Benedict Alter, MD, PhD
University of Pittsburgh
Clinical Assistant Professor
Pittsburgh, PA

Mechanisms and translational application of endogenous analgesia

The overall goal of this research is to better understand endogenous analgesia and optimize it for clinical translation. Endogenous systems modulate pain and underlie “conditioned analgesia,” which contributes to placebo analgesia. Although placebo analgesia elicits powerful effects, systematic translation to the clinic has been challenging, since most placebo manipulations rely on deception to maintain expectations about getting an active drug. Patient deception prevents clinical translation since it is unethical. An alternative and novel approach utilized in this proposal is to capitalize on a component mechanism underlying placebo analgesia, i.e. “conditioned analgesia”. Associative conditioning techniques are combined with a psychophysical analgesic manipulation, leading to a conditioned association between conditioning cues and analgesia. Preliminary data indicate that visual conditioning cues can be used to condition offset analgesia. In Aim 1, the underlying mechanisms of conditioned offset analgesia are investigated. In Aim 2, aspects of the conditioning paradigm are optimized for translation. The relevance to anesthesiology is high given exciting potential applications in acute and chronic pain management. This research is high impact because future translation of this conditioning technique is likely to reduce total opioid requirement for pain management. Given opioid-associated side effects like respiratory depression and abuse potential contributing to the current opioid epidemic, any reduction in opioid consumption with equivalent pain control is highly desirable. Using an extremely safe, nonpharmacologic approach like conditioned analgesia is even better, since nonopioid drugs carry their own side-effects and risks. For these reasons, examining the potential role of conditioned analgesia in pain management deserves special attention and rigorous evaluation.