Yokukansan, a Japanese Herbal Medicine, Suppresses Substance PInduced Production of Interleukin-6 and Interleukin-8 by Human U373 MG Glioblastoma Astrocytoma Cells.

BACKGROUND: Yokukansan is a traditional Japanese herbal medicine that has an antiallodynic effect in patients with chronic pain. However, the mechanisms by which yokukansan inhibits neuropathic pain are unclear. OBJECTIVE: This study aimed to investigate the molecular effects of yokukansan on neuroinflammation in U373 MG glioblastoma astrocytoma cells, which express a functional high-affinity neurokinin 1 receptor (substance P receptor), and produce interleukin (IL)-6 and IL-8 in response to stimulation by substance P (SP). METHODS: We assessed the effect of yokukansan on the expression of ERK1/2, P38 MAPK, nuclear factor (NF)-κB, and cyclooxygenase-2 (COX-2) in U373 cells by western blot assay. Levels of IL-6 and IL-8 in conditioned medium obtained after stimulation of cells with SP for 24 h were measured by enzyme-linked immunosorbent assay. All experiments were conducted in triplicate. Results were analyzed by one-way ANOVA, and significance was accepted at p < 0.05. RESULTS: Yokukansan suppressed SP-induced production of IL-6 and IL-8 by U373 MG cells, and downregulated SP-induced COX-2 expression. Yokukansan also inhibited phosphorylation of ERK1/2 and p38 MAPK, as well as nuclear translocation of NF-κB, induced by SP stimulation of U373 MG cells. CONCLUSION: Yokukansan exhibits anti-inflammatory activity by suppressing SP-induced production of IL-6 and IL-8 and downregulating COX-2 expression in U373 MG cells, possibly via inhibition of the activation of signaling molecules, such as ERK1/2, p38 MAPK, and NF-κB.

Changes in circadian rhythm for mRNA expression of melatonin 1A and 1B receptors in the hypothalamus under a neuropathic pain-like state.

Several clinical reports on neuropathic pain of various etiologies have shown that it significantly interferes with sleep. Inadequate sleep due to neuropathic pain may contribute to the stressful negative consequences of living with pain. It is generally recognized that melatonin (MT) system in the hypothalmus is crusial for circadian rhythm and sleep-wake transition. However, little, if any, is known about whether neuropathic pain could affect the MT system associated with sleep disturbance. In this study, we investigated the possible changes in circadian rhythm for the expression of MT receptors, especially MT1A and MT1B receptors, in the hypothalamus of mice with sciatic nerve ligation. The samples for real-time RT-PCR assay were prepared at 8:00, 14:00, 20:00, and 2:00 on day 7 after sciatic nerve ligation or sham operation. The mRNA expression of MT1A and MT1B receptors at 2:00 in sciatic nerve-ligated mice, which exhibited thermal hyperalgesia along with an increase in wakefulness and a decrease in nonrapid eye movement sleep, was significantly greater than those in sham-operated mice, whereas the levels of both MT1A and MT1B receptors at 8:00 in sciatic nerve-ligated mice were significantly lower than those in sham-operated mice. These findings suggest that neuropathic pain-like stimuli lead to sleep disturbance in parallel with changes in circadian rhythm for mRNA expression of MT 1A and 1B receptors in the hypothalamus of mice.

Efficacy of limited-duration spinal cord stimulation for subacute postherpetic neuralgia.

Excellent outcomes were achieved with spinal cord stimulation (SCS) for 7 to 10 days on 2 patients who developed postherpetic neuralgia. Both patients were within 2 to 3 months of the onset of the condition, and nerve blocks provided only temporary pain relief and drug therapies had poor efficacy. The authors believe that limited-duration SCS for subacute postherpetic neuralgia is a useful treatment approach that may prevent the pain from progressing to chronic postherpetic neuralgia.

[A case of intractable lower limb pain treated successfully by spinal cord stimulation with an electrode inserted retrogradely].

We experienced a case of intractable lower limb pain successfuly treated by spinal cord stimulation with an electrode inserted retrogradely. The patient is a 32 year-old-man suffering from intractable lower limb pain on the area innervated by the sciatic nerve from unidentified cause for about 4 years. We tried various treatments such as epidural block, S 1 nerve-root block including thermocoagulation technique, opiate. Nevertheless, his pain became worse further. Therefore, 6 years after the onset of the symptom, we tried to stimulate electrically the nerve with an electrode inserted retrogradely. This method of spinal cord stimulation produced enough pain reduction. The method of retrograde insertion of an electrode for spinal cord stimulation seems to be a good way to treat intractable pain of the area innervated by a single spinal nerve.

[Sensory nerve anesthesia with 4% liposomal lidocaine cream in healthy subjects by use of the neuroselective current perception threshold].

BACKGROUND: ELA-Max, an external liposomal preparation of lidocaine (4%) available without prescription in United States, has a recommended application time of 15 to 45 min without occlusive dressing, and the side effect has been reported to be rare. To investigate external anesthetic preparations to reduce neuropathic pain, we evaluated sensory nerve anesthesia by ELA-Max in comparison with placebo and other lidocaine topical preparations by double blind method. METHODS: We measured the neuroselective current perception threshold (N-CPT) 30 min after the application of ELA-Max on 30 healthy Japanese volunteers. Evaluation of anesthetic effect was performed by change in N-CPT rate before and after the application of 0.025 g x cm(-2) to the skin where stimulation was performed. RESULTS: ELA-Max increased N-CPT ratio in 4 out of 9 subjects stimulated at 5 Hz. However these CPT values were within normal ranges, and the change in N-CPT ratio was not statistically significant throughout all stimulation frequencies. CONCLUSIONS: The application of 0.025 g x cm(-2) ELA-Max for 30 min was not effective to induce therapeutic level of anesthesia. Extended application times as well as occlusive dressing may be needed for this preparation to be used clinically.