• 대한물리의학회지
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• 제8권1호
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• pp.79-89
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• 2013

PURPOSE: To identify the effects of single trial transcutaneous electrical nerve stimulation (TENS) application on chronic neuropathic pain and the repeated TENS application to development of neuropathic pain following peripheral nerve injury. METHODS: First, 20 rats were given the median nerve ligation to induce chronic neuropathic pain. After the ligation, neuropathic pain was assessed by measuring the forepaws withdrawal threshold to von Frey filaments for 3 weeks. Afterward, rats were randomly divided into TENS group and placebo-TENS group. TENS (frequency 100Hz, pulse width $200{\mu}s$) was applied to the forearm for 20 minutes. Second, 34 rats were randomly allocated into two group after median nerve ligation: TENS group and placebo-TENS group. Both interventions were applied to the forearm for 20 minutes from 1 day to 3 weeks after injury. Neuropathic pain to mechanical was measured on each rat for 3 weeks. RESULTS: Exeprimental rats showed a clear neuropathic pain-like behaviors, such as reduced forepaw withdrawal threshold to mechanical stimulation for 3 weeks, after median nerve ligation. And, TENS decreased effectively the chronic neuropathic pain originated from median nerve injury. TENS also diminished the development of neuropathic pain after nerve injury. CONCLUSION: Our animal model studying for neuropathic pain following median nerve injury may be useful to investigate peripheral neuropathic pain in human. Also, TENS may be used to mediate chronic neuropathic pain and to prevent the development of neuropathic pain following median nerve injury.

• The Korean Journal of Pain
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• 제9권2호
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• pp.311-317
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• 1996

Background: Following peripheral nerve injury, rats will show a tactile allodynia and hyperalgesia. But the mechanism of allodynia is still obscure. Previous studies have shown this allodynia was reversed by intrathecal alpha-2 agonists and NMDA antagonists, but not by morphine. In formalin test, either the pretreatment of NMDA antagonist or morphine prevents the hyperalgesia. The present studies, using rats rendered allodynic by ligation of the left L5 and L6 nerves, aimed to investigate the effects of pretreatment of MK-801 and morphine on the development of tactile allodynia. Methods and Material: Male Sprague-Dawley rats (100~150g) were anesthetized with halothane, the left L5 and L6 spinal nerves were ligated tightly by 6-0 black silk. For sham operation muscle dissection was performed but the spinal nerve was not ligated. For pretreatment of drugs, MK-801 (NMDA antagonist; 0.3 mg/kg). CNQX (non-NMDA) antagonist; 0.3 mg/kg), morphine (1 mg/kg) or saline (placebo) was administered subcutaneously 30 minutes before operation. A second dose was administered subcutaneously 24 hours after operation and further doses were given daily for 2 days further. The volume of injection was 5 ml/kg. To assess the mechanical allodynia, paw withdrawal thresholds of ipsilateral limb were determined using 8 von Frey hairs. Results: Within 2 days saline, CNQX or morphine injected rats developed tactile allodynia (paw withdrawal threshold was about 2g), and persisted for over 2 weeks. Pretreatment of MK-801 delayed the development of tactile allodynia for 3 days comparing to that of saline injected rat. Conclusion: NMDA receptor in the central nerve system plays an important role in the development of tactile allodynia induced by peripheral nerve injury. But the mechanism may be different from hyperalgesia developed in formalin test.

• The Korean Journal of Pain
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• 제21권3호
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• pp.179-186
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• 2008

Background: The adrenergic nervous system in the spinal cord contributes to the development of neuropathic pain after nerve injury. Brain derived neurotrophic factor may facilitate the sympathetic change in the spinal cord and influence the state of neuropathic pain. We probed the effect of chronic repetitive administration of systemic 4-methylcatechol, which is known to be a neurotrophic factor inducer, in a spinal nerve ligation model. Methods: We made the rat neuropathic pain model by the ligation of the L5 spinal nerve. Intraperitoneal 4-methylcatechol ($10{\mu}g/kg$) or the same volume of saline wasadministrated twice daily just after the operation for 7 days. The tactile allodynia was measured by using von Frey filaments and its change was followed up from 3 days after SNL. The lumbosacral enlargement of the spinal cord was taken out and the mRNA contents of the ${\alpha}_2-adrenoceptor$ subtypes were measured by real time polymerase chain reaction and this was then compared with the control groups. The antiallodynic effect of intrathecal clonidine (3, 10, $30{\mu}g$) was evaluated and compared in the 4-methylcatechol treated rats and the control rats. Results: The expression of the ${\alpha}_{2A}$ and ${\alpha}_{2C}$ adrenoceptor subtypes did not change after 4-methylcatechol treatment. Intrathecal clonidine showed an earlier and better effect at the highest dose ($30{\mu}g$ intrathecal), but not with any other doses. Conclusions: Chronic intraperitoneal administration of 4-methylcatechol may improve the effect of intrathecal clonidine, but we could not prove the increase of ${\alpha}_{2A}$ and ${\alpha}_{2C}$ adrenoceptors in the spinal cord of 4-methylcatechol treated rats.

• The Korean Journal of Physiology and Pharmacology
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• 제1권3호
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• pp.251-262
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• 1997

Peripheral nerve injury sometimes leads to neuropathic pain and depletion of calcitonin gene related-peptide (CGRP) and substance P (SP) in the spinal cord. However, the pathophysiological mechanisms for depletion of CGRP and SP following the neurorathic injury are still unknown. This study was performed to see whether the distribution of immunoreactivity for CGRP and SP in the superficial dorsal horn and dorsal root ganglia(DRG) was related to the distance between the DRG and injury site. To this aim, we compared two groups of rats; one group was subjected to unilateral inferior and superior caudal trunk transections at the level between the S3 and S4 spinal nerves (S34 group) and the other group at the levels between the S1 and S2, between S2 and S3 and between S3 and S4 spinal nerve (S123 group). The transections in both groups equally eliminated the inputs from the tail to the S1-3 DRG, but the distance from the S1/S2 DRG to the injury site was different between the two groups. Immunostaining with SP and CGRP antibody was done in the S1-S3 spinal cord and DRG of the two groups 1 and 12 weeks after the injury. The results obtained are as follows: 1. The immunoreactivity for CGRP and SP in the ipsilateral superficial dorsal horn and DRG decreased 1 and 12 weeks after neuropathic nerve injury. 2. The immunoreactive area of SP and CGRP in the S1 dorsal horn was smaller in the S123 group than in the S34 group, whereas that in the S3 dorsal horn was not significantly different between the two groups. The number of SP-immunoreactive DRG cells decreased on the neuropathic side as compared to the sham group's in all DRGs of experimental groups except the S1 DRG of the S34 group. These results suggest that the amounts of SP and CGRP in the dorsal horn and DRG following neuropathic injury inversely decrease according to the distance between the DRG and injury site.

• 동의생리병리학회지
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• 제32권1호
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• pp.35-42
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• 2018

TRPA1 and TRPV1 are members of the TRP superfamily of structurally related, nonselective cation channels. TRPA1 and TRPV1 are often co-expressed in sensory neurons and play an important role in mechanical hyperalgesia and allodynia during neuropathic pain. Scutellariae Radix was reported to possess anti-inflammation properties and similar patterns of therapeutic action against different diseases. also Baicalin(a known principal constituent of Scutellaria Radix) was shown to down-regulate the mRNA expression levels of TRPV1. In this study, we observed the effects of Scutellariae Radix extract(SRE) in neuropathic pain induced SD rats via modulation of TRPV1 and TRPA1. Oral administration of a Scutellaria Radix extract(in doses of 300mg/kg, SRE(300)) showed a meaningful increase in the withdrawal threshold of mechanical allodynia and showed a meaningful decrease in the expression of c-fos compared to the control group. SRE(100) and SRE(300) showed a meaningful decrease in the expression of TRPV1 level compared to the control group. These results suggest that Scutellariae Radix extract could decrease mechanical allodynia by down-regulate the TRPV1 on the model of neuropathic pain.

• The Korean Journal of Physiology and Pharmacology
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• 제1권3호
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• pp.241-249
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• 1997

The aim of the present study is to examine the brainstem sites where the electrical stimulation produces a suppression of dorsal horn neuron responses of neuropathic rats. An experimental neuropathy was induced by a unilateral ligation of L5-L6 spinal nerves of rats. Ten to 15 days after surgery, the spinal cord was exposed and single-unit recording was made on wide dynamic range (WDR) neurons in the dorsal horn. Neuronal responses to mechanical stimuli applied to somatic receptive fields were examined to see if they were modulated by electrical stimulation of various brainstem sites. Electrical stimulation of periaqueductal gray (PAG), n. raphe magnus (RMg) or n. reticularis gigantocellularis (Gi) significantly suppressed responses of WDR neurons -to both noxious and non-noxious stimuli. Electrical stimulation of other brainstem areas, such as locus coeruleus. (LC) and n. reticularis paragigantocellularis lateralis (LPGi), produced little or no suppression. Microinjection of morphine into PAG, RMg, or Gi also produced a suppression as similar pattern to the case of electrical stimulation, whereas morphine injection into LC or LPGi exerted no effects. The results suggest that PAG, NRM and Gi are the principle brainstem nuclei involved in the descending inhibitory systems responsible for the control of neuropathic pain. These systems are likely activated by endogenous opioids and exert their inhibitory effect by acting on WDR neurons in the spinal cord.

• Korean Journal of Acupuncture
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• 제36권4호
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• pp.264-273
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• 2019

Objectives : Microglia play a crucial role in electroacupuncture (EA) analgesia on neuropathic pain. The role of chemokines in producing analgesic effects of EA, however, is largely unknown. In the present study, we investigated the role of chemokines in producing analgesic effects of EA in the neuropathic pain model. Methods : Sprague-Dawley rats were randomly assigned into three groups (anesthetized group (ANE), non-acupoint EA group (NAP), and ST36 - GB34 EA group (ACU)). Neuropathic pain was induced by tight ligation of L5 spinal nerve. Mechanical and thermal hypersensitivity of hind paw was tested. Western blot tests and immunofluorescence assay for C-C motif chemokine ligand 2 (CCL2) levels and microglia activation were performed on spinal cord L5/6. EA was treated once daily from the 3rd day after surgery for 5 days. Results : EA treatments applied to ST36 and GB34 significantly reduced both mechanical and thermal hypersensitivity after two and three times of treatment, respectively. While CCL2 expression significantly increased in neuropathic rats, it was significantly reduced in the ACU. In addition, co-localization of CCL2 and activated microglia significantly decreased in the ACU compared to those of ANE and NAP in the spinal cord L5/L6 dorsal horn. Conclusions : The present results suggest that EA applied to ST36 and GB34 modulates the reduction of CCL2 release from the injured neurons and consequently decreases microglia activation in the spinal cord. Regulation of chemokine induced spinal activation of microglia plays a key role in analgesic effects of EA in the rat model of neuropathic pain.

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

• 대한치과마취과학회지
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• 제3권1호
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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.

• 대한한의학방제학회지
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• 제29권4호
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• pp.229-237
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• 2021

Objectives: This study aimed to analyze the effectiveness of Sogunjung-tang on neuropathic pain. Methods: This study was conducted on 50 cases of patients with neuropathic pain who were treated in LUA clinic from Jun 2021, to Oct 2021. All patients were treated with Sogunjung-tang, and in some cases, acupuncture or moxibustion was also performed. We measured the efficacy of treatment with a numerical rating scale (NRS), frequency, and duration of pain before treatment, after 1 week, and 3 weeks. Results: Both average pain NRS and worst pain NRS significantly decreased 1 week and 3 weeks after treatment compared to pre-treatment. The frequency and duration of pain did not differ after 1 week of treatment but showed a significant difference after 3 weeks. Conclusions: This study suggests that herbal medicine treatment with Sogunjung-tang reduces pain intensity, frequency, and duration in patients with neuropathic pain.