INTRODUCTION: The use of periarticular (PA) tranexamic acid (TXA) and its efficacy in comparison with intra-articular (IA) TXA have not been well explored in the literature. This retrospective cohort study aimed to compare the effects of IA and PA TXA with analgesic components in reducing blood loss and improving immediate postoperative pain relief and functional outcomes in patients after unilateral primary total knee arthroplasty (TKA). METHODS: A total of 63 patients underwent TKA, and they were divided into the IA TXA delivery group ( n = 42) and PA TXA delivery group ( n = 21). All patients were administered 1 g of TXA. They also received pericapsular infiltration consisting of 0.5 mL of adrenaline, 0.4 mL of morphine, 1 g of vancomycin, 1 mL of ketorolac and 15 mL of ropivacaine. Outcomes for blood loss and surrogate markers for immediate functional recovery were measured. RESULTS: Of the 63 patients, 54% were female and 46% male. The mean drop in postoperative haemoglobin levels in the PA and IA groups was 2.0 g/dL and 1.6 g/dL, respectively, and this was not statistically significant ( P = 0.10). The mean haematocrit drop in the PA and IA groups was 6.1% and 5.3%, respectively, and this was also not statistically significant ( P = 0.58). The postoperative day (POD) 1 and discharge day flexion angles, POD 1 and POD 2 visual analogue scale (VAS) scores, gait distance on discharge and length of hospitalisation stay were largely similar in the two groups. CONCLUSION Our study showed that both IA and PA TXA with analgesic components were equally efficient in reducing blood loss and improving immediate postoperative pain relief and functional outcomes.
Humans ; Male ; Female ; Tranexamic Acid/adverse effects* ; Arthroplasty, Replacement, Knee/adverse effects* ; Antifibrinolytic Agents/adverse effects* ; Retrospective Studies ; Postoperative Hemorrhage ; Blood Loss, Surgical/prevention & control* ; Administration, Intravenous ; Analgesia ; Analgesics/therapeutic use* ; Pain, Postoperative/drug therapy* ; Injections, Intra-Articular

Opioid use disorder (OUD) has become a considerable global public health challenge; however, potential medications for the management of OUD that are effective, safe, and nonaddictive are not available. Accumulating preclinical evidence indicates that antagonists of the dopamine D₃ receptor (D₃R) have effects on addiction in different animal models. We have previously reported that YQA14, a D₃R antagonist, exhibits very high affinity and selectivity for D₃Rs over D₂Rs, and is able to inhibit cocaine- or methamphetamine-induced reinforcement and reinstatement in self-administration tests. In the present study, our results illustrated that YQA14 dose-dependently reduced infusions under the fixed-ratio 2 procedure and lowered the breakpoint under the progressive-ratio procedure in heroin self-administered rats, also attenuated heroin-induced reinstatement of drug-seeking behavior. On the other hand, YQA14 not only reduced morphine-induced expression of conditioned place preference but also facilitated the extinguishing process in mice. Moreover, we elucidated that YQA14 attenuated opioid-induced reward or reinforcement mainly by inhibiting morphine-induced up-regulation of dopaminergic neuron activity in the ventral tegmental area and decreasing dopamine release in the nucleus accumbens with a fiber photometry recording system. These findings suggest that D₃R might play a very important role in opioid addiction, and YQA14 may have pharmacotherapeutic potential in attenuating opioid-induced addictive behaviors dependent on the dopamine system.
Rats ; Mice ; Animals ; Analgesics, Opioid ; Dopamine ; Heroin/pharmacology* ; Dopamine Antagonists/pharmacology* ; Receptors, Dopamine D3/metabolism* ; Morphine/pharmacology* ; Behavior, Addictive/drug therapy* ; Self Administration

Investigation of pain requires measurements of nociceptive sensitivity and other pain-related behaviors. Recent studies have indicated the superiority of gait analysis over traditional evaluations (e.g., skin sensitivity and sciatic function index [SFI]) in detecting subtle improvements and deteriorations in animal models. Here, pain-related gait parameters, whose criteria include (1) alteration in pain models, (2) correlation with nociceptive threshold, and (3) normalization by analgesics, were identified in representative models of neuropathic pain (spared nerve injury: coordination data) and inflammatory pain (intraplantar complete Freund's adjuvant: both coordination and intensity data) in the DigiGait™ and CatWalk™ systems. DigiGait™ had advantages in fixed speed (controlled by treadmill) and dynamic SFI, while CatWalk™ excelled in intrinsic velocity, intensity data, and high-quality 3D images. Insights into the applicability of each system may provide guidance for selecting the appropriate gait imaging system for different animal models and optimization for future pain research.
Analgesics ; administration & dosage ; Animals ; Freund's Adjuvant ; administration & dosage ; Gait ; drug effects ; Gait Analysis ; methods ; Image Processing, Computer-Assisted ; Inflammation ; chemically induced ; Male ; Neuralgia ; physiopathology ; prevention & control ; Pain ; etiology ; physiopathology ; prevention & control ; Rats, Sprague-Dawley

Objective To investigate the 50% effective dose(ED)and 95% effective dose(ED)of dexmedetomidine(DEX)combined with 0.032 μg/(kg·h)sufentanil as well as its analgesic effect for patient-controlled intravenous analgesia(PCIA)after video-assisted thoracoscopic surgery(VATS).Methods Totally 25 patients undergoing elective VATS were enrolled. DEX and 0.032 μg/(kg·h)sufentanil were used for postoperative PCIA. The loading dose of DEX was 0.048 μg/(kg·h),and the dose difference between two adjacent patients was 0.008 μg/(kg·h). The DEX dose of a current patient was determined by whether the previous patient was satisfied with postoperative analgesic effect. If the previous patient was satisfied with postoperative analgesic effect,the DEX dose of the current patient was decreased by 0.008 μg/(kg·h);and if the previous analgestic effect was not satisfactory,DEX dose of the current patient was increased by 0.008 μg/(kg·h). The study endpoint was dexmedetomidine dose was<0.008 μg/(kg· h) within 7 upper and lower cycles in 7 consecutive cases. Finally,the probability unit regression was used to estimate the ED and ED of DEX and their 95% .Results When DEX combined with 0.032 μg/(kg·h) sufentanil was used for postoperative PCIA in young patients undergoing VATS,the ED and EDof DEX were 0.0346 μg/(kg· h)[95%:0.0283-0.0408 μg/(kg·h)] and 0.0459 μg/(kg·h)[95%:0.0400-0.0880 μg/(kg·h)],respectively. No adverse reaction such as vomiting,respiratory depression,or bradycardia occurred. The average Visual Analogue Scale(VAS)scores at rest(=-5.128,=0.000)and cough(Z=-6.642,=0.000)and the Ramsay sedation score(Z=-2.335,=0.020)within 6 hours after surgery were higher than those after 6 hour.Conclusion DEX combined with 0.032 μg/(kg·h) sufentanil are effective for postoperative PCIA in patients undergoing VATS when the ED and ED are 0.0346 μg/(kg·h)and 0.0459 μg/(kg·h),respectively.
Analgesia, Patient-Controlled ; Analgesics, Non-Narcotic ; administration & dosage ; therapeutic use ; Dexmedetomidine ; administration & dosage ; therapeutic use ; Dose-Response Relationship, Drug ; Drug Therapy, Combination ; Humans ; Pain, Postoperative ; drug therapy ; Sufentanil ; administration & dosage ; therapeutic use ; Thoracic Surgery, Video-Assisted

Isoflavones are widely consumed by people around the world in the form of soy products, dietary supplements and drugs. Many isoflavones or related crude extracts have been reported to exert pain-relief activities, but the mechanism remains unclear. Voltage-gated sodium channels (VGSCs) play important roles in excitability of pain sensing neurons and many of them are important nociceptors. Here, we report that several isoflavones including 3'-methoxydaidzein (3MOD), genistein (GEN) and daidzein (DAI) show abilities to block VGSCs and thus to attenuate chemicals and heat induced acute pain or chronic constriction injury (CCI) induced pain hypersensitivity in mice. Especially, 3MOD shows strong analgesic potential without inducing addiction through inhibiting subtypes Na1.7, Na1.8 and Na1.3 with the IC of 181 ± 14, 397 ± 26, and 505 ± 46 nmol·L, respectively, providing a promising compound or parent structure for the treatment of pain pathologies. This study reveals a pain-alleviating mechanism of dietary isoflavones and may provide a convenient avenue to alleviate pain.
Analgesics ; administration & dosage ; chemistry ; Animals ; Humans ; Isoflavones ; administration & dosage ; chemistry ; Male ; Mice ; Mice, Inbred C57BL ; Pain ; drug therapy ; genetics ; metabolism ; Voltage-Gated Sodium Channel Blockers ; administration & dosage ; Voltage-Gated Sodium Channels ; genetics ; metabolism

INTRODUCTION: Adductor canal block (ACB) is hypothesised to provide superior analgesia to femoral nerve block (FNB) for total knee arthroplasty (TKA) while preserving quadriceps strength. METHODS: 30 patients undergoing TKA were randomised to receive either ACB or FNB. Baseline tests of quadriceps strength were performed. Ultrasound-guided blocks with 30 mL of 0.5% ropivacaine were administered before induction of general anaesthesia. Patient-controlled analgesia (morphine) was prescribed for postoperative analgesia. The primary outcome of this prospective, double-blinded, randomised controlled trial was morphine consumption (mean ± standard deviation) in the first 24 hours. Secondary outcomes were pain scores using a numeric rating scale (median and interquartile range [IQR]), quadriceps strength (% of baseline) and functional outcomes at 24 hours and 48 hours postoperatively. RESULTS: There was no statistically significant difference in morphine consumption at 24 hours between the ACB and FNB groups (21 ± 11 mg vs. 20 ± 12 mg; p = 0.85). No statistically significant differences were observed between the ACB and FNB groups in pain scores at 24 hours (at rest: 0 [IQR 0-2] vs. 0 [IQR 0-2]; on movement: 5 [IQR 4-8] vs. 5 [IQR 3-8]) and quadriceps strength (24 hours: 28.8% ± 26.1% vs. 26.8% ± 19.6% of baseline; 48 hours: 31.5 ± 23.1% vs. 33.7% ± 20.1% of baseline). There were also no statistically significant differences in functional outcomes and length of stay. CONCLUSION We found no statistically significant differences in analgesic effects, quadriceps strength or functional recovery postoperatively between ACB and FNB.
Aged ; Aged, 80 and over ; Analgesia, Patient-Controlled ; methods ; Analgesics, Opioid ; therapeutic use ; Anesthetics, Local ; administration & dosage ; Arthroplasty, Replacement, Knee ; Double-Blind Method ; Female ; Femoral Nerve ; Humans ; Male ; Middle Aged ; Morphine ; therapeutic use ; Nerve Block ; methods ; Pain Management ; methods ; Pain Measurement ; Pain, Postoperative ; drug therapy ; Prospective Studies ; Quadriceps Muscle ; drug effects ; Treatment Outcome ; Ultrasonography

BACKGROUND: The aim of this study was to identify the painkillers preferred for self-administration by doctors working at general hospitals in the capital of the Republic of Korea.METHODS: We collected data, using a questionnaire, from 224 doctors working at secondary or tertiary hospitals in the capital of the Republic of Korea from July 1, 2017 to August 31, 2017. The questionnaire included questions on the preferred type of painkiller for each type of pain and the frequency of painkiller intake. Further, we evaluated the participants on the Likert scale to analyze the consideration and cognition of self-administration of painkillers.RESULTS: The doctors in this study tended to state the trade name of the painkillers rather than the generic name. They preferred acetaminophen for headache and nonsteroidal anti-inflammatory drugs for gastrointestinal (GI) pain, dysmenorrhea, toothache, and musculoskeletal pain. In the choice of painkiller for self-administration, they set utmost importance on the effectiveness of the medicine, followed by the potential side effects, physician's prescription, and the pharmacy's recommendation, in that order. The side effects attribute GI complications, hepatotoxicity, drug tolerance, and delayed diagnosis to painkiller use. There were some remarkable differences between surgeons and non-surgeons, men and women, and specialists and trainees in the conception of painkillers and pain control.CONCLUSION: This is the first study worldwide on the trait of the self-administration of painkillers by doctors, which can serve as a useful reference in clinical settings.
Acetaminophen ; Analgesics ; Cognition ; Delayed Diagnosis ; Drug Tolerance ; Dysmenorrhea ; Female ; Fertilization ; Headache ; Hospitals, General ; Humans ; Male ; Musculoskeletal Pain ; Prescriptions ; Republic of Korea ; Self Administration ; Self Medication ; Specialization ; Surgeons ; Tertiary Care Centers ; Toothache

Novel series of limonin derivatives (V-A-1-V-A-8, V-B-1-V-B-8) were synthesized by adding various tertiary amines onto the C (7)-position of limonin. The synthesized compounds possessed favorable physicochemical property, and the intrinsic solubility of the novel compounds were significantly improved, compared with limonin. Different pharmacological models were used to evaluate the analgesic and anti-inflammatory activities of the target compounds. Compound V-A-8 exhibited the strongest in vivo activity among the novel limonin analogs; its analgesic activity was more potent than aspirin and its anti-inflammatory activity was stronger than naproxen under our testing conditions.
Analgesics ; administration & dosage ; chemical synthesis ; chemistry ; Animals ; Anti-Inflammatory Agents ; administration & dosage ; chemical synthesis ; chemistry ; Drug Discovery ; Edema ; drug therapy ; Humans ; Limonins ; administration & dosage ; chemical synthesis ; chemistry ; Mice ; Molecular Structure ; Pain ; drug therapy

Two new sesquiterpenes, trivially named ricinusoids A (1) and ricinusoids B (2), were isolated from ethyl acetate fraction of Ricinus communis. The structures of new compounds were elucidated by detailed spectroscopic techniques, including 1D- and 2D-NMR, UV, IR spectroscopy, and mass spectrometry. The compounds (1-2) were also assessed for in-vivo sedative and analgesic like effects in open field and acetic acid induced writhing tests respectively at 5, 10, and 20 mg·kg i.p. Pretreatment of both test compounds caused significant (P ≤ 0.05) reduction in locomotive activity like sedative agents and abdominal constrictions like analgesics. Both compounds (1-2) possessed marked sedative and antinociceptive effects in animal models.
Analgesics ; administration & dosage ; chemistry ; isolation & purification ; Animals ; Humans ; Hypnotics and Sedatives ; administration & dosage ; chemistry ; isolation & purification ; Locomotion ; drug effects ; Male ; Mice ; Mice, Inbred BALB C ; Molecular Structure ; Pain ; drug therapy ; physiopathology ; Plant Extracts ; administration & dosage ; chemistry ; isolation & purification ; Plant Leaves ; chemistry ; Ricinus ; chemistry ; Sesquiterpenes ; administration & dosage ; chemistry ; isolation & purification

Due to ineffectiveness and side effects of existing analgesics, chronic pain has become one of the most complex and difficult problems in the clinic. Monoacylglycerol lipase (MAGL) is an essential hydrolase in the endocannabinoid system and has been identified as a potential target for the treatment of pain. In the present study, we designed and synthesized twelve tanshinone IIA analogs and screened their activity against MAGL. Selected compounds were tested for analgesic activity in vivo, with the acetic acid writhing test model. Among the test compounds, compound III-3 (IC 120 nmol·L) showed significant activity against MAGL and ameliorated the clinical progression in the mouse pain model. Additionally, compound III-3, substitution with N-methyl-2-morpholinoacetamide, demonstrated improved solubility relative to tanshinone IIA.
Abietanes ; administration & dosage ; chemical synthesis ; chemistry ; Analgesics ; administration & dosage ; chemical synthesis ; chemistry ; Animals ; Chronic Pain ; drug therapy ; enzymology ; Drug Evaluation, Preclinical ; Enzyme Inhibitors ; administration & dosage ; chemical synthesis ; chemistry ; Female ; Humans ; Male ; Mice ; Mice, Inbred ICR ; Monoacylglycerol Lipases ; antagonists & inhibitors ; metabolism ; Structure-Activity Relationship