Normalization of temporal summation and of conditioned pain modulation may be associated with pain reduction in knee osteoarthritis, according to a systematic review and meta-analysis published in Pain Medicine.

Researchers conducted this study to evaluate the effects of therapeutic interventions on pain analgesia and endogenous pain modulation in patients with knee osteoarthritis. A total of 8 randomized clinical trials and 3 observational studies (n=559 participants) were reviewed, in which the effects of a therapeutic intervention vs control were examined on pain intensity, temporal summation, and conditioned pain modulation. In 2 studies, an exercise intervention was examined, 3 studies investigated the effects of a pharmacologic intervention, another 3 examined neuromodulation, and 3 studies evaluated surgical interventions. In 5 studies, temporal summation only was evaluated, in 3 studies, conditioned pain modulation only was assessed, and another 3 studies examined both temporal summation and conditioned pain modulation.

No changes in pain modulation, temporal summation, or conditioned pain modulation were observed as a result of all interventions across the 11 studies. This lack of effect, according to the review authors, may be because surgical and nonsurgical interventions yielded opposite effects.

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A sensitivity analysis by intervention type was conducted to palliate the heterogeneity of observed effects. Significant effects of exercise interventions were observed on pain reduction (mean difference, –0.52; P =.008) and conditioned pain modulation increase (mean difference, 0.54; P =.004), but not on temporal summation. Neuromodulation interventions were not found to result in pain reduction but led to increased conditioned pain modulation (mean difference, 0.79; P =.007) and decreased temporal summation (mean difference, –1.88; P =.01). Pharmacologic interventions were found to increase conditioned pain modulation (mean difference, 0.64; P =.05). Surgical interventions were not found to improve any of the outcomes examined. Correlations were established between pain reduction and reduced temporal summation (P =.02) and between pain reduction and increased conditioned pain modulation (P =.04).

Study limitations include a lack of generalizability because of the small sample size.

“Phenotyping [patients with] knee osteoarthritis with temporal summation/conditioned pain modulation may be useful for understanding therapeutic approaches. To validate temporal summation and conditioned pain modulation as robust clinical biomarkers, it will be necessary to further investigate their mechanisms — and any patient factors driving responses — in a strict methodological manner,” concluded the review authors.


O’Brien AT, El-Hagrassy MM, Rafferty H, et al. Impact of therapeutic interventions on pain intensity and endogenous pain modulation in knee osteoarthritis: a systematic review and meta-analysis [published online January 5, 2019]. Pain Med. doi: 10.1093/pm/pny261

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