Pain processing in PTSD - Investigating neural correlates of dissociative analgesia

Post-traumatic stress disorder (PTSD) depicts high comorbidity with chronic
pain conditions indicative of dysfunctional pain processing. Experimental pain
research suggests that many PTSD patients show decreased pain perception, thus
are less sensitive to painful stimuli. Most evidence points towards a model of
stress-induced analgesia, in which exposure or reminders of aversive
experiences leads to numbing of sensory and emotional processing, including
reduced pain sensitivity and elevated levels of dissociation. It is
hypothesized that the analgesic effect derives from excessive top-down
inhibition of subcortical regions via the opiate-based pain modulation system
as a compensatory reaction to the greater initial (emotional) distress
experienced in PTSD patients. However, the neurobehavioural mechanisms
underlying the maladaptive coping with acute pain have not been well-understood
and imaging studies on the neural underpinnings of pain processing in PTSD are
scarce. To date, only one fMRI study investigated neural markers of
stress-induced analgesia in PTSD. Mickleborough et al., (2011) employed a pain
processing paradigm combining script-driven imagery and thermal stimulation.
Imaging data suggested that the analgesic effect is related increased
activation in the caudate head and that subjective ratings of dissociation are
related to inhibited amygdala activity. However, replication of the detected
neural markers is strongly warranted given the scarcity and methodological
limitations of the prior imaging studies.

The current study aims to elucidate neural correlates of pain processing and
dissociative analgesia in PTSD. To this end, we want to replicate the pilot
study by Mickleborough et al., (2011) and test the functional pain processing
protocol with sufficient statistical power. Additionally, assessment of
psychophysiological reactivity, e.g. heart rate variability, and an emotional
processing task will be included to gain further insight into the objective
markers of pain processing and dissociative symptoms.

The current research is a replication study of Mickleborough et al., (2011) and
employs functional neuroimaging to experimentally investigate pain processing
in PTSD. Within a 2-by-2-by-2 study design, participants (PTSD patients vs.
trauma-exposed controls) will undergo a fMRI paradigm in which participant
receive thermal stimulation (painful vs. nonpainful) after listening to
autobiographical memory scripts (traumatic vs. neutral). Former research will
be extended with the additional assessment of psychophysiological markers and
an emotion reactivity task. The tasks tests bottom-up emotion processing by
presenting fearful vs. neutral faces above (supraliminal) and below
(subliminal) the perceptive threshold.

A blocked fMRI paradigm will be employed to test brain activity in response to
the thermal stimulation after listening to an autobiographical script.
The paradigm begins with a 60 second baseline measurement in which participants
are asked to focus on their breathing. Then, participants will listen to a
30-second pre-recorded script of a personal event via in-ear headphones and are
asked to concentrate on the feelings and sensations elicited by the memory.
They are asked to remember olfactory, auditory, somatosensory, and visual
sensations associated with the autobiographical memory and continue doing so
for another 30 seconds after the tape has ended, so 60 seconds in total.
Participants will listen to the neutral script six times (Block 1) followed by
listening to the traumatic script six times. It is crucial that the neutral
script precedes the traumatic script because the reverse could lead to
carry-over effects of the distress resulting from the trauma-recall. Each tape
listening is followed by a 25 second thermal stimulation, three painful (warm)
and three non-painful (hot) presented in a pseudorandomized order. Stimulation
will be counterbalanced across groups to avoid anticipation potentially
affecting the pain intensity ratings. After the stimulation has ended,
participants rate the pain intensity and unpleasantness and how strong they
experienced dissociative symptoms. After each scan, participants are given 120
seconds to relax and concentrate on their breathing before the beginning of the
next script. The participants* well-being will be repeatedly assessed
throughout the experiment, and participants can stop their participation at any
timepoint.

Study participation consists of two main components. Firstly, participants
undergo a clinical interview session (90 minutes) to determine their PTSD
symptom severity, and collect autobiographical scripts required for the
functional paradigm. At the end of the session, participants are given and
asked to fill out a questionnaire booklet (30 minutes). Secondly, participants
will follow a fMRI scanning session (125 min) in which they undergo two tasks
(pain processing paradigm and emotional reactivity task). During scanning, the
participants* psychophysiological data (heart rate and skin conductance
reactivity) will be recorded. Total duration is 5 hours.
Concerning the fMRI scanner, participants will be exposed to a field strength
of 3 Tesla and scanner noise. Thus far, there is no evidence to suggest that
exposing humans to a magnetic field of this strength has a negative influence
on health. With regard to the noise, earplugs will be provided. To minimize the
risk of claustrophobic sensations in the scanner, patients will be screened for
a history of claustrophobia and will be offered to lay in a mock scanner to
estimate their comfort level inside an MRI scanner. No disadvantages of the
heart rate and skin conductance measures are known or expected. The thermal
heat stimulation leading to temporary pain sensations will be carefully
adjusted to the subjective pain thresholds, and to our knowledge no major risks
have been associated with the procedure. The study is not intended to benefit
the participants directly, but they will receive a compensation of ¤ 50,- for
their participation.