Analgesia Following Exercise- A Review

Analgesia Following ExerciseA Review

Kelli F. KoltynSport Psychology Laboratory, Department of Kinesiology, University of Wisconsin, Madison,Wisconsin, USA

ContentsAbstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 851. Human Research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86

1.1 Cycling, Running and Step Exercise . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 861.1.1 Noxious Stimulation: Electrical . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 861.1.2 Noxious Stimulation: Temperature . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 881.1.3 Noxious Stimulation: Pressure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89

1.2 Resistance Exercise . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 901.3 Isometric Exercise . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 901.4 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91

2. Animal Research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 913. Discussion and Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97

Abstract Over the past 20 years a number of studies have examined whether analgesiaoccurs following exercise. Exercise involving running and cycling have beenexamined most often in human research, with swimming examined most often inanimal research. Pain thresholds and pain tolerances have been found to increasefollowing exercise. In addition, the intensity of a given pain stimulus has beenrated lower following exercise. There have been a number of different noxiousstimuli used in the laboratory to produce pain, and it appears that analgesia fol-lowing exercise is found more consistently for studies that used electrical orpressure stimuli to produce pain, and less consistently in studies that used tem-perature to produce pain. There is also limited research indicating that analgesiacan occur following resistance exercise and isometric exercise. Currently, themechanism(s) responsible for exercise-induced analgesia are poorly understood.Although involvement of the endogenous opioid system has received mixed sup-port in human research, results from animal research seem to indicate that thereare multiple analgesia systems, including opioid and non-opioid systems. It ap-pears from animal research that properties of the exercise stressor are importantin determining which analgesic system is activated during exercise.

REVIEW ARTICLE Sports Med 2000 Feb; 29 (2): 85-980112-1642/00/0002-0085/$20.00/0

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Stressful conditions have been found to be a nat-ural stimulus which can trigger pain suppression.[1]

A number of anecdotal observations suggest thatpain perception is altered during exposure to variousstressors, and the phenomenon has been referred to

as stress-induced analgesia. Among the earliest re-ports of stress-induced analgesia are results pub-lished by Beecher,[2,3] who found that soldiers se-verely wounded in battle reported little pain, andrequired considerably less analgesic medication com-

pared with civiliansundergoingsimilarsurgery. Stress-induced analgesia appears to be elicited by a widerange of stressors. Research has been conductedwith humans and animals, and some of the stressorsthat have been studied include thermal challenges,restraint, rotation, electric shock and exercise.

Dramatic anecdotes from dancers and athleteswho continue strenuous exercise in the face of se-vere injuries, and later report that they felt no pain,have contributed to the notion that exercise can al-ter pain perception. Some investigators have re-ferred to this as exercise-induced analgesia. One ofthe early reports of analgesia following exercisewas published by Black et al.,[4] who found thatpain threshold was elevated immediately following40 minutes of running in a single individual. Overthe past 20 years a number of studies have exam-ined whether analgesia occurs following exercise.Exercise such as running and cycling has been ex-amined most often in human research, with swim-ming being examined most often in animal research.Typically, a noxious stimulus is applied before andfollowing exercise to see if analgesia occurs follow-ing exercise. There have been a number of differentnoxious stimuli used in the laboratory to producepain, including electrical, ischaemic, temperatureand pressure stimulation. Investigators have alsoexamined potential mechanisms that may be respon-sible for the analgesic response following exercise.The most commonly tested hypothesis for exercise-induced analgesia has been that activation of theendogenous opioid system during exercise may beresponsible for the analgesic response that occursfollowing exercise. Naloxone (an opioid antago-nist) has been administered in some of the studiesto test for this possibility, but other potential mech-anisms, such as growth hormone (GH) and cortico-tropin (adrenocorticotropic hormone) have also beenexamined.

The purpose of this paper is to summarise thehuman and animal research that has been conductedin this area. Two previous review papers have beenpublished examining exercise-induced analgesia inhumans.[5,6] The intent of including findings fromanimal research in this review is to provide an ad-

ditional perspective which may expand our under-standing of exercise-induced analgesia and themechanisms responsible for this response.

1. Human Research

1.1 Cycling, Running and Step Exercise

1.1.1 Noxious Stimulation: ElectricalA number of investigators have studied changes

in pain perception following cycling exercise usingnoxious dental pulp stimulation techniques. Forexample, Pertovaara et al.[7] assessed changes indental pain thresholds during and following exer-cise at different intensities. Dental pain thresholdswere determined with a Bofors Pulp Tester, inwhich a cathode was attached to an upper tooth, andassessments were completed before, during and fol-lowing exercise. Four different levels of exercise(50, 100, 150 and 200W) were completed on a bi-cycle ergometer by 6 men. Workloads were increasedstepwise without rest between the different levels,and each work period lasted 8 minutes. It was re-ported that dental pain thresholds tended to increasewith the increasing workloads. However, a signif-icant increase in pain thresholds was only evidentat the 200W workload. Dental pain thresholds re-mained elevated 30 minutes following exercise.

Similar results were found in a study by Kemp-painen et al.[8] Seven men cycled continuously for8 minutes at workloads of 100, 200, 250 and 300W.Heart rate, blood pressure, dental pain thresholdand blood samples were taken before, during, and15 and 30 minutes following exercise. Asignificantincrease in dental pain thresholds became apparentbetween 200 and 250W, and remained elevated forapproximately 15 minutes. In addition, thermalsensitivity was decreased following exercise, witha more marked decrease in leg sensitivity comparedto thermal sensitivity of the hand. These changesin pain perception were correlated positively withheart rate, blood pressure and GH levels.

Kemppainen et al.[9] next examined the associ-ation between pain threshold elevation found withexercise and GH release. Six men completed cycleergometry exercise at workloads of 200, 250 and

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300W in 2 randomly assigned conditions. One con-dition consisted of administration of cyprohepta-dine [a serotonin (5-hydroxytryptamine; 5-HT) re-ceptor antagonist] which has been shown to inhibitGH release, and the other condition consisted ofthe administration of a placebo every 6 hours, be-ginning 2 days before testing. Dental pain thresh-olds were determined with a constant current toothstimulator, and heart rate, dental pain threshold andblood samples were assessed before exercise, ateach workload, and 15 and 30 minutes followingexercise. Pain thresholds were found to be signifi-cantly higher at 300W than before exercise in bothconditions. Cyproheptadine was not found to havea significant effect on dental pain thresholds, al-though it suppressed the exercise-induced GH re-lease. The investigators concluded that exercise-induced analgesia was not associated with GHrelease in this study.

Results from another study by Kemppainen etal.[10] indicated that mechanisms related to the releaseof corticotropin are involved in exercise-inducedanalgesia. Corticotropin is released concomitantlywith β-endorphin,[11] and can be selectively blockedwith dexamethasone administration. Six men per-formed cycle ergometer exercise at workloads of100, 150 and 200W in 2 randomly assigned condi-tions consisting of the administration of dexameth-asone or saline 60 minutes before exercise. It wasfound that dental pain thresholds were significantlyelevated in the placebo condition at workloads of100, 150 and 200W and remained elevated for 30minutes following exercise. However, dental painthresholds were significantly elevated only at aworkload of 200W in the dexamethasone condi-tion. The authors concluded that dexamethasoneattenuated pain threshold elevations, indicating thatcorticotropin is potentially involved in exercise-induced analgesia.

In a study by Olausson et al.,[12] the separateeffects of exercise and transcutaneous nerve stim-ulation (TNS) on pain threshold were studied. Den-tal pain thresholds were assessed in 8 men and 3women before and following 20 minutes of leg andarm exercise, as well as after low frequency TNS

of the hands or face in 2 conditions (naloxone andplacebo administration). Pain thresholds increasedsignificantly following leg and arm exercise, andgradually decreased to baseline levels by 50 min-utes after exercise. Also, pain thresholds increasedsignificantly following electrical stimulation of theface and hands. Changes in pain thresholds wereunaffected by injections of naloxone (0.8mg) thatwere administered after exercise. However, nalox-one administration did result in a short-lasting at-tenuation of analgesia following arm exercise.

Dental pulp and finger pain thresholds andplasma hormone levels (β-endorphin, cortisol, andcatecholamines) were measured in 10 men before,during and following exercise by Droste et al.[13]

Participants completed cycle ergometer exercise toexhaustion (approximately 15 minutes) followingnaloxone (20mg) and placebo administration. Plas-ma β-endorphin, cortisol and catecholamines werefound to be significantly elevated at maximal ex-ercise in both conditions. Dental pulp and fingerpain thresholds were also found to be significantlyelevated at maximal exercise in both conditions,with a gradual return to baseline levels by 60 min-utes after exercise. In addition, magnitude estimatesof the pain stimuli using a visual analogue scalewere found to be significantly lower following ex-ercise, indicative of an analgesic response in bothnaloxone and placebo conditions. Results from thisstudy indicate that naloxone administration did notinfluence the analgesic response that occurred fol-lowing exercise.

In a study examining analgesia following exercisein patients with silent and symptomatic myocardialischaemia, Droste et al.[14] did not find significantchanges in pain thresholds following exercise.Eight men with symptomatic myocardial ischaemiaand 9 men with asymptomatic myocardial ischaemiacompleted cycle ergometer exercise to exhaustionin naloxone (6mg) and placebo conditions admin-istered immediately prior to exercise in a double-blind fashion. Ischaemic and finger pain thresholdswere assessed before, during and following exercisewith plasma β-endorphin, cortisol and catechola-mines assessed at the same time-points. Results in-

Analgesia Following Exercise 87


dicated that ischaemic and electrical pain thresholdswere higher in the asymptomatic patients comparedwith symptomatic patients at baseline. A moderate,but statistically insignificant, increase in painthresholds was found following exercise. Nalox-one administration was found to attenuate ischaemicpain thresholds following exercise but had no ef-fect on finger pain thresholds. Plasma β-endorphinswere found to increase during exercise with signif-icantly higher increases in the asymptomatic pa-tients compared with symptomatic patients. Nalox-one administration was found to attenuate theβ-endorphin increase in the asymptomatic patients,and the investigators concluded that ‘there may bequantitative differences in the endorphinergic reg-ulation of pain in patients with symptomatic andasymptomatic myocardial ischaemia’.

Guieu et al.[15] used electrical stimulation of thesural nerve to assess changes in the threshold of thenociceptive flexion reflex following cycle ergom-eter exercise. Thresholds were assessed at rest in 8non-athletes, and at rest, as well as following 20minutes of cycling, in 6 high level athletes whoregularly participated in national or internationalathletic competitions. Pain thresholds at rest werefound to be significantly higher in the athletes com-pared to the non-athletes. Also, cycle ergometryexercise resulted in a significant increase in thethresholds of the nociceptive reflex in the athletes.

1.1.2 Noxious Stimulation: TemperatureEven though there appears to be evidence in

support of analgesia following exercise, Padawerand Levine[16] contend that analgesia following ex-ercise may be an artifact of the pre-test exposure toa noxious stimulus that occurs when pre-test/post-test designs are employed. Studies investigatingexercise-induced analgesia usually involve expos-ing participants to a pre-test measurement of pain,then to exercise, and finally to a post-test painmeasurement. Exposure to a painful stimuli can re-sult in reduced sensitivity to subsequent exposuresof the noxious stimulus, and Padawer and Levinesuggest that previous exercise-induced analgesiastudies did not control for this possibility. Padawerand Levine[16] tested 91 participants using a Solo-

mon design, in which some participants were pre-and post-tested, while other participants were post-tested only in exercise and control conditions todetermine if exercise or pre-testing with a coldpressor stimulus would produce analgesia. Resultsindicated no significant analgesic response associ-ated with exercise, but there was a significant an-algesic response found for the pre-exposure to thepain stimulus, and the investigators concluded thatthe ‘so-called exercise-induced analgesia effect maybe entirely, or in part, a pain test-reactivity artifact’.

Pertovaara and Kemppainen[17] and Droste andGreenlee[18] responded to the issues raised by Pad-awer and Levine,[16] and questioned whether theexercise intensity (50 and 70% of maximum heartrate) selected by Padawer and Levine was suffi-cient to provoke an analgesic response. Previously,Kemppainen reported that the lowest workloadwhich was found to be associated with an analgesicresponse was a workload of 74% of maximum aer-obic capacity. Also, use of the cold pressor stimuluswas criticised because the replicability of analgesiawith repeated cold pressor tests has been mixed.For example, Janal et al.[19] showed using multiplepain stimuli that cold pressor pain was not influ-enced by exercise, although in the same partici-pants thermal and ischaemic pain were attenuatedfollowing exercise. In this study, 12 runners com-pleted a 10km run at 85% of maximal aerobic ca-pacity in naloxone (0.8mg in 2ml vehicle each) andplacebo conditions administered after each sessionin a double-blind fashion. Sensory decision theoryanalyses were employed to assess both discrimin-ability of pain stimuli, as well as pain report crite-rion to 3 different stimuli (thermal, ischaemic andcold pressor). Discriminability represents how well aperson can distinguish between different intensitiesof painful stimuli, while pain report refers to theperson’s willingness to report a stimulus as painful.Results indicated that an analgesic response occurredfollowing exercise because thermal discriminabil-ity and ischaemic discriminability were significantlyreduced following running. However, there was nosignificant analgesic response found for the coldpressor test. Naloxone was found to reverse the

88 Koltyn


post-run analgesic response for ischaemic stimula-tion but not for thermal stimulation.

On the other hand, Sternberg et al.[20] did findsignificant reductions in pain reports on the coldpressor test in athletes following an athletic com-petition. Male and female basketball players, fencersand track runners were exposed to cold pressor andnoxious heat stimuli 2 days before, immediatelyfollowing and 2 days after an athletic competition.Cold pressor pain ratings decreased immediatelyfollowing the competition, and it was also reportedthat withdrawal latencies to noxious heat were al-tered by competition. No changes in pain reportswere observed across time in the non-athletes whoparticipated in the study.

Mixed results regarding the analgesic effect ofexercise on cold pain sensitivity in pilots were foundby Kemppainen et al.[21] Eight pilots who had pre-viously experienced acute in-flight neck pains and8 pilots who had not previously experienced acutein-flight neck pains (controls) completed cycleergometry exercise at increasing workloads (50 to200W). Pain thresholds were found to increase sig-nificantly following exercise at 200W in the pilotswho had previously experienced acute in-flightneck pains, but not in the control pilots. However,ratings of pain intensity and unpleasantness werefound to decrease significantly following exerciseat 200W in both groups of pilots.

Fuller and Robinson[22] used a signal detectionanalysis of pain perception in a post-test only de-sign with endurance athletes in a naturalistic set-ting. Twenty-two men completed 2 randomly as-signed conditions, including an exercise conditionwhere participants completed a 10km run outdoors,and a control condition consisting of sitting quietlyin a laboratory for 40 minutes. Radiant heat wasapplied to the forearm following each condition,and results indicated that discriminability meas-ures from intensities of 44° and 46°C were signif-icantly lower following exercise in comparison tothe control condition. This finding was reported tobe consistent with discriminability decreases seenwith the administration of analgesic chemicals suchas morphine and nitrous oxide. However, discrim-

inability measures at a temperature of 48°C werenot significantly different from the control condition.

1.1.3 Noxious Stimulation: PressureHaier et al.[23] examined the effects of a 1-mile

run on pressure pain thresholds in 9 men and 6women. A 3lb weight was rested on the first jointof the index finger until the participant reportedpain, and assessments were completed before andfollowing a 1-mile run at self-selected intensities.Naloxone administration (2mg) and saline adminis-tration were administered in a double-blind fashionright before the run. Results indicated that althoughpain thresholds increased following exercise in bothconditions, the increase was found to be signifi-cantly higher in the naloxone condition. A secondstudy was then conducted employing a larger doseof naloxone (10mg) administered before exerciseto examine the influence of naloxone dosage onexercise-induced analgesia. In this study, 4 menand 2 women completed a 1-mile run followingnaloxone or placebo administration, and results in-dicated that 10mg of naloxone completely blockedthe analgesic response following exercise.

Gurevich et al.[24] employed a Solomon 4 groupdesign in which 60 men were randomly assignedto: (i) an experimental pre/post-test group; (ii) anexperimental post-test only group; (iii) a controlpre/post-test group; or (iv) a control post-test onlygroup. The experimental groups completed 12 min-utes of step exercise at approximately 63% of max-imal oxygen uptake (V

.O2max), while the control

group completed 2 unrelated questionnaires whichrequired approximately 12 minutes to complete.Pain tolerance was assessed by the amount of timethat participants could endure 2300g of pressure tothe index finger of the dominant hand. Participantsalso rated the intensity of the pain stimulus usingan 11-point scale. Results showed no significantanalgesic response for the pain pre-test. However,there was a significant analgesic response foundfor exercise, with the exercise groups having higherpain tolerances and lower pain ratings followingexercise in comparison to the control group.

Koltyn et al.[25] found increases in pressure painthresholds following exercise. Fourteen men and 2



women completed 2 randomly assigned conditionsincluding exercise and no-exercise control sessions.Exercise consisted of 30 minutes of cycle ergome-ter exercise at 75% of V

.O2max, while the control

condition consisted of resting quietly in a sound-dampened chamber for 30 minutes. Pressure wasapplied to the finger with the Forgione-Barber pres-sure stimulator before, immediately following and15 to 20 minutes following the exercise and controlconditions. Pain thresholds were found to be sig-nificantly elevated immediately, as well as 15 to 20minutes following exercise, compared with nochange in pain thresholds following the no-exercisecontrol condition. In addition, pain ratings werefound to be significantly lower following exercisein comparison to the control condition.

There is one report of a hyperalgesic responsefollowing exercise. Vecchiet et al.[26] examinedmuscular pain sensitivity following 30 minutes ofexercise in 10 healthy men. The intensity of painwas reported with a visual analogue scale every 30seconds after the injection of: (i) 1ml of 10% so-dium chloride hypertonic solution at rest; (ii) 1mlof 20% sodium chloride hypertonic solution at rest;and (iii) 1ml of 10% sodium chloride hypertonicsolution 1 minute and 60 minutes following sub-maximal exercise. The injection of 10% sodiumchloride solution 1 minute after exercise was asso-ciated with an increase in pain, similar to that in-duced by the 20% sodium chloride solution givenduring rest. The investigators concluded that exer-cise produced a hyperalgesic response because painwas elevated 1 minute following exercise.

1.2 Resistance Exercise

There have been only a limited number of stud-ies that have examined whether analgesia occursfollowing a resistance exercise session. Bartholo-mew et al.[27] investigated the effects of 20 minutesof self-selected exercise on pressure pain thresh-olds and pain tolerance. Seventeen men who wereregular exercisers completed a self-selected exercisesession in a gym and a control session in a labora-tory. Exercise consisted of 13 of the participantscompleting 20 minutes of resistance exercise (cir-

cuit weight training), while 4 participants performedstationary cycling. There were significant increasesin pressure pain tolerances following exercise incomparison to the control condition. However, painthresholds were not found to change following ex-ercise or control conditions. It is unclear why paintolerances changed following exercise but painthresholds remained unchanged.

Koltyn and Arbogast[28] examined whether an-algesia occurred following a resistance exercise ses-sion in comparison to a no-exercise control session.Thirteen participants completed 2 randomly assignedconditions (resistance exercise and control), andpressure pain thresholds and pain ratings were as-sessed immediately before, as well as 5 and 15 to20 minutes following the 2 conditions. Resistanceexercise consisted of 45 minutes of lifting 3 sets of10 repetitions at 75% of the individual’s 1 repetitionmaximum, with the control condition consisting ofsitting quietly in a room free from distractions for45 minutes. Pain thresholds were found to increasesignificantly 5 minutes following resistance exer-cise, with a return to baseline by 15 to 20 minutesfollowing exercise. Pain ratings were found to belower 5 minutes following resistance exercise, andthis was observed in conjunction with changes inblood pressure and heart rate following resistanceexercise. Pain thresholds and pain ratings were notfound to change significantly following quiet rest.

1.3 Isometric Exercise

Several studies have examined changes in painperception following isometric exercise. Pressurepain thresholds were examined before, during andfollowing isometric contractions of the quadricepby Kosek and Ekholm.[29] Fourteen women com-pleted an isometric contraction to exhaustion(maximum = 5 minutes) of the quadricep at 21% ofmaximal voluntary contraction. Pressure painthresholds of the quadriceps were assessed before,every 30 seconds during, immediately followingand 5 minutes following isometric exercise. Painthresholds were found to increase significantlyduring isometric exercise, and remained elevatedduring the 5-minute recovery period. In a subsequent

90 Koltyn


study, Kosek et al.[30] examined the effect of sub-maximal isometric exercise on pressure pain thres-holds in 14 patients with fibromyalgia and 14 healthyvolunteers. The same design was employed in thisstudy, and results showed that pain thresholds in-creased significantly during isometric exercise andremained elevated during the 5-minute recoveryperiod in the healthy control participants. In com-parison, pain thresholds decreased significantlyduring isometric exercise and remained below pre-contraction levels during the 5-minute recoveryperiod in the patients with fibromyalgia. The re-sults for the patients with fibromyalgia are inagreement with results reported by Bengsston etal.,[31] who found that lower body pain reports wereelevated following cycle ergometry exercise per-formed at 80% of the participant’s estimated V

.O2max.

The effect of isometric leg exercise and cycleergometer exercise on skin sensitivity was exam-ined by Paalasmaa et al.[32] Skin sensitivity to innoc-uous and noxious thermal stimuli was examined us-ing a thermostimulator which could be warmed orcooled, and electrical stimulation was used to ex-amine tactile sensitivity in 11 men. Isometric exerciseconsisted of pressing the right foot against a staticload of 30 and 70% of maximum force for approx-imately 2 minutes, while cycle ergometer exerciseconsisted of pedalling 6 to 8 minutes at increasinglevels of intensities (100, 150, 200, 250W). Isomet-ric exercise produced an attenuation of thermal stim-uli of the exercised limb to innocuous stimuli, butdid not have an effect on tactile or heat pain thresh-olds. In comparison, cycle ergometer exercise pro-duced an intensity-dependent multisegmental at-tenuation of tactile and thermal sensitivity lastingapproximately 15 to 30 minutes following exercise.

1.4 Summary

Analgesia following exercise has been found bya number of investigators using a variety of nox-ious stimuli, and results have been summarised intable I. Increased pain thresholds and tolerances,as well as lower pain ratings, have been found tooccur following exercise, and 2 other reviews ofliterature have also reported similar results.[5,6] The

results for exercise-induced analgesia appear to bemore consistent for studies that used electrical orpressure stimuli to produce pain, and less consis-tent for studies that used temperature stimulationto produce pain. The equivocal results for temper-ature stimulation may be due to changes in skin andbody temperature that can occur during exercisedepending upon the intensity and duration of theexercise. Previously, it has been shown that withan increase in skin temperature, both warm andcool thresholds are obtained at a higher stimulationtemperature.[32,33] However, Kojo and Pertovaara[33]

also reported that heat pain thresholds were onlyminimally, if at all, influenced by a change in skinor body temperature. It is currently unclear howchanges in skin or body temperature associated withexercise interacts with heat or cold pain thresholds.Thus, additional research is needed in this area.Analgesia following exercise appears to be mostconsistent when the exercise stimulus involves ex-ercise performed at higher intensities (i.e. > 70%of maximal aerobic capacity). Currently, the mech-anism(s) for analgesia following exercise are poorlyunderstood. Results from studies that have exam-ined the involvement of the endogenous opioidsystem in the analgesic response following exer-cise are mixed. Some investigators have found thatnaloxone administration attenuated the post-exerciseanalgesic response.[12,14,19,23] However, other inves-tigators did not find that analgesia following exercisewas affected by naloxone administration.[4,12,13,19]

2. Animal Research

The most compelling evidence to support anal-gesia following exercise and the involvement ofthe endogenous opioid system have been providedby animal experimentation. Most of this researchhas investigated whether exercise-induced analge-sia is mediated by endogenous opioid mechanisms,and the predominant exercise stimulus used in theanimal research has been swimming. For example,Bodnar et al.[34] examined whether different dosesof naloxone would eliminate analgesia producedby cold water swims in 18 male rats. Naloxone atdoses of 0, 1, 5, 10 and 20 mg/kg were adminis-



Table I. Human studies of exercise-induced analgesia

Investigators Participants Exercise stimulus Results

Electrical stimulusPertovaara et al.[7] 6 men Cycle ergometer (50-200W) Increase in dental pain thresholds at 200W

Kemppainen et al.[8] 7 men Cycle ergometer (100-300W) Increase in dental pain thresholds at 200W

Kemppainen et al.[9] 6 men Cycle ergometer (200-300W), placeboand cyroheptadine conditions

Increase in dental pain thresholds at 300W inboth conditions

Kemppainen et al.[10] 6 men Cycle ergometer (100-200W) placeboand dexamethasone conditions

Increase in dental pain thresholds at 100-200Win placebo condition but only at 200W indexamethasone condition

Olausson et al.[12] 8 men, 3 women Arm and leg ergometer (20 minutes),placebo and naloxone conditions

Increase in dental pain thresholds in placeboand naloxone conditions

Droste et al.[14] 17 men withmyocardial ischaemia

Cycle ergometer (to exhaustion),placebo and naloxone condition

No increase in finger pain thresholds in placeboor naloxone conditions

Droste et al.[13] 10 men Cycle ergometer (to exhaustion),placebo and naloxone conditions

Increase in dental and finger pain thresholds inplacebo and naloxone conditions

Guieu et al.[15] 6 athletes Cycle ergometer (20 minutes) Increase in the thresholds of the nociceptivereflex

Temperature stimulusPadawer & Levine[16] 91 men and women Cycle ergometer (50 and 70% of HRmax) No analgesic response for cold pressor stimuli

following exercise

Janal et al.[19] 12 runners 10km run at 85% of max, placebo andnaloxone conditions

Analgesic response following exercise forthermal and ischaemic pain stimuli but not forcold pressor stimuli

Sternberg et al.[20] 34 male athletes, 33female athletes

Athletic competition Decrease in pain reports following competitionfor cold pressor stimuli

Kemppainen et al.[21] 8 pilots with pain, 8pilots without pain

Cycle ergometer (50-200W) Increase in pain thresholds for pilots with pain.Pain ratings decreased for both groups

Fuller & Robinson[22] 22 men 10km run Discriminability decreased for 44 and 46°Cradiant heat but not for 48°C

Paalasmaa et al.[32] 11 men Isometric and cycle ergometer Increase in heat thresholds following cycleexercise but not for isometric exercise

Pressure stimulusHaier et al.[23]

(study 1)9 men, 4 women 1-mile run, placebo and naloxone

conditionsIncrease in pain thresholds for both conditions

Haier et al.[23]

(study 2)4 men, 2 women 1-mile run, placebo and naloxone

conditionsIncrease in pain thresholds for placebo condition

Gurevich et al.[24] 60 men 12 minutes step exercise at 63% ofmaximum

Increase in pain tolerance and lower painratings following exercise

Koltyn et al.[25] 14 men, 2 women 30-minute cycle ergometer (75% ofmaximum)

Increase in pain thresholds and decrease inpain ratings following exercise

Bartholomew et al.[27] 17 men 20 minutes self-selected exercise (cycleergometer or resistance exercise)

Increase in pain tolerances but not painthresholds

Koltyn & Arbogast[28] 7 men, 6 women 45 minutes resistance exercise at 75%of maximum

Increase in pain thresholds and decrease inpain ratings following exercise

Kosek & Ekholm[29] 14 women Isometric exercise at 21% of maximumto exhaustion

Increase in pain thresholds during and followingexercise

Kosek et al.[30] 28 women (14 withfibromyalgia, 14healthy controls)

Isometric exercise at 21% of maximumto exhaustion

Increase in pain thresholds during and followingexercise in the healthy control women but not inthe women with fibromyalgia

Other stimulusVecchiet et al.[26] 10 men 30 minutes cycle ergometer at 70%

HRmax

Increase in pain associated with an injection of10% sodium chloride after exercise

HRmax = maximum heart rate.

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tered at weekly intervals immediately precedingcold water swims (3.5 minutes in 2°C water). Al-terations in flinch jump-thresholds were determined30 minutes following the swims. Thresholds werefound to be elevated following cold water swim-ming in comparison to a control condition, and nal-oxone produced a mild, dose-dependent reductionin analgesia following the swim. However, even atdoses normally sufficient to block opiate analge-sia, naloxone did not fully reverse the analgesia,which may indicate the possible existence of a par-allel non-opiate system.

Willow et al.[35] examined the analgesic responsefollowing swimming in female mice. Changes inpain thresholds were assessed by placing mice ona hot plate maintained at 56°C, and recording thetime it took for a flick of a hind limb to occur. Twogroups of mice were swum in 20°C for 3 minutes.One group received 100 µg/kg of naloxone 1 hourprior to the swim, while the other group receivedsaline. Results indicated that there was a signifi-cant increase in pain thresholds in the saline groupbut no increase in pain thresholds in the group thatreceived naloxone. The investigators concluded thatthe stress of swimming, or some consequence ofthe swimming, was sufficient to activate a mecha-nism which reduced sensitivity to pain. This effectwas greater than the analgesia obtained with theinjection of 15 mg/kg of morphine. Furthermore,since analgesia following swimming was eliminatedby naloxone, ‘it seems likely that this mechanisminvolves enkephalins, endorphins or some compa-rable endogenous opioid’.

Changes in tail flick latencies following warmwater swims were examined by Christie et al.[36]

Female mice were swum for 3 minutes in 32°Cwater. Results indicated a significantly longer tailflick latency after swimming compared to controlmice which did not swim. The leu-enkephalin (LE)binding to brain homogenates was also examined,and it was found that the LE binding was signifi-cantly reduced following swimming compared withthe control condition, which may suggest involve-ment of endogenous opioids.

Cooper and Carmody[37] examined the time courseof analgesia induced by swimming, as well as theeffect of water temperature on body temperature andthe analgesic response in mice. Male mice were swumfor different time periods in different water tem-peratures, and pain thresholds were assessed be-fore and following the swim by recording the timeof a flick of a hind limb after the animal was placedon a hot plate. Results showed that pain thresholdswere increased significantly 1 minute after the swim,with a linear decline in pain thresholds through 30minutes. A swim as short as 15 seconds was asso-ciated with a significant increase in pain thresh-olds, and with longer swims (up to 7.5 minutes) themagnitude of analgesia was found to increase. Painthresholds were found to be elevated followingswims in water temperatures of 31 and 38°C in theabsence of a significant change in body tempera-ture, and with further decreases in water tempera-ture, body temperature dropped and the magnitudeof the analgesic response increased significantly.

O’Connor and Chipkin[38] investigated the effectsof warm and cold water swims on tail flick latenciesin male mice. Response latencies were measured byshining a radiant heat lamp on the middle section ofthe tail and measuring the withdrawal response timebefore and after warm (32°C) and cold (2°C) waterswims. To first determine the appropriate controlgroup, tail flick latencies of dry versus wet micewere compared. Separate groups of mice were testedin 3 different conditions: (i) dry; (ii) briefly (< 2seconds) dunked in water with excess moisture wipedfrom the tails; and (iii) tails that were moistenedwith water outside the bath and then dried. Resultsindicated that the dry mice had significantly shortertail flick latencies than the wet mice, implying thatthe dampness of the tail can contribute to the in-crease in tail flick latencies. Therefore, in the nextstudy, wet mice were used as the relevant controlgroup and were compared to the group of mice thatwere swum. Cold water swimming was associatedwith a significant increase in tail flick latencies whichwas not blocked by naloxone. Warm water swimmingup to 3 minutes produced an inconsistent effect ontail flick latencies, and naloxone was found to atten-



uate the response. These results suggested the an-algesic effect following exercise in warm and coldwater may be mediated by different mechanisms.

Examination of the influence of various param-eters of cold water (2°C) swims on exercise-inducedanalgesia were conducted by Giradot and Hollo-way.[39] Male rats were exposed to: (i) various du-rations of cold water swims; (ii) intermittent vs con-tinuous cold water swims; and (iii) 60 consecutivecold water swims in naltrexone and saline conditions.Naltrexone administered 10 minutes before the swimpartially antagonised continuous cold water swimanalgesia, but only at high doses of naltrexone (21mg/kg). However, at lower doses (14 mg/kg) nal-trexone did significantly antagonise intermittent coldwater swims and enhanced the analgesic responseproduced by 60 consecutive swims. These resultsdemonstrate that naltrexone differentially influencescold water swim analgesia depending upon specificparameters of the exercise condition, including theduration of the swim, whether the swim was inter-mittent or continuous, or whether a large number ofconsecutive cold water swims were completed.

Examination of the interaction between exerciseand water temperature in determining the opioid ornon-opioid analgesic response to swimming wasinvestigated by Terman et al.[40] Seventy-two malerats were divided into 6 groups (n = 12), and swamin water of different temperatures (10, 15, 20 or40°C water) for either 3, 5 or 10 minutes. Half ofthe rats received naltrexone hydrochloride and theother half received saline. Pain sensitivity was as-sessed using the tail-flick test, with analgesia de-fined as a significant increase in response latencytime relative to baseline. No significant changes intail-flick latencies were found following swimmingin 40°C water for 5 minutes. However, there weresignificant increases in tail-flick latencies follow-ing swimming in the other water temperatures.Naltrexone was found to significantly attenuate theanalgesic response for the 3 and 5 minute swims in15 and 20°C water, but had no effect on the anal-gesic response for the 10-minute swims in 15°Cwater or for the 5-minute swims in 10°C water.Thus, analgesia from the longest duration or coldest

water swims was insensitive to naltrexone, whereasanalgesia induced by briefer or warmer water swimswas reduced by naltrexone. It appears that the se-verity of the stressor plays a role in determining theneurochemical mediation of analgesia.

Carmody and Cooper[41] examined the influenceof swimming on chronic pain in mice. Chronic paincan be induced in mice with subcutaneous formalininjections, and Carmody and Cooper found that 3minutes of swimming in 20 to 21°C water produceda significant reduction in pain behaviours whichpersisted for 30 minutes following the swim. Also,this analgesia appears to be opioid in nature sincenaloxone (1 mg/kg) abolished the analgesic responsefollowing swimming.

Tierney et al.[42] examined the influence of theduration of swim on the analgesic response. Fe-male mice completed swims between 15 secondsand 5 minutes in 20 to 22°C water. Half of the an-imals were pre-treated with naloxone (5 mg/kg) andthe other half were pre-treated with saline. Resultsindicated that there was a significant increase inanalgesia as measured by tail-flick latencies follow-ing the 15-second swim, and this analgesia increasedprogressively as the swim duration was extendedto 5 minutes. No significant differences were foundbetween the naloxone and saline conditions follow-ing the 15-second swim. However, an opioid anal-gesia was reported to develop as the duration ofswim increased. The investigators concluded thatthe duration of the swim influences the nature ofthe analgesia, and that there appears to be multipleanalgesia systems (opioid and non-opioid) involvedin this type of analgesia.

Shyu et al.[43] conducted one of the few studiesthat has used a running protocol rather than a swim-ming protocol as the exercise stimulus. Male spon-taneously hypertensive (SHR) and normotensive(WKY) rats were trained to run spontaneously inrunning wheels. After 3 to 4 weeks of training, painsensitivity (squeak threshold to electrical stimula-tion) was measured between 8 and 9am when theanimals were at the end of their running activityduring the dark phase. Squeak thresholds were foundto be significantly elevated in the early morning in

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those rats that ran during the dark phase. The mag-nitude of change of squeak thresholds varied acrossanimals, and was found to correlate significantly (r= 0.80) with the amount of running activity. Also,the effect of naloxone and saline administration onsqueak thresholds was examined between 8 and9am in 6 SHR rats. Saline administration was notfound to change squeak thresholds, but naloxoneadministration was found to decrease squeak thres-holds to baseline levels, indicating involvement ofthe endogenous opioid system.

Hoffman et al.[44] investigated whether skeletalmuscle stimulation in the rat would alter painthresholds, because it has been suggested that theanalgesic effect of exercise is mediated by activa-tion of group III and/or IV afferents from skeletalmuscle. Sixty minutes of low frequency musclestimulation of the hind leg was found to increasepain thresholds in male SHR rats. The analgesicresponse peaked after 120 minutes following stim-ulation, and lasted for an additional 2 hours. Addi-tionally, 1 group of rats was pretreated with dl-p-chlorophenylalanine (PCPA), a serotonin synthesisblocker, to examine the role of serotonin in the an-algesic response to muscle stimulation. Results in-dicated that PCPA completely abolished the post-stimulatory analgesia, indicating that serotoninsystems are involved in the analgesic response fol-lowing muscle stimulation.

Yao et al.[45] activated group III muscle affer-ents using prolonged low frequency stimulation ofthe sciatic nerve, and examined the role of endorphinand serotonin systems on pain thresholds andblood pressure responses. Pain thresholds, bloodpressure and heart rate were assessed before andfollowing 30 minutes of low frequency stimulationof the sciatic nerve in adult, male, SHR rats. Sciaticstimulation significantly elevated pain thresholds,and a dose of naloxone (1 ml/kg IV) had an imme-diate antagonistic effect on the analgesic response.However, a larger dose of naloxone (10 to 15 mg/kgIV) was required to attenuate the blood pressureresponses following stimulation. Furthermore, se-rotonin was found to be involved in the blood pres-sure responses following sciatic stimulation.

Very little is known about the neurochemicalbasis of non-opioid analgesia. Marek et al.[46] ex-amined the involvement of N-methyl-D-aspartic acid(NMDA) subtype of excitatory amino acid receptorsin non-opioid analgesia. The influence of a NMDAantagonist dizocilpine (MK-801) on the analgesicresponse following swimming was studied in con-trol (C) mice, and in mice selectively bred for high(HA) or low (LA) swim-induced analgesia. Mice(C, HA and LA) were randomly assigned to 1 of 4groups consisting of: (i) naloxone; (ii) dizocilpine;(iii) a combination of naloxone and dizocilpine;and (iv) saline administered 20 minutes before thebaseline assessment of hot-plate latencies. The micethen completed 3 minutes of swimming in watertemperatures of 15, 20 and 32°C in 3 separate ex-periments. Dizocilpine was found to attenuate theanalgesic response following the swim in 15°Cwater in which naloxone was ineffective, but hadno influence on the analgesic response followingthe swim in 32°C water, which naloxone blockedcompletely. A combination of naloxone and dizo-cilpine was found to attenuate the analgesic responsefollowing swimming in 20°C water in the C andHA mice. It was concluded that dizocilpine selec-tively blocked non-opioid mechanisms of analgesiafollowing swimming in 15°C water.

In summary, exercise-induced analgesia has beendemonstrated in male rats and male and female mice,and results from this research are summarised intable II. However, most of the research has employeda forced swimming protocol, and a question hasarisen regarding whether the analgesia produced fol-lowing swimming is a result of the stressful natureof forced swimming itself or secondary to changesin body temperature (i.e. hypothermia) produced bythe swim.[40,46] However, Terman et al.[40] and Mareket al.[46] argue against the notion that analgesia is aresult of hypothermia due to a number of differentreasons including: (i) swim-induced analgesia andhypothermia can be pharmacologically dissociatedin that naloxone can block the analgesic responsefollowing swimming but not the hypothermic re-sponse;[40] (ii) analgesia has been found to occurfollowing swimming in the absence of a significant



change in body temperature;[37] and (iii) analgesiahas been found following other stressors, includingfootshock and rotation, that do not result in a changein body temperature.[40] Furthermore, in order toaddress the question of whether analgesia follow-ing swimming is a function of the forced nature ofthe swim, Shyu et al.[43] used spontaneous wheelrunning as the exercise stimulus, and found analgesiato occur in those animals that ran spontaneously.

It appears from animal research that multipleanalgesia systems exist (opioid and non-opioid) andthat properties of the exercise stressor are impor-tant in determining which system is activated duringexercise. It has been shown that by manipulating

the parameters of the exercise stressor, it is possibleto elicit either naloxone-reversible or naloxone-insensitive analgesia following exercise. Some ofthe parameters that have been manipulated in theanimal research include: (i) duration of the exercisesession; (ii) using continuous vs intermittent exer-cise; and (iii) varying the water temperature for theswim protocols. Naloxone has been found to atten-uate the analgesic response following exercise inwarmer water temperatures but has not had a con-sistent effect on analgesia following exercise incolder water temperatures. These results suggestthat multiple analgesia systems, including opioidand non-opioid systems, exist in this type of anal-

Table II. Animal studies of exercise-induced analgesia

Investigators Study animals Exercise stimulus Results

Electrical stimulusBodnar et al.[34] Male albino rats 3.5-minute swim in 2°C water,

various naloxone conditionsIncrease in flinch jump thresholds, but naloxoneproduced dose-dependent decrease in analgesia

Christie et al.[36] Female QS mice 3-minute swim in 32°C water Increase in tail flick latency

Shyu et al.[43] Male SHR andnormotensive rats

Wheel running during dark phase Increase in squeak thresholds but naloxoneattenuated the analgesic response

Yao et al.[45] Male SHR rats 60-minute muscle stimulation, controland PCPA groups

Increase in squeak threshold but PCPA blockedanalgesic response

Terman et al.[40] Male rats Swim in various water temperatures,placebo and naltrexone conditions

Increase in tail flick latencies in all watertemperatures except 40°C. Naltrexone attenuatedanalgesic response in 15 and 20°C water

Hoffman et al.[44] Male SHR rats 60-minute muscle stimulation, controland PCPA groups

Increase in squeak threshold but PCPA blockedanalgesic response

Temperature stimulusWillow et al.[35] Female albino mice 3-minute swim in 20°C water,

placebo and naloxone conditionsIncrease in hind limb flick when exposed to hotplate in placebo but not naloxone group

Cooper & Carmody[37] Male mice Swims of different durations andwater temperatures

Increase in hind limb flick in all conditions

O’Connor & Chipkin[38] Male mice Swim in 2 and 32°C water, placeboand naloxone conditions

Increase in tail flick latency in 2°C water butinconsistent effects in 32°C. Naloxone blockedresponse in 32°C water

Giradot & Holloway[39] Male albino rats Various swims in 20-21°C water,placebo and naltrexone conditions

Mixed results

Tierney et al.[42] Female albino mice Swims of various durations in20-22°C water, placebo andnaloxone groups

Increase in tail flick latencies. However, naloxoneattenuated increase in longer duration swims

Marek et al.[46] Male and femalemice

3-minute swim in 15, 20 and 32°Cwater, placebo, dizocilpine andnaloxone conditions

Dizocilpine blocked analgesia in 15°C water,naloxone blocked analgesia in 32°C water,combination blocked analgesia in 20°C water

Other stimulusCarmody & Cooper[41] Male mice 3-minute swim in 20-21°C water,

placebo and naloxone conditionsDecrease in pain behaviour and naloxoneabolished the response

PCPA = dl-p-chlorophenylalanine; SHR = spontaneously hypertensive.

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gesia. The specific neurochemistry of non-opioidanalgesia is unclear, but several neurotransmitters,such as serotonin and norepinephrine (noradrena-line), have been implicated.[44] Also, NMDA hasrecently been examined for its potential involve-ment in non-opioid analgesic responses that occurfollowing exercise.[46]

3. Discussion and Conclusions

Analgesia following exercise has been found tooccur in humans and animals by a number of in-vestigators. Running, cycling and swimming haveconsistently been associated with an analgesic re-sponse following exercise, although analgesia fol-lowing swimming has only been studied in rodents.Research with other modes of exercise, such as re-sistance exercise and isometric exercise, has beenvery limited. However, preliminary results indicatethat analgesia can occur following resistance exer-cise and isometric exercise, but the time course ofthe analgesic response following these types of ex-ercise needs further examination. More research isneeded to expand our understanding of analgesicresponses following different modes of exercise.Also, the mechanisms underlying exercise-inducedanalgesia have proven to be complex, and the exactmechanism(s) responsible for exercise-induced anal-gesia are not entirely clear at this time. The mostcommonly tested hypothesis in both the human andanimal literature is that activation of the endogenousopioid system during exercise may be responsiblefor the analgesic response following exercise. How-ever, the data regarding this hypothesis are mixedin human research. There appears to be more consis-tent support for involvement of endogenous opioidsin exercise-induced analgesia in animal research,but non-opioid analgesia following exercise has alsobeen identified in animals. Additional research isneeded to clarify and expand our understanding ofthe mechanisms responsible for exercise-inducedanalgesia. Furthermore, application of the latest neu-ral imagining techniques (e.g. positron emissiontomography, regional cerebral blood flow) couldpotentially expand our understanding of the braincircuitry involved in analgesia following exercise.

There is also a need for more research examiningwhether analgesia occurs following exercise inwomen. Most of the research in this area has in-volved the testing of men. In several of the studiesthat have been conducted, a mixed sample of menand women were used, but the number of womenin these studies was very small. In the general painliterature, there are reports of gender differences inexperimentally-induced pain.[47-49] Currently, it isunclear if men and women differ in exercise-inducedanalgesia because very little research has been con-ducted in this area. Further research is needed ex-amining exercise-induced analgesia in women, andwhether men and women differ in analgesic responsesfollowing exercise.

Research is also needed to examine whether an-algesia occurs following exercise in individualsexperiencing chronic painful conditions. Most ofthe exercise-induced analgesia research has involvedthe testing of healthy individuals who regularly ex-ercise, and it is currently unclear whether individ-uals who are experiencing a chronic painful conditionwill experience analgesia following an exercisesession. It is possible that exercise may exacerbatean already existing painful condition, and there issome research with patients with fibromyalgia tosupport this possibility.[30,31] However, there are anumber of different chronic conditions (e.g. lowback pain, arthritic pain, headache pain) and re-search is needed to determine if exercise can serveas an effective pain management intervention.

References1. Terman GW, Shavit Y, Lewis JW, et al. Intrinsic mechanisms of

pain inhibition: activation by stress. Science 1984; 226: 1270-72. Beecher HK. Pain in men wounded in battle. Ann Surg 1946;

123: 96-1053. Beecher HK. Relationship of significance of wound to pain

experienced. JAMA 1956; 161: 1609-134. Black J, Chesher GB, Starmer GA. The painlessness of the long

distance runner. Med J Aust 1979; 1: 522-35. Janal MN. Pain sensitivity, exercise and stoicism. J R Soc Med

1996; 89: 376-816. O’Connor PJ, Cook DB. Exercise and pain: the neurobiology,

measurement, and laboratory study of pain in relation to exercisein humans. Exerc Sport Sci Rev 1999; 27: 119-66

7. Pertovaara A, Huopaniemi T, Virtanen A, et al. The influenceof exercise on dental pain thresholds and the release of stresshormones. Physiol Behav 1984; 33: 923-6



8. Kemppainen P, Pertovaara A, Huopaniemi T, et al. Modificationof dental pain and cutaneous thermal sensitivity by exercisein man. Brain Res 1985; 360: 33-40

9. Kemppainen P, Pertovaara A, Huopaniemi T, et al. Elevation ofdental pain threshold induced in man by physical exercise isnot reversed by cyproheptadine-mediated suppression ofgrowth hormone release. Neurosci Lett 1986; 70: 388-92

10. Kemppainen P, Paalasmaa P, Pertovaara A, et al. Dexamethasoneattenuates exercise-induced dental analgesia in man. BrainRes 1990; 519: 329-32

11. Guillemin R, Vargo T, Rossier J, et al. Beta-endorphin and ad-renocorticotropin are secreted concomitantly by the pituitarygland. Science 1997; 197: 1367-9

12. Olausson B, Eriksson E, Ellmarker L, et al. Effects of naloxoneon dental pulp pain threshold following muscle exercise andlow frequency transcutaneous nerve stimulation: a comparativestudy in man. Acta Physiol Scand 1986; 126: 299-305

13. Droste C, Greenlee MW, Schreck M, et al. Experimental painthresholds and plasma beta-endorphin levels during exercise.Med Sci Sports Exerc 1991; 23: 334-42

14. Droste C, Meyer-Blankenburg M, Greenlee MW, et al. Effect ofphysical exercise on pain thresholds and plasma beta-endorphinsin patients with silent and symptomatic myocardial ischemia.Eur Heart J 1988; 9: 25-33

15. Guieu R, Blin O, Pouget J, et al. Nociceptive threshold andphysical activity. Can J Neurol Sci 1992; 19: 69-71

16. Padawer WJ, Levine FM. Exercise-induced analgesia: fact orartifact? Pain 1992; 48: 131-5

17. Pertovaara A, Kemppainen P. Comments on Padawer and Lev-ine [letter]. Pain 1992; 50: 239-40

18. Droste C, Greenlee MW. Comments on Padawer and Levine[letter]. Pain 1992; 50: 241

19. Janal MN, Colt EWD, Clark WC, et al. Pain sensitivity, moodand plasma endocrine levels in man following long distancerunning: effects of naloxone. Pain 1984; 19: 13-25

20. Sternberg WF, Bailin D, Grant M, et al. Competition alters theperception of noxious stimuli in male and female athletes.Pain 1998: 76: 231-8

21. Kemppainen P, Hamalainen O, Kononen M. Different effects ofphysical exercise on cold pain sensitivity in fighter pilots withand without the history of acute in-flight neck pain attacks.Med Sci Sports Exerc 1998; 30: 577-82

22. Fuller AK, Robinson ME. A test of exercise analgesia usingsignal detection theory and a within-subjects design. PerceptMot Skills 1993; 76: 1299-310

23. Haier RJ, Quaid K, Mills JSC. Naloxone alters pain perceptionafter jogging. Psychiatry Res 1981; 5: 231-2

24. Gurevich M, Kohn PM, Davis C. Exercise-induced analgesiaand the role of reactivity in pain sensitivity. J Sports Sci 1994;12: 549-59

25. Koltyn KF, Wertz AL, Gardiner RL, et al. Perception of pain fol-lowing aerobic exercise. Med Sci Sports Exerc 1996; 28: 1418-21

26. Vecchiet L, Marini I, Colozi A, et al. Effects of aerobic exerciseon muscular pain sensitivity. Clin Ther 1984; 6: 354-63

27. Bartholomew JB, Lewis BP, Linder DE, et al. Post-exercise anal-gesia: replication and extension. J Sports Sci 1996; 14: 329-34

28. Koltyn KF, Arbogast RW. Perception of pain after resistanceexercise. Br J Sports Med 1998; 32: 20-4

29. Kosek E, Ekholm J. Modulation of pressure pain thresholds duringand following isometric contractions. Pain 1995; 61: 481-6

30. Kosek E, Ekholm J, Hansson P. Modulation of pressure pain thres-holds during and following isometric contraction in patients withfibromyalgia and in healthy controls. Pain 1996; 64: 415-23

31. Bengtsson M, Bengsston A, Jorfeld L. Diagnostic epidural opioidblockade in primary fibromyalgia at rest and during exercise.Pain 1989; 39: 171-80

32. Paalasmaa P, Kemppainen P, Pertovaara A. Modulation of skinsensitivity by dynamic and isometric exercise in man. Eur JAppl Physiol 1991; 62: 279-85

33. Kojo I, Pertovaara A. The effects of stimulus area and adaptationtemperature on human heat pain and warm thresholds. Int JNeurosci 1987; 32: 875-80

34. Bodnar RJ, Kelly DD, Spiaggia KA, et al. Dose-dependent re-ductions by naloxone of analgesia induced by cold-water stress.Pharmacol Biochem Behav 1978; 8: 667-72

35. Willow M, Carmody J, Carroll P. The effects of swimming inmice on pain perception and sleeping time in response to hyp-notic drugs. Life Sci 1980; 26: 219-24

36. Christie MJ, Chesher GB, Bird KD. The correlation betweenswim-stress induced antinociception and [3H] Leu-enkephalinbinding to brain homogenates in mice. Pharmacol BiochemBehav 1981; 15: 853-7

37. Cooper K, Carmody J. The characteristics of the opioid-relatedanalgesia induced by the stress of swimming in the mouse.Neurosci Lett 1982; 31: 165-70

38. O’Connor P, Chipkin RE. Comparisons between warm and coldwater stress in mice. Life Sci 1984; 35: 631-9

39. Giradot MN, Holloway FA. Cold water stress analgesia in rats:differential effects of naltrexone. Physiol Behav 1984; 32: 547-55

40. Terman GW, Morgan MJ, Liebeskind JC. Opioid and non-opioidstress analgesia from cold water swim: importance of stressseverity. Brain Res 1986; 372: 161-71

41. Carmody J, Cooper K. Swim stress reduces chronic pain in micethrough an opioid mechanism. Neurosci Lett 1987; 74: 358-63

42. Tierney G, Carmody J, Jamieson D. Stress analgesia: the opioidanalgesia of long swims surpasses the non-opioid analgesiainduced by short swims in mice. Pain 1991; 46: 89-95

43. Shyu BC, Andersson SA, Thoren P. Endorphin mediated in-crease in pain threshold induced by long-lasting exercise inrats. Life Sci 1982; 30: 833-40

44. Hoffman P, Skarphedinsson JO, Delle M, et al. Electrical stimula-tion of the gastrocnemius muscle in the spontaneously hyper-tensive rat increases the pain threshold: role of serotonergicreceptors. Acta Physiol Scand 1990; 138: 125-31

45. Yao T, Andersson S, Thoren P. Long-lasting cardiovascular de-pressor response following sciatic stimulation in spontaneouslyhypertensive rats: evidence for the involvement of central en-dorphin and serotonin systems. Brain Res 1982; 244: 295-303

46. Marek P, Mogil JS, Sternberg WF, et al. N-Methyl-D-Aspartic acid(NMDA) receptor antagonist MK-801 blocks non-opioid stress-induced analgesia: II. Comparison across three swim-stress par-adigms in selectively bred mice. Brain Res 1992; 578: 197-203

47. Riley JL, Robinson ME, Wise EA, et al. Sex differences in theperception of noxious experimental stimuli: a meta-analysis.Pain 1998; 74: 181-7

48. Fillingim RB, Maixner W. Gender differences in the responsesto noxious stimuli. Pain Forum 1995; 4: 209-21

49. Berkley KJ. From psychophysics to the clinic? Pain Forum1995; 4: 225-7

Correspondence and offprints: Kelli Koltyn, Department ofKinesiology, 2000 Observatory Drive, University of Wiscon-sin, Madison, WI 53706-1189, USA.E-mail: [email protected]

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Analgesia Following Exercise- A Review

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