Oxytocin, Astrocytes, Modification of Amygdala Circuits and Pain – IASP Early Research Career Grant Report


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As a physician who prescribes Oxytocin [OT] and sees profound relief of many forms of intractable pain and/or relief of treatment refractory Major Depressive Disorder or Anxiety and Panic Disorder, this research on mechanisms is deeply meaningful and long awaited. Oxytocin is a hormone made in the brain, but also in the heart and other organs in women and men. It is rare to find work on glia and oxytocin.

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Today the International Association for Study of Pain announced the final report from their 2012 Early Research Career Grant:

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“Dr. Alexander Charlet of the Centre National de la Recherche Scientifique (CNRS) in Strasbourg, France, has submitted his final report for his project “Involvement of astrocytes in the endogenous oxytocin modification of amygdala microcircuits….”

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“Dr. Charlet’s project focuses on the functional consequences of endogenous OT release in amygdala microcircuits on nociception and pain. In addition, he aims to decipher the precise mechanism, cellular and molecular, by which OT exerts its action. Thus, the purposes of his project are to characterize in vivo and in vitro the effects of endogenous OT in the amygdala on pain-related symptoms….

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.….”In addition, he was surprised to discover that perceptions of his project’s importance grew once it was awarded and triggered future collaborations: a Marie Curie European Action Career Integration Grant and the French Initiative d’Excellence Attractivity.”

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“As a result, Dr. Charlet also received two major personal prizes: an award from Swiss Society for Biological Psychiatry in 2012 and award from the French Académie nationale de medicine with the prestigious Albert Sézary price in 2013. Finally, he has been recruited as a neurosciences permanent researcher by the CNRS and recently opened his independent lab.”

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The material on this site is for informational purposes only.

It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

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Please understand that it is not legal for me

to give medical advice without a consultation.

If you wish an appointment, please telephone my office.

.

For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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Botox Combined with Substance P Relieves Chemotherapy Induced Neuropathic Pain in Mice


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After my post on the exciting research published in Great Britain on Botox Chimeras earlier today, Dr. Robert Caudle graciously notified me of his team’s recent research publication on Botox conjugates injected into the cerebral spinal fluid cisterns in mice. The abstract is below:

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Anti-nociceptive effect of a conjugate of substance P and light chain of botulinum neurotoxin type A

published online 12 August 2013 in PAIN, the Journal of the International Association for the Study of Pain. 

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Summary 

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A conjugate of substance P and the light chain of botulinum toxin type A (BoNT/A-LC:SP) possesses an anti-nociceptive effect. The conjugate has been reported to reduce neuropathic pain in a chemotherapy-induced neuropathic pain model.

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Abstract 

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Neuropathic pain is a debilitating condition resulting from damage to sensory transmission pathways in the peripheral and central nervous system. A potential new way of treating chronic neuropathic pain is to target specific pain-processing neurons based on their expression of particular receptor molecules. We hypothesized that a toxin–neuropeptide conjugate would alter pain by first being taken up by specific receptors for the neuropeptide expressed on the neuronal cells. Then, once inside the cell the toxin would inhibit the neurons’ activity without killing the neurons, thereby providing pain relief without lesioning the nervous system. In an effort to inactivate the nociceptive neurons in the trigeminal nucleus caudalis in mice, we targeted the NK1 receptor (NK1R) using substance P (SP). The catalytically active light chain of botulinum neurotoxin type A (LC/A) was conjugated with SP. Our results indicate that the conjugate BoNT/A-LC:SP is internalized in cultured NK1R-expressing neurons and also cleaves the target of botulinum toxin, a component-docking motif necessary for release of neurotransmitters called SNAP-25. The conjugate was next tested in a murine model of Taxol-induced neuropathic pain. An intracisternal injection of BoNT/A-LC:SP decreased thermal hyperalgesia as measured by the operant orofacial nociception assay. These findings indicate that conjugates of the light chain of botulinum toxin are extremely promising agents for use in suppressing neuronal activity for extended time periods, and that BoNT/A-LC:SP may be a useful agent for treating chronic pain.

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.

~~~~~

The material on this site is for informational purposes only.

It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

~~~~~

Please understand that it is not legal for me

to give medical advice without a consultation.

If you wish an appointment, please telephone my office.

.

For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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.

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