• The Korean Journal of Pain
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• v.30 no.3
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• pp.183-191
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• 2017

Background: Current therapy for the treatment of neuropathic pain is often unsatisfactory. Considerable variation in treatment pattern still exists in spite of availability of sufficient literature from various guidelines. Recent Indian market data suggested that the utilization (sale) of drugs such as amitriptyline, pregabalin, and gabapentin was more for low-dose unit packs than that of the high-dose unit packs, raising the belief that these drugs are prescribed at a lower dose than is actually recommended in the guidelines. To test this hypothesis, a survey was conducted across speciality throughout the country to observe the prescription pattern of these drugs amongst the health care providers in India. Methods: Three hundred fifty survey forms were distributed of which 281 forms were included for analysis. Results: It was observed that the commonly used initiation and maintenance dose for amitriptyline, pregabalin, and gabapentin was 5-10 mg/day, 50-75 mg/day, and 100-300 mg/day, respectively. The reason to select the lower dosages was to have a balancing effect to achieve good efficacy with minimum side effects. Care-givers reported no side effects/not many side effects as a reason in 22.2%, 16.88%, and 23.86% patients with amitriptyline, pregabalin, and gabapentin, respectively. Sedation and giddiness were commonly reported with all three drugs. Conclusions: Commonly prescribed drugs for management of neuropathic pain, such as amitriptyline, pregabalin, and gabapentin are preferred at lower doses in Indian clinical settings. Acceptable efficacy and low tolerance to the standard dosage is believed to be the reason behind the prescribed dose.

• The Korean Journal of Pain
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• v.34 no.1
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• pp.4-18
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• 2021

Except for carbamazepine for trigeminal neuralgia, gabapentinoid anticonvulsants have been the standard for the treatment of neuropathic pain. Pregabalin, which followed gabapentin, was developed with the benefit of rapid peak blood concentration and better bioavailability. Mirogabalin besylate (DS-5565, Tarlige®) shows greater sustained analgesia due to a high affinity to, and slow dissociation from, the α2δ-1 subunits in the dorsal root ganglion (DRG). Additionally, it produces a lower level of central nervous system-specific adverse drug reactions (ADRs), due to a low affinity to, and rapid dissociation from, the α2δ-2 subunits in the cerebellum. Maximum plasma concentration is achieved in less than 1 hour, compared to 1 hour for pregabalin and 3 hours for gabapentin. The plasma protein binding is relatively low, at less than 25%. As with all gabapentinoids, it is also largely excreted via the kidneys in an unchanged form, and so the administration dose should also be adjusted according to renal function. The equianalgesic daily dose for 30 mg of mirogabalin is 600 mg of pregabalin and over 1,200 mg of gabapentin. The initial adult dose starts at 5 mg, given orally twice a day, and is gradually increased by 5 mg at an interval of at least a week, to 15 mg. In conclusion, mirogabalin is anticipated to be a novel, safe gabapentinoid anticonvulsant with a greater therapeutic effect for neuropathic pain in the DRG and lower ADRs in the cerebellum.

• The Korean Journal of Pain
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• v.34 no.4
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• pp.463-470
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• 2021

Background: Although neuropathic pain is a severe and common pain, its pathophysiology has not been elucidated yet. Studies in recent years have focused on the immune system's role in the pathogenesis of neuropathic pain. The aim of this study was to investigate the role of immunological mechanisms in neuropathic pain and the effect of pregabalin by measuring immunological marker levels in peripheral blood before and after pregabalin treatment in postherpetic neuralgia (PHN) patients with neuropathic pain. Methods: Forty patients diagnosed with PHN were included in the study. CD4, T follicular cells (Tfh: CD4⁺CXCR5⁺PD1⁺), Th17 (CD4⁺CCR6⁺ and CD4⁺IL17A⁺), regulatory T cells (Treg: CD4⁺ CD25⁺foxp3⁺), Th1 (CD4⁺ CXCR3⁺ and CD4⁺ IFN-γ⁺) and Th2 (CD4⁺ IL-4⁺) cell ratios were measured in peripheral blood samples before treatment and after 3 months of treatment. Results: When immunological marker and inflammation parameter levels were compared before and after treatment, the helper T cell ratio (CD3⁺, CD4⁺) was 30.28 ± 12.27% before treatment and 34.93 ± 11.70% after treatment, so there was a statistically significant increase (P = 0.028). Th17 was 4.75 ± 5.02% before treatment and 5.80 ± 3.13% after treatment, and there was a statistically significant increase (P = 0.036). Conclusions: Immunological mechanisms play an essential role in the pathogenesis of neuropathic pain, immunologically based treatment approach will be the critical point of treatment.

• The Korean Journal of Pain
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• v.34 no.2
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• pp.210-216
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• 2021

Background: Postherpetic neuralgia (PHN) is the most common complication of acute herpes zoster. The treatment of PHN remains a challenge for clinical pain management. Despite the effectiveness of anticonvulsants, antidepressants, and lidocaine patches in reducing PHN, many patients still face intractable pain disorders. In this randomized controlled study, we evaluated whether hydromorphone through intravenous patient-controlled analgesia (IV PCA) was effective in relieving PHN. Methods: Patients with PHN were randomly divided into two groups, one group received oral pregabalin with IV normal saline, another group received oral pregabalin with additional IV PCA hydromorphone for two weeks. Efficacy was evaluated at 1, 4, and 12 weeks after the end of the treatments. Results: Two hundred and one patients were followed up for 12 weeks. After treatment, numerical rating scale (NRS) score of patients in the hydromorphone group was significantly lower than that of the control group, and the difference of NRS scores between the two groups was statistically significant at 4 and 12 weeks after treatment. The frequency of breakthrough pain in the hydromorphone group was significantly lower than that in the control group 1 and 4 weeks after treatment. After treatment, the quality of sleep in the hydromorphone group was significantly improved compared with the control group. The most common adverse reactions in the hydromorphone group were dizziness and nausea, with no significant respiratory depression. Conclusions: IV PCA hydromorphone combined with oral pregabalin provides superior pain relief in patients with PHN, which is worthy of clinical application and promotion.

• The Korean Journal of Pain
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• v.33 no.1
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• pp.3-12
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• 2020

Neuropathic pain after spinal cord injury (SCI) has a significant negative impact on the patients' quality of life. The objective of this systematic review is to examine the safety and efficacy of pregabalin (PGB) and gabapentin (GBP) in the treatment of neuropathic pain due to SCI. PubMed, the Cochrane Library, Embase, Scopus, and the Web of Science were searched up to December 2018. The reference lists of key and review studies were reviewed for additional citations. The quality of the studies was evaluated using the Cochrane Collaboration's tools for assessing the risk of bias. A meta-analysis was performed for primary and secondary outcomes. Eight studies were eligible for inclusion. Meta-analysis of PGB vs. placebo showed that PGB was effective for neuropathic pain (standardized mean difference [SMD] = -0.40; 95% confidence interval [CI]: -0.78, -0.01), anxiety (MD = -0.68; 95% CI: -0.77, -0.59), depression (mean difference [MD] = -0.99; 95% CI: -1.08, -0.89), and sleep interference (MD = -1.08; 95% CI: -1.13, -1.02). Also, GBP was more effective than a placebo for reducing pain. No significant difference was observed between the efficacy of the two drugs (MD = -0.37; 95% CI: -1.67, 0.93). There was no significant difference between the two drugs for discontinuation due to adverse events (risk ratio = 3.00; 95% CI: 0.81, 11.15). PGB and GBP were effective vs. placebos in decreasing neuropathic pain after SCI. Also, there was no significant difference between the two drugs for decreasing pain and adverse events.

• The Korean Journal of Pain
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• v.34 no.2
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• pp.185-192
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• 2021

Background: It is known that some analgesics as well as pain can affect the immune system. The aim of this study was to investigate the analgesic effect and immunomodulation of pregabalin (PGB) in a mouse incisional pain model. Methods: A postoperative pain model was induced by hind paw plantar incision in male BALB/c mice. Mice were randomly divided into four groups (n = 8): a saline-treated incision (incision), PGB-treated incision (PGB-incision), sham controls without incision or drug treatment (control), and a PGB-treated control (PGB-control). In the PGB treated groups, PGB was administered intraperitoneally (IP) 30 minutes before and 1 hour after the plantar incision. Changes of the mechanical nociceptive thresholds following incision were investigated. Mice were euthanized for spleen harvesting 12 hours after the plantar incision, and natural killer (NK) cytotoxicity to YAC 1 cells and lymphocyte proliferation responses to phytohemagglutinin were compared among these four groups. Results: Mechanical nociceptive thresholds were decreased after plantar incision and IP PGB administration recovered these decreased mechanical nociceptive thresholds (P < 0.001). NK activity was increased by foot incision, but NK activity in the PGB-incision group was significantly lower than that in the Incision group (P < 0.001). Incisional pain increased splenic lymphocyte proliferation, but PGB did not alter this response. Conclusions: Incisional pain alters cell immunity of the spleen in BALB/c mice. PGB showed antinocieptive effect on mouse incisional pain and attenuates the activation of NK cells in this painful condition. These results suggest that PGB treatment prevents increases in pain induced NK cell activity.

• Investigative Magnetic Resonance Imaging
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• v.18 no.4
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• pp.341-351
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• 2014

Purpose : In this study, the medication effects of Milnacipran and Pregabalin, as well known as fibromyalgia treatment medicine, in fibromyalgia syndrome patients were compared through the change of BOLD signal in pain related functional MRI. Materials and Methods: Twenty fibromyalgia syndrome patients were enrolled in this study and they were separated into two groups according to the treatment medicine: 10 Milnacipran (MLN) treatment group and 7 Pregabalin (PGB) treatment group. For accurate diagnosis, all patients underwent several clinical tests. Pre-treated and post-treated fMRI image with block-designed pressure-pain stimulation for each group were obtained to conduct the statistical analysis of paired t-test and two sample t-test. All statistical significant level was less than 0.05. Results: In clinical tests, the clinical scores of the two groups were not significantly different at pre-treatment stage. But, PGB treatment group had lower Widespread Pain Index (WPI) and Brief Fatigue Inventory (BFI) score than those of MLN treatment group at post-treatment stage. In functional image analysis, BOLD signal of PGB treatment group was higher BOLD signal at several regions including anterior cingulate and insula than MLN treatment group at post-treatment stage. Also, paired t-test values of the BOLD signal in MLN group decreased in several regions including insula and thalamus as known as 'pain network'. In contrast, size and number of regions in which the BOLD signal decreased in PGB treatment group were smaller than those of MLN treatment group. Conclusion: This study showed that MLN group and PGB group have different medication effects. It is not surprising that MLN and PGB have not the same therapeutic effects since these two drugs have different medicinal mechanisms such as antidepressants and anti-seizure medication, respectively, and different detailed target of fibromyalgia syndrome treatment. Therefore, it is difficult to say which medicine will work better in this study.

• The Korean Journal of Pain
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• v.33 no.2
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• pp.108-120
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• 2020

From the perspective of the definition of pain, pain can be divided into emotional and sensory components, which originate from potential and actual tissue damage, respectively. The pharmacologic treatment of the emotional pain component includes antianxiety drugs, antidepressants, and antipsychotics. The anti-anxiety drugs have anti-anxious, sedative, and somnolent effects. The antipsychotics are effective in patients with positive symptoms of psychosis. On the other hand, the sensory pain component can be divided into nociceptive and neuropathic pain. Non-steroidal anti-inflammatory drugs (NSAIDs) and opioids are usually applied for somatic and visceral nociceptive pain, respectively; anticonvulsants and antidepressants are administered for the treatment of neuropathic pain with positive and negative symptoms, respectively. The NSAIDs, which inhibit the cyclo-oxygenase pathway, exhibit anti-inflammatory, antipyretic, and analgesic effects; however, they have a therapeutic ceiling. The adverse reactions (ADRs) of the NSAIDs include gastrointestinal problems, generalized edema, and increased bleeding tendency. The opioids, which bind to the opioid receptors, present an analgesic effect only, without anti-inflammatory, antipyretic, or ceiling effects. The ADRs of the opioids start from itching and nausea/vomiting to cardiovascular and respiratory depression, as well as constipation. The anticonvulsants include carbamazepine, related to sodium channel blockade, and gabapentin and pregabalin, related to calcium blockade. The antidepressants show their analgesic actions mainly through inhibiting the reuptake of serotonin or norepinephrine. Most drugs, except NSAIDs, need an updose titration period. The principle of polypharmacy for analgesia in case of mixed components of pain is increasing therapeutic effects while reducing ADRs, based on the origin of the pain.

• The Korean Journal of Pain
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• v.31 no.4
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• pp.253-260
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• 2018

Background: One of the most frequent problems caused by diabetes is the so called painful diabetic neuropathy. This condition can be treated through numerous types of therapy. The purpose of this study was to analyze, as a meta-analysis, different treatments used to alleviate painful diabetic neuropathy, with the aim of generating results that help making decisions when applying such treatments to tackle this pathology. Methods: A search was conducted in the main databases for Health Sciences, such as PUBMED, Web of Science (WOS), and IME biomedicina (Spanish Medical Reports in Biomedicine), to gather randomized controlled trials about treatments used for painful diabetic neuropathy. The analyzed studies were required to meet the inclusion criteria selected, especially those results related to pain intensity. Results: Nine randomized controlled trials were chosen. The meta-analysis shows significant positive effects for those treatments based on tapentadol [g: -1.333, 95% CI (-1.594; -1.072), P < 0.05], duloxetine [g: -1.622, 95 % CI (-1.650; -1.594), P < 0.05], pregabalin [g: -0.607, 95% CI (-0.980; -0.325), P < 0.05], and clonidine [g: -0.242, 95 % CI (-0.543; -0.058), P < 0.05]. Conclusions: This meta-analysis indicates the effectiveness of the treatments based on duloxetine, gabapentin and pregabalin, as well as other drugs, such as tapentadol and topic clonidine, whose use is better prescribed in more specific situations. The results provided can help increase the knowledge about the treatment of painful diabetic neuropathy and also in the making of clinical practice guidelines for healthcare professionals.

• Sleep Medicine and Psychophysiology
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• v.25 no.1
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• pp.5-8
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• 2018

Restless legs syndrome (RLS) is a sleep disorder characterized by an urge to move the legs or arms and uncomfortable paresthesia in the legs. Treatment of RLS can be various depending on the causes, severity, and frequency of the symptoms. In the case of secondary RLS, it is important to identify and manage the cause of RLS. Dopamine agonists have been used as firstline treatments for primary RLS treatment. However, due to augmentation, which is a common side effect of dopamine agonists, recent treatment guidelines are changing to prefer to anticonvulsants such as pregabalin and gabapentin. Iron, opioid, or benzodiazepine may be used when anticonvulsants or dopamine agonists are not adequately treated. Because RLS is a chronic disease, it is essential to establish a long-term treatment plan considering both efficacy and side effects.