Purpose: We tested whether repetitive transcranial magnetic stimulation (rTMS) improved recovery following spinal cord injury (SCI) in rats with transplantation of adipose tissue-derived stromal cells (ATSCs). Methods: Twenty Sprague-Dawley rats (200-250 g, female) were used. Moderate spinal cord injury was induced at the T9 level by a New York University (NYU) impactor. The rat ATSCs (approximately $5{\times}10^5$ cells) were injected into the perilesional area at 9 days after SCI. Starting four days after transplantation, rTMS (25 Hz, 0.1 Tesla, pulse width=$370{\mu}s$, on/off time=3 sec/3 sec) was applied daily for 7 weeks. Functional recovery was assessed using the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale as well as pain responses for thermal and cold stimuli. Results: Both groups showed similar, gradual improvement of locomotor function. rTMS stimulation decreased thermal and cold hyperalgesia after 7 weeks, but sham stimulation did not. Conclusion: rTMS after transplantation of ATSCs in an SCI model may reduce thermal hyperalgesia and cold allodynia, and may be an adjuvant therapeutic tool for pain control after stem cell therapy in SCI.
Gupta, Pushpraj S;Singh, Sunil K;Tripathi, Abhishek K
Journal of Pharmacopuncture
/
v.23
no.1
/
pp.30-36
/
2020
Objectives: The objective of the study was to prepare Bauhinia variegata loaded nanoemulsion(formulation and determine the efficacy of herbal drug formulation against diabetic peripheral neuropathic pain through acupuncture technique. Methods: Nine different ba tches of nanoemulsion (NE1 NE9) of BVN was prepared by varying the Smix ratio and the concentration of oil. BVN was characterized to determine particle size, shape, zeta potential, polydispersity index, optical transmittance, drug release profile and stora ge stability. The optimized formulation was subjected to plantar test, behavioral tests of neuropathic pain and Von Frey filament stimulation test. Diabetes was induced by intraperitoneal injection of freshly prepared solution of Streptozotocin (60 mg/kg) to the experimental rats. Animals were made diabetic divided into four groups, Group I was untreated normal control group, Group II was diabetic control group, Group III was Bauhinia variegata extract ( treated group (100 mg/kg/day, p.o) and Group IV was BVN treated groups (100 mg/kg/day, p.o) acute and chronically. Results: The prepared B. variegata loaded nanoemulsion was nanosized (124 nm), spherical, uniform and stable over the period of 180 days with no change in physiochemical properties. The bl ood glucose and body weight of animals was normalizing after four weeks of treatment that was significant with BVN in comparison to diabetic control group. The chronic administration of BVN significantly (P<0.001) decreased hind paw withdrawal latency an d attenuated mechanical allodynia as compared with diabetic rats. Conclusion: Thus, BVN may be an effective drug formulation against diabetic peripheral neuropathic pain.
Objectives The purpose of this study was to find out the effects of ChondroT on arthralgia of the Collagenase-induced osteoarthritis in rats. Methods Osteoarthritis was induced into rat by injecting Collagenase in its knee joint. Rats are divided into a total of 8 groups (n=6). Normal group was not induced for osteoarthritis whereas control groups were induced for osteoarthritis by Collagenase. Positive-A (Indomethacin) was injected with Collagenase and after 8 days, 2 mg/kg of Indomethacin was medicated. Positive-B (JOINS TAB) was injected with Collagenase and after 8 days, 20 mg/kg of JOINS TAB was medicated. Experimental groups (Chondro T) at three dose levels (50, 100 and 200 mg/kg) were injected with Collagenase and after 8days they were medicated with 10 ml/kg. Indomethacin, JOINS TAB and ChondroT were medicated each substances once a day for 10 days. Thereafter, the changes in plantar withdrawal response of osteoarthritis rats by dynamic plantar aesthesiometer were observed and then RT-PCR analysis was done to investigate the expression of related proteins. Results 1. ChondroT significantly decreased withdrawal response of mechanical allodynia compared with control group in all of the experimental groups (ChondroT-A, ChondroT-B, ChondroT-C). 2. ChondroT significantly reduced Bax/Bcl-2 ratio in all of the experimental groups (ChondroT-A, ChondroT-B, ChondroT-C). 3. ChondroT significantly reduced the expression of INF-${\gamma}$ compared with control group in group ChondroT-B, ChondroT-C. Conclusions This results suggest that ChondroT may be meaningful for suppressing the pain of osteoarthritis. Further study is needed to conduct a rigorous clinical research.
Kim, Jong Han;Yoo, Je Hyuk;Park, Ji Min;Lee, Seung Min;Im, Se Hoon;Lee, Sang Hoon;Lee, Jae Dong;Nam, Dong Woo
Journal of Acupuncture Research
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v.30
no.3
/
pp.165-171
/
2013
Objectives : The purpose of this study is to investigate the effect of acupuncture treatment on a patient suffering from CRPS Type 1. Methods : A 30-year-old female patient suffering from CRPS Type 1 with symptoms of intense burning pain, joint stiffness, restricted mobility, rapid hair and nail growth, allodynia, hyperalgesia and coldness of the right leg was treated with acupuncture on six acupuncture points on the leg from 13 July to 18 July of 2011. Improvement of the patient's symptoms was evaluated by Numerical Rating Scale(NRS), Digital Infrared Thermographic Image(DITI). Results : After 6 days of treatment, NRS score decreased significantly and the DITI results showed moderate improvement in temperature. Conclusions : The results suggest that acupuncture may be an effective in reducing the symptoms of CRPS. Further study is needed to evaluate the significancy of this report.
Suh, Jeong Hun;Koo, Mi Suk;Nahm, Francis Sahngun;Shin, Hwa Yong;Choi, Yong Min;Jo, Ji Yon;Lee, Sang Chul;Kim, Yong Chul
The Korean Journal of Pain
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v.20
no.2
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pp.190-194
/
2007
Complex regional pain syndrome (CRPS), which is a syndrome that is defined by pain and sudomotor and/or vasomotor instability, is usually resistant to conventional treatment. Here, a case involving a 30-year-old male patient with CRPS type I who showed severe intractable right shoulder pain with allodynia and hyperalgesia despite being treated with oral medications, nerve blocks including thoracic sympathetic neurolysis, and spinal cord stimulation is described. The patient frequently visited the emergency room due to severe uncontrollable breakthrough pain. Although a favorable effect was observed in response to intermittent ketamine infusion therapies that were performed on an outpatient basis, acute exacerbation of pain occurred frequently during the night and could not be controlled. Therefore, subcutaneous ketamine infusion therapy using a patient-controlled analgesic system was attempted and found to effectively control acute exacerbation of pain during 6 weeks of infusion without serious complications.
Jung, Ki Tae;Yoon, Myung Ha;Lee, Hyun Young;Yu, Bo Yeon;Kim, Dong Kyu;Lim, Kyung Joon
The Korean Journal of Pain
/
v.26
no.2
/
pp.125-129
/
2013
Background: 5-hydroxytryptamine 3 (5-HT3) receptors have been known to be associated with the modulation of nociceptive transmission. However, it is uncertain whether 5-HT3 plays a role in the antinociceptive or pronociceptive pathway for incisional pain. In this study, we evaluated the effects of palonosetron, a 5-HT3 receptor antagonist, on incisional pain in rats when administered intrathecally or intraplantarly. Methods: An intrathecal catheter was implanted through the cisterna magna and placed in the intrathecal space of rats. An incision in the plantaris muscle of the right hind paw was done under anesthesia with sevoflurane. Withdrawal thresholds were evaluated with the von Frey filament after 2 hours. Palonosetron (0.5 and 0.1 ${\mu}g$ intrathecally; 0.5 ${\mu}g$ intraplantarly) was administered and the thresholds were observed for 4 hours. Results: Mechanical hypersensitivity developed after the incision. Intrathecal palonosetron (0.5 ${\mu}g$ and 0.1 ${\mu}g$) did not alter the paw withdrawal threshold. Intraplantar palonosetron (0.5 ${\mu}g$) also did not change the paw withdrawal threshold. Conclusions: Intrathecal and intraplantar palonosetron (0.5 ${\mu}g$) had no effect on modulating the mechanical hypersensitivity in the incisional pain model of rats.
Background: The continuous search for a novel neuropathic pain drug with few or no side effects has been a main focus of researchers for decades. This study investigated the antinociceptive and neuroprotective effects of bromelain in sciatic nerve ligation-induced neuropathic pain in Wistar rats. Methods: Forty-eight Wistar rats randomly divided into eight groups comprised of six animals each were used for this study. Peripheral neuropathy was induced via chronic constriction of the common sciatic nerve. Thermal hyperalgesic and mechanical allodynia were assessed using a hotplate and von Frey filaments, respectively. The functional recovery and structural architecture of the ligated sciatic nerve were evaluated using the sciatic functional index test and a histological examination of the transverse section of the sciatic nerve. The neuroprotective effects of bromelain were investigated in the proximal sciatic nerve tissue after 21 days of treatment. Results: Bromelain significantly (P < 0.05) attenuated both the thermal hyperalgesia and mechanical allodynic indices of neuropathic pain. There were improvements in sciatic function and structural integrity in rats treated with bromelain. These rats showed significant (P < 0.05) increases in sciatic nerve nuclear transcription factors (nuclear factor erythroid-derived-2-related factors-1 [NrF-1] and NrF-2), antioxidant enzymes (superoxide dismutase and glutathione), and reduced membranelipid peroxidation compared with the ligated control group. Conclusions: This study suggest that bromelain mitigated neuropathic pain by enhancing the activities of nuclear transcription factors (NrF-1 and NrF-2) which increases the antioxidant defense system that abolish neuronal stress and structural disorganization.
Oh, Seon Hee;Kim, Suk Whee;Kim, Dong Joon;Kim, Sang Hun;Lim, Kyung Joon;Lee, Kichang;Jung, Ki Tae
The Korean Journal of Pain
/
v.34
no.4
/
pp.405-416
/
2021
Background: This study investigated the effect of intrathecal Sec-O-glucosylhamaudol (SOG) on the p38/c-Jun N-terminal kinase (JNK) signaling pathways, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-related inflammatory responses, and autophagy in a spinal nerve ligation (SNL)-induced neuropathic pain model. Methods: The continuous administration of intrathecal SOG via an osmotic pump was performed on male Sprague-Dawley rats (n = 50) with SNL-induced neuropathic pain. Rats were randomized into four groups after the 7th day following SNL and treated for 2 weeks as follows (each n = 10): Group S, sham-operated; Group D, 70% dimethylsulfoxide; Group SOG96, SOG at 96 ㎍/day; and Group SOG192, SOG at 192 ㎍/day. The paw withdrawal threshold (PWT) test was performed to assess neuropathic pain. Western blotting of the spinal cord (L5) was performed to measure changes in the expression of signaling pathway components, cytokines, and autophagy. Additional studies with naloxone challenge (n = 10) and cells were carried out to evaluate the potential mechanisms underlying the effects of SOG. Results: Continuous intrathecal SOG administration increased the PWT with p38/JNK mitogen-activated protein kinase (MAPK) pathway and NF-κB signaling pathway inhibition, which induced a reduction in proinflammatory cytokines with the concomitant downregulation of autophagy. Conclusions: SOG alleviates mechanical allodynia, and its mechanism is thought to be related to the regulation of p38/JNK MAPK and NF-κB signaling pathways, associated with autophagy during neuroinflammatory processes after SNL.
Koh, Gi-Ho;Song, Hyun;Kim, Sang Hun;Yoon, Myung Ha;Lim, Kyung Joon;Oh, Seon-Hee;Jung, Ki Tae
The Korean Journal of Pain
/
v.32
no.2
/
pp.87-96
/
2019
Background: This study was performed in order to examine the effect of intrathecal sec-O-glucosylhamaudol (SOG), an extract from the root of the Peucedanum japonicum Thunb., on incisional pain in a rat model. Methods: The intrathecal catheter was inserted in male Sprague-Dawley rats (n = 55). The postoperative pain model was made and paw withdrawal thresholds (PWTs) were evaluated. Rats were randomly treated with a vehicle (70% dimethyl sulfoxide) and SOG ($10{\mu}g$, $30{\mu}g$, $100{\mu}g$, and $300{\mu}g$) intrathecally, and PWT was observed for four hours. Dose-responsiveness and ED50 values were calculated. Naloxone was administered 10 min prior to treatment of SOG $300{\mu}g$ in order to assess the involvement of SOG with an opioid receptor. The protein levels of the ${\delta}$-opioid receptor, ${\kappa}$-opioid receptor, and ${\mu}$-opioid receptor (MOR) were analyzed by Western blotting of the spinal cord. Results: Intrathecal SOG significantly increased PWT in a dose-dependent manner. Maximum effects were achieved at a dose of $300{\mu}g$ at 60 min after SOG administration, and the maximal possible effect was 85.35% at that time. The medial effective dose of intrathecal SOG was $191.3{\mu}g$ (95% confidence interval, 102.3-357.8). The antinociceptive effects of SOG ($300{\mu}g$) were significantly reverted until 60 min by naloxone. The protein levels of MOR were decreased by administration of SOG. Conclusions: Intrathecal SOG showed a significant antinociceptive effect on the postoperative pain model and reverted by naloxone. The expression of MOR were changed by SOG. The effects of SOG seem to involve the MOR.
Objectives : The purpose of this study is to analyze animal behavioral changes and related neurobiological mechanisms in recent studies using animal models with pain and depression. Methods : We conducted database search in Pubmed, NDSL, and EMBASE up to January 2021. Included studies were classified as depression-like behavior observed in pain model, pain-like behavior observed in depression model, and pain and depression comorbidity model. The results of pain- and depression-like behaviors, the changes of neurobiological mechanisms, and the treatment methods such as drugs, natural substance-derived chemicals, or acupuncture were analyzed. Results : We included 124 studies (81 studies in depression-like behavior observed in pain model, 19 studies in pain-like behavior observed in depression model, and 24 studies in pain and depression comorbidity model). Pain and depression comorbidity animal models were induced using various methods by drugs or surgery. Von frey test, a method for evaluating mechanical allodynia was the most commonly used for measuring pain-like behavior and the forced swimming test was the most commonly used for measuring depression-likes behavior. The changes of neurobiological factors, such as decrease of 5-hydroxytryptamine and increase of oxidative stress and pro-inflammation cytokines were generally changed in the frontal cortex, hippocampus, thalamus, and spinal cord in all types of models. For treating pain and depression-like behaviors, various types of drugs such as antidepressant, tranquilizer, analgesic, and natural substance-derived chemicals were used. Acupuncture treatment was used in 4 studies. Conclusions : In the future, more diverse studies on the combined model of pain and depression need to be conducted. In addition, it is necessary to establish a mechanistic basis for the development of various treatments by identifying the common mechanisms of pain and depression.
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