Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03484728 |
| Other study ID # |
574-17_RMB_CTIL |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
March 27, 2018 |
| Est. completion date |
June 30, 2020 |
Study information
| Verified date |
May 2021 |
| Source |
Rambam Health Care Campus |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The interaction between conditioned pain modulation and expectation in understanding the
placebo effect of pain reduction
Description:
Conditioned pain modulation (CPM) has recently been coined for the psychophysical protocols
that assess the functioning of descending pain inhibitory pathways in humans. There is a
growing body of evidence points to the important role of spinal serotonin (5-HT) and
noradrenaline (NA) in mediation of pain inhibition via CPM. On the other hand, there is also
evidence on synergistic modulatory effect of the opioidergic control on CPM, however this
issue is under debates. It seems therefore, that pre-treatment CPM assessment may be relevant
for prediction of analgesic drug interaction and additive effects.
Placebo effects are inherent to every treatment and significantly contribute to clinical
outcomes even in the presence of strong verum analgesic effects. From a psychological point
of view, a series of recent studies supported the nature of the placebo effect as a learning
phenomenon wherein verbally-induced expectations, cued and contextual conditioning or social
learning are considered as the core mechanisms to produce a benefit. Placebo analgesic
effects can be elicited by verbal instructions that generate anticipation for a benefit, thus
creating expectations of analgesia. The effect of placebo is, primarily mediated by
mu-receptors associated opioidergic neurotransmission. Alike brain structures activated by
placebo manipulations, prefrontal cortex, cingulate cortex, PAG and RVM are the most
important brain structures involved in initiating of opioid-mediated anti-nociception.
An interesting question that emerges is the extent of overlap between the
serotono-noradrenergic analgesia represented by CPM, and opioidergic analgesia represented by
expectation-based placebo manipulation, for pain reduction. It seems that the final pathway
for the two systems is the descending analgesia tract(s). It is unclear, though, if such
final common pathway dictates a limited analgesic effect, i.e., it can only be activated to a
certain extent, regardless of which system activates it, and therefore additive effects of
expectation and CPM are limited to a certain ceiling. Alternatively, different tracts of
descending pain inhibition are activated by each system, and the analgesic effect is
additive.
Cognitive cortical brain potentials (especially, a P300 waveform) evoked in response to a
combination of rare and frequent innocuous sensory stimuli represent a neurophysiological
tool for assessment attention. As this test bases on uncertainty and the expectation of
upcoming stimuli, the recording of P300 may be relevant for evaluation cognitive processes
associated with expectation-related placebo analgesia.
The main aim of this study is to explore the interaction between serotono-noradrenergic and
opioidergic systems of analgesia in healthy subjects. More specifically, the investigator
will study whether these two systems work in an additive or a complementary way, and whether
the neurophysiological assessment of individual expectation capabilities can predict the
placebo magnitude.
