Abstract
Endogenous opiates, endorphins and enkephalins, influence numerous processes within the body including pain, cardiac function, cellular growth, immunity, and blood glucose regulation. Both opiates are released in the brain and stay within the brain compartment. Beta-endorphins (βE) released into the blood arise primarily from the anterior pituitary gland but are also released from immune cells. Generally, acute aerobic exercise of sufficient intensity (>60 % VO2 max) can also increase circulating βE, with higher exercise intensity increasing βE to a greater extent. Exercise duration may also influence βE blood concentration. High-intensity anaerobic exercise can increase circulating βE. Resistance exercise depending on total work volume and relative intensity level can elevate blood βE. Aerobically trained individuals need to work at a greater absolute workload to manifest similar blood βE increases compared to untrained individuals. Circulating βE levels at rest are unaffected in both men and women after aerobic training with both genders being comparable. Resistance training does not appear to influence resting βE blood levels. However, it should be noted that most resistance studies utilized trained subjects. The elevation in βE appears to help modify the immune response, alter blood pressure, pain, and assists with blood glucose regulation during exercise. Limited research on enkephalins and exercise has been reported and the results are equivocal. A limited number of studies have reported an increased enkephalin level within certain regions of the brain. There are discrepancies with the enkephalin response to endurance training. Clearly more research is needed in the area of endogenous opioids and exercise especially within the CNS compartment.
Keywords
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Angelopoulos TJ. Beta-endorphin immunoreactivity during high-intensity exercise with and without opiate blockade. Eur J Appl Physiol. 2001;86(1):92–6.
Band LC, Pert A, Willams W, et al. Central u-opioid receptors mediate suppression of natural killer activity in vivo. Prog Neuroendocrinimmunol. 1992;5:95–101.
Bement MK, Sluka KA. Low-intensity exercise reverses chronic muscle pain in the rat in a naloxone-dependent manner. Arch Phys Med Rehabil. 2005;86:1736–40.
Boone Jr JB, Corry JM. Proenkephalin gene expression in the brainstem regulates post-exercise hypotension. Brain Res Mol Brain Res. 1996;42(1):31–8.
Boone Jr JB, Sherraden T, Pierzchala K, et al. Plasma Met-enkephalin and catecholamine responses to intense exercise in humans. J Appl Physiol. 1992;73(1):388–92.
Bradbury AF, Smyth DG, Snell CR, et al. C fragment of lipotropin has a high affinity for brain opiate receptors. Nature. 1976;260:793–5.
Bullen BA, Skrinar GS, Beitins IZ, et al. Endurance training effects on plasma hormonal responsiveness and sex hormone excretion. J Appl Physiol. 1984;56(6):1453–63.
Bush JA, Mastro AM, Kraemer WJ. Proenkephalin peptide F immunoreactivity in different circulatory biocompartments after exercise. Peptides. 2006;27(6):1498–506.
Carr DB, Ballantyene JC. Denorphins and analgesia. Compr Ther. 1987;13(12):7–13.
Carr DB, Bullen BA, Skrinar GS, et al. Physical conditioning facilitates the exercise-induced secretion of beta-endorphin and beta-lipotropin in women. N Engl J Med. 1981;305:560–3.
Chen JX, Zhao X, Yue GX, et al. Influence of acute and chronic treadmill exercise on rat plasma lactate and brain NPY, L-ENK, DYN A1-13. Cell Mol Neurobiol. 2007;27(1):1–10.
Colt EW, Wardlaw SL, Frantz AG. The effect of running on plasma beta-endorphin. Life Sci. 1981;28:1637–40.
Dearman J, Francis KT. Plasma levels of catecholamines, cortisol, and beta-endorphins in male athletes after running 26.2, 6, and 2 miles. J Sports Med Phys Fitness. 1983;23:30–8.
Denning GM, Ackermann LW, Barna TJ, et al. Proenkephalin expression and enkephalin release are widely observed in non-neuronal tissues. Peptides. 2008;29(1):83–92.
de Oliveira MS, da Silva Fernandes MJ, Scorza FA. Acute and chronic exercise modulates the expression of MOR opioid receptors in the hippocampal formation of rats. Brain Res Bull. 2010;83(5):278–83.
Donevan RH, Andrew GM. Plasma beta-endorphin immunoreactivity during graded cycle ergometry. Med Sci Sports Exerc. 1987;19(3):229–33.
Droste C, Greenlee MW, Schreck M, et al. Experimental pain thresholds and plasma beta-endorphin levels during exercise. Med Sci Sports Exerc. 1991;23(3):334–42.
Elliot DL, Goldberg L, Watts WJ, et al. Resistance exercise and plasma beta-endorphin/beta-lipotrophin immunoreactivity. Life Sci. 1984;34(6):515–8.
Engfred K, Kjaer M, Secher NH, et al. Hypoxia and training-induced adaptation of hormonal responses to exercise in humans. Eur J Appl Physiol Occup Physiol. 1994;68(4):303–9.
Farrell PA, Gates WK, Maksud MG, et al. Increases in plasma beta-endorphin/beta-lipotropin immunoreactivity after treadmill running in humans. J Appl Physiol. 1982;52(5):1245–9.
Farrell PA Gates WK, Morgan WP. Pert, CB. Plasma leucine enkephalin-like radioreceptor activity and tension-anxiety before and after competitive running. In: Knuttgen HG, Vogel JA, Poortmans J, editors. Biochemistry of exercise, vol. 13. Champaign, IL: Human Kinetics; 1983, p. 637–44.
Farrell PA, Kjaer M, Bach FW, et al. H Beta-endorphin and adrenocorticotropin response to supramaximal treadmill exercise in trained and untrained males. Acta Physiol Scand. 1987;130(4):619–25.
Fatouros J, Goldfarb AH. Low carbohydrate diet induces changes in central and peripheral beta-endorphins. Nutr Res. 1995;15(11):1683–94.
Fatouros J, Goldfarb AH, Jamurtas AZ, et al. Beta-endorphin infusion alters pancreatic endocrines and plasma glucose during exercise in rats. Eur J Appl Physiol. 1997;76:203–8.
Fry AC, Bonner E, Lewis DL, et al. The effects of gamma-oryzanol supplementation during resistance exercise training. Int J Sport Nutr. 1997;7(4):318–29.
Gannon GA, Rhind SG, Suzui M, et al. beta-Endorphin and natural killer cell cytolytic activity during prolonged exercise Is there a connection? Am J Physiol. 1998;275(6 Pt 2):1725–34.
Gilman SC, Schwartz JM, Milner RJ, et al. Beta-Endorphin enhances lymphocyte proliferative responses. Proc Natl Acad Sci U S A. 1982;79(13):4226–30.
Goldfarb AH. Effect of gender and menstrual cycle on Beta-endorphin response to activity. Am J Med Sports. 2001;3:363–6.
Goldfarb AH, Hatfield BD, Armstrong D, et al. Plasma beta-endorphin concentration: response to intensity and duration of exercise. Med Sci Sports Exerc. 1990;22:241–4.
Goldfarb AH, Hatfield BD, Potts J, et al. Beta-endorphin at the same relative exercise intensity: Training effects. Int J Sports Med. 1991;12(3):264–8.
Goldfarb AH, Hatfield BD, Sforzo GA, et al. Serum beta-endorphins levels during a graded exercise test to exhaustion. Med Sci Sports Exerc. 1987;19(2):78–82.
Goldfarb AH, Jamurtas AZ, Kamimori G, et al. Gender and menstrual cycle effects on circulating beta-endorphin in response to exercise. Med Sci Sports Exerc. 1998;30(12):1672–6.
Goldstein A, Tachibana S, Lowney LI, et al. Dynorphin-(1–13), an extraordinarily potent opioid peptide. Proc Natl Acad Sci U S A. 1979;76(12):6666–70.
Harber VJ, Sutton JR, MacDougall JD, et al. Plasma concentrations of beta-endorphin in trained eumenorrheic and amenorrheic women. Fertil Steril. 1997;67(4):648–53.
Hedner T, Cassuto J. Opioids and opioid receptors in peripheral tissues. Scand J Gastroenterol Suppl. 1987;130:27–46.
Heitkamp HC, Huber W, Scheib K. Beta-Endorphin and adrenocorticotrophin after incremental exercise and marathon running—female responses. Eur J Appl Physiol Occup Physiol. 1996;72(5–6):417–24.
Heitkamp HC, Schmid K, Scheib K. Beta-endorphin and adrenocorticotropic hormone production during marathon and incremental exercise. Eur J Appl Physiol Occup Physiol. 1993;66(3):269–74.
Hemmick LM, Bidlack JM. Beta-endorphin stimulates rat T lymphocyte proliferation. J Neuroimmunol. 1990;29(1–3):239–348.
Hoffman P, Terenius L, Thoren P. Cerebrospinal fluid immunoreactive beta- endorphin concentration is increased by voluntary exercise in the spontaneously hypertensive rat. Regul Pept. 1990;28:233–9.
Howlett TA, Tomlin S, Ngahfoong L, et al. Release of beta endorphin and met-enkephalin during exercise in normal women: response to training. Br Med J (Clin Res Ed). 1984;288(6435):1950–2.
Hughes J, Smith TW, Kosterlitz HW, et al. Identification of two related pentapeptides from the brain with potent opiate agonist activity. Nature. 1975;258:577–9.
Ishide T, Mancini M, Maher TJ, et al. Rostral ventrolateral medulla opioid receptor activation modulates glutamate release and attenuates the exercise pressor reflex. Brain Res. 2000;865(2):177–85.
Jamurtas AZ, Goldfarb AH, Chung SC, et al. β-Endorphin infusion during exercise in rats: blood metabolic effects. Med Sci Sports Exerc. 2000;32(9):1570–5.
Jamurtas AZ, Tofas T, Fatouros I, et al. The effects of low and high glycemic index foods on exercise performance and beta-endorphin responses. J Int Soc Sports Nutr. 2011;8(1):15.
Janal MN, Colt EW, Clark WC, et al. Pain sensitivity, mood and plasma endocrine levels in man following long-distance running: effects of naloxone. Pain. 1984;19(1):13–25.
Jarmukli NF, Ahn J, Iranmanesh A, et al. Effect of raised plasma beta endorphin concentrations on peripheral pain and angina thresholds in patients with stable angina. Heart. 1999;82(2):204–9.
Jaskowski MA, Jackson AS, Raven PB, et al. Enkephalin metabolism: effect of acute exercise stress and cardiovascular fitness. Med Sci Sports Exerc. 1989;21(2):154–60.
Jiang CL, Xu D, Lu CL, et al. Interleukin-2: structural and biological relatedness to opioid peptides. Neuroimmunomodulation. 2000;8(1):20–4.
Jonsdottir IH, Hellstrand K, Thorén P, et al. Enhancement of natural immunity seen after voluntary exercise in rats. Role of central opioid receptors. Life Sci. 2000;66(13):1231–9.
Kahn S, Anthony A, Hughes S, et al. β-Endorphin decreases fatigue and increases glucose uptake independently in normal and dystrophic mice. Muscle Nerve. 2005;31:481–6.
Kamphuis S, Eriksson F, Kavelaars A, et al. Role of endogenous pro-enkephalin A-derived peptides in human T cell proliferation and monocyte IL-6 production. J Neuroimmunol. 1998;84:53–60.
Kapasi ZF, Catlin PA, Beck J, et al. The role of endogenous opioids in moderate exercise training-induced enhancement of the secondary antibody response in mice. Phys Ther. 2001;81(11):1801–9.
Kay N, Allen J, Morley JE. Endorphins stimulate normal human peripheral blood lymphocyte natural killer activity. Life Sci. 1984;35(1):53–9.
Khachaturian H, Lewis ME, Schafer MK-H, et al. Anatomy of the CNS opioid systems. Trends Neurosci. 1985;8:111–9.
Kraemer RR, Acevedo EO, Dzewaltowski D, et al. Effects of low-volume resistive exercise on beta-endorphin and cortisol concentrations. Int J Sports Med. 1996;17(1):12–6.
Kraemer WJ, Dziados JE, Marchitelli LJ, et al. Effects of different heavy-resistance exercise protocols on plasma beta-endorphin concentrations. J Appl Physiol. 1993;74(1):450–9.
Kraemer WJ, Fry AC, Warren BJ, et al. Acute hormonal responses in elite junior weightlifters. Int J Sports Med. 1992;13(2):103–9.
Kraemer WJ, Kim SK, Bush JA, et al. Influence of the menstrual cycle on proenkephalin peptide F responses to maximal cycle exercise. Eur J Appl Physiol. 2006;96(5):581–6.
Kraemer WJ, Nobles B, Culver B, et al. Changes in plasma proenkephalin peptide F and catecholamine levels during graded exercise in men. Proc Natl Acad Sci U S A. 1985;82:6349–51.
Labuz D, Schreiter A, Schmidt Y, et al. T lymphocytes containing β-endorphin ameliorate mechanical hypersensitivity following nerve injury. Brain Behav Immun. 2010;24(7):1045–53.
Langenfeld ME, Hart LS, Kao PC. Plasma β-endorphin responses to one-hour bicycling and running at 60% VO2max. Med Sci Sports Exerc. 1987;19:83–6.
Lee YW, Chaplan SR, Yaksh T. Systemic and supraspinal, but not spinal, opiates suppress allodynia in a rat neuropathic pain model. Neruosci Lett. 1995;199:111–4.
Li CH, Chung D. Isolation and structure of an untriakontapeptide with opiate activity from camel pituitary glands. Proc Nat Acad Sci USA. 1976;73(4):1145–8.
Livett BG, Dean DM, Whelan LG, et al. Co-release of enkephalin and catecholamines from cultured adrenal chromaffin cells. Nature. 1981;289:317–9.
Lobstein DD, Ismail AH. Decreases in resting plasma beta-endorphin/-lipotropin after endurance training. Med Sci Sports Exerc. 1989;21(2):161–6.
Luger A, Deuster PA, Kyle SB, et al. Acute hypothalamic-pituitary-adrenal responses to the stress of treadmill exercise physiologic adaptations to physical training. N Engl J Med. 1987;316:1309–15.
McGowan RW, Pierce EF, Eastman N, et al. Beta-endorphins and mood states during resistance exercise. Percept Motor Skills. 1993;76(2):376–8.
McMurray RG, Forsythe WA, Mar MH, et al. Exercise intensity-related responses of beta-endorphin and catecholamines. Med Sci Sports Exerc. 1987;6:570–4.
Metzger JM, Stein EA. Beta-endorphin and sprint training. Life Sci. 1984;34(16):1541–7.
Millar DB, Hough CJ, Mazorow DL, et al. Beta-endorphin’s modulation of lymphocyte proliferation is dose, donor, and time dependent. Brain Behav Immun. 1990;4(3):232–42.
Mougin C, Baulay A, Henriet MT, et al. Assessment of plasma opioid peptides, beta-endorphin and met-enkephalin, at the end of an international Nordic ski race. Eur J Appl Physiol Occup Physiol. 1987;56(3):281–6.
Mousa SA, Zhang Q, Sitte N, et al. β-Endorphin-containing memory-cells and μ-opioid receptors undergo transport to peripheral inflamed tissue. J Neuroimmunol. 2001;15(1–2):71–8.
Nauli SM, Maher TJ, Pearce WJ, et al. Effects of opioid receptor activation on cardiovascular responses and extracellular monoamines within the rostral ventrolateral medulla during static contraction of skeletal muscle. Neurosci Res. 2001;41(4):373–83.
Navolotskaya EV, Malkova NV, Zargarova TA, et al. Synthetic beta-endorphin-like peptide immunorphin binds to non-opioid receptors for beta-endorphin on T lymphocytes. Peptides. 2001;22(12):2009–13.
Oleshansky MA, Zoltick JM, Herman RH, et al. The influence of fitness on neuroendocrine responses to exhaustive treadmill exercise. Eur J Appl Physiol Occup Physiol. 1990;59(6):405–10.
Owen DL, Morley JS, Ensor DM, et al. The C-terminal tetrapeptide of beta-endorphin (MPF) enhances lymphocyte proliferative responses. Neuropeptides. 1998;32(2):131–9.
Paolisso G, Giugliano D, Scheen A, et al. Primary role of glucagon release in the effect of β-endorphin on glucose homeostasis in normal man. Acta Endocrinol. 1987;115:161–9.
Pasnik J, Tchorzewski H, Baj Z, et al. Priming effect of met-enkephalin and β-endorphin on chemiluminescence, chemotaxis and CD11b molecule expression on human neutrophils in vitro. Immunol Lett. 1999;67(2):77–83.
Paulev PE, Thorbøll JE, Nielsen U, et al. Opioid involvement in the perception of pain due to endurance exercise in trained man. Jpn J Physiol. 1989;39(1):67–74.
Pert CB, Snyder SH. Properties of opiate-receptor binding in rat brain. Proc Natl Acad Sci U S A. 1973;70(8):2243–7.
Pierce EF, Eastman NW, McGowan RW, et al. Resistance exercise decreases beta-endorphin immunoreactivity. Br J Sports Med. 1994;28(3):164–6.
Pierce EF, Eastman NW, Tripathi HT, et al. Plasma beta-endorphin immunoreactivity: response to resistance exercise. J Sports Sci. 1993;11(6):499–502.
Radosevich PM, Nash JA, Lacy DB, et al. Effects of low- and high-intensity exercise on plasma and cerebrospinal fluid levels of ir-beta-endorphin, ACTH, cortisol, norepinephrine and glucose in the conscious dog. Brain Res. 1989;498(1):89–98.
Rahkila P, Hakala E, Alén M, et al. Beta-endorphin and corticotropin release is dependent on a threshold intensity of running exercise in male endurance athletes. Life Sci. 1988;43(6):551–8.
Rahkila P, Hakala E, Salminen K, et al. Response of plasma endorphins to running exercises in male and female endurance athletes. Med Sci Sports Exerc. 1987;19(5):451–5.
Reid RL, Yen SS. Beta-endorphin stimulates the secretion of insulin and glucagon in humans. J Clin Endocrinol Metab. 1981;52(3):592–4.
Sadigh B, Berglund M, Fillingim RB, et al. Beta-endorphin modulates adenosine provoked chest pain in men, but not in women-a comparison between patients with ischemic heart disease and healthy volunteers. Clin J Pain. 2007;23(9):750–5.
Saland LC, Van Epps DE, Maez D, et al. Acute infusion of chemotactic or enkephalin-analog peptides into rat cerebral ventricles: scanning and transmission electron microscopy of leukocyte immigration in vivo. J Neuroimmunol. 1988;18(3):197–206.
Schwarz L, Kindermann W. Beta-endorphin, adrenocorticotropic hormone, cortisol and catecholamines during aerobic and anaerobic exercise. Eur J Appl Physiol Occup Physiol. 1990;61(3–4):165–71.
Sforzo GA, Seeger TF, Pert CB, et al. In vivo opioid receptor occupation in the rat brain following exercise. Med Sci Sports Exerc. 1986;18(4):380–4.
Sohn JH, Lee BH, Park SH, et al. Microinjection of opiates into the periaqueductal gray matter attenuates neuropathic pain symptoms in rats. Neuroreport. 2000;11:413–6.
Sommers DK, Simpson SF, Loots JM, et al. Effect of exercise on met-enkephalin in unfit and superfit individuals. Eur J Clin Pharmacol. 1989;37(4):399–400.
Sommers DK, Loots JM, Simpson SF, et al. Circulating met-enkephalin in trained athletes during rest, exhaustive treadmill exercise and marathon running. Eur J Clin Pharmacol. 1990;38(4):391–2.
Stagg NJ, Mata HP, Ibrahim MM, et al. Regular exercise reverses sensory hypersensitivity in a rat neuropathic pain model: role of endogenous opioids. Anesthesiology. 2011;114(4):940–8.
Sylvén C, Eriksson B, Sheps DS, et al. Beta-endorphin but not metenkephalin counteracts adenosine-provoked angina pectoris-like pain. Neuroreport. 1996;7(12):1982–4.
Triplett-McBride NT, Mastro AM, McBride JM, et al. Plasma proenkephalin peptide F and human B cell responses to exercise stress in fit and unfit women. Peptides. 1998;19(4):731–8.
Tsuchimochi H, McCord JL, Kaufman MP. Peripheral mu-opioid receptors attenuate the augmented exercise pressor reflex in rats with chronic femoral artery occlusion. Am J Physiol Heart Circ Physiol. 2010;299(2):H557–65.
van den Bergh P, Rozing J, Nagelkerken L. Two opposing modes of action of beta-endorphin on lymphocyte function. Immunology. 1991;72(4):537–43.
van Epps DE, Saland L. Beta-endorphin and met-enkephalin stimulate human peripheral blood mononuclear cell chemotaxis. J Immunol. 1984;132(6):3046–53.
Viru A, Tendzegolskis Z, Smirnova T. Changes of beta-endorphin level in blood during prolonged exercise. Endocrinol Exp. 1990;1–2:63–8.
Vissing J, Iwamoto GA, Fuchs IE, et al. Reflex control of glucoregulatory exercise responses by group III and IV muscle afferents. Am J Physiol. 1994;266(3):R824–30.
Walberg-Rankin J, Franke WD, Gwazdauskas FC. Response of beta-endorphin and estradiol to resistance exercise in females during energy balance and energy restriction. Int J Sports Med. 1992;13(7):542–7.
Wen T, Peng B, Pintar JE. The MOR-1 opioid receptor regulates glucose homeostasis by modulating insulin secretion. Mol Endocrinol. 2009;23(5):671–8.
Zitnik RJ, Whiting NL, Elias JA. Glucocorticoid inhibition of interleukin-1-induced interleukin-6 production by human lung fibroblasts: evidence for transcriptional and post-transcriptional regulatory mechanisms. Am J Respir Cell Mol Biol. 1994;10(6):643–50.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer Science+Business Media New York
About this chapter
Cite this chapter
Goldfarb, A.H. (2013). Exercise and Endogenous Opiates. In: Constantini, N., Hackney, A. (eds) Endocrinology of Physical Activity and Sport. Contemporary Endocrinology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-314-5_2
Download citation
DOI: https://doi.org/10.1007/978-1-62703-314-5_2
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-62703-313-8
Online ISBN: 978-1-62703-314-5
eBook Packages: MedicineMedicine (R0)