The opioid receptor mu 1 (OPRM1) rs1799971 and catechol-O-methyltransferase (COMT) rs4680 as genetic markers for placebo analgesia.
Level 2 - randomized trial
Randomized controlled experimental trial in humans
PubMed 30130297 · doi:10.1097/j.pain.0000000000001370
What was done
296 healthy volunteers participated in a repeated-measures experimental pain trial using thermal heat pain stimuli. Participants were randomized to either a placebo group (inert cream applied with verbal suggestion that it would reduce pain) or a natural history group (identical pain stimuli without cream or expectation manipulation). Researchers assessed whether single nucleotide polymorphisms in the mu-opioid receptor (*OPRM1* rs1799971) and catechol-O-methyltransferase (*COMT* rs4680) genes, and their interaction, predicted placebo analgesic responses and affective changes.
What was found
The interaction between *OPRM1* rs1799971 and *COMT* rs4680 was significantly associated with the placebo analgesic response. Participants with the *OPRM1* Asn/Asn genotype combined with *COMT* Met/Met or Val/Met genotypes experienced significant pain relief following placebo administration, while other genotype combinations showed no significant placebo effect. Neither gene significantly influenced affective changes. No numerical values or effect sizes were reported in the abstract.
Why it matters
This study provides evidence that individual variation in placebo responsiveness depends on joint genetic modulation of both opioid and dopaminergic neurotransmitter pathways.
Limits
The study tested acute experimental heat pain in healthy volunteers rather than clinical pain in patients. The abstract does not report specific numerical values, effect sizes, confidence intervals, or cell counts across the genotype combinations.
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