The main purpose of exercise therapy for KOA is not only muscular strength improvement (the quadriceps femoris muscle in particular) and but also pain relief (19, 20). Muscular strength improvement protects joints and relieves nociceptive stimulation. However, exercise sometimes increases pain. In addition to the pathological change in articular structures, changes in central pain processing or central sensitization appear to be involved in KOA pain (19). Murphy et al. reported that 36% of a heterogenous sample of patients with hip and KOA demonstrated evidence of central sensitization (22). This finding has been incompletely characterized, but it is necessary to consider central sensitization in the treatment of patients with KOA. From a theoretical perspective, exercise has the potential to treat the process of central sensitization: e.g. exercise activates brain-orchestrated endogenous analgesia (23). An initial bout of high intensity eccentric exercise induces central sensitization, but a repeated round of exercise facilitates inherent protective spinal mechanisms (repeated bout effect) (24). Moreover, ipsilateral resistance exercise may possibly prevent the central sensitization (25). Therefore, a time-contingent approach which implies that the patient does not cease exercise bouts once local pain severity increases is recommended (22). A few reports about the dysfunctional endogenous analgesia for patients with musculoskeletal pain response to aerobic exercise were shown, but neither type of aerobic exercise was able to activate endogenous analgesia (24). At present, there is no report of an exercise method that is effective in central sensitization pain patients. Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophic family of growth factors. The loss of BDNF usually leads to neurodegeneration in these motor centers and eventually results in several severe motor diseases, such as amyotrophic lateral sclerosis, spinocerebellar ataxias, Parkinson's disease, Huntington's disease, as well as vestibular syndrome. These neurotrophic factors (e.g., decreasing brain-derived neurotrophic factor) are promising new avenues for diminishing hyperexcitability of the CNS in central sensitization pain patients (2). Da Graca-Tarrago et al. showed that a 30-minute electrical intramuscular stimulation in osteoarthritis decreased pain, increased the local pain pressure threshold (PPT), and decreased BDNF (27). Gajewska-Wozniak et al. reported that low-threshold electrical stimulation of peripheral nerves to stimulate Ia afferent fibers (proprioceptive signaling) might affect the expression of BDNF in rats (28). HTS is an exercise technique that uses electrically eccentric muscle contraction. Yamaguchi et al. showed that the soleus H-reflex increased after one HTS adversely in conventional resistance exercise (29). This seems to indicate that HTS serves to activate Ia fibers. HTS may affect central sensitization and relieve pain in KOA patients.