Aerobic Exercise and Pain Modulation: Examining the Impact on Pain Sensitivity in Healthy Adults

Background:

Pain and Its Burden Pain is a prevalent and complex health condition that significantly impacts individuals, families, and society as a whole. Of the 39.4 million adults experiencing pain most days and persisting for over three months, nearly two-thirds report it as "constantly present," with over half describing it as "unbearable and excruciating". Pain can be categorized into physiological and pathological types. Nociceptive and inflammatory pain are physiological responses that serve protective and adaptive functions, whereas pathological pain is considered non-protective and maladaptive.

Central Mechanisms in Pain Modulation Laboratory-based quantitative sensory testing (QST) evaluates sensory function using psychophysical methods, teasing out components of the nervous system that demonstrate loss or gain of sensory function contributing to pain. Pain-specific QST is categorized into static QST and dynamic QST. The static measure of QST is believed to provide simple and unidirectional assessments of static pain sensitivity in local regions and provide insight into peripheral mechanisms. Static QST measures include the determination of thresholds (pain thresholds and pain tolerance) and rating the intensity of the quantified stimulus. Pain processing is a complex system, and static QST provides one point on the scales of sensations. In addition, static QST is limited in capturing the pain modulatory ability of the central nervous system. Therefore, to overcome this limitation, dynamic QST measures come into play.

Dynamic QST provides insight into pain modulatory mechanisms such as pain facilitation or inhibition, or the extent to which the nervous system enhances or suppresses the pain. Dynamic QST assesses the central mechanism by temporal summation (TS) and conditioned pain modulation (CPM). TS assesses the heightened pain perception towards an identical repetitive noxious stimulus (heat or pressure) applied with consistent intensity and frequency (lower than 3 seconds). TS represents pain facilitation and is a behavioral measure of activity at the dorsal horn of the spinal cord. The CPM refers to the endogenous pain modulatory system that assesses the effects of the nociceptive system through the decrease in pain from one stimulus (test stimulus (thermal or electrical or tactile) to one part of the body due to the application of a second pain stimulus (conditioning stimulus (hot or cold bath or ischemia) applied at a distant another body part. CPM represents a pain inhibitory process and is a proxy measure of descending pain inhibition through the spino-bulbar- spinal loop. CPM may be a valuable tool in directing mechanistic-based approaches for treating painful conditions. For example, individuals with painful diabetic neuropathy and poorly functioning CPM have more significant analgesia when given duloxetine, a medication that augments conditioned pain modulation. Additionally, identifying and treating the source of pain is associated with positive changes in CPM. Healthy individuals demonstrate more efficient CPM when compared with people in pain and a systematic review of adults with chronic pain revealed that CPM efficiency improves after a reduction in clinical pain. For example, total hip arthroplasty for treating painful osteoarthritis reduces joint pain and improves post-operative CPM. Collectively, these studies suggest that the CPM test has the potential to predict risk and treatment outcomes for chronic pain, therefore CPM may be considered an essential treatment moderator and mediator. The activation of central mechanisms, particularly endogenous inhibitory systems, is proposed as a fundamental process underlying various pain management interventions. Descending pain inhibitory systems, which are part of central mechanisms, play a crucial role in mediating the analgesic effects of interventions such as manual therapy. Manual therapy stimulates afferent neuronal inputs that activate the central nervous system's descending pathways to inhibit pain. Conditioned Pain Modulation (CPM) shares a similar mechanism, inhibiting pain through descending modulation pathways.

Role of Aerobic Exercise in Pain Inhibition The impact of exercise on pain reduction is well-documented, with initial investigations and subsequent evidence in both animal and human studies. Exercise has proven effective in managing pain associated with various chronic conditions, including fibromyalgia, chronic neck pain, osteoarthritis, rheumatoid arthritis, and chronic low back pain. Additionally, it has been shown to prevent chronic low back pain (CLBP) recurrence and mitigate the progression of chronic musculoskeletal pain conditions. This pain-reducing effect, known as Exercise-Induced Hypoalgesia (EIH), involves several underlying mechanisms. The endogenous opioid system is the most extensively studied mechanism explaining EIH. Another proposed mechanism involves endocannabinoids, which modulate pain through an inhibitory feedback loop that reduces glutamate release at nociceptive synapses. It has been reported that increases in circulating endocannabinoids following exercise were associated with reduced pain perception, as evidenced by pressure pain thresholds (PPT) and decreased thermal heat temporal summation. Acute aerobic exercise has also been shown to enhance Conditioned Pain Modulation (CPM) analgesia in healthy individuals. Studies suggest that higher CPM efficiency correlates with greater EIH. For example, it is found that active participants exhibited higher EIH and more effective CPM after 15 minutes of cycling at 75% VO₂max, compared to inactive participants. Similarly, it has been observed that enhanced CPM analgesia in athletes versus non-athletes, further linking CPM efficiency to physical activity levels. This study aims to investigate the effects of repeated high-intensity aerobic exercise on CPM analgesia in non-athletic populations, addressing gaps in understanding how exercise-induced pain modulation operates beyond athletic contexts.