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Researchers
  • Prof.  Alexander Binshtok
Dr Alexander Binshtok
 
Tree of Pain – Image of Dorsal Root Ganglion labelled by PainBow
"Tree of Pain" – Image of Dorsal Root Ganglion labelled by PainBow
(Leibowich H., Binshtok Lab, cover of Frontiers in Molecular Neuroscience, 2017)
We are studying the complex mechanisms that underlie the experience of pain with the hope that a better understanding can lead to more successful methods of control and treatment. Our research into the diversity of pain phenomena adopts a multidisciplinary approach; it incorporates novel imaging techniques and electrophysiological, histological and behavioral experiments, to study pain-related mechanisms at the molecular and cellular level, as well as the level of neuronal networks and behavior. It is anticipated that this integrative approach will yield a fundamental understanding of the multidimensional mechanisms involved in the unremitting suffering of pain experienced by so many people. New targets for the treatment of pain will be identified and lead to the development of new pain-specific anesthetic drugs which could eliminate the sensation of pain much more effectively than currently available painkillers.
Research Topics

Follow the pain

The morphological and physiological complexity of multidimensional and multilevel processing of pain-related information limits our ability to understand pain perception. all levels difficult. To be able to comprehend pain related information from many levels along the pain neuroaxis, an integrative approach, which encompasses both information about neuronal activity but also predefined and novel undefined connectivity within networks associated to pain related sensory information, is required. To this end, my lab is undertaking the following: (1) developing novel approaches to investigate the fundamental site of signal detection: the nociceptive terminals. (2) Pain perception and pain related synaptic plasticity can only be resolved if a profound understanding of the exact mapping from individual peripheral receptors to central neurons is known and this is at the base of our research. The information on track and connectivity of nociceptors opens important avenues for exploring and characterising synaptic properties of pain related networks at different levels. To do so we use multiple patch-in-slice recordings, together with voltage-sensitive dye imaging. We also integrate optogenetic methods for both ex-vivo and in-vivo models in order to activate specific pathways. However, the optimal method to evaluate the activity of cortical neurons in response to noxious stimulation is to monitor their activity in-vivo while simultaneously stimulating peripheral receptors. To this end we use advanced in-vivo multiphoton imaging, together with electrophysiological recordings, in order to define and characterize the neuronal networks, which respond to stimulation of individual pain receptors at the periphery.
We hope to map out connections through the nociceptive related neuroaxis that convey information from single receptors to their destination, at the level of primary somatosensory cortex. By identifying this pathway, we will define local circuits processing of nociceptive information at each transmission junction. These results will explain the “physiological” behaviour of neuronal circuits during acute noxious stimuli. This behaviour will underlie the sensory-descriptive component of nociceptive pain. Moreover, it will produce a basis for studying modulations of circuits which are mediated by perpetual “pathological” stimuli.
The results of this work will yield significant novel and fundamental insights into the mechanisms of pain sensation and will elucidate new potential targets for the treatment of inflammatory and neuropathic pain.
Time-lapse of changes in calcium in the nociceptive terminal following focal application of capsaicin.
Time-lapse of changes in calcium in the nociceptive terminal following focal application of capsaicin. Note, that calcium enters locally into the terminal tip and then propagates along the terminal process.
From Goldstein et al JBO, 2017
This project is funded by ERC, DIP and ISF

Molecular and Cellular Determinants of Pain and Itch Sensation

Molecular and Cellular Determinants of Pain and Itch Sensation
From Binshtok et al, Nature, 2007 and Robinson et al, Nature Neuroscience, 2013
We recently discovered for the first the mechanism by which pain and itch is encoded by peripheral neurons. Using combined electrophysiology recordings and ion imaging together with the behavioral experiments, we demonstrated that that although pain and itch stimuli are detected by similar transduced channels - TRPV1 and TRPA1, these channels are expressed by functionally distinct pain and itch neurons thus the encoding of pain and itch is achieved already at the level of the peripheral fibers.
This project is funded by ERC and DIP

Mechanisms of Inflammatory Pain

Mechanisms of Inflammatory Pain
From Gudes et al, Journal of Neurophysiology, 2015
We are studying the biophysical mechanisms of inflammatory pain-induced hyperexcitability of peripheral pain related neurons
This project is funded by ERC and DIP

PainBow

We are using Neuronal Positioning System which we developed (Tsuriel et al, Nature Methods, 2015) to follow nociceptive information from the periphery to the spinal cord and trigeminal nucleus. Moreover, we have modified NPS to study nerve injury related peripheral plasticity. Using this new technique, we named PAINBOW, we show that nerve-injury lead to changes in the innervation pattern of the target organs, such that the denervated areas become reinnervated mostly by non-nociceptive neurons. This injury-mediated peripheral plasticity may underlie neuropathy-induced increases in pain.
This project is funded by ERC

Pain and itch selective analgesia

Mechanisms of Inflammatory Pain
From Binshtok et al, Nature, 2007 and Robinson et al, Nature Neuroscience, 2013
Targeted delivery of therapeutic compounds to selective cell types is of great clinical importance and can minimize undesired side effects. Recently, we developed a novel method for the targeted delivery of charged, and therefore membrane impermeant molecules, selectively into pain-sensing neurons. This approach could be used clinically to produce long lasting regional analgesia while preserving motor and autonomic function. In addition to the application of this technology for surgery and childbirth, this technique could also be used to diminish postoperative and cancer pain, as well as inflammatory and neuropathic pain. We now further explore the utility of this technique for clinical use as an analgesic and also study if the strategy can be used in a more generalized way for targeted delivery of charged compounds, to specific types of cells. This approach represents a novel concept of targeted delivery of impermeant compounds and can be used not only to block activity but also to modulate intracellular signal transduction and metabolism pathways in pain- sensing neurons a well as cancer or any other TRP-expressing cells, while minimizing effects on other types of cells.
This project is funded by ERC, DIP, Marie Curie and Rosetrees Fund
Lab Members
Dr Shaya Lev
Dr. Shaya Lev
Dr Ben Katz
Dr. Ben Katz
Dr Yishai Kushnir
Dr. Yishai Kushnir
Dr Yoav Mazor
Dr. Yoav Mazor
Robert Goldstein
Robert Goldstein
Sagi Gudes
Sagi Gudes
Omer Barkai
Omer Barkai
Hodaya Leibovich
Hodaya Leibovich
Yaki Casrpi
Yaki Casrpi

Alumni

Dr Arik Tzour
Dr. Arik Tzour
Dr David Roberson
Dr. David Roberson
Hagit Raizel
Hagit Raizel
Dr Shlomo Tsuriel
Dr. Shlomo Tsuriel
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