Hormonal and metabolic responses to electrically induced cycling during epidural anesthesia in humans
Abstract
Hormonal and metabolic responses to electrically induced dynamic exercise were investigated in eight healthy young men with afferent neural influence from the legs blocked by epidural anesthesia (25 ml of 2% lidocaine) at L3-L4. This caused cutaneous sensory anesthesia below T8-T9 and complete paralysis of the legs. Cycling increased oxygen uptake to 1.90 +/- 0.13 (SE) l/min, and fatigue developed after 22.7 +/- 2.7 min. Compared with voluntary exercise at the same oxygen uptake and heart rate, concentrations of blood and muscle lactate (musculus vastus lateralis) as well as plasma potassium increased more while muscle glycogen decreased more during electrically induced exercise. Hepatic glucose production always rose during exercise. However, during involuntary exercise with sensory blockade, it did not match the rise in peripheral glucose uptake and plasma glucose decreased (P < 0.05). Plasma glycerol increased less in electrically induced vs. voluntary exercise, and free fatty acids and beta-hydroxybutyrate decreased only during electrically induced exercise. Epinephrine, growth hormone, adrenocorticotropic hormone, and cortisol levels were higher during involuntary vs. voluntary exercise (P < 0.05). In conclusion, neural and humoral mechanisms exert redundant control with regard to responses of catecholamines and pituitary hormones (growth hormone and adrenocorticotropic hormone). In contrast, neural input from motor centers and feedback from working muscle are important for glucose production and lipolysis during exercise in humans. Humoral feedback is apparently not sufficient to trigger normal mobilization of extramuscular fuel stores.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Signaling pathways from exercising skeletal muscle to other organs are not solely mediated via the nervous system.
“It was clear that signaling pathways from exercising skeletal muscle to other organs were not solely mediated via the nervous system, since electrical stimulation of paralyzed muscles in patients with no efferent or afferent nerve impulses induced the same types of physiological changes as were found in healthy human beings (1, 2).”
From Muscle–Organ Crosstalk: The Emerging Roles of Myokines (2020) · cites this paper as [1]
Cited by
Sorted by citations
Muscles, exercise and obesity: skeletal muscle as a secretory organ
Pedersen, B. K., & Febbraio, M. A. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2012.49 · Cited by 2,909 · see citing works
Muscle–Organ Crosstalk: The Emerging Roles of Myokines
Severinsen, M. C. K., & Pedersen, B. K. (2020) · Endocrine Reviews · doi:10.1210/endrev/bnaa016 · Cited by 1,226 · see citing works
“Healthy young males underwent 2 hours of bicycle exercise on 3 separate occasions at (1) a relatively high intensity; (2) a low intensity, and (3) a low intensity + infusion of IL-6 to mimic the plasma levels of IL-6 observed during high-intensity exercise.”
BackgroundDishman, R. K., Berthoud, H., Booth, F. W., Cotman, C. W., Edgerton, V. R., Fleshner, M. R., Gandevia, S. C., Gomez‐Pinilla, F., Greenwood, B. N., Hillman, C. H., et al. (2006) · Obesity · doi:10.1038/oby.2006.46 · Cited by 958 · see citing works
“In contrast, neural input from motor centers and feedback from active muscles both seem important for glucose production and lipolysis during exercise in humans (92).”
BackgroundSearching for the exercise factor: is IL-6 a candidate?
Pedersen (2003) · Journal of Muscle Research and Cell Motility · doi:10.1023/a:1026070911202 · Cited by 564 · see citing works
“…muscles to other organs are not the nervous system as electrical stimulation of paralysed muscles in spinal cord injured patients, with no afferent and efferent nerve impulses, induces in essence the same physiological changes as in intact human beings (Kjaer et al., 1996; Mohr et al., 1997).”
BackgroundPedersen, B. K. (2013) · Comprehensive physiology · doi:10.1002/cphy.c120033 · Cited by 516 · see citing works
Beneficial health effects of exercise – the role of IL-6 as a myokine
Pedersen, B. K., & Fischer, C. P. (2007) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2007.02.002 · Cited by 371 · see citing works
The metabolic role of IL-6 produced during exercise: is IL-6 an exercise factor?
Pedersen, B. K., Steensberg, A., Fischer, C. P., Keller, C., Keller, P., Plomgaard, P., Petersen, E. W., & Febbraio, M. A. (2004) · Proceedings of The Nutrition Society · doi:10.1079/pns2004338 · Cited by 273 · see citing works
“It is clear that the signalling pathways from contracting muscles to other organs are not associated with the nervous system, as electrical stimulation of paralysed muscles in patients with spinal cord injuries induces in essence the same physiological changes as those in intact subjects (Kjaer et al. 1996).”
Physiological roles of muscle-derived interleukin-6 in response to exercise
Pedersen, B. K., & Fischer, C. P. (2007) · Current Opinion in Clinical Nutrition and Metabolic Care · doi:10.1097/mco.0b013e3280ebb5b3 · Cited by 227 · see citing works
Heinemeier, K. M., Olesen, J. L., Schjerling, P., Haddad, F., Langberg, H., Baldwin, K. M., & Kjær, M. (2006) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00866.2006 · Cited by 189 · see citing works
“Furthermore, it should be kept in mind that the training employed in the present study was based on involuntary muscle contractions and we cannot be certain that the effect of this type of training is identical to that of a voluntary type (28).”
ResultSelf-citationA Randomized Trial of Exercise and Dietary Counseling After Liver Transplantation
Krasnoff, J. B., Vintro, A. Q., Ascher, N. L., Bass, N. M., Paul, S. M., Dodd, M. J., & Painter, P. (2006) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2006.01391.x · Cited by 167 · see citing works
Exercise-Released Myokines in the Control of Energy Metabolism
Laurens, C., Bergouignan, A., & Moro, C. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.00091 · Cited by 159 · see citing works
“Because myokines allow muscle contractions to modulate other tissues through a pathway independent of the nervous system (Kjaer et al., 1996), the adverse health effects of physical inactivity and sedentary behaviors may result from the lack of muscle contraction.”
BackgroundSoya, H., Mukai, A., Deocaris, C. C., Ohiwa, N., Chang, H., Nishijima, T., Fujikawa, T., Togashi, K., & Saito, T. (2007) · Neuroscience Research · doi:10.1016/j.neures.2007.04.004 · Cited by 156 · see citing works
“Moreover, reflexive roles of contractile muscles through the afferent signals have been examined as among the causes of such hypothalamic activation (Scheurink et al., 1989b; Vissing et al., 1989; Antoni et al., 1991; Kjaer et al., 1991; Galbo, 1992; Kjaer et al., 1996; Li et al., 1997).”
BackgroundJubeau, M., Sartório, A., Marinone, P. G., et al. (2007) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00335.2007 · Cited by 112 · see citing works
“(21) showed that plasma GH level was significantly higher during NMES than voluntary cycling exercise at a similar level of oxygen consumption, and they suggested that the decrease in plasma glucose concentration during NMES probably was a feedback stimulus to enhance the GH response.”
BackgroundExercise effects on postprandial glucose metabolism in type 1 diabetes: a triple-tracer approach
Mallad, A., Hinshaw, L., Schiavon, M., Dalla Man, C., Dadlani, V., Basu, R., Lingineni, R., Cobelli, C., Johnson, M. L., Carter, R., et al. (2015) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00014.2015 · Cited by 94 · see citing works
“, lactate, free fatty acids), or potential blood-borne feedback and afferent mechanisms that have been shown more recently to modulate glucose Ra (6, 18, 19).”
BackgroundExercise as a Positive Modulator of Brain Function
Alkadhi, K. A. (2017) · Molecular Neurobiology · doi:10.1007/s12035-017-0516-4 · Cited by 90 · see citing works
Objective measures of health‐related quality of life over 24 months post‐liver transplantation
Krasnoff, J. B., Vintro, A. Q., Ascher, N. L., et al. (2004) · Clinical Transplantation · doi:10.1111/j.1399-0012.2004.00306.x · Cited by 83 · see citing works
Kjær, M., Hanel, B., Worm, L., Perko, G., Lewis, S. F., Sahlin, K., Galbo, H., & Secher, N. H. (1999) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1999.277.1.r76 · Cited by 80 · see citing works
Self-citationCaffeine ingestion and metabolic responses of tetraplegic humans during electrical cycling
Mohr, T. T., van Soeren, M., Graham, T. E., & Kjær, M. (1998) · Journal of Applied Physiology · doi:10.1152/jappl.1998.85.3.979 · Cited by 76 · see citing works
“However, this exaggerated lactate response has been reported previously (17, 19) in healthy men who received epidural anesthesia at L3-4 followed by FES.”
BackgroundResultSelf-citationGrowth hormone responses to sub-maximal and sprint exercise
Stokes, K. (2003) · Growth Hormone & IGF Research · doi:10.1016/s1096-6374(03)00016-9 · Cited by 67 · see citing works
Hepatic glucose production during exercise.
Kjær, M. (1998) · Advances in Experimental Medicine and Biology · doi:10.1007/978-1-4899-1928-1_11 · Cited by 66 · see citing works
Self-citationGlucoregulation During Exercise: The Role of the Neuroendocrine System
Coker, R. H., & Kjaer, M. (2005) · Sports Medicine · doi:10.2165/00007256-200535070-00003 · Cited by 60 · see citing works
Self-citationPedersen, B. K. (2013) · Comprehensive physiology · doi:10.1002/j.2040-4603.2013.tb00522.x · Cited by 59 · see citing works
Human investigations into the exercise pressor reflex
Secher, N. H., & Amann, M. (2011) · Experimental Physiology · doi:10.1113/expphysiol.2011.057679 · Cited by 56 · see citing works
Self-citationMyokine-mediated muscle-organ interactions: Molecular mechanisms and clinical significance
Yi, J., Chen, J., Yao, X., Zhao, Z., Niu, X., Li, X., Sun, J., Ji, Y., Shang, T., Gong, L., et al. (2025) · Biochemical Pharmacology · doi:10.1016/j.bcp.2025.117326 · Cited by 59 · see citing works
Tong, T. K., Zhang, H., Shi, H., Liu, Y., Ai, J., Nie, J., & Kong, Z. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01048 · Cited by 47 · see citing works
“Moreover, the greater central motor activity (Kjaer et al., 1996) in accomplishing”
BackgroundAsynchronous Muscle and Tendon Adaptation After Surgical Tensioning Procedures
Takahashi, M., Ward, S. R., Marchuk, L. L., Frank, C. B., & Lieber, R. L. (2010) · Journal of Bone and Joint Surgery · doi:10.2106/jbjs.i.00694 · Cited by 45 · see citing works
Kjaer, M., Dela, F., Sørensen, F. B., Secher, N., Bangsbo, J., Mohr, T., & Galbo, H. (2001) · American Journal of Physiology. Regulatory Integrative and Comparative Physiology · doi:10.1152/ajpregu.2001.281.5.r1492 · Cited by 48 · see citing works
Self-citationIrisin: A promising treatment for neurodegenerative diseases
Qi, J., Yang, L.-K., Wang, X., Wang, M., Li, X., Feng, B., Wu, Y., Zhang, K., & Liu, S. (2022) · Neuroscience · doi:10.1016/j.neuroscience.2022.07.018 · Cited by 44 · see citing works
Growth hormone responses to repeated maximal cycle ergometer exercise at different pedaling rates
Stokes, K., Nevill, M. E., Hall, G. M., & Lakomy, H. K. A. (2002) · Journal of Applied Physiology · doi:10.1152/jappl.2002.92.2.602 · Cited by 41 · see citing works
Sui, H., Dou, J., Shi, B., & Cheng, X. (2024) · Frontiers in Physiology · doi:10.3389/fphys.2024.1349253 · Cited by 32 · see citing works
Legaard, G. E., & Pedersen, B. K. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-814593-7.00013-x · Cited by 24 · see citing works
The new emergence of exercise neurobiology
Dishman, R. K. (2006) · Scandinavian Journal of Medicine and Science in Sports · doi:10.1111/j.1600-0838.2006.00609.x · Cited by 20 · see citing works
Howlett, K. F., Watt, M. J., Hargreaves, M., & Febbraio, M. A. (2003) · Metabolism · doi:10.1016/s0026-0495(03)00330-5 · Cited by 16 · see citing works
Paulson, T. A. W., BISHOP, N. C., Smith, B. M., & Goosey-Tolfrey, V. L. (2014) · The Journal of Rehabilitation Research and Development · doi:10.1682/jrrd.2013.08.0184 · Cited by 15 · see citing works
“The lack of humoral and reflex activation of the SNS and HPA-axis may be explained by the lower stimulation intensities and subsequent lower level of muscle recruitment and concentration of circulating metabolites (BLa = 4 vs 8 mmol·l1) in the present study [28].”
BackgroundLi, C., Zhang, T., Yu, K., Xie, H., Bai, Y., Zhang, L., Wu, Y., & Wang, N. (2017) · Acupuncture in Medicine · doi:10.1136/acupmed-2016-011148 · Cited by 15 · see citing works
The Effect of Exercise on the Hypothalamo—Pituitary—Adrenal Axis
Wittert, G. (2000) · Humana Press eBooks · doi:10.1007/978-1-59259-016-2_3 · Cited by 12 · see citing works
RNAkines are secreted messengers shaping health and disease
Li, J., Fang, J., Jiang, X., Zhang, Y., Vidal‐Puig, A., & Zhang, C. (2023) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2023.12.004 · Cited by 11 · see citing works
“Skeletal muscle-secreted RNAkines Skeletal muscle, traditionally known for its role in movement and energy storage, has emerged as a dynamic endocrine organ capable of secreting factors into circulation in response to various environmental and physiological challenges [42 – 44].”
Berg, R. M. G. (2025) · The Journal of Physiology · doi:10.1113/jp289744 · Cited by 8 · see citing works
“Consequently, as the absence of increased hepatic glucose production could be attributable to the inhibitory effect of persistently elevated insulin levels, a similar experiment was conducted on healthy individuals whose lower limbs had been paralysed with epidural anaesthesia (Kjær et al., 1996).”
Muscle-to-organ cross-talk mediated by interleukin 6 during exercise: a review
Rad, R. S., & Panahzadeh, F. (2023) · Sport Sciences for Health · doi:10.1007/s11332-023-01102-7 · Cited by 5 · see citing works
Imai, K., & Nakajima, H. (2008) · Springer eBooks · doi:10.1007/978-1-4020-8716-5_14 · Cited by 4 · see citing works
“In contrast, neural input from motor centers and feedback from active muscles both seem important for glucose production and lipolysis during exercise in humans (Kjaer et al., 1996).”
BackgroundState-of-the-art insights into myokines as biomarkers of sarcopenia: a literature review
Moussaoui, O. R. (2025) · International Journal of Physiology Pathophysiology and Pharmacology · doi:10.62347/rneq8696 · Cited by 4 · see citing works
Adrenal Gland: Fight or Flight Implications for Exercise and Sports
Kjær, M. (2005) · doi:10.1002/9780470757826.ch15 · Cited by 3 · see citing works
Self-citationEndocrine and skeletal muscle physiology optimizing avian migratory capabilities
Schlinger, B. A., Fuxjager, M. J., & Ramenofsky, M. (2025) · Journal of Avian Biology · doi:10.1002/jav.03415 · Cited by 2 · see citing works
10.1016/b978-1-4160-2911-3.50027-3
(2000) · Time to knit · doi:10.1016/b978-1-4160-2911-3.50027-3 · Cited by 2 · see citing works
The Effect of Acute and Chronic Exercise on Inflammatory Markers in SCI
Leicht, C. A., & BISHOP, N. C. (2016) · Springer eBooks · doi:10.1007/978-1-4939-6664-6_11 · Cited by 2 · see citing works
Excercised Muscles and the Brain
Alkadhi, K. A. (2012) · Clinical and Experimental Pharmacology · doi:10.4172/2161-1459.1000e116 · Cited by 1 · see citing works
“The latter possibility, however, seems unlikely inasmuch as it has been reported that in individuals with severed spinal cord or those under epidural anesthesia (no afferent or efferent impulses), contraction of paralyzed muscles by electrical stimulation produces physiological changes similar to those of normal indiv…”
BackgroundPedersen, B. K. (2015) · Springer eBooks · doi:10.1007/978-3-319-12125-3_31-1 · Cited by 1 · see citing works
the effect of muscle fatigue and damage on endurance performance
Bosio, A. (2010) · Bangor University Research Portal (Bangor University)
Exercise With Lack of Motor Control: Lessons From Studies on Spinal Cord Patients
Kjær, M. (2001) · European Journal of Sport Science · doi:10.1080/17461390100071102
Self-citationKjær, M., Heinemeier, K. M., Olesen, J., Schjerling, P., Haddad, F., Langberg, H., Novotny, S. A., Warren, G. L., & Hamrick, M. W. (2015)
Self-citationergometer exercise at different pedaling rates Growth hormone responses to repeated maximal cycle
Nevill, M. E., Hall, G. M., Barnett, M., et al. (2015)
Neurobiologische Aspekte körperlicher Aktivität
Frasch, K., & Neumann, N.-U. (2009) · Nervenheilkunde · doi:10.1055/s-0038-1627160
Supporting the prescription of exercise in spinal cord injured populations
Paulson, T. A. W. (2013) · Loughborough University Institutional Repository (Loughborough University)
- Authors
- Kjaer, M., Secher, N. H., Bangsbo, J., Perko, G., Horn, A., Mohr, T., & Galbo, H.
- Affiliations
- Copenhagen Muscle Research Center, Rigshospitalet, Denmark.
- Rigshospitalet (DK)
- Venue
- Journal of Applied Physiology
- Publisher
- American Physiological Society
- Published
- 1996-06-01
- Volume
- 80
- Issue
- 6
- Pages
- 2156-2162
- ISSN
- 0161-7567 (ISSN-L)
- 8750-7587
- 1522-1601
- OpenAlex
- W2145774047
- Cited by
- 53
- References
- 0
- Citations by year
- 2025: 4 · 2024: 1 · 2023: 3 · 2022: 1 · 2020: 2 · 2018: 2 · 2017: 2 · 2016: 1 · 2015: 4 · 2014: 1 · 2013: 3 · 2012: 2
- FWCI
- 3.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Applied Physiology (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Sports Performance and Training
- Keywords
- epidural anesthesia, endocrine response, metabolic response, epinephrine, growth hormone, ACTH, cortisol, hepatic glucose production, plasma glucose, lactate, muscle glycogen, plasma potassium, glycerol, free fatty acids, beta-hydroxybutyrate, fatigue
- MeSH terms
- Adult, Anesthesia, Epidural, Epinephrine, Feedback, Glucose, Hormones, Humans, Hydrocortisone, Insulin, Male, Exercise, Lipid Metabolism
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
