• The Korean Journal of Pain
• /
• 제13권1호
• /
• pp.19-30
• /
• 2000

Background: Partial nerve injury to a peripheral nerve may induce the development of neuropathic pain which is characterized by symptoms such as spontaneous burning pain, allodynia and hyperalgesia. Though underlying mechanism has not fully understood, sensitization of dorsal horn neurons may contribute to generate such symptoms. Nitric oxide acts as an inter- and intracellular messenger in the nervous system and is produced from L-arginine by nitric oxide synthase (NOS). Evidence is accumulating which indicate that nitric oxide may mediate nociceptive information transmission. Recently, it has been reported that NOS inhibitor suppresses neuropathic pain behavior in an neuropathic pain animal model. This study was conducted to determine whether nitric oxide could be involved in the sensitization of dorsal horn neurons in neuropathic animal model. Methods: Neuropathic animal model was made by tightly ligating the left L5 and L6 spinal nerves and we examined the effects of iontophoretically applied NOS inhibitor (L-NAME) on the dorsal horn neuron's responses to mechanical stimuli within the receptive fields. Results: In normal animals, NOS inhibitor (L-NAME) specifically suppressed the responses to the noxious mechanical stimuli. In neuropathic animals, the dorsal horn neuron's responses to mechanical stimuli were enhanced and NOS inhibitor suppressed the dorsal horn neuron's enhanced responses to non-noxious stimuli as well as those to noxious ones. Conclusions: These results suggest that nitric oxide may mediate nociceptive transmission in normal animal and also mediate sensitization of dorsal horn neurons in neuropathic pain state.

• The Korean Journal of Pain
• /
• 제27권1호
• /
• pp.54-62
• /
• 2014

Background: The recently known analgesic action mechanisms of nefopam (NFP) are similar to those of anticonvulsants and antidepressants in neuropathic pain treatment. It is difficult to prescribe high doses of oral neuropathic drugs without titration due to adverse effects. Unfortunately, there are few available intravenous analgesics for the immediate management of acute flare-ups of the chronic neuropathic pain. The aim of this study was to determine the additional analgesic effects for neuropathic pain of NFP and its adverse effects during the titration of oral medications for neuropathic pain among inpatients with postherpetic neuralgia (PHN). Methods: Eighty inpatients with PHN were randomly divided into either the NFP or normal saline (NS) groups. Each patient received a 3-day intravenous continuous infusion of either NFP with a consecutive dose reduction of 60, 40, and 20 mg/d, or NS simultaneously while dose titrations of oral medications for neuropathic pain gradually increased every 3 days. The efficacy of additional NFP was evaluated by using the neuropathic pain symptom inventory (NPSI) score for 12 days. Adverse effects were also recorded. Results: The median NPSI score was significantly lower in the NFP group from days 1 to 6 of hospitalization. The representative alleviating symptoms of pain after using NFP were both spontaneous and evoked neuropathic pain. Reported common adverse effects were nausea, dizziness, and somnolence, in order of frequency. Conclusions: An intravenous continuous infusion of NFP reduces spontaneous and evoked neuropathic pain with tolerable adverse effects during the titration of oral medications in inpatients with PHN.

• Journal of Korean Neurosurgical Society
• /
• 제57권1호
• /
• pp.6-11
• /
• 2015

Objective : Neuropathic pain causes patients feel indescribable pain. Deep Brain Stimulation (DBS) is one of the treatment methods in neuropathic pain but the action mechanism is still unclear. To study the effect and mechanism of analgesic effects from DBS in neuropathic pain and to enhance the analgesic effect of DBS, we stimulated the ventral posterolateral nucleus (VPL) in rats. Methods : To observe the effect from VPL stimulation, we established 3 groups : normal group (Normal group), neuropathic pain group (Pain group) and neuropathic pain+DBS group (DBS group). Rats in DBS group subjected to electrical stimulation and the target is VPL. Results : We observed the behavioral changes by DBS in VPL (VPL-DBS) on neuropathic pain rats. In our study, the pain score which is by conventional test method was effectively decreased. In specific, the time of showing withdrawal response from painful stimulation which is not used measuring method in our animal model was also decreased by DBS. Conclusion : The VPL is an effective target on pain modulation. Specifically we could demonstrate changes of pain response duration which is not used, and it was also significantly meaningful. We thought that this study would be helpful in understanding the relation between VPL-DBS and neuropathic pain.

• Journal of Acupuncture Research
• /
• 제18권6호
• /
• pp.215-224
• /
• 2001

Objcetive : Neuropathic pain sometimes arises from a partial peripheral nerve injury. This kind of pain is usually accompanied by spontaneous burning pain, allodynia and hyperalgesia. It has been well known that acupuncture is effective to the pain control from ancient time in Asia. However, it is not clear whether acupuncture can control neuropathic pain. The aim of the present study is to examine if acupuncture stimulation may be effective to the mechanical allodynia in a rat model of neuropathic pain. Methods : To produce neuropathic pain, under sodium pentobarbital anesthesia, the right superior caudal trunk was resected between the S3 and S4 spinal nerves. After the neuropathic surgery, we examined if the animals exhibited the behavioral signs of mechanical allodynia. The mechanical allodynia was assessed by stimulating the tail with von Frey hair (bending force : 2.0g). three or 6 weeks after the neuropathic surgery, acupuncture stimulation was delivered to Houxi (SI 3) as the following parameters (2HZ frequency, 0.07mA intensity and 3msec duration) for 30 minutes. Results : The stimulation of Houxi (SI 3) acupoint relieved the behavioral signs of mechanical allodynia. Conclusion : Our results suggest that acupuncture can control the mechanical allodynia of neuropathic pain.

• The Korean Journal of Physiology and Pharmacology
• /
• 제23권1호
• /
• pp.1-20
• /
• 2019

Neuropathic pain is a complex chronic pain state caused by the dysfunction of somatosensory nervous system, and it affects the millions of people worldwide. At present, there are very few medical treatments available for neuropathic pain management and the intolerable side effects of medications may further worsen the symptoms. Despite the presence of profound knowledge that delineates the pathophysiology and mechanisms leading to neuropathic pain, the unmet clinical needs demand more research in this field that would ultimately assist to ameliorate the pain conditions. Efforts are being made globally to explore and understand the basic molecular mechanisms responsible for somatosensory dysfunction in preclinical pain models. The present review highlights some of the novel molecular targets like D-amino acid oxidase, endoplasmic reticulum stress receptors, sigma receptors, hyperpolarization-activated cyclic nucleotide-gated cation channels, histone deacetylase, $Wnt/{\beta}-catenin$ and Wnt/Ryk, ephrins and Eph receptor tyrosine kinase, Cdh-1 and mitochondrial ATPase that are implicated in the induction of neuropathic pain. Studies conducted on the different animal models and observed results have been summarized with an aim to facilitate the efforts made in the drug discovery. The diligent analysis and exploitation of these targets may help in the identification of some promising therapies that can better manage neuropathic pain and improve the health of patients.

• Journal of Acupuncture Research
• /
• 제21권3호
• /
• pp.145-167
• /
• 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.

• Journal of Acupuncture Research
• /
• 제22권5호
• /
• pp.67-77
• /
• 2005

Objectives : The purpose of this study is to examine if Bee Venom 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 alloynia. The allodynia was assessed by stimulating the medial malleolus with von Frey filament and acetone. Three weeks after the neuropathic surgery, Bee Venom 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 yon 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 : The Bee Venom Acupuncture injected Hwando(GB30) decreased the withdrawl response of mechanical allodynia in BV-2, BV-3 group as compared with control group. The Bee Venom Acupuncture injected Hwando(GB30) decreased the withdrawl response of chemical allodynia(cold allodynia) in BV-2, BV-3 group as compared with control group. The Bee Venom Acupuncture injected Hwando(GB30) showed the significant difference between control group and BV-2 group, control group and BV-3 group in the c-Fos expression and U count. Conclusion : We have noticed that Bee Venom Acupuncture at Hwando(GB30) decreased mechanical allodynia and cold allodynia in the model of neuropathic pain compared with the control group. C-Fos expression in the central gray of that group was also decreased compared with the control group. Psin control using Bee Venom Acupuncture was accumulated as time goes by. This study can be used as a basic resource on a study and a treatment of pain.

• Journal of Acupuncture Research
• /
• 제30권4호
• /
• pp.69-78
• /
• 2013

Objectives : The purpose of this study is to examine whether Eucommiae Cortex pharmacopuncture may affect to the neuropathic pain in a rat model. Methods : To produce the model of neuropathic pain, under isoflurane 2.5 % anesthesia, underwent tight ligation by 6.0 silk thread and transection of the tibial and sural nerves, leaving the common peroneal nerve intact. After neuropathic surgery, the author examined if the exhibited the behavioral sign of allodynia. The allodynia was assessed by stimulating the plantar with Dynamic Plantar Aesthesiometer. Three days after the neuropathic surgery, Eucommiae Cortex pharmacopuncture was injected at Sinsu($BL_{23}$) once every week for 6 weeks. After that, the author examined the withdrawal response of neuropathic rats' leg by Dynamic Plantar Aesthesiometer. And also the author examined Bax, Bcl-2, Bax/Bcl-2 ratio in the spinal cord of neuropathic rats and the change of WBC, RBC, HGB, HCT count in the blood of neuropathic rats. Results : 1. The Eucommiae Cortex pharmacopuncture decreased the withdrawal response of mechanical allodynia that assessed with Dynamic Plantar Aesthesiometer in EC2-$BL_{23}$ group as compared with control group. 2. The Eucommiae Cortex pharmacopuncture decreased Bax/Bcl-2 ratio in EC1-$BL_{23}$, EC2-$BL_{23}$ group. But The Eucommiae Cortex pharmacopuncture injected at Sinsu($BL_{23}$) didn't change Bax, Bcl-2 expression level in the all group. 3. The Eucommiae Cortex pharmacopuncture decreased WBC count in EC1-$BL_{23}$, EC2-$BL_{23}$ group. Conclusions : We have noticed that Eucommiae Cortex pharmacopuncture decreased mechanical allodynia in the model of neuropathic pain compared with the control group. Bax/Bcl-2 ratio in spinal cord of that group was also decreased compared with the control group. This study can be used as a basic resource on a study and a treatment of neuropathic pain.

• The Korean Journal of Pain
• /
• 제33권4호
• /
• pp.359-377
• /
• 2020

Background: This study investigated whether current smoking and a higher nicotine dependency were associated with chronic low back pain (LBP), lumbar related leg pain (sciatica) and/or radicular neuropathic pain. Methods: A cross-sectional study was conducted on 150 patients (mean age, 60.1 ± 13.1 yr). Demographic data, the International Association for the Study of Pain (IASP) neuropathic pain grade, STarT Back tool, and the Fagerström test were completed. A control group (n = 50) was recruited. Results: There was a significant difference between current smokers and nonsmokers in the chronic LBP group in the mean pain score (P = 0.025), total STarT Back score (P = 0.015), worst pain location (P = 0.020), most distal pain radiation (P = 0.042), and in the IASP neuropathic pain grade (P = 0.026). There was a significant difference in the mean Fagerström score between the four IASP neuropathic pain grades (P = 0.005). Current smoking yielded an odds ratio (OR) of 3.071 (P = 0.011) for developing chronic LBP and sciatica, and an OR of 4.028 (P = 0.002) for obtaining an IASP "definite/probable" neuropathic pain grade, for both cohorts. The likelihood for chronic LBP and sciatica increased by 40.9% (P = 0.007), while the likelihood for an IASP neuropathic grade of "definite/probable" increased by 50.8% (P = 0.002), for both cohorts, for every one unit increase in the Fagerström score. Conclusions: A current smoking status and higher nicotine dependence increase the odds for chronic LBP, sciatica and radicular neuropathic pain.

• BMB Reports
• /
• 제35권4호
• /
• pp.420-427
• /
• 2002

Partial nerve injury is the main cause of neuropathic pain disorders in humans. Acupuncture has long been used to relieve pain. It is known to relieve pain by controlling the activities of the autonomic nervous system. Although the mechanism of neuropathic pain and analgesic effects of electroacupuncture (EA) have been studied in a rat model system, its detailed mechanism at the molecular level remains unclear. To identify genes that might serve as either markers or explain these distinct biological functions, a cDNA microarray analysis was used to compare the expression of 8,400 genes among three sample groups. Messenger RNAs that were pooled from the spinal nerves of 7 normal. 7 neuropathic pain, and 7 EA treatment rat models were compared. Sixty-eight genes were differentially expressed more than 2-fold in the neuropathic rat model when compared to the normal, and restored to the normal expression level after the EA treatment. These genes are involved in a number of biological processes, including the signal transduction, gene expression, and nociceptive pathways. Confirmation of the differential gene expression was performed by a dot-blot analysis. Dot-blotting results showed that the opioid receptor sigma was among those genes. This indicates that opioid-signaling events are involved in neuropathic pain and the analgesic effects of EA. The potential application of these data include the identification and characterization of signaling pathways that are involved in the EA treatment, studies on the role of the opioid receptor in neuropathic pain, and further exploration on the role of selected identified genes in animal models.