Seminar – Nicolas MASSALY

Behavioral Models to Dissect Opioid Circuits Underlying Pain Aversiveness and Substance Use Disorders

Pain and substance use disorders remain major public health challenges in North America. Massaly’s lab is dedicated to elucidating the neural circuits that underlie the affective dimension of pain and opioid use disorders, by using integrated neuropharmacological approaches, sophisticated behavioral paradigms, and the development of innovative technological platforms.

The endogenous dynorphin/kappa opioid receptor system plays a central role in stress responsivity, anxiety-like behavior, drug withdrawal, relapse vulnerability, and aversion. Massaly’s work identified dynorphin-expressing neurons as key drivers of pain-induced negative affect. They have obtained data demonstrating that a specific subset of these neurons projecting to the lateral hypothalamus is dysregulated by pain and may mediate these affective responses. The contribution of this pathway to the neural encoding of emotional pain will be further discussed.

In parallel, Massaly’s lab found that pain disrupts the regulation of both food and fentanyl intake, promoting binge-like consumption patterns. To address the technical limitations inherent to dual-tethered paradigms—particularly when simultaneously recording pulse oximetry and/or neuronal activity during operant self-administration—they are developing novel wireless intravenous self-administration systems. These tools will enable more precise and physiologically relevant interrogation of the neural circuits underlying binge consumption. Data validating this innovative approach will be presented.

Overall, Massaly’s research program is aligned with the urgent need to advance mechanistic insight and therapeutic strategies for individuals living with chronic pain and for those who develop opioid use disorders, whether directly or indirectly following exposure to prescription opioids.