To the best of our knowledge, our trial will be the first to assess the modulatory effect of Tuina on the descending pain inhibitory system in patients with KOA. The results of this study have significant implications for understanding the mechanisms of Tuina in managing KOA-related pain and may provide valuable insights for its clinical application.
KOA can cause joint dysfunction, reduce physical fitness and the capability to tackle activities of daily living, and cause depression and anxiety [3, 36, 37]. Previous researchers have indicated that peripheral factors, such as synovial inflammation and articular cartilage devastation, may have a cardinal role [38–40]. However, many studies have found that the severity of radiographic KOA and the inflammatory response of the synovial membrane are not positively correlated with KOA [41–43]. Consequently, peripheral mechanisms cannot completely explain KOA. Patients with KOA have simultaneously raised pain sensitivity in affected and non-affected areas. Therefore, some investigators suggest that “abnormal central processing” of afferent pain messages may be a cardinal factor in KOA [28].
Moreover, Tuina is safe and effective for pain, physical function, stiffness, and other clinical symptoms associated with KOA [44]. It has been demonstrated to activate and modulate functional connectivity in the hippocampus to ameliorate cognitive function in patients with poststroke depression [45]. The brain has powerful control over nociceptive input in the spinal cord at the level of the brain stem. This top-down control takes place by means of the “descending modulation” of the pain transmission pathway mechanism [46–48]. The descending pain inhibitory system has a cardinal role in normal pain consciousness, and its malfunction may be one of the pathophysiological mechanisms in KOA. This factor possibly clarifies how other centrally mediated processes, such as sleep, mood, the placebo effect, and cognition, influence the pain experience [49]. Crucially, the PAG and RVM, as important components of the descending pain inhibitory system, directly modulate the activity of the spinal neurons involved in pain transmission [50]. Furthermore, animal experiments have demonstrated that the PAG is involved in opioid-mediated analgesia since the microinjection of morphine into this nucleus produces a reduction in sensory pain behaviors [51]. Similarly, the analgesic effects of directly stimulating the PAG have also been evidenced in humans [52]. Moreover, direct PAG stimulation is used to diminish chronic pain intensity in individuals [53]. The RVM is the pontomedullary area in which opioid microinjection generates analgesia [50]. Making allowances for this, the PAG-RVM axis, as a significant component of the descending pain inhibitory system, can possess an inhibitory implication on harmful transmission.
There are some limitations to this study. First, there is a potential for methodological bias, as blinding is particularly difficult when delivering a physical intervention or health education. Second, the long-term implications of Tuina will not be investigated, warranting further research in this area.