Leptin Replacement Restores Supraspinal Cholinergic Antinociception in Leptin-Deficient Obese Mice

Research output: Contribution to journalArticle

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Abstract

A single gene deletion causes lack of leptin and obesity in B6.V-Lepob (obese; ob) mice compared with wild-type C57BL/6J (B6) mice. This study compared the phenotype of nociception and supraspinal antinociception in obese and B6 mice by testing 2 hypotheses: (1) microinjection of cholinomimetics or an adenosine receptor agonist, but not morphine, into the pontine reticular formation (PRF) is antinociceptive in B6 but not obese mice, and (2) leptin replacement in obese mice attenuates differences in nociceptive responses between obese and B6 mice. Adult male mice (n = 22) were implanted with microinjection guide tubes aimed for the PRF. The PRF was injected with neostigmine, carbachol, nicotine, N6-p-sulfophenyladenosine (SPA), morphine, or saline (control), and latency to paw withdrawal (PWL) from a thermal stimulus was recorded. B6 and ob mice did not differ in PWL after saline microinjection into the PRF. Neostigmine, carbachol, and SPA caused PWL to increase significantly in B6 but not obese mice. An additional 15 obese mice were implanted with osmotic pumps that delivered leptin for 7 days. Leptin replacement in obese mice restored the analgesic effect of PRF neostigmine to the level displayed by B6 mice. The results show for the first time that leptin significantly alters supraspinal cholinergic antinociception. Perspective: This study specifies a brain region (the pontine reticular formation), cholinergic neurotransmission, and a protein (leptin) modulating thermal nociception. The results are relevant for efforts to understand the association between obesity, disordered sleep, and hyperalgesia.

Original languageEnglish (US)
Pages (from-to)836-843
Number of pages8
JournalJournal of Pain
Volume10
Issue number8
DOIs
StatePublished - Aug 1 2009

Fingerprint

Obese Mice
Leptin
Cholinergic Agents
Neostigmine
Microinjections
Nociception
Carbachol
Morphine
Obesity
Hot Temperature
Purinergic P1 Receptor Agonists
Hyperalgesia
Gene Deletion
Nicotine
Synaptic Transmission
Analgesics
Pontine Tegmentum
Sleep
Phenotype
Brain

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

Cite this

Leptin Replacement Restores Supraspinal Cholinergic Antinociception in Leptin-Deficient Obese Mice. / Wang, Wenfei; Baghdoyan, Helen; Lydic, Ralph.

In: Journal of Pain, Vol. 10, No. 8, 01.08.2009, p. 836-843.

Research output: Contribution to journalArticle

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