Background & Aims
The aim of this study is to understand how previous analgesic treatment experiences influence expectations about current analgesic treatments and how these expectations modulate central pain processing. Traditional dosing schemes for e.g. opioids recommend starting at a low dose and carefully increasing doses until an adequate level of analgesia is obtained (Jovey et al., 2003, Häuser et al., 2014). While this approach might be beneficial in terms of side effects and overdosing, it might miss on opportunities exploiting expectation-induced analgesic effects. Instead of starting with a low dose, starting with a high dose might establish more positive expectations about the treatment’s efficacy and thus, increase the analgesic efficacy of future treatments. Furthermore, this study will investigate how positive expectations influence neural processing between the spinal cord, brainstem and cortex.
Methods
Fifty-seven participants underwent a heat-pain paradigm while receiving a sham analgesic treatment whose efficacy changed over time. In one group of participants (N=29), the efficacy of the treatment increased while in the other group (N=28), the efficacy decreased, thus simulating different dosing schemes or treatment histories. The sham treatment consisted of TENS stimulation at supposedly different frequencies to obtain different levels of efficacy while in reality and unbeknownst to the participant the temperature was lowered to different calibrated levels. During the test phase, both experimental groups received the same treatment with medium efficacy to test whether the increasing and decreasing treatment histories resulted in different levels of pain relief. The same paradigm is currently realized in the MRI using cortico-spinal fMRI to investigate how treatment-history generated expectations modulate pain processing within the pain system from spinal cord to prefrontal cortex.
Results
In the treatment history phase, which consisted of a low, medium and high treatment block and which were applied in different orders based on group assignment, pain ratings were consistently lower in the decreasing treatment history group compared to the increasing treatment history group but this difference was not significant. Pain ratings during the test phase show that participants in the decreasing treatment history group reported less pain than participants in the increasing treatment history group. This difference in pain rating was significant (t(55) = 2.23, p = 0.03) and was around 10 VAS points on a VAS rating scale from 0 to 100. fMRI data collection is still ongoing but soon to be finished and MRI results in the brain and spinal cord are expected to be presented during the conference.
Conclusions
Participants that started with a strong analgesic treatment and whose efficacy subsequently decreased showed stronger pain relief than participants that started with a weak analgesic treatment and whose efficacy subsequently increased. These results suggest that a dosing scheme that rather starts with a high dose reinforces positive expectations about the treatment and increases the amount of placebo/expectation-related analgesia that is associated with every treatment while a dosing scheme that starts with a low dose might hinder the development of such positive expectations about the treatment and thus result in weaker placebo-related analgesia.
References
Häuser, W., Bock, F., Engeser, P., Tölle, T., Willweber-Strumpf, A., and Petzke, F. (2014). Long-Term Opioid Use in Non-Cancer Pain. Dtsch. Aerzteblatt Online.
Jovey, R.D., Ennis, J., Gardner-Nix, J., Goldman, B., Hays, H., Lynch, M., and Moulin, D. (2003). Use of opioid analgesics for the treatment of chronic noncancer pain–a consensus statement and guidelines from the Canadian Pain Society, 2002. Pain Res. Manag. 8 Suppl A, 3A-28A.
Pattullo, G.G., and Colloca, L. (2019). The opioid epidemic: could enhancing placebo effects be part of the solution? Br. J. Anaesth. 122, e209–e210
Presenting Author
Alexandra Tinnermann
Poster Authors
Alexandra Tinnermann
PhD
University Medical Center Hamburg-Eppendorf
Lead Author
Topics
- Pain Imaging