Multicenter Perioperative Opioid Pharmacogenetic Study

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.

Inclusion Criteria:

- children 6-17 years of age

- ASA physical status 1 and 2

- scheduled for tonsillectomy (T) and tonsillectomy and adenoidectomy (T and A)

- Children with obstructive sleep apnea will also be included.

Exclusion Criteria:

- children with developmental delay

- liver and renal diseases,

- preoperative pain requiring analgesics (e.g. chronic tonsillitis).