Hyperalgesia
Conditions
Keywords
opioid induced hyperalgesia
Brief summary
The purpose of this study was to follow a person's response to experimental pain after multiple consecutive exposures to alfentanil or diphenhydramine to see if the person can tolerate the pain more, less, or the same at the end of the study.
Detailed description
This project investigates the phenomenon of opioid-induced hyperalgesia (OIH). Opioid analgesics, in addition to their therapeutic anti-nociceptive effects, under some conditions produce pro-nociceptive effects. This phenomenon of pain or pain sensitivity being increased by prior opioid administration is called opioid-induced hyperalgesia. It is thought to be relevant both to pain management complications and to complications of opioid dependence and its treatment. This study investigated the time-course of opioid-induced hyperalgesia development in healthy normal volunteers (N=12 completers), using a series of acute alfentanil administrations (15 mg/kg mg intramuscular (IM) per day) spaced at 3-4 day intervals, with testing for pain tolerance using the cold pressor test (CPT), and mechanical quantitative sensory testing (MQST) each administered repeatedly over time within each testing day. The goal was to determine the time course of OIH development following acute opioid administration, and to assess whether this changes over repeated acute opioid administrations.
Interventions
DRUGAlfentanil
15 mcg/kg IM
DRUGDiphenhydramine
25 mg IM
Sponsors
National Institute on Drug Abuse (NIDA)
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Age 18-55 * No active medical conditions * BMI between 20-30 * Able and willing to perform/tolerate pain procedures * Able to communicate in English
Exclusion criteria
* Lifetime substance use disorder, except for alcohol abuse/dependence in remission * Use of opiates in last 3 months * Ongoing marijuana use * Acute or chronic pain * Neurologic or psychiatric condition known to influence cold pressor testing (peripheral neuropathy, major depression, or schizophrenia) * Current use of prescribed or over the counter pain medications * Previous adverse reaction to opiate medications or diphenhydramine * Use of tobacco or caffeine on study days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain Tolerance | 8 sessions over 4-6 weeks | The participant places their hand in a water bath kept at 4 degrees Celsius (cold pressor test). They then continue to hold the hand in the water bath until they can no longer tolerate the pain (pain tolerance) or until the end of the testing (truncated at 300 seconds for safety purposes). Reported as the mean (time to hand removal in seconds) at the 30 minute time point. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain Threshold | 8 sessions over 4-6 weeks | The amount of time (in seconds) before the participant first verbally reports feeling pain after placing hand in 4 degree Celsius circulating water bath at the 30 minute time point. Truncated at 300 seconds for safety purposes. |
Countries
United States
Participant flow
Recruitment details
Study enrollment began in February 2009 after Institutional Review Board (IRB) approval. Screening started on 2/9/09. The last person was screened on 3/12/2010 and finished the study in April 2010. A total of 42 screenings occurred and 12 persons completed the study. Recruitment was conducted at the Behavioral Pharmacology Research Unit (BPRU).
Pre-assignment details
Since study initiation in February 2009, there were 42 persons consented. There were 13 screen failures \[4 had urines positive for illicit substances, 4 had BMI\>30, 5 had active medical problems\]. Seven met study criteria but decided not to start as they could not commit to study schedule (N=6) or did not like blood draws (N=1)
Participants by arm
| Arm | Count |
|---|---|
| Alfentanil These subjects will receive a series of acute alfentanil administrations each session (15 mcg/kg IM per session), with sessions spaced at 3-4 day intervals.
Alfentanil : 15 mcg/kg IM | 12 |
| Diphenhydramine Subjects will receive a series of acute diphenhydramine administrations each session (25 mg IM per session), with sessions spaced at 3-4 day intervals.
Diphenhydramine : 25 mg IM | 10 |
| Total | 22 |
Baseline characteristics
| Characteristic | Alfentanil | Diphenhydramine | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 10 Participants | 22 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 4 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 6 Participants | 5 Participants | 11 Participants |
| Region of Enrollment United States | 12 participants | 10 participants | 22 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 12 Participants | 10 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 12 | 0 / 10 |
| serious Total, serious adverse events | 0 / 12 | 0 / 10 |
Outcome results
Primary
Pain Tolerance
The participant places their hand in a water bath kept at 4 degrees Celsius (cold pressor test). They then continue to hold the hand in the water bath until they can no longer tolerate the pain (pain tolerance) or until the end of the testing (truncated at 300 seconds for safety purposes). Reported as the mean (time to hand removal in seconds) at the 30 minute time point.
Time frame: 8 sessions over 4-6 weeks
Population: One person in the diphenhydramine group was dropped from analysis, even though he completed the study as he tolerated cold pressor testing for the maximum amount of time in sessions 2-8.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Alfentanil | Pain Tolerance | 105.3 seconds |
| Diphenhydramine | Pain Tolerance | 19.2 seconds |
Secondary
Pain Threshold
The amount of time (in seconds) before the participant first verbally reports feeling pain after placing hand in 4 degree Celsius circulating water bath at the 30 minute time point. Truncated at 300 seconds for safety purposes.
Time frame: 8 sessions over 4-6 weeks
Population: One person in the diphenhydramine group was dropped from analysis, even though he completed the study as he tolerated cold pressor testing for the maximum amount of time in sessions 2-8.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Alfentanil | Pain Threshold | 20.7 seconds |
| Diphenhydramine | Pain Threshold | 8.6 seconds |