Altered relationship between anandamide and glutamate in circulation after 30 min of arm cycling: A comparison of chronic pain subject with healthy controls

Abstract

The insufficient knowledge of biochemical mechanisms behind the emergence and maintenance of chronic musculoskeletal pain conditions constrains the development of diagnostic and therapeutic tools for clinical use. However, physical activity and exercise may improve pain severity and physical function during chronic pain conditions. Nevertheless, the biochemical consequences of physical activity and exercise in chronic pain need to be elucidated to increase the precision of this therapeutic tool in chronic pain treatment. The endocannabinoid system has been suggested to play an important role in exercise-induced reward and pain inhibition. Moreover, glutamatergic signalling has been suggested as an important factor for sensation and transmission of pain. In addition, a link has been established between the endocannabinoid system and glutamatergic pathways. This study examines the effect of dynamic load arm cycling (30 min) on levels of lipid mediators related to the endocannabinoid system and glutamate in plasma of chronic pain subjects and pain-free controls. Pain assessments and plasma levels of arachidonoylethanolamide (anandamide), 2-aracidonoylglycerol, oleoylethanolamide, palmitoylethanolamide, stearoylethanolamide and glutamate from 21 subjects with chronic neck pain (chronic pain group) and 11 healthy controls were analysed pre and post intervention of dynamic load arm cycling. Pain intensity was significantly different between groups pre and post exercise. Post exercise, anandamide levels were significantly decreased in health controls but not in the chronic pain group. A strong positive correlation existed between anandamide and glutamate in the control group post exercise but not in the chronic pain group. Moreover, the glutamate/anandamide ratio increased significantly in the control group and differed significantly with the chronic pain group post exercise. The altered relationship between anandamide and glutamate after the intervention in the chronic pain group might reflect alterations in the endocannabinoid-glutamate mechanistic links in the chronic pain group compared to the painfree control group.

Influence of diet on acute endocannabinoidome mediator levels post exercise in active women, a crossover randomized study

“…Conversely, another study in healthy people found that the long-term impact of exercise intervention was to reduce plasma AEA concentration 53 . After 30 min of arm cycling at a steady pace and incremental load, plasma levels of OEA, PEA, SEA and 2-AG were similar to levels prior to exercise after 60 min recovery, while AEA levels were slightly lower after recovery 54 , which supports the short-lasting effect of exercise on eCBome mediators. While incongruences in intervention and inclusion criteria are existent in the cited studies, these past results are coherent with the observations of the current study.…”

Pain intensity and pressure pain thresholds after a light dynamic physical load in patients with chronic neck-shoulder pain

“…Additional descriptions of the design and methods of the study can be found in two previous articles, investigating biomarkers on sub-sets of the subjects in the present study [12,13]. The overall time schedule for assessments is presented in Table 1.…”

Neurobiological Processes Induced by Aerobic Exercise through the Endocannabinoidome

“…Despite these reports, a recent review has highlighted many gaps in our knowledge of how the ECS participates in controlling pain under an exercise-rich lifestyle [21]. In the study of Stensson and Grimby-Ekman (2019), a 30 min arm-cycling intervention significantly altered the relationship between plasmatic AEA and Glu levels in the chronic pain group compared to the pain-free group [86]. This conclusion indicated that the ECS and glutamatergic pathways are not just altered with stressing stimuli but also with physical exercise, where they play a major role in the perception and transmission of pain [86], as indicated in Figure 2A (periphery section).…”

“…In the study of Stensson and Grimby-Ekman (2019), a 30 min arm-cycling intervention significantly altered the relationship between plasmatic AEA and Glu levels in the chronic pain group compared to the pain-free group [86]. This conclusion indicated that the ECS and glutamatergic pathways are not just altered with stressing stimuli but also with physical exercise, where they play a major role in the perception and transmission of pain [86], as indicated in Figure 2A (periphery section). In addition, the possible mechanisms of headache prevention by exercise would include the elevation of eCB and serum brainderived neurotrophic factor (BDNF) levels, which would reduce neuroinflammation and improve brain oxygenation [9], and beta-endorphin, which is presumably implicated in reward and pleasure post-exercise.…”