Although pain is indispensable for survival, chronic pain places a heavy burden on humans. As the efficacy of opioid treatment is limited, the development of alternative methods of pain relief without medication is desirable. Recently, we have developed a novel method of physical analgesia using an adhesive “pyramidal thorn patch.” When we apply about 3 trials of these patches on the skin of a pain region, the pain region moves toward the spinal cord like a “cutaneous rabbit,” and finally, the pain vanishes. In the present review, we propose a molecular mechanism for this analgesic method or pain relief following application of the pyramidal thorn patch where firstly the mechanoreceptors and their related nerves under the skin are activated in response to touch. Transient receptor potential (TRP) channels serve as mechanosensitive channels within these mechanoreceptors. We further propose that activation of the nerves connected with the mechanoreceptors releases oxytocin, which has an antinociceptive function and activates TRP channels to hyperpolarize the pain signal nerves. We believe that our system will pave the way for alternative pain treatment.

We review the involvement of a small molecule, oxytocin, in various effects of physical stimulation of somatosensory organs, mindfulness meditation, emotion and fragrance on humans, and then propose a hypothesis that complex human states and behaviors, such as well-being, social bonding, and emotional behavior, are explained by oxytocin. We previously reported that oxytocin can induce pain relief and described the possibility how oxytocin in the dorsal horn and/or the dorsal root ganglion relieves joint and muscle pain. In the present article, we expand our research target from the physical analgesic effects of oxytocin to its psychologic effects to upregulate well-being and downregulate stress and anxiety. For this purpose, we propose a "hypothalamicpituitary-adrenal (HPA) axis-oxytocin model" to explain why mindfulness meditation, placebo, and fragrance can reduce stress and anxiety, resulting in contentment. This new proposed model of HPA axis-oxytocin in the brain also provides a target to address other questions regarding emotional behaviors, learning and memory, and excess food intake leading to obesity, aimed at promoting a healthy life.

Pain in athletes is ideally treated without systemic medicine. Therefore, complementary and alternative medicine, including patch treatments, is often used. The physiologic mechanisms of pain relief produced by patch treatment, however, are not well elucidated. In the present study, we introduce a pyramidal thorn (PT) patch that we developed, demonstrate the effects of this PT patch for the treatment of various types of pain in 300 subjects, and suggest a physiologic mechanism for the pain relief effects. One treatment with the PT patch effectively relieved pain in almost half the subjects evaluated. Except for pain generated deeply under the skin, such as low‐back pain, pain was eliminated within four treatments with the PT patch in almost all of the subjects. Interestingly, the pain‐sensing region moved along the nerve fibers after each trial. Further, patches without PT also provided some pain relief. We considered that this effect was due to hair deflection on the skin; that is, adhesion of the PT patch activates Merkel cells directly as well as Merkel cell‐neurite complexes around the hair follicles by deflecting the hair follicles, whereas adhesion of a patch without PT only activates the Merkel cell‐neurite complexes. In any case, patch adhesion stimulates Aβ fibers to alleviate pain. Finally, we found that the pain threshold is increased by electric stimulation, suggesting that the gentle adhesion of a PT patch would be more effective. To our knowledge, this is the first study to demonstrate physiologically the validity of an adherent patch for pain relief.

Pain in the elbow, shoulder, knee, lower back, and various other joints is relieved by adhesion of pyramidal thorn patches. To elucidate the pain relief mechanism induced by the patches, we established a quantitative method for estimating the pain reduction and investigated the brain regions that change in association with pain relief. We first attempted to quantify the pain relief using transcutaneous electric stimulation (TCES) and a visual analog scale (VAS), and then applied near-infrared spectroscopy (NIRS) to the prefrontal cortex, including the dorsolateral prefrontal cortex (DLPFC) and the orbitofrontal cortex (OFC). We also examined the salivary oxytocin levels, which are thought to reflect oxytocin secretion levels from the posterior pituitary in the brain. Application of pyramidal thorn patches to pain regions decreased the pain degree estimated using TCES and VAS. Oxyhemoglobin levels were likely to be decreased in the left DLPFC on the basis of NIRS measurements during patch treatment, suggesting that the left DLPFC is involved in pain relief. On the other hand, the salivary oxytocin levels varied widely. A potential reason for the varying salivary oxytocin levels is its utilization in the pain region as an analgesic agent. Our results suggest that the left DLPFC will become a target brain region for pain therapy.