Pain Expectations in Subjects With Osteoarthritis
Condition: Osteoarthritis
MeSH terms: Osteoarthritis
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this research study is to test whether or not researchers can alter or change
      expectations on pain. The researchers will test whether there is an effect on the size of the
      pupil and responses to thermal heat temperatures in subjects with osteoarthritis of the knee
      or hip or healthy subjects for comparison.

      One of 3 possible treatment groups will be administered to qualifying subjects: (1)
      gabapentin, a medication that is commonly used to treat nerve pain, (2) modafinil, a
      medication that is commonly used to treat people with narcolepsy (a disorder that causes
      people to fall asleep) and (3) a placebo, which is an inactive substance, like a sugar pill,
      that is not thought to have any effect on your disease or condition
    

Detailed description: 
      Purpose and rationale for this study: Both chronic pain and disability after total knee
      replacement surgery are predicted by negative cognitive-affective state, characterized by
      depression, anxiety, and a cognitive style dominated by catastrophizing. How this negative
      state results in chronic pain and disability is not known, but we hypothesize that it causes
      dysfunction of the release of the neurotransmitter, norepinephrine in several regions of the
      brain, mid-brain, and spinal cord that are important to many processes involved in recovery
      from surgery.

      Objectives: (1) Gabapentin and modafinil will increase resting pupil diameter with a moderate
      effect size in patients with osteoarthritis; (2) Expectations will modify pain experience
      with a moderate effect size in these patients

      Methods: 30 subjects with moderate average daily pain from osteoarthritis of the knee or hip
      or healthy subjects will be recruited and will come to the clinical research unit at Wake
      Forest. Informed consent will be confirmed and they will complete the questionnaires. We will
      take a verbal medical and medication history and obtain blood pressure and heart rate
      measurements. Verbal pain intensity report (0-10 from no pain to worst pain imaginable) will
      be obtained from a 5 second heat stimuli, separated by 30 seconds, delivered to a nonpainful
      area of skin on the arm as described in preliminary data. During pain testing, study subjects
      will sit in a comfortable chair in a low-ambient light room with their head positioned on a
      chin rest for continuous recording of pupil diameter using a near infrared recording system
      as described in preliminary data. Pupil diameter and probe temperature will be passed through
      an analog to digital converter and acquired at 60 Hertz (Hz) for subsequent analysis.

      Five sequences of test stimuli will be presented, with a brief break in between each
      sequence. The first sequence will consist of 7 stimuli, from 39⁰ to 51⁰ Celsius (C) in 2⁰C
      increments, in ascending order. Data from this training sequence will not be used for
      analysis. Sequences 2 and 3 will consist of 5, 5-second stimuli, presented in random order,
      to generate moderate (50⁰C) and mild (47⁰C) pain (random condition). Sequences 4 and 5 will
      also consist of random presentation of 5 stimuli at these temperatures, but with different
      auditory tones 6 s prior to stimulus onset to correctly cue the stimulus temperature (cued
      condition).

      Subjects will then be randomized to receive oral gabapentin, 900 milligram (mg), modafinil,
      200 mg, or placebo, followed 2 hours later by pain testing with pupillometry, consisting of
      different sequences. The random and cued paradigms will be presented twice each followed by a
      sequence with one miscue in the positive expectation for pain direction (signal for 50⁰C but
      deliver 47⁰C) and one in the negative expectation for pain direction. Subjects will provide
      verbal pain intensity scores after each stimulus.
    

Intervention name(s): Modafinil; Gabapentin; Placebo
Intervention type(s): Drug; Drug; Drug
Other intervention name(s): Provigil; Neurontin
Intervention MeSH terms: Gabapentin; Modafinil
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Osteoarthritis; Knee pain; Hip pain; Total Knee Replacement Surgery