NYSCF—Robertson Investigator Discovers Differences Between Opioid Receptors

If anyone has ever told you that your pain is “all in your head”, in a way, they’re right. The brain modulates how we feel pain through interactions with sensory nerves. For example, when you get a paper cut on your finger, a signal is sent from your hand to your spinal cord to your brain that essentially tells the brain “this is bad”, and as a result, you experience pain. This system, however, can be modulated through opioids.

The reason drugs like morphine help dull pain is because they stimulate a certain type of receptor in the central nervous system: the opioid receptor. When the opioid receptor is activated, a signal is sent to the brain that reduces pain. These receptors exist in three types: mu opioid receptors (MORs), delta opioid receptors (DORs), and kappa opioid receptors (KORs).

It is thought that MORs and DORs interact to regulate analgesia (the inability to feel pain), but we don’t fully understand the relationship between the two. That’s where a recent study from NYSCF—Robertson Investigator Gregory Scherrer, PhD, PharmD, and colleagues at Stanford University comes in.

The team wanted to see how these receptor types were distributed within the central nervous system and whether they carried different functions. Using immunolabeling (a tool for determining the locations of certain receptors), they found that DORs and MORs are mostly located in different populations of pain neurons. This suggests that they might control different types of pain or different aspects of the pain experience. Further experiments showed that DORs appear to regulate mechanical pain (pain caused from excessive stress placed on the body) by controlling the activity of certain interneurons in the spinal cord.

The study found that DOR/MOR co-expression isn’t as common as we thought and happens mostly in dorsal horn projection neurons or in ventral horn neurons (regions of the spinal cord) rather than in the brain circuitry. And in neurons where DORs and MORs are co-expressed, they still function independently.

These results are important because they give further insight into the dynamics of pain receptors, allowing researchers to create more effective opioid analgesics. For more information, check out the paper in Neuron.