• The Korean Journal of Pain
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• v.23 no.3
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• pp.172-178
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• 2010

Background: Tumor necrosis factor-alpha and other proinflammatory cytokines are becoming well recognized as key mediators in the pathogenesis of many types of neuropathic pain. Thalidomide has profound immunomodulatory actions in addition to their originally intended pharmacological actions. There has been debate on the analgesic efficacy of opioids in neuropathic pain. The aim of this study was to investigate the effect of thalidomide and morphine on a spinal nerve ligation model in rats. Methods: Male Sprague-Dawley rats weighing 100-120 g were used. Lumbar (L) 5 and 6 spinal nerve ligations were performed to induce neuropathic pain. For assessment of mechanical allodynia, mechanical stimulus using von Frey filament was applied to the paw to measure withdrawal threshold. The effects of intraperitoneal thalidomide (6.25, 12.5, 25 and 50 mg/kg, respectively) and morphine (3 and 10 mg/kg, respectively) were examined on a withdrawal threshold evoked by spinal nerve ligation. Results: After L5 and 6 spinal nerve ligation, paw withdrawal thresholds on the ipsilateral side were significantly decreased compared with pre-operative baseline and with those in the sham-operated group. Intraperitoneal thalidomide and morphine significantly increased the paw withdrawal threshold compared to controls and produced dose-responsiveness. Conclusions: Systemic thalidomide and morphine have antiallodynic effect on neuropathic pain induced by spinal nerve ligation in rat. These results suggest that morphine and thalidomide may be alternative therapeutic approaches for neuropathic pain.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.2
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• pp.59-69
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• 2010

Impairment in spinal inhibition caused by quantitative alteration of GABAergic elements following peripheral nerve injury has been postulated to mediate neuropathic pain. In the present study, we tested whether neuropathic pain could be induced or reversed by pharmacologically modulating spinal GABAergic activity, and whether quantitative alteration of spinal GABAergic elements after peripheral nerve injury was related to the impairment of GABAergic inhibition or neuropathic pain. To these aims, we first analyzed the pain behaviors following the spinal administration of GABA antagonists ($1{\mu}g$ bicuculline/rat and $5{\mu}g$ phaclofen/rat), agonists ($1{\mu}g$ muscimol/rat and $0.5{\mu}g$ baclofen/rat) or GABA transporter (GAT) inhibitors ($20{\mu}g$ NNC-711/rat and $1{\mu}g$ SNAP-5114/rat) into naive or neuropathic animals. Then, using Western blotting, PCR or immunohistochemistry, we compared the quantities of spinal GABA, its synthesizing enzymes (GAD65, 67) and its receptors (GABAA and GABAB) and transporters (GAT-1, and -3) between two groups of rats with different severity of neuropathic pain following partial injury of tail-innervating nerves; the allodynic and non-allodynic groups. Intrathecal administration of GABA antagonists markedly lowered tail-withdrawal threshold in naive animals, and GABA agonists or GAT inhibitors significantly attenuated neuropathic pain in nerve-injured animals. However, any quantitative changes in spinal GABAergic elements were not observed in both the allodynic and non-allodynic groups. These results suggest that although the impairment in spinal GABAergic inhibition may play a role in mediation of neuropathic pain, it is not accomplished by the quantitative change in spinal elements for GABAergic inhibition and therefore these elements are not related to the generation of neuropathic pain following peripheral nerve injury.

• Biomolecules & Therapeutics
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• v.27 no.4
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• pp.414-422
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• 2019

There is accumulating evidence that microRNAs are emerging as pivotal regulators in the development and progression of neuropathic pain. MicroRNA-15a/16 (miR-15a/16) have been reported to play an important role in various diseases and inflammation response processes. However, whether miR-15a/16 participates in the regulation of neuroinflammation and neuropathic pain development remains unknown. In this study, we established a mouse model of neuropathic pain by chronic constriction injury (CCI) of the sciatic nerves. Our results showed that both miR-15a and miR-16 expression was significantly upregulated in the spinal cord of CCI rats. Downregulation of the expression of miR-15a and miR-16 by intrathecal injection of a specific inhibitor significantly attenuated the mechanical allodynia and thermal hyperalgesia of CCI rats. Furthermore, inhibition of miR-15a and miR-16 downregulated the expression of interleukin-$1{\beta}$ and tumor-necrosis factor-${\alpha}$ in the spinal cord of CCI rats. Bioinformatic analysis predicted that G protein-coupled receptor kinase 2 (GRK2), an important regulator in neuropathic pain and inflammation, was a potential target gene of miR-15a and miR-16. Inhibition of miR-15a and miR-16 markedly increased the expression of GRK2 while downregulating the activation of p38 mitogen-activated protein kinase and $NF-{\kappa}B$ in CCI rats. Notably, the silencing of GRK2 significantly reversed the inhibitory effects of miR-15a/16 inhibition in neuropathic pain. In conclusion, our results suggest that inhibition of miR-15a/16 expression alleviates neuropathic pain development by targeting GRK2. These findings provide novel insights into the molecular pathogenesis of neuropathic pain and suggest potential therapeutic targets for preventing neuropathic pain development.

• Women's Health Nursing
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• v.17 no.3
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• pp.215-224
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• 2011

Purpose: This study was to investigate the effect of music therapy as intervention on peripheral neuropathic pain and anxiety of gynecologic cancer patients who were undergoing paclitaxel chemotherapy. Methods: Hospitalized 62 patients were assigned to an experimental group (n=30) and a control group (n=33) in this quasi-experimental study. The experimental group participated in music therapy that includes listening, singing and song writing during 1 hour. The peripheral neuropathic pain, anxiety and depression were examined as pre-intervention evaluation by using pain scale, anxiety scale (20 questions) and depression scale (20 questions) in both groups. There were no further treatments for the control group while the experimental group involved in music therapy. The peripheral neuropathic pain and anxiety were evaluated in both groups as post-intervention evaluation. Results: Outcomes were verified through hypothesis testing. The level of peripheral neuropathic pain and anxiety in the experimental group was decreased, compared to the control group. Conclusion: According to the study, music therapy is a beneficial intervention that reduces peripheral neuropathic pain and anxiety in gynecologic cancer patients. These findings are encouraging and suggest that music therapy can be applied as an effective intervention for minimizing chemotherapy related symptoms.

• Clinical Pain
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• v.18 no.1
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• pp.1-7
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• 2019

Objective: To investigate the cortical disinhibition in diabetic patients with neuropathic pain and without pain. In addition, we assessed the cortical disinhibition and pain relief after repetitive transcranial magnetic stimulation (rTMS). Method: We recruited diabetic patients with neuropathic pain (n = 15) and without pain (n = 15). We compared the TMS parameters such as motor evoked potential (MEP) amplitude, cortical silent period (CSP), intracortical inhibition (ICI %) and intracortical facilitation (ICF %) between two groups. Moreover, we evaluated the changes of pain and TMS parameters after five consecutive high frequency (10 Hz) rTMS sessions in diabetic patients with neuropathic pain. The neuropathic pain intensity (visual analog scale) and TMS parameters were assessed on pre-rTMS, post-rTMS 1day, and post-rTMS 5 day. Results: The comparison of the CSP, ICI % revealed significant differences between two groups (p<0.01). After rTMS sessions, the decrease in pain intensity across the three time points revealed a pattern of significant differences (p<0.01). The change of CSP and ICI % across the three test points revealed a pattern of significant differences (p<0.01). The ICI % revealed immediate increase after first rTMS application and significant increase after five rTMS application (p<0.01) in diabetic patients with neuropathic pain. The MEP amplitude and ICF % did not reveal any significant changes. Conclusion: Our findings demonstrate that cortical inhibition was decreased in diabetic patients with neuropathic pain compared with patients without pain. Furthermore, we also identified that five daily rTMS sessions restored the defective intracortical inhibition which related to improvement of neuropathic pain in diabetic patients.

• Journal of Korean Neurosurgical Society
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• v.38 no.3
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• pp.234-237
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• 2005

The neuropathic pain caused by lumbosacral plexopathy as a sequela to extensive pelvic and sacral fractures is rare because many posttraumatic cases remain undiagnosed as a result of the high mortality associated with these types of injury and because of the survivors of multiple trauma, including pelvic fractures, frequently have an incomplete work-up. Although surgical treatments for medically refractory lumbosacral plexus avulsion pain have been reported, an effective surgical technique for pain relief in lumbosacral plexopathy has not been well documented. We describe the effectiveness of spinal cord stimulation [SCS] in a patient suffering from severe neuropathic pain caused by lumbosacral plexopathy after an extensive pelvic fracture.

• Journal of Korean Neurosurgical Society
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• v.47 no.6
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• pp.420-423
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• 2010

Objective : Peripheral nerve injury often leads to neuropathic pain, which is characterized by burning pain, allodynia, and hyperalgesia. The role of the sympathetic nervous system in neuropathic pain is a complex and controversial issue. It is generally accepted that the alpha adrenoreceptor (AR) in sympathetic nerve system plays a significant role in the maintenance of pain. Among alpha adrenoreceptor, alpha-1 receptors play a major role in the sympathetic mediated pain. The primary goal of this study is to test the hypothesis that sympathetically maintained pain involves peripheral alpha-2 receptors in human. Methods : The study was a randomized, prospective, double-blinded, crossover study involving twenty patients. The treatments were : Yohimbine (30 mg mixed in 500 mL normal saline), and Phentolamine (1 mg/kg in 500 mL normal saline) in 500 mL normal saline at 70 mL/hr initially then titrated. The patients underwent infusions on three different appointments, at least one month apart. Thus, all patients received all 2 treatments. Pain measurement was by visual analogue scale, neuropathic pain questionnaire, and McGill pain questionnaire. Results : There were significant decreases in the visual analogue scale, neuropathic score, McGill pain score of yohimnine, and phentolamine. Conclusion : We conclude that alpha-2 adrenoreceptor, along with alpha-2 adrenoreceptor, may be play role in sympathetically maintained pain in human.

• Journal of Acupuncture Research
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• v.33 no.3
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• pp.1-16
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• 2016

Objectives : The objective of this study was to investigate the effects of Gentianae Macrophyllae Radix pharmacopuncture (GP) at Hwando (GB30) in neuropathic pain induced rats. Methods : Neuropathic pain in rats was induced by tibial and sural nerve transection. The rat subjects were divided into 6 groups : normal (Nor, n = 5), control (Con, n = 5), neuropathic pain- induced injected at GB30 with 1 mg/kg GP (GP-A, n = 5), 5 mg/kg GP (GP-B, n = 5) and 20 mg/kg GP (GP-C, n = 5), and neuropathic pain-induced injected with 1mg/kg Tramadol (Tramadol, n＝5). Injections were administered 2 times a week for a total of 5 treatments. After each treatment plantar withdrawal response was measured and after all 5 treatments were completed c-fos, Bax, Bcl-2, mGlu5 and leukocytes in the blood were analyzed. Results : 1. Groups GP-A, GP-B and GP-C showed a meaningful decrease in the withdrawal response of mechanical allodynia compared to the control group. 2. Groups GP-A, GP-B and GP-C showed a meaningful decrease in the expression of c-fos compared to the control group. 3. Groups GP-A and GP-C showed a meaningful increase in the expression of mGluR5 compared to the control group. 4. Groups GP-A, GP-B and GP-C showed a meaningful decrease in Bax/Bcl-2 ratio compared to the control group. Conclusion : These results suggest that Gentianae Macrophyllae Radix pharmacopuncture at Hwando (GB30) could decrease mechanical allodynia and could have analgesic and neuroprotective effects on the model of neuropathic pain.

• 대한약리학회:학술대회논문집
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• 2006.10a
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• pp.84.1-84.1
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• 2006

• The Korean Journal of Pain
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• v.27 no.2
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• pp.103-111
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• 2014

Nefopam (NFP) is a non-opioid, non-steroidal, centrally acting analgesic drug that is derivative of the nonsedative benzoxazocine, developed and known in 1960s as fenazocine. Although the mechanisms of analgesic action of NFP are not well understood, they are similar to those of triple neurotransmitter (serotonin, norepinephrine, and dopamine) reuptake inhibitors and anticonvulsants. It has been used mainly as an analgesic drug for nociceptive pain, as well as a treatment for the prevention of postoperative shivering and hiccups. Based on NFP's mechanisms of analgesic action, it is more suitable for the treatment of neuropathic pain. Intravenous administration of NFP should be given in single doses of 20 mg slowly over 15-20 min or with continuous infusion of 60-120 mg/d to minimize adverse effects, such as nausea, cold sweating, dizziness, tachycardia, or drowsiness. The usual dose of oral administration is three to six times per day totaling 90-180 mg. The ceiling effect of its analgesia is uncertain depending on the mechanism of pain relief. In conclusion, the recently discovered dual analgesic mechanisms of action, namely, a) descending pain modulation by triple neurotransmitter reuptake inhibition similar to antidepressants, and b) inhibition of long-term potentiation mediated by NMDA from the inhibition of calcium influx like gabapentinoid anticonvulsants or blockade of voltage-sensitive sodium channels like carbamazepine, enable NFP to be used as a therapeutic agent to treat neuropathic pain.