Inhibitory Functions as Predictors of Chronic Pain: a Pilot Study

Chronic pain is a major cause of disability, affecting approximately 20% of the
general population. Up until now, chronic pain remains a difficult to treat
condition. Our knowledge is particularly lacking regarding the mechanisms
underlying the development of chronic pain. In this study, we will focus on the
predictive value of endogenous inhibitory functions for the development of
postoperative pain. These endogenous inhibitory functions refer to functions
that are part of normal cognitive and pain control mechanisms. It has been
shown that these functions predict experimental, acute, pain sensitivity in
healthy volunteers; never have inhibitory functions been examined as predictors
of chronic pain. The aim of the present study is to overcome this limitation,
by examining the level of inhibitory functions in relation to the development
of postoperative pain.
To examine this in detail, we will focus on three different forms of endogenous
inhibition: 1. Cognitive inhibition as measured with cognitive tests, 2.
Conditioned pain modulation as measured with the pain inhibits pain phenomenon,
and 3. Placebo- and nocebo-like effects, in which the effect of suggestions on
pain experience will be evaluated. These functions will be assessed
pre-operatively in a sample of patients scheduled for pancreatic resection
surgery for (pre)cancer. These patients normally do not report pain
pre-operatively; incidence rates of postoperative pain are high, in that as
much as 30-40% of these patients may develop persistent pain (PP) following
surgery. This model is therefore suitable for identifying those at an increased
risk for developing chronic pain.
Our hypothesis is that reduced pre-operative endogenous inhibitory functioning
predicts the development of PP as well as a higher intensity of PP. In
addition, it is expected that the different inhibition functions partially act
in a complementary way, in that they uniquely predict part of the variance in
postoperative pain.

The primary objective is to examine the predictive value of several types of
endogenous inhibitory functions for the risk and severity of acute and
persistent pain after surgery. As primary outcome parameter, patients will be
asked to keep a pain diary during three days, the first starting approximately
7 to 10 days after surgery (T1) and the second 3 months later (T2). In this
diary, daily ratings of pain intensity will be recorded on visual analogue
scales. The primary predictors consist of the three endogenous inhibitory
functions: 1. Cognitive inhibition, which will be measured with computer tasks
measuring respectively interference control and prepotent response inhibition;
2. Conditioned pain modulation, measured using a validated paradigm in which
pressure pain threshold (PPT) and electrical pain threshold tolerance (EPTT)
are first determined, followed by a cold pressor test (holding one*s hand in
cold water) followed again by a PPT and EPTT measurement. An increase in the
second PPT and EPTT indicates the presence of pain inhibitory functions, also
referred to as diffuse noxious inhibitory controls (DNIC); 3. Placebo- and
nocebo-suggestions, in which cues indicating low and high painful stimulation
are followed by either a correct stimulus (respectively low and high
stimulation) or an incorrect stimulus (respectively high and low stimulation).

A secondary objective is quality of life assessed with the SF -36. Next to the
pain ratings, participants will perform daily indications of distress and mood.

A prospective pilot study in which the predictive value of several endogenous
inhibitory functions for postoperative pain will be assessed.

All tests and methods that are used are non-invasive and not stressful for the
patient. All cognitive tests and questionnaires are widely-used validated and
reliable paper-pencil or computerized tasks. The CPM measurement and the
placebo- and nocebo-like measurements will be based on validated protocols. The
participant can work at his/her work pace, and if desired additional breaks
will be taken. The preoperative testing will take approximately 1.5 hours; the
two postoperative measurements will take approximately 45 minutes each.