Exercise-induced pain within endurance exercise settings: Definitions, measurement, mechanisms and potential interventions.

Pain can be defined as an unpleasant sensory and emotional experience associated with or resembling that associated with actual or potential tissue damage. Though consistent with this definition, different types of pain result in different behavioural and psychophysiological responses. For example, the transient, non-threatening, acute muscle pain element of exercise-induced pain (EIP) is entirely different from other pain types like delayed onset muscle soreness, muscular injury or chronic pain. However, studies often conflate the definitions or assume parity between distinct pain types. Consequently, the mechanisms through which pain might impact exercise behaviour across different pain subcategories may be incorrectly assumed, which could lead to interventions or recommendations that are inappropriate. Therefore, this review aims to distinguish EIP from other subcategories of pain according to their aetiologies and characteristics, thereby providing an updated conceptual and operational definition of EIP. Secondly, the review will discuss the experimental pain models currently used across several research domains and their relevance to EIP with a focus on the neuro-psychophysiological mechanisms of EIP and its effect on exercise behaviour and performance. Finally, the review will examine potential interventions to cope with the impact of EIP and support wider exercise benefits. HIGHLIGHTS: What is the topic of this review? Considerations for future research focusing on exercise-induced pain within endurance exercise settings. What advances does it highlight? An updated appraisal and guide of research concerning exercise-induced pain and its impact on endurance task behaviour, particularly with reference to the aetiology, measurement, and manipulation of exercise-induced pain.

Elevated muscle pain induced by a hypertonic saline injection reduces power output independent of physiological changes during fixed perceived effort cycling.

Pain is a naturally occurring phenomenon that consistently inhibits exercise performance by imposing unconscious, neurophysiological alterations (e.g., corticospinal changes) as well as conscious, psychophysiological pressures (e.g., shared effort demands). Although several studies indicate that pain would elicit lower task outputs for a set intensity of perceived effort, no study has tested this. Therefore, this study investigated the impact of elevated muscle pain through a hypertonic saline injection on the power output, psychophysiological, cerebral oxygenation, and perceptual changes during fixed perceived effort exercise. Ten participants completed three visits (1 familiarization + 2 fixed perceived effort trials). Fixed perceived effort cycling corresponded to 15% above gas exchange threshold (GET) [mean rating of perceived effort (RPE) = 15 "hard"]. Before the 30-min fixed perceived effort exercise, participants received a randomized bilateral hypertonic or isotonic saline injection in the vastus lateralis. Power output, cardiorespiratory, cerebral oxygenation, and perceptual markers (e.g., affective valence) were recorded during exercise. Linear mixed-model regression assessed the condition and time effects and condition × time interactions. Significant condition effects showed that power output was significantly lower during hypertonic conditions [t107 = 208, P = 0.040, ß = 4.77 W, 95% confidence interval (95% CI) [0.27 to 9.26 W]]. Meanwhile, all physiological variables (e.g., heart rate, oxygen uptake, minute ventilation) demonstrated no significant condition effects. Condition effects were observed for deoxyhemoglobin changes from baseline (t107 = -3.29, P = 0.001, ß = -1.50 ΔµM, 95% CI [-2.40 to -0.61 ΔµM]) and affective valence (t127 = 6.12, P = 0.001, ß = 0.93, 95% CI [0.63 to 1.23]). Results infer that pain impacts the self-regulation of fixed perceived effort exercise, as differences in power output mainly occurred when pain ratings were higher after hypertonic versus isotonic saline administration.NEW & NOTEWORTHY This study identifies that elevated muscle pain through a hypertonic saline injection causes significantly lower power output when pain is experienced but does not seem to affect exercise behavior in a residual manner. Results provide some evidence that pain operates on a psychophysiological level to alter the self-regulation of exercise behavior due to differences between conditions in cerebral deoxyhemoglobin and other perceptual parameters.

Acute hypoalgesic, neurophysiological and perceptual responses to low-load blood flow restriction exercise and high-load resistance exercise.

This study compared the acute hypoalgesic and neurophysiological responses to low-load resistance exercise with and without blood flow restriction (BFR), and free-flow, high-load exercise. Participants performed four experimental conditions where they completed baseline measures of pain pressure threshold (PPT), maximum voluntary force (MVF) with peripheral nerve stimulation to determine central and peripheral fatigue. Corticospinal excitability (CSE), corticospinal inhibition and short interval intracortical inhibition (SICI) were estimated with transcranial magnetic stimulation. Participants then performed low-load leg press exercise at 30% of one-repetition maximum (LL); low-load leg press with BFR at 40% (BFR40) or 80% (BFR80) of limb occlusion pressure; or high-load leg press of four sets of 10 repetitions at 70% one-repetition maximum (HL). Measurements were repeated at 5, 45 min and 24 h post-exercise. There were no differences in CSE or SICI between conditions (all P > 0.05); however, corticospinal inhibition was reduced to a greater extent (11%-14%) in all low-load conditions compared to HL (P < 0.005). PPTs were 12%-16% greater at 5 min post-exercise in BFR40, BFR80 and HL compared to LL (P ≤ 0.016). Neuromuscular fatigue displayed no clear difference in the magnitude or time course between conditions (all P > 0.05). In summary, low-load BFR resistance exercise does not induce different acute neurophysiological responses to low-load, free-flow exercise but it does promote a greater degree of hypoalgesia and reduces corticospinal inhibition more than high-load exercise, making it a useful rehabilitation tool. The changes in neurophysiology following exercise were not related to changes in PPT.

Remote ischaemic preconditioning increase tolerance to experimentally induced cold pain.

Ischaemic preconditioning (IPC) applied locally and remotely has been shown to reduce pain which may underpin its ergogenic effect on exercise performance, however, it is unclear how many IPC cycles are needed to induce hypoalgesia. Therefore the purpose of this study was to examine the number of cycles of IPC on experimental pain perception. Sixteen healthy participants underwent four, randomised, experimental sessions where they either underwent a sham protocol (1 × 5 min at 20 mmHg), and 1, 2 or 3 cycles × 5 min of remote IPC at 105% of limb occlusion pressure. Ten minutes post-intervention, participants underwent a cold-pressor test where pain threshold, pain tolerance and pain intensity were examined and compared between conditions with a one-way repeated measure analysis of variance. Pain threshold was not different between conditions (P = 0.065); but pain tolerance was increased by ∼30% in the 1 × 5 condition, 2 × 5 condition, and 3 × 5 condition compared to the sham condition. No differences in pain tolerance were seen between the different numbers of cycles (all P > 0.05). There was also no difference in the perception of pain 30 s into the cold pressor test (P = 0.279). Remote IPC appears to significantly improve tolerance to pain which may have significant implications for endurance performance and exercise rehabilitation, but this warrants further investigation.

We found that one, two or three cycles of ischaemic preconditioning improved cold pain tolerance by 30% compared to a sham protocol, but there was no clear effect of IPC on pain threshold or pain intensity.The pain reported during IPC decreased from cycle one to cycle three in the three cycle condition, suggesting a potential conditioned pain modulation effect.An increase in pain tolerance may explain why IPC can improve exercise performance and IPC itself could be used as a tool to improve tolerance to pain.

Intra- and interindividual reliability of muscle pain induced by an intramuscular injection of hypertonic saline injection into the quadriceps.

BACKGROUND: Intramuscular injections of hypertonic saline are commonly used to induce experimental muscle pain, but reliability data on this technique are lacking. This study investigated the intra- and interindividual reliability of pain measures from a hypertonic saline injection into the vastus lateralis. METHODS: Fourteen healthy participants (6 female) attended three laboratory visits where they received an intramuscular injection of 1 mL hypertonic saline into the vastus lateralis. Changes in pain intensity were recorded on an electronic visual analogue scale, and pain quality was assessed after pain had resolved. Reliability was assessed with the coefficient of variation (CV), minimum detectable change (MDC) and intraclass correlation coefficient (ICC) with 95% CIs. RESULTS: Mean pain intensity displayed high levels of intraindividual variability (CV = 16.3 [10.5-22.0]%) and 'poor' to 'very good' relative reliability (ICC = 0.71 [0.45-0.88]) but had a MDC of 11 [8-16] au (out of 100). Peak pain intensity exhibited high levels of intraindividual variability (CV = 14.8 [8.8-20.8]%) with 'moderate' to 'excellent' levels of relative reliability (ICC = 0.81 [0.62-0.92]), whereas the MDC was 18 [14-26] au. Measures of pain quality exhibited good reliability. Interindividual variability in pain measures was high (CV > 37%). CONCLUSIONS: Intramuscular injections of 1 mL of hypertonic saline into the vastus lateralis display substantial levels of interindividual variability, but MDC is below the clinically important changes in pain. This model of experimental pain is suitable for studies involving repeated exposures. SIGNIFICANCE: Many pain research studies have performed intramuscular injections of hypertonic saline to investigate responses to muscle pain. However, the reliability of this technique is not well established. We examined the pain response over three repeated sessions of a hypertonic saline injection. The pain induced by hypertonic saline has considerable interindividual variability but has largely acceptable intraindividual reliability. Therefore, the injections of hypertonic saline to induce muscle pain are a reliable model of experimental muscle pain.

The effect of hypertonic saline evoked muscle pain on neurophysiological changes and exercise performance in the contralateral limb.

Non-local muscle pain may impair endurance performance through neurophysiological mechanisms, but these are relatively unknown. This study examined the effects of muscle pain on neuromuscular and neurophysiological responses in the contralateral limb. On separate visits, nine participants completed an isometric time to task failure (TTF) using the right knee extensors after intramuscular injection of isotonic saline (CTRL) or hypertonic saline (HYP) into the left vastus lateralis. Measures of neuromuscular fatigue were taken before, during and after the TTF using transcranial magnetic stimulation (TMS) and peripheral nerve stimulation. Mean pain intensity was greater in the left leg in HYP (3.3 ± 1.9) compared to CTRL (0.4 ± 0.7; P < 0.001) which was combined with a reduced TTF by 9.8% in HYP (4.54 ± 0.56 min) compared to CTRL (5.07 ± 0.77 min; P = 0.005). Maximum voluntary force was not different between conditions (all P > 0.05). Voluntary activation was lower in HYP compared to CTRL (P = 0.022). No difference was identified between conditions for doublet amplitude (P > 0.05). Furthermore, no difference in MEP·Mmax-1 or the TMS silent period between conditions was observed (all P > 0.05). Non-local pain impairs endurance performance of the contralateral limb. This impairment in performance is likely due to the faster attainment of the sensory tolerance limit from a greater amount of sensory feedback originating from the non-exercising, but painful, left leg.

The effect of elevated muscle pain on neuromuscular fatigue during exercise.

PURPOSE: Muscle pain can impair exercise performance but the mechanisms for this are unknown. This study examined the effects of muscle pain on neuromuscular fatigue during an endurance task. METHODS: On separate visits, twelve participants completed an isometric time-to-task failure (TTF) exercise of the right knee extensors at ~ 20% of maximum force following an intramuscular injection of isotonic saline (CTRL) or hypertonic saline (HYP) into the vastus lateralis. Measures of neuromuscular fatigue were taken before, during and after the TTF using transcranial magnetic stimulation (TMS) and peripheral nerve stimulation. RESULTS: The mean pain intensity was 57 ± 10 in HYP compared to 38 ± 18 in CTRL (P < 0.001). TTF was reduced in HYP (4.36 ± 0.88 min) compared to CTRL (5.20 ± 0.39 min) (P = 0.003). Maximum voluntary force was 12% lower at minute 1 (P = 0.003) and 11% lower at minute 2 in HYP (P = 0.013) compared to CTRL. Voluntary activation was 4% lower at minute 1 in HYP compared to CTRL (P = 0.006) but not at any other time point (all P > 0.05). The TMS silent period was 9% longer at 100 s during the TTF in HYP compared to CTRL (P = 0.026). CONCLUSION: Muscle pain reduces exercise performance through the excacerbation of neuromuscular fatigue that is central in origin. This appears to be from inhibitory feedback from group III/IV nociceptors which acts to reduce central motor output.