Nicotine withdrawal hyperalgesia and opioid-mediated analgesia depend on nicotine receptors in nucleus accumbens

Brian Schmidt, C. H. Tambeli, R. W. Gear, J. D. Levine

Research output: Contribution to journalArticle

Abstract

The nucleus accumbens, as part of the mesolimbic dopaminergic reward pathway, mediates both addiction to and withdrawal from substances of abuse. In addition, activity of substances of abuse such as opioids in the nucleus accumbens has been implicated in pain modulation. Because nucleus accumbens nicotinic receptors are important in nicotine addiction and because nicotinic activity can interact with opioid action, we investigated the contribution of nucleus accumbens nicotinic receptors to opioid-mediated analgesia/antinociception. The response of the nociceptive jaw-opening reflex to opioids was studied in the rat, both before and during chronic nicotine exposure. In nicotine-naive rats, intra-accumbens injection of the nicotinic receptor antagonist mecamylamine blocked antinociception produced by either systemic morphine, intra-accumbens co-administration of a μ- and a δ-opioid receptor agonist, or noxious stimulation (i.e., subdermal capsaicin in the hindpaw); intra-accumbens mecamylamine alone had no effect. The antinociceptive effect of either morphine or noxious stimulation was unchanged during nicotine tolerance; however, intra-accumbens mecamylamine lost its ability to block antinociception produced by either treatment. Intra-accumbens mecamylamine by itself precipitated significant hyperalgesia in nicotine-tolerant rats which could be suppressed by noxious stimulation as well as by morphine. These results indicate that nucleus accumbens nicotinic receptors play an important role in both opioid- and noxious stimulus-induced antinociception in nicotine-naive rats. This role was attenuated in the nicotine-dependent state. The suppression of withdrawal hyperalgesia by noxious stimulation suggests that pain can ameliorate the symptoms of withdrawal, thus suggesting a possible mechanism for pain-seeking behavior.

Original languageEnglish (US)
Pages (from-to)129-136
Number of pages8
JournalNeuroscience
Volume106
Issue number1
DOIs
StatePublished - Sep 3 2001

Fingerprint

Hyperalgesia
Nucleus Accumbens
Nicotine
Analgesia
Opioid Analgesics
Mecamylamine
Nicotinic Receptors
Morphine
Pain
Substance-Related Disorders
Nicotinic Antagonists
Substance Withdrawal Syndrome
Aptitude
Capsaicin
Opioid Receptors
Jaw
Reward
Reflex
Injections

Keywords

  • Antinociception
  • Morphine
  • Nicotine tolerance
  • Nucleus accumbens
  • Pain-induced analgesia
  • Withdrawal hyperalgesia

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Nicotine withdrawal hyperalgesia and opioid-mediated analgesia depend on nicotine receptors in nucleus accumbens. / Schmidt, Brian; Tambeli, C. H.; Gear, R. W.; Levine, J. D.

In: Neuroscience, Vol. 106, No. 1, 03.09.2001, p. 129-136.

Research output: Contribution to journalArticle

Schmidt, Brian ; Tambeli, C. H. ; Gear, R. W. ; Levine, J. D. / Nicotine withdrawal hyperalgesia and opioid-mediated analgesia depend on nicotine receptors in nucleus accumbens. In: Neuroscience. 2001 ; Vol. 106, No. 1. pp. 129-136.
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