BACKGROUND: Patients commonly develop postoperative pain after total knee arthroplasty (TKA). Acupuncture-related techniques and low-level laser therapy could be beneficial for pain management for older individuals. OBJECTIVE: To examine the effect of low-level laser acupuncture (LA) in reducing postoperative pain, pain-related interference in daily life, morphine consumption, and morphine-related side effects in older patients with knee osteoarthritis who underwent TKA. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: A single-blind randomized placebo-controlled trial was conducted. Patients (N = 82) were recruited and randomly assigned via a computer-generated list to the LA group or a placebo group. The LA group received low-level laser therapy at Sanyinjiao (SP6), Taixi (KI3), Kunlun (BL60), Fengshi (GB31), Futu (ST32) and Neiguan (PC6) after TKA, while the placebo acupuncture group received the same treatment procedure without laser energy output. MAIN OUTCOME MEASURES: The primary outcome was postoperative pain intensity, and it was measured at baseline and hours 2, 6, 10, 24, 48 and 72 after TKA. The secondary outcomes, including relative pain, postoperative pain-related interference in daily life and morphine consumption, were measured at hours 24, 48 and 72 after TKA. RESULTS: Generalized estimating equations revealed significant between-group differences in pain intensity (P = 0.01), and trend differences in pain intensity for the LA group starting at hours 10 to 72 (P < 0.05) and morphine consumption at hours 48 and 72 (P < 0.05). The changes in pain-related interference in daily life were significant (P < 0.05) at 72 h, with the exception of the parameters for worst pain, mood, and sleep. Nausea and vomiting side effects from morphine had significant between-group differences at hours 10 and 24 (P < 0.05). CONCLUSION: Low-level LA gradually reduced older patients' postoperative pain intensity and morphine consumption within the first 72 h after their TKA for osteoarthritis. Low-level LA may have benefits as an adjuvant pain management technique for clinical care. TRIAL REGISTRATION ClinicalTrials.gov registration number NCT03995446.
Acupuncture Therapy ; Aged ; Analgesics, Opioid/therapeutic use* ; Arthroplasty, Replacement, Knee/adverse effects* ; Double-Blind Method ; Humans ; Morphine/therapeutic use* ; Pain, Postoperative/drug therapy* ; Single-Blind Method

Fentanyl is a fully synthetic opioid with analgesic and anesthetic properties. It has become a primary driver of the deadliest opioid crisis in the United States and elsewhere, consequently imposing devastating social, economic, and health burdens worldwide. However, the neural mechanisms that underlie the behavioral effects of fentanyl and its analogs are largely unknown, and approaches to prevent fentanyl abuse and fentanyl-related overdose deaths are scarce. This review presents the abuse potential and unique pharmacology of fentanyl and elucidates its potential mechanisms of action, including neural circuit dysfunction and neuroinflammation. We discuss recent progress in the development of pharmacological interventions, anti-fentanyl vaccines, anti-fentanyl/heroin conjugate vaccines, and monoclonal antibodies to attenuate fentanyl-seeking and prevent fentanyl-induced respiratory depression. However, translational studies and clinical trials are still lacking. Considering the present opioid crisis, the development of effective pharmacological and immunological strategies to prevent fentanyl abuse and overdose are urgently needed.
Humans ; Fentanyl/therapeutic use* ; Opioid-Related Disorders/drug therapy* ; Drug Overdose/prevention & control* ; Analgesics, Opioid/adverse effects* ; Vaccines/therapeutic use* ; Brain

The widespread use of opioids to treat chronic pain led to a nation-wide crisis in the United States. Tens of thousands of deaths annually occur mainly due to respiratory depression, the most dangerous side effect of opioids. Non-opioid drugs and non-pharmacological treatments without addictive potential are urgently required. Traditional Chinese medicine (TCM) is based on a completely different medical theory than academic Western medicine. The scientific basis of acupuncture and herbal treatments as main TCM practices has been considerably improved during the past two decades, and large meta-analyses with thousands of patients provide evidence for their efficacy. Furthermore, opinion leaders in the United States favor non-pharmacological techniques including TCM for pain management to fight the opioid crisis. We advocate TCM as therapeutic option without addictive potential and without life-threatening side effects (e.g., respiratory depression) to treat chronic pain patients suffering from opioid misuse. The evidence suggests that: (1) opioid misuse cannot be satisfactorily managed with standard medication; (2) opinion leaders in the United States favor to consider non-opioid and non-pharmacological treatment strategies including those from TCM to treat acute and chronic pain conditions; (3) large meta-analyses provide scientific evidence for the clinical activity of acupuncture and herbal TCM remedies in the treatment of chronic pain. Future clinical trials should demonstrate the safety of TCM treatments if combined with Western medical practices to exclude negative interactions between both modalities.
Acupuncture Therapy ; Analgesics, Opioid/adverse effects* ; Drugs, Chinese Herbal ; Epidemics ; Humans ; Medicine, Chinese Traditional ; Opioid Epidemic ; United States

Drug poisoning has a high incidence and serious consequences in medical institutions; its epidemiological characteristics also directly affect the changes in national laws and policies and the implementation of local management policies. Chinese statistics on drug-related abnormal death cases generally come from judicial appraisal centers and medical units. However, due to differences in work content and professional restrictions, there are differences in information management forms, which makes it difficult for appraisers to conduct a professional and systematic analysis of drug-related cases. This article focuses on the analysis of epidemiological characteristics of sedative-hypnotics and opioid painkillers and their exposure patterns in cases of poisoning death by analyzing the annual report of the American Association of Poison Control Center, combined with the characteristics of drug exposure in China.
Analgesics, Opioid/adverse effects* ; China/epidemiology* ; Databases, Factual ; Hypnotics and Sedatives ; Poison Control Centers ; United States

Abuse of pharmaceutical drugs is a major public health and social problem worldwide. Mostly abused drugs mainly include opioids such as morphine, tramadol, methadone and fentanyl, sedative-hypnotics such as benzodiazepines and non-benzodiazepines, and central stimulants such as Ritalin (methylphenidate), Adderall (amphetamine and dextroamphetamine) and modafinil. Abuse of pharmaceutical drugs not only causes direct damage to multiple systems of the body, but also significantly increases risks of mental and physical diseases, imposing a heavy burden on individuals, families and society. Therefore, the prevention and control of pharmaceutical drug abuse are of vital importance. The Chinese government has taken strict administration measures for pharmaceutical drugs with abuse risk. However, confronting endless new drugs and changing abuse trends, it is necessary to further strengthen management and prevention of pharmaceutical drugs, monitor the trend of abuse, establish rapid response mechanisms, popularize relevant knowledge, and develop specific therapeutic drugs and intervention means, in order to promote prevention and treatment of pharmaceutical drug abuse.
Analgesics, Opioid/adverse effects* ; Central Nervous System Stimulants/adverse effects* ; Humans ; Illicit Drugs/adverse effects* ; Substance-Related Disorders/prevention & control*

Aged ; Aged, 80 and over ; Analgesics, Opioid ; adverse effects ; Benzodiazepines ; adverse effects ; Cognitive Dysfunction ; chemically induced ; mortality ; Female ; Humans ; Male ; Postoperative Complications ; Randomized Controlled Trials as Topic ; Risk Factors

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

BACKGROUND: A prolonged-release formulation of oxycodone/naloxone has been shown to be effective in European populations for the management of chronic moderate to severe pain. However, no clinical data exist for its use in Korean patients. The objective of this study was to assess efficacy and safety of prolonged-release oxycodone/naloxone in Korean patients for management of chronic moderate-to-severe pain. METHODS: In this multicenter, single-arm, open-label, phase IV study, Korean adults with moderate-to-severe spinal disorder-related pain that was not satisfactorily controlled with weak opioids and nonsteroidal anti-inflammatory drugs received prolonged-release oral oxycodone/naloxone at a starting dose of 10/5 mg/day (maximum 80/40 mg/day) for 8 weeks. Changes in pain intensity and quality of life (QoL) were measured using a numeric rating scale (NRS, 0–10) and the Korean-language EuroQol-five dimensions questionnaire, respectively. RESULTS: Among 209 patients assessed for efficacy, the mean NRS pain score was reduced by 25.9% between baseline and week 8 of treatment (p < 0.0001). There was also a significant improvement in QoL from baseline to week 8 (p < 0.0001). The incidence of adverse drug reactions was 27.7%, the most common being nausea, constipation, and dizziness; 77.9% of these adverse drug reactions had resolved or were resolving at the end of the study. CONCLUSIONS: Prolonged-release oxycodone/naloxone provided significant and clinically relevant reductions in pain intensity and improved QoL in Korean patients with chronic spinal disorders. (ClinicalTrials.gov identifier: NCT01811238)
Adult ; Analgesia ; Analgesics, Opioid ; Chronic Pain* ; Constipation ; Dizziness ; Drug-Related Side Effects and Adverse Reactions ; Humans ; Incidence ; Nausea ; Quality of Life ; Spine

The opioid epidemic has become a signifificant public health crisis in the United States of America. This crisis has elicited a response at high levels of governmental and health care organizations including the American College of Physicians, the Food and Drug Administration, the Joint Commission, the National Academies of Science, Engineering and Medicine, the National Association of Attorneys General, and the White House. In various ways, these organizations have recognized that acupuncture can play an important role in dealing with the opioid epidemic. This paper presents and analyzes the scientifific evidence supporting the effificacy of acupuncture in regard to opioid addiction.
Acupuncture Therapy ; Analgesics, Opioid ; adverse effects ; Clinical Trials as Topic ; Epidemics ; Humans ; Opioid-Related Disorders ; epidemiology ; therapy

OBJECTIVE: To compare the analgesic effects and adverse drug reactions (ADRs) of fentanyl intravenous patient-controlled analgesia (ivPCA) with nefopam, a centrally acting analgesic agent with demonstrated opioid sparing activity, as compared to ketorolac in a tertiary teaching hospital. METHODS: A retrospective evaluation of electronic medical records was conducted on patient records including either nefopam or ketorolac with opioid ivPCA for post-operative pain management in general surgery department from January to December 2014. The status of pain control and ADRs were collected. RESULTS: Out of 6,330 general surgery cases, nefopam was given in 153 prescriptions (6.9%) and ketorolac in 81 prescriptions (3.6%). The level of pain control was not different between two groups (70.9% vs. 75.3%; p = 0.51), but ADRs were more frequently reported in nefopam group (9.8% vs. 2.5%; p < 0.05). New ADRs of hot flushes (n = 1) and paresthesia in hands (n = 1) were reported in nefopam group and they were unlisted in the approved package insert. No serious ADRs were reported in both groups. CONCLUSION: Our findings presented that nefopam showed a similar analgesic effect and higher ADR rates compared to ketorolac as an adjuvant to fentanyl iv PCA for postoperative pain management in general surgery patients in South Korea.
Analgesia, Patient-Controlled ; Analgesics, Opioid ; Drug-Related Side Effects and Adverse Reactions ; Electronic Health Records ; Fentanyl ; Hand ; Hospitals, Teaching ; Humans ; Ketorolac* ; Korea ; Nefopam* ; Pain Management* ; Pain, Postoperative ; Paresthesia ; Passive Cutaneous Anaphylaxis ; Prescriptions ; Product Labeling ; Retrospective Studies