Department of Anesthesiology/Critical Care Medicine
The Johns Hopkins University School of Medicine
720 Rutland Ave, Ross 359
Baltimore, MD 21205
Dr. Feng Tao’s research interests focus on the central mechanisms of analgesia and anesthesia. The goal of his work is to understand how the effects of analgesics and anesthetics on their neuronal targets are regulated. Specifically, he is interested in the regulation of central sensitization mediated by glutamate receptors and their interacting proteins. It is through these pathways that pain sensation is modulated in the central nervous system, especially at the spinal cord level. Dr. Tao uses a DNA antisense technique to knock down PSD-95/SAP90, a molecular scaffolding protein that has been identified to attach NMDA receptors to internal signaling molecules at neuronal synapses. He revealed for the first time that the PSD-95/SAP90 antisense oligodeoxynucleotide dose-dependently attenuated nerve injury-induced mechanical and thermal hyperalgesia during both the development and maintenance phases of chronic neuropathic pain. Meanwhile, he also found that PSD-95/SAP90 knockdown produced by the PSD-95/SAP90 antisense oligodeoxynucleotide reduced the minimum alveolar anesthetic concentration (MAC) of halothane. These studies provide novel insights into the mechanisms that underlie the chronic neuropathic pain state and clinical inhalational anesthetic application.
Dr. Tao has further investigated the role of PSD-95/SAP90 in chronic pain and anesthesia mechanisms by using peptide to disrupt NMDA receptor-PSD-95/SAP90 protein interactions. He constructed and purified an HIV Tat fusion peptide, “pTat-PSD-95 PDZ2”, which can be delivered intracellularly by the Tat protein transduction domain. GST pull-down and co-immunoprecipitation experiments have shown that this peptide dose-dependently inhibited the protein-protein interactions between NMDA receptors and PSD-95/SAP90. In vivo pharmacological studies have demonstrated that intraperitoneal injection of the cell-permeant fusion peptide pTat-PSD-95 PDZ2 significantly diminished CFA-induced chronic inflammatory pain and reduced halothane MAC in mice. These results indicate that this fusion peptide can potentially be developed for the treatment of chronic pain and use as an adjuvant agent in clinical anesthesia.
As an extension of his pain research, Dr. Tao recently has begun a collaboration with Dr. John McDonald’s laboratory in the International Center for Spinal Cord Injury at Kennedy Krieger Institute to address the problems of central chronic pain after spinal cord injury using a unique stem cell approach.
- Society for Neuroscience
- American Pain Society
- International Association for the Study of Pain
- Tao F, Tao Y-X, Mao P, Johns RA. Role of postsynaptic density protein-95 in the maintenance of peripheral nerve injury-induced neuropathic pain in rats. Neuroscience 117:731–9, 2003.
- Zhang B, Tao F, Liaw W-J, Bredt DS, Johns RA, Tao Y-X. Effect of knock down of spinal cord PSD-93/chapsin-110 on persistent pain induced by complete Freund’s adjuvant and peripheral nerve injury. Pain 106:187–96, 2003.
- Tao F, Tao Y-X, Zhao C, Doré S, Liaw W-J, Raja SN, Johns RA. Differential roles of neuronal and endothelial nitric oxide synthases during carrageenan-induced inflammatory hyperalgesia. Neuroscience 128:421–30, 2004.
- Tao F, Skinner J, Su Q, Johns RA. New role for spinal stargazin in AMPA receptor-mediated pain sensitization after inflammation. J Neurosci Res 84:867–73, 2006.
- Tao F, Johns RA. Effect of disrupting N-methyl-d-aspartate receptor/postsynaptic density protein -95 interactions on the threshold for halothane anesthesia in mice. Anesthesiology (in press).