Scherrer Laboratory: Pain & Opioids
The Scherrer Laboratory investigates the neural mechanisms that underlie the sensory and affective dimensions of pain experience. We also study how opioids interfere with these mechanisms to provide pain relief, but also deleterious effects such as tolerance, addiction and respiratory depression. Our goal is to discover novel treatments that block pain more efficiently and safely than current opioid drugs.
Studies conducted in the Scherrer Lab identify the different types of neurons that constitute pain neural circuits in nerves (left, dorsal root ganglion neurons), spinal cord (middle, dorsal horn neurons), and brain (right, amygdala neurons), and the molecular mechanisms that control neural activity and behavior associated with pain perception and opioid analgesia.
Dissecting the Neural Circuits and Molecular Mechanisms of Pain and its Control by Opioids
Physiological Acute Pain versus Chronic Pathological Pain
Pain is normally an acute sensory and emotional state that we experience when our body is exposed to noxious and potentially damaging stimuli (e.g., noxious heat of an open flame). The unpleasantness of pain drives us to engage in adaptive behaviors for avoiding these stimuli and favoring healing. However, when chronic, pain is a disease that severely affects the quality of life of many patients. Thus, injuries or diseases (e.g., trauma, diabetes, arthritis, cancer) induce neuroplasticity in somatosensory circuits that lead to chronic pain: pain can then be perceived in the absence of actual stimuli (spontaneous pain), and normally innocuous stimuli such as light touch can generate excruciating pain (allodynia).
Pain & Opioid Epidemic: Two Outstanding and Related Problems
The magnitude of pain in the United States is outstanding, with more than 116 million Americans suffering from chronic pain. The lack of effective alternative treatments resulted in a dramatic increase in opioid prescription in the past two decades, driving an alarming augmentation in cases of transitions to addiction and deaths from opioid overdose, a phenomenon termed the Opioid Epidemic. In the US today, hydrocodone tops all prescriptions, and deaths from opioid overdose represents the first cause of accidental death, ahead of car accidents. Elucidating pain mechanisms is urgently needed to develop novel analgesic therapies and end the Opioid Epidemic.
Our Approach
The members of the Scherrer Laboratory aim to elucidate the mechanisms by which our nervous system generates pain, at the neural circuit, cellular, and molecular levels. We want to identify the pathological changes that occur within neural circuits when chronic pain develops, for discovering new molecular targets to treat this disease. One of our approaches is to gain understanding of how our endogenous opioid system modulates pain thresholds. Opioid receptors mediate the effects of opioid pain killers, such as morphine. By determining how opioids generate analgesia and detrimental side effects (e.g. tolerance, addiction, respiratory depression), we hope to develop more efficient and safer analgesics for the treatment of chronic pain. These studies will also identify novel approaches to counteract opioid side effects and battle the current Opioid Epidemic. To reach our goals, we combine a variety of experimental approaches including molecular and cellular biology, neuroanatomy, electrophysiology, opto- and pharmacogenetics, in vivo calcium imaging and behavior.
Lab News
2018
March - New article published in Neuron: "Functional divergence of delta and mu opioid receptor organization in CNS pain circuits", by Dong Wang et al. Our article was selected for the cover, congrats everyone!
2017
November - Jessica Ross joins the lab as a postdoc: welcome Jess!
October - Greg is named New York Stem Cell Foundation – Robertson Investigator in Neurosciences
September - The lab receives funding from the National Institute on Drug Abuse for the “Identification of cells and signaling mechanisms underlying opioid analgesia and side effects”.
September - “TrkA-ing the chronic pain” collaboration project with Bianxiao Cui (Chemistry Dept.) is selected by the Stanford Neurosciences Institute for a seed grant.
September - Will MCallum joins the lab as our new Lab Manager and Technician: welcome Will!
August - Dan Berg joins the lab as a postdoc: welcome Dan!
August - Greg C awarded a Carl Storm Fellowship to give a talk at the Gordon Research Conference, Amygdala in Health & Disease in Easton, MA.
July - Greg and Greg C give talks at the International Narcotics Research Conference in Chicago, IL. Greg C also receives a Travel Award.
May - The lab receives a FIDL seed grant from the Dept. of Anesthesiology, Perioperative and Pain Medicine.
May - Amaury receives a CR2 position (Principal Investigator) at the French National Center for Scientific Research.
May - Greg C awarded a NIH K99/R00 Pathway-to-Independence award from National Institute on Drug Abuse.
March - Elizabeth attended the Glial Biology Gordon Research Conference in Ventura, CA.
February - New publication in Neuron: “A brainstem-spinal cord inhibitory circuit for mechanical pain modulation by GABA and enkephalins” by François et al.
