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

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

OBJECTIVE: To investigate the relationship between OPRM1 118A/G gene polymorphism and oxycodone analgesic dose in patients with cancer pain. METHODS: DNA sequencing was used to detect the genotypies of OPRM1 118 A/G site in 203 patients with moderate and severe cancer pain, and to compare the relationship between the pain degree and the dose of oxycodone at 3 and 30 days after treatment in patients with different genotypes. RESULTS: The fequencies of AA, AG and GG genotypes at the OPRM1 118 A/G site were 34.78%, 52.70%, and 12.52%, respectively. The dosage of oxycodone in GG genotype was significantly higher than that in AA genotype and AG genotype (15.44±10.19 vs. 10.25±4.53, 10.49±5.26; 89.15±27.69 vs. 43.59±12.19, 48.27±18.79) on the 3 and 30 day after treatment, difference was statistically significant (P< 0.05). CONCLUSION For cancer pain patients with GG genotype of OPRM1 118A/G site, if they need to achieve the same analgesic effect as patients with AA and AG genotype, the dose of oxycodone should be increased.
Analgesics, Opioid ; administration & dosage ; Cancer Pain ; drug therapy ; Dose-Response Relationship, Drug ; Genotype ; Humans ; Oxycodone ; administration & dosage ; Polymorphism, Single Nucleotide ; Receptors, Opioid, mu ; genetics

PURPOSE: Intrathecal morphine pump (ITMP) infusion therapy is efficient in managing malignant and nonmalignant chronic pain refractory to standard treatment. However, the high cost of an ITMP is the greatest barrier for starting a patient on ITMP infusion therapy. Using the revised Korean reimbursement guidelines, we investigated the cost effectiveness of ITMP infusion therapy and conducted a patient survey. MATERIALS AND METHODS: A retrospective chart review of 12 patients who underwent ITMP implantation was performed. Morphine dose escalation rates were calculated, and numeric rating scale (NRS) scores were compared before and after ITMP implantation. We surveyed patients who were already using an ITMP as well as those who were candidates for an ITMP. All survey data were collected through in-person interviews over 3 months. Data on the cost of medical treatment were collected and projected over time. RESULTS: The NRS score decreased during the follow-up period. The median morphine dose increased by 36.9% over the first year, and the median time required to reach a financial break-even point was 24.2 months. Patients were more satisfied with the efficacy of ITMP infusion therapy than with conventional therapy. The expected cost of ITMP implantation was KRW 4000000-5000000 in more than half of ITMP candidates scheduled to undergo implantation. CONCLUSION: The high cost of initiating ITMP infusion therapy is challenging; however, the present results may encourage more patients to consider ITMP therapy.
Adult ; Aged ; Analgesics, Opioid/*administration & dosage/economics/therapeutic use ; Chronic Pain/*drug therapy ; Cost-Benefit Analysis ; Female ; Humans ; Infusion Pumps, Implantable/*economics ; Injections, Spinal ; Male ; Middle Aged ; Morphine/*administration & dosage/economics/therapeutic use ; Pain Management/*methods/trends ; Patient Satisfaction ; Republic of Korea ; Retrospective Studies ; Surveys and Questionnaires ; Treatment Outcome

Dentists often sedate patients in order to reduce their dental phobia and stress during dental treatment. Sedatives are administered through various routes such as oral, inhalation, and intravenous routes. Intravenous administration has the advantage of rapid onset of action, predictable duration of action, and easy titration. Typically, midazolam, propofol or dexmedetomidine are used as intravenous sedatives. Administration of these sedatives via infusion by using a syringe pump is more effective and successful than infusing them as a bolus. However, during intravenous infusion of sedatives or opioids using a syringe pump, fatal accidents may occur due to the clinician's carelessness. To prevent such risks, smart syringe pumps have been introduced clinically. They allow clinicians to perform effective sedation by using a computer to control the dose of the drug being infused. To ensure patient safety, various alarm features along with a drug library, which provides drug information and prevents excessive infusion by limiting the dose, have been added to smart pumps. In addition, programmed infusion systems and target-controlled infusion systems have also been developed to enable effective administration of sedatives. Patient-controlled infusion, which allows a patient to control his/her level of sedation through self-infusion, has also been developed. Safer and more successful sedation may be achieved by fully utilizing these new features of the smart pump.
Administration, Intravenous ; Analgesics, Opioid ; Dental Anxiety ; Dentists ; Dexmedetomidine ; Humans ; Hypnotics and Sedatives ; Infusion Pumps ; Infusions, Intravenous ; Inhalation ; Midazolam ; Patient Safety ; Propofol ; Syringes*

OBJECTIVETo investigate the effect of a single dose of ropivacaine combined with sufentanilfor thoracic paravertebral block (TPVB) on pain and enhanced recovery after surgery (ERAS) in patients undergoing video-assisted thoracosopic surgery.

METHODSSixty patients undergoing video-assisted thoracosopic surgery were randomly divided into three groups to receive intravenous combined general anesthesia (group C), a single dose of ropivacainefor thoracic paravertebral block before surgery combined with intravenous and general anesthesia(group T), or a single dose of ropivacaineand sufentanilfor thoracic paravertebral blockcombined with intravenous and general anesthesia (group T). None of the patients used postoperative analgesia pump, and tramadol hydrochoride injection (100 mg) was given in cases with NRS scores > 4 after the surgery. The data were recorded including analgesics used for nerve block before the operation, intravenous dosage of sufentanilduring operation, total dose of sufentanilused (intravenous+nerve block), intravenous remifentanil dose during operation, NRS scores at 4, 6, 24, 48 h after the surgery, rescue analgesia in the first postoperative 24 h after surgery, ICU stay and hospital stay after the surgery.

RESULTSCompared with those in group C, the intravenous sufentanildose, total sufentanildose, intravenous remifentanildose during operation, NRS scores at 4 and 6, 24 h, and ICU stay and hospital stay after the surgery were significantly decreased in groups Tand T(P<0.05). The total dose of opioids during the operation and NRS scores at 4 and 6 h were significantly lower in group Tthan in group T(P<0.05), but the total dose of sufentanil, ICU stay and hospital stay were simialr between the two groups.

CONCLUSIONA single dose of ropivacaine combined with sufentanilfor thoracic paravertebral blockbefore surgery can reduce the total dose opioids, produce the optimal analgesic effect, and promote postoperative recovery of the patients.

Amides ; administration & dosage ; therapeutic use ; Analgesics, Opioid ; therapeutic use ; Anesthesia, General ; Anesthetics, Intravenous ; therapeutic use ; Humans ; Injections ; Nerve Block ; methods ; Pain Management ; Pain Measurement ; Pain, Postoperative ; Piperidines ; therapeutic use ; Postoperative Period ; Sufentanil ; therapeutic use ; Thoracic Surgery, Video-Assisted

OBJECTIVETo evaluate the efficacy and safety of patient-controlled intravenous analgesia (PCIA) of dezocine combined with sufentanil in burn patients after escharectomy or tangential excision followed by autologous skin grafting.

METHODSSixty burn patients hospitalized in Department of Burns and Plastic Surgery of our hospital from February 2011 to December 2013, conforming to the study criteria and going to have escharectomy or tangential excision followed by autologous skin grafting, were divided into sufentanil group (S, n = 30) and dezocine+sufentanil group (DS, n = 30) according to the random number table. Patients in group S were given 150 mL normal saline containing 2.5 µg/kg sufentanil citrate and 6 mg tropisetron after skin grafting for 48 hours. Patients in group DS were given 150 mL normal saline containing 0.25 mg/kg dezocine, 1.5 µg/kg sufentanil citrate, and 6 mg tropisetron for 48 hours. Visual Analog Scale (VAS), Bruggrmann Comfort Scale (BCS), and Ramsay Sedation Scale were used to evaluate the sedative effect or analgesic effect, and their scores were recorded at administration hour (AH) 2, 6, 12, 24, and 48. The times of efficient injection and incidence of adverse effect within the 48 AH were recorded. Data were processed with analysis of variance for repeated measurement, t test, chi-square test, and Fisher's exact test.

RESULTSThere were no obvious differences in the scores of VAS and BCS between two groups at each time point (with t values from -0.426 to 0.864, P values above 0.05). The scores of Ramsay Sedation Scale in group S at AH 2, 6, 12, 24, and 48 were respectively (3.2 ± 0.6), (3.2 ± 0.5), (3.3 ± 0.7), (3.2 ± 0.4), and (3.3 ± 0.4) points, which were higher than those in group DS [(2.4 ± 0.6), (2.5 ± 0.5), (2.4 ± 0.6), (2.4 ± 0.4), and (2.4 ± 0.5) points, with t values from 5.302 to 8.391, P values below 0.001]. The times of efficient injection within the 48 AH was 6.8 ± 0.7 in group S and 6.5 ± 0.9 in group DS, showing no significantly statistical difference (t = 1.260, P > 0.05). Respiratory depression was not observed in both groups; the incidence of pruritus was the same, and that of urine retention was similar between the 2 groups within the 48 AH (with P values above 0.05). Within the 48 AH, the incidence of nausea and vomiting in group S was 26.7% (8/30), which was obviously higher than that in group DS (6.7%, 2/30, P < 0.05); the incidence of drowsiness in group S was 20.0% (6/30), which was significantly higher than that in group DS (no patient, P < 0.05).

CONCLUSIONSDezocine combined with sufentanil can provide effective postoperative analgesia with little adverse effect for PCIA in burn patients after escharectomy or tangential excision followed by autologous skin grafting, therefore it can be widely used.

Analgesia, Patient-Controlled ; adverse effects ; Analgesics, Opioid ; administration & dosage ; Bridged Bicyclo Compounds, Heterocyclic ; administration & dosage ; adverse effects ; Burns ; surgery ; Female ; Humans ; Hypnotics and Sedatives ; administration & dosage ; Infusions, Intravenous ; Male ; Pain, Postoperative ; drug therapy ; Reconstructive Surgical Procedures ; Skin Transplantation ; Sufentanil ; administration & dosage ; adverse effects ; Tetrahydronaphthalenes ; administration & dosage ; adverse effects ; Treatment Outcome

BACKGROUND: Postoperative pain relief can be achieved with various modalities. However, there are only few reports that have analyzed postoperative analgesic techniques in total hip arthroplasty patients. The aim of this retrospective study was to compare the postoperative outcomes of three different analgesic techniques after total hip arthroplasty. METHODS: We retrospectively reviewed the influence of three analgesic techniques on postoperative rehabilitation after total hip arthroplasty in 90 patients divided into three groups (n = 30 patients per group). Postoperative analgesia consisted of continuous epidural analgesia (Epi group), patient-controlled analgesia with morphine (PCA group), or a continuous femoral nerve block (CFNB group). We measured the following parameters relating to postoperative outcome: visual analog scale scores, the use of supplemental analgesia, side effects, length of the hospital stay, plasma D-dimer levels, and the Harris hip score. RESULTS: Each group had low pain scores with no significant differences between the groups. The PCA group had a lower frequency of supplemental analgesia use compared to the Epi and CFNB groups. Side effects (nausea/vomiting, inappetence) and day 7 D-dimer levels were significantly lower in the CFNB group (p < 0.05). There were no significant differences between the groups in terms of the length of the hospital stay or the Harris hip score. CONCLUSIONS: Although there were no clinically significant differences in outcomes between the three groups, the CFNB provided good pain relief which was equal to that of the other analgesics with fewer side effects and lower D-dimer levels in hospitalized patients following total hip arthroplasty.
Adult ; Aged ; Aged, 80 and over ; *Analgesia, Epidural/methods ; *Analgesia, Patient-Controlled ; Analgesics, Opioid/*administration & dosage ; *Arthroplasty, Replacement, Hip ; Female ; *Femoral Nerve ; Fibrin Fibrinogen Degradation Products/analysis ; Humans ; Length of Stay ; Male ; Middle Aged ; Morphine/*administration & dosage ; *Nerve Block/methods ; Pain, Postoperative/*prevention & control ; Retrospective Studies ; Treatment Outcome

PURPOSE: The purpose of this study was to determine the effect-site concentration (Ce) of remifentanil in 50% of patients (EC50) and 95% of patients (EC95) for smooth laryngeal mask airway (LMA) removal in adults under propofol and remifentanil anesthesia. MATERIALS AND METHODS: Twenty-five patients of ASA physical status I-II and ages 18-60 years who were to undergo minor gynecological or orthopedic surgery were assessed in this study. Anesthesia was induced and maintained with propofol and remifentanil target-controlled infusion (TCI). Remifentanil was maintained at a predetermined Ce during the emergence period. The modified Dixon's up-and-down method was used to determine the remifentanil concentration, starting from 1.0 ng/mL (step size of 0.2 ng/mL). Successful removal of the LMA was regarded as absence of coughing/gagging, clenched teeth, gross purposeful movements, breath holding, laryngospasm, or desaturation to SpO2<90%. RESULTS: The mean+/-SD Ce of remifentanil for smooth LMA removal after propofol anesthesia was 0.83+/-0.16 ng/mL. Using isotonic regression with a bootstrapping approach, the estimated EC50 and EC95 of remifentanil Ce were 0.91 ng/mL [95% confidence interval (CI), 0.77-1.07 ng/mL] and 1.35 ng/mL (95% CI, 1.16-1.38 ng/mL), respectively. CONCLUSION: Our results showed that remifentanil TCI at an established Ce is a reliable technique for achieving safe and smooth emergence without coughing, laryngospasm, or other airway reflexes.
Adolescent ; Adult ; Analgesics, Opioid/*administration & dosage ; Anesthetics, Inhalation/*administration & dosage ; Cough/prevention & control ; Device Removal ; Dose-Response Relationship, Drug ; Female ; Gynecologic Surgical Procedures ; Humans ; *Laryngeal Masks ; Male ; Middle Aged ; Orthopedic Procedures ; Piperidines/*administration & dosage ; Propofol/*administration & dosage ; Treatment Outcome ; Young Adult

BACKGROUND/AIMS: Little is known about the efficacy of low-dose transdermal fentanyl (TDF) patches in opioid-naive patients with moderate-to-severe cancer pain. METHODS: This study had an open-label, prospective design, and was conducted between April 2007 and February 2009 in seven tertiary cancer hospitals; 98 patients were enrolled. TDF was started using a low-dose formulation (12.5 microg/hr), and the dose was adjusted according to the clinical situation of individual patients. Pain intensity, the TDF doses used, and adverse events (AEs) were monitored over 4 weeks. Data were analyzed using the intent-to-treat and per-protocol principles. RESULTS: Of the 98 patients enrolled, 64 (65%) completed the study. The median pain intensity decreased from 6.0 to 3.0 (p < 0.001) at the follow-up visit. The efficacy of low-dose TDF on pain relief was consistent across groups separated according to gender (p < 0.001), age (p < 0.001), metastasis (p < 0.001), previous treatment (p < 0.001), and baseline pain intensity (p < 0.001). The decrease in pain intensity was significantly greater in the severe group compared with the moderate group (mean +/- SD, 5.10 +/- 2.48 vs. 2.48 +/- 1.56; p < 0.001). TDF dose (27.8 microg/hr vs. 24.8 microg/hr, p = 0.423) and the mean treatment time (7.5 days vs. 7.9 days, p = 0.740) required for pain control were not different between the two pain-intensity groups. Patients had AEs of only mild or moderate intensity; among these, nausea (38%) was the most common, followed by vomiting (22%) and somnolence (22%). CONCLUSIONS: Low-dose TDF was an effective treatment for patients with cancer pain of moderate-to-severe intensity. Further randomized trials assessing the efficacy of TDF for severe pain and/or optimal starting doses are warranted.
Administration, Cutaneous ; Adult ; Aged ; Aged, 80 and over ; Analgesics, Opioid/*administration & dosage/adverse effects ; Female ; Fentanyl/*administration & dosage/adverse effects ; Humans ; Intention to Treat Analysis ; Male ; Middle Aged ; Neoplasms/*complications ; Pain/diagnosis/*drug therapy/etiology ; Pain Measurement ; Prospective Studies ; Republic of Korea ; Severity of Illness Index ; Tertiary Care Centers ; Time Factors ; Transdermal Patch ; Treatment Outcome