Psychopharmacology (2011) 215:537–548 Fig. 4 P2 amplitudes. a Mean P2 amplitudes (± SEM) across b conditions. b There was a correlation between reduction in P2 amplitude and reduction in pain in the placebo condition (r=.49, p=.03). c Reduction in P2 amplitude correlated with reduction in pain in the active placebo condition (r=.59, p<.01) placebo condition correlated with N2 and P2 amplitude reduction, showing that pain report was reliable. There was a significant interaction of gender by information due to smaller P2 amplitudes in males in the placebo condition compared to the control condition. The reduction in P2 amplitude could be interpreted as a decrease in nociceptive processing in the brain, although it did not cause a placebo effect on pain report for men. This effect must be interpreted with caution due to the small sample. However, the finding is similar to the effect found in Alsaksen et al. (2010), from the same laboratory, who also found a placebo effect on P2 amplitude for males only. Placebo analgesia can activate an endogenous descending pain inhibitory pathway implicating the release of endog- enous opioids (Eippert et al. 2009a, b). Hence, one possibility is that this pathway was activated more strongly in males than females. One way to trigger endogenous analgesia is by diffuse noxious inhibitory control (DNIC). Some studies report gender differences in DNIC with a more effective inhibition of pain in males (Pud et al. 2009; Staud et al. 2003), although some report no gender differences (Lautenbacher et al. 2008). Alter- natively, the endogenous inhibitory pathway is function- ally equivalent in males and females, but they respond differently to verbal information about analgesia. For instance, information that a painkiller had been adminis- tered might have dampened physiological stress and arousal in males, but not females. Reductions in physio- logical arousal can decrease laser-evoked vertex potentials (Beydoun et al. 1993). Although the present gender difference must be treated with caution, future studies should address the possible gender differences in endog- enous pain inhibition and placebo responding. The placebo effect on P2 amplitude did not cause a placebo effect on pain intensity for males. Aslaksen et al. (2010) found no placebo effect on pain intensity, although a placebo effect was observed on pain unpleasantness. In Colloca et al. (2008), a placebo effect was observed on P2 amplitude, but not on pain intensity. One possible explana- tion is that P2 amplitude reduction must exceed a certain magnitude in order to produce a unit reduction in pain report (Colloca et al. 2008). A small reduction in P2 amplitude would constitute an ambiguous signal for the subject with a consequent uncertainty as to whether pain was reduced in the posttest or not (Allan and Siegel 2002). The sensory information may or may not be interpreted as a reduction in pain depending on expectancies and suggest- ibility (Morton et al. 2010). 545