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The mechanism of human neural stem cell secretomes improves neuropathic pain and locomotor function in spinal cord injury rat models: through antioxidant, anti-inflammatory, anti-matrix degradation, and neurotrophic activities

  • I Nyoman Semita;Dwikora Novembri Utomo;Heri Suroto;I Ketut Sudiana;Parama Gandi
    • The Korean Journal of Pain
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    • v.36 no.1
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    • pp.72-83
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    • 2023
  • Background: Globally, spinal cord injury (SCI) results in a big burden, including 90% suffering permanent disability, and 60%-69% experiencing neuropathic pain. The main causes are oxidative stress, inflammation, and degeneration. The efficacy of the stem cell secretome is promising, but the role of human neural stem cell (HNSC)-secretome in neuropathic pain is unclear. This study evaluated how the mechanism of HNSC-secretome improves neuropathic pain and locomotor function in SCI rat models through antioxidant, anti-inflammatory, anti-matrix degradation, and neurotrophic activities. Methods: A proper experimental study investigated 15 Rattus norvegicus divided into normal, control, and treatment groups (30 µL HNSC-secretome, intrathecal in the level of T10, three days post-traumatic SCI). Twenty-eight days post-injury, specimens were collected, and matrix metalloproteinase (MMP)-9, F2-Isoprostanes, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, and brain derived neurotrophic factor (BDNF) were analyzed. Locomotor recovery was evaluated via Basso, Beattie, and Bresnahan scores. Neuropathic pain was evaluated using the Rat Grimace Scale. Results: The HNSC-secretome could improve locomotor recovery and neuropathic pain, decrease F2-Isoprostane (antioxidant), decrease MMP-9 and TNF-α (anti-inflammatory), as well as modulate TGF-β and BDNF (neurotrophic factor). Moreover, HNSC-secretomes maintain the extracellular matrix of SCI by reducing the matrix degradation effect of MMP-9 and increasing the collagen formation effect of TGF-β as a resistor of glial scar formation. Conclusions: The present study demonstrated the mechanism of HNSC-secretome in improving neuropathic pain and locomotor function in SCI through antioxidant, anti-inflammatory, anti-matrix degradation, and neurotrophic activities.

Effects of Transversus Abdominal Muscle Stabilization Exercise to Spinal Segment Motion on Trunk Flexion-Extension (복횡근 강화운동이 체간 신전-굴곡 시 척추 분절 운동에 미치는 영향)

  • Kim, Suhn-Yeop;Baek, In-Hyeub
    • Physical Therapy Korea
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    • v.10 no.1
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    • pp.63-76
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    • 2003
  • This research was performed to compare spinal segment motion angle between low back pain (LBP) group and painless group during trunk flexion-extension and to investigate the effect of transversus abdominis strengthening exercise on spinal segment motion angle in LBP group. Nine subjects with LBP and ten subjects without LBP participated. Transversus abdominis strengthening exercise was performed in LBP group for three weeks, and spinal segment motion angles were compared before and after the exercise performance. Spinal segment motion angles were measured both in sitting and standing position. Results were as followed: 1) Subjects' average age was 24.79 years, height was 167.84 cm, and weight was 59.95 kg. 2) Spinal segment motion angle of T10/l1 was significantly higher in LBP group compared with painless group (p<.05) in sitting position during trunk flexion-extension. 3) In sitting position, whereas entire lumbar segment motion angles were lower in LBP group compared with painless group (p<.05), angle of L4/5 was higher in LBP group compared with painless group (p<.05). 4) There was no significant difference in thoracic segment motion angle in standing position. 5) After three weeks of transversus abdominis strengthening exercise, thoracic segment motion angle increased both in sitting and standing position (p<.05). 6) In painless group, there was no significant difference in entire spinal segment motion angles in sitting and standing position (p>.05). When spinal segment motion angles were compared between sitting and standing position, there were slight differences. In sitting position, there was no difference in spinal segment motion angle between LBP group and painless group while hip joint motion angle and sacral inclination angle of LBP group was lower than those of painless group (p<.05). In standing position, lumbar segment motion angle was significantly lower in LBP group than that of painless group. Transversus abdominis strengthening exercise influenced thoracic segment motion angle more significantly than lumbar segment motion angle.

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Spinal Epidural Hematoma Occuring after Bloody Tap during Epidural Catheter for Cancer Pain Control -A case report- (암성통증치료를 위한 경막외카테테르 거치술중 혈성천자로 발생한 경막외혈종 -증례 보고-)

  • Woo, Sung-Chang;Cha, Dong-Suk;Kang, Keon;Kim, Young-Ki
    • The Korean Journal of Pain
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    • v.11 no.1
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    • pp.160-164
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    • 1998
  • We report a case of epidural hematoma occuring after bloody tap during epi-dural catheter for cancer pain control in thrombocytopenic patient. Two hours after epidurl puncture, patient experienced severe back pain and numbness of both legs. Following day, patient complained of motor paralysis and urinary difficulty. Diagnosis utilizing magnetic reasonance imaging, showed epidural hematoma extending from $T_{11}$ to $T_{12}$. Thrombocytopenia prevented surgical intervention. Therefore we restored conservative therapy with packed red cell, platelet concentration, steroid and hemostatic, which provided complete neurologic recovery, spontaneously over several days without surgical intervention.

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Spinal Myoclonus Developed during Cervical Epidural Drug Infusion in Postherpetic Neuralgia Patient

  • Jeon, Young-Hoon;Baek, Sung-Uk;Yeo, Jin-Seok
    • The Korean Journal of Pain
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    • v.24 no.3
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    • pp.169-171
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    • 2011
  • Postherpetic neuralgia is the most frequent complication of herpes zoster. Treatment of this neuropathic pain syndrome is difficult and often disappointing. Although postherpetic neuralgia is generally a self-limited condition, it can last indefinitely. Continuous epidural blockade for patients with acute zoster can shorten the duration of treatment. However, continuous epidural block has some complications such as infection, dural puncture, and total spinal and nerve damages. We report a case of myoclonus during continuous epidural block with ropivacaine, morphine, and ketamine in an acute zoster patient.

Effects of spinal stabilization training on Chronic Low Back Pain in Private Guard and Security (척추안정화 운동이 민간 경호.경비원들의 허리통증에 미치는 영향)

  • Kim, Seong-Ho;Lee, Wan-Hee
    • Korean Security Journal
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    • no.20
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    • pp.71-93
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    • 2009
  • The purpose of this study was to evaluate the effects of using spinal stabilization exercise for the improvement of atrophy of the multifidus and psoas major, of pain and disability with chronic low back pain in private guard and security. For 42 patients diagnosed with CLBP, and divided into spinal stabilization exercise group(SSEG) and general spinal strengthening exercise group(GSSEG). Each exercise was conducted for 10 weeks. Pain and disability were measured before and after exercise using the Visual analogue scale(VAS) and the Oswestry disability index(ODI). Cross section area(CSA) of both the left and right multifidus and the psoas major at the upper end plate of L4 were measured before and after exercise using computed tomography(CT). After 10 weeks of exercise, the both group's pain and lumbar disability were significantly decreased(p<0.01). Also there was significant difference in both group(p<0.05). In addition, the CSA of the left and right multifidus and posas major were significantly increased as compared to the pre-exercise in both group(p<0.01). But SSEG's cross sectional areas of multifidus was more significantly increase than GSSEG(p<0.05). In summary, Spinal stabilization exercise is more effective in improving atrophy in private guard and security patients, in reducing patients' pain and disability. It is an effective treatment to aid rehabilitation in these cases.

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Brain Activation Evoked by Sensory Stimulation in Patients with Spinal Cord Injury : Functional Magnetic Resonance Imaging Correlations with Clinical Features

  • Lee, Jun Ki;Oh, Chang Hyun;Kim, Ji Yong;Park, Hyung-Chun;Yoon, Seung Hwan
    • Journal of Korean Neurosurgical Society
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    • v.58 no.3
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    • pp.242-247
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    • 2015
  • Objective : The purpose of this study is to determine whether the changes of contralateral sensorimotor cortical activation on functional magnetic resonance imaging (fMRI) can predict the neurological outcome among spinal cord injury (SCI) patients when the great toes are stimulated without notice. Methods : This study enrolled a total of 49 patients with SCI and investigated each patient's preoperative fMRI, postoperative fMRI, American Spinal Injury Association (ASIA) score, and neuropathic pain occurrence. Patients were classified into 3 groups according to the change of blood oxygenation level dependent (BOLD) response on perioperative fMRI during proprioceptive stimulation with repetitive passive toe movements : 1) patients with a response of contralateral sensorimotor cortical activation in fMRI were categorized; 2) patients with a response in other regions; and 3) patients with no response. Correlation between the result of fMRI and each parameter was analyzed. Results : In fMRI data, ASIA score was likely to show greater improvement in patients in group A compared to those belonging to group B or C (p<0.001). No statistical significance was observed between the result of fMRI and neuropathic pain (p=0.709). However, increase in neuropathic pain in response to the signal change of the ipsilateral frontal lobe on fMRI was statistically significant (p=0.030). Conclusion : When there was change of BOLD response at the contralateral sensorimotor cortex on perioperative fMRI after surgery, relief of neurological symptoms was highly likely for traumatic SCI patients. In addition, development of neuropathic pain was likely to occur when there was change of BOLD response at ipsilateral frontal lobe.

Comparing the Immediate Effectiveness of Lumbar Flexion and Extension Exercise With Regards to Pain, Range of Motion, Pelvic Tilt, and Functional Gait Ability in Patients With Lumbar Spinal Stenosis

  • Do, Hyun-ho;Chon, Seung-chul
    • Physical Therapy Korea
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    • v.26 no.4
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    • pp.10-19
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    • 2019
  • Background: In patients with lumbar spinal stenosis (LSS), lumbar flexion exercise (LFE) is considered a standard therapeutic exercise that widens the space between the spinal canal and intervertebral foramen. However, some researchers have reported that lumbar extension exercise (LEE) may improve lumbar pain and functional ability in patients with LSS. Although exercise intervention methods for patients with LSS have been widely applied in clinical settings, few studies have conducted comparative analysis of these exercise methods. Objects: This study aimed to compare the effects of LFE, LEE, and lumbar flexion combined with lumbar flexion-extension exercise (LFEE) on pain, range of motion (ROM), pelvic tilt angle, and functional gait ability in patients with LSS. Methods: A total of 30 patients with LSS, LFE (n1=10), LEE (n2=10), and LFEE (n3=10) were assigned to each of the three exercise groups. The numerical pain rating scale (NPRS), modified-modified schober test (MMST)-flexion, MMST-extension, pelvic tilt inclinometer, and 6-minute walking test (6MWT) were measured. Results: After the intervention, statistically significant differences were observed in the NPRS (p=.043), MMST-flexion (p<.001), MMST-extension (p<.001), and 6MWT (p=.005) between groups. According to the post hoc test, the NPRS was statistically significant difference between the LFEE and LEE groups (p=.034). The MMST-flexion was statistically significantly different between the LFE and LEE (p=.000), LFE and LFEE (p=.001), and LEE and LFEE (p=.001) groups. The MMST-extension was statistically significantly different between the LFE and LEE (p<.001), LFE and LFEE (p=.002), and LEE and LFEE (p=.008) groups. The 6MWT was statistically significantly different between the LFE and LFEE (p=.042) and the LEE and LFEE (p=.004) groups. Conclusion: This study suggested that LFEE was the most effective exercise for pain and functional gait ability in patients with LSS, LFE was the most effective exercise for lumbar flexion ROM, and LEE was the most effective exercise for lumbar extension ROM.

Synergistic interaction between acetaminophen and L-carnosine improved neuropathic pain via NF-κB pathway and antioxidant properties in chronic constriction injury model

  • Owoyele, Bamidele Victor;Bakare, Ahmed Olalekan;Olaseinde, Olutayo Folajimi;Ochu, Mohammed Jelil;Yusuff, Akorede Munirdeen;Ekebafe, Favour;Fogabi, Oluwadamilare Lanre;Roi, Treister
    • The Korean Journal of Pain
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    • v.35 no.3
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    • pp.271-279
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    • 2022
  • Background: Inflammation is known to underlie the pathogenesis in neuropathic pain. This study investigated the anti-inflammatory and neuroprotective mechanisms involved in antinociceptive effects of co-administration of acetaminophen and L-carnosine in chronic constriction injury (CCI)-induced peripheral neuropathy in male Wistar rats. Methods: Fifty-six male Wistar rats were randomly divided into seven experimental groups (n = 8) treated with normal saline/acetaminophen/acetaminophen + L-carnosine. CCI was used to induce neuropathic pain in rats. Hyperalgesia and allodynia were assessed using hotplate and von Frey tests, respectively. Investigation of spinal proinflammatory cytokines and antioxidant system were carried out after twenty-one days of treatment. Results: The results showed that the co-administration of acetaminophen and L-carnosine significantly (P < 0.001) increased the paw withdrawal threshold to thermal and mechanical stimuli in ligated rats compared to the ligated naïve group. There was a significant (P < 0.001) decrease in the levels of nuclear factor kappa light chain enhancer B cell inhibitor, calcium ion, interleukin-1-beta, and tumour necrotic factor-alpha in the spinal cord of the group coadministered with acetaminophen and L-carnosine compared to the ligated control group. Co-administration with acetaminophen and L-carnosine increased the antioxidant enzymatic activities and reduced the lipid peroxidation in the spinal cord. Conclusions: Co-administration of acetaminophen and L-carnosine has anti-inflammatory effects as a mechanism that mediate its antinociceptive effects in CCI-induced peripheral neuropathy in Wistar rat.

Back Pain of Muscular Origin (근긴장성 요통의 치료에 대한 새로운 소견)

  • Choi, Joong-Rieb
    • The Korean Journal of Pain
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    • v.6 no.1
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    • pp.83-95
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    • 1993
  • In out-patient clinic, it seems to be common that most back pain arise from muscular origins rather than from skeletal origins. Most physicians have wished to diagnose lower back pain from the radiologic findings only. From clinical experiences and anatomical studies, I have gotten a different opinion from common sense about backaches. If I met a patient who had lower back pain around the posterior superior iliac crest(P.S.I.C.) area, I would had to search a trigger point in the erector spinae muscles at the level of thoraco-lumber junction rather than at the level of the painful site. It is why that sensory innervation over the posterior superior iliac crest area is the posterior primary branch of T12 spinal nerve running down through the erector spinae muscles. Pain on the iliac crest area is supposedly due to hyperirritability of the sensory nerve distributing to this area. Hyperirritability of the posterior primary branch of $T_{12}$ spinal nerve may be due to the spasm of the longissimus thoracis muscle in the erector spinae muscles at the level of the thoraco-lumbar junction. So finally, I would like to insist that spasmolytic treatment on the muscle at the level of the thoraco-lumbar junction would be better for pain relief around P.S.I.C. than treatment at the painful site only.

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SKF96365 impedes spinal glutamatergic transmission-mediated neuropathic allodynia

  • Qiru Wang;Yang Zhang;Qiong Du;Xinjie Zhao;Wei Wang;Qing Zhai;Ming Xiang
    • The Korean Journal of Physiology and Pharmacology
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    • v.27 no.1
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    • pp.39-48
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    • 2023
  • Spinal nerve injury causes mechanical allodynia and structural imbalance of neurotransmission, which were typically associated with calcium overload. Storeoperated calcium entry (SOCE) is considered crucial elements-mediating intracellular calcium homeostasis, ion channel activity, and synaptic plasticity. However, the underlying mechanism of SOCE in mediating neuronal transmitter release and synaptic transmission remains ambiguous in neuropathic pain. Neuropathic rats were operated by spinal nerve ligations. Neurotransmissions were assessed by whole-cell recording in substantia gelatinosa. Immunofluorescence staining of STIM1 with neuronal and glial biomarkers in the spinal dorsal horn. The endoplasmic reticulum stress level was estimated from qRT-PCR. Intrathecal injection of SOCE antagonist SKF96365 dose-dependently alleviated mechanical allodynia in ipsilateral hind paws of neuropathic rats with ED50 of 18 ㎍. Immunofluorescence staining demonstrated that STIM1 was specifically and significantly expressed in neurons but not astrocytes and microglia in the spinal dorsal horn. Bath application of SKF96365 inhibited enhanced miniature excitatory postsynaptic currents in a dosage-dependent manner without affecting miniature inhibitory postsynaptic currents. Mal-adaption of SOCE was commonly related to endoplasmic reticulum (ER) stress in the central nervous system. SKF96365 markedly suppressed ER stress levels by alleviating mRNA expression of C/ EBP homologous protein and heat shock protein 70 in neuropathic rats. Our findings suggested that nerve injury might promote SOCE-mediated calcium levels, resulting in long-term imbalance of spinal synaptic transmission and behavioral sensitization, SKF96365 produces antinociception by alleviating glutamatergic transmission and ER stress. This work demonstrated the involvement of SOCE in neuropathic pain, implying that SOCE might be a potential target for pain management.