Pain, Opioids and Pro-Inflammatory Immune Responses

Providing pain management to the patient who abuses prescription opioids presents a clinical challenge, not only due to concerns about "drug-seeking", but because they have increased sensitivity to pain, a phenomenon identified as opioid-induced hyperalgesia (OIH). In an effort to improve pain treatment, the aims of the proposed work are to evaluate the analgesic and hyperalgesic effects of opioids to acute pain in this vulnerable population, and to examine the role of opioid-induced proinflammatory changes in these responses.

Both acute pain and opioid administration have been shown to induce a systemic pro-inflammatory response. However, the presence of these inflammatory responses is unknown in situations where a co-occurrence of pain and opioid administration exists as is the common clinical case of a patient with acute pain and taking opioid analgesics. A patient population for whom the combined effects of pain and opioids on immune function are particularly complex are the estimated 5.2 million Americans aged 12 or older who abuse prescription opioids. Not only are these individuals at risk for poor pain management due to their status as an "addict", but there is good preclinical evidence to suggest that their chronic opioid use brings with it a general state of systemic inflammation, and thus setting the patient up for a unique or enhanced inflammatory response to the combination of acute opioids and pain. To better understand the health implications of treating acute pain with opioids in patients and in particular, those who abuse prescription opioids, inflammatory responses to the main and interaction effects of acute pain and opioid administration will be examined in well-characterized samples of each. Specifically, we will evaluate the inflammatory and cytokine responses to: (1) experimental pain; (2) an acute opioid challenge; and (3) the combination of opioid administration followed by cold-pressor pain, in healthy control subjects and age- and gender-matched prescription opioid abusers.

Eligibility Criteria:
Inclusion criteria:

* male and non-pregnant female, non-smoking adults in good general health
* between the ages of 21-40 years old
* fluent in English with willingness to participate in the research study

Supplementary Inclusion Criteria: Prescription Opioid Abusers

* DSM-IVR diagnosis of prescription opioid abuse or dependence disorder
* compliance in treatment and on a stable dose of buprenorphine (6-24mg/day) x at least 10 days prior to screening
* Participation in an ISAP treatment program or a qualified community-based opioid treatment program or private clinic for the entire duration of their study participation

Exclusion criteria:

* regular use of any medication that influences immune status or immune system function
* regular use of a medication that influences pain perception, including opioids (\* only for healthy subjects population\*)
* Regular use of a medication that influences pain perception, except for buprenorphine (\*\* only for POA population\*\*)
* known hypersensitivity to opioids or no previous opioid exposure (\*only healthy controls)
* presence of acute or chronic pain syndrome
* neuropsychiatric illness (i.e., peripheral neuropathy, schizophrenia) known to affect pain perception
* presence of chronic immune compromise (hepatitis C, HIV) or acute infection within the last four weeks
* current or past history of high blood pressure, heart disease, or stroke, or currently have a pacemaker.
* current DSM-IV diagnosis
* BMI less than 18.5 or greater than 29.9
* History of sleep apnea