PAG is known to be directly involved in opioid antinociception (Yaksh et al., 1976). The cortical and subcortical brain regions activated by nociceptive stimulation include the anterior cingulate, insular, frontal, and somatosensory cortices, and amygdala, which are often referred to as the “pain matrix” (Ingvar, 1999; Peyron et al., 2000; Brooks and Tracey, 2005). The findings that G/G mice showed reduced MOPR expression in the cingulate and insular cortices, amygdala, and PAG compared with A/A mice were in line with the report that G/G mice showed attenuated morphine-induced antinociception (Mague et al., 2009), which was consistent with decreased analgesic responses to morphine associated with G118 allele in humans (Chou et al., 2006a, b; Sia et al., 2008; Hayashida et al., 2008; Campa et al., 2008).
