We herein report 988 primary headache patients who came to our hospitals. About 90% of patients’ symptoms improved after a week in both those treated by kampo medicine and those by NSAIDs. This report is important because there are few reports on the kampo medicine as an acute treatment for primary headache.
Kampo medicine for TTH
TTH is the most prevalent form of primary headache in the general population, but the least studied headache. Peripheral factors have traditionally been considered important in TTH, and many studies have reported increased tenderness and hardness of pericranial myofascial tissues in TTH patients. In addition, the increased myofascial pain sensitivity in TTH could also be caused by central factors; (a) sensitization of second-order neurons at the level of the spinal dorsal horn/trigeminal nucleus; (b) sensitization of supraspinal neurons; and (c) decreased antinociceptive activity from supraspinal structures. Furthermore, increased excitability of the central nervous system generated by repetitive and sustained pericranial myofascial input may be responsible for the transformation of non-chronic TTH into the chronic one.[2] Appropriate exercise, bathing, and massage are alternative therapies, and NSAIDs are used as acute treatment.[3]
Kakkonto (TJ-1) is composed of 7 herbal components. It is available as OTC drugs in Japan and is often used to treat common cold at the early stage. Empirically, kakkonto is effective for headache, shoulder stiffness, muscle pain, and pain in hands and shoulder, presumably because its herbal components perform each effect; mao has adrenergic effects improving capillary circulation in the muscles, shakuyaku has an analgesic effect, kanzo has an anti-inflammatory effect, and keihi warms up the body. Also, some of these effects are basically studied and revealed in animal and in vitro experimental models.[1] These effects may have favorable effects on TTH, but further basic studies are desired.
Kampo medicine for migraine
There are some hypotheses of the pathogeneses of migraine; vascular, neural, and trigeminovascular theory. In the vascular theory, platelet hyper-aggregation may be caused by collagen, thrombin, adenosine diphosphate, serotonin, thromboxane A2. Serotonin is excessively released from platelets, and the elevation of cerebral blood levels of serotonin is thought to cause the aura of the first stage of migraine by contracting the cerebral blood vessels with cortical spreading depression. Furthermore, it is thought that because the excessive serotonin released is immediately metabolized, the second stage of migraine with severe headache is due to the relaxation of the cerebral blood vessels. Also, in the trigeminovascular theory, it has been postulated that the release of inflammatory neuropeptides such as calcitonin gene-related peptide and substance P by trigeminal nerve fibers causes neurogenic inflammation and subsequent sensitization.[9] Therefore, serotonin, vascular constriction, and inflammation seem important.
Goshuyuto (TJ-31) is composed of 4 herbal components. In basic research, goshuyuto inhibits platelet aggregation in guinea-pig whole blood,[5] constricts the isolated rat aorta.[4] These findings suggested that goshuyuto decreases platelet hyper-aggregation, preventing the excess serotonin release, and it constricts vessels appropriately, avoiding acute relaxation of the blood vessel constriction. In clinical research, after 12 weeks of treatment by goshuyuto for its responder with chronic headache, the blood serotonin level increased[13] and lateralization of the pupillary dynamics decreased.[23] These findings suggest that raising serotonin levels beforehand by goshuyuto may suppress the hyper-reactivity of serotonin receptors for serotonin, and goshuyuto would maintain the appropriate autonomic nerve conditions.
Goreisan (TJ-17) is composed of 5 herbal components and is used to adjust the water balance of the body, both edema and dehydration, by inhibiting mainly aquaporin 4 (AQP4)[10] channels as well as other AQP subtypes. AQP 3, 4, and 5 enhance chemokine production,[18] and goreisan has a potential of anti-inflammatory effect through inhibiting AQPs[6] as well as adjusting water balance. These two mechanisms would contribute to migraine relief by goreisan.
Limitation of this study
First, the number of the sample was small, and this study performed in a single hospital. Other home doctors or internal medicine hospitals also treat headaches, so not all headache patients in the Kesennuma area could necessarily be studied. Second, we did not separate chronic migraine and TTH (15 or more days per month) and those non-chronic (less than 15 days per month). Its mechanism and efficacy of the medication are supposed to be different in each type.[3] Therefore, we should have investigated the frequency per month and use it to make prediction models. Third, the follow-up period is short as 1 week, and it is difficult to judge whether the improvement is due to medication, the placebo effect, or spontaneous remission. We also should have investigated the number of intake of prescribed medication and the change of severity, frequency, or duration of the headache. Fourth, the effect of comorbidities, such as orthopedic diseases treated by analgesic or psychotic drugs, should be considered in detail.