Background & Aims
Exercise-induced hypoalgesia (EIH) is influenced by exercise type and intensity, pain modality tested, and demographic factors1,2. To date, there is no conclusive evidence for sex differences in EIH1. EIH is greatest when tested using pressure pain at the exercising muscle2, suggesting the importance of muscle nociceptors on EIH outcome measures. Also, given that pressure pain testing is influenced by the mechanical properties of the tissue3, observed increases in pressure pain tolerance and threshold following exercise may be in part due to tissue property changes that occur with exercise4.
The aim of the present study was to investigate the role of muscle nociceptors on EIH, using a topical anesthetic paradigm to knock out cutaneous nociceptor input5. Secondary aims were to i) determine if changes in muscle biomechanical properties influenced EIH, and ii) investigate sex effects on EIH.
Methods
Healthy female and male participants between the ages of 18-40 were recruited for this study. Topical anesthetic (emla 2.5% topical) or topical placebo were placed on participants’ quadriceps muscles for 30 mins5 in a 3cmx3cm square, after which pressure pain and muscle biomechanical6 testing (i.e., stress, strain, elasticity) was completed at all sites. A cycling high-intensity interval training (HIIT) bout was done, then pressure pain and muscle biomechanical testing were repeated. The main outcome measure was the amount of pressure (kgf) required to elicit a 4/10 pain rating by the participant.
The HIIT cycling bout consisted of a 5 min warm-up followed immediately by 6×1 min intervals at 85% heartrate reserve (HRR), with 1 min at 60% HRR between intervals, followed by a 5 min cooldown7. All participants were blinded to topical allocation, and were unaware which sites received the anesthetic or placebo topicals.
Repeated measure ANOVAs were used to test the effect of time (pre- vs. post-exercise) on pressure pain measurements for the trapezius and quadriceps testing sites, with sex (female vs. male) and condition (anesthetic vs. placebo) considered as factors.
Results
Preliminary data in 24 participants (14 females, mean age 29 ± 7.01) are reported. There was a main effect of time (F(1,22)=13.254, p<0.001), and of sex (F(1,22)=8.906, p=0.007) on the pressure equalling a 4/10 pain rating, and a significant ‘time x sex’ interaction effect on pressure equalling a 4/10 pain rating (F(1,22)=8.327, p=0.009). There was no main effect of condition on pressure equalling a 4/10 pain rating (F(1,22)=0.816, p=0.376), but there was a significant ‘condition x sex’ interaction effect (F(1,22)=0.041, p=0.041).
Post-hoc analysis indicated that the amount of pressure equalling a 4/10 pain rating increased following exercise in both the anesthetized (pre-: 417.47kgf ± 157.28 to post-exercise: 491.00kgf ± 214.35) and placebo (pre-: 413.61kgf ± 130.59 to post-exercise: 480.60kgf ± 184.35) quadriceps. Males reported higher baseline pressure equalling a 4/10 pain rating in both the anesthetized (males: 497.37kgf ± 146.59 vs females: 360.41kgf ± 143.08) and placebo (males: 454.70kgf ± 129.84 vs females: 384.26kgf ± 127.57) quadriceps, and higher post-exercise pressures in the anesthetized (males: 640.43kgf ± 205.48 vs females: 384.26kgf ± 150.38) and placebo (males: 601.87kgf ± 157.11 vs females: 393.98kgf ± 153.78) of the quadriceps.
For the trapezius testing locations, there was a main effect of time (pre- vs. post-exercise, F(1,22)=8.27, p<0.009) on pressure equalling a 4/10 pain rating, but no significant effect of condition (F(1,22)=0.164, p=0.689) or sex (F(1,22)=0.714, p=0.407).
Conclusions
Our preliminary findings indicate increased EIH independent of topical anesthetic application, suggesting muscle nociceptors may not be pivotal in the phenomenon. Sex may be an important factor for the effects of exercise and topical anesthetic on pressure pain ratings. Similar to previous data8, males responded strongly to the application of a topical anesthetic whereas females did not. The sex differences in EIH seen in this study are similar to other endogenous inhibitory pain phenomena such as conditioned pain modulation4. Results from this study will be used to inform a larger exercise trial, continuing further investigation into the role of sex, topical anesthetic, as well as muscle biomechanical properties on EIH.
This study demonstrates muscle and cutaneous peripheral input may be equally important in EIH, which could be relevant to how EIH is tested and used clinically in the future. Sex differences in the pressure pain response to exercise may be clinically relevant, as there are sex differences in many musculoskeletal disorders9. The diminished analgesic response of topical anesthetic in females should be considered in clinical environments where this is used. Moving forward, evidence of influence from muscle biomechanical properties on EIH could change our understanding of the phenomenon – if the observed pain changes are related to muscle biomechanical changes that occur with exercise, perhaps EIH is more of a measurement error than a true occurrence.
Understanding how exercise impacts human pain processing could allow for tailored exercise prescription and treatment for those suffering from chronic pain. Specifically, results from this study could inform future studies examining pain modulation, and could impact the testing and exercise protocols for acute and chronic pain rehabilitation studies.
References
- Rice, D. et al. Exercise-Induced Hypoalgesia in Pain-Free and Chronic Pain Populations: State of the Art and Future Directions. Journal of Pain 20, 1249–1266 (2019).
- Wewege, M. A. & Jones, M. D. Exercise-Induced Hypoalgesia in healthy individuals and people with chronic musculoskeletal pain: A systematic review and meta-analysis. Journal of Pain 22, 21–31 (2021).
- Finocchietti, S., Dahl Mørch, C., Arendt-Nielsen, L. & Graven-Nielsen, T. Effects of Adipose Thickness and Muscle Hardness on Pressure Pain Sensitivity: Correction. Clin J Pain 27, 735–745 (2011).
- Goto, M. et al. Temporal increase in muscle cross-sectional area as an acute effect of resistance exercise in resistance-trained and untrained individuals. Journal of Human Sport and Exercise 15, 457–469 (2020).
- Takahashi, K. et al. Influence of surface anesthesia on the pressure pain threshold measured with different-sized probes. Somatosens Mot Res 22, 299–305 (2005).
- Bizzini, M. & Mannion, A. F. Reliability of a new, hand-held device for assessing skeletal muscle stiffness. Clinical Biomechanics 18, 459–461 (2003).
- Milanović, Z., Sporiš, G. & Weston, M. Effectiveness of High-Intensity Interval Training (HIT) and Continuous Endurance Training for VO2max Improvements: A Systematic Review and Meta-Analysis of Controlled Trials. Sports Medicine 45, 1469–1481 (2015).
- Robinson, M., Riley 3rd, J., Brown, F. & Gremillion, H. Sex differences in response to cutaneous anesthesia: a double blind randomized study. Pain 77, 143149 (1998).
- Fillingim, R. B. Sex, gender, and pain: women and men really are different. Curr Rev Pain 4, 24–30 (2000).
Presenting Author
Jessie McDougall
Poster Authors
Jessica McDougall
MA, MPT
International Collaboration on Repair Discoveries, University of British Columbia, Vancouver, BC, Canada
Lead Author
A William Sheel
PhD
School of Kinesiology, Faculty of Education, University of British Columbia, Vancouver, BC, Canada;
Lead Author
John LK Kramer
PhD
International Collaboration on Repair Discoveries, University of British Columbia, Vancouver, BC, Canada
Lead Author
Alex Scott
MPT
Department of Rehabilitation Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
Lead Author
Topics
- Mechanisms: Biological-Systems (Physiology/Anatomy)