Opioid self-administration in the nerve-injured rat: Relevance of antiallodynic effects to drug consumption and effects of intrathecal analgesics

Thomas J. Martin, Susy A. Kim, Nancy L. Buechler, Frank Porreca, James C. Eisenach

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

BACKGROUND: Neuropathic pain is associated with several sensory abnormalities, including allodynia as well as spontaneous pain. Opioid intake in neuropathic pain patients is motivated by alleviation of both pain and allodynia. However, laboratory animal studies rely almost exclusively on reflexive withdrawal measures of allodynia. The authors examined the pharmacology of self-regulated intake of opioids in rats with or without nerve injury and compared the rate of drug intake to reversal of allodynia. METHODS: Rats were implanted with intravenous catheters, and the L5 and L6 spinal nerves were ligated in half of these animals. Rats were then trained to self-administer a commonly abused opioid (heroin) and commonly prescribed opioids (morphine, fentanyl, hydromorphone, and methadone). In addition, rats trained to self-administer heroin were given either clonidine or adenosine spinally before self-administration sessions to assess opioid-sparing effects. RESULTS: Nerve injury significantly decreased the reinforcing effects of low doses of opioids, and only doses of each opioid that reduced mechanical hypersensitivity maintained self-administration after spinal nerve ligation. The rate of drug consumption was correlated with the duration of the antiallodynic effect for each dose of opioid. Intrathecal administration of clonidine or adenosine reversed mechanical hypersensitivity, but only clonidine reduced heroin self-administration in rats with spinal nerve ligation. CONCLUSION: Opioid self-administration is significantly altered by nerve injury, with rate of drug intake being correlated with reversal of allodynia. Intrathecal clonidine, but not adenosine, produces opioid-sparing effects in self-administering rats. The neurobiologic mechanisms that regulate opioid consumption in rats therefore seem to be altered after nerve injury.

Original languageEnglish (US)
Pages (from-to)312-322
Number of pages11
JournalAnesthesiology
Volume106
Issue number2
DOIs
StatePublished - Feb 2007

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Self Administration
Opioid Analgesics
Analgesics
Hyperalgesia
Pharmaceutical Preparations
Clonidine
Spinal Nerves
Heroin
Adenosine
Wounds and Injuries
Neuralgia
Ligation
Hypersensitivity
Hydromorphone
Pain
Methadone
Laboratory Animals
Fentanyl
Morphine
Catheters

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Opioid self-administration in the nerve-injured rat : Relevance of antiallodynic effects to drug consumption and effects of intrathecal analgesics. / Martin, Thomas J.; Kim, Susy A.; Buechler, Nancy L.; Porreca, Frank; Eisenach, James C.

In: Anesthesiology, Vol. 106, No. 2, 02.2007, p. 312-322.

Research output: Contribution to journalArticle

Martin, Thomas J. ; Kim, Susy A. ; Buechler, Nancy L. ; Porreca, Frank ; Eisenach, James C. / Opioid self-administration in the nerve-injured rat : Relevance of antiallodynic effects to drug consumption and effects of intrathecal analgesics. In: Anesthesiology. 2007 ; Vol. 106, No. 2. pp. 312-322.
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