Abstract
Yokukansan, one of the traditional Japanese herbal medicines, ameliorated neuropathic pain symptoms in patients. In this study, we investigated the effects of yokukansan on neuropathic pain in chronic constriction injury (CCI) model. Oral administration of yokukansan significantly inhibited mechanical and cold allodynia in the von Frey hair or acetone test, respectively. In comparison, amitriptyline, a tricyclic antidepressant, demonstrated moderate, but not significant, antiallodynic effects in the mechanical and cold tests. Yokukansan significantly inhibited the cerebrospinal fluid dialysate level of glutamate that had increased by the stimulation of brush or acetone. Glutamate transporter inhibitors, DL-threo-beta-hydroxy aspartate and dihydrokainate, decreased the yokukansan-induced antiallodynic actions in CCI rats. Our results suggest that yokukansan was confirmed to have antiallodynic effects in CCI rats, which are related to a blockade of glutamatergic neurotransmission via activation of glutamate transporters in the spinal cord.
Highlights
Chronic pain related to peripheral neuropathy is clinically important
We evaluated the effects of yokukansan on Evidence-Based Complementary and Alternative Medicine allodynia using rats with constriction injury (CCI)-induced neuropathy in this study
Cold allodynia of the injured hind paw was dose dependently reduced by administration of yokukansan (0.3, 1.0 g/kg, p.o.) when compared with the control (Figure 1(b))
Summary
Chronic pain related to peripheral neuropathy is clinically important. Neuropathic pain is often characterized by pathological symptoms such as hyperalgesia and allodynia, as reported for spontaneous pain [1, 2]. For the treatment of neuropathic pain, opioid analgesics, tricyclic antidepressants, anticonvulsive agents such as gabapentin, and topical anesthetics have been administered, and nonpharmacological treatments including acupuncture and electrical stimulation have been performed. They are not completely effective in ameliorating neuropathic pain, new treatments and drugs are necessary [3, 4]. Yokukansan is one of the traditional Japanese medicines called kampo in Japan. It is composed of seven kinds of medicinal herbs. We previously found that yokukansan clinically attenuates neuropathic pain due to postherpetic neuralgia, complex regional pain syndrome, and central cord syndrome and reported that yokukansan ameliorates neuropathic pain symptoms in patients [7]
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