Changes in Affective Pain Processing in Human Volunteers
Condition: Pain, Acute; Pain, Chronic; Low Back Pain
MeSH terms: Back Pain; Low Back Pain; Acute Pain; Chronic Pain
Study type: Interventional

Summary: 
      The experience of pain is more than the conscious perception of nociceptive signals.
      Emotional and motivational aspects accompany pain, leading to its aversiveness and motivation
      for avoidance. In chronic pain, a negative hedonic shift has been proposed that is
      characterized by disproportionally increased emotional-motivational compared to
      sensory-discriminative pain responses. Such a negative hedonic shift is, for example,
      mirrored in very high comorbidity rates of chronic pain and affective disorders such as
      depression and anxiety. The aim of this study is to develop methods that allow the
      differentiation of sensory-discriminative and emotional-motivational pain response and to
      characterize mechanisms of the negative hedonic shift.
    

Detailed description: 
      The experience of pain is more than the conscious perception of nociceptive signals.
      Emotional and motivational aspects accompany pain, leading to its aversiveness and motivation
      for avoidance. In chronic pain, a negative hedonic shift has been proposed that is
      characterized by disproportionally increased emotional-motivational compared to
      sensory-discriminative pain responses. Such a negative hedonic shift is, for example,
      mirrored in very high comorbidity rates of chronic pain and affective disorders such as
      depression and anxiety. However, appropriate psychophysical methods to differentiate
      sensory-discriminative and emotional-motivational pain processing in humans are lacking.
      Therefore, only indirect evidence on the assumed negative hedonic shift in chronic pain is
      available, albeit understanding the mechanisms of such a shift would increase our knowledge
      on the development and maintenance of chronic pain in important ways with impact beyond pain
      research. The aim of this study is to develop methods that allow the differentiation of
      sensory-discriminative and emotional-motivational pain response and to characterize
      mechanisms of the negative hedonic shift.

      A potential benefit of the study will be an increase in the knowledge on mechanisms of the
      development and maintenance of chronic pain with a focus on emotional-motivational processes
      likely also relevant in other diseases such as affective disorders.

      This study involves only minimal risks for participants. The methods that will be used in the
      experimental investigations are within the range of standard procedures in pain research and
      experimental psychology and are frequently used in healthy participants and patients.
      Experimental pain stimulation will be adjusted to individual pain sensitivity, rendering the
      applied stimulation tolerable.

      Substudy 1 Each participant will perform one testing session of approximately 1.5h duration
      at the Balgrist Campus, Balgrist University Hospital, Zurich. Healthy volunteers (N=31) will
      be recruited. The testing session will comprise a discrimination task and an avoidance task
      to assess sensory-discriminative and emotional-motivational pain components independently of
      each other. The tasks will be performed in counterbalanced order. After obtaining written
      informed consent, participants' individual heat pain threshold and tolerance will be
      determined, based on which the stimulation intensity to be used in the discrimination and the
      avoidance task will be calculated. After this assessment, participants either perform the
      discrimination or the avoidance task. Within the discrimination task, participants have to
      indicate whether they perceived a small increase in temperature or not. In the avoidance
      task, participants can avoid a painful stimulation by reacting fast enough to a visual cue.
      Participants will be randomly (balanced randomization) assigned to one of two learning
      conditions, either reinforcing successful discrimination or avoidance, to increase
      sensory-discriminative or emotional-motivational pain responses. Reinforcement, implemented
      by small monetary wins, will start depending on the condition after half the trials of the
      discrimination or the avoidance task. Subjective ratings of perceived pain intensity and
      unpleasantness will be assessed within both tasks as control variables to test whether
      increases in sensory-discriminative or emotional-motivational pain processing generalize to
      the subjective response channel. At the end of the testing session, participants will
      complete several questionnaires to investigate whether certain personality traits are related
      to learning capacity as tested in these tasks.

      Substudy 2 Each participant will perform one testing session of approximately 1.5h duration
      at the Balgrist Campus, Balgrist University Hospital, Zurich. The sample will consist of
      patients with unspecific musculoskeletal chronic pain (N=31) and age- and sex-matched healthy
      controls (N=31). As in Substudy 1, the testing session will comprise the discrimination task
      and the avoidance task to assess sensory-discriminative and emotional-motivational pain
      components independently of each other. The tasks will be performed in counterbalanced order.
      After obtaining written informed consent, participants' individual heat pain threshold and
      tolerance will be determined, based on which the stimulation intensity to be used in the
      discrimination and the avoidance task will be calculated. After this assessment, participants
      either perform the discrimination or the avoidance task as in Substudy 1. In contrast to
      Substudy 1, reinforcement in the avoidance task will be implemented to decrease
      emotional-motivational pain responses because it is assumed that patients show already
      increased emotional-motivational compared to sensory-discriminative pain processing.
      Subjective ratings of perceived pain intensity and unpleasantness will be assessed within
      both tasks as control variables to test whether increases in sensory-discriminative or
      emotional-motivational pain processing generalize to the subjective response channel. At the
      end of the testing session, participants will complete several questionnaires, to investigate
      whether certain personality traits are related to heightened emotional-motivational pain
      processing.

      Sample sizes for Substudy 1 and 2 are based on a priori sample size calculations using
      G*Power 3.1 with a desired medium effect size f=0.25, alpha=0.05, beta=0.80, repeated
      measures ANOVA between-within-subject designs, and an attrition rate of 10%. Outcome
      variables () will be analyzed in separate mixed model analyses for ANOVA designs with
      appropriate within- and between-subject factors. Associations of primary endpoints () with
      personality traits (secondary outcomes) will be analyzed using Person- or Spearman
      correlation coeffients, where appropriate. Significance levels will be set to 5%, adjusted
      with false discovery rate for multiple testing. Effect sizes will be calculated in terms of
      generalized η2 and Cohen's d.

      Substudy 3 Each participant will perform one testing session of approximately 1.25h duration
      at the Balgrist Campus, Balgrist University Hospital, Zurich. Healthy volunteers (N=30) will
      be recruited. During testing session participants will perform a psychophysical task to
      assess metacognition in pain perception as an indicator of the cognitive-evaluative pain
      component. The objective is to assess whether metacognition on pain perception are involved
      and subjective ratings of perceived pain and how metacognition relates to pain intensity.
      After obtaining written informed consent, participants' individual heat pain threshold and
      tolerance will be determined, based on which the stimulation intensity to be used in the
      experiment will be calculated. After this assessment, participants perform the cognitive pain
      task. Within this task, participants have to indicate whether they perceived a first or
      second heat pain stimulus as higher in intensity, whether the higher one was perceived as
      painful or not, and their confidence in both these answers. In addition, participants will
      complete several questionnaires to investigate whether certain personality traits and
      personal states are related to metacognition in pain.

      The sample size of Substudy 3 is determined according to Kreft and Leeuw (2007) after which a
      great enough power will be reached with a sample size of 30 participants and 30 observations
      to identify cross-level interactions. Substudy 3 follows a within subject design with
      repeated measures. The tasks that will be performed by each participant include the
      within-subject factor 'temperature difference' (differences in temperature between first and
      second stimulus) and the within-subject factor 'temperature level' (temperature relative to
      individual pain threshold of each stimulus). The order of the different conditions in each
      task will be applied using a balanced pseudo-randomized order. For testing hypothesis 1ai,
      1bi and 1c t-test will be conducted. For Hypothesis 1aii and 1bii chi square tests are
      planned. To test hypothesis 2a, 2c and 3 logistic hierarchic liner models and for hypothesis
      2b and 2d hierarchic linear models will be performed.

      Within this study methods that allow the separation of different components of the perception
      of pain will be developed and validated and which are currently not available. In addition,
      based on theses methods, a human model on how such components of pain can dissociate will be
      developed, thereby allowing investigating a prominent assumption on factors that crucially
      contribute to the development and maintenance of chronic pain. The expected results will form
      the basis for the development of novel mechanism-based pain therapies.

      Psychophysical methods based on experimental psychology and pain research will be used, which
      have been shown before to be successful in investigating different aspects of pain perception
      and the modulation of pain perception. The methods used are in the standard range of methods
      from human pain research and experimental psychology and hold only minimal risk for
      participants (see above "Risk / Benefit Assessment").
    

Intervention name(s): psychophysical tasks; cognitive task
Intervention type(s): Behavioral; Behavioral
Intervention description(s): All participants perform two psychophysical tasks to assess sensory-discriminative and emotional-motivational pain responses independently from each other.
In addition, in Substudy 1 an operant learning paradigm will be implement to dissociate these responses, increasing the sensory-discriminative pain responses compared to emotional-motivational pain responses by contingent monetary reinforcement or vice versa.
In Substudy 2, responses of chronic pain patients will be compared to those of healthy participants to characterize possible alterations and operant learning will be operationalized to decrease emotional-motivational pain responses, which are assumed to be already increased in the patients.; In Substudy 3 participants will perform a psychophysical task to assess metacognition in pain perception as an indicator of the cognitive-evaluative pain component.
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Study comprises an intervention that is neither a therapeutic or transplant product nor a transplant. Study involves minimal risks for participants. Used methods are within the range of standard methods frequently used in pain research. All participants will perform 2 psychophysical tasks to assess sensory-discriminative & emotional-motivational pain responses independently from each other.
Substudy1: An operant learning paradigm will be implemented to dissociate these responses, increasing the sensory-discriminative compared to emotional-motivational pain responses by contingent monetary reinforcement & vice versa. Substudy2: Responses of chronic pain patients will be compared to those of healthy participants to characterize possible alterations. Operant learning will be operationalized to decrease emotional-motivational pain responses, which are assumed to be increased in patients. Substudy3: Participants will perform a psychophysical task to assess metacognition in pain perception.
Masking: Single (Participant)
Primary purpose: Basic Science
Keywords: acute pain; chronic pain; low back pain; hedonic shift; emotional-motivation components of pain; sensory-discriminative components of pain; operant conditioning; metacognition