Skip to main content

Advertisement

Log in

Capsaicin Receptors in Sleep Regulation

  • Review
  • Published:
Sleep and Vigilance Aims and scope Submit manuscript

Abstract

Capsaicin receptors are found not only in the skin, but also in many neural and non-neural tissues. Though their involvement in many functions is now known, their role in sleep regulation has not gained proper attention. As capsaicin receptors can alter body temperature, it has led to the belief that sleep changes result from an alteration in body temperature. There is now convincing evidence to show that the capsaicin receptors are an integral part of sleep regulation. The role of capsaicin receptors in sleep in rats was reported as early as the1980s. Most of the sleep-related studies were carried out on capsaicin-desensitized animal model. Sleep, especially slow wave sleep (SWS), was increased, while Rapid Eye Movement (REM) sleep reduced after the destruction of peripheral and central capsaicin receptors in rats. When peripheral capsaicin receptors were selectively destroyed, the sleep was increased, particularly due to an increase in REM sleep. Reduction in SWS and REM sleep after lesion of the preoptic area (POA) showed that the capsaicin receptors, in this sleep regulating area, play a major role in facilitating SWS and REM sleep. It is important to understand the sleep-related functions of the ion channels activated by capsaicin, to develop drugs for sleep-related disorders.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Availability of Data and Material

Not applicable.

References

  1. The Nobel Prize in physiology or medicine 2021. https://www.nobelprize.org/prizes/medicine/2021/summary/ (Accessed on 5th Oct 2021)

  2. Indian lab may have helped validate research that fetched the medicine Nobel. https://www.newindianexpress.com/nation/2021/oct/06/indian-lab-may-have-helped-validate-research-that-fetched-the-medicine-nobel-2368133.html (Accessed on 5th Oct 2021)

  3. Kumar VM, Pandi-Perumal SR. Why Indian scientific contributions do not fetch Nobel Prize. Sleep Vigilance. 2021;5:171–3. https://doi.org/10.1007/s41782-021-00175-z.

    Article  Google Scholar 

  4. Szolcsányi J. Forty years in capsaicin research for sensory pharmacology and physiology. Neuropeptides. 2004;38:377–84. https://doi.org/10.1016/j.npep.2004.07.005 (PMID: 15567473).

    Article  CAS  PubMed  Google Scholar 

  5. Szolcsányi J. Effect of capsaicin on thermoregulation: an update with new aspects. Temperature (Austin). 2015;2:277–96. https://doi.org/10.1080/23328940.2015.1048928 (Published 2015 Jun 2).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Benedek G, Obál F Jr, Jancsó-Gábor A, Obál F. Effects of elevated ambient temperatures on the sleep-waking activity of rats with impaired warm reception. Waking Sleeping. 1980;4:87–94 (PMID: 7395198).

    CAS  PubMed  Google Scholar 

  7. Jancsó-Gabor A. Anaesthesia-like condition and/or potentiation of hexobarbital sleep produced by pungent agents in normal and capsaicin-desensitized rats. Acta Physiol Acad Sci Hung. 1980;55:57–62 (PMID: 7395532).

    PubMed  Google Scholar 

  8. Obál F Jr, Tobler I, Borbély AA. Effect of ambient temperature on the 24-hour sleep-wake cycle in normal and capsaicin-treated rats. Physiol Behav. 1983;30:425–30. https://doi.org/10.1016/0031-9384(83)90148-8 (PMID: 6867140).

    Article  PubMed  Google Scholar 

  9. Caterina MJ, Leffler A, Malmberg AB, Martin WJ, Trafton J, Petersen-Zeitz KR, et al. Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science. 2000;288:306–13. https://doi.org/10.1126/science.288.5464.306.

    Article  CAS  PubMed  Google Scholar 

  10. Davis JB, Gray J, Gunthorpe MJ, Hatcher JP, Davey PT, Overend P, et al. Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia. Nature. 2000;405:183–7. https://doi.org/10.1038/35012076.

    Article  CAS  PubMed  Google Scholar 

  11. Bucholz CF. Chemische Untersuchung der trockenenreifenspanischenPfeffers [Chemical investigation of dry, ripe Spanish peppers]. Almanachoder Taschenbuch für Scheidekünstler und Apotheker [Almanac or Pocketbook for Analysts and Apothecaries]. 1816;37:1–30.

    Google Scholar 

  12. Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature. 1997;389:816–24. https://doi.org/10.1038/39807.

    Article  CAS  PubMed  Google Scholar 

  13. Clapham DE. TRP channels as cellular sensors. Nature. 2003;426:517–24. https://doi.org/10.1038/nature02196.

    Article  CAS  PubMed  Google Scholar 

  14. Xue Q, Yu Y, Trilk SL, Jong BE, Schumacher MA. The genomic organization of the gene encoding the vanilloid receptor: evidence for multiple splice variants. Genomics. 2001;76:14–20. https://doi.org/10.1006/geno.2001.6582 (PMID11549313).

    Article  CAS  PubMed  Google Scholar 

  15. Shuba YM. Beyond neuronal heat sensing: diversity of TRPV1 heat-capsaicin receptor-channel functions. Front Cell Neurosci. 2021. https://doi.org/10.3389/fncel.2020.612480.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Shibasaki K. Physiological significance of TRPV2 as a mechanosensor, thermosensor and lipid sensor. J Physiol Sci. 2016;66:359–65. https://doi.org/10.1007/s12576-016-0434-7 (PMID 26841959. S2CID 582291).

    Article  CAS  PubMed  Google Scholar 

  17. Sulk M, Steinhoff M. Role of TRP channels in skin diseases. In TRP channels as therapeutic targets. Academic Press. 2015. pp 293–323. https://doi.org/10.1016/B978-0-12-420024-1.00017-5

  18. Liedtke W, Choe Y, Martí-Renom MA, Bell AM, Denis CS, Hudspeth AJ, Friedman JM, Heller S. Vanilloid receptor–related osmotically activated channel (VR-OAC), a candidate vertebrate osmoreceptor. Cell. 2000;103:525–35.

    Article  CAS  Google Scholar 

  19. van Abel M, Hoenderop JGJ, Bindels RJM. The epithelial calcium channels TRPV5 and TRPV6: regulation and implications for disease. Naunyn-Schmiedeberg’s Arch Pharmacol. 2005;371:295–306. https://doi.org/10.1007/s00210-005-1021-2.

    Article  CAS  Google Scholar 

  20. Edwards SJ, Montgomery IM, Colquhoun EQ, Jordan JE, Clark MG. Spicy meal disturbs sleep: an effect of thermoregulation? Int J Psychophysiol. 1992;13:97–100. https://doi.org/10.1016/0167-8760(92)90048-G.

    Article  CAS  PubMed  Google Scholar 

  21. Kumar VM. Body temperature and sleep: Are they controlled by the same mechanism? Sleep Biol Rhythms. 2004;2:103–24.

    Article  Google Scholar 

  22. Harding EC, Franks NP, Wisden W. Sleep and thermoregulation. CurrOpin Physiol. 2020;15:7–13. https://doi.org/10.1016/j.cophys.2019.11.008.

    Article  Google Scholar 

  23. Schlader ZJ, Sarker S, Mündel T, Coleman GL, Chapman CL, Sackett JR, Johnson BD. Hemodynamic responses upon the initiation of thermoregulatory behavior in young healthy adults. Temperature (Austin). 2016;3:271–85. https://doi.org/10.1080/23328940.2016.1148938 (PMID: 27857957; PMCID: PMC4965002).

    Article  Google Scholar 

  24. Ray B, Mallick HN, Kumar VM. Changes in thermal preference, sleep-wakefulness, body temperature and locomotor activity of rats during continuous recording for 24 hours. Behav Brain Res. 2004;154:519–26.

    Article  Google Scholar 

  25. Ray B, Mallick HN, Kumar VM. Changes in sleep-wakefulness in the medial preoptic area lesioned rats: role of thermal preference. Behav Brain Res. 2005;158(1):43–52 (Epub 2005 Jan 7).

    Article  Google Scholar 

  26. Aristakesian EA, Vataev SI. The development of sleep phases and thermoregulation in the early ontogeny of rats. Zh Evol Biokhim Fiziol. 1993;29:53–9.

    CAS  PubMed  Google Scholar 

  27. Jancso G, Kiraly E, Jancso-Gabor A. Pharmacologically induced selective degeneration of chemosensitive primary sensory neurons. Nature. 1977;270:741–3.

    Article  CAS  Google Scholar 

  28. Dib B. Dissociation between peripheral and central heat loss mechanisms induced by neonatal capsaicin. Behav Neurosci. 1983;97:822–5.

    Article  CAS  Google Scholar 

  29. Gulia KK, Mallick HN, Kumar VM. Ambient temperature related sleep changes in rats neonatally treated with capsaicin. Physiol Behav. 2005;85:414–8. https://doi.org/10.1016/j.physbeh.2005.05.001 (PMID: 15963539).

    Article  CAS  PubMed  Google Scholar 

  30. Jeong KY. Changes in TRPV1-mediated physiological function in rats systemically treated with capsaicin on the neonate. Int J Mol Sci. 2020;21:3143. https://doi.org/10.3390/ijms21093143 (PMID: 32365623; PMCID: PMC7247669).

    Article  CAS  PubMed Central  Google Scholar 

  31. Jeong KY, Kim HM. Neonatal capsaicin treatment in rats induces chronic hyperthermia resulting in infectious disease. Exp Ther Med. 2015;10:2417–23. https://doi.org/10.3892/etm.2015.2829 (Epub 2015 Oct 23. PMID: 26668650; PMCID: PMC4665930).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Kim J, Woo Y, Kim G, Kim C, Ma J, Hwang T, Lee M. Congenital insensitivity to pain with anhidrosis: a case report. J Korean Med Sci. 1999;14:460–4.

    Article  CAS  Google Scholar 

  33. Parmeggiani PL. Thermoregulation during sleep. Rev Neurol. 1977;47:485–91.

    CAS  Google Scholar 

  34. Horne JA, Staff LH. Exercise and sleep: body-heating effects. Sleep. 1983;6:36–46.

    Article  CAS  Google Scholar 

  35. Horne JA, Shackell BS. Slow wave sleep elevations after body heating: proximity to sleep and effects of aspirin. Sleep. 1987;10:383–92.

    Article  CAS  Google Scholar 

  36. Morairty SR, Szymusiak R, Thomson D, McGinty DJ. Selective increases in non-rapid eye movement sleep following whole body heating in rats. Brain Res. 1993;617:10–6.

    Article  CAS  Google Scholar 

  37. Kumar D, Kumar VM, Mallick HN. Warm sensitive neurons of the preoptic area regulate ambient temperature related changes in sleep in the rat. Indian J Physiol Pharmacol. 2011;55:262–71 (PMID: 22471234).

    PubMed  Google Scholar 

  38. Kumar VM. Why the medial preoptic area is important for sleep regulation. Indian J Physiol Pharmacol. 2004;48:137–49.

    PubMed  Google Scholar 

  39. Rothhaas R, Chung S. Role of the preoptic area in sleep and thermoregulation. Front Neurosci. 2021;15: 664781. https://doi.org/10.3389/fnins.2021.664781.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Tsuneoka Y, Funato H. Cellular composition of the preoptic area regulating sleep, parental, and sexual behavior. Front Neurosci. 2021. https://doi.org/10.3389/fnins.2021.649159.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Kumar D, Kumar VM, Mallick HN. Ambient temperature-dependent thermoregulatory role of REM sleep. J Thermal Biol. 2012;37:392–6. https://doi.org/10.1016/j.jtherbio.2012.02.005.

    Article  Google Scholar 

  42. Obál F Jr, Benedek G, Jancsó-Gábor A, Obál F. Salivary cooling, escape reaction and heat pain in capsaicin-desensitized rats. Pflugers Arch. 1979;382:249–54.

    Article  Google Scholar 

  43. Obál F Jr, Benedek G, Jancsó-Gábor A, Obál F. Tail skin vasodilatation and bath test in capsaicin-desensitized rats. Pflugers Arch. 1980;387:183–8.

    Article  Google Scholar 

  44. Jancsó-Gábor A, Szolcsányi J, Jancsó N. Irreversible impairment of thermoregulation induced by capsaicin and similar pungent substances in rats and guinea-pigs. J Physiol. 1970;206:495–507.

    Article  Google Scholar 

  45. Hori T, Tsuzuki S. Thermoregulation in adult rats which have been treated with capsaicin as neonates. Pflugers Arch. 1981;390:219–23.

    Article  CAS  Google Scholar 

  46. Yonghak P, Miyata S, Kurganov E. TRPV1 is crucial for thermal homeostasis in the mouse by heat loss behaviors under warm ambient temperature. Sci Rep. 2020;10:8799. https://doi.org/10.1038/s41598-020-65703-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. McGaraughty S, Segreti JA, Fryer RM, Brown BS, Faltynek CR, Kym PR. Antagonism of TRPV1 receptors indirectly modulates activity of thermoregulatory neurons in the medial preoptic area of rats. Brain Res. 2009;1268:58–67. https://doi.org/10.1016/j.brainres.2009.02.018 (ISSN 0006-8993).

    Article  CAS  PubMed  Google Scholar 

  48. Yadav R, Mallick HN, Jaryal AK. Role of TRPV1 antagonist microinjection in the preoptic area on brain and body temperature. Indian J Physiol Pharmacol. 2015;59: 68 https://ijpp.com/IJPP%20archives/2015_59_5/APPICON%202015%20Abstract%20Book.pdf

  49. Yadav R, Jaryal AK, Mallick HN. Participation of preoptic area TRPV4 ion channel in regulation of body temperature. J Therm Biol. 2017;66:81–6. https://doi.org/10.1016/j.jtherbio.2017.04.001 (Epub 2017 Apr 6 PMID: 28477913).

    Article  CAS  PubMed  Google Scholar 

  50. Kumar VM. Sleep is an auto-regulatory global phenomenon. Front Neurol. 2012;3:94. https://doi.org/10.3389/fneur.2012.00094 (ISSN=1664-2295).

    Article  PubMed  PubMed Central  Google Scholar 

  51. Menigoz A, Boudes M. The expression pattern of TRPV1 in brain. J Neurosci. 2011;31:13025–7. https://doi.org/10.1523/JNEUROSCI.2589-11.2011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Tian Y, Du G, Jin J, Yang Z, Hu F, Lu W, Wang K, Zheng J. Capsaicin changes the pattern of brain rhythms in sleeping rat. Feder Am Soc Experiment Biol FASEB J. 2020;34:Issue S1. https://doi.org/10.1096/fasebj.2020.34.s1.01792.

    Article  Google Scholar 

Download references

Funding

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kamalesh K. Gulia.

Ethics declarations

Conflict of Interests

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kumar, V.M., Kumar, D., Mallick, H.N. et al. Capsaicin Receptors in Sleep Regulation. Sleep Vigilance 6, 41–49 (2022). https://doi.org/10.1007/s41782-022-00193-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s41782-022-00193-5

Keywords

Navigation