• Journal of Korean Academy of Nursing
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• v.40 no.5
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• pp.611-619
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• 2010

The purpose of this study was to examine the effects of exercise on muscle weight and Type I and II fiber cross-sectional area of affected and unaffected hindlimb muscles in rats with neuropathic pain induced by unilateral peripheral nerve injury. Methods: Neuropathic pain was induced by ligation and cutting of the left L5 spinal nerve. Adult male Sprague-Dawley rats were randomly assigned to one of two groups: The Pain+Exercise (PE) group (n=21) and the Sham+Exercise (SE) group (n=20). All rats had 28 sessions of treadmill exercise at grade 10 for 30 minutes, twice/day at 10 m/min for 14 days. Body weight, food intake and activity were measured every day. At 15 days all rats were anesthetized and soleus, plantaris and gastrocnemius muscles were dissected. Muscle weight and Type I, II fiber cross-sectional area of the dissected muscles were measured. Results: The PE group showed significant increases (p<.05), as compared to the SE group for body weight and total diet intake, muscle weight of the unaffected soleus and plantaris, and in Type I and II fiber cross-sectional area of unaffected three muscles and affected plantaris. Conclusion: Exercise for 14 days attenuates unaffected soleus, plantaris and gastrocnemius muscle atrophy in neuropathic pain model.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.6
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• pp.387-392
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• 2012

In this study, we examined the antinociceptive effect of Cyperi rhizoma (CR) and Corydalis tuber (CT) extracts using a chronic constriction injury-induced neuropathic pain rat model. After the ligation of sciatic nerve, neuropathic pain behavior such as mechanical allodynia and thermal hyperalgesia were rapidly induced and maintained for 1 month. Repeated treatment of CR or CT (per oral, 10 or 30 mg/kg, twice a day) was performed either in induction (day 0~5) or maintenance (day 14~19) period of neuropathic pain state. Treatment of CR or CT at doses of 30 mg/kg in the induction and maintenance periods significantly decreased the nerve injury-induced mechanical allodynia. In addition, CR and CT at doses of 10 or 30 mg/kg alleviated thermal heat hyperalgesia when they were treated in the maintenance period. Finally, CR or CT (30 mg/kg) treated during the induction period remarkably reduced the nerve injury-induced phosphorylation of NMDA receptor NR1 subunit (pNR1) in the spinal dorsal horn. Results of this study suggest that extracts from CR and CT may be useful to alleviate neuropathic pain.

• Korean Journal of Acupuncture
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• v.39 no.4
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• pp.132-141
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• 2022

Objectives : Some acupoints are commonly utilized to treat a variety of diseases. The acupoints appear to have a wide range of effects caused by several mechanisms. The purpose of this study is to investigate into the potential role of microRNAs (miRNAs) in the multipotent effects of individual acupoint stimulation. Methods : We examined the miRNA expressions in the dorsal root ganglia (DRG) of neuropathic or inflammatory pain rats following ST36 and GB34 electroacupuncture (EA) stimulation. Neuropathic pain was induced by L5 spinal nerve ligation. Inflammatory pain was induced by knee joint injection of Complete Freund's adjuvant (CFA). EA was given under gaseous anesthesia with the same parameters (1mA, 2Hz, 30 min) in 5 consecutive days. Pain behaviors and miRNA expressions were analyzed. Results : In rats with neuropathic and inflammatory pain, EA treatments significantly enhanced the paw withdrawal threshold and weight-bearing force. After nerve injury, 36 miRNAs were upregulated in the DRG of neuropathic rats, while EA downregulated 10 of them. Furthermore, 14 miRNAs were downregulated following nerve damage, while one was increased by EA. 15 miRNAs were increased in the DRG of inflammatory rats following CFA injection, while 5 were downregulated by EA. Furthermore, 17 miRNAs were downregulated following CFA injection, while 7 were increased by EA. The miRNAs rno-miR-335, rno-miR-381-5p, rno-miR-1306-3p, and rno-miR-1839-3p were regulated by EA in both models. Conclusions : In two pain models, EA applied to ST36 and GB34 regulated miRNA expression differently. There appeared to be both acupoint-specific and non-specific miRNAs, and miRNA regulation of differential protein expression may modulate a variety of EA mechanisms.

• Korean Journal of Acupuncture
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• v.22 no.2
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• pp.9-24
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• 2005

Objective: We have studied the effects of acupuncture and low level He-Ne laser therapy(LLLT) at $SI_3$, $BL_{40}$ on the tibial, sural nerve injury due to sports-damage or traffic accident and L5 spinal nerve ligature model like general herniation of nucleus pulposus(HNP) in a rat of neuopathic pain. Methods: A model of neuropathic pain was made by injuring tibial nerve and sural nerve while common peroneal nerve was maintained. Also, it was made by isolating left 5th lumbar spinal nerve. Three weeks after the neuropathic surgery, acupuncture and LLLT was injected at $SI_3$,$BL_{40}$ one time a day for one week. LLLT was divided three groups, that is LLLT-1(5mW), LLLT-2(10mW) and LLLT-3(30mW). After that, we examined the withdrawal response of neuropathic rats' legs by Von frey filament and acetone stimulation. And also we examined c-Fos, Nocieptin and KOR-3 in the midbrain central gray of neuropathic rats. Results: As we have observed the effect of mechanical allodynia, LLLT-3 group were diminished on 4 day, 5 day, 6 day and 7 day in the resection model compared with control model, LLLT-1 group were diminished on 5 day, LLLT-2 group were diminished on 3 day and 6 day, LLLT-3 group were diminished on 3 day, 4 day, 5 day, 6 day and 7 day in connected model compared with control group. As we have observed the effect of cold allodynia, LLLT-3 group were diminished on 7 day in the resection model compared with control model, LLLT-1 group were diminished on 6 day, 7 day, LLLT-3 group were diminished on 7 day in connected model compared with control group. As we have observed the effect of activity of c-Fos in the central gray part, LLLT-3 were diminished in resection model compared with control group, LLLT-1 group were diminished in connected model compared with control group. As we have observed the effect of activity of Nociceptin in the central gray part, resection model were not increased compared with control group, LLLT-1 group and LLLT-3 group were increased in connected model compared with control model. As we have observed the effect of activity of KOR-3 in the central gray part, resection model were not increased compared with control group, LLLT-3 group were increased in connected model compared with control model. Conclusions: We have noticed that LLLT-1 and LLLT-3 group have more controllable effect than acupuncture group. This study can be used in clinical therapy for neuropathic pain. But it is not reliability that Nociceptin and KOR-3 have effectively to control pain. Therefore We have to follow up about that.

• The Korean Journal of Pain
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• v.33 no.1
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• pp.30-39
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• 2020

Background: This study examined the effects of gabexate mesilate on spinal nerve ligation (SNL)-induced neuropathic pain. To confirm the involvement of gabexate mesilate on neuroinflammation, we focused on the activation of nuclear factor-κB (NF-κB) and consequent the expression of proinflammatory cytokines and inducible nitric oxide synthase (iNOS). Methods: Male Sprague-Dawley rats were used for the study. After randomization into three groups: the sham-operation group, vehicle-treated group (administered normal saline as a control), and the gabexate group (administered gabexate mesilate 20 mg/kg), SNL was performed. At the 3rd day, mechanical allodynia was confirmed using von Frey filaments, and drugs were administered intraperitoneally daily according to the group. The paw withdrawal threshold (PWT) was examined on the 3rd, 7th, and 14th day. The expressions of p65 subunit of NF-κB, interleukin (IL)-1, IL-6, tumor necrosis factor-α, and iNOS were evaluated on the 7th and 14th day following SNL. Results: The PWT was significantly higher in the gabexate group compared with the vehicle-treated group (P < 0.05). The expressions of p65, proinflammatory cytokines, and iNOS significantly decreased in the gabexate group compared with the vehicle-treated group (P < 0.05) on the 7th day. On the 14th day, the expressions of p65 and iNOS showed lower levels, but those of the proinflammatory cytokines showed no significant differences. Conclusions: Gabexate mesilate increased PWT after SNL and attenuate the progress of mechanical allodynia. These results seem to be involved with the antiinflammatory effect of gabexate mesilate via inhibition of NF-κB, proinflammatory cytokines, and nitric oxide.

• The Korean Journal of Pain
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• v.34 no.4
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• pp.405-416
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• 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.

• The Korean Journal of Pain
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• v.34 no.1
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• pp.58-65
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• 2021

Background: Supraspinal delivery of neurotensin (NTS), which may contribute to the effect of a systemically administered agonist, has been reported to be either pronociceptive or antinociceptive. Here, we evaluated the effects of systemically administered NTSR1 agonist in a rat model of neuropathic pain and elucidated the underlying supraspinal mechanism. Methods: Neuropathic pain was induced by L5 and L6 spinal nerve ligation in male Sprague-Dawley rats. The effects of intraperitoneally administered NTSR1 agonist PD 149163 was assessed using von Frey filaments. To examine the role of 5-HT neurotransmission, a serotonin (5-HT) receptor antagonist dihydroergocristine was pretreated intrathecally, and spinal microdialysis studies were performed to measure the change in extracellular level of 5-HT in response to PD 149163 administration. To investigate the supraspinal mechanism, NTSR1 antagonist 48692 was microinjected into the rostral ventromedial medulla (RVM) prior to systemic PD 149163. Additionally, the effect of intrathecal DHE on intra-RVM PD 149163 was assessed. Results: Intraperitoneally administered PD 149163 exhibited a dose-dependent attenuation of mechanical allodynia. This effect was partially reversed by intrathecal pretreatment with dihydroergocristine and was accompanied by an increased extracellular level of 5-HT in the spinal cord. The PD 149163-produced antinociception was also blocked by intra-RVM SB 48692. Direct injection of PD 149163 into the RVM mimicked the maximum effect of the same drug delivered intraperitoneally, which was reversed by intrathecal dihydroergocristine. Conclusions: These observations indicate that systemically administered NTSR1 agonist produces antinociception through the NTSR1 in the RVM, activating descending serotonergic projection to release 5-HT into the spinal dorsal horn.

• The Korean Journal of Pain
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• v.26 no.4
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• pp.356-360
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• 2013

Background: Nerve injury sometimes leads to chronic neuropathic pain associated with neuroinflammation in the nervous system. In the case of chronic neuropathic pain, the inflammatory and algesic mediators become predominant and result in pain hypersensitivity following nervous system damage. It is well known that urinary trypsin inhibitor (ulinastatin, UTI) has an anti-inflammatory activity. Recently, the neuroprotective action of UTI on the nervous system after ischemic injury has been reported. Thus, we evaluated the neuroprotective effect of ulinastatin in a rat model of neuropathic pain. Methods: Neuropathic pain was induced with L5 spinal nerve ligation (SNL) in male Sprague-Dawley rats weighing 100-120 g. The rats were divided into 3 groups, with n = 8 in each group. The rats in the control group (group 1) were administered normal saline and those in group 2 were administered UTI (50,000 U/kg) intravenously through the tail vein for 3 days from the day of SNL. Rats in group 3 were administered UTI (50,000 U/kg) intravenously from the $5^{th}$ day after SNL. The paw withdrawal threshold was measured using the von Frey test for 3 days starting from the $5^{th}$ day after SNL. Results: The paw withdrawal thresholds were significantly increased in the rats of group 2 compared to the other groups (P < 0.05). Conclusions: Ulinastatin, which was administered for 3 days after SNL, increased the paw withdrawal threshold and it could have a neuroprotective effect in the rat model of neuropathic pain.

• Korean Journal of Acupuncture
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• v.28 no.2
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• pp.37-47
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• 2011

Objectives : We have studied the effects of GaAlAs (808 nm) low level laser therapy (LLLT) and acupuncture at BL40 on neuropathic pain in rats induced by lumbar spinal nerve 5 ligation. Methods : To produce the model of neuropathic pain, under isoflurane 2.5% anesthesia, the lumbar spinal nerve 5 was ligated by 6-0 silk thread. After neuropathic surgery, we examined if the animals exhibited the behavioral sign of allodynia. The allodynia was assessed by stimulating the medial malleolus with von Frey filament and acetone. Three weeks after the neuropathic surgery, GaAlAs (808 nm) low level laser and acupuncture was inserted at BL40 once a day for 6 days. We examined the withdrawal response of neuropathic rats' legs by von Frey filament and acetone stimulation. And also the author examined c-Fos, nociceptin and nociceptin receptor in the midbrain central gray of neuropathic rats. Results : The GaAlAs (808 nm) low level laser therapy and acupuncture at BL40 decreased the withdrawal response of mechanical allodynia that assessed with von Frey filament in LLLT group on 5 and 6 times and with acetone in AT group and LLLT on 6times. The LLLT and acupuncture at BL40 decreased the c-Fos protein expression in AT and LLLT groups. The 808 nm LLLT and acupuncture at BL40 decreased the nociceptin protein and nociceptin receptor protein in LLLT group. Conclusions : We have noticed that GaAlAs (808 nm) LLLT and acupuncture at BL40 decreased mechanical allodynia in the model of neuropathic pain. c-Fos, nociceptin and nociceptin receptor expression in the central gray of that group was also decreased. This study can be used as a basic resource on a study and a treatment 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.