Michelino Puopolo

Assistant Professor
Ph.D., University of Ferrara, Italy

Department of Anesthesiology
http://anesthesia.stonybrook.edu/faculty/Puopolo

Phone: (631)-638-2145
michelino.puopolo@stonybrook.edu

Training

Michelino Puopolo attended the University of Bologna, Italy, and received a PhD in Neurobiology and Neurophysiology from the University of Ferrara, Italy, in 1998. From 1998 to 2003 he was postdoctoral fellow in the laboratory of Dr. Elio Raviola, Department of Neurobiology, Harvard Medical School, Boston. After a brief period in Italy, in 2004 he returned to the Department of Neurobiology, Harvard Medical School, Boston, for a second postdoctoral training in the laboratory of Dr. Bruce Bean. In 2011 he joined the faculty of the Department of Anesthesiology at Stony Brook Medical Center as an Assistant Professor. He is member of the Society for Neuroscience. 

Research

Laboratory of molecular and cellular mechanism of pain

My laboratory is interested in the molecular and cellular mechanism of pain. The ability to detect noxious stimuli is critical for the survival and wellbeing of an organism. As a result, individuals respond with appropriate protective behaviors to dangerous or life threatening conditions. Pain is initiated when noxious stimuli excite the peripheral terminals of small dorsal root ganglia (DRG) neurons (nociceptors). Nociceptors express a variety of different ion channels (TRP channels, acid sensing ion channels, etc.) which allow these sensory neurons to transduce different types of noxious stimuli (mechanical, thermal, and chemical stimuli) into electrical signals. The initial depolarization of the cell membrane induced by a noxious stimulus leads to activation of voltage-dependent sodium channels, increase in firing rate and release of neurotransmitter (glutamate) in the dorsal horn spinal horn. In the setting of injuries (peripheral inflammation and/or nerve injury) ion channels expressed in nociceptors can change their level of expression or their function such that nociceptors became sensitized and hyperactive. Alterations of the pain pathway can ultimately lead to chronic, debilitating pain. As a result, innocuous stimuli (light touch or warmth) are able to induce pain (a phenomenon referred to as allodynia), or normally painful stimuli induce pain of greater intensity (a phenomenon referred to as hyperalgesia).

We use patch clamp electrophysiology, optogenetic tools, and behavioral measurements in vivo to study the effect of inflammation and nerve injury on the intrinsic excitability and synaptic transmission from nociceptors. There are two main lines of research in my laboratory: 1) Using acutely dissociated DRG neurons, we are interested in understanding how inflammation and nerve injury may affect the functional properties of ion channels and the intrinsic excitability of DRG neurons. 2) A second line of research is focusing on the descending modulation of pain. Different regions of the Central Nervous System, including noradrenergic, serotonergic, and dopaminergic nuclei, send their projections to different levels of the spinal cord. A major interest of the laboratory is to understand how dopamine (released from A11 hypothalamic dopaminergic neurons) modulates the synaptic transmission between nociceptors and lamina I projection neurons in the dorsal horn spinal cord. 

Fig. 1: Dopamine inhibition of synaptic transmission in lamina I projection neurons. A) EPSC recorded from a lamina I neuron in 10 µM bicuculline and 5 µM strychnine at 35 ºC. The dorsal root (L4) was stimulated with 500 µA (0.1 ms) of constant current every 1 min. B) 20 µM dopamine reduced the EPSC (transfer charge) by 97%. C) EPSC upon washing out dopamine. D) The EPSC was partially blocked by 20 µM D-AP5, and completely blocked by D-AP5 + 10 µM CNQX (E). F) Summary data: 20 µM dopamine reduced the EPSC by 79±23% (n=31, repeated measures one-way ANOVA followed by Dunnett’s post hoc test, *p<0.05 ).

Fig. 2: Expression of GCaMP6 in nociceptors. GCaMP6 was expressed in DRG neurons (left) and primary afferent fibers in lamina I (right) by injecting AAV1.CAG.GCaMP6s.WPRE.SV40 in the sciatic nerve. The images were taken in epifluorescence from fresh tissue using a 40X objective after 2 weeks post injection. 

A better understanding of the molecular and cellular mechanisms of acute and chronic pain will help us to identify potential therapeutic targets for the treatment of pathological conditions such as inflammatory or neuropathic pain.