Selective targeting of TRPV1 expressing sensory nerve terminals in the spinal cord for long lasting analgesia

Chronic pain is a major clinical problem and opiates are often the only treatment, but they cause significant problems ranging from sedation to deadly respiratory depression. Resiniferatoxin (RTX), a potent agonist of Transient Receptor Potential Vanilloid 1 (TRPV1), causes a slow, sustained and irr...

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Bibliographic Details
Published in:PloS one 2009-09, Vol.4 (9), p.e7021-e7021
Main Authors: Jeffry, Joseph A, Yu, Shuang-Quan, Sikand, Parul, Parihar, Arti, Evans, M Steven, Premkumar, Louis S
Format: Article
Language:English
Subjects:
Ablation
Analgesia
Anesthesiology and Pain Management
Anesthesiology and Pain Management/Acute Pain Management
Anesthesiology and Pain Management/Basic Science of Pain Management
Anesthesiology and Pain Management/Chronic Pain Management
Anesthesiology and Pain Management/Palliative Care
Animals
Capsaicin - pharmacology
Capsaicin receptors
Chronic pain
Depolarization
Diabetes
Diterpenes - pharmacology
Dorsal root ganglia
Edema
Excitatory postsynaptic potentials
Excitatory Postsynaptic Potentials - drug effects
Ganglia, Spinal - drug effects
Insulin
Male
Medicine
Mental depression
Narcotics
Nerve endings
Neurons - drug effects
Neurons - metabolism
Opiates
Opioids
Pain
Pain perception
Pharmacology
Rats
Rats, Sprague-Dawley
Resiniferatoxin
Rodents
Spinal cord
Spinal Cord - drug effects
Spinal Cord - metabolism
Synaptic transmission
Synaptic Transmission - drug effects
Terminals
Transient receptor potential proteins
TRPV Cation Channels - metabolism
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Summary:Chronic pain is a major clinical problem and opiates are often the only treatment, but they cause significant problems ranging from sedation to deadly respiratory depression. Resiniferatoxin (RTX), a potent agonist of Transient Receptor Potential Vanilloid 1 (TRPV1), causes a slow, sustained and irreversible activation of TRPV1 and increases the frequency of spontaneous excitatory postsynaptic currents, but causes significant depression of evoked EPSCs due to nerve terminal depolarization block. Intrathecal administration of RTX to rats in the short-term inhibits nociceptive synaptic transmission, and in the long-term causes a localized, selective ablation of TRPV1-expressing central sensory nerve terminals leading to long lasting analgesia in behavioral models. Since RTX actions are selective for central sensory nerve terminals, other efferent functions of dorsal root ganglion neurons can be preserved. Preventing nociceptive transmission at the level of the spinal cord can be a useful strategy to treat chronic, debilitating and intractable pain.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0007021