Does conditioned pain modulation predict the magnitude of
placebo effects in patients with neuropathic pain?
, K. Moslemi
, C. Baastrup
, K. Grosen
, P. Svensson
, T.S. Jensen
, L. Vase
1 Department of Psychology and Behavioural Sciences, School of Business and Social Sciences, Aarhus University, Aarhus, Denmark
2 Department of Neurology, Aarhus University Hospital, Aarhus, Denmark
3 Department of Clinical Biochemistry, Regional Hospital Horsens, Horsens, Denmark
4 Department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Aarhus, Denmark
5 Danish Pain Research Center, Aarhus University Hospital, Aarhus, Denmark
6 Section of Orofacial Pain and Jaw Function, Department of Dentistry, Aarhus University, Aarhus, Denmark
7 Department of Dental Medicine, Karolinska Institutet, Huddinge, Sweden
The study was supported by the (Danish)
Foundation for Neurological Research and
the Augustinus Foundation.
Conﬂicts of interest
Accepted for publication
21 November 2017
Background: Conditioned pain modulation (CPM) is a validated measure
of the function of endogenous pain inhibitory pathways. Placebo effects
reﬂect top-down inhibitory modulation of pain. CPM and placebo effects
are both inﬂuenced by expectations, albeit to varying degrees, and are
related to neurotransmitter systems such as the endogenous opioid system,
and it can be speculated that CPM responses are positively associated with
the magnitude of placebo effects. Yet, no studies have tested this.
Methods: The study included 19 patients with neuropathic pain. CPM
was quantiﬁed as the difference in pressure pain threshold (PPT) as
measured at the middle deltoid muscle before and after 5-min exposure to
the cold pressor test (CPT) (conditioning pain stimulus). Placebo effects
were tested via open and hidden applications of the pain-relieving agent
lidocaine (2 mL) using a disinfection napkin controlled for no treatment.
Results: The mean (SD) PPT was 668.7 (295.7) kPa before and 742.3
(370.8) kPa after the CPT. The mean (SD) CPM response was À73.6
(214.0) kPa corresponding to an 11% increase in PPT, reﬂecting a
normally functioning endogenous pain modulatory system. Large and
signiﬁcant placebo effects were observed in ongoing neuropathic pain
intensity (p = 0.002). The CPM response did not predict the magnitude
of the placebo effect (p = 0.765). Moreover, there were no interaction
effects for the moderator variables: clinical pain level (p = 0.136), age
(p = 0.347) and gender (p = 0.691).
Conclusions: Conditioned pain modulation and placebo effects do not
seem to be associated in patients with neuropathic pain.
Signiﬁcance: Conditioned pain modulation and placebo effects are
endogenous pain-modulating phenomena that are inﬂuenced by some
of the same mechanisms. This study suggests that CPM and placebo
effects in neuropathic pain are independent phenomena that may be
mediated by different mechanisms.
Conditioned pain modulation (CPM) is a validated
measure of the function of endogenous pain
inhibitory pathways (Kennedy et al., 2016) and has
a well-documented analgesic effect in both animals
(Le Bars et al., 1979a,b) and humans (Willer et al.,
1989; De Broucker et al., 1990). CPM is assessed via
Eur J Pain 22 (2018) 784--792 © 2017 European Pain Federation - EFIC