www.elsevier.com/locate/brainres

Brain Research 1023

Research report

Eccentric exercise alters muscle sensory motor control

through the release of inflammatory mediators

Tanguy Marquestea,b, Patrick Decherchia,*, Folly Messana,b, Nathalie Kipsonb,

Laurent Grelota, Yves Jammesb

aLaboratoire des Determinants Physiologiques de l’Activite Physique (UPRES EA 3285), Institut Federatif de Recherches Etienne-Jules Marey (IFR107),

Faculte des Sciences du Sport de Marseille-Luminy, Universite de la Mediterranee (Aix-Marseille II), CC910 - 163, avenue de Luminy,

13288 Marseille cedex 09, FrancebLaboratoire de Physiopathologie Respiratoire (UPRES EA 2201), Institut Federatif de Recherches Jean Roche (IFR11),

Faculte de Medecine Secteur Nord, Universite de la Mediterranee (Aix-Marseille II),

Boulevard Pierre Dramard, 13916 Marseille cedex 20, France

Accepted 6 July 2004

Available online 26 August 2004

Abstract

Following downhill exercise, muscle damage and local inflammatory reactions, induced by lengthening contractions, are observed and

voluntary muscle activation decreases. The hypothesis that feedback carried by the group IV muscle afferents could be involved has often

been raised but never measured in vivo in these conditions. In this experiment, we tested the response of the group IV muscle afferents from

the lower limb to injections of KCl and lactic acid in non-exercising rats and at 1, 2, and 8 days after one running session (�138, 16 m/min).

At days 1 and 2, the baseline discharge of the group IV afferents increased, but further activation by test agents was absent. After 8 days, the

afferent response was equivalent to the control response. Pretreatment with betamethasone before exercise abolished the effects of downhill

exercise. In non-exercising rats, arachidonic acid evoked group IV afferent discharge and suppressed their further response to another

stimulus. These results demonstrate that exhaustive downhill running highly activates, for at least 2 days, the sensory feedback carried by

group IV afferents through the local release of inflammatory mediators. Such an altered sensori-motor control, accompanying the post-

eccentric inflammatory syndrome, could play a key role in deterioration of muscle performance and of its voluntary activation.

D 2004 Elsevier B.V. All rights reserved.

Theme: Sensory systems

Topic: Somatic and Visceral Afferents

Keywords: Downhill exercise; Lengthening; Pliometric; Group IV afferent; DOMS; Rat

0006-8993/$ - see front matter D 2004 Elsevier B.V. All rights reserved.

doi:10.1016/j.brainres.2004.07.027

Abbreviations: Ar-Ac, group of non exercising rats receiving acute

injection of arachidonic acid; Betamethasone-Non-Ex, group of non

exercising rats pretreated with betamethasone; Betamethasone-postDH1,

day 1 post-downhill exercise in animals pretreated with betamethasone;

DOMS, delayed-onset muscle soreness; KCl, potassium chloride; Non-Ex,

group of control rats without exercise; LA, lactic acid; post-DH1, -DH2,

-DH8, post-downhill exercise in animal at day 1, 2 and 8, respectively

* Corresponding author. Tel.: +33 (0) 491 828 360; fax: +33 (0) 491

828 377.

E-mail address: patrick.decherchi@staps.univ-mrs.fr (P. Decherchi).

URL: http://www.physiologie.staps.univ-mrs.fr.

1. Introduction

The occurrence of a delayed-onset muscle soreness

(DOMS) after exhaustive downhill exercise, due to eccen-

tric actions, is well documented in both animals and

humans. During an eccentric action the muscles must be

active when stretched [31]. Force generation by the muscle

and the load against which the muscle is battempting to

shortenQ result either in a shortening, an isometric or a

lengthening contraction [18]. The use of the adjectives

beccentricQ, bpliometricQ or blengtheningQ action can be

found in the literature to describe the fact that the muscle is

(2004) 222–230

T. Marqueste et al. / Brain Research 1023 (2004) 222–230 223

subjected to an external strength greater than the internal

strength within the muscle. Muscle lengthening occurs

despite the contraction induced by the central motor drive,

and this actin–myosin interaction. This situation is mainly

induced in muscles involved in the anti-gravity actions,

heavy weight, muscle action of an antagonistic muscle

group, and also in slowing down a movement. The

associated symptoms after eccentric exercises are muscle

stiffness, pain during active movement and reduced

flexibility [2,10,19,42]. Moreover, a decrement of muscle

strength immediately occurs after the end of the exercise,

and lasts for several days [11,12]. Clinical and functional

signs related to DOMS are associated with the release of

muscle enzymes and myoglobin into the blood [3,43], the

disruption of myofilaments with sarcolemma damage [24],

and also an inflammatory reaction associating intramuscular

invasion of neutrophiles and macrophages, and local

production of inflammatory mediators, (e.g., prostaglandins,

leukotrienes, interleukins). This post-exercise inflammatory

reaction may last 1 week [19,35,50].

Data about rodents, in the literature, reported the

damage associated to lengthening contraction in the hind

limb muscles during downhill treadmill exercise [1,44,51].

Some authors [3,31] have hypothesized that exhaustive

eccentric exercise could alter the afferent nervous feed-

back supported by the group IV afferent fibers. These

small unmyelinated afferent fibers are known to be meta-

bosensitive, i.e., they detect the release in the muscular

interstitial media of several metabolites including lactic

acid [14,26,27,45], H+ [53], KCl [27,48], and inflamma-

tory mediators [13,23,28,29,30,45]. Such activation of

group IV afferent following eccentric exercise could play a

key role in deterioration of the muscle performance.

However, no recording of these muscle afferents in these

conditions has been carried out to support this hypothesis.

The present studies were designed to test group IV

afferent activity from the hind limb muscles after a downhill

exercise. We questioned first if this eccentric exercise could

modify the sensory feedback, i.e., the baseline activity and

the activation of the group IV muscle afferents; and second,

if the exercise-induced local inflammation could participate

in the altered afferent response.

2. Methods

2.1. Animals

Experiments were conducted in 58 female, 4–5 months

old, Sprague–Dawley rats, obtained from Iffa Credo (Les

Oncins, France). Housing, surgical procedures, and

assessment of analgesia were performed according to

the French law on Animal Care Guidelines, and the

Animal Care Committee of our University approved the

protocols. Animals were housed in smooth-bottomed

plastic cages at 22 8C with a 12-h light/dark cycle.

Food (Purina rat chow) and water were available ad

libitum. Theses animals were randomly placed into seven

groups (see Protocols).

2.2. Recording protocol

Rats were anesthetized by an intra-peritoneal injection of

1.0 ml 100 g�1 body weight of solution containing sodium

pentobarbital and 0.9% saline in 1/10 volume proportion.

The trachea was cannulated for artificial ventilation (Har-

vard volumetric pump: rate 40–60 min�1, tidal volume 2–4

ml; Southmatick, MA USA). A catheter was inserted into

the right femoral artery and retrogradely advanced as far as

the fork of the abdominal aorta in order to transport the

chemicals, i.e., potassium chloride (KCl) and lactic acid

(LA), to the contralateral muscle. This catheter was

positioned so that the blood flow to the left lower limb

muscles was not interrupted. Animals were paralyzed by an

intra-arterial injection of pancuronium bromide (Pavulon, 10

mg kg�1; Sanofi, Fresne, France).

The sciatic nerve, under the left quadriceps muscle, was

dissected free from surrounding tissues at a length of 3–4

cm and its proximal portion was cut. To record the afferent

activity from the leg muscles, the free end of the distal

nerve portion was divided into several filament bundles on

a nerve support with paraffin oil, using an operating

microscope (�40, OPM 11 Zeiss, Oberkochen, Germany).

Each bundle was placed sequentially on a monopolar

tungsten electrode. The nerve activity was referred to a

nearby ground electrode, amplified (50 to 100 K) and

filtered (30 Hz to 10 kHz) by a differential amplifier

(MP2R SARL, Marseille, France). The afferent discharge

was displayed on a chart recorder (TA 4000 Gould,

Balainvilliers, France) and the potentials fed into pulse

window discriminators built in our laboratory, which

simultaneously analyzed afferent populations. The output

of these discriminators provided noise-free tracings (dis-

criminated units), which were counted by two frequency

meters at 1-s intervals (in Hz), and then displayed on the

chart recorder. The discriminated units were counted and

recorded on separate tracings. Due to the small sizes of

action potentials of the thin afferent fibers in each bundle,

the window discriminators allowed us to select 1 or 2 units

in each afferent population, i.e. 2 to 4 units per filament

bundle, and to study the activities of the afferent

populations. The discriminated units were also displayed

on a storage oscilloscope (DSO 400 Gould) to average the

nerve action potentials evoked by the stimulation of the

distal nerve with single shocks (1-ms-long rectangular

pulses, supramaximal) delivered by a Grass S8800 stim-

ulator throughout an isolation unit. The conduction velocity

of the different afferent fibers was estimated with an

interelectrode distance of 2.5–3 cm. It ranged between 0.37

and 2.60 md s�1 (mean=1.52F0.13 md s�1), i.e. in the

conduction velocity range of the unmyelinated (group IV)

fibers [20,27,30].

T. Marqueste et al. / Brain Research 1023 (2004) 222–230224

2.3. Identification of afferent fibers

The following tests were performed for each selected

filament bundle: (1) Measurements of the conduction

velocity of discriminated units. (2) Determination of the

receptive field: to ensure that the recorded afferent activity

was initiated from the muscles when pressure was exerted

on the belly with a blunt rod. (3) Measurement of the

baseline activity, i.e., action potentials per second (in Hz).

(4) Response of afferent units to intra-arterial bolus injection

of KCl (1, 5, 10 and 20 mM in 0.5-ml saline) and lactic acid

(LA) solutions (0.5, 1, 2 and 3 mM in 0.1-ml saline) were

sequentially recorded for each filament bundle. All the KCl

injections were first realized followed by the LA injections.

There was 15-min recovery between each injection, in order

to recover the baseline activity of the recorded afferents.

These tests were used in previous studies [14,15,36].

2.4. Protocols

In a control group of 10 non-exercising rats (Non-Ex),

we studied the response of the group IV afferents to their

classical test agents (KCl, LA).

Another group of eight non-exercising rats received an

intra-arterial injection of arachidonic acid (Ar-Ac group) 1

min before measuring the response of the group IV muscle

afferent to the test agents. The arachidonic acid solution was

the same as previously described by Rotto et al. [46]: a stock

solution was prepared by dissolving 100 mg of arachidonic

acid in 10 ml of sodium carbonate (100 mM) and diluted in

90 ml of saline (NaCl 0.9% in water) to obtain a final

concentration of 1 mg ml�1 (i.e., 1 mgd kg�1). Arachidonic

acid is the precursor of prostaglandins and leukotrienes, and

was chosen to induce a local inflammatory response.

A group of 24 rats were fatigued during one downhill

running trial. To produce fatigue, animals ran on a treadmill

(Medical Developpement, Saint Etienne, France) in decline

condition (�138) at 1 kmd h�1. Exhaustion was measured at

the time when the animals lose their righting reflex and

could no longer run on the treadmill [54]. After the end of

the downhill running trial, this group was divided in three

subgroups and recordings of nerve afferents were carried out

at 1 day (post-DH1 group, n=8), 2 days (post-DH2 group,

n=8) and 8 days (post-DH8 group, n=8).

In another group of eight running rats, a powerful steroid,

betamethasone, which has an anti-inflammatory power 25

times higher than cortisol, was used before exercise.

Betamethasone (1 mgd kg�1) diluted in saline was subcuta-

neously injected 24 and 1 h before exercising on the

treadmill (Betamethasone-post-DH1 group), and the afferent

activity was recorded 1 day later, as in the post-DH1 group.

In order to assess the specific effect of betamethasone on

the response of the group IV afferent to their test agents, a

group of eight non-exercising rats received the same

betamethasone doses 1 day and 1 h before recording

protocol (Betamethasone Non-Ex group) without exercise.

2.5. Statistical analysis

Baseline value of afferent fibers activity was averaged

at time zero, irrespective of the stimulus applied later.

Then, significant changes in afferent activity induced by

each test agent were determined with respect to the cor-

responding averaged baseline value. Frequencies expressed

in hertz are given as meanFS.E.M. and corresponded to

raw values measured. Data processing was realized using a

software program (SigmaStatR, Jandel, Chicago, Illinois).Analysis of variance allowed us to assess significant

modifications of the afferent activity, followed by a

Student–Newman–Keuls post-hoc test to indicate the

direction and magnitude of differences between the differ-

ent conditions.

3. Results

3.1. Time to exhaustion

The time to exhaustion was similar when the animals

were pretreated with (272F17 min) or without (297F12

min) betamethasone.

3.2. Functional characteristics of muscle afferents

The total number of recorded afferents was 116. Non-Ex

Control, n=20; Post-DH1, n=16; Post-DH2, n=16; Post-

DH8, n=16; betamethasone-Non-Ex, n=16; betamethasone-

Post-DH1, n=16; and Ar-Ac, n=16. Identification of the

receptive fields of afferents revealed that all the recorded

116 afferent populations recorded arose from leg muscles.

Among the recorded fibers, a total of 106 units (91%) were

stimulated by the various test agents used to activate groups

IV muscle afferents [Non-Ex Control=17/20 (85%); Post-

DH1=15/16 (94%); Post-DH2=14/16 (87%), Post-DH8=15/

16 (94%), Betamethasone-Non-Ex=15/16 (94%), Betame-

thasone-post-DH1=14/16 (87%) and Ar-Ac=16/16 (100%)].

These afferents were identified as metaboreceptors. They

had a tonic low frequency spontaneous baseline activity (3–

10 Hz) under our experimental conditions. Their responses

consisted in increase in basic tonic activity. The response to

KCl or LA occurred within the first 20 s following bolus

injection and it approximately lasted for 3 min. During the

time recovery between each injection, the afferent discharge

frequency returned for each filament bundle to baseline

values.

3.2.1. Exercise-induced changes

Compared to the mean value of baseline spontaneous

frequency of the group IV afferents (Fig. 1) measured in

Non-Ex control rats (4.4F0.5 Hz), the baseline afferent

activity significantly increased ( pb0.05) in rats explored at

days 1 and 2 after the downhill running session (7.0F0.9

and 7.2F0.8 Hz, respectively). At day 8, the baseline

Fig. 1. Baseline activity of the group IV afferents before (control) and after

exercise in black, and with betamethasone pretreatment in white. The

control value is measured in the control non-exercising group (Non-Ex).

Asterisks (***, pb0.001) indicate that the changes in the baseline activity

were significantly higher than the value measured in the Non-Ex group.

T. Marqueste et al. / Brain Research 1023 (2004) 222–230 225

discharge did not differ from the Non-Ex group discharge

(5.6F0.6 Hz).

In Non-Ex control rats, the discharge rate of the group IV

afferents significantly increased after injections of potas-

sium chloride and lactic acid solutions (Fig. 2). As reported

Fig. 2. Responses (in Hz) of the group IV muscle afferents in the control non-e

(respectively post-DH1, post-DH2 and post-DH8 groups) to injection of different

Asterisks (***, pb0.001) indicate that the changes in activity were significantly h

each group (i.e., 4.4F0.5 Hz for Non-Ex; 7.0F0.9 Hz for post-DHI1; 7.2F0.8 H

in pervious study [14], our data indicate that the response of

Non-Ex rats to lactic acid culminated for the 1 mM LA

concentration whereas the response to KCl plateaued at the

time the 10 mM concentration was used.

In exercising rats (post-DH1 and post-DH2), Fig. 2 shows

that the exhaustive eccentric exercise produced by downhill

running markedly alters the activation of the group IVmuscle

afferents by LA and KCl. Regardless of stimulus (LA or KCl)

or dosage used in these animals, their values did not change as

compared to their baseline activity. However, the group IV

afferent activity remained high as compared to Non-Ex group

responses. This saturation effect induced by eccentric

exercise was observed 1 and 2 days after the running session

had stopped, and a complete recovery of afferent activation

and baseline activity were observed at 8 days.

3.2.2. Effects of betamethasone

In rats pretreated with betamethasone (Fig. 1), the

eccentric exercise did not significantly modify the baselines

spontaneous discharge rate of group IV afferents (5.4F0.5

Hz) compared to Non-Ex group and to betamethasone-Non-

Ex group (4.8F0.6 Hz).

Pretreatment with betamethasone of non-exercising rats

did not modify the response of the group IVafferents to their

test agents (Fig. 3). This pretreatment with betamethasone

xercising group (Non-Ex), and 1, 2 and 8 days after the downhill running

concentrations of potassium chloride (KCl) in A, and lactic acid (LA) in B.

igher than the baseline, represented by arrow and dotted line, measured in

z for post-DH2; and 5.6F0.6 Hz for post-DH8).

Fig. 3. Comparison of the responses (in Hz) of the group IV muscle afferents recorded in the Non-Ex, post-DH1 and betamethasone-post-DH1 and

betametahsone-Non-Ex groups to injection of different concentrations of potassium chloride (KCl) in A, and lactic acid (LA) in B. Asterisks (*, pb0.05; ***,

pb0.001) indicate that the changes in activity were significantly higher than the baseline, represented by arrow and dotted line, measured in each group (i.e.,

4.4F0.5 Hz for Non-Ex; 7.0F0.9 Hz for post-DHI1; 5.4F0.5 Hz for betamethasone-post-DH1; and 4.8F0.6 Hz for betamethasone-Non-Ex).

T. Marqueste et al. / Brain Research 1023 (2004) 222–230226

before running on the treadmill blocked the post-exercise

alteration of the group IV afferent response to test agents

observed in the post-DH1 group, and a standard activation

of these afferent fibers was recovered in comparison with

the Non-Ex group.

Fig. 4. In non-exercising rats, a single injection of arachidonic acid (dashed line, 1

but a further lactic acid (dotted line, 1 mM) injection (LA 1 mM) did not enhance

units are represented. The horizontal bar indicates 1 min and the vertical bar repr

3.2.3. Response of the group IV muscle afferents to

arachidonic acid in non-exercising rats

In the Ar-Ac group, single injection of arachidonic acid

initially increased the baseline group IV afferent discharge

(Fig. 4 and Table 1). The response of the afferents stimulated

mgd kg�1) initially increased the baseline activity of the group IV afferents

the afferent discharge (see also Table 1). Counted spikes and discriminated

esents 5 Hz.

Table

1

Thebaselineactivityofthesetwononexercisinggroupwas

4.41+0.53Hz

Baselineactivity:4.41F0.53Hz

Non-ExGroup

stim

ulus:

KCl1mM

KCl5mM

KCl10mM

KCl20mM

LA

0,5

mM

LA

1mM

LA

2mM

LA

3mM

activity:

5.12F0.39

6.18F0.33***

6.53F0.38***

6.54F0.40***

5.44F0.63

7.43F0.84***

6.30F0.64***

5.21F0.55

Ar-AcGroup

firststim

ulus:

Arachidonic

acid

(1mg/kg)

activity:

6.20F0.48***

6.38F0.30***

6.78F0.31***

6.73F0.48***

7.30F0.66***

6.34F0.36***

6.21F0.84***

6.73F0.48***

secondstim

ulus:

KCl1mM

KCl5mM

KCl10mM

KCl20mM

LA

0,5

mM

LA

1mM

LA

2mM

LA

3mM

activity:

6.52F0.70***

6.69F0.27**

7.01F0.31***

6.78F0.35***

7.57F0.57***

6.60F0.48***

6.64F0.70***

6.56F0.57***

Dactivity(second

vs.firststim

ulus):

0.32F0.61

0.31F0.13

0.23F0.09

0.05F0.35

0.27F0.18

0.26F0.18

0.43F0.31

�0.17F0.22

Thechanges

intheafferentactivityarerepresentedin

response

toinjectionsofdifferentconcentrationsofsolutionscontainingpotassium

chloride(K

Cl)orlacticacid

(LA).In

theAr-Acgroupwesearched

forthe

effectsofarachidonicacid

injectiononthebaselinedischargeandthefurther

nerveafferentresponse

toinjectionsofthedifferentLAandKClconcentrations.Asterisksdepictsignificantdifferencesin

comparison

withthebaselinevalue(***,pb0.001).

T. Marqueste et al. / Brain Research 1023 (2004) 222–230 227

by arachidonic acid was slow in the onset, usually beginning

30 s after the start of injection, and frequency remained above

the pre-injection level during 3–5 min. During this inflam-

mation state, we tested the second stimuli. However, after

arachidonic acid injection, the different test agents did not

elicit any further enhancement of the afferent discharge (Fig.

4: example for the response to 1 mM LA bolus injection).

4. Discussion

The present animal study demonstrates that exhaustive

eccentric running elicits a significant increase in the baseline

spontaneous activity of the group IV muscle afferents in a

muscle participating to downhill running and that it also

saturates or prevents their response to a further attempt of

activation by KCl and LA. These effects persisted for at

least 2 days after running, and complete recovery of a

normal response of muscle afferents to their stimuli

occurred within 8 days. Pretreatment of rats with an anti-

inflammatory steroid suppressed the alterations induced by

eccentric exercise on the discharge and response of group

IV afferents. A single injection of arachidonic acid, which

promotes the local release of inflammatory mediators

[45,46], reproduced in non-exercising animals similar

effects to that of downhill running, i.e., an increased

baseline activity of the group IV afferents and the absence

of their further activation by specific stimuli. Thus, the

effects of downhill running exercise on muscle sensory

feedback seem to result simply from a saturation of the

group IV afferents discharge elicited by the local release of

inflammatory mediators [2,3]. We could exclude

ddesensitizationT of group IV afferents following multiple

injections of KCl and LA because in the non-exercised

animals, after betametasone or at 8 days after exercise, an

increased discharge frequency was observed for each KCl or

LA injection, and baseline activities of the recorded

afferents were obtained after a 15-min recovery period

between each injection.

In both animal and human, Armstrong [2] and Armstrong

et al. [3] identify four successive phases of muscle fiber

alteration during and after repetitive lengthening contrac-

tion: (1) During exercise, cytoskeletal, sarcolemma and

microtubule lesions already occur; they are characterized by

Z-band disruption, sarcoplasmic reticulum fragmentation

and mitochondrial swelling [24,52]. These alterations

prevail in the type II muscle fibers [33]. (2) Three to four

hours after the end of exercise, there is an bautogenicQ stepwhich is associated with prostaglandin and leukotriene

production. (3) Two to five days after the exercise session,

the inflammatory response is associated with neutrophile

migration and with blood release of muscular proteins [43].

(4) Four to six days after the exercise, muscle regeneration

begins; it consists in neutrophil, monocyte and macrophage

elimination of necrotic tissues [35], and increased protein

synthesis. This regenerating step may last several weeks

T. Marqueste et al. / Brain Research 1023 (2004) 222–230228

after the eccentric exercise has ended [33]. In our study, the

lack of additive response of the group IV muscle afferents to

their test agents assessed 1 and 2 days after the downhill

running trial had ended, and the recovery of their response

after 8 days coincided with the bautogenicQ (step 2) and

inflammatory (step 3) periods, i.e., the periods during which

inflammatory mediators are locally produced. Thus, the

local release of inflammatory mediators during these epochs

should markedly enhance the baseline group IV discharge,

explaining the suppression of their further response to other

stimuli. This hypothesis is supported by the absence of

saturation of the group IV sensory feedback in rats

performing downhill exercise with betamethasone pretreat-

ment. This drug inhibits inflammation, through a reduced

adhesion and infiltration of macrophages and monocytes,

and a reduced production of TNF-alpha, interleukins,

arachidonic acid and derived mediators over a long period

[37,41]. We showed in non-exercising rats that betametha-

sone treatment had no direct effect on the background

activity of the group IV muscle endings and did not modify

the response of these afferents to their stimuli. All together,

these observations support the hypothesis of the existence of

a nonspecific saturation of group IV afferent activity by

inflammatory molecules released in injured muscles. More-

over, this post-exercise muscle injury could also result in a

local release of K+ by the damage cells, which could also

participate in the activation of the group IV afferent fibers

[14,27,48]. No difference in the time to exhaustion between

our different groups could indicate that betamethasone

mainly reduces the autogenic and inflammation phases

during the post-eccentric period, but has no effect on the

mechanical muscle damages induced during the eccentric

exercise.

Many human studies relate a peak of muscle soreness 2–

3 days after eccentric exercise [11,39,42] accompanied by a

prolonged loss of capacity of activation and thus of muscle

strength, a reduced range of motion [39], and also some

disturbances of the sensorimotor control of muscle charac-

terized by an altered stretch-reflex activation and a reduced

bmuscle wisdomQ phenomenon in response to fatiguing

contractions [4–6,21]. Some experimental situations involv-

ing the activation of the group IV muscle afferents clearly

demonstrate the accompanying depression of the response

of muscle mechanoreceptors, including the muscle spindles,

to muscle stretch or contraction. This was observed in non-

exercising animals during muscle ischemia or hypoxemia

[13,32], and also during muscle fatigue induced by

repetitive electrical stimulation [26]. Thus, the altered

sensorimotor control of muscles documented after an

eccentric exercise in humans may combine the alteration

of the response of mechanosensitive afferents and the

saturation of group IV afferent activity. Many articles

[5,31,40,49] reported the changes in motor control follow-

ing eccentric exercise during maximal voluntary contrac-

tions. It is well known that the group IV afferents inputs

inhibit the alpha-motoneurones discharges [9,20,26], and

also depress the facilitating effect exercised by the Ia

afferents from muscle spindles on the spinal interneurones

network [8,16]. The group IV muscle afferents also exert

supraspinal influences on the mesencephalon, which in turn

depresses the activity of interneurones in the lamina Vof the

dorsal horn [8,25]. Type IV afferent nerve fibers are

receptive to physiological increases in KCl and lactic acid

concentrations released during exercise in extracellular

muscle fluid. Their subsequent reflex influences the spinal

motoneurones [20] and the cardio-respiratory adaptive

responses [34,47]. The role played by these afferents seems

to be crucial during exercise and fatigue tolerance adaptive

mechanisms. Furthermore, the protective mechanism of

skeletal muscle against fatigue (muscle wisdom) modulating

central motor command at spinal and supraspinal level

could be due to these afferent fibers. After an eccentric

exercise, the saturation of these afferents may disorganize

the sensory-motor loop, in order to reduce the activation of

the damaged muscle during its inflammation.

Recent data [17] hypothesized that the group IV

afferents, which may be activated by a painful stimulus,

could affect motoneurons activation, via interneurons or

within the gamma loop. It is known that the thin afferent

fibers (named group IV or C fibers) are also involved in

nociception. Thus, these afferents could be involved in the

symptom of muscle allodynia and hyperalgesia [22,38]

following tissue injuries and inflammation. On the other

hand, after lengthening contractions, the sensation of pain in

the muscles occurs during muscle activation, stretching or

palpation, but not at rest [2,4,12,31], and DOMS-associated

allodynia [7], in specific conditions, may be greatly

associated with large-diameter muscle afferents.

With the present study confirming that pro-inflammatory

mediator locally injected into resting skeletal muscle

stimulates the group IV afferents [45,46], it is tempting to

propose that a post-exercise release of these mediators after

an eccentric exercise could markedly modify the sensor-

imotor control of muscle during the recovery period. This

situation of nonspecific saturation or prevention of the

response of the group IV muscle afferents to their stimuli is

also encountered in the conditions of acute as well as

chronic hypoxemia [13].

We conclude that the saturation of the group IV afferent

activity measured in our different animal models performing

eccentric exercise or placed in hypoxemia could partly

explain a durable decrease in muscle performances

described in humans exposed to similar conditions.

Acknowledgments

We are grateful to Ferdinand TAGLIARINI (EA 2201,

Faculte de Medecine, Marseille), Duane BUTTON (Uni-

versity of Manitoba) and Andrea STEFANYSHEN (Uni-

versity of Winnipeg) for technical assistance and DGA-DSP

(no. 00.34.029.00.470.75.01) for grant.

T. Marqueste et al. / Brain Research 1023 (2004) 222–230 229

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