• Journal of Korean Biological Nursing Science
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• 제10권1호
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• pp.88-95
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• 2008

Purpose: The purpose of this study was to examine the effect of neuropathic pain by peripheral nerve injury on mass and Type I and II fiber cross-sectional areas on hindlimb muscles of the neuropathic pain model rat. Method: Adult male Sprague-Dawley rats (body weight 200-220 g) were assigned to one of two groups: a neuropathic pain group (n=7) that had a ligation of the left L5 spinal nerve, a control group (n=5), a naive rat without any procedures. Withdrawal threshold, activity, body weight and food intake were measured daily. At 8 days after neuropathic pain, all rats were anesthetized and the soleus and plantaris muscles were dissected from the both hindlimbs. Body weight, food intake, muscle weight and Type I and II fiber cross-sectional area of the dissected muscles were determined. Result: The neuropathic pain group showed a significant decreases (p<.05) as compared with the control rats, in diet intake, body weight, muscle weight and Type II fiber cross-sectional area of the left (affected side) soleus and plantaris muscles, and the right (unaffected side) muscle weight of plantaris and Type II fiber cross-sectional area of the soleus muscle. Conclusion: The hindlimb muscle atrophy occurs in both affected and unaffected side due to neuropathic pain by the peripheral nerve injury. The hindlimb muscle atrophy of the affected side is more pronounced than that of the unaffected side.

• The Korean Journal of Pain
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• 제13권2호
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• pp.156-163
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• 2000

Background: Peripheral nerve injury sometimes leads to chronic neuropathic pain such as causalgia. A subset of patients with causalgia have a sympathetically maintained pain which is often evoked by cooling stimuli. However, our knowledge on adrenergic receptor types responsible for cold-evoked pain that is sympathetically dependent is lacking. The present study was conducted to investigate subtypes of adrenoceptors involved in mediating cold-evoked pain that developed following peripheral nerve injury. Methods: Neuropathic surgery was performed by a unilateral ligation of L5 and L6 spinal nerves of rats. Behavioral sign of cold-evoked pain was examined for 5 min by measuring cumulative duration of time that the rat lifted its foot off a metal plate held at cold temperature ($5^{\circ}C$). Whether cold-evoked pain behavior was affected by antagonists of various subtypes of adrenoceptors, which were administered intraperitoneally before and after the ligation, was investigated. Results: After ligation, duration of foot lifting on the ligated side at cold temperature increased as compared to the pre-operative period. This increase maintained for the entire 40-day test period. Pretreatment with alpha-antagonist phentolamine produced a suppression of cold-evoked pain behavior that was not affected by beta-antagonist propranolol pretreatment. Prazosin, alpha-1 antagonist, suppressed cold- evoked pain behavior when treated either before or after nerve ligation. On the other hand, alpha-2 antagonist yohimbine was without effect on cold-evoked pain behavior whether it was treated before or after the ligation. Conclusions: The results suggest that peripheral nerve injury develops cold-evoked pain that is sympathetically dependent, and that alpha-1 adrenoreceptor plays a critical role for the generation of this type of pain in its initiation as well as maintenance.

• The Korean Journal of Pain
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• 제9권2호
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• pp.318-325
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• 1996

Background: Sympathectomy relieves pain in sympathectically maintained pain, and subcutaneous injection of norepinephrine(NE) can rekindle mechanical allodynia. However, the mechanism of rekindling is not clear. The purpose of this study is to investigate which subtype of $\alpha$-adrenoceptor is involved in NE-induced rekindling of mechanical allodynia in sympathectomized neuropathic rats. Methods: Neuropathic injury was produced by tightly ligating the left L5 and L6 spinal nerves of 36 male Sprague-Dawley rats and bilateral lumbar sympathectomy was done at two weeks postoperatively. Starting at 7 days after sympathectomy, rekindling of mechanical allodynia was induced by NE and clonidine injected into the left paw, which was reversed by pretreatment of phentolamine and idazoxan. Mechanical allocynia was quantified by measuring the frequency of foot lifts to two von Frey filaments applied to the paw. Results: All tested rats displayed well-developed signs of mechanical allodynia at the left paw that were abolished by a bilateral lumbar sympathectomy. Subcutaneous (s.c.) injection of NE (0.05 ${\mu}g$) into the affected paw of sympathectomized neuropathic rats rekindled previous mechanical allodynia. These effects could be mimicked by an ${\alpha}_2$-receptor agonist clonidine, but not by an ${\alpha}_1$-receptor agonist phenylephrine. The NE-induced rekindling of mechanical allodynia was significantly reduced by prior s.c. injection of a mixed $\alpha$-receptor antagonist phentolamine (20${\mu}g$) and ${\alpha}_2$-receptor antagonist idazoxan(20${\mu}g$), but not by a ${\alpha}_1$-receptor antagonist terazosin (20${\mu}g$). The pretreatment of idazoxan produced dose-related inhibition of NE-induced rekindling of mechanical allodynia. The rekindling induced by ${\alpha}_2$-receptor agonist clonidine (5${\mu}g$) was also reversed by prior s.c. injection of ${\alpha}_2$-receptor antagonist idazoxan (20${\mu}g$). Conclusion: Subcutaneous injection of NE into the paw of sympathectomized neuropathic rats rekindles mechanical allodynia, which is reversed by an ${\alpha}_2$-, but not by an ${\alpha}_1$-receptor antagonist. Therefore, rekindling of mechanical allodynia in sympathectomized neuropathic rats is mediated by ${\alpha}_2$-adrenoceptor.

• The Korean Journal of Pain
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• 제14권1호
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• pp.98-103
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• 2001

Neuropathic pain originating from multiple condition of nerve cell injury is common, but is difficult to treat. Even though many drugs such as anti-convulsants, anti-depressants, NSAIDs, opioids have been used, their clinical analgesic action were not satisfactory due to occur severe side effects. Gabapentin was introduced in 1994 as a novel antiepileptic drug and has been used to treat partial seizure. After 1995 gabapentin treatment for reflex sympathetic dystrophy (RSD) started, 45% of the reports about the analgesic efficacy of gabapentin were restricted to the treatments of non-epileptic pain syndrome. This drug is preferred to treat neuropathic pain because of a lower incidence of its side effects than those of other anti-convulsants and anti-depressants. For evaluating it's analgesic efficacy, the changes in the patients' subjective pain intensity was measured by the score on the visual analogue scale (VAS) and patient's objective pain intensity by measuring the skin temperature via infrared thermography were investigated respectively. Side effects of gabapentin were look into. We observed successful relief of neuropathic pain in the three patients which included post-herpetic neuraligia, complex regional pain syndrome (CRPS) and diabetic neuropathic pain, and the side effects of gabapentin were at acceptable levels.

• The Korean Journal of Pain
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• 제11권2호
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• pp.201-209
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• 1998

Background: Tricyclic antidepressants (TCA) have been used for various pain syndromes for their analgesic effects. They, however, often have anticholinergic side effects and therefore search for more selective drugs with fewer side effects is justified. Paroxetine, a selective serotonin reuptake inhibitor devoid of autonomic side effects, was evaluated for its role as an analgesic adjuvant in the management of neuropathic pain. Method: According to individual diagnostic group as diabetic neuropathy, postherpetic neuralgia, central pain syndrome and cancer related plexopathy, 10 patients per each group were equally accumulated. Patients have been stabilized in their analgesic regimen at least four weeks prior to enrollment into study. TCA, if taken, was discontinued for two weeks for wash out period. Baseline four point verbal pain intensity score was obtained and oral administration of paroxetine 20 mg was initiated. At two weeks follow-up visit, pain intensity scores, pain improvement scores judged by family, drug efficacy, tolerability and overall evaluation were assessed. The incidence of side effects were also obtained. Result: After two weeks of treatment, pain intensity scores decreased in 77.5% of patients and no patients experienced aggravation. These findings were objectively reflected in pain improvement scores judged by family members. But, the number of nonresponders was different among groups. In drug efficacy, tolerability and overall evaluation, the proportions of patients who scored as excellent or good were 75%, 80% and 80% respectively. Incidence of side effects was 27.5%, but the side effects spontaneously disappeared after discontinuation of medication. Conclusion: Paroxetine, a selective serotonin reuptake inhibitor, appears to be effective as adjuvant analgesic for the management of various neuropathic pain syndromes.

• The Korean Journal of Pain
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• 제14권2호
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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.

• The Korean Journal of Pain
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• 제22권3호
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• pp.210-215
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• 2009

Background: Several studies have indicated that a nerve injury enhances the expression of the voltage-gated calcium channel ${\alpha}2{\delta}1$ subunit (Cav ${\alpha}2{\delta}1$) in sensory neurons and the dorsal spinal cord. This study examined whether NMDA receptor activation is essential for Cav ${\alpha}2{\delta}1$-mediated tactile allodynia in Cav ${\alpha}2{\delta}1$ overexpressing transgenic mice and L5/6 spinal nerve ligated rats (SNL). These two models show similar Cav ${\alpha}2{\delta}1$ upregulation and behavioral hypersensitivity, without and with the presence of other injury factors, respectively. Methods: The transgenic (TG) mice were generated as described elsewhere (Feng et al., 2000). The left L5/6 spinal nerves in the Harlan Sprague Dawley rats were ligated tightly (SNL) to induce neuropathic pain, as described by Kim et al. (1992). Memantine 2 mg/kg (10 ul) was injected directly into the L5/6 spinal region followed by $10{\mu}l$ saline. Tactile allodynia was tested for any mechanical hypersensitivity. Results: The tactile allodynia in the SNL rats could be reversed by an intrathecal injection of memantine 2 mg/kg at 1.5 hours. The tactile allodynia in the Cav ${\alpha}2{\delta}1$ over-expressing TG mice could be reversed by an intrathecal injection of memantine 2 mg/kg at 1.5, 2.0 and 2.5 hours. Conclusions: The behavioral hypersensitivity was similar in the TG mice and nerve injury pain model, supporting the hypothesis that elevated Cav ${\alpha}2{\delta}1$ mediates similar pathways that underlie the pain states in both models. The selective activation of spinal NMDA receptors plays a key role in mediating the pain states in both the nerve-injury rats and TG mice.

• Journal of Korean Biological Nursing Science
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• 제4권1호
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• pp.101-112
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• 2002

Peripheral nerve injury results in plastic changes in the dorsal ganglia (DRG) and spinal cord, and is often complicated with neuropathic pain. The mechanisms underlying these changes are not known, but these changes seem to be most likely related to the neurotrophic factors. This study investigated the effects of mechanical peripheral nerve injury on expression of brain-derived neurotrophic factor(BDNF) in the DRG and spinal cord in rats. 1) Bennett model and Chung model groups showed significantly increased percentage of small, medium and large BDNF-immunoreactive neurons in the ipsilateral $L_4$ DRG compared with those in the contralateral side at 1 and 2 weeks of the injury. 2) In the ipsilateral $L_5$ DRG of the Chung model, percentage of medium and large BDNF-immunoreactive neurons increased significantly at 1 week, whereas that of large BDNF-immunoreactive neurons decreased at 2 week when compared with those in the contralateral side. The intensity of immunoreactivity of each neuron was lower in the ipsilateral than in the contralateral DRG. 3) In the spinal cord, the Bennett and Chung model groups showed a markedly increased BDNF-immunoreactivity in axonal fibers of both superficial and deeper laminae. The present study demonstrates that peripheral nerve injury in neuropathic models altered the BDNF expression in the DRG and spinal cord. This may suggest important roles of BDNF in sensory abnormalities after nerve injury and in protecting the large-sized neurons in the damaged DRG.

• 생물정신의학
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• 제18권3호
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• pp.163-167
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• 2011

Complex regional pain syndrome (CRPS) is a disease that causes chronic spontaneous pain and hyperesthesia of one or more parts of legs and arms, which is accompanied with problems of the automatic nervous system or the motor nervous system. However, up to date, it is unclear what causes the syndrome and how to diagnose and treat it. Although several treatments including medication and sympathetic nerve block are performed against CRPS, the therapeutic effect of the treatments is limited. The electroconvulsive thera-py (ECT), of which the mechanism is not clarified, is a treatment used for treatment-resistant depression. ECT is also reported to be effective against pain. Therefore, we performed the ECT for a 24-year-old female patient who has been diagnosed as CRPS. Her pain had not been much improved by medications and interventional procedures. At admission to a psychiatric ward for ECT, she com-plained of over 8 points of pain on visual analogue scale and the constrained movement around the painful part. Eight ECTs-three times a week-were performed for three weeks in hospital and then the ECT once a week was performed after her leaving the hospital. During the ECTs, pain had been reduced and the range of movement in the constrained parts had increased. Further systematic re-search is needed to confirm the effect of electroconvulsive therapy against CRPS.

• 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.