Anatomical and Physiological Factors Contributing to Chronic Muscle Pain

Abstract

Chronic muscle pain remains a significant source of suffering and disability despite the adoption of pharmacologic and physical therapies. Muscle pain is mediated by free nerve endings distributed through the muscle along arteries. These nerves project to the superficial dorsal horn and are transmitted primarily through the spinothalamic tract to several cortical and subcortical structures, some of which are more active during the processing of muscle pain than other painful conditions. Mechanical forces, ischemia, and inflammation are the primary stimuli for muscle pain, which is reflected in the array of peripheral receptors contributing to muscle pain-ASIC, P2X, and TRP channels. Sensitization of peripheral receptors and of central pain processing structures are both critical for the development and maintenance of chronic muscle pain. Further, variations in peripheral receptors and central structures contribute to the significantly greater prevalence of chronic muscle pain in females.

Spontaneous and Bite-Evoked Muscle Pain Are Mediated by a Common Nociceptive Pathway With Differential Contribution by TRPV1

“…Inflammatory mediators also appear to contribute to chronic muscle pain conditions, such as myofascial pain syndrome 52 . Therefore, rodent models of muscle inflammation have been widely used to study mechanisms of muscle pain 21 . However, multiple chronic muscle pain conditions, e.g., fibromyalgia, often do not involve overt muscle inflammation.…”

“…These conditions also interfere with normal muscle functions, e.g., limited range of motion in low back pain or decreased bite force in TMJD. Although mechanisms underlying muscle pain have been studied in multiple preclinical models 21,37 , molecular mechanisms and neural circuits underlying spontaneous muscle pain or muscle function-related pain, such as reduced bite force 34,36 , are not well understood. Scarcity of readily available rodent models for assessing spontaneous pain and muscle function-related pain is an impediment to progress.…”

Serotonin-gated inward currents are three times more frequent in rat hairy skin sensory afferents than in those innervating the skeletal muscle

“…1 On the other side, the deep somatic (musculoskeletal) system mediates a dull or aching pain associated with ongoing activation of nociceptors in muscles, tendons, joint capsules, fasciae, or bones, and it is produced by overuse strain, mechanical injury, cramping, ischemia, or inflammation. 2 , 3 …”

“…Thus, superficial cutaneous pain is subjectively described as a well-localized sharp, pricking, or burning sensation; musculoskeletal deep somatic pain, as a diffuse, dull, or aching sensation; and visceral pain, as a deep cramping sensation that may be referred. 1 In general, it is considered that musculoskeletal pain is more diffuse and longer lasting than cutaneous pain, 2 , 3 and these differences in quality may rely on peripheral and central mechanisms. 4 Like that, muscle pain more strongly activates regions of the brain associated with emotional processing than skin pain, 5 and peripheral nociceptors are considered a heterogeneous population of neuronal afferents that are classified in several ways, such as by their expression of transducer molecules or peptidergic content.…”

Effect of Intramuscular Protons, Lactate, and ATP on Muscle Hyperalgesia in Rats

“…A decrease in withdrawal thresholds was interpreted as muscle hyperalgesia. This measurement represents pressure pain thresholds and tenderness typically observed clinically in people with muscle pain [ 16 ].…”