- About CURE
Juan Carlos Marvizon, PhD
Associate Professor, Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA
Dr. Marvizón’s research field is the neurophysiology of pain and analgesia. His overall research goal is investigating cellular and molecular mechanisms that mediate central sensitization in the spinal cord. Central sensitization is a process that underlies numerous chronic pain disorders, including functional bowel disorders like Irritable Bowel Syndrome. Recent discoveries have revealed the important role played by substance P and its receptor, the neurokinin 1 (NK1) receptor, in mediating central sensitization. In contrast, opioid neuropeptides act on mu, delta and kappa opioid receptors to produce analgesia. Dr. Marvizón has utilized a new methodology for measuring the activation of neuropeptide receptors by their internalization. Internalization of neurokinin 1 receptors or mu-opioid receptors is detected using immunohistochemistry with antibodies against these receptors. Electrophysiology is used to deliver precise electrical stimulation to spinal cord slices or to live animals while performing intracellular and axonal recordings to monitor neuronal activity evoked by the stimulation. Animal behavioral responses to pain are measured as well and correlated with receptor internalization. Recently, his studies, in collaboration with James McRoberts, are based on their results indicating that NMDA receptors (NMDARs) are normally in a non-functional state but become functional during the induction of chronic pain. Dr. Marvizon found that intrathecal NMDA preceded by brain-derived neurotrophic factor (BDNF) elicited a substantial amount of substance P release. Co-injection of a Src family kinase (SFK) inhibitor with BDNF suppressed the effect of NMDA, suggesting that BDNF induces the SFK phosphorylation of NMDARs. In addition to BDNF, ephrinB2 also appears to enable NMDA-induced substance P release. He also found that in a nerve injury model, these NMDARs become functional for days, consistent with evidence that nerve injury induces BDNF release from activated microglia and activates the ephrinB/EphB receptor system. Accordingly, he is now testing whether functional, NMDARs in primary afferents require Tyr-phosphorylation of their NR2B subunit, which is initiated by BDNF and ephrins, and whether NMDARs in primary afferent terminals are non-functional (i.e. not phosphorylated) under normal conditions and become phosphorylated in some chronic pain states.