Our latest preprint with Dr. Elyssa Margolis just went live this week at BioRxiv. In this paper we demonstrate that mu opioid receptors in the lateral habenula are important for driving pain relief and negative reinforcement. Moreover, we demonstrate for the first time that the primary input to the lateral habenula responsible for this pain relief is the lateral preoptic area (LPO) of the hypothalamus.

Neurons in the LPO responsible for signaling pain are glutamatergic, and these neurons appear to become sensitized in a mouse model of chronic pain. However, these signals can be blocked by inhibition at presynaptic mu opioid receptors. What is particularly exciting about this story is that the lateral preoptic- lateral habenula pathway can drive pain relief, but does not appear to support positive reinforcement and may therefore be an important target for driving pain relief without the liability for opioid addiction.