Pain, Opioids and Pro-Inflammatory Immune Responses

Sponsor

University of California, Los Angeles (Other)

Overall Status

Terminated

CT.gov ID

NCT01210066

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Pro-inflammatory Activity Immunologic Activity Alteration	Drug: Fentanyl Other: Cold pressor test Other: Fentanyl plus cold pressor test	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

21 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Pain, Opioids and Pro-Inflammatory Immune Responses

Study Start Date :

Jul 1, 2010

Actual Primary Completion Date :

May 1, 2012

Actual Study Completion Date :

May 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Pain Challenge Cold pressor test	Other: Cold pressor test Non-dominant arm submerged in ice water (0 degrees Celsius) until it is no longer tolerable but less than 5 minutes Other Names: cold pressor task
Active Comparator: Pain + Opioid Challenge IV fentanyl 1mcg/kg followed by cold pressor test	Other: Fentanyl plus cold pressor test fentanyl IV 1mcg/kg fifteen minutes prior to cold pressor test (arm submerged in ice water until no longer tolerable but no longer than 5 minutes) Other Names: opioid and cold pressor
Active Comparator: Opioid Challenge Administration of fentanyl 1mcg/kg of subject weight	Drug: Fentanyl IV fentanyl 1mcg/kg Other Names: opioid

Arm

Intervention/Treatment

Active Comparator: Pain Challenge

Cold pressor test

Other: Cold pressor test

Non-dominant arm submerged in ice water (0 degrees Celsius) until it is no longer tolerable but less than 5 minutes

Other Names:

cold pressor task

Active Comparator: Pain + Opioid Challenge

IV fentanyl 1mcg/kg followed by cold pressor test

Other: Fentanyl plus cold pressor test

fentanyl IV 1mcg/kg fifteen minutes prior to cold pressor test (arm submerged in ice water until no longer tolerable but no longer than 5 minutes)

Other Names:

opioid and cold pressor

Active Comparator: Opioid Challenge

Administration of fentanyl 1mcg/kg of subject weight

Drug: Fentanyl

IV fentanyl 1mcg/kg

Other Names:

opioid

Outcome Measures

Primary Outcome Measures

plasma levels of pro-inflammatory cytokine IL-6 [15 minutes prior to fentanyl administration, 60 and 180 minutes post fentanyl administration,]
inflammatory cytokine activity will be evaluated with an in vivo approach over a three hour period of time to enable observation of the duration of opioid activity

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 40 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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