Background & Aims
Exercise-induced hypoalgesia (EIH) refers to an attenuated pain perception following different types of exercise in healthy humans (Koltyn, 2000). Although numerous studies have investigated EIH over the past decades, results remain controversial (Naugle et al., 2012; Vaegter et al., 2020; Wewege & Jones, 2020). The pharmacological underpinnings of EIH contribute to these controversial findings, where administering a µ-opioid antagonist in some studies decreased (Janal et al., 1984; Saanijoki et al., 2018) or did not affect EIH (Koltyn et al., 2014). Only a few fMRI studies have investigated the brain regions involved in EIH. The descending pain modulatory system (including PAG and insula) has been identified (Scheef et al., 2012) as a crucial system for exercise-induced pain modulation. Our objective was to induce EIH after aerobic exercise for heat and pressure pain while characterising the brain regions involved and disentangle the involvement of the endogenous opioid system.
Methods
In this study, we examined the opioid dependency of EIH in healthy individuals of diverse fitness levels, with a specific focus on both male and female subjects. Utilizing a double-blind cross over design spanning three days, we administered a placebo saline and the µ-opioid antagonist naloxone to each participant. Thirty-nine healthy participants (21 females, age: 18 – 45 years, BMI: 18 – 30) of varying fitness levels completed two experimental days with 4 blocks. Each block consisted of 10 minutes of high-intensity (HI) or low-intensity (LI) cycling and was immediately followed by an fMRI scan where participants received multiple 15-second-long painful heat stimuli and pressure stimuli. Teatment (saline or naloxone) was administered intravenously. The behavioural data We investigated all effects was analysed using linear mixed models with pain ratings as the dependent variable and subject as random effect. In this report we focus on the heat pain only.
Results
We identified the PAG and right central operculum to show increased activation in the naloxone compared to the saline condition. Furthermore, a significant interaction of fitness level and exercise intensity was evident behaviourally: With increasing fitness level pain ratings were perceived less painful after HI exercise. This effect was mirrored cortically, where we identified the right pregenual ACC to be activated, where an increasing fitness level was associated with a decreased activation after HI exercise. Furthermore, a significant interaction between fitness level, treatment and sex on pain ratings was observed: Males showed a hypoalgesic response to HI exercise in the saline condition with increasing fitness level which was attenuated when naloxone was administered. This interaction was mirrored in the PAG, where males showed a decreased activation with increasing fitness level in the saline condition which was reversed under naloxone. Females did not show this effect.
Conclusions
This study examined the mechanisms of exercise-induced hypoalgesia after aerobic exercise in healthy subjects of varying fitness levels. Overall, it appears that exercise-induced hypoalgesia in heat pain is mediated by different factors such as physical fitness and sex where especially males with higher fitness levels showed the largest hypoalgesic response to acute exercise. This hypoalgesic response was attenuated by naloxone. Furthermore, structures of the descending pain modulatory system (PAG, rpregACC) with high µ-opioid receptor density were identified to be potentially involved in mediating this effect suggest the involvement of the endogenous opioid system in mediating exercise-induced hypoalgesia.
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Presenting Author
Janne Nold
Poster Authors
Janne Nold
MSc
University Clinic Hamburg Eppendorf (UKE)
Lead Author
Topics
- Pain Imaging