• The Korean Journal of Pain
• /
• v.35 no.1
• /
• pp.66-77
• /
• 2022

Background: Thrombospondin-4 (TSP4) upregulates in the spinal cord following peripheral nerve injury and contributes to the development of neuropathic pain (NP). We investigated the effects of cyanocobalamin alone or in combination with morphine on pain and the relationship between these effects and spinal TSP4 expression in neuropathic rats. Methods: NP was induced by chronic constriction injury (CCI) of the sciatic nerve. Cyanocobalamin (5 and 10 mg/kg/day) was administered 15 days before CCI and then for 4 and 14 postoperative days. Morphine (2.5 and 5 mg/kg/day) was administered only post-CCI. Combination treatment included cyanocobalamin and morphine, 10 and 5 mg/kg/day, respectively. All drugs were administered intraperitoneally. Nociceptive thresholds were detected by esthesiometer, analgesia meter, and plantar test, and TSP4 expression was assessed by western blotting and fluorescence immunohistochemistry. Results: CCI decreased nociceptive thresholds in all tests and induced TSP4 expression on the 4th postoperative day. The decrease in nociceptive thresholds persisted except for the plantar test, and the increased TSP4 expression reversed on the 14th postoperative day. Cyanocobalamin and low-dose morphine alone did not produce any antinociceptive effects. High-dose morphine improved the decreased nociceptive thresholds in the esthesiometer when administered alone but combined with cyanocobalamin in all tests. Cyanocobalamin and morphine significantly induced TSP4 expression when administered alone in both doses for 4 or 14 days. However, this increase was less when the two drugs are combined. Conclusions: The combination of cyanocobalamin and morphine is more effective in antinociception and partially decreased the induced TSP4 expression compared to the use of either drug alone.

• Archives of Reconstructive Microsurgery
• /
• v.10 no.1
• /
• pp.12-17
• /
• 2001

Recovery of nerve injury is conditioned by various factors including physical state, injured site, cause of injury, and neurorrhaphy Many researchers have reported on regeneration of nerve using end to side neurorrhaphy. The purpose of this study was to examine regeneration of nerve in various conditioned side to side neurorrhaphy. Total of 25 male Sprague-Dawley rats weighing 220 to 250 gm were divided into five groups of five rats each. The group 1, sham group, composed of dissection only without nerve transaction. The group 2, control group, composed of nerve division only without neurorrhaphy or sural nerve graft. The group 3 composed of one segmental sural nerve graft between the tibial and peroneal nerve after division. Group 4 had two segment graft, and the group 5 with three segment graft, each segment being 6mm long and 5 mm apart. The side to side neurorrhaphy was performed between peroneal nerve and tibial nerve using segmental sural nerve graft in rats. We exposed the sciatic nerve, tibial nerve, peroneal nerve, and sural nerve on left side with prone position. The peroneal nerve was cut on the bifurcation site from tibial nerve and the side to side epineurial neurorrhaphy was performed between peroneal nerve and tibial nerve through 6 mm sural nerve segment graft with 11-0 nylon under operating microscope. The electromyography and the weight from ipsilateral tibialis anterior muscle was performed at one month after neurorrhaphy Peroneal and tibial nerve was examined at distal and proximal to the neurorrhaphy site by methylene blue stain under light microscope for histologic appearance. The number of nerve fibers were counted using the image analyzer. Statistically, both in electromyography and number of nerve fibers, the differences in values between the groups were significant.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.26 no.4
• /
• pp.462-468
• /
• 2012

The present study was conducted with the object of examining how ST36 and LR3 electro acupuncture affects the injured side and the intact side in rats with sciatic nerve injury. For this study, we divided rats into a control group that were injured but not treated, experimental group I that were injured and had electro acupuncture on the intact side, experimental group II that were injured and had electro-acupuncture on the injured side, and experimental group III that were injured and had electro-acupuncture on both the intact side and the injured side, and performed behavioral and immunohistochemical tests. The results of this study are as follows. In the results of hot plate test, on Day 1 of experiment, experimental group I did not show a statistically significant difference but experimental group II and III showed a statistically significant difference, and on Day 2 and 3, all of experimental group I, II and III showed a statistically significant difference. In the results of SFI test, on Day 7 of experiment, experimental group I did not show a statistically significant difference but experimental group II and III showed a statistically significant difference, and on Day 14 and 21, all of experimental group I, II and III showed a statistically significant difference. In the results of immunohistochemical test, the expression of c-fos decreased gradually on Day 1, 2 and 3 in all the experimental groups, and the decrease was larger in the experimental groups that had electro-acupuncture than in the control group. In the results of immunohistochemical test, the expression of BDNF increased gradually on Day 7, 14 and 21 in all the experimental groups, and the expression was higher in the experimental groups than in the control group. Summing up the results, ST36 and LR3 electro acupuncture was effective when it was applied to the injured side and to both sides after sciatic nerve injury, but it was also effective in pain relief and nerve regeneration when it was applied to the intact side.

• Journal of Pharmacopuncture
• /
• v.16 no.3
• /
• pp.7-10
• /
• 2013

Objectives: This study aimed to evaluate the evidence available in the literature for the safety and efficacy of Dioscoreae Rhizoma (DR) for the treatment of peripheral neuropathy. Methods: Literature searches were performed in MEDLINE and three Korean medical databases up to April 2013. All studies evaluating the effects on peripheral neuropathy or the safety of DR monopreparations were considered. Results: Three studies - DR extract per os (po) on diabetic neuropathy in mice, DR extract injection on the peripheral sciatic nerve after crush injury in rats and DR extract injection to patients with peripheral facial paralysis proved that DR treatments were effective for the treatment of nerve injuries. Conclusions: In conclusion, we found the DR has a strong positive potential for the treatment of peripheral neuropathy, but studies addressing direct factors related to the nerve still remain insufficient.

• The Journal of Korean Physical Therapy
• /
• v.16 no.2
• /
• pp.128-139
• /
• 2004

말초신경은 외상이나 질병 등 여러 가지 원인으로 손상되기 쉬우며, 손상의 정도가 심하거나 치료가 지연되는 경우에는 심각한 기능 소실을 초래할 수 있다. 본 연구에서는 수영이 말초신경손상후 운동기능의 회복과 뇌유인성 신경영양인자 (brain-derived neurotrophic factor, BDNF) mRNA의 발현에 미치는 효과를 알아보기 위하여, 흰쥐 좌골신경에 압박 손상을 가하고 수영을 적용한 후 보행궤적분석 (walking track analysis)과 역전사연쇄반응 (reverse transcription-polymerase chain reaction, RT-PCR)을 실시하였다. 그 결과, 좌골신경 압박손상된 쥐는 특징적인 보행패턴을 나타내어 좌골신경기능지수 (sciatic function index, SFI)가 현저히 낮아졌으며, BDNF mRNA의 발현이 증가하였다. 좌골신경 압박 손상후 수영을 한 쥐에서는 SFI가 현저히 향상되었으며, BDNF mRNA의 발현은 억제되었다. 이러한 결과는 말초신경손상후 수영이 BDNF mRNA의 발현을 조절함으로써 기능 회복을 촉진시키는 효과적인 치료방법이 될 수 있음을 제안하고 있다.

• The Journal of the Korean bone and joint tumor society
• /
• v.3 no.2
• /
• pp.80-88
• /
• 1997

Malignant tumors of extremeties involving major neurovascular structures have been treated by amputation. However recent development of diagnostic tools(CT, MRI etc.), surgical techniques, anticancer chemotherapeutic agents, and radiation techniques allow surgeons to treat malignant tumors in the limb without amputation. It has been reported that a local application of low-heat to the tissue with tumor can kill tumor cells. It is, however, not known if the attendant neural and vascular injuries may be recovered. The present study was, therefore, undertakn to address this question in rabbit sciatic nerves. A low-heat injury to the sciatic nerve was induced by perfusing the nerve with $60^{\circ}C$ saline for 30 minutes and the courses of functional and morphological recovery of the nerve were evaluated for 16 weeks. The results are summerized as follows : 1. In the electromyographic nerve conduction test the average amplitude was markedly attenuated at 4 and 8 weeks after the low-heat treatment, but it progressively increased to the level 89.5% of the control at 16 week post-treatment. The average latency in the control group was 0.62 msec. The latency in the experimental group was much longer than this at 4 and 8 week post-treatment, but it progressively reverted to the control level, showing 0.622 msec at 16 weeks. 2. In the needle EMG, many fibrillation potentials and positive sharp waves were appeared until 8 weeks post-treatment. After 16 weeks, however, no fibrillation potential was observed. 3. In the early phase of post-treatment period, the myelinated nerve fibers contained many vacuoles and the number of myelinated nerve fibers appeared to be considerably reduced. However, as time goes myelinated nerve fibers were regenerated, such that after 16 weeks the histologic appearance of the nerve was similar to that of the control group.

• Journal of Ginseng Research
• /
• v.27 no.3
• /
• pp.103-109
• /
• 2003

We investigated the effect of ginseng total saponin (GTS) on the regeneration process of experimentally crush injured rat sciatic nerves. The bilateral sciatic nerves of fifty adult male Sprague-Dawley rats were compressed surgically with a straight hemostat for 30 seconds with 1 mm width. Twenty rats were divided into four groups to test the dose-dependent effect of GTS (0, 50, 100, or 150 mg/kg, i.p.). Saline for vehicle control group or GTS dissolved in saline was administerd for three weeks. After that period of time, the numbers of total myelinated axon and degenerated myelin in the sciatic nerves of bilateral legs were examined and analyzed using image analysis system to confirm a morphological effect of GTS. We found that the most effective concentration of GTS for the regeneration of damaged sciatic nerve was 150 mg/kg. In another set of experiment, thirty rats were divided into two groups as saline-treated vehicle group and GTS-treated group (150 mg/kg, i.p.) for three weeks. Every week we examined the numbers of total myelinated axon and degenerated myelin in the sciatic nerves of bilateral legs using image analysis system to evaluate the effect of GTS on injured nerves. We found that the regeneration of damaged sciatic nerves was facilitated in GTS-treated group compared to saline-treated group until two weeks. However, after that period of time we could not observe the significant difference between saline-treated group and GTS-treated group. These results suggest that GTS is a useful adjuvant therapy for the regeneration of the peripheral nerve injury in short period of treatment.

• The Korean Journal of Physiology and Pharmacology
• /
• v.13 no.3
• /
• pp.161-168
• /
• 2009

In the peripheral nerves, injury-induced cytokines and growth factors perform critical functions in the activation of both the MEK/ERK and JAK/STAT3 pathways. In this study, we determined that nerve injury-induced ERK activation was temporally correlated with STAT3 phosphorylation at the serine 727 residue. In cultured Schwann cells, we noted that ERK activation is required for the serine phosphorylation of STAT3 by neuropoietic cytokine interleukin-6 (IL-6). Serine phosphorylated STAT3 by IL-6 was transported into Schwann cell nuclei, thereby indicating that ERK may regulate the transcriptional activity of STAT3 via the induction of serine phosphorylation of STAT3. Neuregulin-1 (NRG) also induced the serine phosphorylation of STAT3 in an ERK-dependent fashion. In contrast with the IL-6 response, serine phosphorylated STAT3 induced by NRG was not detected in the nucleus, thus indicating the non-nuclear function of serine phosphorylated STAT3 in response to NRG. Finally, we determined that the inhibition of ERK prevented injury-induced serine phosphorylation of STAT3 in an ex-vivo explants culture of the sciatic nerves. Collectively, the results of this study show that ERK may be an upstream kinase for the serine phosphorylation of STAT3 induced by multiple stimuli in Schwann cells after peripheral nerve injury.

• The Journal of Korean Physical Therapy
• /
• v.19 no.4
• /
• pp.33-41
• /
• 2007

Purpose: To investigate environmental enrichment and nerve stimulation follows in application times with the change of BDNF & Trk-B receptor in the motor cortex and spinal cord. Methods: Experimental groups were divided into the five groups. Group I: normal control group, Group II: experiment control group, Group III: sciatic never electrical stimulation after MCAO, Group IV: application of only environmental enrichment after MCAO, Group V: never electrical stimulation with environmental enrichment after MCAO. Histologic observation and coronal sections were processed individually in goat polyclonal antibody phosphorylated BDNF and rabbit polyclonal antibody Trk-B receptor. Results: In immunohistochemistric response of BDNF and Trk-B, group II were showed that lower response effect at postischemic 1 days, 3 days, and 7 days. Group V were showed that increase response effect at postischemic 3 days, 7 days and 14 days. Specially showed that the most response effect at postischemic 14 days. In neurobehavioral assessment, group V were significantly difference from other groups on between-subject effects. Conclusion: The above results suggest that combined environmental enrichment with peripheral nerve electrical stimulation in focal ischemic brain injury were more improved that the change of BDNF & Trk-B receptor expression than non treatment.

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