The magnitude of nocebo effects in pain: A meta-analysis

The investigation of nocebo effects is evolving, and a few literature reviews have emerged, although so far without quantifying such effects. This meta-analysis investigated nocebo effects in pain. We searched the databases PubMed, EMBASE, Scopus, and the Cochrane Controlled Trial Register with the term “nocebo.” Only studies that investigated nocebo effects as the effects that followed the administration of an inert treatment along with verbal suggestions of symptom worsening and that included a no-treatment control condition were eligible. Ten studies fulfilled the selection criteria. The effect sizes were calculated using Cohen’s d and Hedges’ g. The overall magnitude of the nocebo effect was moderate to large (lowest g = 0.62 [0.24–1.01] and highest g = 1.03 [0.63–1.43]) and highly variable (range of g = −0.43 to 4.05). The magnitudes and range of effect sizes was similar to those of placebo effects (d = 0.81) in mechanistic studies. In studies in which nocebo effects were induced by a combination of verbal suggestions and conditioning, the effect size was larger (lowest g = 0.76 [0.39–1.14] and highest g = 1.17 [0.52–1.81]) than in studies in which nocebo effects were induced by verbal suggestions alone (lowest g = 0.64 [−0.25 to 1.53] and highest g = 0.87 [0.40–1.34]). These findings are similar to those in the placebo literature. As the magnitude of the nocebo effect is variable and sometimes large, this meta-analysis demonstrates the importance of minimizing nocebo effects in clinical practice.     

Lamotrigine in spinal cord injury pain: a randomized controlled trial

The objective was to investigate the effectiveness of lamotrigine for the treatment of spinal cord injury pain and clinical signs of neuronal hyperexcitability. Thirty patients with spinal cord injury (SCI) and at or below level neuropathic pain participated in a randomized double blind, placebo-controlled, crossover trial. A 1-week baseline period was followed by two treatment periods of 9 weeks duration with lamotrigine slowly increased to a maximum of 400 mg or placebo separated by a 2-week washout period. The primary outcome measure was the change in median pain score from baseline week to the last week of treatment. Secondary outcome measures included thresholds to standardized sensory stimuli using quantitative sensory testing. Twenty-two patients completed the trial. We found no statistically significant effect of lamotrigine as evaluated in the total sample. However, in patients with incomplete SCI, lamotrigine significantly reduced pain at or below SCI level. Patients with brush evoked allodynia and wind-up-like pain in the area of maximal pain were more likely to have a positive effect to lamotrigine than patients without these evoked pains (7 of 7 vs. 1 of 14). Lamotrigine was generally well tolerated. While this trial showed no significant effect on spontaneous and evoked pain in complete and incomplete spinal cord injury, lamotrigine reduced spontaneous pain in patients with incomplete spinal cord injury and evoked pain in the area of spontaneous pain.     

Increased contact heat pain and shortened latencies of contact heat evoked potentials following capsaicin-induced heat hyperalgesia

ObjectiveTo examine changes in contact heat evoked potentials (CHEPs) and perceived pain intensity following acute sensitization with topical capsaicin.MethodsCHEPs were recorded before and after 20 min of topical capsaicin application (200 μl, 5%) during skin warming in 22 healthy subjects. To evaluate the sequence effects and skin warming on CHEPs, 10 of these subjects also participated in a control study.ResultsTopical capsaicin yielded an increase in contact heat evoked pain ratings (p < 0.0001) and a shortening in N2 latency from a mean 345.2 ± 37.2 ms to 310.2 ± 38.5 ms recorded from the vertex position (p = 0.003, paired t-test). No difference was found in the N2–P2 peak-to-peak amplitude (p = 0.83). These results were unchanged after controlling for sequence effects and skin warming. Following capsaicin, ultralate CHEPs (N2a latencies 970–1352 ms) were recorded in three subjects.ConclusionsOur study showed a decrease in late CHEPs latencies and appearance of ultralate potentials compatible with sensitization of Aδ fibers and C fibers.SignificanceContact heat may be a useful tool to assess sensitization of the pain system.