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

JOURNAL OF PAIN

卷:10

Article

Wang, Wenfei¹  Baghdoyan, Helen A.¹  Lydic, Ralph¹ 

[1] Univ Michigan, Dept Anesthesiol, Ann Arbor, MI 48109 USA

关键词: Acetylcholine;    adenosine;    morphine;    obesity;    sleep;    pain;   

DOI  :  10.1016/j.jpain.2009.02.003

来源: Elsevier

【 摘 要 】

A single gene deletion causes lack of leptin and obesity in B6.V-Lep(ob) (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, N-6-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 anti nociception. 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. (C) 2009 by the American Pain Society

【 授权许可】

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