The effect of epidural resiniferatoxin in the neuropathic pain rat model

Research output: Contribution to journalArticle

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Abstract

Background: Resiniferatoxin (RTX) is a potent synthetic agonist for transient receptor potential vanilloid subtype 1 (TRPV1), which has a selectivity for antinociception. The analgesic effect of epidural RTX in a rat model of neuropathic pain has not yet been studied. Objectives: The purpose of this study was to evaluate the analgesic effect of epidural RTX on neuropathic pain in a rat model to mechanical and thermal stimulation. The dose-related behavior changes and side effects were also studied. Study design: A randomized, experimental trial. Setting: Department of Anesthesiology and Pain Medicine, Korea University Guro Hospital Methods: A spinal nerve ligation model was prepared using male Sprague-Dawley rats (7 weeks old, weight 230-250 g). An epidural catheter was placed at the L4-L5 level. Each study group (n = 6) received a different dose of RTX: 100 ng, 500 ng, 1 μg, 2 μg, 4 μg and 10 μg. All substances were administered in 20 μL volume doses. The control group (n = 6) received 20 μL of normal saline. We evaluated the response to mechanical and thermal stimuli as well as the sedation score at both short-term (3 hours) and long-term (20 days) after the epidural RTX injection. Results: Prolonged analgesia to thermal stimulation was preceded by a transient dose-dependent hyperalgesia (500 ng, 1 μg) or sedation (≥ 2 μg) during the initial 60 minutes after RTX administration. Marked sedation and hyperventilation were noted at higher doses (≥ 2 μg), while 2 out of 6 rats died with a 10 μg dose. ED50 for epidural RTX was 265 ng (95% confidence interval 216.1-324.9 ng). The increased latency to thermal stimulation continued for 20 days at RTX ≥ 1 μg. But the threshold to mechanical stimulation increased only in the acute period and returned to the baseline after 3-5 days, regardless of the administered dose. Limitations: A histological examination by electron-microscopic staining was not performed. The observation period was not very long (20 days). Conclusion: RTX has potential to be used in an epidural route for neuropathic pain in a rat model with a relatively small amount, which produces transitory improvement of mechanical hypersensitivity and prolonged thermal analgesic response.

Original languageEnglish
Pages (from-to)287-296
Number of pages10
JournalPain Physician
Volume15
Issue number4
Publication statusPublished - 2012 Jul 1

Fingerprint

Neuralgia
Hot Temperature
Analgesics
Epidural Injections
resiniferatoxin
Spinal Nerves
Anesthesiology
Hyperventilation
Hyperalgesia
Korea
Analgesia
Ligation
Sprague Dawley Rats
Hypersensitivity
Catheters
Observation
Medicine
Electrons
Confidence Intervals
Staining and Labeling

Keywords

  • Epidural administration
  • Mechanical allodynia
  • Mechanical hypersensitivity
  • Resiniferatoxin
  • Sedation
  • Spinal nerve ligation rat model
  • Thermal hyperalgesia

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

The effect of epidural resiniferatoxin in the neuropathic pain rat model. / Lee, Mi Geum; Huh, Billy K.; Choi, Sang Sik; Lee, Dong Kyu; Lim, Byung Gun; Lee, Mi Kyoung.

In: Pain Physician, Vol. 15, No. 4, 01.07.2012, p. 287-296.

Research output: Contribution to journalArticle

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abstract = "Background: Resiniferatoxin (RTX) is a potent synthetic agonist for transient receptor potential vanilloid subtype 1 (TRPV1), which has a selectivity for antinociception. The analgesic effect of epidural RTX in a rat model of neuropathic pain has not yet been studied. Objectives: The purpose of this study was to evaluate the analgesic effect of epidural RTX on neuropathic pain in a rat model to mechanical and thermal stimulation. The dose-related behavior changes and side effects were also studied. Study design: A randomized, experimental trial. Setting: Department of Anesthesiology and Pain Medicine, Korea University Guro Hospital Methods: A spinal nerve ligation model was prepared using male Sprague-Dawley rats (7 weeks old, weight 230-250 g). An epidural catheter was placed at the L4-L5 level. Each study group (n = 6) received a different dose of RTX: 100 ng, 500 ng, 1 μg, 2 μg, 4 μg and 10 μg. All substances were administered in 20 μL volume doses. The control group (n = 6) received 20 μL of normal saline. We evaluated the response to mechanical and thermal stimuli as well as the sedation score at both short-term (3 hours) and long-term (20 days) after the epidural RTX injection. Results: Prolonged analgesia to thermal stimulation was preceded by a transient dose-dependent hyperalgesia (500 ng, 1 μg) or sedation (≥ 2 μg) during the initial 60 minutes after RTX administration. Marked sedation and hyperventilation were noted at higher doses (≥ 2 μg), while 2 out of 6 rats died with a 10 μg dose. ED50 for epidural RTX was 265 ng (95{\%} confidence interval 216.1-324.9 ng). The increased latency to thermal stimulation continued for 20 days at RTX ≥ 1 μg. But the threshold to mechanical stimulation increased only in the acute period and returned to the baseline after 3-5 days, regardless of the administered dose. Limitations: A histological examination by electron-microscopic staining was not performed. The observation period was not very long (20 days). Conclusion: RTX has potential to be used in an epidural route for neuropathic pain in a rat model with a relatively small amount, which produces transitory improvement of mechanical hypersensitivity and prolonged thermal analgesic response.",
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AU - Lee, Mi Kyoung

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N2 - Background: Resiniferatoxin (RTX) is a potent synthetic agonist for transient receptor potential vanilloid subtype 1 (TRPV1), which has a selectivity for antinociception. The analgesic effect of epidural RTX in a rat model of neuropathic pain has not yet been studied. Objectives: The purpose of this study was to evaluate the analgesic effect of epidural RTX on neuropathic pain in a rat model to mechanical and thermal stimulation. The dose-related behavior changes and side effects were also studied. Study design: A randomized, experimental trial. Setting: Department of Anesthesiology and Pain Medicine, Korea University Guro Hospital Methods: A spinal nerve ligation model was prepared using male Sprague-Dawley rats (7 weeks old, weight 230-250 g). An epidural catheter was placed at the L4-L5 level. Each study group (n = 6) received a different dose of RTX: 100 ng, 500 ng, 1 μg, 2 μg, 4 μg and 10 μg. All substances were administered in 20 μL volume doses. The control group (n = 6) received 20 μL of normal saline. We evaluated the response to mechanical and thermal stimuli as well as the sedation score at both short-term (3 hours) and long-term (20 days) after the epidural RTX injection. Results: Prolonged analgesia to thermal stimulation was preceded by a transient dose-dependent hyperalgesia (500 ng, 1 μg) or sedation (≥ 2 μg) during the initial 60 minutes after RTX administration. Marked sedation and hyperventilation were noted at higher doses (≥ 2 μg), while 2 out of 6 rats died with a 10 μg dose. ED50 for epidural RTX was 265 ng (95% confidence interval 216.1-324.9 ng). The increased latency to thermal stimulation continued for 20 days at RTX ≥ 1 μg. But the threshold to mechanical stimulation increased only in the acute period and returned to the baseline after 3-5 days, regardless of the administered dose. Limitations: A histological examination by electron-microscopic staining was not performed. The observation period was not very long (20 days). Conclusion: RTX has potential to be used in an epidural route for neuropathic pain in a rat model with a relatively small amount, which produces transitory improvement of mechanical hypersensitivity and prolonged thermal analgesic response.

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