Table 1.

Central nervous system analgesic mechanisms in exercise [48,68,69,70].

	Brain Area	Neurotransmitters Involved	Receptors	Exercise Program	Intensity	Effect
Endogenous opioids	Hypothalamus, periaqueductal gray, rostral ventromedial medulla	β-endorphin, met-enkephalin	Mu-opioid	Aerobic training performed for 5–8 weeks	85% of maximum heart rate or 80% of VO2max	Training >9 weeks or 45 sessions produces downregulation
Endocannabinoid system	Rostral ventromedial medulla, periaqueductal gray dorsal horn	Anandamide, 2-arachidonoylglycerol	Endocannabinoid CB1 and CB2	Aerobics and resistance (running, followed by cycling)	70–85% of maximum heart rate or 25% maximum isometric contraction	“Runner’s high”, anxiolytic, sedative, and euphoriant
Serotonergic system	Brain stem, lumber spinal cord, and parieto-occipital cortex	Serotonin transporter (SERT)	5-HT	1 session of 60 min swimming or swimming 30 min/day, 6 days per week; run on a treadmill 30 min, 5 days per week, 2 weeks	Low intensity (75% maximal blood lactate steady state)	Emotional regulation and facilitated memory function in the hippocampus
NMDA receptor alteration	Rostral ventromedial medulla	Phosphorylation of N-methyl D-aspartate (NMDA)	Receptor NR1 subunit (p-NR1)	Exercise 1 h for 1 week	75–85% HRmax	Modulates nervous system’s response to pain stimuli and injury
Nor-adrenergic system	Periaqueductal gray, dorsal raphe, and spinal cord dorsal root ganglion	Catecholamines	α1, α2, β2 adrenergic	1 or 2 h treadmill running (A), 20 min of stationary bicycle (B)	Moderate (25 m/min with a 3% slope) (A), intense (Borg 15) (B)	Improves cognitive performance, modulates thermoregulation during exercise