Conditions: Pain
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 242
Healthy volunteers: yes

Brief summary:
Proposed twin study will test to what degree inter-individual differences in pain sensitivity and amount of pain relief in response to opioid therapy are inherited or alternatively, are due to environmental factors. This knowledge is important to guide future studies trying to explain such inter-individual differences. For example, finding that differences are largely due to environmental factors would discourage genomic studies and emphasize epidemiological studies.

Detailed description:
The principal hypothesis to be evaluated is that the degree of analgesia provided by opioids in humans displays substantial familial aggregation, and is, in fact, heritable. These studies will use a classical twin paradigm to determine the role of genetics and the environment in influencing analgesia and a range of other opioid effects.

Specific Aims: (1) Determine the degree to which opioid analgesic responses show familial aggregation and make preliminary estimates of heritability using both a heat and cold pressor pain model, and (2) determine the degree to which non-analgesic opioid responses show familial aggregation and make preliminary estimates of heritability. Side effects such as sedation, nausea, respiratory depression, and pruritus, as well as the positive affective response, a measure of abuse potential, will be monitored. Monozygotic (MZ) and dizygotic (DZ) twin pairs (125 total pairs) will be tested under controlled pain laboratory conditions for their responses to opioid infusion using the complementary pain models while monitoring side effects and additional psychometric indices of mood, sleep, and abuse potential. The selected models provide unique mechanistic information because they involve different peripheral and/or central pain pathways. DNA samples will be collected for zygosity testing and banked for future studies.

Arms:
arm 1: Subjects will receive an intravenous infusion of normal saline. arm 2: Subjects will receive an intravenous infusion of alfentanil.

Interventions: intervention 1: Alfentanil intervention 2: Saline placebo infusion
Intervention descriptions: intervention 1: Target controlled intravenous infusion of alfentanil at a plasma concentration of 100ng/ml intervention 2: Intravenous infusion of normal saline

Protocol document: