• The Korean Journal of Pain
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• v.31 no.2
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• pp.73-79
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• 2018

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 ${\mu}$ opioid receptor and non-selectively activates two intracellular signaling pathways: the G protein pathway induce analgesia, while the ${\beta}$-arrestin pathway is responsible for the opioid-related adverse reactions. An ideal opioid should activate the G protein pathway while deactivating the ${\beta}$-arrestin pathway. Oliceridine (TRV130) has a novel characteristic mechanism on the action of the ${\mu}$ receptor G protein pathway selective (${\mu}$-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 ${\mu}$ 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.

• The Korean Journal of Pain
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• v.19 no.2
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• pp.187-191
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• 2006

Background: Patient-controlled epidural analgesia (PCEA), using a local anesthetic-opioid mixture, has been effectively applied after total knee replacement (TKR) surgery, which is associated with intense postoperative pain that requires postoperative analgesia for both rehabilitation and the pain itself. However, adverse opioid-related effects, such as nausea, vomiting and pruritus, are commonly encountered. It was our hypothesis that the adverse opioid-related effects could be reduced by the addition of naloxone, an opioid antagonist, to a mixture of fentanyl-ropivacaine PCEA. Methods: In 120 patients undergoing elective TKR surgery, epidural or combined spinal-epidural (CSE) anesthesia was performed and PCEA applied. In the control group (n = 65), 0.16% ropivacaine and $3{\mu}g/ml$ fentanyl ($2.4{\mu}g/ml$ for those older than 65 yrs) were administered. In the naloxone group (n = 55), naloxone ($2{\mu}g/ml$) was coadministered with the above regimen. The incidence and severity of postoperative nausea and vomiting, and the frequency of pruritus, the visual analog score (VAS) and the PCEA volume used were assessed 6 and 24 hrs after surgery. Results: The incidence of nausea and vomiting during the early postoperative period, and those of pruritus during the late postoperative period were significantly lower in the naloxone group. The VAS pain scores, the PCEA volume used and amount of rescue IV meperidine were similar in the two groups. Conclusions: A small dose of naloxone mixed with an opioid significantly reduces the incidence and severity of adverse opioid-related effects in PCEA, without reducing the analgesic effect.

• Journal of Digestive Cancer Research
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• v.1 no.2
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• pp.67-72
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• 2013

• The Korean Journal of Pain
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• v.37 no.1
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• pp.73-83
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• 2024

Background: Failed back surgery syndrome (FBSS) is a chronic condition that is characterized by persistent back pain following one or more spinal surgeries. Pharmacological interventions, such as the use of opioids and gabapentinoids, are frequently used in the treatment of FBSS. However, prolonged and excessive use of these medications can lead to dependence and adverse effects. This study investigates trends in opioid and gabapentinoid prescriptions among patients with FBSS in Korea from 2016 to 2020. Methods: Data from the Health Insurance and Review Agency were analyzed, and claims listing FBSS were selected for the study. Prescription patterns of opioids and gabapentinoids were classified based on the number of days prescribed per year. Results: Of the 390,095 patients diagnosed with FBSS, 41.6% of the patients were prescribed gabapentinoids, and 42.0% of them were prescribed opioids, while 10.6% of the patients were classified as long-term gabapentinoid users, 11.4% as long-term opioid users, and 7.4% of the patients were found to have long-term prescriptions for both drugs. The proportion of patients who received both gabapentinoid and opioid prescriptions increased annually. The doses of opioids prescribed have also increased along with the increase in the number of patients receiving opioid prescriptions. Conclusions: The prescription rates of opioids and gabapentinoids among patients with FBSS in Korea continue to increase steadily, posing potential risks of addiction and adverse effects. Further research is needed to better understand the actual status of addiction in patients with FBSS.

• The Korean Journal of Pain
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• v.33 no.2
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• pp.183-191
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• 2020

Background: Opioids can present intolerable adverse side-effects to patients who use these analgesics to mitigate chronic pain. In this retrospective analysis, cooled radiofrequency (CRF) denervation was evaluated to provide pain and disability relief and reduce opioid use in patients with sacroiliac joint (SIJ) derived low back pain (LBP). Methods: Twenty-seven patients with pain from SIJ refractory to conservative treatments, and taking opioids chronically (> 3 mo), were included. Numeric rating scale (NRS) and Oswestry disability index (ODI) scores were collected at 1, 6, and 12 months post-procedure. Opioid use between baseline and each follow-up visit was compared for the entire group and for those who experienced successful (pain reduction ≥ 50% of baseline value) or unsuccessful CRF denervation. Results: Severe initial mean pain (NRS score: 7.7 ± 1.0) and disability (ODI score: 50.1 ± 9.0), and median opioid use (morphine equivalent daily dose: 40 ± 37 mg) were significantly reduced up to 12 months post-intervention. CRF denervation was successful in 44.4% of the patients at 12 months. Regardless of procedure success, patients demonstrated similar opioid reductions and changes in opioid use at 12 months. Two patients (7.4%) experienced neuritis following CRF denervation. Conclusions: CRF denervation of the SIJ can safely elicit pain and disability relief, and reduce opioid use, regardless of intervention success. Future studies may support CRF denervation as a dependable therapy to alleviate opioid use in patients with SIJ-derived LBP and show that opioid use measurements can be a surrogate indicator of pain.

• The Korean Journal of Pain
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• v.33 no.3
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• pp.234-244
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• 2020

Background: Chronic pain affects approximately 22% of the world's population. Opioids can be useful in chronic pain management. However, some patients have negative perception of opioids. The purpose of this research was to evaluate patients' perception about opioids and investigate problems associated with prescribing and taking opioids in South Korea. Methods: Patients who visited a pain clinic in 14 university hospitals of South Korea from September through October 2018 were asked to complete anonymous questionnaires about taking opioids. Results: Of the 368 patients that were surveyed (female 53.3%, male 46.7%), 56.8% were prescribed opioids. In the opioid group, 92.8% patients had heard of opioids from their doctor and 72.6% of them had a positive perception about opioids. The side effects associated with opioid use were constipation (35.4%), dizziness (24.6%), nausea and vomiting (17.4%), dysuria (6.2%), and addiction (2.0%). In the no opioid group, the primary sources of information about opioids were doctors (49.2%), mass media (30.8%), and the internet (16.2%). The main reasons why 39.0% patients did not take opioids were fear of addiction (57.7%) and side effects (38.5%). There were 71.5% and 60.9% patients in the opioid and no opioid group, respectively, who wished to take opioids when their numeric rating scale pain score was ≥ 7. Conclusions: Perception of opioids among patients who take them was either neutral or positive. However, 39.0% patients who have not been prescribed opioids did not want an opioid prescription, citing fear of addiction and side effects as the primary reasons.

• The Korean Journal of Pain
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• v.37 no.2
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• pp.119-131
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• 2024

There are growing concerns regarding the safety of long-term treatment with opioids of patients with chronic non-cancer pain. In 2017, the Korean Pain Society (KPS) developed guidelines for opioid prescriptions for chronic non-cancer pain to guide physicians to prescribe opioids effectively and safely. Since then, investigations have provided updated data regarding opioid therapy for chronic non-cancer pain and have focused on initial dosing schedules, reassessment follow-ups, recommended dosage thresholds considering the risk-benefit ratio, dose-reducing schedules for tapering and discontinuation, adverse effects, and inadvertent problems resulting from inappropriate application of the previous guidelines. Herein, we have updated the previous KPS guidelines based on a comprehensive literature review and consensus development following discussions among experts affiliated with the Committee on Hospice and Palliative Care in the KPS. These guidelines may assist physicians in prescribing opioids for chronic non-cancer pain in adult outpatient settings, but should not to be regarded as an inflexible standard. Clinical judgements by the attending physician and patient-centered decisions should always be prioritized.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2937-2943
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• 2013

Backgrounds: Polymorphisms of OPRM1 A118G and ABCB1 C3435T have been suggested to contribute to inter-individual variability regarding pain sensitivity, opioid usage, tolerance and dependence and incidence of adverse effects in patients with chronic pain. This study aimed to investigate the association of both two polymorphisms with opioid requirements in Chinese patients with cancer pain. Methods: The genotypes of rs1799971 (OPRM1) and rs1045642 (ABCB1) were determined by PCR-RFLP and direct sequencing methods respectively in 112 patients with cancer-related pain. Comparisons between the different genotype or allele groups were performed with t-tests or one-way ANOVA tests, as appropriate. The potential relationship of allele number with opioid response was performed with a trend Jonckheere-Terpstra test. Results: In the 112 subjects, the frequencies of variant 118 G and 3435T allele were 38.4% and 37.9%, respectively. Significant higher 24h-opioid doses were observed in patients with GG (P=0.0004) and AG + GG (P=0.005) genotypes than the AA carriers. The dominant mutant 118G allele tended to be associated with progressively increasing 24h-opioiddoses (P=0.001). Compared with CC/CT, patients with ABCB1 TT genotype received higher 24h- and weight-surface area-adjusted-24h- opioids doses (P=0.057 and 0.028, respectively). Conclusions: The OPRM1 A118G single nucleotide polymorphism (SNP) is a key contributor for the inter-individual variability in opioidrequirements in Chinese cancer pain patients. This may possibly extend to the ABCB1 C3435T SNP.

• 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.29 no.2
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• pp.110-118
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• 2016

Background: Nefopam is a non-opioid, non-steroidal, centrally acting analgesic drug. The concomitant use of opioids and nefopam is believed to have many advantages over the administration of opioids alone for postoperative pain management. We conducted a randomized, double-blind study to determine the fentanyl-sparing effect of co-administration of nefopam with fentanyl for postoperative pain management via patient controlled analgesia (PCA). Methods: Ninety female patients who underwent laparoscopic total hysterectomy under general anesthesia were randomized into 3 groups, Group A, fentanyl $1,000{\mu}g$; Group B, fentanyl $500{\mu}g$ + nefopam 200 mg; and Group C, fentanyl $500{\mu}g$ + nefopam 400 mg, in a total volume of 100 ml PCA to be administered over the first 48 h postoperatively without basal infusion. The primary outcome was total fentanyl consumption during 48 h; secondary outcomes included pain scores and incidence of side effects. Results: Eighty-one patients were included in the analysis. The overall fentanyl-sparing effects of PCA with concomitant administration of nefopam during the first 48 h postoperatively were 54.5% in Group B and 48.9% group C. Fentanyl use was not significantly different between Groups B and C despite the difference in the nefopam dose. There were no differences among the three groups in terms of PCA-related side effects, although the overall sedation score of Group B was significantly lower than that of Group A. Conclusions: The concomitant administration of nefopam with fentanyl for postoperative pain management may allow reduction of fentanyl dose, thereby reducing the risk of opioid-related adverse effects.