INFLUENCE OF ACETAMINOPHEN CONSUMPTION ...

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mmol . I-' occurred between 3 and 5 mmol . 1-I (Aunola & Rusko, 1992). Perceived Exertion Measurements. The perception of exertion was expressed according ...
Perceptual and Motor Skills, 2005, 101,675-683. O Perceptual and Motor Skills 2005

INFLUENCE O F ACETAMINOPHEN CONSUMPTION ON PERCEIVED EXERTION AT T H E LACTATE CONCENTRATION THRESHOLD ',' M. GARCIN AND L. MILLE-HAMARD Faculte' des Sciences du Sport et de lJEducation Physique Universitk de Lille 2

V. BILLAT

L. HUMBERT, M. LHERMITTE

Universite' dJEvry Val d'Essonne

Laboratoire de Biocbimie et Biologie Molkculaire, CHRU, Lille

Summay.-The purpose of this investigation was to study effects of acetaminophen consumption on ratings of perceived exertion and estimated time limit responses at the lactate threshold. 98 young regional to national level athletes performed a graded exhausting exercise on an outdoor running track to estimate their maximal aerobic velocity and the velocity associated with their lactate concentration threshold. Urine (30 mL) was collected during this test and analysed for numerous substances. During urinary screening for doping substances, 9 acetaminophen consumers (9.2%) among the 98 included athletes were detected. These acetaminophen consumers have significantly lower perceived exertion at velocity corresponding to the lactate concentration threshold than nonconsumers (11.9 f 2.1 vs 13.6 2.1, respectively) although they were at the same relative exercise intensity. This result shows that acetaminophen consumption may have mediated the perceived exertion response at the lactate concentration threshold. This may then suggest that the pain induced by training load could be a factor in use of self-prescribed pain relievers. Such consumption must be taken into account by medical staff, trainers, or educators who have to give information on the use and adverse effects of this substance and to propose palliative methods to their athletes.

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The rating scale of perceived exertion (WE),scaled from 6 to 20 as described by Borg in 1970, is the most commonly used for clinical, ergonomic, pedagogical and sporting applications (Robertson & Noble, 1997). Recently, Garcin, Vandewalle, and Monod (1999) proposed a second perceived exertion scale based on subjective estimation of exhaustion time (rating scale of Estimated Time Limit, ETL) which may be used in addition to W E during exercise to understand further how the subject is feeling. Therefore, the W E scale is concerned with the current status of the subject (how hard he feels the exercise currently is) whereas the Estimated Time Limit scale deals 'This study was supported by grants from a Projet Hospitalier de Recherche Clinique (No. :8/1959). Address correspondence to Murielle Garcin, Laboratoire d'Etudes de la Motriciti. Humaine EA 3608, Faculti: des Sciences du Sport et de 1'Education Physique, Universiti. de Lille 2, 9 rue de l'universiti., 59790 Ronchin, France or e-mail ([email protected]).

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with a subjective prediction of how long the current exercise intensity can be maintained. Some studies have paidt particular interest to drug-consumption effects on W E . The substances investigated have included alcohol (Berg, Domserius, & Kaijser, 1990)) caffeine (Costill, Dalsky, & Fink, 1978; Rodrigues, Russo, Silva, Picarro, Silva, & Zogaib, 1990), creatine (Biwer, Jensen, Schmidt, & Watts, 2003), codeine (Cook, O'Connor, & Ray, 2OOO), or nicotine by inhalation (Perkins, Sexton, Solberg-Kassel, & Epstein, 1991). According to Biwer, et al. (2003), neither W E nor time to exhaustion differentiated substance ingestion whereas the studies by Borg, et al. (1990)) and Perkins, et al. (1991) showed that W E was not affected by such consumption, although physical performance was modified (Borg, et al., 1990) or cardiovascular measurements were increased (Perkins, et al., 1991). Conversely, Costill, et al. (1978), Rodrigues, et al. (1990), and Cook, et al. (2000) showed that W E was significantly lower after caffeine or codeine ingestion, respectively. In this study, athletes were checked for drugs and doping products, and during urinary screening acetaminophen was detected. Acetaminophen belongs to a class of drugs called analgesics (pain relievers) and antipyretics (fever reducers) (Reynolds, Parfitt , Parsons, & Sweetman, 1996). Acetaminophen also is known as paracetamol and N-acetyl-p-aminophenol. It is sold in France as 1000-mg and 500-mg immediate release tablets. It can be found as a liquid suspension, coated caplets, gelcaps, geltabs, and suppositories. Furthermore, acetaminophen is found as a component of combination drugs such as propoxyphene-acetaminophen (e.g., i-antalvicB) or codeine-acetaminophen (e.g., ~aracttamol@, codtine). Acetaminophen is the most widely used pharmaceutical analgesic and antipyretic agent in France and in the world (Dyment, 1986; Gossel & Bricker, 1994). Most athletes will use an over-the-counter pain reliever at some time. Indeed, Wagner, Ulrich, McKean, and Blankenbaker (1989) showed that acetaminophen was among the drugs most comrnonly prescribed at the tenth Pan American Games. To our knowledge, none of these studies has particularly covered acetaminophen's effect on RPE at an intensity corresponding to the lactate or ventilatory threshold. This exercise intensity is particularly characterized by dyspnea and acidosis which often leads to pain in athletes. Moreover, this exercise intensity is currently part of programs for training or rehabilitation (Boutcher, Seip, Hetzler, Pierce, Snead, & Weltman, 1989; Garcin, Mille-Hamard, & Billat, 2004). To our knowledge, only one study has dealt with W E and acetaminophen ingestion (Trappe, White, Lambert, Cesar, Hellerstein, & Evans, 2002). That study showed no influence of such use on rating of perceived muscle soreness compared with a placebo. Therefore, the purpose of this experiment was to study the effect of acetaminophen consumption on perceived exertion and estimated time limit responses at the lactate concentra-

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tion threshold. As the analgesic activity of acetaminophen is used to relieve mild to moderate pain (Insel, 1996), it was hypothesized that perceived exertion and estimated time limit values would be lower in acetaminophen consumers compared with nonconsumers at this intensity.

Participants Ninety-eight young regional to national level athletes (Ma,, = 19.5 yr., SD = 2.7; M,,,, = 64.1 kg, SD = 10.6; Mheighr = 174.6 cm, SD = 8.9) participated. This population was made up of 63 men and 35 women. These athletes practiced one or several endurance activities or team sports and trained between three and five times per week. The study was carried out during a period of training. The subjects were medically examined before they signed an informed consent form about the purpose and procedures of the experiment. Approval was obtained for the experiment from the ComitP Consultatif de Protection des Personnes pour la Recherche Biomkdicale de LiUe (CP OO/lO). Procedure The subjects performed a graded exhausting exercise on an outdoor running track (400 m) to estimate their maximal aerobic velocity and the velocity associated with their lactate concentration threshold. Maximal aerobic velocity, which was defined as the minimal speed eliciting the maximal oxygen uptake, is currently used by trainers to individualise training whatever the aerobic fitness of the athlete (Billat & Koralsztein, 1996; Billat, Slawinsky, Bocquet, Demarle, Laffite, Chassaing, & Koralsztein, 2000; Demarle, Slawinski, Laffite, Bocquet, Koralsztein, & Billat, 2001). Moreover, the reliabilities of the performance measures (maximal aerobic velocity, velocity to the lactate concentration threshold) have previously been attested (Billat, Renoux, Pinoteau, Petit, & Koralsztein, 1994; Bdat & Koralsztein, 1996). According to the performances of these athletes, the initial speed was set at 8 km . h-l for the women and 20 km . h-' for the men, and was increased by 1 km . h-' every 3 min. until voluntary exhaustion. Each stage was separated by a 30-sec. rest period allowing blood sampling. Each subject was verbally encouraged to give maximum effort. Speed was checked during the graded exercise by the experimenters. O n the running track, the runners followed a pacing cyclist travelling at the required velocity. The cyclist received audio cues via a Walkman (Sonya), the cue rhythm determining the speed necessary to cover 25 m. Visual marks were set at 25-m intervals along the running track (inside the first lane) (Billat, et al., 2000). Moreover, the experimenters independently measured the time required to complete 25 m to check the pacer's and runner's speed. Exhaustion was defined when the

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subject was unable to sustain the velocity, i.e., when the runner was more than S m behind the cyclist for at least 100 m. The speed during the last fully completed stage corresponded to the maximal aerobic velocity. Fingertip capillary blood samples were collected in a capillary tube at the end of every stage, during each 30-sec. rest period, during the graded exercise and were analysed for lactate concentration using a spectrophotometric method (Dr. ~ a n ~ eLP20, @ , Germany). Blood lactate concentration was determined by an enzymatic oxidation analysis which had previously been validated (Kamber, 1992). The accuracy of the analyser was checked before each test using standard solutions. The velocity at the lactate concentration threshold was determined from the relationship between blood lactate concentrations and velocity. It was defined as the speed corresponding to the starting point of an accelerated accumulation of lactate in the blood. The velocity at the lactate concentration threshold was identified as the speed at which an increase in lactate concentration corresponding to at least 1 mmol . I-' occurred between 3 and 5 mmol . 1-I (Aunola & Rusko, 1992). Perceived Exertion Measurements The perception of exertion was expressed according to two scales, a French translation (Shephard, Vandewalle, Gil, Bouhlel, & Monod, 1992) of the Rating of Perceived Exertion scale (Borg, 1970) and a second scale based on subjective Estimation of Time Limit (Garcin, et al., 1999). The W E scale consisted of 15 assessment ratings of 6 = "very very light" to 20 = "very very hard," whereas the ETL consisted of 20 ratings of 1 ="more than 16 hours" to 20 ="less than 2 minutes." This scale was designed to show the function of the logarithm of estimated exhaustion time, tlim (ETL = 21 - 212, with n = log2 tlim where tlim is expressed in minutes). A base 2 logarithm was chosen to have enough assessments for exhaustion times ranging from less than 2 min. (anaerobic exercise) to many hours. For example, ETL was 19 for tlim equal to 2 min. and 15 for tlim equal to 8 min. To facilitate the use of this scale, ETL equal to 13 and 11 were set to 15 and 30 min. instead of 16 and 32 min., respectively. The values of ETL equal to or lower than 9 were expressed in multiples of one hour. ETL's reliability during progressive and maximal constant run exercises to exhaustion in physical education students has already been shown (Garcin, Wolff, & Bejma, 2003). The scales were explained before each exercise. These scales were written on a board fixed on the back of the experimenter riding in front of the subject. The subjects were asked "How hard do you feel this exercise is?" and "How long would you be able to perform an exercise at this intensity to exhaustion?" Up to exhaustion, the subjects had to point to a value on the perceived exertion scales at the end of each stage and the ratings were collected during the 30-sec. rest. Instructions for the scales were given one after

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another. W E or ETL at the lactate concentration threshold were defined as the perceived exertion value collected during the last 30 sec. of the velocity at the lactate threshold stage.

Urine Sampling Urine (30 mL) was collected during the incremental day test and transferred to the toxicology laboratory and analysed for numerous substances. For acetaminophen detection, 0.5 mL acetate 1M buffer p H 3.5 was added to 1.0 mL of urine. The mixture was vortexed for 3 min. Three mL of an extracting solvent [dichloromethane, dioxyde ether, hexane, and isoamylic alcohol (3 : 5 : 2 : 0.05 V N ) ]were added, and the mixture vortexed for 3 min.; 0.5 mL saturated borate buffer at p H 9.0 was added to another 1 mL of urine, and after vortexing for 3 min. the mixture was extracted under the same conditions as described above. The two organic phases were pooled, and the solvent was evaporated to dryness under nitrogen. To the dry residue were added 100 pL of a mixture of acetonitrile-phosphate buffer, 5 mM at p H 3.6 (50 : 50 V/V) and 20 pL of the solution were injected onto a Symmetry C8 column (250 mm x 4.6 mm) (WatersB, France) equipped with Mlllenium software (HPLC Alliance, watersB, France). The column was eluted by a mobile phase of acetonitrile-phosphate buffer 50 : 50 V/V using an eluting gradient and acetaminophen was detected at 280 nm. The acetaminophen was identified by retention time and characteristics of absorbance. The detection limit was 1 mg . L-' and the coefficient of variation was below 10% at a concentration of 5 mg . L-'. Analysis Statistical significance differences for W E , ETL, and percentage of maximal aerobic velocity at the lactate concentration threshold between men and women consumers of acetaminophen were evaluated with a Mann-Whitney rank test. Thereafter, men and women were grouped together and statistical differences between consumers and nonconsumers of acetaminophen at the lactate concentration threshold were tested with a Mann-Whitney rank test. Statistics of this paper were examined using Sigma StatB (Jandel, Germany). RESULTS Urinary screening allowed detection of 9 acetaminophen consumers (4 men and 5 women) among the 98 subjects (Table 1). As both men and women were consumers, and results of the Mann-Whitney test showed no statistical differences between men and women consumers for WE, ETL and percentage of maximal aerobic velocity at the lactate concentration threshold ( p > .05), the men and women were grouped together. Perceived exertion values were statistically significantly different between consumers

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and nonconsumers ( p < .05), whereas there was no difference for maximal aerobic velocity, ETL, and percentage of maximal aerobic velocity at the lactate concentration threshold values ( p > .05) (Table 1). TABLE 1 MEANSAND STANDARD DEVIATIONS ACCORDING TO MAXIMAL AEROBIC VELOCITY (MAv),PERCEIVED (RPE), AND ESTIMATED TIMELIMIT(ETL) AT VELOCITY CORRESPONDING TO LACTATE EXERTION CONCENTRATION THRESHOLD AND PERCENTAGE OF MAXIMAL AEROBIC VELOCITY AT LACTATE (%MAv)FORACETAMINOPHEN CONSUMING AND NONCONSUMING ATHLETES (N=98) THRESHOLD Acetaminophen

n

Mav (km . h)-'

M Nonconsumption 89 16.0 Consumption 9 15.4 "Significantly different ( p < .05).

ETL

WE

%Mav

SD

M

SD

M

SD

M

SD

2.4 2.3

13.6" 11.9"

2.1 2.1

12.0 11.8

2.8 0.9

87.3 85.9

4.5 3.9

The main results of this study were that acetaminophen consumers have lower perceived exertion at the velocity corresponding to the lactate concentration threshold than nonconsumers, although they were at the same relative exercise intensity. It means that acetaminophen may have mediated this perceptual response at the lactate concentration threshold. The exact mechanism of acetaminophen action is not known. Acetaminophen relieves pain by elevating the pain threshold, that is, by requiring a greater amount of pain to develop before it is felt by a person (Insel, 1996). Consequently, it might be supposed that these athletes consumed acetaminophen in a selfmedication attempt both to prevent and to better tolerate pain associated with training or resulting from training intensity and duration or competition. However, Barlas, Craig, Robinson, Walsh, Baxter, and Allen (2000) showed the absence of beneficial effect of medication with acetaminophen (1000 mg) in the management of delayed-onset of muscle soreness over an extended I 1-day period on healthy men and women students. These authors suggested that the increasing of the dosage of paracetamol may provide significant beneficial effect on any of the symptoms associated with this condition. O n the other hand, it may also be hypothesized that athletes who have larger pain tolerance may be more likely to overwork and hurt themselves, and consequently may consume mild analgesics such as acetaminophen. Thus, the lower perceived exertion values at the velocity corresponding to the lactate concentration threshold in these consumers would seem to be more related to the characteristics of the subjects as their pain sensibility, their personality, or their experience. The values obtained in this study at the lactate concentration threshold were slightly higher than the values obtained by Boutcher, et al. (1989)) Hetzler, Seip, Boutcher, Pierce, Snead, and Weltman (1991), and Seip, Snead,

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Pierce, Stein, and Weltman (1991), but were similar to the values obtained at the lactate concentration threshold for Demello, Cureton, Boineau, and Singh (1987) and Haskvitz, Seip, Weltman, Rogol, and Weltman (1992). This finding may be due in part to the fact that the first studies were conducted on men whereas the latter were obtained for women or mixed subjects. Whatever the method used, observation, interviews, questionnaire, laboratory tests, it is difficult to collect epidemiological data on doping or drug consumption (Laure, 2000). The lower frequency of acetaminophen consumers (9.2%) can be explained in part by the experimental protocol. First, subjects in the present study were informed about the substances which were being studied according to recommendations made by the ethic committee, and consequently many individuals may have refused to participate in this study. However, as acetaminophen is not an illicit substance and is commonly prescribed in sports competitions (Wagner, et al., 1989), perhaps such a methodological point would probably not have greatly altered these results. Secondly, as urine was collected on one occasion, the subjects had consumed acetaminophen in the past few days, but consumption may be chronic or merely occasional. An occasional consumer can test negative if the acetaminophen use was not close to the sampling date or if the amount of acetaminophen consumed was low. In conclusion, the results of the present study demonstrated that acetaminophen consumption may have mediated perceived exertion at the intensity corresponding to the lactate concentration threshold. Consequently, such consumption must be taken into account by medical staff, trainers, or educators who have to give information on the use and adverse effects of this substance and to propose palliative methods such as training orders which allow athletes to present lower perceived exertion values (Rejeski & Ribisl, 1980), or training sessions to higher intensities to better tolerate the intensity corresponding to the lactate concentration threshold. REFERENCES AUNOLA, S., & RUSKO,H. (1992) Does anaerobic threshold correlate with maximal lactate steady state. Journal of Sports Science, 10, 309-323. BARLAS, I?, CRAIG,J. A., ROBINSON, J., WALSH,D. M., BAXTER,G. D., &ALLEN,J. M. (2000) Managing delayed-onset muscle soreness: lack of effect of selected oral systemic analgesics. Archives of Phsyical Mediczne and Rehabilitatzon, 81, 966-992. BILLAT, V., &KORALSZTEIN, J. I? (1996) Significance of the velocity at V 0 2 max and time to exhaustion at this velocity. Sports Medicine, 22, 90-108. BILLAT, V., RENOUX, J. C., PINOTEAU, J., PETIT,B., &KORALSZTEIN, J. P. (1994) Reproducibility of running time to exhaustion at V 0 2 max in subelite runners. Medicine and Science i~ Sports and Exercise, 26, 254-257. BILLAT,V., SLAWINSKI, J., BOCQUET, V., DEMARLE, A., LAFFITE, L., CHASSAING, I?, &KORALSZTEIN, J. I? (2000) Intermittent runs at the velocity associated with maximal oxygen uptake enables subjects to remain at maximal oxygen uptake for a longer time than intense but submaximal runs. European Journal of Applied Physiology, 81, 188-196. BIWER, C. J., JENSEN, R. L., SCHMIDT, W. D., &WATTS,I? B. (2003) The effect of creatine on

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Accepted October 10, 2005.