The Journal of Pain
Volume 10, Issue 8 , Pages 836-843 , August 2009

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

  • Wenfei Wang
    • ,
  • Helen A. Baghdoyan
    • ,
  • Ralph Lydic

      Affiliations

    • Corresponding Author InformationAddress reprint requests to Dr Ralph Lydic, Department of Anesthesiology, University of Michigan, 7433 Medical Sciences Building I, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5615.

Received 29 July 2008 ,Revised 28 December 2008 ,Accepted 2 February 2009.

References 

  1. Ahima RS, Bjorbaek C, Osei S, Flier JS. Regulation of neuronal and glial proteins by leptin: Implications for brain development. Endocrinology. 1999;140:2755–2762
  2. Banks WA, Coon AB, Robinson SM, Moinuddin A, Shultz JM, Nakaroke R, et al. Triglycerides induce leptin resistance at the blood-brain barrier. Diabetes. 2004;53:1253–1260
  3. Banks WA, DiPalma CR, Farrell CL. Transport of leptin across blood-brain barrier in obesity. Peptides. 1999;20:1341–1345
  4. Bhargava HN, Zhao GM. Effect of nitric oxide synthase inhibition on tolerance to the analgesic action of D-Pen2, D-Pen5 enkephalin and morphine in the mouse. Neuropeptides. 1996;30:219–223
  5. Bjorvatn B, Sagen IM, Oyane N, Waage S, Fetveit A, Pallesen S, et al. The association between sleep duration, body mass index and metabolic measures in the Hordaland Health Study. J Sleep Res. 2007;16:66–76
  6. Bockamp E, Maringer M, Spangenberg C, Fees S, Fraser S, Eshkind L, et al. Of mice and models: Improved animal models for biomedical research. Physiol Genomics. 2002;11:115–132
  7. Bonafide CP, Aucutt-Walter N, Divittore N, King T, Bixler EO, Cronin AJ. Remifentanil inhibits rapid eye movement sleep but not the nocturnal melatonin surge in humans. Anesthesiology. 2008;108:627–633
  8. Bonica JJ. The Management of Pain, Vol I. Philadelphia: Lea & Febiger; 1990;
  9. Chen H, Charlat O, Tartaglia LA, Woolf EA, Weng X, Ellis SJ, et al. Evidence that the diabetes gene encodes the leptin receptor: Identification of a mutation in the leptin receptor gene in db/db mice. Cell. 1996;84:491–495
  10. Coleman CG, Baghdoyan HA, Lydic R. Dialysis delivery of an adenosine A2A agonist into the pontine reticular formation of C57BL/6J mouse increases pontine acetylcholine release and sleep. J Neurochem. 2006;96:1750–1759
  11. Collins JG. Spinally administered neostigmine: Something to celebrate. Anesthesiology. 1995;82:327–328
  12. Dhillon H, Zigman JM, Ye C, Lee CE, McGovern RA, Tang V, et al. Leptin directly activates SF1 neurons in the VMH, and this action by leptin is required for normal body-weight homeostasis. Neuron. 2006;49:191–203
  13. Di Marco A, Demartis A, Gloaguen I, Lazzaro D, Delmastro P, Ciliberto G, et al. Leptin receptor-mediated regulation of cholinergic neurotransmitter phenotype in cells of central nervous system origin. Eur J Biochem. 2000;267:2939–2944
  14. Douglas CL, Bowman GN, Baghdoyan HA, Lydic R. C57BL/6J and B6.V-LEPOB mice differ in the cholinergic modulation of sleep and breathing. J Appl Physiol. 2005;98:918–929
  15. Flood P, Daniel D. Intranasal nicotine for postoperative pain treatment. Anesthesiology. 2004;101:1417–1421
  16. Friedman JM: Leptin, leptin receptors, and the control of body weight. Nutr Rev 56:S38–S46; discussion S54–S75, 1998
  17. Geisser ME, Wang W, Smuck M, Koch LG, Britton SL, Lydic R. Nociception before and after exercise in rats bred for high and low aerobic capacity. Neurosci Lett. 2008;443:37–40
  18. Guan Z, Vgontzas AN, Bixler EO, Fang J. Sleep is increased by weight gain and decreased by weight loss in mice. Sleep. 2008;31:627–633
  19. Hargreaves K, Dubner R, Brown F, Flores C, Joris J. A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain. 1988;32:77–88
  20. Hasler G, Buysse DJ, Klaghofer R, Gamma A, Ajdacic V, Eich D, et al. The association between short sleep duration and obesity in young adults: A 13-year prospective study. Sleep. 2004;27:661–666
  21. Hitt HC, McMillen RC, Thornton-Neaves T, Koch K, Cosby AG. Comorbidity of obesity and pain in a general population: Results from the Southern Pain Prevalence Study. J Pain. 2007;8:430–436
  22. Ingalls AM, Dickie MM, Snell GD. Obese, a new mutation in the house mouse. J Hered. 1950;41:317–318
  23. Kshatri AM, Baghdoyan HA, Lydic R. Cholinomimetics, but not morphine, increase antinociceptive behavior from pontine reticular regions regulating rapid-eye-movement sleep. Sleep. 1998;21:677–685
  24. Lamberg L. Chronic pain linked with poor sleep: Exploration of causes and treatment. JAMA. 1999;281:691–692
  25. Laposky AD, Shelton J, Bass J, Dugovic C, Perrino N, Turek FW. Altered sleep regulation in leptin-deficient mice. Am J Physiol Regul Integr Comp Physiol. 2006;290:R894–R903
  26. Lord G: Role of leptin in immunology. Nutr Rev 60:S35–S38; discussion S68–S84, S85–S37, 2002
  27. Lydic R, Baghdoyan HA. Neurochemical mechanisms mediating opioid-induced REM sleep disruption. In:  Lavigne G,  Sessle BJ,  Choinière M,  Soja PJ editor. Sleep and Pain. Seattle: International Association for the Study of Pain (IASP) Press; 2007;p. 99–122
  28. Lydic R, Douglas CL, Baghdoyan HA. Microinjection of neostigmine into the pontine reticular formation of C57BL/6J mouse enhances rapid eye movement sleep and depresses breathing. Sleep. 2002;25:835–841
  29. Lydic R, Keifer JC, Baghdoyan HA, Becker L. Microdialysis of the pontine reticular formation reveals inhibition of acetylcholine release by morphine. Anesthesiology. 1993;79:1003–1012
  30. Marcus DA. Obesity and the impact of chronic pain. Clin J Pain. 2004;20:186–191
  31. Mouse Genome Sequencing Consortium. Initial sequencing and comparative analysis of the mouse genome. Nature. 2002;420:520–562
  32. Muncey AR, Salleus A, Baghdoyan HA, Koch LG, Britton SL, Lydic R. Rats bred for low intrinsic aerobic running capacity runners (LCR) recover more slowly from chronic pain compared to rats bred for high intrinsic aerobic capacity runners (HCR). FASEB J. 2008;22:945–949
  33. Muncey A, Saulles A, Baghdoyan HA, Koch LG, Britton SL, Lydic R. Rats bred for low intrinsic aerobic running capacity exhibit decreased and more disrupted sleep compared to those bred for high intrinsic aerobic running capacity. Sleep. 2008;31(Abstr Suppl):A27
  34. O'Donnell CP, Tankersley CG, Polotsky VP, Schwartz AR, Smith PL. Leptin, obesity, and respiratory function. Respir Physiol. 2000;119:163–170
  35. Ogier V, Ziegler O, Mejean L, Nicolas JP, Stricker-Krongrad A. Obesity is associated with decreasing levels of the circulating soluble leptin receptor in humans. Int J Obes Relat Metab Disord. 2002;26:496–503
  36. Paxinos G, Franklin K. The Mouse Brain in Stereotaxic Coordinates. San Diego: Academic Press; 2001;
  37. Roehrs T, Hyde M, Blaisdell B, Greenwald M, Roth T. Sleep loss and REM sleep loss are hyperalgesic. Sleep. 2006;29:145–151
  38. Saper CB, Chou TC, Elmquist JK. The need to feed: Homeostatic and hedonic control of eating. Neuron. 2002;36:199–211
  39. Seicean A, Redline S, Seicean S, Kirchner HL, Gao Y, Sekine M, et al. Association between short sleeping hours and overweight in adolescents: Results from a US Suburban High School survey. Sleep Breath. 2007;11:285–293
  40. Singh M, Drake CL, Roehrs T, Hudgel DW, Roth T. The association between obesity and short sleep duration: A population-based study. J Clin Sleep Med. 2005;1:357–363
  41. Spiegel K, Leproult R, L'Hermite-Baleriaux M, Copinschi G, Penev PD, Van Cauter E. Leptin levels are dependent on sleep duration: relationships with sympathovagal balance, carbohydrate regulation, cortisol, and thyrotropin. J Clin Endocrinol Metab. 2004;89:5762–5771
  42. Steriade M, McCarley RW. Brain Control of Wakefulness and Sleep. New York: Kluwer Academic/Plenum Publishers; 2005;
  43. Taheri S, Lin L, Austin D, Young T, Mignot E. Short sleep duration is associated with reduced leptin, elevated ghrelin, and increased body mass index. PLoS Med. 2004;1:e62
  44. Tanase D, Baghdoyan HA, Lydic R. Microinjection of an adenosine A1 agonist into the medial pontine reticular formation increases tail flick latency to thermal stimulation. Anesthesiology. 2002;97:1597–1601
  45. Van Dort CJ, Baghdoyan HA, Lydic R. Adenosine A1 and A2A receptors in mouse prefrontal cortex modulate acetylcholine release and behavioral arousal. J Neurosci. 2009;29:871–881
  46. Vgontzas AN, Lin H-M, Papaliaga M, Calhoun S, Vela-Bueno A, Chrousos GP, et al. Short sleep duration and obesity: The role of emotional stress and sleep disturbance. Int J Obes. 2008;32:801–809
  47. Wang W, Watson SL, Baghdoyan HA, Lydic R. Nociceptive responses following pontine reticular formation microinjection of cholinomimetics, the adenosine A1 receptor agonist N6-p-sulfophenyladenosine, and morphine differ between C57BL/6J and B6.V-Lepob mice. Soc Neurosci Abstr. 2006;248.4:
  48. Wang W, Baghdoyan HA, Lydic R. Leptin increases antinociceptive responses in B6.V-Lepob mice following microinjection of neostigmine into the pontine reticular formation. Sleep. 2007;30:0009
  49. Wang W, Watson SL, Baghdoyan HA, Lydic R. Nociception is decreased by cholinomimetics and the adenosine A1 receptor agonist N6-p-sulfophenyladenosine, but not morphine, microinjected into the pontine reticular formation of C57BL/6J mouse. Sleep. 2006;29(Abstr Suppl):0012
  50. Watson SL, Watson CJ, Baghdoyan HA, Lydic R. Microinjection of hypocretin-1 into the pontine reticular nucleus, oral part (PnO) of Sprague-Dawley rat decreases response to nociceptive input. J Pain. 2008;9(Suppl 2):7
  51. Winters B, Mo Z, Brooks-Asplund E, Kim S, Shoukas A, Li D, et al. Reduction of obesity, as induced by leptin, reverses endothelial dysfunction in obese (Lep(ob)) mice. J Appl Physiol. 2000;89:2382–2390
  52. Wisloff U, Najjar SM, Ellingsen O, Haram PM, Swoap S, Al-Share Q, et al. Cardiovascular risk factors emerge after artificial selection for low aerobic capacity. Science. 2005;307:418–420
  53. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372:425–432

 Supported by National Institutes of Health grants HL65272, HL57120, HL40881, and MH45361 and the Department of Anesthesiology, University of Michigan, Ann Arbor.

PII: S1526-5900(09)00387-3

doi: 10.1016/j.jpain.2009.02.003

The Journal of Pain
Volume 10, Issue 8 , Pages 836-843 , August 2009

Article Tools

* Image Usage & Resolution