The Influence of Expectations, Attention and the Test Paradigm on the Efficacy of the Pain Processing System
Condition: Pain
Study type: Observational

Summary: 
      Conditioned pain modulation (CPM) is the endogenous pain relief mechanism responsible for the
      "pain-inhibits-pain" phenomenon. This mechanism can be activated experimentally, and its
      efficiency evaluated by experimental pain tests. According to the "pain-inhibits-pain"
      principle, during such an experimental testing paradigm, a painful test stimulus is typically
      applied, followed by a conditioning stimulus. The effect of the conditioning stimulus on the
      test stimulus is examined to determine whether or not the conditioning stimulus elicits an
      inhibitory effect. With this study, the investigators want to examine in pain-free adults
      whether and to what extend the efficacy of CPM is influenced by 1) attention (focus versus
      distraction), 2) intrinsic expectations (pain reduction versus no change versus pain
      increase) with regard to pain due to the CPM paradigm used, and 3) the order of application
      of the test stimulus and conditioning stimulus (sequential versus parallel paradigm).
    

Detailed description: 
      Despite the widespread use of CPM by researchers, there is still no gold standard for
      conducting this test. Both a sequential and a parallel application of the test stimulus and
      the conditioning stimulus are often used interchangeably and side by side. In both paradigms,
      the pain intensity or pain threshold of the test stimulus is first determined. Subsequently,
      in the parallel protocol, the test stimulus is reapplied while simultaneously applying the
      conditioning stimulus. In the sequential protocol, the conditioning stimulus is applied
      first, and after removing the latter stimulus, the test stimulus is reapplied (the CPM effect
      is visible up to 5 minutes after removal of the conditioning stimulus). The difference
      between the initial and repeated test stimulus (during or after conditioning) is quantified
      to express the CPM effect.

      Even the publication of an expert opinion, which decided in favor of the sequential paradigm,
      has so far changed little in the use of the two paradigms. In that same publication,
      international CPM experts considered the sequential order 'purer' than the parallel order, as
      the results of the latter can be attributed to a shift of attention to the conditioning
      stimulus. However, this claim has little support from the literature. Some researchers even
      argue that cognitive mechanisms such as attentional shift might be part of the underlying
      mechanism of the CPM effect. Existing research also shows that CPM effectiveness is
      influenced by expectations. For this, previous studies conditioned test subjects by telling
      them in advance that the conditioning stimulus would reduce or increase pain. However, when
      the experimental CPM paradigm is used to investigate the effectiveness of the pain-inhibiting
      system, no such suggestions are made. However, this does not preclude that when the test
      protocol is explained to the subject, he or she does not create intrinsic expectations
      regarding the pain that is provoked. However, few studies have investigated this and the
      results of these studies are inconsistent and therefore do not allow conclusions to be drawn.

      The aim of this study is to compare a sequential protocol with a parallel protocol on the one
      hand, and to measure the influence of expectations, attention and distraction on the CPM
      effect on the other.

      In this study, the test stimulus of the CPM measurement will consist of a mechanical stimulus
      applied with an analog algometer (Force Dial model FDK 10 and 40 Push Pull Force Gage, Wagner
      instruments, Greenwich, Connecticut) on the Brachioradialis and Quadriceps muscle of the
      dominant side. The pressure pain threshold will be determined and used as an outcome measure.
      The conditioning stimulus consists of immersing the hand (up to 10 cm above the wrist) of the
      non-dominant side in warm water at a temperature of 45,5°C for 6 minutes. This temperature
      has been proven to be a reliable stimulus, eliciting solid effects.

      At the time of testing, the CPM measurement will therefore be performed four times, each time
      with a small variation. The order of the variations is determined at random. There is a break
      of 10 minutes between each performance, so that the effect of the previous performance has
      worn off. The four variations of the CPM paradigm are the following:

        1. Sequential protocol: the test stimulus is applied before and after the conditioning
           stimulus

        2. Parallel protocol: the test stimulus is applied before, after and during immersion (at
           minute 4)

        3. Focus protocol: this protocol works like the sequential protocol. In addition, the
           subject will be asked to give a pain score from 0 (no pain) to 100 (excruciating pain)
           every 30 seconds during immersion, thereby focusing on the conditioning stimulus.

        4. Distraction protocol: this protocol works like the sequential protocol. During the
           immersion, attention will be diverted away from the conditioning stimulus by having the
           subject perform a cognitive test known as the Paced Auditory Serial Addition Test
           (PASAT). The latter implies that the subject must listen to an auditory series of
           numbers, memorize them and add them.

      Before the actual test begins, a familiarization moment will take place, in which the subject
      becomes acquainted with the test and the conditioning stimulus by undergoing it for the first
      time. There will also be a practice session of the PASAT at that time.

      Before the start of the CPM test, two questionnaires are taken: a general questionnaire
      assessing sociodemographic and health-related characteristics, and the Hospital Anxiety and
      Depression Scale (HADS), which provides an indication of feelings of anxiety and depression
      that the subject might experience, as such factors may have an influence (i.e. known
      confounders) on the CPM effect.

      Finally, for each variation on the CPM paradigm, it will be briefly explained what the
      protocol to be undergone entails. This involves assessing the subject's expectations with
      regard to the related protocol. The subject will have to indicate whether he / she expects
      the immersion to have an influence on the pressure threshold measurement (yes, pain increase;
      yes, pain reduction; no, no effect). If the participants answer "yes", the subjects are asked
      to quantify the expected impact by indicating how much more or less pressure is expected to
      be tolerated (in percentages).

      This study has a cross-sectional design and the familiarization and the experimental CPM
      assessments take place during during a single test session of about 2 hours.
    

Observational model: Case-Only
Time perspective: Cross-Sectional
Sampling method: Probability Sample
Study population: 
        Healthy pain-free Dutch-speaking men and women between the age of 18 and 65 years.
        Participants will be recruited amongst friends, relatives and fellow students of the
        researchers.
      
Keywords: endogenous pain modulation; conditioned pain modulation; expectations; attention; test paradigm