Spinal cord stimulation (SCS) is one of the most effective modalities for management of refractory neuropathic pain unresponsive to conservative therapies. The SCS has been successful in providing analgesia, improving function, and enhancing quality of life for patients suffering from chronic pain conditions such as failed back surgery syndrome, complex regional pain syndrome, ischaemic and phantom limb pain, and coronary artery disease. This technique has proven to be cost effective in the long term despite its high initial cost. In this review article, we discuss the history of SCS development, mechanism of action, and indications for SCS.
Cost-Benefit Analysis ; Electric Stimulation Therapy ; adverse effects ; economics ; methods ; Failed Back Surgery Syndrome ; therapy ; Humans ; Treatment Outcome

BACKGROUND: Methadone is a synthetic opioid that is widely used for the treatment of chronic pain. The association between methadone treatment and QT interval prolongation or which can lead to torsades de pointes has been confirmed with larger studies on high dose methadone. The aim of this study was to determine the effect of methadone on the QTc interval in patients, whether the daily dose of methadone should be lower than what has been previously investigated. METHODS: A total of 130 patients were included, with 90 patients in the methadone group and 40 patients in the control group. For each ECG, heart rate, QT interval and corrected QT (QTc) interval were recorded. The patient demographics, methadone dose and serum level, duration of methadone use and past medical history were collected. RESULTS: The QTc interval was significantly longer in the treatment group than in the control group (443 +/- 30.0 ms versus 408 +/- 28.0 ms, respectively, P < 0.0001) and more patients in the treatment group had a QTc interval greater than 450 ms (36.7% versus 7.5%, respectively, P = 0.0005). The QTc interval was not associated with methadone dose P = 0.9278), serum level (P = 0.2256) or duration of treatment (P = 0.1822). CONCLUSIONS: This study has shown that methadone use is associated with longer QTc intervals, even among patients with daily doses of less than 80 mg. In this study, no correlation was found between QTc duration and methadone dose, serum levels or duration of use. However, the magnitude of the QTc interval was associated with female gender and the use of antidepressants.
Antidepressive Agents ; Chronic Pain ; Demography ; Electrocardiography ; Female ; Heart Rate ; Humans ; Methadone ; Retrospective Studies ; Torsades de Pointes

There has been a growing interest in opioid-induced hyperalgesia (OIH), which is an increased sensitivity to pain caused by opioid exposure. Multiple underlying pathways may contribute to the development of OIH, and the mechanism may vary with the duration of opioid exposure, dose, type and route of administration. In addition, the distinction between OIH, tolerance and withdrawal should be made in both the basic and clinical science literature so as to help translate findings to the clinical phenomenon and to help determine the best strategies to prevent or treat OIH.
Analgesics, Opioid ; adverse effects ; Drug Tolerance ; Humans ; Hyperalgesia ; chemically induced ; prevention & control ; Pain Measurement

This report presents the application of occipital nerve stimulation in two patients with severe and disabling bilateral occipital neuralgia. Pain persisted despite the use of several procedures and the administration of medication in the patients. The patients underwent peripheral nerve stimulation for the treatment of headache. Peripheral nerve stimulation was accomplished via implantation of a subcutaneous electrode to stimulate the peripheral nerve in the occipital area. The patients reported a 90% improvement in overall pain. These cases illustrate the possible utilization of peripheral nerve stimulation for the treatment of occipital neuralgia.
Electrodes ; Headache ; Humans ; Neuralgia ; Peripheral Nerves

BACKGROUND: Chronic low back pain (CLBP) has a significant effect on quality of life and imposes a great economical burden on society. In a number of studies, validated questionnaires had been given to CLBP patients to determine their health-associated quality of life, sleep disturbance, and psychological status. However, such outcome studies had not been performed previously in Korea. METHODS: We used self-report questionnaires to compare CLBP patients with an age- and sex-matched healthy control group. Between September 2012 and August 2013, we enrolled 47 patients who had CLBP for more than 3 months (group P) and 44 healthy age- and sex-matched controls (group C), who completed the following self-report questionnaires: 36-Item Short Form Health Survey (SF-36), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Oswestry Disability Index (ODI), and Pittsburgh Sleep Quality Index (PSQI). RESULTS: The scores from the ODI, BDI, and BAI were significantly higher in group P than in group C. The SF-36 scores were significantly lower in group P than in group C, suggesting lower quality of life in group P. The incidence of depression and anxiety was significantly higher in group P than in group C. However, neither the PSQI score nor the incidence of sleep disturbance was significantly different between the groups. CONCLUSIONS: Patients with CLBP showed considerable functional disability and significant impairment of psychological status with a low quality of life. Hence, it is important to evaluate CLBP patients to provide adequate psychological support.
Anxiety* ; Depression* ; Dyssomnias ; Health Surveys ; Humans ; Incidence ; Korea ; Low Back Pain* ; Outcome Assessment (Health Care) ; Quality of Life*

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.

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 α2 δ-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 α2 δ-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.

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 α2 δ-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 α2 δ-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.

All drugs have both favorable therapeutic and untoward adverse effects. Conventional opioid analgesics possess both analgesia and adverse reactions, such as nausea, vomiting, and respiratory depression. The opioid ligand binds to µ opioid receptor and non-selectively activates two intracellular signaling pathways: the G protein pathway induce analgesia, while the β-arrestin pathway is responsible for the opioid-related adverse reactions. An ideal opioid should activate the G protein pathway while deactivating the β-arrestin pathway. Oliceridine (TRV130) has a novel characteristic mechanism on the action of the µ receptor G protein pathway selective (µ-GPS) modulation. Even though adverse reactions (ADRs) are significantly attenuated, while the analgesic effect is augmented, the some residual ADRs persist. Consequently, a G protein biased µ opioid ligand, oliceridine, improves the therapeutic index owing to increased analgesia with decreased adverse events. This review article provides a brief history, mechanism of action, pharmacokinetics, pharmacodynamics, and ADRs of oliceridine.
Analgesia ; Analgesics, Opioid ; Animals ; Bias (Epidemiology) ; Drug-Related Side Effects and Adverse Reactions ; GTP-Binding Proteins ; Intracellular Signaling Peptides and Proteins ; Ligands ; Mice ; Mice, Knockout ; Nausea ; Patient Safety ; Pharmacokinetics ; Receptors, Opioid ; Receptors, Opioid, mu ; Respiratory Insufficiency ; Vomiting