Adenosine A1 receptors in mouse pontine reticular formation modulate nociception only in the presence of systemic leptin

S. L. Watson, C. J. Watson, Helen Baghdoyan, Ralph Lydic

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Human obesity is associated with increased leptin levels and pain, but the specific brain regions and neurochemical mechanisms underlying this association remain poorly understood. This study used adult male C57BL/6J (B6, n=14) mice and leptin-deficient, obese B6.Cg-Lepob/J (obese, n=10) mice to evaluate the hypothesis that nociception is altered by systemic leptin levels and by adenosine A1 receptors in the pontine reticular formation. Nociception was quantified as paw withdrawal latency (PWL) in s after onset of a thermal stimulus. PWL was converted to percent maximum possible effect (%MPE). After obtaining baseline PWL measures, the pontine reticular formation was microinjected with saline (control), three concentrations of the adenosine A1 receptor agonist N6-p-sulfophenyladenosine (SPA), or super-active mouse leptin receptor antagonist (SMLA) followed by SPA 15min later, and PWL was again quantified. In obese, leptin-deficient mice, nociception was quantified before and during leptin replacement via subcutaneous osmotic pumps. SPA was administered into the pontine reticular formation of leptin-replaced mice and PWL testing was repeated. During baseline (before vehicle or SPA administration), PWL was significantly (p=0.0013) lower in leptin-replaced obese mice than in B6 mice. Microinjecting SPA into the pontine reticular formation of B6 mice caused a significant (p=0.0003) concentration-dependent increase in %MPE. SPA also significantly (p<0.05) increased %MPE in B6 mice and in leptin-replaced obese mice, but not in leptin-deficient obese mice. Microinjection of SMLA into the pontine reticular formation before SPA did not alter PWL. The results show for the first time that pontine reticular formation administration of the adenosine A1 receptor agonist SPA produced antinociception only in the presence of systemic leptin. The concentration-response data support the interpretation that adenosine A1 receptors localized to the pontine reticular formation significantly alter nociception.

Original languageEnglish (US)
Pages (from-to)531-539
Number of pages9
JournalNeuroscience
Volume275
DOIs
StatePublished - Sep 5 2014
Externally publishedYes

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Adenosine A1 Receptors
Nociception
Leptin
Obese Mice
Adenosine A1 Receptor Agonists
Pontine Tegmentum
Microinjections
Obesity
Hot Temperature

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Adenosine A1 receptors in mouse pontine reticular formation modulate nociception only in the presence of systemic leptin. / Watson, S. L.; Watson, C. J.; Baghdoyan, Helen; Lydic, Ralph.

In: Neuroscience, Vol. 275, 05.09.2014, p. 531-539.

Research output: Contribution to journalArticle

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