Opioid receptor-mediated hyperalgesia and antinociceptive tolerance induced by sustained opiate delivery

Luis R. Gardell, Tamara King, Michael H. Ossipov, Kenner C. Rice, Josephine Lai, Todd W Vanderah, Frank Porreca

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Opiates are commonly used to treat moderate to severe pain and can be used over prolonged periods in states of chronic pain such as those associated with cancer. In addition, to analgesic actions, studies show that opiate administration can paradoxically induce hyperalgesia. At the pre-clinical level, such hyperalgesia is associated with numerous pronociceptive neuroplastic changes within the primary afferent fibers and the spinal cord. In rodents, sustained opiate administration also induces antinociceptive tolerance. The mechanisms by which prolonged opiate exposure induces hyperalgesia and the relationship of this state to antinociceptive tolerance remain unclear. The present study was aimed at determining whether sustained opiate-induced hyperalgesia, associated neuroplasticity and antinociceptive tolerance are the result of specific opiate interaction at opiate receptors. Enantiomers of oxymorphone, a mu opioid receptor agonist, were administered to rats by spinal infusion across 7 days. Sustained spinal administration of (-)-oxymorphone, but not its inactive enantiomer (+)-oxymorphone or vehicle, upregulated spinal dynorphin content, produced thermal and tactile hypersensitivity, and produced antinociceptive tolerance. These results indicate that these pronociceptive actions of sustained opiate administration require specific interaction with opiate receptors and are unlikely to be the result of accumulation of potentially excitatory metabolic products. While the precise mechanisms, which may account for these pronociceptive changes remain to be unraveled, the present data point to plasticity initiated by opiate receptor interaction.

Original languageEnglish (US)
Pages (from-to)44-49
Number of pages6
JournalNeuroscience Letters
Volume396
Issue number1
DOIs
StatePublished - Mar 20 2006

Fingerprint

Opiate Alkaloids
Hyperalgesia
Opioid Receptors
Oxymorphone
Spinal Infusions
Dynorphins
Neuronal Plasticity
mu Opioid Receptor
Touch
Chronic Pain
Analgesics
Rodentia
Spinal Cord
Hypersensitivity
Hot Temperature
Pain

Keywords

  • Antinociceptive tolerance
  • Dynorphin
  • Hyperalgesia
  • Opioid
  • Tactile hyperesthesia

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Opioid receptor-mediated hyperalgesia and antinociceptive tolerance induced by sustained opiate delivery. / Gardell, Luis R.; King, Tamara; Ossipov, Michael H.; Rice, Kenner C.; Lai, Josephine; Vanderah, Todd W; Porreca, Frank.

In: Neuroscience Letters, Vol. 396, No. 1, 20.03.2006, p. 44-49.

Research output: Contribution to journalArticle

Gardell, Luis R. ; King, Tamara ; Ossipov, Michael H. ; Rice, Kenner C. ; Lai, Josephine ; Vanderah, Todd W ; Porreca, Frank. / Opioid receptor-mediated hyperalgesia and antinociceptive tolerance induced by sustained opiate delivery. In: Neuroscience Letters. 2006 ; Vol. 396, No. 1. pp. 44-49.
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