Muscular mechanical hyperalgesia after lengthening contractions in rats depends on stretch velocity and range of motion

Background: The current study investigated stretch variables and mechanical factors of lengthening contractions (LC) in the processes leading to muscular mechanical hyperalgesia in rats to understand mechanisms underpinning delayed onset muscle soreness (DOMS). Methods: Under isoflurane anaesthesia, ankle extensor muscles were loaded with repetitive LC with angular stretch velocities (50 degrees, 100 degrees, 200 degrees and 400 degrees/s) at a fixed range of motion (ROM) of 90 degrees, and with ROMs (30 degrees, 60 degrees, 90 degrees and 120 degrees) at a fixed velocity of 200 degrees/s. Results: Mechanical hyperalgesia was observed in a velocity-and ROM-dependent manner. Under the fixed ROM, integrated torque generated during LC (iTq([max])) was inversely correlated with the velocity, but the rate of torque increase during LC (rTq([max])) was positively and significantly correlated with the velocity, and the magnitude of hyperalgesia was correlated with rTq([max]) (p < 0.001). When the velocity was fixed, iTq[ max] was significantly correlated with ROM, and the magnitude of hyperalgesia was correlated with iTq[ max] (p < 0.01). Necrotic myofibres were observed only sparsely (< 0.8%) after any of the LC protocols tested. Up-regulation of nerve growth factor and glial cell line-derived neurotrophic factor mRNA in the muscle was positively correlated with the increases in the LC velocity and ROM (p < 0.05 similar to 0.001). Conclusions: Both velocity and ROM are pivotal variables determining the initiation of mechanical hyperalgesia. Neurotrophic factor-mediated peripheral mechanisms, but apparently not inflammatory changes caused by myofibre damage, are responsible for the mechanical hyperalgesia. Significance: Mechanical hyperalgesia appears after LC in a stretch velocity-and range of motion-dependent manner. The rate of torque increase and integrated torque are the crucial factors. Neurotrophic factor-mediated peripheral pain mechanisms without robust inflammatory changes caused by myofibre damage were required for this mechanical hyperalgesia.