Prolonged Analgesic Effect Research Articles

TECHNICAL AND QUANTITATIVE ANALYSIS OF PAIN MANAGEMENT IN MAJOR SURGERIES USING REGIONAL ANESTHESIA WITH OPIOID-SPARING DRUGS

The management of acute postoperative pain (APP) in major abdominal surgeries remains a critical challenge due to the adverse effects associated with opioid use, such as respiratory depression, nausea, vomiting, and decreased gastrointestinal motility. These complications underscore the need for alternative pain management strategies that minimize opioid dependence while ensuring effective analgesia. This study systematically reviews the opioid-sparing effects of regional anesthesia techniques, with a specific focus on the transversus abdominis plane (TAP) block and quadratus lumborum block (QLB). Both techniques are increasingly recognized as essential components of multimodal analgesia strategies, which aim to optimize postoperative recovery and reduce opioid-related complications. The findings reveal that TAP and QLB are highly effective in controlling postoperative pain, significantly decreasing opioid requirements and enhancing recovery outcomes. TAP block has demonstrated particular efficacy in reducing pain and opioid consumption in colorectal and bariatric surgeries, while QLB has shown promise in managing pain for more extensive abdominal procedures, offering prolonged analgesic effects. Despite their shared benefits, each technique presents unique efficacy profiles, which are influenced by factors such as surgical type, patient characteristics, and the choice of local anesthetic. These distinctions highlight the importance of tailoring regional anesthesia techniques to individual patient needs. This study also emphasizes the role of multimodal analgesic approaches that combine regional anesthesia with other non-opioid analgesics, such as ketamine and lidocaine, to further enhance pain control and minimize opioid use. Such approaches not only improve pain management but also contribute to faster recovery and fewer complications, such as postoperative nausea and delayed gastrointestinal transit. In conclusion, integrating regional anesthesia techniques like TAP and QLB into multimodal pain management protocols offers substantial benefits in reducing opioid consumption and enhancing postoperative recovery. Future research should focus on direct comparisons between regional techniques, their long-term effects, and their potential to reduce chronic pain recurrence, ensuring continued advancements in perioperative care.

Botulinum Toxin and Electrophysiological Intervention Improve Post-Surgical Breast Entdoprosthetics: A Clinical Trial Study.

The majority of plastic surgeon specialists note a distinct tendency to increase the number of breasts endoprosthetic surgeries with silicone implants in the Republic of Uzbekistan - the number of such surgeries now reaches 3-4 thousand annually. Breast replacement for aesthetic purposes is widespread throughout the world and has been rapidly spreading in Uzbekistan in recent years. Due to surgical endoprosthetics of mammary gland tissue with silicone implants, both in the early and late postoperative periods, quite often the patient's body experiences typical postoperative pain, which, if subclinical, requires constant dynamic monitoring and preventive rehabilitation procedures. Rehabilitation measures are a prerequisite for a successfully performed aesthetic surgery to enlarge the mammary glands. To address the effectiveness of intramuscular botulinum toxin A and the INDIBA electromagnetic field electrophysiology we used, a prospective randomized trial was designed to evaluate the effectiveness of patient-reported postoperative pain and pain reduction in these settings. The results of the conducted research allow us to conclude that the course of electrophysiological influence by INDIBA preparation, conducted in the first week, daily, i.e. 7 procedures after aesthetic breast endoprosthetics, significantly increases the efficiency of anesthetic effect of botulinum toxin type A drug administration 14 days before the intervention. These studies results allow us to conclude that a course of electrophysiological treatment with INDIBA, conducted in the first week after aesthetic breast endoprosthetics, significantly increases the effectiveness of the analgesic effect of botulinum toxin. Thus, the given results are convincing in terms of the fact that the proposed complex of rehabilitation measures after aesthetic endoprosthetics of mammary glands in the form of parenteral intramuscular administration of botulinum toxin preparation and a course of electrophysiological influence by electromagnetic field has a statistically significant pathogenetically-based pronounced and prolonged analgesic effect in the postoperative period.

Preparation and Evaluation of the In situ Gel-forming Chitosan Hydrogels for Nasal Delivery of Morphine in a Single Unit dose in Rats to Enhance the Analgesic Responses.

In this study, an in situ gel-forming chitosan hydrogel was prepared with the use of glutamate salt of chitosan (Ch-Ga), β-glycerophosphate (Gp), and morphine (Mor). The paper is focused on in vitro physicochemical properties and in-vivo analgesic effects of the prepared chitosan hydrogel. The thermosensitive properties of prepared chitosan hydrogel were evaluated during the different temperatures and times. The physicochemical properties of chitosan hydrogel were investigated by infrared (IR) spectroscopy and X-ray diffraction analysis (XRD). Also, its cell cytotoxicity effects were evaluated in murine NIH/3T3 normal cells. Subsequently, the distribution of chitosan hydrogel in the nasal cavity of rats and its analgesic responses were evaluated. The prepared chitosan hydrogel showed that it could be gelled at the temperature of 34 °C before leaving the nose in the shortest possible time of 30 s. The analgesic responses of the intranasal (IN) injection of chitosan hydrogel (IN-chitosan hydrogel, 10 mg Mor/kg) in a single unit dose in rat relative to the placebo and intranasal or intraperitoneal (IP) injection of free morphine solution (IN-Free Mor or IP-Free Mor, 10 mg Mor/kg) via the hot plate test, reveal that the IN-chitosan hydrogel could induce fast analgesic effects of morphine with maximum possible effect (MPE) of 93% after 5 min compare to the IN-Free Mor and IP-Free Mor with MPE of 80% after 15 min and 66% after 30 min, respectively. Also, prolonged analgesic effects with MPE of 78 % after 6 h of injection were only seen in the IN-chitosan hydrogel injected group. The obtained fluorescent images of rat's brain injected with IN-chitosan hydrogel containing doxorubicine (Dox) as a fluorescent agent showed that the mucosal adhesive and absorption enhancer properties of IN-chitosan hydrogel resulting in longer presence of them in the nasal cavity of rats followed by more absorption of Dox from the blood vessels of olfactory bulbs with a 74% color intensity compared to the IN-Free Mor and IN-Free Dox with 15%. These data reveal that the IN-chitosan hydrogel could induce fast and prolonged analgesic effects of morphine compare to the IN/IP-Free Mor, which could be considered as an in situ gel-forming thermosensitive chitosan hydrogel for nasal delivery of wide ranges of therapeutic agents.

Amphiphilic NLC-Gel formulation loaded with Sebacoyl dinalbuphine ester and Nalbuphine for localized postoperative pain management

Opioids are powerful analgesics; however, their significant systemic adverse effects and the need for frequent administration restrict their use. Nalbuphine (NA) is a κ-agonist narcotic with limited adverse effects, but needs to be frequently administrated due to its short elimination half-life. Whereas sebacoyl dinalbuphine ester (SDE) is a NA prodrug, which can effectively prolong the analgesic effect, but lacks immediate pain relief. Therefore, in this study, a rapid and sustained local delivery formulation to introduce NA and SDE directly into surgical sites was developed. An amphiphilic nanostructured lipid carrier (NLC) poloxamer 407 (P407) gel (NLC-Gel) was developed to permit concurrent delivery of hydrophobic SDE from the NLC core and hydrophilic NA from P407, offering a dual rapid and prolonged analgesic effect. Benefiting from the thermal-sensitive characteristic of P407, the formulation can be injected in liquid phase and instantly transit into gel at wound site. NLC-Gel properties, including particle size, drug release, rheology, and stability, were assessed. In vivo evaluation using a rat spinal surgery model highlighted the effect of the formulation through pain behavior test and hematology analysis. NLC-Gels demonstrated an analgesic effect comparable with that of commercial intramuscular injected SDE formulation (IM SDE), with only 15 % of the drug dosage. The inclusion of supplemental NA in the exterior gel (PA12-Gel + NA) provided rapid drug onset owing to swift NA dispersion, addressing acute pain within hours along with prolonged analgesic effects. Our findings suggest that this amphiphilic formulation significantly enhanced postoperative pain management in terms of safety and efficacy.

General anesthesia with local infiltration reduces urine retention rate and prolongs analgesic effect than spinal anesthesia for hemorrhoidectomy.

Postoperative pain and complications pose significant challenges following a hemorrhoidectomy. Attaining effective anesthesia with minimal complications is crucial. The ideal anesthesia method for ambulatory hemorrhoidectomy remains uncertain. This study aimed to investigate whether the combination of general anesthesia plus local infiltration (GAL) is associated with lower complications and reduced pain compared to spinal anesthesia (SA) in the context of hemorrhoidectomy. This retrospective single-center cohort study, conducted in a tertiary medical center in East Asia, evaluated excisional hemorrhoidectomies performed between January 1, 2017, and March 31, 2023, utilizing GAL or SA. Data on the six most common complications-pain, constipation, acute urine retention (AUR), bleeding, nausea, and headache-were extracted from medical records. A total of 550 hemorrhoidectomies were included: 220 in the GAL group and 330 in the SA group. Patient characteristics were comparable between the two groups. The AUR rate was significantly lower in the GAL group compared to the SA group (15.5% vs. 32.1%, P < 0.001). Although the proportion of pain scores ≥4 did not differ significantly between the GAL and SA groups (36.2% vs. 39.8%, P = 0.429), the pain score curve indicated a stable trend. Overall, the GAL group exhibited a lower rate of adverse effects (56.9% vs. 67.4%, P = 0.023). There were no significant differences in the rates of other complications and emergency department readmission between the GAL and SA groups. GAL emerges as a favorable choice for anesthesia in hemorrhoidectomy, demonstrating a lower incidence of urine retention and a prolonged analgesic effect in multiple hemorrhoidectomies. These findings support the conclusion that GAL represents an optimal anesthetic method for enhancing the postoperative experience in patients undergoing hemorrhoidectomy.

Superior analgesic efficacy of preemptive low-dose ketorolac compared with parecoxib after total knee arthroplasty: A retrospective propensity score matching study.

Total knee arthroplasty (TKA) is a routine orthopedic procedure often associated with significant postoperative pain. Efficient pain management is paramount for patient recovery, with nonsteroidal anti-inflammatory drugs (NSAIDs) being a common choice. Nevertheless, the specific NSAID and its dosing regimen can have varying impacts on outcomes. In this retrospective cohort study spanning from January 2016 to December 2020, we analyzed patients who underwent TKA. These patients were divided into two groups: one receiving preemptive low-dose ketorolac (15mg) followed by 15mg every 6h for 48h, and the other receiving parecoxib (40mg) every 12h for the same duration. We assessed pain scores, opioid consumption, and monitored adverse events. Our findings reveal that ketorolac yielded superior results compared to parecoxib. Specifically, patients receiving ketorolac reported significantly lower Visual Numeric Rating Scale (VNRS) scores at 8- and 20-h post-surgery. This trend was further confirmed by linear mixed models (p = .0084). Additionally, ketorolac was associated with reduced opioid consumption during the initial 24h. Importantly, the rates of adverse events were comparable between the two groups. The utilization of preemptive low-dose ketorolac demonstrates promising potential in bolstering pain control within the initial 24h post-TKA, potentially reducing the need for opioids. However, further exploration is required to thoroughly assess its prolonged analgesic effects and safety across various surgical contexts. These investigations could provide invaluable insights for optimizing pain management protocols.

Amphiphilic block copolymers bearing fatty acid derivatives as vehicles for THC in the development of analgesic oral formulations

Cannabis-based therapeutics have gained increasing attention for their potential health benefits; however, the efficient administration of hydrophobic constituents such as Δ9-tetrahydrocannabinol (THC) remains a challenge. This study explores a novel approach employing amphiphilic block copolymers to encapsulate a THC-rich extract to enhance its analgesic effect. The synthesis of amphiphilic block copolymers involves sequential ring-opening polymerization of caprolactone and a cyclic carbonate with pedant alkyne moieties. This is followed by an alkyne/azide click reaction with fatty acid derivatives. These copolymers are used to encapsulate the THC-rich extract. These extract-loaded micelles exhibit nanometric sizes, uniform distribution, and high colloidal stability in simulated gastrointestinal fluids. The release kinetic assessment of THC from the micelles displays controlled and sustained profiles, which are influenced by the hydrophobic nature of the copolymer core. In vivo evaluations using a murine model revealed the safety of micellar formulations, with minimal impact on behavior and organ health. Remarkably, micellar systems demonstrated prolonged analgesic effects in both mechanical and chemical pain models, outperforming nonencapsulated THC. This study introduces a pioneering approach to cannabis-based analgesics with prolonged activity, harnessing the potential of the tailored design of amphiphilic block copolymers to enhance the delivery and efficacy of hydrophobic cannabinoids.

Transcutaneous electrical acupoint stimulation for cancer-related pain management in patients receiving chronic opioid therapy: a randomized clinical trial.

The opioid crisis resulting from its use disorder and overdose poses additional challenges for cancer pain management. The American Society of Clinical Oncology Practice Guideline recommends acupuncture therapy for the management of adult cancer-related pain (CRP), but the effectiveness of transcutaneous electrical acupoint stimulation (TEAS) on CRP remains uncertain. This 5-week prospective randomized clinical trial was conducted at 2 hospitals in China, and participants with CRP receiving chronic opioid therapy were randomized 1:1 into two groups between December 2014 and June 2018. The true TEAS group underwent 15 sessions of TEAS treatments over 3 consecutive weeks, while the control group received sham stimulation. The primary outcome was the numerical rating scale (NRS) score in the past 24h at week 3. The secondary outcomes included morphine equivalent daily dose, quality of life and adverse events. A total of 159 participants were included in the modified intention-to-treat population. The baseline characteristics were similar in both groups. The mean NRS scores were 0.98 points at week 3 in the true TEAS group and 1.41 points in the sham group, with the mean difference between groups of -0.43 points (P < 0.001; OR = 0.68, P < 0.05). The proportion of patients with NRS reduction more than thirty percentage at week 3 was 50.00% in the true TEAS group and 35.44% in the sham group (RD = 0.15, P > 0.05; RR = 1.41, P > 0.05). No significant difference in pain intensity between the two groups was observed during the follow-up period without TEAS intervention (week 4, OR = 0.83, P > 0.05; week 5, OR = 0.83, P > 0.05). The Karnofsky Performance Status value suggested that patients in the true TEAS group experienced an improved quality of life (Between-group differences: week 3, 3.5%, P < 0.05; week 4, 4.6%, P < 0.001; week 5, 5.6%, P < 0.001). The 3-week application of TEAS in patients with CRP receiving chronic opioid therapy resulted in a statistically significant reduction in pain scores, but the observed reduction was of uncertain clinical significance. The prolonged analgesic effect of TEAS was not confirmed in this trial. GOV: ChiCTR-TRC-13003803.

Ultrasound-guided platelet-rich plasma injection versus steroids injection for pain relief in partial rotator cuff tears

ABSTRACT Background Platelet-rich plasma injection has become an effective treatment for partial rotator cuff tears. This study evaluates the efficacy of PRP versus steroids injection in pain relief for partial rotator cuff tears. Study design Prospective clinical trial. Setting Alexandria Main University Hospital. Patients and methods Sixty patients with symptomatic partial RCTs undergoing US-guided subacromial injection were randomly allocated into two equal groups: either steroids or PRP. Pain score, shoulder function, failure rate after injection, and complications were recorded. Results VAS score was significantly lower in the steroid group at week 2 follow-up than the PRP group (p 0.001). However, it was shorter, extended for 8 weeks in steroid in comparison to 4 months in PRP group. There was an insignificant difference among groups in the simple shoulder test at 2 and 4 weeks follow-up, and the test was significantly higher in PRP group at 6, 8, 12 weeks, and 4 month follow-up (P = 0.049, 0.001, 0.001, 0.001). Pain did not improve in six patients in steroid group and one patient in PRP group. Pain on injection was reported by six patients in the steroid group and 13 patients in PRP group (p = 0.052). Elevated blood sugar was significantly higher in the steroid group after the injection (p 0.001). Conclusion Subacromial PRP injection may have a prolonged analgesic effect and superior shoulder functional improvement than steroids in patients with partial RCTs.

Electroacupuncture exerts prolonged analgesic and neuroprotective effects in a persistent dental pain model induced by multiple dental pulp injuries: GABAergic interneurons-astrocytes interaction.

Pain within the trigeminal system, particularly dental pain, is poorly understood. This study aimed to determine whether single or multiple dental pulp injuries induce persistent pain, its association with trigeminal central nociceptive pathways and whether electroacupuncture (EA) provides prolonged analgesic and neuroprotective effects in a persistent dental pain model. Models of single dental pulp injury (SDPI) and multiple dental pulp injuries (MDPI) were used to induce trigeminal neuropathic pain. The signs of dental pain-related behavior were assessed using the mechanical head withdrawal threshold (HWT). Immunofluorescence and western blot protocols were used to monitor astrocyte activation, changes in apoptosis-related proteins, and GABAergic interneuron plasticity. SDPI mice exhibited an initial marked decrease in HWT from days one to 14, followed by progressive recovery from days 21 to 42. From days 49 to 70, the HWT increased and returned to the control values. In contrast, MDPI mice showed a persistent decrease in HWT from days one to 70. MDPI increased glial fibrillary acidic protein (GFAP) and decreased glutamine synthetase (GS) and glutamate transporter-1 (GLT1) expression in the Vi/Vc transition zone of the brainstem on day 70, whereas no changes in astrocytic markers were observed on day 70 after SDPI. Increased expression of cleaved cysteine-aspartic protease-3 (cleaved caspase-3) and Bcl-2-associated X protein (Bax), along with decreased B-cell lymphoma/leukemia 2 (Bcl-2), were observed at day 70 after MDPI but not after SDPI. The downregulation of glutamic acid decarboxylase (GAD65) expression was observed on day 70 only after MDPI. The effects of MDPI-induced lower HWT from days one to 70 were attenuated by 12 sessions of EA treatment (days one to 21 after MDPI). Changes in astrocytic GFAP, GS, and GLT-1, along with cleaved caspase-3, Bax, Bcl-2, and GAD65 expression observed 70 days after MDPI, were reversed by EA treatment. The results suggest that persistent dental pain in mice was induced by MDPI but not by SDPI. This effect was associated with trigeminal GABAergic interneuron plasticity along with morphological and functional changes in astrocytes. EA exerts prolonged analgesic and neuroprotective effects that might be associated with the modulation of neuron-glia crosstalk mechanisms.

Nanomaterial-Based Drug Delivery Systems for Pain Treatment and Relief: From the Delivery of a Single Drug to Co-Delivery of Multiple Therapeutics.

The use of nanomaterials in drug delivery systems for pain treatment is becoming increasingly common. This review aims to summarize how nanomaterial-based drug delivery systems can be used to effectively treat and relieve pain, whether via the delivery of a single drug or a combination of multiple therapeutics. By utilizing nanoformulations, the solubility of analgesics can be increased. Meanwhile, controlled drug release and targeted delivery can be realized. These not only improve the pharmacokinetics and biodistribution of analgesics but also lead to improved pain relief effects with fewer side effects. Additionally, combination therapy is frequently applied to anesthesia and analgesia. The co-encapsulation of multiple therapeutics into a single nanoformulation for drug co-delivery has garnered significant interest. Numerous approaches using nanoformulation-based combination therapy have been developed and evaluated for pain management. These methods offer prolonged analgesic effects and reduced administration frequency by harnessing the synergy and co-action of multiple targets. However, it is important to note that these nanomaterial-based pain treatment methods are still in the exploratory stage and require further research to be effectively translated into clinical practice.

Long-Circulating Lipid Nanospheres Loaded with Flurbiprofen Axetil for Targeted Rheumatoid Arthritis Treatment.

Flurbiprofen axetil (FA) is a non-steroidal anti-inflammatory drug with good analgesic and anti-inflammatory effects. However, it suffers from poor solubility, short circulation time, and off-target binding profile, which significantly limit its clinical application. Here, we loaded FA into stealth lipid microspheres modified with the arginine-glycine-aspartic acid (RGD) peptide (cRGD-FA-SLM), and examined the therapeutic potential of the resulting platform for the treatment of rheumatoid arthritis (RA). cRGD-FA-SLM was prepared by high pressure homogenization, and its toxicity and uptake by macrophages were examined using cultures of RAW264.7 cells. Hemolysis and hepatotoxicity tests were performed to assess the safety of the developed platform, while its pharmacokinetics, biodistribution, and therapeutic efficacy were investigated in a collagen-induced arthritis rat model. cRGD-FA-SLM showed homogeneous spherical morphology and efficient encapsulation of FA. The developed platform was non-toxic to normal macrophages and was selectively internalized by lipopolysaccharide-activated macrophages in vitro, while it distributed mainly to arthritic joints and significantly prolonged FA in circulation in vivo. cRGD-FA-SLM also significantly reduced the expression of prostaglandin E2 and alleviated joint edema and bone erosion, showing prolonged analgesic effects in arthritic rats. cRGD-FA-SLM shows good inflammation-targeting ability and prolongs drug circulation in vivo, suggesting promise as an anti-inflammatory and analgesic agent for targeted RA treatment.

Comparison of Ketamine, Clonidine, and Fentanyl as Anesthetics in the Pediatric Population: A Review of Literature

This literature review examines the evidence on the safety profile and effectiveness of various adjuncts, such as clonidine, fentanyl, and ketamine, in pediatric anesthesia. Several studies were reviewed to evaluate the duration and quality of analgesia provided by these adjuncts, as well as their adverse effects. The results showed that adding clonidine to bupivacaine significantly prolonged the mean duration of analgesia compared to the fentanyl and clonidine groups. Children in the clonidine group also experienced lower pain scores and required fewer rescue medications. Furthermore, clonidine exhibited a higher safety margin with a lower incidence of adverse effects, such as urinary retention and pruritus, compared to other adjuncts. Regarding comparisons between fentanyl and clonidine, intrathecal fentanyl resulted in a better hemodynamic profile but required more propofol for sedation. On the other hand, intrathecal clonidine provided a more favorable sedation level. Adverse events like respiratory obstruction and apnea were more likely associated with deep sedation caused by propofol rather than the specific properties of clonidine or fentanyl.&#x0D; In terms of ketamine versus clonidine, caudal blocks using ketamine were found to prolong postoperative anesthesia, particularly for lower limb and abdominal surgeries. When comparing the duration of caudal analgesia achieved by bupivacaine combined with different adjuncts, ketamine exhibited a longer duration compared to clonidine and adrenaline. However, ketamine use was found to be linked with a greater incidence of adverse effects, including urinary retention and pruritus.&#x0D; In conclusion, clonidine demonstrated a relatively higher safety margin with prolonged analgesic effects in pediatric anesthesia compared to fentanyl and ketamine. Its addition to local anesthetics resulted in extended analgesia duration and reduced rescue medication requirements without significant side effects. However, careful monitoring is necessary to manage potential adverse effects.

Efficacy of Oral Toradol (Ketorolac) Compared to Oral Tramadol as a Preemptive Analgesic in Impacted Third Molar Surgery.

To compare ketorolac with Tramadol as a preemptive analgesic in impacted third molar surgery in terms of mean pain score, mean time of first analgesic and mean total analgesic consumption postoperatively. Experimental study. Place and Duration of the Study: Department of Oral and Maxillofacial Surgery, Islamic International Dental Hospital, (IIDH) Riphah International University, Islamabad, from March 2018 to March 2020. Ninety-four patients, aged 18-45 years with impacted third molars were divided into two groups. Preoperatively oral tramadol 50 mg was given in group A and oral ketorolac 10 mg was given in group B. Pain score was measured 3 hours postoperatively, using the visual analogue scale (VAS), the time was noted for first analgesic consumption in hours and total consumption of analgesics. The mean postoperative pain was measured for both groups. Pain was significantly less in Group B. The mean pain score was 4.02+1.20 in group A and 3.42+1.08 in group B measured at 3 hours postoperatively (p=0.02). The mean time interval for 1st postoperative analgesic was 2.90+1.24 hours in group A and 3.61+1.02 in group B (p=0.007). The mean total analgesic consumption was 3.75+1.27 grams in Group A and 2.27+1.74 grams min Group B (p=0.006). Preemptive Ketorolac has a more prolonged analgesic effect as compared to tramadol. Preemptive analgesia, Tramadol, Ketorolac, Pain score, Third molar surgery.

Sustained release of levobupivacaine from temperature-sensitive injectable hydrogel for long-term local anesthesia in postoperative pain management

Postoperative pain is a major concern for most of the surgical patients, and an inadequate postoperative pain control may cause a series of complications. With an effective pain control and lesser side effects, local anesthetics are preferred for use in postoperative pain management. However, the action duration of current local anesthetics is too short to meet the requirements of postoperative analgesia. In this study, an injectable levobupivacaine (LB)-loaded thermo-sensitive hydrogel system based on biodegradable poly(D,L-lactide)-poly(ethylene glycol)-poly(D,L-lactide) (PLEL) was developed for long-acting local anesthetic, in which the soluble charged cation form of LB (LB HCl) was partly alkalified to the poorly soluble base form (LB base). This hybrid LB loaded PLEL system (hLB/PLEL) is a free flowable liquid at room temperature and changes into a semi-solid hydrogel once injection in response to the physiological temperature. Then, the dissolved LB HCl could release firstly from the hydrogel contributing to a quick work, and the insoluble LB base dissolved and released gradually as the decrease of the pH during the biodegradation of PLEL hydrogel, resulting in a long-term LB release in local. The drug release behavior, pharmacokinetic, and biocompatibility of the thermo-sensitive hLB/PLEL were studied in vitro and in vivo. The anesthetic effects of hLB/PLEL system were evaluated in the rat models of sciatic nerve block, subcutaneous infiltration anesthesia and postoperative pain as well. This hLB/PLEL system generated a significantly prolonged analgesic effect in rat models, which produced approximately 7 times longer duration than 0.75% LB HCl and effectively relieved the spontaneous pain for 3 days. In general, the presented hLB/PLEL system can not only achieve a fast-acting but also sustainably release LB to block the nerve and significantly extend the effect of local analgesia, which means a promising candidate for long-acting postoperative pain management.

Comparative Outcome of Lidocaine Versus Bupivacaine for Cervical Medial Branch Block in Chronic Cervical Facet Arthropathy: A Randomized Double-Blind Study

This study evaluated the effect of prolonged concordant response and functional clinical improvement between lidocaine and bupivacaine for cervical medial branch block (CMBB) in chronic cervical facet syndrome. Sixty-two patients diagnosed with chronic cervical facet syndrome were randomized into either lidocaine or bupivacaine groups. The therapeutic CMBB was performed under ultrasound guidance. Either 2% lidocaine or 0.5% bupivacaine with a volume of 0.5-1 ml per level, according to the patient's pain symptoms. The patients, pain assessor, and pain specialist were blinded. The primary outcome was the duration of pain reduction by at least 50%. The numerical rating scale (NRS) of 0-10 and the Neck Disability Index (NDI) questionnaire were recorded. There was no significant difference in the duration of 50% and 75% pain reduction and NDI between the lidocaine and bupivacaine groups. Lidocaine provided significant pain reduction up to 16 weeks (P<0.05) and significant improvement in neck functional outcomes up to 8 weeks (P<0.01) compared to the baseline. Whist bupivacaine yielded significant pain alleviation for up to 8 weeks for pain upon neck mobilization (P<0.05) and demonstrated notable improvement in neck function up to 4 weeks (P<0.01) compared to the baseline. CMBB using lidocaine or bupivacaine provided clinical benefits in prolonged analgesic effect and improving neck functions for chronic cervical facet syndrome. Lidocaine illustrated better performance and could be considered a local anesthetic of choice regarding the prolonged concordance response.

The use of the combined anesthesia method using local anesthesia and percutaneous electroneurostimulation for dental implantation

The purpose of the work: to conduct a comparative assessment of the adequacy of pain relief based on the study of the dynamics of pain indicators, the autonomic nervous system and the psycho-emotional status of patients with a combination of local anesthesia and percutaneous electroneurostimulation.&#x0D; Materials and methods. 40 patients aged 38 to 63 years took part in the study. The number of patients in the first group amounted to 20 people aged 38 to 63 years, and they all completed the study. In the first group, only local anesthesia (MA) was used by a 4% solution of articaine with epinephrine in a concentration of 1: 200000. In the second group, the number of patients was 20 people aged 38 to 60 years, and all of them also completed the study. In the second group — a combination of percutaneous electroneurostimulation (Chens) with subsequent local anesthesia (Chens+Ma); Electroneurostimulation was carried out using the EPB50-01 Electronics device (Russia), which generates bipolar asymmetric current pulses of 20 s and a frequency of 10 imp/s. The intensity of electroneurostimulation was selected individually until the patient achieve intense non -pain sensations.&#x0D; Results. The use of percutaneous electroneurostimulation potentiates the analgesic effect of local anesthesia in the intraoperative period and has a prolonged analgesic effect, which manifests itself in a decrease in the intensity of pain throughout the postoperative period. Analysis of the features of the action of percutaneous electroneurostimulation indicates that this effect is due to exacerbation of not pain sensitivity, but by sensitization (exacerbation of sensitivity) of non -column peripheral nerves and oral trigeminal core, transmitting signals from receptors that are excited with no damaging effects (touches, displacement of tissues). This sensitization can develop as a result of prolonged preliminary electroneurostimulation, which was carried out before the injection. Against the background of sensitization of sensation from any mechanical effects on the tissue, more acute will be perceived, which was evaluated by patients as more intense pain. This feature of the action of percutaneous electroneurostimulation must be taken into account when compiling methods of its application in clinical practice.&#x0D; Conclusion. The use of percutaneous electroneurostimulation creates favorable conditions for the period of adaptation and integration of implants in the early stages of the postoperative period.

Neuronal Nitric Oxide Synthase Suppression Confers the Prolonged Analgesic Effect of Sciatic Nerve Block With Perineural Dexamethasone in Postoperative Pain Model Mice

Dexamethasone supplementation to local anesthetics prolongs its action, yet the underlying mechanism is unclear. Previous studies have reported that increased p-p38 mitogen-activated protein kinase (MAPK) in the dorsal root ganglia (DRG) is associated with pain-associated behavior and that nitric oxide (NO), which is known to be a pronociceptive substance, directly inhibits sciatic nerve conduction. Here, we investigated the temporal changes in the hyperalgesic effect and p-p38 MAPK and NO synthase (NOS) expression levels in the DRG when dexamethasone was added to ropivacaine used for a sciatic nerve block (SNB) in postoperative pain model mice. Dexamethasone supplementation to ropivacaine significantly prolonged the analgesic effect of SNB via glucocorticoid receptor activation. Histological examination revealed that ropivacaine suppressed p-p38 MAPK expression in the DRG regardless of dexamethasone supplementation, suggesting that p-p38 MAPK was not involved in the prolonging effect of dexamethasone on nerve block. Contrastingly, plantar incision markedly increased the expression of neuronal NOS (nNOS) in DRG, and dexamethasone supplementation to ropivacaine significantly suppressed nNOS expression. Supplementation of L-NAME, an inhibitor of NOS, to ropivacaine markedly prolonged the effect of SNB, similar to dexamethasone. These results suggest that dexamethasone supplementation to local anesthetics prolongs the analgesic effect by inhibiting nNOS activity. PerspectiveThe current study revealed that dexamethasone supplementation to local anesthetics prolongs the analgesic effect by inhibiting the activity of neuronal NOS and that p-p38 MAPK may not be involved in this phenomenon. Our findings offer a new target for the discovery of long-acting local anesthetics.

Preparation and evaluation of liposome with ropivacaine ion-pairing in local pain management

Local analgesia is one of the most desirable methods for postoperative pain control, while the existing local anesthetics have a short duration of analgesic effect. Nano-drug carriers have been widely used in various fields and provide an excellent strategy for traditional drugs. Although the existing liposomes for local anesthetics have certain advantages, their instability and complexity of the preparation process still cannot be ignored. Here, we developed novel ropivacaine hydrochloride liposomes with improved stability and sustained release performance by combining ropivacaine hydrochloride with sodium oleate in liposomes via hydrophobic ion-pairing (HIP). The liposomes are easy to prepare, inexpensive, and suitable for mass production. The infrared (IR), particle size, and Zeta potential measurements adequately characterized the complex, which showed a diameter of 81.09 nm and a zeta potential of −83.3 mV. Animal behavioral experiments, including the hot plate test and von Frey fiber test, demonstrated that the liposome system had a prolonged analgesic effect of 2 h versus conventional liposome preparations, consistent with the results of in vitro release experiments. In addition, in vitro cytotoxicity evaluations in RAW264.7 cells and in vivo evaluations revealed the biocompatibility and safety of the ropivacaine-sodium oleate ion-paired liposome (Rop-Ole-Lipo) system as a suitable local anesthetic for local pain management. Our findings provide a new idea for the preparation of local anesthetics.

Opioid-Free Labor Analgesia: Dexmedetomidine as an Adjuvant Combined with Ropivacaine.

Background Side effects of the use of opioid analgesics during painless delivery are the main factors that affect rapid postpartum recovery. Opioid use can result in dangerous respiratory depression in the patient. Opioids can also disrupt the baby's breathing and heart rate. The nonopioid analgesic dexmedetomidine, a new a2-adrenergic agonist, possesses higher selectivity, greater analgesic effects, and fewer side effects. Moreover, epidural administration of dexmedetomidine also reduces local anesthetic consumption. Objective Our study aims to compare the analgesic effects as well as the side effects of ropivacaine with dexmedetomidine against sufentanyl as an epidural labor analgesia. Methods This study is a randomized, double-blinded, controlled trial (registration no. ChiCTR2200055360) involving 120 primiparous (a woman who has given birth once), singleton pregnancy women who are greater than 38 weeks into gestation and have requested epidural labor analgesia. The participants were randomized to receive 0.1% ropivacaine with sufentanyl (0.4 μg/ml) or dexmedetomidine (0.4 μg/ml). The primary outcomes included Visual Analogue Score (VAS), duration of first epidural infusions, the requirement of additional PCEA bolus, and adverse reactions during labor analgesia. Results Of the 120 subjects who consented, 91 parturient women (women in the condition of labor) had complete data for analysis. Demographics and VAS, as well as maternal and fetal outcomes, were similar between the groups. The duration of first epidural infusions in dexmedetomidine was significantly longer than sufentanyl (median value: 115 vs 68 min, P < 0.01); the parturient women who received dexmedetomidine and who required additional PCEA bolus were fewer in comparison to those who received sufentanyl (27.5% vs 49.0%, P < 0.05). Furthermore, the incidence of pruritus in the dexmedetomidine group was lower in comparison to the sufentanyl group (0% vs 11.8%, P < 0.05). Conclusions Dexmedetomidine, a nonopioid, is superior to the opioid analgesic sufentanyl in providing a prolonged analgesic effect as an epidural during labor. It also reduces local anesthetic consumption and has fewer side effects. The trial is registered with ChiCTR2200055360.