The review of innovative integration of Kampo medicine and Western medicine as personalized medicine at the first multidisciplinary pain center in Japan

Background The Japanese medical system is unique because it is the only country in the world where Western medicine and traditional Japanese medicine including Kampo medicine, traditional Japanese herbal medicine, are used in our daily clinical practice. Pain is essentially an interactive psychophysiological behavior pattern. Thus, an interdisciplinary approach is often recommended in providing appropriate therapeutic care for the patients suffering from chronic and intractable pain. In addition, we have been prescribing Kampo medicines in combination with Western medicines as personalized medicine in order to treat patients with chronic pain at our pain center. The aim of our study was to conduct a survey on the current use and the effect of Kampo medicines in our multidisciplinary pain center. Methods Retrospective analysis was performed on 221 out of 487 patients suffering from chronic pain. Results The most frequent medical complaints for which Kampo medicines were prescribed were lower back/lower limb pain, neck/upper limb pain, various facial pains, headache/migraine, whiplash-associated disorder, and frozen shoulder. Kampo medicines were prescribed based on patient-centered Kampo diagnosis. Moreover, several Kampo medicines generally for the management of psychological symptoms were prescribed for about 70% of the patients. Pain improvement in the patients was categorized as follows: 26.3% with marked improvement, 12.7% with moderate improvement, 38.9% with some improvement, and 19.9% with no improvement. Conclusions Two thirds of the chronic pain patients with the use of Kampo medicines combined with Western medicine experienced further pain improvements.

Pain is essentially an interactive psychophysiological behavior pattern, so an appreciation of the biopsychosocial model is essential for understanding and caring for patients with chronic pain. Thus, an interdisciplinary approach is often recommended and considered to be extremely relevant in providing appropriate therapeutic care for patients suffering from chronic and intractable pain [5]. Our center is the first multidisciplinary pain center established in Japan at July 2007. At our center, we have been prescribing Kampo extract formulations in combination with Western medicines in our daily clinical practice as an interdisciplinary approach in order to treat patients with chronic pain. However, to date, there have not been any reports on Kampo practice in multidisciplinary pain centers anywhere in the world because of the health insurance systems. We thus conducted a survey on the use of Kampo extract formulations and the effect of the formulations on patients with chronic pain in our multidisciplinary pain center.

Methods
Retrospective analysis from August 2012 to July 2013 was performed on 487 patients suffering from chronic pain who visited the pain center of Aichi Medical University Hospital. All patients were referred from other hospitals to the pain center. Patients who were prescribed Kampo extract formulations were included.
After obtaining approval from the Ethics Committee of Aichi Medical University (a reference number, 13-097) and written informed consent, we routinely recorded demographics, symptoms, and course of pain in all patients. The intensity of pain was rated by the patients using a numerical rating scale (NRS) where 0 indicated no pain and 10 the greatest pain possible. All demographic and clinical data were extracted from medical records from August 2012 to March 2014 for the present study. In addition, patients were categorized as having marked improvement (≥60% improvement in NRS for pain compared to initial visit), moderate improvement (≥30% and <60% improvement in NRS compared to initial visit), some improvement (≥20% and <30% improvement in NRS compared to initial visit), and no improvement (<20% improvement in NRS compared to initial visit) depending on the state of pain improvement 6 months to 1 year after the initial visit. Moreover, patients who did not visit the hospital again even with an appointment for a follow-up visit and who visited the hospital for the purpose of receiving a second opinion were categorized separately.

Expert recommendations
Since the 1970s, great attention has been given to traditional, complementary, and alternative therapies around the world [1,2]. One of the reasons for the attention is the limited effectiveness of biomedicine for the treatment of chronic diseases. Based on the Japanese health insurance system, we can use Western medicine and traditional  Japanese medicine including Kampo medicine in our daily clinical practice at the same time in the same medical institution [1,2,4]. Furthermore, Kampo has been used for the treatment of chronic pain in Japan from ancient times to the present [3,6,7]. The results of the present survey showed that Kampo medicines were prescribed to treat lower back/lower limb pain (36.6%, n = 81), neck/upper limb pain (13.1%, n = 29), various facial pains (13.1%, n = 29), headache/ migraine (7.7%, n = 17), whiplash-associated disorder (5.9%, n = 13), and frozen shoulder (3.6%, n = 8). In fact, we had these cases in the same order in our center and Kampo medicines were prescribed when treatment with Western medicine alone was insufficient. And this survey shows that the use of Kampo medicines combined with Western medicine as an interdisciplinary approach provided some improvements for two thirds of these patients refractory to Western medicine alone. Goshajinkigan, Shakuyakukanzoto, Yokukansan, Keishikajutsubuto, Hachimijiogan, and Juzentaihoto were the most frequently prescribed Kampo medicines for lower back/lower limb pain. Goshajinkigan, Shakuyakukanzoto, Keishikajutsubuto, and Hachimijiogan have been used since ancient times to treat melosalgia, low back pain, and numbness [8][9][10][11]. Yokukansan has been used to treat excitability, depression, and excessive muscle tension [8,9,12].
Keishibukuryogan, Kamishoyosan, Goshuyuto, and Jidabokuippo were the most frequently prescribed Kampo medicines for headache/migraine. Goshuyuto has been used since ancient times to treat a very severe headache accompanied by vomiting [8,9,15]. Moreover, Keishibukuryogan and Kamishoyosan have been prescribed for the treatment of emotional distress, a heavy feeling in the head and headache [8,9,13,14].
Nijutsuto and Keishikajutsubuto were the most frequently prescribed Kampo medicines for frozen shoulder. Nijutsuto has been the first-line Kampo medicine for the treatment of frozen shoulder [8,9]. Keishikajutsubuto has been used to treat arthritis [9].
The interesting thing about the present survey is that we usually prescribed Yokukansan, Kamishoyosan, and Kososan, which have generally been prescribed for the management of psychological symptoms [3,12,13,16,17]. Yokukansan and Kamishoyosan have anxiolytic effects [12,13,17] and especially Yokukansan which is known to exert these effects via serotonin receptors [12]. Pain is essentially an interactive psychophysiological behavioral pattern [5]. Our previous study also showed that about 70% of patients were moderate to high psychopathological patients [3]. We thus postulated that Yokukansan, Kamishoyosan, and Kososan were used for psychopathological patients suffering from chronic pain at our center.
Since pain is an interactive psychophysiological behavioral pattern, it is important for medical staffs to recognize the biopsychosocial model when understanding and caring for patients with chronic pain. Thus, an interdisciplinary approach is often recommended and considered to be extremely relevant in providing appropriate therapeutic care for patients with chronic and intractable pain [5]. That is, inter-, multidisciplinary integrated approach is needed for patients with chronic and intractable pain as personalized medicine. Kampo has been used for the treatment of chronic pain in Japan from ancient times to the present [3,6,7]. Also, Kampo medicines have been prescribed based on patient-centered Kampo diagnosis. Thus, we postulate that Kampo could be part of personalized medicine. Accordingly, we have been prescribing Kampo extract formulations in combination with Western medicines in our daily clinical practice as personalized medicine in order to treat patients with chronic pain at our center. And we expect that the number of physicians who use Kampo in this way will increase soon.
There are merits and demerits for the clinical application of Kampo medicine, when compared with Western medicine. A lot of patients value Kampo medicine as a holistic, body harmonizing treatment and as a stimulant for self-healing without severe side effects [1]. In contrast, some patients suffering from chronic pain are likely to be so dependent and tend to be reluctant to receive the treatments based on its holistic, self-healing philosophy.
There are several limitations of the study. The present report is a retrospective and nonrandomized control analysis of Kampo treatment and thus lacks the reproducibility. Since we have to clarify the specific kind of pain for personalized approach and detailed points for multidisciplinary integration, we need prospective and comparative study that might be more appropriate to support predictive, preventive, personalized value, and the reproducibility of Kampo treatment, thereby obtaining solid evidence of Kampo medicine in personalized pain management algorithm.

Conclusion
The retrospective analysis on 221 out of 487 patients suffering from chronic pain who visited the pain center of Aichi Medical University Hospital showed that the most frequent medical complaints for which Kampo medicines were prescribed were lower back/lower limb pain, neck/upper limb pain, various facial pains, headache/migraine, whiplash-associated disorder, and frozen shoulder. Two thirds of the chronic pain patients with the use of Kampo medicines combined with Western medicine experienced further pain improvements. Moreover, we usually used several Kampo medicines generally prescribed for the management of psychological symptoms.