Non-steroidal anti-inflammatory drug-activated gene-1 (NAG-1), also known as growth differentiation factor-15 (GDF-15), is associated with cancer, diabetes, and inflammation, while there is limited understanding of the role of NAG-1 in nociception. Here, we examined the nociceptive behaviors of NAG-1 transgenic (TG) mice and wild-type (WT) littermates. Mechanical sensitivity was evaluated by using the von Frey filament test, and thermal sensitivity was assessed by the hot-plate, Hargreaves, and acetone tests. c-Fos, glial fibrillary acidic protein (GFAP), and ionized calcium binding adaptor molecule-1 (Iba-1) immunoreactivity was examined in the spinal cord following observation of the formalin-induced nociceptive behaviors. There was no difference in mechanical or thermal sensitivity for NAG-1 TG and WT mice. Intraplantar formalin injection induced nociceptive behaviors in both male and female NAG-1 TG and WT mice. The peak period in the second phase was delayed in NAG-1 TG female mice compared with that of WT female mice, while there was no difference in the cumulative time of nociceptive behaviors between the two groups of mice. Formalin increased spinal c-Fos immunoreactivity in both TG and WT female mice. Neither GFAP nor Iba-1 immunoreactivity was increased in the spinal cord of TG and WT female mice. These findings indicate that NAG-1 TG mice have comparable baseline sensitivity to mechanical and thermal stimulation as WT mice and that NAG-1 in female mice may have an inhibitory effect on the second phase of inflammatory pain. Therefore, it could be a novel target to inhibit central nervous system response in pain.

Background: Scalding burn injuries can occur in everyday life but occur more frequently in young children. Therefore, it is important to develop more effective burn treatments. Objectives: This study examined the effects of bee venom (BV) stimulation on scalding burn injury-induced nociception in mice as a new treatment for burn pain. Methods: To develop a burn injury model, the right hind paw was immersed temporarily in hot water (65°C, 3 seconds). Immediately after the burn, BV (0.01, 0.02, or 0.1 mg/kg) was injected subcutaneously into the ipsilateral knee area once daily for 14 days. A von Frey test was performed to assess the nociceptive response, and the altered walking parameters were evaluated using an automated gait analysis system. In addition, the peripheral and central expression changes in substance P (Sub P) were measured in the dorsal root ganglion and spinal cord by immunofluorescence. Results: Repeated BV treatment at the 2 higher doses used in this study (0.02 and 0.1 mg/kg) alleviated the pain responses remarkably and recovered the gait performances to the level of acetaminophen (200 mg/kg, intraperitoneal, once daily), which used as the positive control group. Moreover, BV stimulation had an inhibitory effect on the increased expression of Sub P in the peripheral and central nervous systems by a burn injury. Conclusions These results suggest that a peripheral BV treatment may have positive potency in treating burn-induced pain.

We have previously demonstrated that the neurosteroid dehydroepiandrosterone sulfate (DHEAS) induces functional potentiation of N-methyl-D-aspartate (NMDA) receptors via increases in phosphorylation of NMDA receptor GluN1 subunit (pGluN1). However, the modulatory mechanisms responsible for the expression of the DHEA-synthesizing enzyme, cytochrome P450c17 following peripheral nerve injury have yet to be examined. Here we determined whether oxidative stress induced by the spinal activation of nitric oxide synthase type II (NOS-II) modulates the expression of P450c17 and whether this process contributes to the development of neuropathic pain in rats. Chronic constriction injury (CCI) of the sciatic nerve induced a significant increase in the expression of NOS-II in microglial cells and NO levels in the lumbar spinal cord dorsal horn at postoperative day 5. Intrathecal administration of the NOS-II inhibitor, L-NIL during the induction phase of neuropathic pain (postoperative days 0~5) significantly reduced the CCI-induced development of mechanical allodynia and thermal hyperalgesia. Sciatic nerve injury increased the expression of PKC- and PKA-dependent pGluN1 as well as the mRNA and protein levels of P450c17 in the spinal cord at postoperative day 5, and these increases were suppressed by repeated administration of L-NIL. Co-administration of DHEAS together with L-NIL restored the development of neuropathic pain and pGluN1 that were originally inhibited by L-NIL administration alone. Collectively these results provide strong support for the hypothesis that activation of NOS-II increases the mRNA and protein levels of P450c17 in the spinal cord, ultimately leading to the development of central sensitization and neuropathic pain induced by peripheral nerve injury.
Animals ; Central Nervous System Sensitization ; Constriction ; Cytochromes ; Dehydroepiandrosterone ; Dehydroepiandrosterone Sulfate ; Hyperalgesia ; N-Methylaspartate ; Neuralgia ; Nitric Oxide Synthase Type II ; Nitric Oxide Synthase ; Nitric Oxide ; Oxidative Stress ; Peripheral Nerve Injuries ; Phosphorylation ; Rats ; RNA, Messenger ; Rodentia ; Sciatic Nerve ; Spinal Cord ; Spinal Cord Dorsal Horn

Respiratory inflammation is a frequent and fatal pathologic state encountered in veterinary medicine. Although diluted bee venom (dBV) has potent anti-inflammatory effects, the clinical use of dBV is limited to several chronic inflammatory diseases. The present study was designed to propose an acupoint dBV treatment as a novel therapeutic strategy for respiratory inflammatory disease. Experimental pleurisy was induced by injection of carrageenan into the left pleural space in mouse. The dBV was injected into a specific lung meridian acupoint (LU-5) or into an arbitrary non-acupoint located near the midline of the back in mouse. The inflammatory responses were evaluated by analyzing inflammatory indicators in pleural exudate. The dBV injection into the LU-5 acupoint significantly suppressed the carrageenan-induced increase of pleural exudate volume, leukocyte accumulation, and myeloperoxidase activity. Moreover, dBV acupoint treatment effectively inhibited the production of interleukin 1 beta, but not tumor necrosis factor alpha in the pleural exudate. On the other hand, dBV treatment at non-acupoint did not inhibit the inflammatory responses in carrageenan-induced pleurisy. The present results demonstrate that dBV stimulation in the LU-5 lung meridian acupoint can produce significant anti-inflammatory effects on carrageenan-induced pleurisy suggesting that dBV acupuncture may be a promising alternative medicine therapy for respiratory inflammatory diseases.
Acupuncture ; Acupuncture Points ; Animals ; Bee Venoms ; Bees ; Carrageenan ; Complementary Therapies ; Exudates and Transudates ; Hand ; Inflammation ; Interleukin-1beta ; Leukocytes ; Lung ; Mice ; Peroxidase ; Pleurisy ; Tumor Necrosis Factor-alpha ; Veterinary Medicine

In this study, we examined the antinociceptive effect of Cyperi rhizoma (CR) and Corydalis tuber (CT) extracts using a chronic constriction injury-induced neuropathic pain rat model. After the ligation of sciatic nerve, neuropathic pain behavior such as mechanical allodynia and thermal hyperalgesia were rapidly induced and maintained for 1 month. Repeated treatment of CR or CT (per oral, 10 or 30 mg/kg, twice a day) was performed either in induction (day 0~5) or maintenance (day 14~19) period of neuropathic pain state. Treatment of CR or CT at doses of 30 mg/kg in the induction and maintenance periods significantly decreased the nerve injury-induced mechanical allodynia. In addition, CR and CT at doses of 10 or 30 mg/kg alleviated thermal heat hyperalgesia when they were treated in the maintenance period. Finally, CR or CT (30 mg/kg) treated during the induction period remarkably reduced the nerve injury-induced phosphorylation of NMDA receptor NR1 subunit (pNR1) in the spinal dorsal horn. Results of this study suggest that extracts from CR and CT may be useful to alleviate neuropathic pain.
Animals ; Constriction ; Corydalis ; Horns ; Hot Temperature ; Hyperalgesia ; Ligation ; N-Methylaspartate ; Neuralgia ; Phosphorylation ; Rats ; Sciatic Nerve

The sigma-1 receptor has recently been implicated in a myriad of cellular functions and biological processes. Previous studies have demonstrated that the spinal sigma-1 receptor plays a pro-nociceptive role in acute pain and that the direct activation of sigma-1 receptor enhances the nociceptive response to peripheral stimuli, which is closely associated with calcium-dependent second messenger cascades including protein kinase C (PKC). In addition, the activation of sigma-1 receptor increases PKC- and protein kinase alpha (PKA)-dependent phosphorylation of the N-Methyl- D-aspartate (NMDA) receptor in the spinal cord, which results in the potentiation of intrathecal NMDA-evoked spontaneous pain behavior. Moreover, the blockade of spinal sigma-1 receptor suppresses the development of neuropathic pain and blocks the increase of phosphorylation of extracellular signal-regulated kinase (ERK) as well as pNR1 in the spinal cord. Recently, it was also reported that spinal neurosteroids such as pregnenolone and dehydroepiandrosterone sulfate, which are recognized as endogenous ligands for sigma-1 receptor, could produce mechanical hypersensitivity via sigma-1 receptor-mediated increase of pNR1. Collectively, these findings demonstrate that the activation of spinal sigma-1 receptor or the increase of neurosteroids is closely associated with the acute pain sensation or the development of chronic pain, and imply that sigma-1 receptor can be a new potential target for the development of analgesics.
Acute Pain ; Analgesics ; Biological Processes ; Central Nervous System Sensitization ; Chronic Pain ; D-Aspartic Acid ; Dehydroepiandrosterone Sulfate ; Hypersensitivity ; Ligands ; Neuralgia ; Neurotransmitter Agents ; Phosphorylation ; Phosphotransferases ; Pregnenolone ; Protein Kinase C ; Protein Kinases ; Receptors, sigma ; Second Messenger Systems ; Sensation ; Spinal Cord

PURPOSE: Patients who have a elbow flexion limitation from burn often contend with a severe functional problem in activity of daily living. Positional splint or serial casting have been invented to prevent from elbow contracture, which splint could not improved the range of motion more than 90 flexion. The purpose of this article is to present a dynamic forced elbow flexion orthosis with limited motion joint to overcome the problem of less effective function of correctability of conventional splints. METHODS: The cases were 3rd degree burned patients of upper extremities who had a elbow joint flexion limitation from the post burn skin or joint contracture. This dynamic elbow flexion brace device was fabricated with the dynamic force of the elbow joint, which was induced by a rubber band or spring device into the orthotic joint. The orthosis kept a lower grade constant corrective force with coustom made design and strong strap fixation with comfortable material. RESULTS: This dynamic elbow flexion brace device was fabricated for two burn patients who had 24% and 37% TBSA in a flame burn with extensive involvement of the upper extremities. They developed hypertrophic scar and skin contracture around both elbow joint. Both patients had moderate to severe elbow joint limitation of motion. Patients with elbow limitation had improved the range of motion more than 90 flexion by this dynamic elbow flexion brace. CONCLUSION: The dynamic forced elbow flexion orthosis with limited motion joint had improved the range of motion more than 90 flexion, however those has some problems which ought to be improved to more effective and comfortable function.
Braces ; Burns ; Cicatrix, Hypertrophic ; Contracture ; Elbow ; Elbow Joint ; Humans ; Joints ; Orthotic Devices ; Range of Motion, Articular ; Rubber ; Skin ; Splints ; Upper Extremity

PURPOSE: To provide epidemiologic data of the burn injuries in stroke patients and to determine the most effective prevention and education methods. METHODS: We retrospectively reviewed the medical records of patients who had been admitted to the burn center at the Hangang Sacred Heart Hospital between January 2002 and June 2008. Burn cause, size, depth, duration of hospital stay, rate of operation performed, outcomes and time from stroke onset to burn were reviewed and compared. RESULTS: We reviewed the charts of total 87 patients (57 men and 30 women with a mean age of 61.95+/-14.48 years). Places of burn were divided into two groups (at home: n=52, outside: n=25) and patients injured at home were more than twice than who were outside. According to etiology of infarction, patients group was divided into ischemic (n=49) and hemorrhagic (n=38) group. Most of the patients were injured from flame burn. The rate of operation for ischemic group was significantly higher than hemorrhagic group. The etiology of infarction and cause of burn were not significant to prognosis. Chronic group (defined as burn occurred 6 months after the onset of stroke) had the higher incidence of burn injuries. But, there was no significant relationship between the time from stroke onset to burn and burn cause, prognosis, rate of operation, total body surface area burned. Non-survivor group had a higher operation rate than survivor group, although there was no difference in total burn surface area. CONCLUSION: Functional recovery of stroke was not associated with burn injury in our study. Flame burn took the highest percentage of burn causes. We believe that studies pooling different center's results are need to improve significance of conclusion drawn from these data.
Body Surface Area ; Burn Units ; Burns ; Female ; Heart ; Humans ; Incidence ; Infarction ; Length of Stay ; Male ; Medical Records ; Prognosis ; Retrospective Studies ; Stroke ; Survivors

PURPOSE: Monoclonal antibody Ki-67 has been employed to evaluate the growth fraction of various tumors. The purpose of this study is to determin the prognostic value of the Ki-67 index for colorectal cancer. METHODS: The Ki-67 index was investigated by counting the immunohistochemically stained cells. We described this as the permillage. We reviewed the test results of 36 colorectal cancer patients and we compared the Ki-67 index with other clinical factors. RESULTS: There was no correlation between the Ki-67 index and the other established risk factors, and only the number of invaded lymph nodes and their degree of differentiation were related with the Ki-67 index. CONCLUSION: The Ki-67 index is an important marker of the growth fraction of tumor. The pattern of tumor growth is determined not only by the growth fraction, so the discovery of other parameters that can reflect tumor growth and the Ki-67 index can help the patients with respect to their prognosis & treatment.
Colorectal Neoplasms* ; Humans ; Lymph Nodes ; Prognosis ; Risk Factors

Recombinant human epidermal growth factor (rhEGF) stimulates the proliferation and migration of epithelial cells in human cell culture systems and animal models of partial-thickness skin wounds. This study investigated the effect of a topical rhEGF ointment on the rate of wound healing and skin re-epithelialization in a rat full thickness wound model, and verified whether or not the rhEGF treatment affected both myofibroblast proliferation and collagen synthesis in the dermis. When rhEGF (10 microgram/g ointment) was applied topically twice a day for 14 days, there was significantly enhanced wound closure from the 5th to the 12th day compared with the control (ointment base treatment) group. A histological examination at the postoperative 7th day revealed that the rhEGF treatment increased the number of proliferating nuclear antigen immunoreactive cells in the epidermis layer. In addition, the immunoreactive area of alpha-smooth muscle actin and the expression of prolyl 4-hydroxylase were significantly higher than those of the control group. Overall, a topical treatment of rhEGF ointment promotes wound healing by increasing the rate of epidermal proliferation and accelerating the level of wound contraction related to myofibroblast proliferation and collagen deposition.
Actins/genetics/metabolism ; Administration, Topical ; Animals ; Cell Proliferation/drug effects ; Collagen/*biosynthesis ; Epidermal Growth Factor/*administration&dosage/*pharmacology ; Gene Expression Regulation ; Male ; Myoblasts, Skeletal/*drug effects ; Proliferating Cell Nuclear Antigen/genetics/metabolism ; Rats ; Rats, Sprague-Dawley ; Wound Healing/*drug effects