Effect of Ketamine on Opioid-Induced Hyperalgesia
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Enrollment
- 79
- Locations
- 1
- Primary Endpoint
- Change in Temperature of Pain Threshold
Study Overview
Brief Summary
The purpose of this study is to compare pain threshold, pain tolerance, and wind up, as measured by QST, before and after a single dose of ketamine infusion under two clinical conditions: chronic pain patients on opioid therapy and chronic pain patients without opioid therapy.
Detailed Description
We hypothesize that:
- Chronic pain patients on chronic opioids would have a lower pain threshold and lower pain tolerance when compared to opioid naïve patients (patients with chronic pain with non-opioids treatment)., as measured by QST in a non-affected neutral limb;
- Chronic pain patients on chronic opioids would have an increased response to painful stimulation, so called "windup" as demonstrated by QST;
- Both "wind-up" and altered pain threshold and tolerance would be indicative of the presence of opioid-induced hyperalgesia;
- Intravenous ketamine, an NMDA receptor antagonist, could be used to differentiate between opioid-induced hyperalgesia and opioid tolerance.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Health Services Research
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Opioid - Ketamine
This group consists of 16 subjects who have chronic pain conditions treated with an opioid regimen. Subjects were randomized to receive a ketamine treatment during the study. They were given an intravenous infusion of ketamine (0.05mg/kg) diluted in 50 ml normal saline over 30 minutes.
Intervention: Ketamine (Drug)
Non-opioid - Ketamine
This group consists of 22 subjects who have chronic pain conditions but were not on an opioid regimen over the last 3 months. Subjects were randomized to receive a ketamine treatment during the study. They were given an intravenous infusion of ketamine (0.05mg/kg) diluted in 50 ml normal saline over 30 minutes.
Intervention: Ketamine (Drug)
Opioid - Placebos
This group consists of 18 subjects who have chronic pain conditions treated with an opioid regimen. Subjects were randomized to receive a placebo treatment during the study. They were given an intravenous infusion of 50 ml normal saline over 30 minutes.
Intervention: Placebos (Drug)
Non-opioid - Placebos
This group consists of 23 subjects who have chronic pain conditions but were not on an opioid regimen over the last 3 months. Subjects were randomized to receive a placebo treatment during the study. They were given an intravenous infusion of 50 ml normal saline over 30 minutes.
Intervention: Placebos (Drug)
Outcomes
Primary Outcomes
Change in Temperature of Pain Threshold
Time Frame: Baseline at visit 1, post inufsion at visit 1, and at visit 2 which was 1 week after visit 1
We measured the change in pain threshold using Quantitative Sensory Testing (QST). QST refers to a set of quantitative testing of individual responses to mechanical, thermal, and/or electrical stimulation. In this study, pain threshold was the thermal stimulation intensity (in°C) first perceived as painful. To measure this, a contact thermode was attached onto the dorsal surface of the forearm. By pressing a computer mouse button, each subject was able to stop stimulation when they first perceived a painful stimulation from the thermode as the temperature increased 1°C/s. This test was repeated 3 times and an average temperature was calculated. The temperatures could range from a minimum of 0°C to 53°C.
Change in Temperature of Pain Tolerance
Time Frame: Baseline at visit 1, post inufsion at visit 1, and at visit 2 which was 1 week after visit 1
Using QST, we measured the change in pain tolerance which was the maximum thermal stimulation intensity (in °C) tolerable. In this test, the subject was instructed to press the computer mouse to stop stimulation when the thermode reached the maximal tolerable temperature. This test was repeated 3 times and an average temperature was calculated. The temperatures could range from a minimum of 0°C to 53°C.
Change in Duration of Supra-threshold Pain Tolerance
Time Frame: Baseline at visit 1, post inufsion at visit 1, and at visit 2 which was 1 week after visit 1
Using QST, we detected the duration (seconds) of tolerance to supra-threshold heat pain stimulation. In this test, subjects were asked to tolerate, as long as he or she could, heat stimulation preset at 47°C for a maximum of 60 seconds. They were given the computer mouse to stop the test if they reached their limit before 60 seconds. If they stopped the test before the 60 seconds, the time that they stopped it was recorded. This test was repeated 3 times and an average duration was calculated. The duration could range from a minimum of 0 seconds to a maximum of 60 seconds.
Secondary Outcomes
No secondary outcomes reported
Investigators
Jianren Mao, MD, PhD
Principal Investigator
Massachusetts General Hospital