15/9/16

Condicionantes Metabólicos
de la Fatiga

Prof. Jorge Cancino L .

Definición

➭ Incapacidad para mantener una tasa de

esfuerzo determinado.

1
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Superposición de los sistemas de producción de energía

Sistema de energía
a plazo intermedio
Sistema de energía
a corto plazo

Sistema de energía
a largo plazo

Tipos de Fatiga según duración

• Fatiga de corto plazo.

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Tipos de Fatiga según duración

• Fatiga de plazo
intermedio.

Tipos de Fatiga según duración

• Fatiga de largo plazo.

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Tipos de Fatiga según orígen

Fatiga Neural
o central

Fatiga Metabólica
o periférica

Fatiga Central

Fatiga Neural
o central

Fatiga Metabólica
o periférica

4
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Fatiga Periférica

Fatiga Neural
o central

Fatiga Metabólica
o periférica

Actores metabólicos involucrados en fatiga

periférica en esfuerzos de alta intensidad

Disminución [PC] Aumento [lactato]

Aumento [ADP] Disminución pH
Aumento [Pi] Disminución [ATP]
Variaciones [Ca++] [K+] extracelular

5
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Disminución [ATP]

6
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Disminución pH Aumento [Pi]

7
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Journal of Nutrition and Metabolism

Volume 2010, Article ID 905612,

Lactato

8
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Journal of Nutrition and Metabolism

Volume 2010, Article ID 905612,

9
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10
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Potasio

• El incremento en las concentraciones de K+

observadas luego de esfuerzos de alta
intensidad, se relacionan con la
hiperpolarización del sarcolema. (Mc Comas A., Skeletal
Muscle: form and function, Human Kinetics, 1996).

• La hiperpolarización del sarcolema tiende a

disminuir la excitabilidad muscular.

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Fatiga Central

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• Se define según Davis (1996) como la

influencia central negativa que existe a
pesar de la motivación total del sujeto.
(Med Sci Sports and Exercise, 29 (1) 45-57, 1997.).

13
 15/9/16

FIG. 1. Early studies of maximal voluntary activation and central fatigue. A: data obtained by Mosso (540) using his
ergograph. Trace indicates the distance moved by the middle finger when lifting a weight of 3 kg each 2 s. Normal “fatigue
tracing” and one obtained 24 h later “after lecturing” are shown. [Redrawn from Mosso (540).] B: Reid’s comparison of
a maximal voluntary contraction (MVC) of finger flexion and force produced by stimulation of the median nerve at the
elbow (stimulus rate not specified) under isometric conditions. Artificial stimulation produced “as strong contraction as
voluntary effort,” although this is not clear in all the records (see horizontal dashed line), and Reid often found that large
weights could be lifted by artificial electrical stimulation and not volition (see Fig. 4). [Redrawn from Reid (607).]

from clinical cases, that muscles would be torn, tendons
ruptured, and bones broken. [We now know that unless
there has been a pathological change in the tendon or
bone, the strength of bone and tendon exceeds that of
muscles (775).] Thus the common view was that the
FIG. 2. Classical study of factors affecting maximal voluntary
strength. Mean value for brief MVCs of elbow flexors made at 1-min pared the response to stimulation of the ulnar nerve
intervals by 10 subjects. Control contractions (open circles), contrac-
Gandevia, S. C. Spinal and Supraspinal Factors in Human Muscle Fatigue.
tions preceded by an unexpected gunshot (solid circles), and a final
contraction (star) in which the subject shouted are shown. [Redrawn tion. Difficulties are that small changes in thumb position
from Ikai and Steinhaus (354).]
maximal contractile force was so high that “strength is
kept in bounds by the inability of the higher centres to
activate the muscles to the full” (528). This quandary
prompted a milestone in 1954 when two reports appeared.
Merton (524) and Bigland and Lippold (59) used electrical
stimulation of the motor nerve to compare directly max-
imal force in a stimulated tetanus and during a maximal
voluntary contraction (MVC). While supramaximal “arti-
ficial” stimulation of the nerve drives all motor units
synchronously, unlike voluntary muscle contractions, this
difference is not critical for the comparison provided that
the stimulation frequency is high enough to produce a
maximal tetanus.
Does the force produced by tetanic electrical stimu-
lation exceed that produced by voluntary action? Both
reports claimed that the two forces were similar, although
the errors associated with the tests were not quantified
and are not trivial (see sect. II). An earlier study by Reid
(1928) had also reached this conclusion, although the raw
records suggest that voluntary contractions did not quite
match the force of an isometric tetanus (Fig. 1B). Using a
special myograph that was said to measure the force
produced only by adduction of the thumb, Merton com-
above the wrist toPhysiol the Revforce of voluntary thumb adduc-
81: 1725–1789, 2001
alter the forces produced by stimulation of the ulnar

Physiol Rev • VOL 81 • OCTOBER 2001 • www.prv.org

Por lo general se piensa que la reducción en el

impulso del sistema nervioso central a la
motoneurona puede ser el resultado de:

– Una reducción de los estímulos corticoespinales.

– Una inhibición de la excitabilidad de la

motoneurona por feedback aferentes mediados
por el músculo esquelético.

J. Ma rk D avis a nd S te ph en P . Bail ey. “Po ssibl e me ch anis ms of ce nt ral ne rv ous sys te m f ati gu e d uri ng ex er cise ”. Me d. S ci. S po rts E xe rc. V ol 29 N° 1 ,
pp 45-57, 1997

14
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AUTNEU-01705; No of Pages 5
Autonomic Neuroscience: Basic and Clinical xxx (2014) xxx–xxx

Contents lists available at ScienceDirect

Autonomic Neuroscience: Basic and Clinical

journal homepage: www.elsevier.com/locate/autneu

Autonomic responses to exercise: Group III/IV muscle afferents

and fatigue☆
Markus Amann a,b,⁎, Simranjit K. Sidhu a, Joshua C. Weavil b, Tyler S. Mangum b, Massimo Venturelli c
a
Department of Medicine, University of Utah, Salt Lake City, UT, USA
b
Department of Exercise & Sport Science, University of Utah, Salt Lake City, UT, USA
c
Department of Biomedical Sciences for Health, University of Milan, Italy

a r t i c l e i n f o a b s t r a c t 2 M. Amann et al. / Autonomic Neuroscience: Basic and Clinical xxx (2014) xxx–xxx

Article history: Group III and IV muscle afferents originating in exercising limb muscle play a significant role in the development et al., 2011a). Peripheral fatigue was quantified via the pre- to post-
Received 12 June 2014 of fatigue during exercise in humans. Feedback from these sensory neurons to the central nervous system (CNS)
M. Amann et al. / Autonomic
Received in revised form 17 September 2014
Neuroscience: Basic and Clinical xxx (2014) xxx–xxx 3 exercise decrease in quadriceps twitch force evoked via supramaximal
reflexively increases ventilation and central (cardiac output) and peripheral (limb blood flow) hemodynamic
Accepted 13 October 2014 femoral nerve stimulation. Earlier studies utilizing an identical pharma-
responses during exercise and thereby assures adequate muscle blood flow and O2 delivery. This response de-
Available online xxxx flexors) not directly involved in the task (Sidhu et al., 2014). These re- cological approach to temporarily block group III/IV muscle afferents
picts a key factor in minimizing the rate of development of peripheral fatigue and in optimizing aerobic exercise
Keywords:
capacity. On the othercent findings
hand, directly
the central emphasize
projection of group the
III/IVsignificant involvement
muscle afferents of group and limitshave documented that exercise in the absence of sensory feedback is
impairs performance
Neural feedback the exercising human via its
III/IV diminishing
muscle effect
afferents inon thedevelopment
the output from spinal motoneurons
of central fatiguewhich
during in- volun-characterized by substantial hypoventilation and an attenuated exercise
decreases
Central fatigue tary muscle activation (i.e. facilitates central fatigue). Accumulating evidence from recent animal studies suggests pressor response including decreased central (i.e. cardiac output) and
Exercise pressor reflex
tense whole body endurance exercise.
the existence of two subtypes of group III/IV muscle afferents. While one subtype only responds to physiological
peripheral (leg blood flow) hemodynamic responses during exercise
Circulation and innocuous levels ofInvestigating the effect metabolites
endogenous intramuscular of group III/IV muscle
(lactate, afferents
ATP, protons) on whole
associated with ‘normal’,
Ventilation predominantly aerobic body exercise
exercise, theperformance
other subtype is challenging.
only responds to The difficulty
higher aris- levels of(Amann et al., 2008, 2009, 2010, 2011a, 2011b; Gagnon et al., 2012).
has beennoxious
and concurrently
metabolites present in muscle during ischemic contractions or following, for example, hypertonic saline infu- Consequently, when constant-load leg cycling is performed in the
ing from the twofold role these neurons play in an exercising human.
sions. This review discusses the mechanisms through which group III/IV muscle afferent feedback mediates absence of locomotor muscle afferent feedback, leg blood flow and O2
Specifically,
both central and peripheral fatiguealthough they
in exercising limit spinal
humans. We also motoneuronal
briefly summarize output and facili- evidence
the accumulating delivery are markedly attenuated compared to the same exercise per-
from recent animal tate centralstudies
and human fatigue (i.e. limiting
documenting theeffect on performance),
existence of two subtypes of their contribu-
group III/IV muscle affer-
formed with an intact neural feedback mechanism. Given the critical
ents and the relevancetionofto
this discovery
the to the of
prevention interpretation
prematureofperipheral
previous work and the
fatigue bydesign of future studies.
facilitating
© 2014 Published by Elsevier B.V.role of blood flow/O2 delivery in the development of fatigue [see
circulatory and ventilatory responses during exercise is essential (i.e. fa- above; (Amann and Calbet, 2008)], the rate of accumulation of periph-
cilitating effect on performance; see above). Therefore, manipulating eral fatigue is up to 60% faster during exercise with impaired vs intact
1. Introduction
muscle afferents during exercise affects both sides and the net effect de-
In order to assure a sufficient link to the original work in the face of agroup III/IV muscle afferent feedback (Amann et al., 2011a; Sidhu
pends on how one effect
restricted outweighs
number the other. In
of references, wea would
recent study be citing designed various otheret al., 2014). Taken together, by facilitating circulatory and ventilatory
Both whole body (e.g. cycling) and single joint (e.g. isometric/ to circumvent review thisarticles.
caveat, subjects were asked to perform dynamic responses, group III/IV muscle afferent feedback ensures adequate mus-
dynamic knee extension) exercise of sufficient duration and intensity single leg knee-extensor exercise to exhaustion in one leg immediately cle blood flow/O2 delivery during exercise and thereby prevents prema-
reduce the force/power generating capacity of muscles involvedfollowed in the by the identical task in the other leg (Amann et al., 2013). The ture fatigue at the level of the locomotor muscle. This neural feedback
task. This exercise-induced decrease is determined by a peripheral and 1.1. Group III/IV muscle afferent feedback and exercise: Some basics mechanism plays an important role in optimizing fatigue resistance
goal was to determine whether afferent feedback arising from the knee-
Fig. 2. Reduction in quadricep[i.e.
a central maximal voluntary
related to thecontraction strength (MVC)
central nervous systeminduced
(CNS)]via component during physical activities in healthy humans.
9 min of constant-load single leg knee-extensor exercise (25/50/80% of peak workload,
(Allen et al., 2008; Gandevia, 2001). ‘Peripheral fatigue’ encompasses extensor exercised/exhausted first inhibits spinal motoneuronal output
With the onset of exercise, contraction-induced mechanical and The arterial baroreflex has been suggested to attenuate the central
3 min each) in patients with chronic
biochemical heart failure.
changes The exercise
within was performed
the contracting muscle leadingand
with intact to thereby 1.limits
an Fig.chemical Discharge endurance
stimuli
frequencybegin exercise
[impulses toper performance
activate
2 s; (Imp/2 s)] of of
molecular the
group IIIconsecutively
receptors
(panel A) and located on the
group IV
effects of group III/IV muscle afferents on the exercise pressor response
(control) and blocked (fentanyl)
attenuated neural feedback
force/power from the to
response lower limb. excitation.
neural From Amann‘Central
et al. exercising
fatigue’, contralateral
terminal
(panel B) muscle end knee-extensor.
of both
afferents thinly
recorded The
dorsaldesign
frommyelinated root before,of the
(group study
during, III)andandandunmyelinated
after ad-
locomotor
(Amann et al., 2014).
structurally including the brain and the spinal cord, refers to the decrease exercise
ditional control(group evoked IV)bynerve
experiments electrical stimulation
allowed
fibers with oftheir
the the mesencephalic
receptive
exclusion locomotor
of other
fields within
limiting in decere- mus-via their interaction in the nucleus tractus solitarii (Kim et al., 2005;
regionskeletal
and
in force/power secondary to a reduction in descending motor drive and
confounding
brate
cle.cats. The horizontal
The exercise-induced
influences
bar denotes the exercise
activation period. Note the
of these receptors immediate increases theSheriff et al., 1990; Waldrop and Mitchell, 1985). In other words,
increase of
III and IV on the endurance performance
discharge at theof theofconsecu-
the efficacy of the afferent pathways which combined result in a de- bothspontaneous group locomotor
discharge muscle afferent
of the thin fiber muscle onset exercise and the
afferents (Adreanigroup III/IV-mediated pressor responses to exercise have been docu-
tively exercising
maintainedcontralateral
response until the knee-extensor
exercise is terminated. (e.g.From lackAdreani
of peripheral
et al. (Adreani fa-et al.,
crease in the output from spinal motoneurons and thus voluntary muscle et al., 1997; Kaufman et al., 1983; Light et al., 2008) (Fig. 1) that projectmented to be larger in the absence of the arterial baroreflex. Based on
available on the effects Both
activation. of other diseasesof
components characterized by abnormal
fatigue have previously tigue,
been linked
1997).
touncompromised
via the dorsalventilatory horn of the spinal and/orcord hemodynamic
(Wilson and responses, Hand, 1997; Wilsonprevious experiments in endurance exercising humans showing that at-
neural feedback from
group III group
and IVIII/IV
musclemuscle
afferentafferents (e.g., hypertension) AUTNEU-01705;
feedback. etc.). Afferent No al.,
et of Pages
feedback
2002) 5 to associated
various spinal with exerciseand supraspinal to exhaustion sites withinin the the CNStenuated feedback from group III/IV locomotor muscle afferents causes
on the development of central and peripheral fatigue during exercise. first leg (~9contribution
min) reduced
(Brooks
to the endurance
et al., 2005;
development
Craig,
of central
time
1995;
Autonomic
fatigue Basic
to Neuroscience:
exhaustion
Craig, 2003).
has only
of and beenxxxinves-
theClinical
consec-
Although the role
(2014) ofa reduced muscle blood flow/O2 delivery and accelerated rate of periph-
xxx–xxx
tigated
group in III/IV
the last 40 years
muscle (Bigland-Ritchie
afferents in the et al., 1986).
circulatory
utively exercised contralateral leg by ~49% (from ~9 min regulation
to ~5 min). during
It exer-eral fatigue (Amann and Secher, 2010, 2011a, 2011b), it could be spec-
☆ Funding for this work was received from the National Institutes of Health (HL-103786 With
cise hasthebeen exception
recognizedof a few nearly experimental
80 yearsfeedback agoapproaches
(Alam andtoSmirk, reduce 1937),ulated that arterial baroreflex buffering of group III/IV-mediated muscle
3. Group III/IVand muscle afferent feedback effects on the development was concluded that group III/IV muscle afferent
Contents associated
HL-116579) and the American Heart Association (AHA 14 17770016).
sensory
for reviewfeedback seeduring
(Secher andand after
Amann,exercise 2012),inlists available
humans
their at (Gandevia
[e.g.
fundamentalScienceDirectimpor-reflexes exacerbates the development of peripheral fatigue during
of central fatigue with
⁎ Corresponding author at: VA Medical Center, 500 Foothill Drive, GRECC 182, Salt exhaustive endurance exercise has an inhibitory effect on the
Lake
City, UT 84148, USA. Tel.: +1 801 582 1565x4358; fax: +1 801 584 5658. et al.,
tance 1990)], the majorityexercise
in determining of investigations
hyperpnea havewas‘artificially’
not unanimously increased agreed
CNS which limits the output of[for
spinal motoneurons and therefore exercise. However, Waldrop and Mitchell have shown that the arterial
theiren-
E-mail address: markus.amann@hsc.utah.edu (M. Amann).
The involvement of group III/IV muscle afferents in the development
upon
neural
durance cardiovascular
until
discharge
performance (Amann
recently
Autonomic
of group
muscle reflex
review
III/IV muscle
et al.,mechanisms
2013). Neuroscience:
see afferents
(Dempsey to et al., 2014)],
study
and central fatigue. This ap-
Basic
roleand
andbaroreflex
in their
Clinical modulates the pressor response without changing muscle
of central fatigue during exercise is mediated through their inhibitory blood flow during induced muscular contraction in anesthetized cats
proach has included, but was not limited to, intramuscular hypertonic
http://dx.doi.org/10.1016/j.autneu.2014.10.018 (Waldrop and Mitchell, 1985). Although unknown in humans, if barore-
effect on the 1566-0702/©
output from 2014spinal motoneurons
Published by Elsevier B.V. (i.e. neural ‘drive’ to 3.1. Howsalinedo group (or other III/IVmetabolite)
musclej oafferents
u r infusions
nal hom limit
eto gthe
p astimulate
e: w output . e from
l s e v i espinal
w wnociceptive r . cmuscle
om/locate/autneu
ceptor buffering of muscle afferents does not restrict blood flow to the
motor units) which causes a reduction in muscle activation and conse- motoneurons?afferents (e.g. (Martin et al., 2008) and post exercise circulatory occlu-
working muscle, it could be argued that it does not affect the develop-
quently exercise performance
Please (Amann
cite this article as: Amann,et al.,
M.,2008, 2009, 2013;
et al., Autonomic sion (PECO)
responses to exercise: Group techniques
III/IV muscle (e.g. (Fisherand
afferents et al., 2010))
fatigue, to trap
Auton. metabolites
Neurosci. (2014),
ment of peripheral fatigue.
Bigland-Ritchie http://dx.doi.org/10.1016/j.autneu.2014.10.018
et al., 1986; Gandevia et al., 1996; Sidhu et al., withinina muscle
Decreases the output via a from
blood spinal
pressure cuff to maintain/raise
motoneurons have been neural sug- feed-
It is important to note that the role of group III/IV muscle afferents in
2014; Taylor et al., 1996). This was initially shown during maximal iso-
metric exercise of a single muscle/muscle group [for a review see
gested toback
Autonomic result for from
as long
responses as theIII/IV
group muscle
to muscle
exercise:is heldafferent
voluntary descending drive ‘upstream’ of the motor cortex and/or an
☆ depression
ischemic.
Group feedback inhibiting
III/IV muscle afferents 15
the development of peripheral fatigue might be different in patients
with heart failure (Amann et al., 2014) which are characterized by
(Gandevia, 2001)]. For example, when the discharge rate, and thus the and fatigue
afferent-mediated
2. Group III/IV muscle afferent of the net responsiveness
feedback effects on the development of the muscle reflex abnormalities (Garry, 2011; Piepoli et al., 2008) with ex-
central projection, of group III/IV muscle afferents is maintained follow- corticospinal tract
of peripheral
a,b,
including
fatigue motor cortical a
cells and spinal motoneu- b aggerated b afferent feedback as c the likely underlying mechanism
ing a 2 min maximal voluntary elbow flexor contraction (via PECO), Markus Amann
rons (Hilty et al., ⁎2011; , SimranjitMartinK. etSidhu
al., 2006; , Joshua
Sidhu et C. al.,
Weavil2014; ,Taylor Tyler S. Mangum (Middlekauff, Massimo Venturelli
and Sinoway, 2007; Notarius et al., 2001; Piepoli and
spinal motoneuronal output and voluntary muscle activation remain a Department et al., of2000, The
Medicine, role of
2006).
University ofgroup
Although III/IV
Utah, Salt muscle
theCity,
Lake inhibition
UT, USA afferents on the development
of voluntary descending of pe- Coats, 2007). Although feedback from these neurons still facilitates
b
low and do not recover until circulation is restored and the firing fre- c Department ripheral
of Exercise
drive through fatigue
&muscle
Sport Science, isUniversity
manifested
afferents Utah, through
ofacting Saltupstream their
Lake City, UT, USA
ofcontribution
the motor to the cardio-
cortex is central hemodynamics in this population (Amann et al., 2014), it has
Department of Biomedical Sciences for Health, University of Milan, Italy
vascular, hemodynamic, and ventilatory adjustments occurring during been documented to account for the excessive hyperventilatory re-
 AUTNEU-01705; No of Pages 5 15/9/16
Autonomic Neuroscience: Basic and Clinical xxx (2014) xxx–xxx

Contents lists available at ScienceDirect

Autonomic Neuroscience: Basic and Clinical

journal homepage: www.elsevier.com/locate/autneu

Autonomic responses to exercise: Group III/IV muscle afferents

and fatigue☆
Markus Amann a,b,⁎, Simranjit K. Sidhu a, Joshua C. Weavil b, Tyler S. Mangum b, Massimo Venturelli c
a
Department of Medicine, University of Utah, Salt Lake City, UT, USA
b
Department of Exercise & Sport Science, University of Utah, Salt Lake City, UT, USA
c
Department of Biomedical Sciences for Health, University of Milan, Italy

a r t i c l e i n f o a b s t r a c t

Article history: Group III and IV muscle afferents originating in exercising limb muscle play a significant role in the development
Received 12 June 2014 of fatigue during exercise in humans. Feedback from these sensory neurons to the central nervous system (CNS)
Received in revised form 17 September 2014 reflexively increases ventilation and central (cardiac output) and peripheral (limb blood flow) hemodynamic
Obsevaciones: Aferentes musculares III y IV juegan un rol significativo
Accepted 13 October 2014
Available online xxxx
responses during exercise and thereby assures adequate muscle blood flow and O2 delivery. This response de-
picts a key factor in minimizing the rate of development of peripheral fatigue and in optimizing aerobic exercise
en el desarrollo de la fatiga durante el ejercicio. Esas neuronas determinan
Keywords:
capacity. On the other hand, the central projection of group III/IV muscle afferents impairs performance and limits
the exercising human via its diminishing effect on the output from spinal motoneurons which decreases volun-
Neural feedback
respuestas autonómicas al ejercicio para asegurar un adecuado flujo sanguíneo
Central fatigue
Exercise pressor reflex
tary muscle activation (i.e. facilitates central fatigue). Accumulating evidence from recent animal studies suggests
the existence of two subtypes of group III/IV muscle afferents. While one subtype only responds to physiological
y aporte de oxígeno. Sin embargo, los mismos aferentes ejercen efectos
Circulation
Ventilation
and innocuous levels of endogenous intramuscular metabolites (lactate, ATP, protons) associated with ‘normal’,
predominantly aerobic exercise, the other subtype only responds to higher and concurrently noxious levels of
inhibitorios en el SNC, lo que facilita la fatiga y deteriora el rendimiento
metabolites present in muscle during ischemic contractions or following, for example, hypertonic saline infu-
sions. This review discusses the mechanisms through which group III/IV muscle afferent feedback mediates
both central and peripheral fatigue in exercising humans. We also briefly summarize the accumulating evidence
from recent animal and human studies documenting the existence of two subtypes of group III/IV muscle affer-
ents and the relevance of this discovery to the interpretation of previous work and the design of future studies.
© 2014 Published by Elsevier B.V.

1. Introduction In order to assure a sufficient link to the original work in the face of a
restricted number of references, we would be citing various other
Both whole body (e.g. cycling) and single joint (e.g. isometric/ review articles.
dynamic knee extension) exercise of sufficient duration and intensity
reduce the force/power generating capacity of muscles involved in the
task. This exercise-induced decrease is determined by a peripheral and 1.1. Group III/IV muscle afferent feedback and exercise: Some basics
a central [i.e. related to the central nervous system (CNS)] component
(Allen et al., 2008; Gandevia, 2001). ‘Peripheral fatigue’ encompasses With the onset of exercise, contraction-induced mechanical and
biochemical changes within the contracting muscle leading to an chemical stimuli begin to activate molecular receptors located on the
attenuated force/power response to neural excitation. ‘Central fatigue’, terminal end of both thinly myelinated (group III) and unmyelinated
structurally including the brain and the spinal cord, refers to the decrease AUTNEU-01705; No of Pages
(group 5
IV) nerve fibers with their receptive fields within skeletal mus-
in force/power secondary to a reduction in descending motor drive and cle. The exercise-induced Autonomic
activation of these
Neuroscience: receptors
Basic and increases
Clinical xxx (2014) xxx–xxx the
the efficacy of the afferent pathways which combined result in a de- spontaneous discharge of the thin fiber muscle afferents (Adreani
crease in the output from spinal motoneurons and thus voluntary muscle et al., 1997; Kaufman et al., 1983; Light et al., 2008) (Fig.
Contents lists available at ScienceDirect
1) that project
activation. Both components of fatigue have previously been linked to via the dorsal horn of the spinal cord (Wilson and Hand, 1997; Wilson
group III and IV muscle afferent feedback. et al., 2002) to various spinal and supraspinal sites within the CNS
Autonomic Neuroscience: Basic and Clinical
(Brooks et al., 2005; Craig, 1995; Craig, 2003). Although the role of
group III/IV muscle afferents in the circulatory regulation during exer-
☆ Funding for this work was received from the National Institutes of Health (HL-103786
cise has been recognized
j o u r nnearly
a l h o m 80
e p ayears
ge: ww agow . (Alam
e l s e v i eand
r.com Smirk,
/ l o c a t1937),
e/autneu
and HL-116579) and the American Heart Association (AHA 14 17770016).
⁎ Corresponding author at: VA Medical Center, 500 Foothill Drive, GRECC 182, Salt Lake
for review see (Secher and Amann, 2012), their fundamental impor-
City, UT 84148, USA. Tel.: +1 801 582 1565x4358; fax: +1 801 584 5658. tance in determining exercise hyperpnea was not unanimously agreed
E-mail address: markus.amann@hsc.utah.edu (M. Amann). upon until recently [for review see (Dempsey et al., 2014)], and their

Autonomic responses to exercise: Group III/IV muscle afferents

http://dx.doi.org/10.1016/j.autneu.2014.10.018
1566-0702/© 2014 Published by Elsevier B.V. and fatigue☆
a,b, a b b
Markus
Please cite this article as: Amann, M., et al., Autonomic responses Amann
to exercise: Group ⁎,III/IV
Simranjit
muscle K.afferents
Sidhu , Joshua C. Weavil
and fatigue, Auton. ,Neurosci.
Tyler S. Mangum
(2014), , Massimo Venturelli c
http://dx.doi.org/10.1016/j.autneu.2014.10.018 a
Department of Medicine, University of Utah, Salt Lake City, UT, USA
b
Department of Exercise & Sport Science, University of Utah, Salt Lake City, UT, USA
c
Department of Biomedical Sciences for Health, University of Milan, Italy

a r t i c l e i n f o a b s t r a c t

Article history: Group III and IV muscle afferents originating in exercising limb muscle play a significant role in the development
Received 12 June 2014 of fatigue during exercise in humans. Feedback from these sensory neurons to the central nervous system (CNS)
Received in revised form 17 September 2014 reflexively increases ventilation and central (cardiac output) and peripheral (limb blood flow) hemodynamic
Accepted 13 October 2014
responses during exercise and thereby assures adequate muscle blood flow and O2 delivery. This response de-
Available online xxxx
picts a key factor in minimizing the rate of development of peripheral fatigue and in optimizing aerobic exercise
Keywords:
capacity. On the other hand, the central projection of group III/IV muscle afferents impairs performance and limits
Neural feedback the exercising human via its diminishing effect on the output from spinal motoneurons which decreases volun-
Central fatigue tary muscle activation (i.e. facilitates central fatigue). Accumulating evidence from recent animal studies suggests
Exercise pressor reflex the existence of two subtypes of group III/IV muscle afferents. While one subtype only responds to physiological
Circulation and innocuous levels of endogenous intramuscular metabolites (lactate, ATP, protons) associated with ‘normal’,
Ventilation predominantly aerobic exercise, the other subtype only responds to higher and concurrently noxious levels of
metabolites present in muscle during ischemic contractions or following, for example, hypertonic saline infu-
sions. This review discusses the mechanisms through which group III/IV muscle afferent feedback mediates
both central and peripheral fatigue in exercising humans. We also briefly summarize the accumulating evidence
from recent animal and human studies documenting the existence of two subtypes of group III/IV muscle affer-
ents and the relevance of this discovery to the interpretation of previous work and the design of future studies.
© 2014 Published by Elsevier B.V.

1. Introduction
Both whole body (e.g. cycling) and single joint (e.g. isometric/
dynamic knee extension) exercise of sufficient duration and intensity
reduce the force/power generating capacity of muscles involved in the
task. This exercise-induced decrease is determined by a peripheral and
a central [i.e. related to the central nervous system (CNS)] component
(Allen et al., 2008; Gandevia, 2001). ‘Peripheral fatigue’ encompasses
biochemical changes within the contracting muscle leading to an
attenuated force/power response to neural excitation. ‘Central fatigue’,
structurally including the brain and the spinal cord, refers to the decrease
in force/power secondary to a reduction in descending motor drive and
the efficacy of the afferent pathways which combined result in a de-
crease in the output from spinal motoneurons and thus voluntary muscle
activation. Both components of fatigue have previously been linked to
group III and IV muscle afferent feedback.
☆ Funding for this work was received from the National Institutes of Health (HL-103786
and HL-116579) and the American Heart Association (AHA 14 17770016).
⁎ Corresponding author at: VA Medical Center, 500 Foothill Drive, GRECC 182, Salt Lake
City, UT 84148, USA. Tel.: +1 801 582 1565x4358; fax: +1 801 584 5658.
E-mail address: markus.amann@hsc.utah.edu (M. Amann).
In order to assure a sufficient link to the original work in the face of a
restricted number of references, we would be citing various other
review articles.
1.1. Group III/IV muscle afferent feedback and exercise: Some basics
With the onset of exercise, contraction-induced mechanical and
chemical stimuli begin to activate molecular receptors located on the
terminal end of both thinly myelinated (group III) and unmyelinated
(group IV) nerve fibers with their receptive fields within skeletal mus-
cle. The exercise-induced activation of these receptors increases the
spontaneous discharge of the thin fiber muscle afferents (Adreani
et al., 1997; Kaufman et al., 1983; Light et al., 2008) (Fig. 1) that project
via the dorsal horn of the spinal cord (Wilson and Hand, 1997; Wilson
et al., 2002) to various spinal and supraspinal sites within the CNS
(Brooks et al., 2005; Craig, 1995; Craig, 2003). Although the role of
group III/IV muscle afferents in the circulatory regulation during exer-
cise has been recognized nearly 80 years ago (Alam and Smirk, 1937),
for review see (Secher and Amann, 2012), their fundamental impor-
tance in determining exercise hyperpnea was not unanimously agreed
upon until recently [for review see (Dempsey et al., 2014)], and their

http://dx.doi.org/10.1016/j.autneu.2014.10.018
1566-0702/© 2014 Published by Elsevier B.V.

Please cite this article as: Amann, M., et al., Autonomic responses to exercise: Group III/IV muscle afferents and fatigue, Auton. Neurosci. (2014),
http://dx.doi.org/10.1016/j.autneu.2014.10.018

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Fatiga Central en pruebas

de larga Duración

SEROTONINA
Albúmina
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Trp
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Reposo
Modificado de J.D. F ernst rom , en Davis, J.M. and Bayley , S. , Me d Sci Spo rts
Exerc., ( 29) N°1, pp. 45-57, 1997) .

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Albúmina
Albúmina
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AGL Albúmina

Trp Albúmina
BCCA AGL
Trp Trp
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5-HT
Trp Neurona
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Ejercicio

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