Objective : Frutus gardeniae, seed of Gardenia jasminoides Ellis is one of the crude drugs used for the treatment of inflammatory condition in oriental medicine. Methodes : The present study aimed to examine the analgesic effect and anti-inflammatory effect of Frutus gardeniae extract (FGE) on a rat model of ankle sprain pain, and the relations between FGE-induced effect and endogenous nitric oxide (NO) and inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and c-Fos protein expression in the spinal cord. As a chronic pain model, ankle sprain pain model was used to test the effect of FCE injection applied to acupuncture point. After the induction of ankle sprain, rats subsequently showed a reduced stepping force of the affected limb for at least the next 4 days. The reduced stepping force of the limb was presumably due to a painful knee. FGE dissolved in normal saline was injected several acupoints. Results : After the treatment, behavioral tests measuring stepping force were periodically conducted during the next 8 hours. FGE produced significant improvement of stepping force of the hindlimb affected by the ankle sprain lasting at least 4 hours. FGE produced the improvement of stepping force of the affected hindlimb in a dose-dependent manner. In addition, FGE injection showed inhibitory effect on the paw edema induced by ankle sprain. Both NO production and iNOS, COX-2 protein expression increased by ankle sprain were suppressed by FGE. FGE on combination with electroacupuncture (EA) produced more powerful and longer lasting improvement of stepping force of the hindlimb affected by the ankle sprain than either FGE or EA did. The present study suggest that FGE produces a potent analgesic effect on the ankle sprain pain model of the rat and that FGE-induced analgesia modulate endogenous NO through the suppression of iNOS/COX-2 protein expression.
Dayem, Ahmed Abdal;Song, Kwonwoo;Lee, Soobin;Kim, Aram;Cho, Ssang-Goo
BMB Reports
/
제55권5호
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pp.205-212
/
2022
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating chronic disorder characterized by suprapubic pain and urinary symptoms such as urgency, nocturia, and frequency. The prevalence of IC/BPS is increasing as diagnostic criteria become more comprehensive. Conventional pharmacotherapy against IC/BPS has shown suboptimal effects, and consequently, patients with end-stage IC/BPS are subjected to surgery. The novel treatment strategies should have two main functions, anti-inflammatory action and the regeneration of glycosaminoglycan and urothelium layers. Stem cell therapy has been shown to have dual functions. Mesenchymal stem cells (MSCs) are a promising therapeutic option for IC/BPS, but they come with several shortcomings, such as immune activation and tumorigenicity. MSC-derived extracellular vesicles (MSC-EVs) hold numerous therapeutic cargos and are thus a viable cell-free therapeutic option. In this review, we provide a brief overview of IC/BPS pathophysiology and limitations of the MSC-based therapies. Then we provide a detailed explanation and discussion of therapeutic applications of EVs in IC/BPS as well as the possible mechanisms. We believe our review will give an insight into the strengths and drawbacks of EV-mediated IC/BPS therapy and will provide a basis for further development.
Objective : Although chronic non-bacterial prostatitis is a common disease, it is very difficult to treat effectively. Toosendan fructus(TOF) has been traditionally used in treatment of abdominal pain and parasite. In this study, we investigated the therapeutic effects and action mechanism of Toosendan fructus (TOF) in the rat model of non-bacterial prostatitis induced by castration and testosterone treatment. Method : Eight-month-old rats were treated with $17{\beta}$-estradiol after castration for induction of experimental non-bacterial prostatitis, which is similar to human chronic prostatitis in histophatological profiles. Toosendan fructus(TOF) and testosterone were administered as an experimental specimen and a positive control, respectively. The prostates were evaluated by histopahological parameters including the epithelial score and epithelio-stromal ratio for glandular damage. Also, the prostates were observed by hematological alterations of WBC, RBC, hemoglobin, hematocrit and platelet. Results : While prostates of control rats revealed severe acinar gland atrophy and stromal proliferation, the rats treated with Toosendan fructus(TOF) showed a diminished range of the tissue damage. Epithelial score was improved in Toosendan fructus(TOF) than that of the control. The epithelio-stromal ratio was lower in Toosendan fructus(TOF) when compared to that of the control. Also, the examination of bloods were not observed hematological change. Conclusions : These findings suggest that Toosendan fructus(TOF) may protect the glandular epithelial cells and may take hematological safety. We concluded that Toosendan fructus(TOF) may could be a useful remedy agents for treating the chronic non-bacterial prostatitis.
Objectives : This study was purposed to investigate the Anti-inflammatory and Analgesic Effects of Gold injection Aqua-acupuncture on the experimental model of rheumatoid arthritis. Methods : The experimental groups were divided into 4 groups : Control group (group injected with normal saline), J-NS (group injected with normal saline into bilateral Choksamni(ST36)), J-GS (group injected with Gold Injection into bilateral Choksamni(ST36)), and N-GS (injected with Gold Injection into the blank locus of the root of mouse tail). In addition, Diclofenac-Na as a comparative medicine is injected into bilateral Choksamni(ST36) and the blank locus of the root of mouse tail. So we measured the mice paw edema induced by Carrageenin and Dextran, the chronic rat paw edema induced by adjuvant, vascular permeability induced by Acetic acid in mice, the writhing syndrome induced by Acetic acid in mice, the heat-induced pain threshold in mice. Results : The following result have been obtained. 1. The mice paw edema induced by Carrageenin was significantly decreased in J-GS as compared with the control group. 2. The mice paw edema induced by Dextran was significantly decreased in J-GS and N-GS as compared with the control group. 3. The chronic rat paw edema induced by Adjuvant was significantly decreased in J-GS and N-GS as compared with the control group. Serum Iron content was significantly decreased in J-GS and N-GS as compared with the control group. But the effect on the Serum Copper contents has no significance statistically. 4. Vascular permeability induced by Acetic acid in mice was significantly decreased in J-GS and N-GS as compared with the control group. 5. The level of Acetic acid-induced Writhing syndrome and Heat-induced Pain Threshold in mice were all significantly decreased in J-GS and N-GS as compared with the control group. Conclusion : According to the result, gold injection aqua-acupuncture has significant anti-inflammatory and analgesic effects on the experimental model of rheumatiod arthiritis.
Background: A nerve ligation injury may produce a tactile allodynia. The effects of intrathecally delivered lamotrigine on allodynia induced due to fifth and sixth lumbar spinal nerves ligation in rats, using lumbar intrathecal catheters were examined. Methods: Sprague-Dawley rats (body weight 160-180 g) were prepared by tightly ligating the fifth and sixth left lumbar spinal nerves, with the implantation of a chronic intrathecal catheter for drug administration. Mechanical allodynia and allodynic threshold were measured using von Frey filaments and the updown method, respectively. After the baseline hind paw withdrawal thresholds had been obtained, lamotrigine (10, 30, 100 and $300{\mu}g$) was administered intrathecally. Thereafter, the dose-response curves and 50% effective dose ($ED_{50}$) were obtained. Motor dysfunction was assessed by observing the righting/stepping reflex responses and abnormal weight bearing. Results: Intrathecal administration of lamotrigine produced a dose-dependent antiallodynic action ($ED_{50}=61.7{\mu}g$). Mild motor weakness was observed with $300{\mu}g$ lamotrigine, but no severe motor impairment was found. Conclusions: It is suggested that intrathecal lamotrigine could produce moderate antagonism of mechanical allodynia at the spinal level in a rat neuropathic pain model with minimal motor weakness.
Background: The purpose of this study was to investigate the relationship between the spine and the flat-foot, the stability and the alignment of the posture of the neck to prevent the alignment of the ankle joint operation and the lower back flexibility of the lumbar region according to the type of treatment using active stretching of the triceps, back pain, and to see how they affect weight bearing differences. Methods: The subjects of this study were 24 chronic low back pain patients. They were randomly divided into experimental group and control group. In the experimental group, ankle joint mobilization and active scraping of triceps were performed three times a week for a total of 6 weeks. The control group was performed in the same way without articulation. The range of flexion and extension motion of the lumbar spine and pain degree and difference of weight-bearing were measured before and after the experiment. Results: The model of ankle joint mobilization and calf muscle elongation of flat foot significantly improved the range of flexion and extension motion of the vertebrae (p<.05) and the VAS and distribution of weight-bearing were decreased in both of two groups (p<.05). In other words, the exercise and mobilization help to recover of the balance of the whole musculoskeletal, the vertebrae. Conclusions: The active exercise of the triceps muscle of the lower leg in this study It affects the flexibility of the lumbar spine, the pain and the difference in the weight support of the lower extremities, when we performed ankle joint mobilization for exercise and cramping, pain and the difference in weight support between the two lower limbs.
Purpose : The purpose of this meta-analysis was to evaluate the effects of electrical stimulation on patients with non-specific low back pain. Methods : Domestic databases were gathered from studies that conducted clinical trials associated with electrical stimulation and its impact on pain of non-specific low back patients. A total of 681 studies were identified, with 12 studies satisfying the inclusion data. The studies consisted of patient, intervention, comparison, outcome, and study design (PICO-SD). The search outcomes were items associated with low back pain. Cochrane risk of bias 2 (RoB 2) was used to evaluate the quality of 12 randomized controlled trials. Effect sizes (Hedges's g) in this study were computed as the corrected standard mean difference (SMD). A random-effect model was used to analyze the effect size because of the high heterogeneity among the studies. Egger's regression and 'trim-and-fill' tests were carried out to analyze the publication bias. Cumulative meta-analysis and sensitivity analysis were conducted to analyze the effect according to the sample size and the consistency of the effect size. Results : The following factors had a large overall effect size (Hedges's g=1.28, 95 % CI=.20~2.36) involving electrical stimulation on non-specific low back pain. The subgroup analysis all showed a statistical difference in the types of study design, electrical stimulation, and assessment tool. No statistically significant difference was found in the meta-regression analysis. Publican bias was found in the data. Conclusion : The findings in this study indicate that electrical stimulation interventions have a positive effect on patients with non-specific low back pain. However, due to the low quality of studies and publication bias, the results of our study should be interpreted cautiously.
Background: Discogenic pain can develop into chronic low back pain that is very difficult to treat effectively, because the pathogenesis of the disease still remains controversial. To clarify the pathogenesis, numerous animal models of intervertebral disc degeneration have been proposed in the literature, each with attendant advantages and disadvantages. The aim of this study was to determine the most efficacious method and dose of complete Freund's adjuvant (CFA) injection into intervertebral disc to develop a discogenic pain in a rat. Methods: CFA was injected into the L5-L6 or L4-L5 disc of male Sprague-Dawley rats in various conditions including a dose of CFA (10, 20, or 50 uL), drilling, injection site sealing using cyanoacrylate, and injection velocity. Sham animals were subjected to the same procedure, except for the CFA injection. Mechanical and heat allodynia were serially measured at both hindpaws until 8 weeks post-operatively. Serial MRI analyses were performed to observe degenerative changes of the discs. In addition, CGRP & Substance P-immunoreactivities (ir) in the superficial dorsal horn were evaluated at 4 weeks using immunohistochemistry. Results: Each condition provoked various problems such as development of hindpaw paralysis, CFA leakage, and no pain development. Mid-sagittal T2 MRI revealed no significant degenerative changes in the CFA injected disc. The CGRP-ir of the bilateral superficial dorsal horns at the level of L5-L6 was significantly increased in the CFA group. Conclusions: A total of 10 uL CFA injection into L5-L6 disc for a period of 10 minutes using a 26-gauge needle without drilling was the most efficacious way to develop discogenic pain animal model.
Background: Nerve ligation injury may produce mechanical allodynia, but this can be reversed after an intrathecal administration of adenosine analogues. In many animal and human studies, ATP-sensitive potassium channel blockers have been known to reverse the antinociceptive effect of various drugs. This study was performed to evaluate the mechanical antiallodynic effects of spinal R-PIA (Adenosine A1 receptor agonist) and the reversal of these effects due to pretreatment with glibenclamide (ATP-sensitive potassium channel blocker). Thus, the relationship between the antiallodynic effects of R-PIA and ATP-sensitive potassium channel were investigated in a neuropathic model. Methods: Male Sprague Dawley rats were prepared by tightly ligating the left lumbar 5th and 6th spinal nerves and implantation of a chronic lumbar intrathecal catheter for drug administration. The mechanical allodynia was measured by applying von Frey filaments ipsilateral to the lesioned hind paw. And the thresholds for paw withdrawal assessed. In study 1, either R-PIA (0.5, 1 and $2{\mu}g$) or saline were administered intrathecally for the examination of the antiallodynic effect of R-PIA. In study 2, glibenclamide (2, 5, 10 and 20 nM) was administered intrathecally 5 min prior to an R-PIA injection for investigation of the reversal of the antiallodynic effects of R-PIA. Results: The antiallodynic effect of R-PIA was produced in a dose dependent manner. In study 1, the paw withdrawal threshold was significantly increased with $2{\mu}g$ R-PIA (P < 0.05). In study 2, the paw withdrawal threshold with $2{\mu}g$ R-PIA was significantly decreased almost dose dependently by intrathecal pretreatment of 5, 10 and 20 nM glibenclamide (P < 0.05). Conclusions: These results demonstrated that an intrathecal injection of ATP-sensitive potassium channel blockers prior to an intrathecal injection of adenosine A1 receptors agonist had an antagonistic effect on R-PIA induced antiallodynia. The results suggest that the mechanism of mechanical antiallodynia, as induced by an intrathecal injection of R-PIA, may involve the ATP-sensitive potassium channel at both the spinal and supraspinal level in a rat nerve ligation injury model.
Background: Lipo-prostaglandin E1 (Lipo-$PGE_1$) has vasodilating and platelet aggregation inhibitory characteristics and it has been used as a treatment for patients with blood flow dysfunction disease. Based on the mechanisms of lumbar spinal stenosis, including veno congestion, neuro-ischemia and mechanical compression, we aimed to study whether intravenous Lipo-$PGE_1$ injection has any therapeutic effect on hyperalgesia in a rat foraminal stenosis model. Methods: In this study, twenty male Sprague-Dawley rats were divided into the control (n = 10) and Lipo-$PGE_1$ (n = 10) groups. A small stainless steel rod was inserted into the L5-6 intervertebral foramen to induce intervertebral foramen stenosis and chronic DRG compression. In the Lipo-$PGE_1$ group, $0.15{\mu}g/kg$ of Lipo-$PGE_1$ were injected intravenously via a tail vein for 10 days starting from the $3^{rd}$ day after operation. Behavioral testing for mechanical and thermal hyperalgesia was performed for 3 weeks after the injections. Results: From the $10^{th}$ day after Lipo-$PGE_1$ injection, the rats in the experimental group showed significant recovery of their mechanical threshold, and this effect was maintained for 3 weeks. No significant differences of the thermal hyperalgesia were observed between the two groups. Conclusions: These findings suggest that intravenously injected Lipo-$PGE_1$ may be effective for alleviating neuropathic pain, which isthe main symptom of spinal stenosis, by improving the blood flow dysfunction.
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