This study aimed to investigate the analgesic effect of substance P (SP) in an animal model of neuropathic pain. An experimental model of neuropathic pain, the chronic constriction injury (CCI) model, was established using ICR mice. An intravenous (i.v.) injection of SP (1 nmole/kg) was administered to the mice to examine the analgesic effects of systemic SP on neuropathic pain. Behavioral testing and immunostaining was performed following treatment of the CCI model with SP. SP attenuated mechanical allodynia in a time-dependent manner, beginning at 1 h following administration, peaking at 1 day post-injection, and decaying by 3 days post-injection. The second injection of SP also increased the threshold of mechanical allodynia, with the effects peaking on day 1 and decaying by day 3. A reduction in phospho-ERK and glial fibrillary acidic protein (GFAP) accompanied the attenuation of mechanical allodynia. We have shown for the first time that i.v. administration of substance P attenuated mechanical allodynia in the maintenance phase of neuropathic pain using von Frey’s test, and simultaneously reduced levels of phospho-ERK and GFAP, which are representative biochemical markers of neuropathic pain. Importantly, glial cells in the dorsal horn of the spinal cord (L4–L5) of SP-treated CCI mice, expressed the anti-inflammatory cytokine, IL-10, which was not seen in vehicle saline-treated mice. Thus, i.v. administration of substance P may be beneficial for improving the treatment of patients with neuropathic pain, since it decreases the activity of nociceptive factors and increases the expression of anti-nociceptive factors.
Administration, Intravenous* ; Animals ; Behavior Rating Scale ; Biomarkers ; Constriction ; Glial Fibrillary Acidic Protein ; Humans ; Hyperalgesia* ; Interleukin-10 ; Mice ; Mice, Inbred ICR ; Models, Animal ; Models, Theoretical ; Neuralgia ; Neuroglia ; Spinal Cord ; Spinal Cord Dorsal Horn ; Substance P*

Medical nutrition therapy (MNT) is considered a keystone of medical treatment of chronic diseases. However, only few studies have evaluated medical and economical outcome of MNT. The study was performed on the patient with type 2 diabetes mellitus to evaluate the effect of clinical and cost-effective outcomes of MNT. Subjects from two general hospitals were randomly assigned to two different groups; One receiving basic nutritional education (BE)(n = 35), and the other receiving intensive nutritional education (IE)(n = 32) for a 6-month clinical trial. The group which received BE had a single visit with a dietitian, while the other group which received IE had an initial visit with a dietitian addition to two visits during the first 4 weeks of the study periods. Anthropometric parameters, blood components, and dietary intake were measures at the beginning of study period and after 6 month. Cost-effective analysis included direct labor costs, educational materials and medication cost difference during 6 months. After 6 month, subjects from IE group showed significant reduction of body weight (p < 0.05) and systolic blood pressure (p < 0.05), whereas BE group did not show any significant changes. Result from biochemical indices showed glycated hemoglobin concentration was significantly reduced by 0.7% (p < 0.05) only in the IE group. The ratio of energy intake to prescribed energy intake decreased significantly in both groups (p < 0.05). Mean time taken for a dietitian to educate the subject was 67.9 +/- 9.3 min/person for BE group, while 96.4 +/- 12.2 min/person for IE group. Mean number of educational materials was 1.9 +/- 0.7/person for BE group and 2.5 +/- 0.7/person for IE group. Change in glycated hemoglobin level along the 6 month period of study can be achieved with an investment of \88,510/% by implementing BE and \53,691/% by implementing IE. Considering the net cost-effect of blood glucose control and HbA1c, IE which provides MNT by dietitian had a cost efficiency advantage than that of BE. According to this study, MNT provided by dietitian had a significant improvements in medical and clinical outcomes compared to that of BE intervention. Therefore, MNT protocol should be performed by systemic intensive nutrition care by dietitian in clinical setting to achieve good therapeutic results of DM with lower cost.
Blood Glucose ; Blood Pressure ; Body Weight ; Chronic Disease ; Cost-Benefit Analysis ; Diabetes Mellitus, Type 2 ; Energy Intake ; Hemoglobins ; Hospitals, General ; Humans ; Imidazoles ; Investments ; Nitro Compounds ; Nutrition Therapy

BACKGROUND: Hair follicles are among a handful of organs that exhibit immune privilege. Dysfunction of the hair follicle immune system underlies the development of inflammatory diseases, such as alopecia areata. METHODS: Quantitative reverse transcription PCR and immunostaining was used to confirm the expression of major histocompatibility complex class I in human dermal papilla cells. Through transcriptomic analyses of human keratinocyte stem cells, major histocompatibility complex class I was identified as differentially expressed genes. Organ culture and patch assay were performed to assess the ability of WNT3a conditioned media to rescue immune privilege. Lastly, CD8? T cells were detected near the hair bulb in alopecia areata patients through immunohistochemistry. RESULTS: Inflammatory factors such as tumor necrosis factor alpha and interferon gamma were verified to induce the expression of major histocompatibility complex class I proteins in dermal papilla cells. Additionally, loss of immune privilege of hair follicles was rescued following treatment with conditioned media from outer root sheath cells. Transcriptomic analyses found 58 up-regulated genes and 183 down-regulated genes related in MHC class I? cells. Using newborn hair patch assay, we demonstrated that WNT3a conditioned media with epidermal growth factor can restore hair growth. In alopecia areata patients, CD8? T cells were increased during the transition from mid-anagen to late catagen. CONCLUSION Identification of mechanisms governing epithelial and mesenchymal interactions of the hair follicle facilitates an improved understanding of the regulation of hair follicle immune privilege.

In this study, we aim to determine the in vivo effect of human umbilical cord blood-derived multipotent stem cells (hUCB-MSCs) on neuropathic pain, using three, principal peripheral neuropathic pain models. Four weeks after hUCB-MSC transplantation, we observed significant antinociceptive effect in hUCB-MSC–transplanted rats compared to that in the vehicle-treated control. Spinal cord cells positive for c-fos, CGRP, p-ERK, p-p 38, MMP-9 and MMP 2 were significantly decreased in only CCI model of hUCB-MSCs-grafted rats, while spinal cord cells positive for CGRP, p-ERK and MMP-2 significantly decreased in SNL model of hUCB-MSCs-grafted rats and spinal cord cells positive for CGRP and MMP-2 significantly decreased in SNI model of hUCB-MSCs-grafted rats, compared to the control 4 weeks or 8weeks after transplantation (p<0.05). However, cells positive for TIMP-2, an endogenous tissue inhibitor of MMP-2, were significantly increased in SNL and SNI models of hUCB-MSCs-grafted rats. Taken together, subcutaneous injection of hUCB-MSCs may have an antinociceptive effect via modulation of pain signaling during pain signal processing within the nervous system, especially for CCI model. Thus, subcutaneous administration of hUCB-MSCs might be beneficial for improving those patients suffering from neuropathic pain by decreasing neuropathic pain activation factors, while increasing neuropathic pain inhibition factor.
Animals ; Cord Blood Stem Cell Transplantation ; Humans* ; Injections, Subcutaneous ; Multipotent Stem Cells* ; Nervous System ; Neuralgia* ; Rats* ; Spinal Cord ; Tissue Inhibitor of Metalloproteinase-2 ; Umbilical Cord*