Molecular Surgery Concept from Bench to Bedside: A Focus on TRPV1+ Pain-Sensing Neurons

“Molecular neurosurgery” is emerging as a new medical concept, and is the combination of two partners: (i) a molecular neurosurgery agent, and (ii) the cognate receptor whose activation results in the selective elimination of a specific subset of neurons in which this receptor is endogenously expres...

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Main Authors: László Pecze, Béla Viskolcz, Zoltán Oláh
Format: Article
Language:English
Published: Frontiers Media S.A. 2017-06-01
Series:Frontiers in Physiology
Subjects:
Online Access:http://journal.frontiersin.org/article/10.3389/fphys.2017.00378/full
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author László Pecze
Béla Viskolcz
Zoltán Oláh
Zoltán Oláh
author_facet László Pecze
Béla Viskolcz
Zoltán Oláh
Zoltán Oláh
author_sort László Pecze
collection DOAJ
description “Molecular neurosurgery” is emerging as a new medical concept, and is the combination of two partners: (i) a molecular neurosurgery agent, and (ii) the cognate receptor whose activation results in the selective elimination of a specific subset of neurons in which this receptor is endogenously expressed. In general, a molecular surgery agent is a selective and potent ligand, and the target is a specific cell type whose elimination is desired through the molecular surgery procedure. These target cells have the highest innate sensitivity to the molecular surgery agent usually due to the highest receptor density being in their plasma membrane. The interaction between the ligand and its receptor evokes an overactivity of the receptor. If the receptor is a ligand-activated non-selective cation channel, the overactivity of receptor leads to excess Ca2+ and Na+ influx into the cell and finally cell death. One of the best known examples of such an interaction is the effect of ultrapotent vanilloids on TRPV1-expressing pain-sensing neurons. One intrathecal resiniferatoxin (RTX) dose allows for the receptor-mediated removal of TRPV1+ neurons from the peripheral nervous system. The TRPV1 receptor-mediated ion influx induces necrotic processes, but only in pain-sensing neurons, and usually within an hour. Besides that, target-specific apoptotic processes are also induced. Thus, as a nano-surgery scalpel, RTX removes the neurons responsible for generating pain and inflammation from the peripheral nervous system providing an option in clinical management for the treatment of morphine-insensitive pain conditions. In the future, the molecular surgery concept can also be exploited in cancer research for selectively targeting the specific tumor cell.
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spelling doaj.art-ecbeb979157e4c778e02f22ad2055f022022-12-21T19:45:36ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2017-06-01810.3389/fphys.2017.00378269628Molecular Surgery Concept from Bench to Bedside: A Focus on TRPV1+ Pain-Sensing NeuronsLászló Pecze0Béla Viskolcz1Zoltán Oláh2Zoltán Oláh3Unit of Anatomy, Department of Medicine, University of FribourgFribourg, SwitzerlandInstitute of Chemistry, Faculty of Materials Science and Engineering, University of MiskolcMiskolc, HungaryInstitute of Chemistry, Faculty of Materials Science and Engineering, University of MiskolcMiskolc, HungaryAcheuron Ltd.Szeged, Hungary“Molecular neurosurgery” is emerging as a new medical concept, and is the combination of two partners: (i) a molecular neurosurgery agent, and (ii) the cognate receptor whose activation results in the selective elimination of a specific subset of neurons in which this receptor is endogenously expressed. In general, a molecular surgery agent is a selective and potent ligand, and the target is a specific cell type whose elimination is desired through the molecular surgery procedure. These target cells have the highest innate sensitivity to the molecular surgery agent usually due to the highest receptor density being in their plasma membrane. The interaction between the ligand and its receptor evokes an overactivity of the receptor. If the receptor is a ligand-activated non-selective cation channel, the overactivity of receptor leads to excess Ca2+ and Na+ influx into the cell and finally cell death. One of the best known examples of such an interaction is the effect of ultrapotent vanilloids on TRPV1-expressing pain-sensing neurons. One intrathecal resiniferatoxin (RTX) dose allows for the receptor-mediated removal of TRPV1+ neurons from the peripheral nervous system. The TRPV1 receptor-mediated ion influx induces necrotic processes, but only in pain-sensing neurons, and usually within an hour. Besides that, target-specific apoptotic processes are also induced. Thus, as a nano-surgery scalpel, RTX removes the neurons responsible for generating pain and inflammation from the peripheral nervous system providing an option in clinical management for the treatment of morphine-insensitive pain conditions. In the future, the molecular surgery concept can also be exploited in cancer research for selectively targeting the specific tumor cell.http://journal.frontiersin.org/article/10.3389/fphys.2017.00378/fullTRPV1vanilloidscapsaicinresiniferatoxinsensory neuronsnecrosis
spellingShingle László Pecze
Béla Viskolcz
Zoltán Oláh
Zoltán Oláh
Molecular Surgery Concept from Bench to Bedside: A Focus on TRPV1+ Pain-Sensing Neurons
Frontiers in Physiology
TRPV1
vanilloids
capsaicin
resiniferatoxin
sensory neurons
necrosis
title Molecular Surgery Concept from Bench to Bedside: A Focus on TRPV1+ Pain-Sensing Neurons
title_full Molecular Surgery Concept from Bench to Bedside: A Focus on TRPV1+ Pain-Sensing Neurons
title_fullStr Molecular Surgery Concept from Bench to Bedside: A Focus on TRPV1+ Pain-Sensing Neurons
title_full_unstemmed Molecular Surgery Concept from Bench to Bedside: A Focus on TRPV1+ Pain-Sensing Neurons
title_short Molecular Surgery Concept from Bench to Bedside: A Focus on TRPV1+ Pain-Sensing Neurons
title_sort molecular surgery concept from bench to bedside a focus on trpv1 pain sensing neurons
topic TRPV1
vanilloids
capsaicin
resiniferatoxin
sensory neurons
necrosis
url http://journal.frontiersin.org/article/10.3389/fphys.2017.00378/full
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