• The Korean Journal of Pain
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• v.29 no.1
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• pp.40-47
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• 2016

Background: Neuropathic pain, including paresthesia/dysesthesia in the lower extremities, always develops and remains for at least one month, to variable degrees, after percutaneous endoscopic lumbar discectomy (PELD). The recently discovered dual analgesic mechanisms of action, similar to those of antidepressants and anticonvulsants, enable nefopam (NFP) to treat neuropathic pain. This study was performed to determine whether NFP might reduce the neuropathic pain component of postoperative pain. Methods: Eighty patients, who underwent PELD due to herniated nucleus pulposus (HNP) at L4-L5, were randomly divided into two equal groups, one receiving NFP (with a mixture of morphine and ketorolac) and the other normal saline (NS) with the same mixture. The number of bolus infusions and the infused volume for 3 days were compared in both groups. The adverse reactions (ADRs) in both groups were recorded and compared. The neuropathic pain symptom inventory (NPSI) score was compared in both groups on postoperative days 1, 3, 7, 30, 60, and 90. Results: The mean attempted number of bolus infusions, and effective infused bolus volume for 3 days was lower in the NFP group for 3 days. The most commonly reported ADRs were nausea, dizziness, and somnolence, in order of frequency in the NFP group. The median NPSI score, and all 5 median sub-scores in the NFP group, were significantly lower than that of the NS group until postoperative day 30. Conclusions: NFP significantly reduced the neuropathic pain component, including paresthesia/dysesthesia until 1 month after PELD. The common ADRs were nausea, dizziness, somnolence, and ataxia.

• Journal of The Korean Dental Society of Anesthesiology
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• v.3 no.1 s.4
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• pp.6-9
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• 2003

Background: The use of neurolytic agents to control neuropathic pain has been described from the last century Phenol and ethyl alcohol have been widely used as neurolytic agents, however, their neurolytic effect is variable in efficacy and duration of action, and infrequently accompanied with grave complications. It has been found that 5% lidocaine causes irreversible conduction blockade in animal studies. The goal of this study was to evaluate the neurolytic effect of 5%o lidocaine on various neuropathic pain syndromes for prolonged analgesia. Methods: Twenty-five patients with a diagnosis of neuropathic pain including trigeminal neuralgia (n = 7), postherpetic neuralgia (n = 10), and postsurgical neuralgia (n = 8) were selected after failure of routine therapeutic regimens. After performing a diagnostic nerve block with 1% lidocaine and 5% lidocaine was injected. The patients were followed for 6 months. Visual analog scale (VAS) scores and side effects were recorded for each patients. Results: A significant decrease in pain scores after neurolytic blockade with 5% lidocaine was seen in all of three pain groups. All the patients reported immediate and prolonged pain relief lasting from 4 weeks to 6 months. None of patients exhibited any appreciable side effects or complications. Conclusions: We suggest that 5% lidocaine may be used safely and effectively for the purpose of prolonged analgesia in selected patients with intractable neuropathic pain syndromes.

• Journal of Acupuncture Research
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• v.21 no.3
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• pp.145-167
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• 2004

Objective : Neuropathic pain can be caused by a partial peripheral nerve injury. This kind of pain is usually accompanied by spontaneous burning pain, allodynia and hyperalgesia. It is not clear that scolopendrid aqua-acupuncture can control neuropathic pain effectively. The purpose of this study is to examine if scolopendrid aqua-acupuncture may be effective to the neuropathic pain (mechanical allodynia, cold allodynia) in a rat model of neuropathic pain. Methods : To produce the model of neuropathic pain, under isoflurane 2.5% anesthesia, tibial nerve and sural nerve was resected. After the neuropathic surgery, the author examined if the animals exhibited the behavioral signs of allodynia. The allodynia was assessed by stimulating the medial malleolus with von Frey filament and acetone. Three weeks after the neuropathic surgery, scolopendrid aqua-acupuncture was injected at Hwando(GB30) one time a day for one week. After that the author examined the withdrawl response of neuropathic rats' legs by von Frey filament and acetone stimulation. And also the author examined c-fos in the midbrain central gray of neuropathic rats and the change of WBC count in the blood of neuropathic rats. Results & Conclusion : 1. The scolopendrid aqua-acupuncture injected at Hwando(GB30) decreased the withdrawl response of mechanical allodynia in SHA-1, SHA-2 and SAH-3 group as compared with control group. 2. The scolopendrid aqua-acupuncture injected at Hwando(GB30) decreased the withdrawl response of chemical allodynia(cold allodynia) in SHA-1, SHA-2 and SAH-3 group as compared with control group. 3. The scolopendrid aqua-acupuncture injected at Hwando(GB30) showed the significant difference between sham group and control group(p=0.01), sham and SHA-3 group(p=0.026), control group and SHA-1 group(p=0.01), control group and SHA-2 group(p=0.024) in the c-fos expression. 4. The scolopendrid aqua-acupuncture injected at Hwando(GB30) showed the significant difference between sham group and SHA-3 group(p=0.010), control group and SHA-3 group(p=0.006) in the WBC count.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.2
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• pp.153-160
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• 2017

In this study, we aim to determine the in vivo effect of human umbilical cord blood-derived multipotent stem cells (hUCB-MSCs) on neuropathic pain, using three, principal peripheral neuropathic pain models. Four weeks after hUCB-MSC transplantation, we observed significant antinociceptive effect in hUCB-MSC-transplanted rats compared to that in the vehicle-treated control. Spinal cord cells positive for c-fos, CGRP, p-ERK, p-p 38, MMP-9 and MMP 2 were significantly decreased in only CCI model of hUCB-MSCs-grafted rats, while spinal cord cells positive for CGRP, p-ERK and MMP-2 significantly decreased in SNL model of hUCB-MSCs-grafted rats and spinal cord cells positive for CGRP and MMP-2 significantly decreased in SNI model of hUCB-MSCs-grafted rats, compared to the control 4 weeks or 8weeks after transplantation (p<0.05). However, cells positive for TIMP-2, an endogenous tissue inhibitor of MMP-2, were significantly increased in SNL and SNI models of hUCB-MSCs-grafted rats. Taken together, subcutaneous injection of hUCB-MSCs may have an antinociceptive effect via modulation of pain signaling during pain signal processing within the nervous system, especially for CCI model. Thus, subcutaneous administration of hUCB-MSCs might be beneficial for improving those patients suffering from neuropathic pain by decreasing neuropathic pain activation factors, while increasing neuropathic pain inhibition factor.

• The Korean Journal of Pain
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• v.14 no.2
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• pp.150-155
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• 2001

Background: Tramadol is known to be a weak opioid. However, it has also been shown that tramadol is an effective norepinephrine and serotonin uptake blocker, which may be effective in the treatment of neuropathic pain. The present study was undertaken in order to assess the antinociceptive action of tramadol and to investigate possible antinociceptive mechanisms by using antagonists in an animal neuropathic pain models in rats. Methods: Rats were prepared with tight ligation at the left 5 and 6th lumbar spinal nerves (Kim and Chung's neuropathic pain model). The antinociceptive effects of tramadol (10, 20, and 50 mg/kg i.p.) in rats with neuropathic pain were assessed. Additionally, following coadministration of antagonists such as naloxone (1 mg/kg i.p.), yohimbine (1 mg/kg i.p.) and ritanserin (1 mg/kg i.p.) with 50 mg/kg of tramadol, the responses to mechanical and thermal stimuli were measured over a two-hour period. Results: Tramadol displayed potent antinociceptive effects in a dose-dependent manner on rats with neuropathic pain (P < 0.05). The effects of tramadol were inhibited by coadministered naloxone and yohimbine in rats with mechanical and thermal allodynia, respectively (P < 0.05). However, there were no significant changes in the pain behaviors in the case of ritanserin. Conclusions: Tramadol showed significant antinociceptive effects in rats with regards to neuropathic pain against both mechanical and thermal allodynia. The antinociceptive effect on the mechanical stimuli is medicated via an opioid receptor. However, it appears that the antinociceptive effects on thermal allodynia are mediated via a noradrenalin receptor vice a serotonergic receptor.

• Annals of Clinical Neurophysiology
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• v.24 no.2
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• pp.53-58
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• 2022

Noninvasive stimulation of the nervous system for treating chronic neuropathic pain has received attention because of its tolerability and relative efficacy. Repetitive transcranial magnetic stimulation (rTMS) is a representative method of noninvasive brain stimulation. Evidence-based guidelines on therapeutic use of rTMS have been proposed recently for several neurological diseases. These guidelines recommend treating neuropathic pain by applying high-frequency (≥ 5 Hz) rTMS to the primary motor cortex contralateral to the painful side. This review summarizes the mechanisms and guidelines of rTMS for treating neuropathic pain, and proposes directions for future research.

• 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.

• Korean Journal of Acupuncture
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• v.21 no.2
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• pp.47-67
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• 2004

Objectives : In the present study, the effect of Scolopendrid Water-Alcohol Extract (SWAE) applied to acupuncture point BL23 (Shinsu) on the neuropathic pain was examined. A common source of persistent pain in humans is the neuropathic pain. Anti-convulsant drugs are used to treat the neuropathic pain. In the oriental medicine, Scolopendrid was used for long time to treat convulsant syndrome and back pain, etc. Methods : On the bases of the Scolopendrid clinical application, the effect of SWAE applied to the acupuncture point was tested in the rat model of neuropathic pain. Neuropathic pain was induced by tight ligation of L5 spinal nerve. When rats developed pain behaviors, One hundred microliter of SWAE was applied into the ipsilateral BL23 point at a dose of 10 mg/ml under enflurane anesthesia. The foot withdraw latency of the hind limb was measured for an indicator of pain level after each manipulation. Results : SWAE injection increased the mechanical threshold of the foot in the rat model of neuropathic pain significantly for the duration of 4h, suggesting a partial alleviation of pain. SWAE applied to BL23 point produced a significant improvement of mechanical sensitivity of the foot lasting for at least 4h. However, neither contralateral BL23 point, ST25 (Chonchu) point, nor LR3 (Taechung) point produce as much increase of mechanical sensitivity as ipsilateral BL23 point. And, this increase of mechanical sensitivity was dose-dependent. The improvement of mechanical threshold was interpreted as an analgesic effect. In addition, the analgesic effect of Scolopendrid 4 mg/kg injection is equivalent to that of gabapentin 50 mg/kg injection. The relations between SWAE-induced analgesia and endogenous nitric oxide(NO), inducible NO synthase (iNOS)/neuronal NO synthase (nNOS) were also examined. Results were turned out that both NO production and nNOS/iNOS protein expression which are increased by nerve injury were suppressed by SWAE injection applied to BL23 point. Conclusions : The data suggest 1) that SWAE produces a potent analgesic effect on the neuropathic pain model in the rat and 2) that SWAE-induced analgesia modulate endogenous NO through the suppression of nNOS/iNOS protein expression.

• The Korean Journal of Pain
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• v.34 no.1
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• pp.35-46
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• 2021

Background: The present investigation explored the therapeutic actions of oleuropein along with the possible signaling pathway involved in attenuating neuropathic pain in chronic constriction injury (CCI) and vincristine-induced neuropathic pain in male rats. Methods: Four loose ligatures were placed around the sciatic nerve to induce CCI, and vincristine (50 ㎍/kg) was injected for 10 days to develop neuropathic pain. The development of cold allodynia, mechanical allodynia, and mechanical hyperalgesia was assessed using different pain-related behavioral tests. The levels of H2S, cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), orexin, and nuclear factor erythroid-2-related factor 2 (Nrf2) were measured in the sciatic nerve. Results: Treatment with oleuropein for 14 days led to significant amelioration of behavioral manifestations of neuropathic pain in two pain models. Moreover, oleuropein restored both CCI and vincristine-induced decreases in H2S, CSE, CBS, orexin, and Nrf2 levels. Co-administration of suvorexant, an orexin receptor antagonist, significantly counteracted the pain-attenuating actions of oleuropein and Nrf2 levels without modulating H2S, CSE and CBS. Conclusions: Oleuropein has therapeutic potential to attenuate the pain manifestations in CCI and vincristine-induced neuropathic pain, possibly by restoring the CSE, CBS, and H2S, which may subsequently increase the expression of orexin and Nrf2 to ameliorate behavioral manifestations of pain.

• Korean Journal of Acupuncture
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• v.21 no.3
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• pp.59-76
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• 2004

Objectives : The usage of acupuncture has gained popularity for certain chronic pain conditions. However, the efficacy of acupuncture in various diseases has not been fully established and the underlying mechanism is not clearly understood. In the present study, the effect of electroacupuncture (EA) applied to yangno$(SI_6)$ on the neuropathic pain was examined. Methods : A common source of persistent pain in human is a neuropathic pain. Neuropathic pain was induced by tight ligation of L5 spinal nerve. When rats developed pain behaviors, EA was applied for 30 min. under enflurane anesthesia with repeated train stimuli at the intensity of 10X of muscle twitch threshold. The foot withdraw latency of the hind limb was measured for an indicator of pain level after each manipulation. Results : EA increased the mechanical threshold of the foot in the rat model of neuropathic pain significantly for the duration of 1 hr. suggesting a partial alleviation of pain. EA applied to SI6 point produced a significant improvement of mechanical sensitivity of the foot lasting for at least 1 h. However, $ST_{36}$ point did not produce any significant increase of mechanical sensitivity. The improvement of mechanical threshold was interpreted as an analgesic effect. The analgesic effort was specific to the acupuncture point since the analgesic effect on the neuropathic pain model could not be mimicked by EA applied to a point, $ST_{36}$. In addition, this analgesic effect of EA is mediated by a adrenergic mechanism of descending control of spinal cord from the brain. Conclusions : The data suggest that EA produces a potent analgesic effect on the neuropathic pain model in the rat; and 2) that EA-induced analgesia is mediated by a adrenergic mechanism of descending control in a point specific manner.