Activation of Different Opioid Systems by Muscle Activity and Exercise

Many positive ef%ects of exercise have been ascribed to the exercise-induced activation of endogenous opioid systems. The hypothesis that different opioid peptides and receptors are involved in the cardiovascular, behavioral, and analgesic responses and that opioid-media ted effects of muscle exercise are triggered by activation of mechanosensitive muscle nerve afferents is reviewed. 0 piates have been used by humans for thousands of years, and their analgesic, euphoric, and addictive effects have been the subject of intense research throughout this cen-tury. Our understanding of the mechanism of action of the opiates was greatly advanced by the discovery of opioid receptors in I973 and the isolation of endogenous opioid peptides in the mid-l 970s. The endogenous opioids can be activated by a variety of stressors, and their influence on a wide range of biological functions has been suggested. A great number of studies show that plasma levels of P-endorphin are increased by physical activity. Also, some physiological ad-aptations to exercise can be reversed by nalox-one, an opioid receptor antagonist, while other functions are not influenced. A confounding factor in these studies is that peripheral levels of opioid peptides do not reflect central nervous system (CNS) opioid activity and that some opioid receptors are poorly antagonized by naloxone. The aim of the present paper is to review evidence from animal and human studies indicating that aerobic exercise can activate CNS opioid systems, with special emphasis on experimental studies using voluntary running in rats. Furthermore, the activation of different opioid systems by (acupuncture-like) stimulation of afferent nerves from skeletal muscles or by electrically induced skeletal muscle contrac-tions is discussed