Does exercise increase or decrease pain? Central mechanisms underlying these two phenomena

Abstract

Exercise is an integral part of the rehabilitation of patients suffering a variety of chronic musculoskeletal conditions, such as fibromyalgia, chronic low back pain and myofascial pain. Regular physical activity is recommended for treatment of chronic pain and its effectiveness has been established in clinical trials for people with a variety of pain conditions. However, exercise can also increase pain making participation in rehabilitation challenging for the person with pain. Animal models of exercise-induced pain have been developed and point to central mechanisms underlying this phenomena, such as increased activation of NMDA receptors in pain-modulating areas. Meanwhile, a variety of basic science studies testing different exercise protocols, show exercise-induced analgesia involves activation of central inhibitory pathways. Opioid, serotonin and NMDA mechanisms acting in rostral ventromedial medulla promote analgesia associated with exercise. This review explores and discusses current evidence on central mechanisms underlying exercised-induced pain and analgesia.

Keywords: animal; central nervous system; exercise; glutamate; hyperalgesia; opioid; pain; physical activity; serotonin.

Figure 1. Overview of the underlying mechanisms of exercise‐induced pain and analgesia

Known neurotransmitters and receptors that have been shown to be involved at different areas of the central nervous system are listed. The majority of studies have focused on the PAG and the RVM. Increases in serotonin and opioids, and activation of μ‐opioid (MOR) and cannabinoid‐1 (CB1) receptors are implicated in the exercise‐induced analgesia. Further, the normally increased phosphorylation of the NR1 subunit of the NMDA receptor and the increased expression of serotonin transporter (SERT) that is increased by acute exercise are reduced by regular physical activity. +, increase; −, decrease; 5‐HT, serotonin; CB1, cannabinoid receptor 1; DH, dorsal horn; MOR, μ‐opioid receptor; PAG, periaqueductal grey; p‐NR1, phosphorylated NR1; RVM, rostral ventromedial medulla.