SHORT COMMUNICATION

Recommendations on practice of conditioned pain modulation

(CPM) testing
D. Yarnitsky1, D. Bouhassira2, A.M. Drewes3, R.B. Fillingim4, M. Granot5, P. Hansson6,7, R. Landau8,
S. Marchand9, D. Matre10, K.B. Nilsen10,11,12, A. Stubhaug6,13, R.D. Treede14, O.H.G. Wilder-Smith15,16
1 Department of Neurology, Technion Faculty of Medicine, Rambam Health Care Campus, Haifa, Israel
2 INSERM, Centre d’Evaluation et de Traitement de la Douleur, Hôpital Ambroise Paré, Boulogne-Billancourt, France
3 Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Denmark
4 College of Dentistry, University of Florida, Gainesville, USA
5 Department of Health and Welfare Studies, University of Haifa, Israel
6 Department of Pain Management and Research, Oslo University Hospital, Norway
7 Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
8 Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, New York, USA
9 Department of Surgery and Neurosurgery, Faculty of Medicine, Sherbrooke University, Canada
10 Department of Work Psychology and Physiology, National Institute of Occupational Health, Oslo, Norway
11 Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway
12 Department of Neurology, Section for Clinical Neurophysiology, Oslo University Hospital – Ullevål, Norway
13 Medical Faculty, University of Oslo, Norway
14 Department of Neurophysiology, CBTM, Medical Faculty Mannheim, Heidelberg University, Germany
15 Department of Anesthesiology, Pain and Palliative Medicine, Radboudumc, Nijmegen, The Netherlands
16 Centre for Sensory-Motor Interaction, Aalborg University, Denmark

Correspondence Abstract
David Yarnitsky
E-mail: davidy@technion.ac.il Protocols for testing conditioned pain modulation (CPM) vary between
different labs/clinics. In order to promote research and clinical application
Funding sources of this tool, we summarize the recommendations of interested researchers
An educational stipend from Medoc
consensus meeting regarding the practice of CPM and report of its results.
supported the logistics of this meeting.

Conflicts of interest
None declared.

Accepted for publication

7 August 2014

doi:10.1002/ejp.605

Researchers interested in conditioned pain modula-
tion (CPM) met during the EFIC meeting in Florence
(October 2013) to discuss current issues relevant to
research on the topic. This was in continuation to the
2009 meeting, where we recommended the use of the
terms ‘test stimulus’ for the painful stimulus upon
which the conditioning effect is tested; ‘conditioning
stimulus’ for the stimulus used to induce the change in
pain perception; and ‘conditioned pain modulation
(CPM)‘ for the phenomenon through which the con-
ditioning stimulus affects perception of the test stimu-
lus (Yarnitsky et al., 2010).
Participants agreed that the lack of uniform proto-
cols for performing CPM is a major problem, hindering
our ability to compare and combine data from various
studies carried out in different laboratories and clinics,
and reach firm conclusions on the clinical utilization
of this test by meta-analyses and systematic reviews.
The following summarizes the expert-opinion-based
recommendations of the forum:
(1) Testing paradigms
Currently, we acknowledge that there are not enough
data to identify a certain CPM protocol as preferable,
generally or for any specific set-up, over the others,

© 2014 European Pain Federation - EFIC® Eur J Pain •• (2014) ••–•• 1

CPM consensus meeting recommendations 2014
requiring further research on CPM methodology. Nev-
ertheless, we believe that a recommendation for a
standardized CPM protocol for clinical studies is
clearly needed. There is a pressing need to enable
proper comparisons of CPM results in various research
projects. It is therefore recommended that CPM pro-
tocols should be enriched, so that comparative data
will be ‘built-in’ within the protocols of testing.
Expert-opinion-based protocols are suggested by the
forum, recommending use of one of following two
options:
(a) An additional test stimulus should be added to the
one planned by the researcher. Since most centres use
either thermal or mechanical stimuli, we recommend
that each protocol should include the two types of test
stimuli. The forum recommends use of one of two
stimulation paradigms: (1) stimulus given at an
ascending intensity, to be discontinued by the subject
at pain40 (pain level of 40/100); or (2) a fixed inten-
sity stimulus, given at predetermined level of pain40.
Time permitting, mechanical and heat test-stimuli
should preferably be performed twice, with at least
10-min inter-stimulus interval, at two different skin
sites. The same conditioning stimulus should be used
for both thermal and mechanical stimuli. The latter
should be painful [typically >20/100 numerical pain
score (NPS)]; mild to moderate pain levels should
suffice to induce an effect (Willer et al., 1984; Granot
et al., 2008; Nir et al., 2011)
(b) A standard additional full CPM protocol should be
added on top of the one planned by the researcher.
The forum felt that a simple, relatively short and non-
expensive protocol is the following: Two successive
mechanical pressure transients as test stimuli, given at
either ascending or fixed protocol, destined at pain40
level, as described above; a 1-min cold water immer-
sion of the hand to the wrist level as conditioning
stimulus.
The forum agreed that a sequential protocol, i.e., pre-
sentation of the ‘conditioned’ test stimulus immedi-
ately after, rather than in parallel, to the conditioning
stimulus, provides a ‘cleaner’ representation of pain
modulation, free of biases such as distraction. Since
CPM effects are generally short-lived (Kakigi, 1994;
Reinert et al., 2000; Sandrini et al., 2005), the interval
between conditioning stimulus and second test stimu-
lus must be short. Further, until additional data on
2 Eur J Pain •• (2014) ••–••
D. Yarnitsky et al.
interrelations between segmental and generalized
pain modulation are obtained, the forum felt that an
upper and a lower limb should be the default two sites
used for the CPM protocol.
(2) Results presentation
The forum recommends that pain inhibition along the
test protocol should be denoted by a negative value,
whereas pain facilitation will be denoted by a positive
value. Thus, when using physical units, such as report-
ing temperature at ‘pain40’ level, a first minus last
calculation should be used, whereas when using rating
data, such as reporting NPS for a fixed temperature
stimulus, the calculation should be last minus first.
This way, results denoting pain inhibition will always
be reported by a negative value, and those denoting
pain facilitation will be reported by a positive value.
The difference between the parameters obtained along
the pain modulation protocol can be presented as
absolute values, percent change or, preferably, both.
Author contributions
All authors participated in the meeting, reviewed and com-
mented on the text.
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© 2014 European Pain Federation - EFIC®