All tags Neuroscience An interview on the neurobiology of pain and itch

An interview on the neurobiology of pain and itch

On 10th and 11th April 2014, Abcam organised a two day conference on pain and itch in San Francisco. The meeting was chaired by Professors Allan Basbaum and David Julius, both of whom spoke with Abcam's Sambhav Dave to answer a few questions about pain and itch research and the Abcam meeting.

Brief biographies

Allan I. Basbaum, PhD

is Professor and Chair of the Department of Anatomy at the School of Medicine, University of California San Francisco, USA. He was elected to the Institute of Medicine and the American Academy of Arts and Sciences and is a fellow of the Royal Society.

David Julius, PhD

is Professor and Chair of the Department of Physiology at the School of Medicine, University of California San Francisco, USA. He has been recognized with numerous awards including the Shaw Prize in Life Sciences and Medicine, Price of Asturias award and Passano award. He was elected to the American Academy of Arts and Sciences, the National Academy and the Institute of Medicine.

Q. Could you briefly describe your lab’s current research interests and projects?

Allan Basbaum:
Our laboratory is interested in the mechanisms through which tissue or nerve injury result in persistent/chronic pain, looking at the changes in the properties of CNS neurons brought on by nerve injury.

We focus on the spinal cord and more recently on the anterior cingulate gyrus. We are also interested in the epigenetic changes that contribute to the nerve injury-induced mechanical hypersensitivity.

In the spinal cord we study the circuits that underlie pain and itch. We are also exploring embryonic cortical and stem cell transplantation into the spinal cord as a therapeutic strategy for the treatment of neuropathic pain and Itch.

David Julius:
My group is interested in understanding how signals are received and transmitted by the nervous system.

We have extensively studied the biophysical and pharmacological properties of sensory receptors (mainly ion channels).

We are also interested in the atomic structure of TRP ion channels. We investigate novel toxins that can be used to probe the structural and/or physiological functions of somatosensory receptors and the cells in which they are expressed.

Finally, we trying to identify novel signal transduction molecules and pathways involved in nociception.

Q. In your opinion, what is the most exciting development in the field of pain and itch in the last year?

Allan Basbaum:
The Bhlhb5 mutant mouse model is characterized by loss of spinal cord GABAergic neurons and exhibit increased itch (manifest as excessive scratching).

We have now shown that that transplantation of GABAergic neuron precursors can ameliorate not only nerve injury-induced mechanical hypersensitivity, but also the exacerbated itch syndrome that occurs in the mutant mouse model.

A review paper recently published in Science provides insight into this novel transplant strategy for modifying neural circuits in a variety of disease conditions.

David Julius:
In our lab, in a paper published in Nature, we have elucidated the atomic structure of the capsaicin receptor, TRPV1, in multiple functional states.

These studies have revealed mechanisms of stimulus-evoked gating and modulation by allosteric agents.

Q. With pain research gathering momentum, are there any articles/reviews that stand out to you?

Both:
The 2009 Cell review published by our lab is still very relevant for cellular and molecular mechanisms of pain and a recent review published by David Julius in Annual Reviews provides a good overview of TRP channels and pain. We also have a review article in press in Neuron on Spinal cord circuits that process pain and itch messages. There have also been a couple of excellent reviews, one by Ru-Rong Ji et al in Pain on the role of glia in pain and another by von Hehn CA et al in Neuron on deconstructing the neuropathic pain phenotype to reveal neural mechanisms.


Q. Looking towards the future, where would you like to see pain research move towards?

Allan Basbaum:
I would like to see continued efforts towards the molecular characterization of the nociceptors and pruritoceptors, as well as those neurons in the spinal cord circuits that are engaged by these nociceptors. There is also a growing need for the development of pharmacological agents that selectively target nociceptors and pruritoceptors. Continued efforts are required to develop animal models of spontaneous pain. Another thing that would benefit the field is a focus on animal imaging, exploring the affective component of the pain experience. Yet another exciting area is to develop further the molecular specificity of pain and itch circuits and continuing studies of the changes in the CNS that occur in morphine-tolerant animals.

David Julius:
I predict the need for more in-depth analysis of the biophysical and pharmacological properties of known channels and receptors on primary afferents, and development of novel and selective pharmacophores for these targets. We also need continued identification of novel signaling molecules (receptors, channels, and endogenous ligands/modulators) that control nociceptor excitability under normal and pathological states.

Q. Can you tell us a bit about your experience of attending and chairing an Abcam meeting?

Both:
To have a successful meeting you need a good speaker line-up and the best part was the keenness and enthusiasm of our invitees to attend and present. The meeting was the right size with plenty of time for discussion after the talks and during poster sessions. Such small meetings are good opportunity for PhD students and Post Docs to engage with the experts in the field. Abcam should continue to encourage such interactions between students and postdocs by subsidizing registration rates.

References

  • Southwell DG et al, 2014. Interneurons from embryonic development to cell-based therapy. Science, 344 (6180).
  • CaoE et al, 2013. TRPV1 structures in distinct conformations reveal activation mechanisms. Nature, 504 (7478), 113-8.
  • Liao M et al, 2013. Structure of the TRPV1 ion channel determined by electron cryo-microscopy. Nature, 504 (7478), 107-12
  • Basbaum AI et al, 2013. Cellular and molecular mechanisms of pain. Cell, 139(2), 267-84.
  • Julius D, 2013. TRP channels and pain. Annu Rev Cell Dev Biol, 29, 355-84.
  • Ji RR et al, 2013. Glia and pain: is chronic pain a gliopathy? Pain, 154 Suppl 1:S10:28.
  • Von Hehn CA et al, 2012. Deconstructing the neuropathic pain phenotype to reveal neural mechanisms. Neuron, 73 (4), 638-52.
  • Braz J et al, 2014. Transmitting pain and itch message: A contemporary view of the spinal cord circuits that generate Gate Control.  Neuron, in press.
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