Transplant-mediated enhancement of spinal cord GABAergic inhibition reverses paclitaxel-induced mechanical and heat hypersensitivity

Pain
Joao M BrazAllan I Basbaum

Abstract

Decreased spinal cord GABAergic inhibition is a major contributor to the persistent neuropathic pain that can follow peripheral nerve injury. Recently, we reported that restoring spinal cord GABAergic signaling by intraspinal transplantation of cortical precursors of GABAergic interneurons from the embryonic medial ganglionic eminence (MGE) can reverse the mechanical hypersensitivity (allodynia) that characterizes a neuropathic pain model in the mouse. We show that MGE cell transplants are also effective against both the mechanical allodynia and the heat hyperalgesia produced in a paclitaxel-induced chemotherapy model of neuropathic pain. To test the necessity of GABA release by the transplants, we also studied the utility of transplanting MGE cells from mice with a deletion of VGAT, the vesicular GABA transporter. Transplants from these mice, in which GABA is synthesized but cannot be stored or released, had no effect on mechanical hypersensitivity or heat hyperalgesia in the paclitaxel model. Taken together, these results demonstrate the therapeutic potential of GABAergic precursor cell transplantation in diverse neuropathic pain models and support our contention that restoration of inhibitory controls through release of GABA...Continue Reading

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Citations

Jun 14, 2015·Neurobiology of Learning and Memory·Maral TajerianJ David Clark
Sep 3, 2016·The Journal of Pain : Official Journal of the American Pain Society·Daniel VardehClifford J Woolf
Oct 21, 2016·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Shehla AkbarKhwaja Fawad
Oct 28, 2017·Pain Medicine : the Official Journal of the American Academy of Pain Medicine·Theodore J Price, Michael S Gold
Dec 5, 2019·Stem Cells Translational Medicine·Martin MarsalaJoseph Ciacci
Sep 2, 2016·Frontiers in Neural Circuits·Muhammad O Chohan, Holly Moore
Jan 11, 2020·Frontiers in Neuroscience·John ManionG Gregory Neely
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Aug 21, 2018·Pain Reports·Dina L Juarez-SalinasAllan I Basbaum
Jan 19, 2016·Pain·Allan I Basbaum, João M Bráz
Aug 19, 2020·The Journal of Headache and Pain·Binbin LinGang Chen
Apr 9, 2021·Expert Opinion on Biological Therapy·William Brett McIntyreMichael G Fehlings
Jun 29, 2021·Frontiers in Molecular Biosciences·Maryam OmranIan R Kleckner
Sep 17, 2021·Journal of Anatomy·Steven J MiddletonJohn M Dawes

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