Differential Opioid Action on Sensory and Affective Cerebral Pain Processing

Low doses of morphine, the most commonly used opioid analgesic, have been shown to significantly reduce the affective but not the sensory intensive dimension of pain. This suggests differential dose–response relationships of opioid analgesia on the sensory and affective components of pain. We investigated the effects of different alfentanil plasma concentration levels (0, 19.6±2.7, 47.2±7.6, and 76.6±11.3 ng/ml) on pain-related brain activation achieved by short pulses of gaseous CO2 delivered to the nasal mucosa, using functional magnetic resonance imaging (fMRI) on a 3.0 T MRI scanner in 16 non-carriers and 9 homozygous carriers of the μ-opioid receptor gene variant OPRM1 118A>G. Increasing opioid concentrations had differential effects in brain regions processing the sensory and affective dimensions of pain. In brain regions associated with the processing of the sensory intensity of pain (primary and secondary somatosensory cortices, posterior insular cortex), activation decreased linearly in relation to alfentanil concentrations, which was significantly less pronounced in OPRM1 118G carriers. In contrast, in brain regions known to process the affective dimension of pain (parahippocampal gyrus, amygdala, anterior insula), pain-related activation disappeared at the lowest alfentanil dose, without genotype differences. Clinical Pharmacology & Therapeutics (2008); 83, 4, 577–588.doi:10.1038/sj.clpt.6100441