relief from osteoarthritis (OA) treatments. Measuring central pain hypersensitivity is crucial for evaluating disease-modifying OA drugs (DMOADs).

Area of Science:

  • Rheumatology
  • Pain Medicine
  • Neuroscience

Background:

  • Osteoarthritis (OA) pain is linked to joint structural changes, often assessed via imaging.
  • Disease-modifying OA drugs (DMOADs) are expected to alleviate OA pain by targeting structural issues.
  • Central sensitization, an overactive central nervous system response to pain, can impede pain relief and complicate clinical trial outcomes.

Purpose of the Study:

  • To explore the role of central sensitization in osteoarthritis pain.
  • To identify methods for measuring central pain hypersensitivity in OA patients.
  • To enhance the evaluation of DMOADs in clinical trials by accounting for central pain mechanisms.

Main Methods:

  • Review of central sensitization mechanisms in OA pain.
  • Identification of validated tools for assessing central pain hypersensitivity, including questionnaires (Central Aspects of Pain, Central Sensitization Inventory-9) and quantitative sensory testing (Pressure Pain Thresholds, Temporal Summation, Conditioned Pain Modulation).

Main Results:

  • Central sensitization alters pain perception, including severity, distribution, and emotional/cognitive aspects.
  • Central pain processing can mask the analgesic effects of structural treatments in clinical trials.
  • Indices of central pain hypersensitivity can reflect central sensitization in humans.

Conclusions:

  • Understanding and measuring central pain hypersensitivity is vital for accurately assessing OA pain.
  • Incorporating central pain assessments can improve the power of clinical trials to demonstrate DMOAD efficacy for both structural and pain outcomes.
  • Managing central sensitization is key to improving the predominant clinical problem of OA pain.
Keywords:
Central sensitizationNociplasticPain

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