• Journal of Trauma and Injury
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• v.35 no.3
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• pp.202-208
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• 2022

Purpose: There is limited research on the effects of neuropathic pain (NP) on quality of life, depression levels, and sleep quality in patients with combat-related extremity injuries. This study evaluated whether patients with combat-related extremity injuries with and without NP had differences in quality of life, sleep quality, and depression levels. Methods: A total of 98 patients with combat-related extremity injuries, 52 with NP and 46 without, were included in this cross-sectional study. The presence of NP was determined using the Leeds Assessment of Neuropathic Symptoms and Signs questionnaire. The outcome measures were a visual analogue scale (VAS), the 36-Item Short Form Survey, the Beck Depression Inventory, and the Pittsburgh Sleep Quality Index (PSQI). Results: The VAS subparameter scores for pain (all P<0.05), PSQI sleep dur ation subscale scores (P=0.025), PSQI sleep disturbance subscale scores (P=0.016), and PSQI total scores (P=0.020) were significantly higher in patients with NP than those without. Logistic regression analysis showed that VAS scores of 5 and above for average pain during the previous 4 weeks contributed independently to the prediction of NP. Conclusions: Patients with combat-related extremity injuries with NP had more pain and poorer sleep quality than those without NP. Sleep quality should be evaluated as part of the diagnostic work-up in patients with combat-related extremity injury with NP, and interventions to improve sleep quality may help manage NP in this patient group.

• The Korean Journal of Pain
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• v.33 no.3
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• pp.226-233
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• 2020

Background: We aimed to compare interlaminar epidural steroid injections (ILESI) and bilateral transforaminal epidural steroid injections (TFESI) on pain intensity, functional status, depression, walking distance, and the neuropathic component in patients with lumbar central spinal stenosis (LCSS). Methods: The patients were divided into either the ILESI or the bilateral TFESI groups. Prime outcome measures include the numerical rating scale (NRS), Oswestry disability index (ODI), Beck depression inventory (BDI), and pain-free walking distance. The douleur neuropathique en 4 questions score was used as a secondary outcome measure. Results: A total of 72 patients were finally included. NRS, ODI, and BDI scores showed a significant decline in both groups in all follow-ups. Third-month NRS scores were significantly lower in the ILESI group (P = 0.047). The percentages of decrease in the ODI and BDI scores between the baseline and the third week and third month were significantly higher in the ILESI group (P = 0.017, P = 0.001 and P = 0.048, P = 0.030, respectively). Pain-free walking distance percentages from the baseline to the third week and third month were significantly higher in the ILESI group (P = 0.036, P < 0.001). The proportion of patients with neuropathic pain in the bilateral TFESI group significantly decreased in the third week compared to the baseline (P = 0.020). Conclusions: Both ILESI and TFESI are reliable treatment options for LCSS. ILESI might be preferred because of easier application and more effectiveness. However, TFESI might be a better option in patients with more prominent neuropathic pain.

• The Korean Journal of Pain
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• v.35 no.1
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• pp.106-113
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• 2022

Background: Coccygodynia is one of the chronic, refractory painful musculoskeletal disorders. Interventional procedures are applied to patients unresponsive to initial treatment in coccygodynia. This study aims to compare the treatment outcomes of ganglion impar block (GIB) and caudal epidural steroid injection (CESI) in patients with chronic coccygodynia. Methods: This study was a prospective randomized comparison study conducted between June 2019 and January 2021. Patients diagnosed with chronic coccygodynia were randomly divided into two groups: the GIB group and the CESI group. The severity of pain, presence of neuropathic pain, and quality of life were evaluated using the Numeric Rating Scale, Leeds Assessment of the Neuropathic Symptoms and Signs Scale, and Short Form-12 Health Survey (SF-12), respectively. Results: A total of 34 patients in each group were included in the final analyses. While there was a significant decrease in pain intensity in both groups in the 3-month follow-up, this decrease was more significant in the GIB group at the 3rd week. There was a significant improvement in the SF-12 physical score and the number of patients with neuropathic pain in both groups in the 3rd week, but this improvement was not observed in the 3rd month. Conclusions: Although GIB may provide more pain relief in short term, both GIB and CESI are useful treatment methods in coccygodynia unresponsive to more conservative treatments.

• 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.

• Molecules and Cells
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• v.25 no.2
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• pp.242-246
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• 2008

To assess the role of $\alpha_{1G}$ T-type $Ca^{2+}$ channels in neuropathic pain after L5 spinal nerve ligation, we examined behavioral pain susceptibility in mice lacking $Ca_{V}3.1$ (${\alpha}_{1G}{^{-/-}}$), the gene encoding the pore-forming units of these channels. Reduced spontaneous pain responses and an increased threshold for paw withdrawal in response to mechanical stimulation were observed in these mice. The ${{\alpha}_{1G}}^{-/-}$ mice also showed attenuated thermal hyperalgesia in response to both low-(IR30) and high-intensity (IR60) infrared stimulation. Our results reveal the importance of ${\alpha}_{1G}$ T-type $Ca^{2+}$ channels in the development of neuropathic pain, and suggest that selective modulation of ${\alpha}_{1G}$ subtype channels may provide a novel approach to the treatment of allodynia and hyperalgesia.

• Journal of Acupuncture Research
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• v.24 no.5
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• pp.137-150
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• 2007

Objectives : To find effects of acupuncture, electro-acupuncture, low level He-Ne laser therapy(LLLT) at $TE_5$, $GB_{41}$ in the neuropathic pain. We made experiment on rats ligated L5 spinal nerve like general herniation of nucleus pulposus(HNP). Methods : A model of neuropathic pain was made by isolating Left 5th lumbar spinal nerve of rats. Three days after the neuropathic surgery, acupuncture and LLLT, electro-acupuncture was injected at $TE_5$, $GB_{41}$ one time a day for a week. Each group was divided two. one is opposite side performed the surgery which is right, another is left side performed the surgery. After that, the author examined the withdrawal response of neuropathic rats' legs by van Frey filament and acetone stimulation. And also the author examined c-Fos, Nociceptin and KOR-3 in the midbrain central gray of neuropathic rats. Results : As we have observed the effect of mechanical allodynia, LT-R group were diminished on 6th day compared with control group, EA-L group, EA-R group and LT-L group were diminished on 7th day compared with control group. As we have observed the effect of cold allodynia, EA-R group were diminished on 6th day, 7th day compared with control group. As we have observed the effect of activity of c-Fos in the central gray part, EA-R group and LT-R group were diminished compared with control group. As we have observed the effect of activity of Nociceptin in the central gray part, EA-R group were a little increased compared with control group but it is not reliability. As we have observed the effect of activity of KOR-3 in the central gray part, EA-R group were significantly increased compared with control group. Conclusions : We have noticed that effect of acupuncture at opposite side of sickness and powerful stimulation could be more effective, because of EA-R group have more controllable effect all test we have done on the other hand EA-L group have only effect on mechanical allodynia. This study can be used in clinical therapy for neuropathic pain. But it is not reliability that Nociceptin have effectively to control pain. Therefore We have to follow up about that.

• Korean Journal of Acupuncture
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• v.38 no.3
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• pp.151-161
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• 2021

Objectives : The effects of a combined stimulation of 658 nm, 830 nm, 904 nm, and 1064 nm laser acupuncture treatment (LAT) and electroacupuncture treatment (EAT) on GB39 and GB34 on neuropathic pain in rats induced by tibial and sural nerve transection were studied in this paper. Methods : To express a neuropathic pain model, surgery was performed to transection rats' tibial and sural nerves. The rats were divided into normal group, control group, and experimental groups. In addition, the experimental groups were divided into 658 nm laser and electroacupuncture (LAT658+EAT), 830 nm laser and electroacupuncture (LAT830+EAT), 904 nm laser and electroacupuncture (LAT904+EAT), and 1064 nm laser and electroacupuncture (LAT830+EAT). For the treatment of the experimental groups, electroacupuncture and different laser wavelengths were alternately applied to GB34 and GB39 twice a week for 3 weeks for 1 minute 30 seconds. The withdrawal response of neuropathic rats' legs by acetone stimulation was observed, as well as the c-Fos in the central gray region in the midbrain of neuropathic rats together with Bax, Bcl2, and mGluR5 expressions associated with apoptosis. Results : Compared with the control group, a significant decrease in the frequency of paw withdrawal in response to acetone allodynia was observed in LAT658+EAT and LAT830+EAT groups in 6th times, LAT904+EAT group in 2^nd, 3^rd, and 6^th times, and LAT1064+EAT group in 2^nd and 6^th times, respectively. For c-fos positive cells in the central gray region, a significant decrease was observed in LAT830+EAT, LAT904+EAT, and LAT1064+EAT groups in comparison with the control group. In Bax expression, LAT1064+EAT group showed a significant decrease compared to the control group. In Bcl-2 expression, the LAT658+EAT,the LAT904+EAT, and the LAT1064+EAT groups increased significantly compared to the control group. LAT830+EAT, LAT904+EAT, and LAT1064+EAT groups showed significantly increased mGlu5 expression compared to the control group. Conclusions : The combination of laser for each wavelength and electroacupuncture alternately performed in this study is thought to be effective in improving neuropathic pain and apoptosis.

• The Korean Journal of Pain
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• v.27 no.4
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• pp.326-333
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• 2014

Background: Nefopam is a centrally acting non-opioid analgesic agent. Its analgesic properties may be related to the inhibitions of monoamine reuptake and the N-methyl-D-aspartate (NMDA) receptor. The antinociceptive effect of nefopam has been shown in animal models of acute and chronic pain and in humans. However, the effect of nefopam on diabetic neuropathic pain is unclear. Therefore, we investigated the preventive effect of nefopam on diabetic neuropathic pain induced by streptozotocin (STZ) in rats. Methods: Pretreatment with nefopam (30 mg/kg) was performed intraperitoneally 30 min prior to an intraperitoneal injection of STZ (60 mg/kg). Mechanical and cold allodynia were tested before, and 1 to 4 weeks after drug administration. Thermal hyperalgesia was also investigated. In addition, the transient receptor potential ankyrin 1 (TRPA1) and TRP melastatin 8 (TRPM8) expression levels in the dorsal root ganglion (DRG) were evaluated. Results: Pretreatment with nefopam significantly inhibited STZ-induced mechanical and cold allodynia, but not thermal hyperalgesia. The STZ injection increased TRPM8, but not TRPA1, expression levels in DRG neurons. Pretreatment with nefopam decreased STZ-induced TRPM8 expression levels in the DRG. Conclusions: These results demonstrate that a nefopam pretreatment has strong antiallodynic effects on STZ-induced diabetic rats, which may be associated with TRPM8 located in the DRG.

• The Korean Journal of Pain
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• v.24 no.3
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• pp.154-157
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• 2011

Background: Postherpetic neuralgia (PHN) is usually managed pharmacologically. It is not uncommon for patients with chronic kidney disease (CKD) to suffer from PHN. It is difficult to prescribe a sufficient dose of anticonvulsants for intractable pain because of the decreased glomerular filtration rate. If the neural blockade and pulsed radiofrequency ablation provide only short-term amelioration of pain, spinal cord stimulation (SCS) with a low level of evidence may be used only as a last resort. This study was done to evaluate the efficacy of spinal cord stimulation in the treatment of PHN in patients with CKD. Methods: PHN patients with CKD who needed hemo-dialysis who received insufficient relief of pain over a VAS of 8 regardless of the neuropathic medications were eligible for SCS trial. The follow-up period was at least 2 years after permanent implantation. Results: Eleven patients received percutaneous SCS test trial from Jan 2003 to Dec 2007. Four patients had successfully received a permanent SCS implant with their pain being tolerable at a VAS score of less than 3 along with small doses of neuropathic medications. Conclusions: SCS was helpful in managing tolerable pain levels in some PHN patients with CKD along with tolerable neuropathic medications for over 2 years.

• The Korean Journal of Pain
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• v.32 no.4
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• pp.245-255
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• 2019

Stem cells are attracting attention as a key element in future medicine, satisfying the desire to live a healthier life with the possibility that they can regenerate tissue damaged or degenerated by disease or aging. Stem cells are defined as undifferentiated cells that have the ability to replicate and differentiate themselves into various tissues cells. Stem cells, commonly encountered in clinical or preclinical stages, are largely classified into embryonic, adult, and induced pluripotent stem cells. Recently, stem cell transplantation has been frequently applied to the treatment of pain as an alternative or promising approach for the treatment of severe osteoarthritis, neuropathic pain, and intractable musculoskeletal pain which do not respond to conventional medicine. The main idea of applying stem cells to neuropathic pain is based on the ability of stem cells to release neurotrophic factors, along with providing a cellular source for replacing the injured neural cells, making them ideal candidates for modulating and possibly reversing intractable neuropathic pain. Even though various differentiation capacities of stem cells are reported, there is not enough knowledge and technique to control the differentiation into desired tissues in vivo. Even though the use of stem cells is still in the very early stages of clinical use and raises complicated ethical problems, the future of stem cells therapies is very bright with the help of accumulating evidence and technology.