The Effects of Opioid Taper on Opioid-Induced Hyperalgesia

Chronic pain impacts the daily lives of fully one-third of Americans over the age of 45, with
prevalence expected to increase as the population ages. In well-intended and industry-driven
efforts to provide relief to chronic pain sufferers, the prescription of opioids has
increased dramatically since the turn of the century, such that it is currently estimated
that between 5 and 8 million Americans use opioids on a daily basis for chronic pain
management. Yet, prescription opioid therapy for chronic pain is not an evidence-based
intervention. In fact, as evaluation data accumulate, it is becoming clear that outcomes are
often poorer for patients on opioid therapy, and that improvements are appreciated when
tapered off the medications. In the midst of an "epidemic of prescription drug abuse" it is
critical that opioid prescription practices be evidence-based and delivered "in the best
possible manner that maximizes effectiveness and minimizes harm".

A theorized explanation for poorer outcomes (functionality, quality of life) for patients on
opioid therapy is the phenomenon of opioid-induced hyperalgesia (OIH). Well-demonstrated in
animal and inferred in patients, ongoing opioid use results in increased sensitivity to
experimental pain, which, in the case of the chronic pain patient, is believed to interfere
with (if not preclude) desired pain relief outcomes. However, the causal relationship between
opioid discontinuation and OIH has received little empirical attention, such that it is not
clear the degree to which opioid taper improves pain responses and outcomes, if at all.
Evidence supporting that prescription opioids makes the pain experience worse for chronic
pain patients would support a sea change in current practice of chronic opioid therapy.

Studying the direct effects of an opioid taper on pain responses in chronic pain patients is
challenging; complicated by the reemergence of pain, variable compliance with taper and
concomitant increased use of non-opioid pain medications, a controlled examination of pain
responses during and following opioid detoxification is not immediately tenable in this
patient population. Thus, funded is a proof-of concept trial to identify and characterize the
direct effects of opioid detoxification on experimental pain responses in opioid-dependent
patients without chronic pain to establish if, in fact, a notable effect size can be
discerned. If supported, these findings will provide a foundation upon which to predict
efficacy in patients with the more complicated picture of chronic pain.

Specifically, in a well-characterized sample of men and women seeking addiction treatment in
a residential setting, experimental pain responses will be serially described over the course
of and for three months following a standard observed opioid (buprenorphine) taper, and
compared to those of matched control patients initiated on buprenorphine maintenance therapy.
Pain responses will be measured with two valid and reliable experimental pain induction
techniques commonly used to measure OIH (cold-pressor, quantitative sensory testing), and
subject-level predictors of response identified.

Inclusion Criteria:

1. between ages of 18-50

2. able to provide a positive urine toxicology test for heroin, morphine and/or methadone
(and free of other drugs of abuse) upon treatment admission

3. without known background disease, including chronic or acute pain

4. otherwise in good physical and mental health, or in the care of a physician who is
willing to take responsibility for such treatment

5. able to understand the purpose and instructions of the study, and provide informed
consent as approved by the Western and Georgetown University Institutional Review
Boards

Exclusion Criteria:

1. meet diagnostic criteria for an active substance use disorder other than opioids and
nicotine

2. be acutely psychotic, severely depressed, and/or in need of inpatient psychiatric
treatment

3. have a neurological (i.e. Raynaud's syndrome or symptomatic cold neuropathy) or
psychiatric illness that would affect pain responses

4. have a history of heart disease, stroke, or a pacemaker or uncontrolled high blood
pressure. Good cardiovascular health is stipulated to ensure subjects can tolerate the
sympathetic nervous system responses associated with the pain induction procedures.

5. have sensory deficits at pain testing site resulting from medical conditions such as
diabetes, alcoholic neuropathy, AIDS neuropathy, severe thyroid, and liver or kidney
diseases