Extended-release paracetamol (ER-APAP) may have a greater analgesic effect than placebo in patients with osteoarthritic knee pain, according to results from a randomized double-blind trial published in Pain Medicine.1

For this study, investigators randomly assigned 25 patients to 3 groups. One group received 4 doses of 8-hour ER-APAP (2 x 665 mg), another group received 4 doses of matched placebo, and the last group received no treatment (control). Pain intensity was assessed before and after painful stimulation of the knee and before and after functional magnetic resonance imaging (fMRI). During the painful stimulation period, participants underwent pressure stimulation tests of the knee and were asked to rate the pain based on a subjective numeric pain scale.

Participants receiving ER-APAP experienced greater relief of prestimulated osteoarthritis knee joint pain compared with those taking placebo (P <.004). After stimulation, patients who had received ER-APAP or placebo experienced a reduction in knee joint pain (P =.014 and P =.032, respectively), with ER-APAP showing a 35% greater reduction in pain compared with placebo.

In addition, significant reductions in blood oxygen level-dependent (BOLD) signal activation were detected in the sensory cortex following stimulation in the ER-APAP group vs controls (P =.002). Compared with the no-treatment group, patients receiving placebo experienced greater poststimulation reductions in BOLD signal activation in the frontal cortex (P <.001), sensory cortex (P <.001), insula (P <.003), and subgenual prefrontal cortex (P <.001).

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According to the investigators, placebo resulted in greater reductions in BOLD signal activation in several brain regions associated with either the limbic system or those regions which “work closely with this system for emotional, cognitive, or psychological functions, suggesting a potential mechanism of the placebo effect in the brain.”

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