Temporal summation of pain from skin,muscle and joint following nociceptive ultrasonic stimulation in humans

This study investigated the phenomenon of temporal summation in response to repetitive focused ultrasound stimulation of skin, muscle and joint in human volunteers. Stimulation was carried out using a custom-designed, focused ultrasonic stimulator with a resonant frequency of 1.66 MHz. A series of stand-off attachments were used to ensure that the focal region of the ultrasound beam projected either cutaneously, within the distal interphalangeal joint of the index finger, or within the first dorsal interosseous muscle. Stimulation was carried out using single pulses and trains of five pulses of different pulse durations (25 ms, 50 ms, 75 ms, 100 ms), and using single pulses and trains of five pulses (50 ms duration) at different frequencies (0.5 Hz, 1 Hz, 2 Hz, 3 Hz, 4 Hz, 5 Hz). Tactile perception thresholds, pain thresholds and summation pain thresholds were recorded. Temporal summation of pain could be elicited by stimulation of both skin, joint and muscle, although the influence of temporal summation appeared to be more pronounced for muscle stimulation. Muscle stimulation also required greater ultrasound intensity compared with joint and skin stimulation. Temporal summation could not be elicited by tactile, low-intensity stimulation. Focused ultrasound is a potent, noninvasive technique with which to investigate temporal summation from somatic structures. A number of factors may account for the higher intensities required to elicit pain in muscle and the increased rate of temporal summation. It is clear, however, that if temporal summation is more pronounced in muscle than other tissues then this may be an important factor contributing to pain in musculoskeletal syndromes.     

Muscle pain in neuromuscular disorders and primary fibromyalgia

Summary Muscle fibre degeneration and regeneration, inflammation in intramuscular connective tissue and hypoxia in resting muscle are not necessarily associated with pain. However, when sustained or dynamic muscle contractions are performed in an ischaemic muscle, severe pain develops. In the chronic muscle pain syndrom called fibromyalgia (or fibrositis) the most likely cause of the pain is a combination of muscle tension and muscle hypoxia. This conclusion is supported by the finding of a pathological distribution of tissue oxygen tension in painful muscles and a subjective feeling of muscle tension and muscle stiffness in the majority of patients. A decrease in high energy phosphates is found in biopsies from painful muscle. The most characheristic morphological finding is the so called ragged red fibre, which is a finding that can been seen in mitochondrial disorders. The morphological and chemical findings are possibly a consequence of a long standing hypoxia. The possibility that activity in muscle sympathetic nerves is important for the development of chronic muscle pain is discussed.     

Estimation of Musculotendon Properties in the Human Upper Limb

The purpose of this study was to develop and apply a general method for estimating the architectural properties of human muscles in vivo. The method consists of a two-phase, nested optimization procedure in which the values of peak isometric force, optimal muscle-fiber length, and tendon slack length are calculated for each musculotendon actuator, knowing muscle volume and the minimum and maximum physiological lengths of the actuator. In phase I, the positions of the bones and the activation levels of the muscles are found by maximizing the isometric torque developed for each degree of freedom at each joint. In phase II, the architectural properties of each musculotendon actuator are found by matching the strength profile of the model to that measured for subjects. The method is used to estimate the architectural properties of 26 major muscle groups crossing the shoulder, elbow, and wrist. Wherever possible, the model calculations are compared against measurements obtained from anatomical studies reported in the literature. Architectural data obtained from our work should be useful to researchers interested in developing musculoskeletal models of the upper limb. © 2003 Biomedical Engineering Society. PAC2003: 8719Rr, 8710+e, 8719Ff     

Development and validation of the therapeutic alliance in physiotherapy questionnaire for patients with chronic musculoskeletal pain

ObjectiveThe purpose of this study is to present the development and analysis of the factorial structure and psychometric properties of a new self-administered questionnaire (Therapeutic Alliance in Physiotherapy Questionnaire-Patients [CAF-P]) designed to measure therapeutic alliance in physiotherapy.MethodsThe sample included 204 patients with chronic pain attending nine primary care centres. The CAF-P was developed and validated using standard methodology, which included developing items, cognitive debriefing and psychometric validation.ResultsCAF-P has excellent internal consistency, with Cronbach’s α of 0.91 and an intraclass correlation coefficient (ICC) of 0.87. We propose a structure of two factors that explain 55.80 % of the variance. The convergent validity showed a moderate positive correlation with the probability of recommending treatment and with the level of satisfaction.ConclusionsThe CAF-P appears to be a valid and reliable instrument for measuring the therapeutic alliance perceived by patients in physiotherapy.Practice implications: The results of the present study leads to further research to identify the differences in the therapeutic alliance construct between different settings or professions.     

Effects of catastrophizing on pain perception and pain modulation

The multidimensional experience of pain is thought to be partially influenced by the pain modulation system as well as by individual psychological components. Recent studies demonstrated possible common neural network mediating both domains. The present study examined the relationships between pain perception, pain modulation, and catastrophizing in healthy subjects. Forty-eight participants (29 females and 19 males) completed the pain catastrophizing scale (PCS) and underwent psychophysical tests in order to evaluate the modulation of pain, using the diffuse noxious inhibitory control (DNIC) paradigm. Contact heat pain (47.0°C applied for 1 min), which was used as the “test” stimulation, was applied before and after a physical effort that induces pain (repeated squeezing of a hand grip device), which was used as a “conditioning” stimulus. Numeric pain scale intensities (NPS, 0–10) were evaluated four times during each of two separate consecutive runs of heat stimulation. Results showed a significant positive correlation of PCS with heat pain (r = 0.48, p < 0.0005) and with muscle pain (r = 0.31, p = 0.03). In addition, significant negative correlations were found between PCS and DNIC effect (r = −0.34, p = 0.02). Moreover, once catastrophizing was entered into the regression analysis, the previously significant effect of gender was no longer found. In conclusion, individuals with high catastrophizing levels demonstrated higher pain intensities and lower effects of DNIC indicating that catastrophizing might have a significant impact on pain perception via an association with pain modulation.     

Effects of neonatal testosterone treatment on sex differences in formalin-induced nociceptive behavior in rats

There are sex differences in nociceptive behavior induced by formalin in rats. To determine whether these sex differences are the result of the sexual differentiation of the brain, that is masculinization and defeminization [A.P. Arnold, R.A. Gorski, Gonadal steroid induction of structural sex differences in the central nervous system, Annu. Rev. Neurosci. 7 (1984) 413–442; M.M. McCarthy, A.T.M. Konkle, When is a sex difference not a sex difference? Front Neuroendocrinol. 26 (2005) 85–102], some female rats were injected with testosterone propionate (TP, 100 μg/25 μl/rat) on the day of birth and on the following day. As controls, other female rats and all male rats were injected with the same volume of sesame oil. They were castrated at the age of 8 weeks, and implanted with a silicon tube containing 20% of 17β-estradiol or cholesterol. Two weeks after the implantation, rats were injected with 50 μl of 2% formalin in the right hind paw and their behavioral changes were observed for 1 h. In cholesterol-implanted rats, all rats exhibited three typical phases of pain response and there were no significant differences in the scores of nociceptive behavior. In 17β-estradiol implanted rats, female and TP-treated female rats had a significantly higher score of nociceptive behavior than male rats. These results indicate that estrogen produces sex differences in nociceptive behavior induced by formalin, and suggest that these differences are not due to the sexual differentiation of the brain, since the dose and the timing of the TP treatment effectively defeminize and masculinize female rats. Alternatively, sexual differentiation of the brain response to formalin-induced nociceptive behavior may be different from ordinary sexual differentiation.     

Psychological factors and self-reports of muscle pain

Summary Factorial analyses of subjectively felt health complaints in a population of 400 males and 74 females revealed nine orthogonal (independent) factors. One factor (Factor 4) involved pain in the neck, pain in the back, pain in arms and shoulders, and migraine. This type of complaint did not relate to anxiety and depression. The prevalence of muscle pains varied between the sexes, and the types of occupations. Shiftwork was also important. 54% of the women and 40% of the men in the total population had some forms of muscle pain, but only 8% of the women and 3% of the men felt this to be a really serious problem. Psychological factors explained only moderate amounts of variance of muscle pain when the population was taken as a whole. However, within each type of occupation, psychological factors explained a considerable amount of the variance.     

Modulation of stretch-evoked reflexes in single motor units in human masseter muscle by experimental pain

The interaction between muscle pain and motor function of the jaw has been examined in recent years, but the nature of the modulation of the short-latency stretch reflex by pain is not fully understood. In this study, the reflex responses to stretch were measured in single low-threshold motor units that were kept discharging at a constant frequency, before, during and after the induction of experimental pain in one masseter muscle by controlled infusion of hypertonic saline. The probability of evoking a reflex response in individual motor units in the painful muscle at near-monosynaptic latency was reduced by a mean of about 20%. However, the overall reflex response in the surface electromyogram of both the ipsi- and contralateral masseter muscles was greater during pain. This was apparently a secondary response to the pain-induced increase in pre-stimulus activity in the motoneurone pools of both muscles, because increased motoneurone excitability may facilitate stretch reflexes. It is concluded that the most likely explanation for the reduced reflex response of low-threshold masseter motor units during experimental pain is a tonic reduction in the fusimotor drive to the masseter spindles.     

Sex-related ERP differences in deviance detection.

The effect of sex on neural mechanisms of auditory mismatch detection was examined using dense sensor array (128 channel) event-related potential recordings (ERPs). ERPs of 32 right-handed subjects (16 males) were recorded to frequent (85%, 880 Hz) and infrequent (15%, 1480 Hz) tones. There were no sex differences in mismatch negativity (80-180 ms), however, the fronto-central P2 (180-260 ms) was less positive in males (F=12.56, P<0.005) and the N2 (260-340 ms) was more negative in males (F=6.28, P<0.05). The increased negativity in males spanning the P2 and N2 may index a top-down process of attention bias towards novelty. This result supports the hypothesis of an adaptive, sexually dimorphic processing of novel events in humans.     

Skeletal muscle damage: a study of isotope uptake,enzyme efflux and pain after stepping

Summary We have studied the occurrence of skeletal muscle uptake of ^99mtechnetium pyrophosphate (Tc-PYP), creatine kinase (CK) release and muscle pain in normal subjects after exercise. Five subjects stepped on and off a high bench in such a way that one leg stepped up and the other down. Pain only developed in the muscles used for descending: quadriceps, adductors and gluteal muscles of one leg and the calf muscle of the other. A large rise in plasma CK occurred in four subjects but no increased Tc-PYP muscle uptake was seen in the quadriceps. In the four subjects with high CK effluxes, increased isotope uptake was seen in the thigh adductors used when stepping down; in the two subjects with the largest CK effluxes there was extensive uptake into the gluteal muscles. Muscle pain preceded and was not well correlated with either the magnitude of the enzyme release or the amount and distribution of increased muscle isotope uptake. We conclude that delayed onset muscle pain, the cause of which remains unknown, is a poor indicator of muscle damage as indicated by circulating muscle enzymes and muscle isotope uptake. Tc-PYP uptake by skeletal muscle can provide useful information about the localisation and time course of muscle damage.     

Differential cerebral responses to aversive auditory arousal versus muscle pain: specific EEG patterns are associated with human pain processing

The specificity of electroencephalogram (EEG) activity in relation to processing of human pain needs further elucidation. This study was designed to determine if nociceptive input and general arousal responses to external stimulation exert different effects on EEG activity. Continuous aversive auditory stimuli (90 dB for 2 min) and painful injection of hypertonic saline (5.8%, 0.2 ml) into the left brachioradialis muscle were administered to 12 male subjects during separate sessions in a counterbalanced design. Intensity, arousal and unpleasantness were assessed during the muscle pain and auditory stimulation using a visual analogue scale and arousal-affective scales. The EEG data (32 channels) was acquired before, during and after application of painful and aversive auditory stimuli. Aversive auditory stimulation and intramuscular injection of hypertonic saline induced similar degrees of arousal and unpleasantness associated with a similarity of intensity of sensation of pain and auditory sensation. However, muscle pain induced a significant decrease of alpha-1 activity (8–14 Hz) at T6, PC2, PC6, Pz, P4, O2 and POz sites compared to the baseline, but aversive auditory stimulation did not produce any significant changes in alpah-1 activity compared to baseline. The alpha-1 EEG powers at P3, Pz, P4, PC1, PC2 and POz, and alpha-2 at Pz and POz sites were significantly decreased during muscle pain when compared with aversive noise stimulation. These results indicate that specific EEG patterns are associated with human pain processing. Electronic Publication     

The consequences of eccentric contractions and their relationship to delayed onset muscle pain

Summary Exercise can cause muscle pain for a number of reasons. Usually the pain is experienced during the exercise and recovers rapidly afterwards. There is one type of muscle pain that has a very different and characteristic time course. In this situation the exercise itself, and the immediate post-exercise period are painfree. The pain is not felt for about eight hours and is maximal 1 or 2 days later. Delayed onset muscle pain occurs after unaccustomed, high force contractions and is particularly associated with eccentric contractions. The concensus of opinion is that the pain is caused by some form of damage, but the mechanism for the pain is not known. This review summarises the literature on the consequences of eccentric contractions and relates them to delayed onset muscle pain. There is clear evidence of damage to the muscle fibres themselves, their membranes and, at a later stage, mononuclear cell infiltration, but all these have very different time courses and none are the same as the pain. Intramuscular pressures are raised in some, but not all, painful compartments and even when raised follow a different time course to the pain. Anti-inflammatory agents do not affect the pain, but due to the incomplete understanding of the action of these drugs, the role of inflammation in delayed onset muscle pain is uncertain.Despite the considerable evidence of damage after eccentric contractions, the cause of delayed onset muscle pain is still unknown.     

Experimental muscle pain changes motor control strategies in dynamic contractions

This study investigated the effect of muscle pain on muscle activation strategies during dynamic exercises. Ten healthy volunteers performed cyclic elbow flexion/extension movements at maximum speed for 2 min after injection of (1) hypertonic (painful) saline in the biceps brachii, (2) hypertonic saline in both biceps brachii and triceps brachii, and (3) isotonic (nonpainful) saline in the biceps brachii muscle. Surface electromyographic (EMG) signals were collected from the upper trapezius, biceps brachii, triceps brachii, and brachioradialis muscles (to estimate EMG amplitude) and with an electrode arrays from biceps brachii (to estimate muscle fiber conduction velocity [CV]). In all conditions, the acceleration of the movement decreased throughout the exercise, and kinematic parameters were not altered by pain. With respect to the control condition, pain induced a decrease of the biceps brachii (mean ± SE, –23±4%) and brachioradialis (–10±0.4%) integrated EMG (IEMG) in the beginning of the exercise, and an increase (45±3.5%) of the upper trapezius IEMG at all time points during the exercise. The biceps brachii IEMG decreased over time during the nonpainful exercises (–11±0.6%) while it remained constant in the painful condition. Biceps brachii CV decreased during painful conditions (–12.8±2.2%) while it remained constant during the nonpainful condition. In conclusion, muscle pain changes the motor control strategy to sustain the required dynamic task both in the relative contribution between synergistic muscles and in the motor unit activation within the painful muscle. Such a changed motor strategy may be highly relevant in models of occupational musculoskeletal pain conditions.     

Effects of muscle fatigue induced by low-level clenching on experimental muscle pain and resting jaw muscle activity: gender differences

The purpose of this study was to investigate the effects of jaw-muscle fatigue evoked by low-level tooth-clenching followed by the induction of experimental muscle pain by injection of glutamate on the perception of fatigue and pain and on the resting electromyographic (EMG) activity. In addition, the role of gender on these interactions was studied. The EMG activities of bilateral masseter (MAL, MAR) and temporalis (TAL, TAR) muscles in 11 healthy young women and 12 men were measured before (Baseline) and after tooth-clenching for 30 min at 10% of maximal force (Post1), after subsequent glutamate (Glu) or isotonic saline (Iso) injection into the MAL following the tooth-clenching (Post2) and 60 min after tooth-clenching (Post3). The intensities of fatigue, fatigue-related muscle pain and headache-like symptoms were scored on 0–10 cm visual analog scales (VAS). The glutamate-evoked pain was continuously scored on an electronic VAS. Sustained low-level tooth-clenching consistently produced fatigue sensation, fatigue-related muscle pain and headache-like symptoms in both genders with significantly higher fatigue VAS scores in men than in women, while the accompanying increase in the resting EMG activity appears higher in women than in men in the masseter muscles. In this study no gender differences were found for the perceived amount of experimental pain induced by glutamate injection. Additional increases of the resting EMG activity after injections occurred only in men in the injected masseter muscle and non-injected temporalis muscles. The present findings provide new information on the complex influence of gender on sensory-motor integration in the trigeminal system which may contribute to differences in susceptibility to develop musculoskeletal pain problems.     

Back extensor muscle oxygenation and fatigability in healthy subjects and low back pain patients during dynamic back extension exertion

The purpose of this study was to assess if chronic low back pain patients have impaired paraspinal muscle O₂ turnover and endurance capacity as compared to healthy control subjects during dynamic exercise. Middle-aged healthy male subjects (n = 12, control) and male patients with chronic low back pain (n = 17, CLBP) participated in the study. L4–L5 level paraspinal muscle fatigue was objectively assessed during earlier validated 90 s dynamic back endurance test (spectral EMG, MPF_slope). Also EMG amplitude (EMG_amplitude) and initial MPF (MPF_initial) were assessed from the initial 5 s of the endurance contraction. Simultaneously near infrared spectroscopy (NIRS) was used for quantitative measurement of local L4–L5 paraspinal muscle O₂ consumption. Subcutaneous tissue thickness (ATT) was measured from the EMG and NIRS recording sites. The results indicated that control and CLBP groups were compatible as regarding anthropometric variables, paraspinal muscle activation levels (EMG_amplitude), initial MPF (MPF_initial) and ATT. When the ATT was used as a covariate in the ANOVA analysis, CLBP group did not show significantly greater paraspinal muscle fatigability (right MPF_slope – 12.2 ± 10.7%/min, left right MPF_slope – 12.6 ± 13.3%/min) or O₂ consumption (right NIRS_slope – 52.8 ± 79.6 μM/l/s) as compared to healthy controls (right MPF_slope – 11.9 ± 7.6%/min, left MPF_slope – 12.7 ± 8.6%/min, right NIRS_slope – 53.7 ± 95.2 μM/l/s). As a conclusion, these CLBP male patients did not show any impaired rate of paraspinal muscle oxygen consumption or excessive paraspinal muscle fatigability during dynamic exercise as compared with healthy controls. Subcutaneous tissue thickness has a strong influence on the NIRS and EMG amplitude measurements and, if unchecked, it could result in the false interpretation of the results.     

Hypotheses of peripheral and central mechanisms underlying occupational muscle pain and injury

Summary In an overview of the problem of occupational muscle pain the evidence indicates that injury is more common the greater the load and the worse the posture in which the work is performed. The commonest are backstrains or ligament or joint damage due to overuse. Fatigue is associated with alterations in energy metabolites in muscle while pain is often due to microscopical damage to the cellular architecture. The progress of pathological changes in muscle following occupational injury may be similar to those seen in primary fibromyalgia (fibrositis) because of a final common pathway involving calcium-induced secondary damage.Occupational muscle pain frequently occurs in the muscles supporting the upper limb girdle and head in workers engaged in repetitively performing skilled manipulations or activities requiring high or sustained mental concentration. It is suggested that both occupational myalgia of this kind may be due to an imbalance in the use of muscles for postural activity (holding or supporting fine movements) compared to phasic use in dynamic work. While there are undoubtedly muscular indications of damage these may be secondary to alterations in (unconscious) central motor control mechanisms.Idiosyncratic Review Article based on Keynote Address to open International Symposium on Occupational Pain and Injury Sundvollen Hotel, Near Oslo, Norway, 5th October 1986     

Effects of local and remote muscle pain on human jaw reflexes evoked by fast stretches at different clenching levels

Muscle pain imposes significant changes on natural motor tasks, but the consequences for stretch reflexes are still disputed. The present study examined the jaw reflexes to fast (10 ms) stretches of the mandible in an experimental model with local pain in the masseter muscle and remote pain in the tibialis anterior muscle. The stretch reflexes were elicited in healthy volunteers (n=13) before, during, and after periods with constant levels of experimental pain and while the subjects clenched at 0%, 15%, 30%, and 45% of the maximal voluntary contraction (MVC) levels. Surface electromyography (EMG) was used to record the reflex responses. Pain in the masseter muscle (mean ± SEM, 3.8±0.4 on a 10-cm visual analogue scale), but not in the tibialis anterior muscle (3.4±0.3; paired t-test, P=0.318) was associated with significant changes in both prestimulus EMG activity (ANOVA, P=0.002) and in peak-to-peak amplitudes of the stretch reflex (ANOVA, P=0.022). However, when the changes in prestimulus EMG activity were taken into consideration a significant increase in the stretch reflex persisted in the painful muscle at 15% and 30% MVC. Local circuits at the trigeminal level involving the fusimotor system are proposed to mediate a significant part of this modulatory effect. Electronic Publication     

The influence of experimentally induced pain on shoulder muscle activity

Muscle function is altered in painful shoulder conditions. However, the influence of shoulder pain on muscle coordination of the shoulder has not been fully clarified. The aim of the present study was to examine the effect of experimentally induced shoulder pain on shoulder muscle function. Eleven healthy men (range 22–27 years), with no history of shoulder or cervical problems, were included in the study. Pain was induced by 5% hypertonic saline injections into the supraspinatus muscle or subacromially. Seated in a shoulder machine, subjects performed standardized concentric abduction (0°–105°) at a speed of approximately 120°/s, controlled by a metronome. During abduction, electromyographic (EMG) activity was recorded by intramuscular wire electrodes inserted in two deeply located shoulder muscles and by surface-electrodes over six superficially located shoulder muscles. EMG was recorded before pain, during pain and after pain had subsided and pain intensity was continuously scored on a visual analog scale (VAS). During abduction, experimentally induced pain in the supraspinatus muscle caused a significant decrease in activity of the anterior deltoid, upper trapezius and the infraspinatus and an increase in activity of lower trapezius and latissimus dorsi muscles. Following subacromial injection a significantly increased muscle activity was seen in the lower trapezius, the serratus anterior and the latissimus dorsi muscles. In conclusion, this study shows that acute pain both subacromially and in the supraspinatus muscle modulates coordination of the shoulder muscles during voluntary movements. During painful conditions, an increased activity was detected in the antagonist (latissimus), which support the idea that localized pain affects muscle activation in a way that protects the painful structure. Further, the changes in muscle activity following subacromial pain induction tend to expand the subacromial space and thereby decrease the load on the painful structures.     

Human intramuscular and cutaneous pain: psychophysical comparisons

 We used psychophysical methods to compare the central processing of nociceptive inputs from skin and muscle in ten normal humans. Both intramuscular electrical and infrared CO₂ laser cutaneous stimulation showed increasing but decelerating (downward concave) stimulus-response curves and similar temporal summation characteristics. Intramuscular stimulation was rated significantly more unpleasant than cutaneous stimulation. The results are consistent with a common mode of central nociceptive processing for skin and muscle pain intensity but suggest a relatively larger activation of affective mechanisms by muscle afferents. Received: 30 July 1996 / Accepted: 28 November 1996     

Sex-related differences in thermoregulatory responses while wearing protective clothing

This study examined the thermoregulatory responses of men (group M) and women (group F) to uncompensable heat stress. In total, 13?M [mean (SD) age 31.8 (4.7) years, mass 82.7 (12.5)?kg, height?1.79?(0.06)?m, surface area to mass ratio 2.46?(0.18)?m²?·?kg^?1?·?10^?2, Dubois surface area 2.01 (0.16)?m², %body fatness 14.6 (3.9)%, V˙O_2peak 49.0?(4.8)?ml?·?kg^?1?·?min^?1] and 17 F [23.2 (4.2) years, 62.4 (7.7)?kg, 1.65 (0.07)?m, 2.71 (0.14)?m²?·?kg^?1?·?10^?2, 1.68 (0.13)?m², 20.2 (4.8)%, 43.2 (6.6)?ml?·?kg^?1?·?min^?1, respectively] performed light intermittent exercise (repeated intervals of 15?min of walking at 4.0?km?·?h^?1 followed by 15?min of seated rest) in the heat (40°C, 30% relative humidity) while wearing nuclear, biological, and chemical protective clothing (0.29?m²?·°C · W^?1 or 1.88 clo, Woodcock vapour permeability coefficient 0.33?i _m). Group F consisted of eight non-users and nine users of oral contraceptives tested during the early follicular phase of their menstrual cycle. Heart rates were higher for F throughout the session reaching 166.7 (15.9) beats?·?min^?1 at 105?min (n?=?13) compared with 145.1 (14.4)?beats?·?min^?1 for M. Sweat rates and evaporation rates from the clothing were lower and average skin temperature ( ) was higher for F. The increase in rectal temperature (T _re) was significantly faster for the F, increasing 1.52 (0.29)°C after 105?min compared with an increase of 1.37?(0.29)°C for M. Tolerance times were significantly longer for M [142.9?(24.5)?min] than for F [119.3?(17.3)?min]. Partitional calorimetric estimates of heat storage (S) revealed that although the rate of S was similar between genders [42.1?(6.6) and 46.1?(9.7) W?·?m^?2 for F and M, respectively], S expressed per unit of total mass was significantly lower for F [7.76?(1.44)?kJ?·?kg^?1] compared with M [9.45?(1.26) kJ?·?kg^?1]. When subjects were matched for body fatness (n?=?8?F and 8?M), tolerance times [124.5?(14.7) and 140.3?(27.4)?min for F and M, respectively] and S [8.67?(1.44) and 9.39?(1.05)?kJ?·?kg^?1 for F and M, respectively] were not different between the genders. It was concluded that females are at a thermoregulatory disadvantage compared with males when wearing protective clothing and exercising in a hot environment. This disadvantage can be attributed to the lower specific heat of adipose versus non-adipose tissue and a higher percentage body fatness.