Endogenous Modulation of Pain

Abstract

Pain is a complex and highly subjective phenomenon that can be modulated by several factors. Based on results from experimental and clinical studies, the existence of endogenous pain modulatory mechanisms that can increase or diminish the experience of pain is now accepted. In this narrative review, the pain modulatory effects of exercise, stress, and cognitions in humans are assessed. Experimental studies on the effect of exercise have revealed that pain-free subjects show a hypoalgesic response after exercise. However, in some patients with chronic pain this response is reduced or even hyperalgesic in nature. These findings will be discussed from a mechanistic point of view. Stress is another modulator of the pain experience. Although acute stress may induce hypoalgesia, ongoing clinical stress has detrimental effects on pain in many patients with chronic pain conditions, which have implications for the understanding, assessment and treatment of stress in patients with pain. Finally, cognitive strategies play differing roles in pain inhibition. Two intuitive strategies, thought suppression and focused distraction, will be reviewed regarding experimental, acute, and chronic pain. Based on current knowledge on the role of exercise, stress, and cognitive pain control strategies on modulation of pain, implications for treatment will be discussed.

Comparison of five conditioned pain modulation paradigms and influencing personal factors in healthy adults

“…In this study the level of stress was determined with questionnaires (LDI and LTE), which displayed larger anti-nociceptive effects at the m. trapezius in case of higher stress levels with HWI, CPT and DIO. This might be explained by the fact that non-pain-related stress may distract attention away from a concurrent painful stimulus (Vaegter et al, 2020). This factor should be confirmed in future studies by additional measures of cardiovascular and endocrine factors (Logan et al, 2001;Vassend & Knardahl, 2004;Larra et al, 2015;Hermann et al, 2019).…”

Distraction by a cognitive task has a higher impact on electrophysiological measures compared with conditioned pain modulation

“…Although CPM has been extensively studied both in animals 16,17 and humans using psychophysiological and electrophysiological methods [18][19][20][21][22][23][24] , it is still under debate whether the pain reduction during CS results solely from the descending noxious inhibitory pathways. Pain modulation can be achieved also by cognitive factors like attention and distraction [25][26][27] . Postsurgical pain is reported as more intense when patients are attending to it 28 ; in contrast, listening to music [29][30][31] , therapeutic play interventions 32 and animal-assisted treatments 33 for children can reduce postoperative pain intensity, presumably by distraction.…”

The Influence of Musculoskeletal Pain On Exercise-Induced Hypoalgesia in Humans: an Experimental and Clinical Exploratory Approach

“…Hypersensitivity of the sensory nervous system may be caused by peripheral and/or central sensitisation 25,26,28,30 and acute exercise may decrease (hyper)-sensitivity. This well-established phenomenon is labelled exercise-induced hypoalgesia (EIH) [31][32][33][34] . The underlying neural substrates influencing sensitivity in relation to acute exercise has been reviewed extensively [31][32][33][35][36][37][38][39][40][41][42][43] and include, but are not limited to, opioids [44][45][46][47][48] , nitric oxide 49,50 and endocannabinoids 48,[51][52][53] as well as cardiovascular 47,54,55 , noradrenergic [56][57][58][59] and serotonergic 60-62 mechanims.…”

“…This well-established phenomenon is labelled exercise-induced hypoalgesia (EIH) [31][32][33][34] . The underlying neural substrates influencing sensitivity in relation to acute exercise has been reviewed extensively [31][32][33][35][36][37][38][39][40][41][42][43] and include, but are not limited to, opioids [44][45][46][47][48] , nitric oxide 49,50 and endocannabinoids 48,[51][52][53] as well as cardiovascular 47,54,55 , noradrenergic [56][57][58][59] and serotonergic 60-62 mechanims. For instance, a recent human study 62 found that greater EIH after an isometric exercise, normally known to be painful 63 , was associated with weaker serotonergic level in combination with a gene for stronger opioid signalling, which may suggest an antagonistic interaction between serotonergic and opioid EIH mechanisms possibly to avoid analgesia.…”

“…Numerous EIH reviews has been published within the last 10 years 31,33,[35][36][37][39][40][41][42][43][76][77][78] . The EIH response is considered a proxy of the balance between endogenous pain facilitatory and pain inhibitory mechanisms during and after one exercise session 37,39 .…”