OBJECTIVE: To investigate the effectiveness of preemptive analgesia with imrecoxib on analgesia after anterior cruciate ligament (ACL) reconstruction. METHODS: A total of 160 patients with ACL injuries who met the selection criteria and were admitted between November 2020 and August 2021 were selected and divided into 4 groups according to the random number table method (n=40). Group A began to take imrecoxib 3 days before operation (100 mg/time, 2 times/day); group B began to take imrecoxib 1 day before operation (100 mg/time, 2 times/day); group C took 200 mg of imrecoxib 2 hours before operation (5 mL of water); and group D did not take any analgesic drugs before operation. There was no significant difference in gender, age, body mass index, constituent ratio of meniscal injuries with preoperative MRI grade 3, constituent ratio of cartilage injury Outerbridge grade 3, and visual analogue scale (VAS) score at the time of injury and at rest among 4 groups (P>0.05). The operation time, hospitalization stay, constituent ratio of perioperative American Society of Anesthesiologists (ASA) grade 1, postoperative opioid dosage, and complications were recorded. The VAS scores were used to evaluate the degree of knee joint pain, including resting VAS scores before operation and at 6, 24, 48 hours, and 1, 3, 6, and 12 months after operation, and walking, knee flexion, and night VAS scores at 1, 3, 6, and 12 months after operation. The knee injury and osteoarthritis score (KOOS) was used to evaluate postoperative quality of life and knee-related symptoms of patients, mainly including pain, symptoms, daily activities, sports and entertainment functions, knee-related quality of life (QOL); and the Lysholm score was used to evaluate knee joint function. RESULTS: All patients were followed up 1 year. There was no significant difference in operation time, hospitalization time, or constituent ratio of perioperative ASA grade 1 among 4 groups (P>0.05); the dosage of opioids in groups A-C was significantly less than that in group D (P<0.05). Except for 1 case of postoperative fever in group B, no complications such as joint infection, deep vein thrombosis of the lower extremities, or knee joint instability occurred in each group. The resting VAS scores of groups A-C at 6 and 24 hours after operation were lower than those of group D, and the score of group A at 6 hours after operation was lower than those of group C, and the differences were significant (P<0.05). At 1 month after operation, the knee flexion VAS scores of groups A-C were lower than those of group D, the walking VAS scores of groups A and B were lower than those of groups C and D, the differences were significant (P<0.05). At 1 month after operation, the KOOS pain scores in groups A-C were higher than those in group D, there was significant difference between groups A, B and group D (P<0.05); the KOOS QOL scores in groups A-C were higher than that in group D, all showing significant differences (P<0.05), but there was no significant difference between groups A-C (P>0.05). There was no significant difference in VAS scores and KOOS scores between the groups at other time points (P>0.05). And there was no significant difference in Lysholm scores between the groups at 1, 3, 6, and 12 months after operation (P>0.05). CONCLUSION Compared with the traditional analgesic scheme, applying the concept of preemptive analgesia with imrecoxib to manage the perioperative pain of ACL reconstruction can effectively reduce the early postoperative pain, reduce the dosage of opioids, and promote the early recovery of limb function.
Humans ; Quality of Life ; Analgesics, Opioid ; Analgesia ; Osteoarthritis, Knee ; Pain, Postoperative/prevention & control* ; Anterior Cruciate Ligament Reconstruction ; Knee Injuries

The chronic use of morphine and other opioids is associated with opioid-induced hypersensitivity (OIH) and analgesic tolerance. Among the different forms of OIH and tolerance, the opioid receptors and cell types mediating opioid-induced mechanical allodynia and anti-allodynic tolerance remain unresolved. Here we demonstrated that the loss of peripheral μ-opioid receptors (MORs) or MOR-expressing neurons attenuated thermal tolerance, but did not affect the expression and maintenance of morphine-induced mechanical allodynia and anti-allodynic tolerance. To confirm this result, we made dorsal root ganglia-dorsal roots-sagittal spinal cord slice preparations and recorded low-threshold Aβ-fiber stimulation-evoked inputs and outputs in superficial dorsal horn neurons. Consistent with the behavioral results, peripheral MOR loss did not prevent the opening of Aβ mechanical allodynia pathways in the spinal dorsal horn. Therefore, the peripheral MOR signaling pathway may not be an optimal target for preventing mechanical OIH and analgesic tolerance. Future studies should focus more on central mechanisms.
Humans ; Morphine/pharmacology* ; Hyperalgesia/metabolism* ; Analgesics, Opioid/pharmacology* ; Neurons/metabolism* ; Signal Transduction

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

Humans ; Chronic Pain ; Analgesics, Opioid ; Pain Management ; Primary Health Care

OBJECTIVES: With the rapid development of aging population, the number of elderly patients undergoing posterior lumbar spine surgery continues to increase. Lumbar spine surgery could cause moderate to severe postoperative pain, and the conventional opioid-based analgesia techniques have many side effects, which are barriers to the recovery after surgery of the elderly. Previous studies have demonstrated that erector spinae plane block (ESPB) could bring about favorable analgesia in spinal surgery. As far as the elderly are concerned, the analgesic and recovery effects of ESPB on posterior lumbar spine surgery are not completely clear. This study aims to observe the effects of bilateral ESPB on elderly patients undergoing posterior lumbar spine surgery, and to improve the anesthesia techniques. METHODS: A total of 70 elderly patients of both sex, who were selected from May 2020 to November 2021, scheduled for elective posterior lumbar spine surgery, and in the age of 60-79 years, with American Society of Anesthesiologists class Ⅱ-Ⅲ, were divided into a ESPB group and a control (C) group using a random number table method, with 35 patients each. Before general anesthesia induction, 20 mL 0.4% ropivacaine was injected to the transverse process of L₃ or L₄ bilaterally in the ESPB group and only saline in the C group. The score of Numerical Rating Scale (NRS) indicating pain at rest and on movement within 48 h after operation, time of first patient control analgesia (PCA), cumulative consumptions of sufentanil within 48 hours, Leeds Sleep Evaluation Questionnaire (LSEQ) scores on the morning of day 1 and day 2 after operation, Quality of Recovery-15 (QoR-15) scores at 24 and 48 h after operation, full diet intake times, perioperative adverse reactions such as intraoperative hypotension, postoperative dizziness, nausea, vomiting, and constipation were compared between the 2 groups. RESULTS: A total of 70 patients were enrolled and 62 subjects completed the study, including 32 in the ESPB group and 30 in the C group. Compared with the C group, the postoperative NRS scores at rest at 2, 4, 6, and 12 h and on movementat at 2, 4, and 6 h were lower, time of first PCA was later, sufentanil consumptions were significantly decreased during 0-12 h and 12-24 h after operation, LSEQ scores on the morning of day 1 and QoR-15 scores at 24 and 48 h after operation were higher, full diet intakes achieved earlier in the ESPB group (all P<0.05). There were no significant differences in the incidences of intraoperative hypotension, postoperative dizziness, nausea, vomiting, and constipation between the 2 groups (all P>0.05). CONCLUSIONS Providing favorable analgesic effects with reduced opioids consumption, bilateral ESPB for posterior lumbar spine surgery in the elderly patients could also improve postoperative sleep quality, promote gastrointestinal functional restoration, and enhance recovery with few adverse reactions.
Aged ; Humans ; Middle Aged ; Sufentanil ; Dizziness ; Pain ; Anesthesia, General ; Constipation ; Hypotension ; Nerve Block ; Pain, Postoperative ; Analgesics, Opioid ; Ultrasonography, Interventional

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

Spinal cord stimulation (SCS)-induced analgesia was characterized, and its underlying mechanisms were examined in a spared nerve injury model of neuropathic pain in rats. The analgesic effect of SCS with moderate mechanical hypersensitivity was increased with increasing stimulation intensity between the 20% and 80% motor thresholds. Various frequencies (2, 15, 50, 100, 10000 Hz, and 2/100 Hz dense-dispersed) of SCS were similarly effective. SCS-induced analgesia was maintained without tolerance within 24 h of continuous stimulation. SCS at 2 Hz significantly increased methionine enkephalin content in the cerebrospinal fluid. The analgesic effect of 2 Hz was abolished by μ or κ opioid receptor antagonist. The effect of 100 Hz was prevented by a κ antagonist, and that of 10 kHz was blocked by any of the μ, δ, or κ receptor antagonists, suggesting that the analgesic effect of SCS at different frequencies is mediated by different endorphins and opioid receptors.
Analgesics ; Animals ; Narcotic Antagonists/pharmacology* ; Neuralgia/therapy* ; Opioid Peptides ; Rats ; Receptors, Opioid/physiology* ; Receptors, Opioid, kappa ; Spinal Cord ; Spinal Cord Stimulation

OBJECTIVE: To explore the effect of thoracic paravertebral anesthesia (TPVB) on prognosis of patients undergoing resection of lung cancer. METHODS: This study was conducted among the patients undergoing surgical resection of primary lung cancer under general anesthesia or TPVB combined with general anesthesia (TPVB+GA) between January, 2017 and May, 2018.The patients were enrolled in TPVB+GA group and GA group (control group) using a propensity score matching (PSM) method at the ratio of 1:2 based on their baseline characteristics.The clinical parameters, 5-year overall survival (OS), progression-free survival (PFS) and intraoperative dosage of opioids were compared between the two groups to assess the impact of TPVB on prognosis of the patients. RESULTS: Forty-seven patients were enrolled in TPVB+GA group and 94 in the control group.Kaplan-Meier survival analysis showed a significantly prolonged PFS in the patients with TPVB+GA (log-rank P=0.034), with an odds ratio (OR) of 0.45(95%CI: 0.33-0.89).Consistently, univariate and multivariate Cox regression analyses identified TPVB as an independent protective prognostic factor for patients with lung cancer resection (P=0.002, OR=0.33, 95%CI: 0.16-0.66).Cox regression analyses indicated that a lower intraoperative dose of remifentanil was significantly correlated with a longer PFS of the patients following lung cancer resection (P=0.017, OR=0.47, 95%CI: 0.25-0.87).Chi-square test confirmed that TPVB, but not general anesthesia, significantly reduced intraoperative dose of remifentanil, indicating a possible synergistic effect of TPVB with opioids to affect the survival of the patients. CONCLUSION TPVB can prolong the survival time and improve the prognosis of the patients undergoing surgical resection of lung cancer.
Humans ; Remifentanil ; Pain, Postoperative ; Nerve Block/methods* ; Analgesics, Opioid ; Prognosis ; Lung Neoplasms/surgery*

OBJECTIVE: To explore the effect of continuous low-dose infusion of esmolamine on intraoperative dosage of opioids and awakening quality in general anesthesia in pediatric surgeries. METHODS: A total of 100 children (6-8 years of age) undergoing pediatric surgery under general anesthesia were randomized equally into observation group and control group.In the observation group, the children received an intravenous injection of 0.1mg/kg esmolamine 10 min before induction of general anesthesia, followed by intravenous infusion of esmolamine at 2 μg•kg^-1•min^-1 until the end of the operation; those in the control group were infused with the same volume of normal saline instead of esmolamine in the same manner.The dosage of remifentanil during operation, recovery time of spontaneous breathing, recovery time of consciousness and extubation time were recorded in all the cases.The VAS score at 15, 30 and 60 min after extubation were assessed, and intravenous injection of naborphine 0.3 mg/kg was given for a VAS score ≥4;the total dosage of naborphine and adverse events were recorded for all the patients. RESULTS: The total dose of remifentanil was significantly lower in the observation group than in the control group, but the spontaneous respiratory recovery time, consciousness recovery time and extubation time did not differ significantly between the two groups.The VAS scores at 15, 30 and 60 min after extubation were all better in the observation group than in the control group; the total intraoperative dose of naborphine was significantly lower in the observation group. CONCLUSION Continuous infusion of low-dose esmolamine during pediatric surgery can effectively lower intraoperative dosage of opioids and reduce pain during recovery without affecting the quality of awakening.
Child ; Humans ; Remifentanil ; Anesthesia, General ; Analgesics, Opioid

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