Reduced Opioid Analgesic Requirements Via Improved Endogenous Opioid Function
Condition: Chronic Pain
MeSH terms: Chronic Pain
Study type: Interventional

Summary: 
      Chronic Pain (CP) management has increasingly utilized long-term opioid analgesic therapy, a
      change associated with increased opioid abuse (via greater exposure in vulnerable
      individuals), non-pain health consequences (hormone changes, falls), and a dramatic rise in
      opioid-related overdoses and deaths. Treatment strategies that minimize the need for chronic
      high-dose opioids are sorely needed. This project will test the novel hypothesis that
      effective pain relief can be achieved at lower opioid analgesic doses by increasing levels of
      endogenous opioids (EOs).
    

Detailed description: 
      There are three separate goals of the study: 1) test the effects of the intervention (versus
      control) on clinical outcomes, 2) test for endogenous opioid mechanisms of the intervention
      (indexed by the difference in laboratory evoked pain response between placebo and naloxone
      drug conditions), and 3) test the effects of the intervention on morphine responses (indexed
      by the difference in evoked pain response between placebo and morphine laboratory drug
      conditions).

      This project will determine whether enhancing endogenous opioids (via aerobic exercise
      training) permits achieving desired levels of analgesia with lower dosages of opioid
      analgesics, and fewer side effects and abuse-relevant drug effects. This 4 year project will
      test study hypotheses in a sample of 116 chronic low back pain patients. The study will have
      two key elements: 1) a randomized, controlled aerobic exercise manipulation in CP patients
      completing daily electronic pain diaries and 2) laboratory evoked thermal pain protocols pre-
      and post-exercise permitting direct examination of changes in both opioid analgesic effects
      (in response to a series of incremental morphine doses) and EO activity (indexed by comparing
      pain responses after placebo vs. opioid blockade).

      The study will use a 6 week supervised aerobic exercise manipulation, with subjects randomly
      assigned to the exercise protocol or a no exercise control condition.

      The study will employ a mixed between/within-subjects design using double-blind,
      counterbalanced, placebo-controlled administration of both an opioid antagonist (naloxone)
      and an opioid agonist (morphine). All participants will undergo three identical laboratory
      pain-induction sessions (each ≈5 days apart) prior to randomization to experimental
      condition, and again at the end of the 6 week exercise manipulation period (regardless of
      exercise group assignment) during which they will receive the 3 study drugs and participate
      in controlled laboratory evaluation of evoked thermal pain responsiveness.
    

Intervention name(s): 6 week aerobic exercise intervention; Placebo; Morphine; naloxone
Intervention type(s): Behavioral; Drug; Drug; Drug
Intervention description(s): Participants randomly assigned to the 6 week aerobic exercise intervention will complete an 18 session aerobic exercise manipulation supervised by an American College of Sports Medicine-certified personal trainer (3 exercise sessions per week for 6 weeks).
Each exercise session will consist of a 5 minute warm-up, 30 minutes of aerobic exercise, followed by a 5 minute cool-down period. Aerobic exercise will consist of treadmill walking/running, stepping, elliptical, or cycling exercise as preferred by the participant. Duration of exercise will be standardized at 30 minutes with a target exercise intensity between 70-85% Heart Rate Reserve (RPE = 15, hard). Because of the focus on de-conditioned individuals with Chronic Low Back Pain, the duration and intensity of exercise will be progressively increased up to target during the first two weeks to avoid symptom exacerbation and minimize study drop-out.; In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will undergo laboratory evoked thermal pain response testing with: 1) 4 doses of saline placebo (20ml each), 2) an 8mg dose of naloxone (in 20ml saline vehicle), followed by saline, 4mg naloxone, and saline, or 3) morphine sulfate (0.03 mg/kg in 20ml saline vehicle initially, followed by 3 incremental doses of 0.02mg/kg each).; In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will undergo laboratory evoked thermal pain response testing with: 1) 4 doses of saline placebo (20ml each), 2) an 8mg dose of naloxone (in 20ml saline vehicle), followed by saline, 4mg naloxone, and saline, or 3) morphine sulfate (0.03 mg/kg in 20ml saline vehicle initially, followed by 3 incremental doses of 0.02mg/kg each).; In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will undergo laboratory evoked thermal pain response testing with: 1) 4 doses of saline placebo (20ml each), 2) an 8mg dose of naloxone (in 20ml saline vehicle), followed by saline, 4mg naloxone, and saline, or 3) morphine sulfate (0.03 mg/kg in 20ml saline vehicle initially, followed by 3 incremental doses of 0.02mg/kg each).
Other intervention name(s): normal saline placebo; Astramorph; narcan
Intervention MeSH terms: Morphine; Naloxone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Chronic Low Back Pain