Pain, Opioids and Pro-Inflammatory Immune Responses

Phase 1

Terminated

• Conditions: Pro-inflammatory Activity; Immunologic Activity Alteration
• Interventions: Other: Cold pressor test; Other: Fentanyl plus cold pressor test; Drug: Fentanyl

• Registration Number: NCT01210066
• Lead Sponsor: University of California, Los Angeles

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.

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 Timeline

• Study Start: 2010-07
• Study First Submitted: 2010-09-27
• Study First Submitted QC: 2010-09-27
• Study First Posted: 2010-09-28
• Primary Completion: 2012-05
• Study Completion: 2012-05
• Status Verified: 2016-12
• Last Update Submitted: 2016-12-27
• Last Update Posted: 2016-12-29

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 21

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Pain Challenge	Cold pressor test	Cold pressor test
Pain + Opioid Challenge	Fentanyl plus cold pressor test	IV fentanyl 1mcg/kg followed by cold pressor test
Opioid Challenge	Fentanyl	Administration of fentanyl 1mcg/kg of subject weight

Primary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

UCLA School of Nursing; 🇺🇸 Los Angeles, California, United States