Journal Article

Selective Targeting of TRPV1 Expressing Sensory Nerve Terminals in the Spinal Cord for Long Lasting Analgesia

Jeffry, Joseph A., Yu, Shuang-Quan, Sikand, Parul, Evans, M. Steven, Premkumar, Louis S., Parihar, Arti

2009

نظرة عامة

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.

• الناشر: Public Library of Science,Public Library of Science (PLoS)
• موضوع: 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