Multicenter Perioperative Opioid Pharmacogenetic Study
Condition: Pain
Study type: Observational

Summary: 
      The purpose of this research study is to identify factors and genes (the DNA material that
      determines the makeup of the human body) that may be associated with how children respond to
      pain medication. Specifically, the investigators want to study factors that may be associated
      with pain sensitivity, morphine requirement after surgery and side-effects from morphine and
      other pain medications. The investigators expect that the information obtained in this
      research study will help us to develop more effective, safe, and tailored treatment options
      in the future.
    

Detailed description: 
      Opioid drugs as a group have withstood the test of time in their ability to relieve pain.
      Morphine is the most frequently used "gold standard" opioid for managing surgical pain. Like
      other opioids, morphine has a narrow therapeutic index and a large inter-patient variability
      in response. Certain genetic and non-genetic factors are believed to be responsible for
      variations in analgesic responses and side effects with morphine. Genetic factors determining
      an individual's pain sensitivity and regulating morphine's pharmacokinetics (transporters)
      and pharmacodynamics (receptors and signal transduction elements) are likely contributors to
      such variability. Frequent variations in analgesic response are unfortunately clinically
      significant with inadequate pain relief at one end of the spectrum of responses and major
      side effects including potentially fatal respiratory depression due to relative overdosing at
      the other end. Much of the inter-individual variability in response to a dose of morphine
      following surgical procedures can be explained by single nucleotide polymorphisms (SNPs) in a
      subset of the genes that encode proteins involved in pain perception, opioid transport and
      opioid receptor signaling. The genetic variants of mu opioid receptor (OPRM1),
      Catechol-O-methyltransferase (COMT), the Multi Drug Resistance Transport protein gene ABC B1,
      have been associated in small adult studies with varying levels of pain sensitivity,
      analgesic response to opioids and susceptibility to serious side-effects of opioids such as
      respiratory depression, sedation and vomiting. Effective and safe acute postoperative pain
      relief in a subset of children is clinically difficult due to frequent clinical variations in
      perceptions of pain and responses to opioids. To the investigator's knowledge, there is no
      other study attempting to individualize perioperative analgesia in children. The
      investigator's long term goal is to identify factors that modify pain sensitivity and
      responses to morphine in order to develop more effective, safe and tailored therapies. The
      overall objective of this application is to evaluate the contribution of individual and
      combined affects of genetic polymorphisms in OPRM1, COMT and ABC B1 genes and their
      association with postoperative pain relief and adverse effects with morphine. The
      investigator's central hypothesis is that specific genetic polymorphisms in genes involved in
      pain perception, opioid transport and opioid receptor signaling pathways contribute
      significantly to pain sensitivity, morphine consumption, and morphine's side-effects in
      children.

      This study will also explore a set of other important SNPs that might influence pain
      perception and responses to morphine in children. The data will be analyzed looking at pain
      scores, morphine doses, incidence of side-effects of morphine including respiratory
      depression, sedation, vomiting and itching.
    

Observational model: Case-Only
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Children undergoing adenotonsillectomy in the United States.
      
Biospecimen description: 
      A database/ repository will be constructed for future research, analysis, and recruitment.
      De-identified study subjects' genetic information and their responses to pain and pain
      medications, side-effects will be included in the database. Blood specimens will be included
      in the repository for exploring potentially important SNPs and biomarkers in future. No
      patient identifiers will be included in the repository and there will be a confidential
      (access limited to investigators only) code or link between the repository/database and other
      information about the participant.
    
Keywords: postoperative,; pediatric; pharmacogenetic; opioid; morphine; perioperative; respiratory depression