Analgesic Effect Research Articles

Treatment of trigeminal neuralgia by acupuncture combined with Chinese medicine from the perspective of modern medicine: A review.

Trigeminal neuralgia (TN) is characterized by recurrent episodes of transient severe pain in its distribution area, with abrupt onset and termination. With the progression of the disease, patients are prone to concurrent psychiatric disorders, such as anxiety and depression, which seriously affect patients' quality of life. Currently, anticonvulsant drugs are commonly used in clinical practice as the primary treatment, but long-term use of drugs is prone to drug resistance, limiting clinical application. Acupuncture and traditional Chinese medicine (TCM), as alternative and complementary therapies, can make up for the deficiencies in modern medicine and are accepted by patients with the advantages of safety and effectiveness. TCM therapy works by promoting the release of endogenous opioid peptides, adjusting the level of inflammatory factors, and improving negative emotions to exert analgesic effects. This paper discusses the clinical efficacy and safety of acupuncture combined with Chinese medicine in the treatment of TN from the perspective of modern medicine and provides a theoretical basis for seeking better therapeutic targets.

Intraoperative Non-Opiate Anesthesia for Patients Undergoing Arthroscopic Temporomandibular Joint Surgery: A Randomized Controlled Trial.

Pain intensity after temporomandibular joint (TMJ) surgery is often underestimated, and inadequate pain control may relate to poor recovery quality, increased opioid consumption, and longer hospital stay. This trial aims to evaluate whether non-opiate anesthesia provides a promising option of pain management for patients undergoing TMJ surgery. Sixty patients receiving TMJ surgery were randomly assigned to either the control group or the non-opiate group. Non-opiate anesthesia used lidocaine, dexmedetomidine, and ketamine infusion therapy for pain management. The primary outcome was the highest documented pain score while in the post-anesthesia care unit (PACU). Secondary outcomes included perioperative opioid consumption, utilization, dosage, and timing of rescue analgesia in the PACU, incidence of postoperative nausea and vomiting in the PACU and at home, pain satisfaction levels, occurrence of opioid-related adverse effects, duration of PACU and hospital stays, and total consumption of oxycodone-acetaminophen tablets at 24 and 48hours post-surgery. Patients were predominantly female (88.3%) and had a median age of 37.5 [IQR 26.0, 52.5] years. There were no significant differences observed in the highest documented pain scores (mean difference [MD] -0.36 points, 95% CI: -1.84, 1.12, p = 0.63), postoperative oxycodone-acetaminophen consumption (MD 6.68 mg, 95% CI: -2.48, 15.84, p = 0.15), pain satisfaction (odds ratio [OR] 0.81, 95% CI: 0.23, 2.81, p = 0.74), time to PACU discharge (hazard ratio [HR] 1.24, 95% CI: 0.67, 2.30, p = 0.49) or time to hospital discharge (HR 1.48, 95% CI: 0.80, 2.75, p = 0.21) between the two groups. Similarly, no significant difference was observed in time to rescue analgesia, calculated in minutes from the end of surgery (HR 1.69, 95% CI: 0.79, 3.61, p = 0.18). Non-opiate anesthesia for pain management shows a similar postoperative analgesia effect, compared to opioid-based anesthesia, in patients undergoing arthroscopic TMJ surgery.

Comparison of the effectiveness of subcostal transversus abdominis plane and rectus sheath blocks in postoperative analgesia in major open gynecological cancer surgeries: a prospective randomized study.

The transversus abdominis plane block (TAPB) is frequently used for postoperative analgesia in abdominal surgery. However, it remains insufficient for analgesia during upper abdominal surgeries. Therefore, we compared the efficacy of the subcostal transversus abdominis plane block (STAPB) or rectus sheath block (RSB), in addition to the posterior transversus abdominis plane block (PTAPB), for postoperative analgesia in major gynecologic cancer surgeries. This prospective randomized study included 50 patients aged > 18 years (American Society of Anesthesiologists physical status II or III), who underwent gynecologic cancer surgery through a midline incision. All patients underwent PTAPB, STAPB, or RSB according to the randomization. The following parameters were recorded and compared: demographic data; intraoperative hemodynamic parameters; numeric rating scale (NRS) pain levels at the 1st, 6th, 12th, and 24th postoperative hours; opioid consumption; number of requests and boluses; adverse effects; surgical complications within 24 h. Forty-seven patients were included in this study. In the STAPB group, postoperative 1, 12 and 24 h NRS values were lower; opioid consumption, opioid demand, and bolus numbers were lower during the postoperative 24 h as compared to RSB (P < 0.05). The intraoperative opioid and hemodynamic values were similar in both groups. STAPB in addition to PTAPB provides more effective analgesia than RSB for postoperative pain management in open gynecologic cancer surgeries.

Comparison of Ultrasound-Guided Single-Injection Erector Spinae Plane Block, Retrolaminar Block and Paravertebral Block for Postoperative Analgesia in Single-Incision Video-Assisted Thoracoscopic Surgery: A Three-Arm, Double-Blind, Randomized Controlled Non-Inferiority Trial.

Effective postoperative analgesia is critical for thoracic surgery. This study compares the analgesic efficacy of the erector spinae plane block (ESPB), retrolaminar block (RLB), and paravertebral block (TPVB) in single-incision video-assisted thoracoscopic surgery (SITS). Seventy-six patients underwent general anesthesia followed by ultrasound-guided nerve blocks with 20mL of 0.5% ropivacaine. Primary outcomes included the area under the curve (AUC) of Numeric Rating Scale (NRS) scores during rest and coughing over 24 hours. Secondary outcomes included perioperative opioid use, plasma biomarkers, and postoperative recovery measures. The AUC for NRS was 107.8±10.53 in the ESPB group, 104.8±8.05 in the RLB group, and 103.6±10.42 in the TPVB group, demonstrating non-inferiority for ESPB (difference: 4.2±3.0, 95% CI -1.82 to 10.22) and RLB (difference: 1.2±2.6, 95% CI -3.97 to 6.37) compared to TPVB. No significant differences were observed in opioid use, plasma biomarkers, QoR-15 scores, or adverse events. ESPB and RLB provide non-inferior analgesia compared to TPVB in SITS patients and are effective alternatives that enhance safety.

COMPARISON OF TWO DIFFERENT DOSES OF ORAL GABAPENTIN FOR POST OPERATIVE ANALGESIA IN LOWER LIMB SURGERY UNDER SPINAL ANAESTHESIA

Background: Pre-emptive analgesia is a technique of pain control where treatment is initiated before intervention and operational during the surgical procedure in order to reduce the physiological consequences of nociceptive transmission provoked by the procedure. Gabapentin has demonstrated analgesic effects in clinical trials as a preemptive analgesic in acute postoperative pain management with very few side effects. Owing to the protective effect of gabapentin on the nociceptive pathways, preemptive analgesia has the potential to be more effective and hence reduce postoperative pain and development of chronic pain. Objective: We therefore designed this study to compare two different doses of Oral Gabapentin (300mg and 600mg) given as pre-emptive analgesic for post-operative pain relief in lower limb surgeries under spinal anaesthesia. Method: After the approval from ethical committee this prospective randomized double blinded clinical study was conducted over a period of two years in department of anaesthesia in M.G.M.s medical college, Aurangabad. Randomly allocated two groups were given Oral Gabapentin 300mg and 600mg respectively, one hour prior to giving spinal anaesthesia for post operative analgesia in lower limb surgeries. Conclusion: There is no statistically significant difference between group G300 (gabapentin 300mg) and group G600 (gabapentin 600mg) regarding age, gender, duration of analgesia (i.e. demand for first rescue analgesic), total dose of analgesics in first twenty four hours after surgery, duration of sensory block (i.e. L1 regression), highest ramsay sedation score and VAS scores. No significant difference was seen in cases hemodynamic stability and incidence of side effects.

Post-Torakotomi Ağrı Sendromu: İnsidans, Nöropatik Bileşen ve Risk Faktörleri

Objective: Pain that recurs or persists at least two months after thoracotomy is defined as post-thoracotomy pain syndrome (PTPS), and neuropathic pain (NP) is expected to develop in approximately half of these patients. This study aimed to examine the frequency of PTPS, the neuropathic component of pain, and the effecting risk factors in patients who underwent thoracotomy. Methods: 862 patients who underwent thoracotomy were monitored between January 2010 and May 2013 at Gazi University Faculty of Medicine Hospital. The study continued with 277 patients who could be contacted by phone at least three months after the operation. In these patients, the presence of pain was questioned, if present, the severity of pain, NP and affecting risk factors were investigated. The pain severity and NP component were evaluated using the Numeric Rating Scale (NRS) and Douleur Neuropathique 4 (DN4) questionnaires, respectively. Results: Severe PTPS frequency after thoracotomy was found to be 19.1 % and NP was present in 53% of patients with NRS 3-10. As the severity of pain increased, the frequency of NP and analgesic drug consumption increased (p&lt;0.05). As risk factors gender, age, operation duration and epidural analgesia application did not significantly affect the frequency and severity of PTPS and NP. As the time after the operation increased; PTSP frequency, neuropathic pain frequency and pain intensity were decreased (p&lt;0.05). Conclusion: Severe PTPS is detected in approximately one in five patients who undergone thoracotomy and half of them had NP. The neuropathic component of pain increases as pain intensity increases and decreases as time passes after surgery. The development of PTPS and NP should be reduced by providing effective analgesia. Keywords: Thoracotomy, chronic pain, post-thoracotomy pain syndrome, neuropathic pain

The Effect of the Application of Adductor and Infiltration of Local Anesthetic Between the Popliteal Artery and Capsule of the Knee (IPACK) Block to Patients on Postoperative Recovery and Sleep Quality Following Total Knee Arthroplasty: a Randomized, Controlled Study

Aim: The adductor canal block (ACB) and IPACK (Infiltration of local anesthetic between the popliteal artery and capsule of the knee) block are motor protective blocks that provide effective analgesia and allow early ambulation. The aim of this study was to investigate the effect on postoperative recovery and sleep quality of patients applied with ACB and IPACK for total knee arthroplasty (TKA). Material and Method: This prospective, double-blinded, randomized, controlled study included 80 patients who underwent unilateral TKA under spinal anesthesia. The patients were separated as those applied with ACB+IPACK (Group ACB+IPACK, n=40) and a control group (Group C, n=40). The primary outcome was the postoperative first-day quality of recovery scale (QoR-15). Secondary outcomes were postoperative first and second-day Timed-Up-and-Go (TUG) test and range of motion (ROM), the total amount of rescue opioid drugs required, pain scales at different time points in the first 48 hours postoperatively, sleep evaluation on the postoperative and 6 following nights, and evaluation of sleep quality for 1 month using the Pittsburgh Sleep Quality Index (PSQI). Results: The QoR on postoperative days 1 and 7 were better in the ACB+ IPACK group than in the control group (p= 0.001, p= 0.002, respectively). On postoperative days 1 and 2, the TUG (p= 0.035, p= 0.019, respectively) and ROM (p=0.003, p=0.000) values were higher in the ACB+ IPCAK group. Postoperative opioid consumption was lower in the ACB+IPACK group (p= 0.012). The PSQI values at 1 month postoperatively were similar in both groups (p =0.095). Conclusion: The study results demonstrated that ACB+IPACK applied with ultrasound for TKA postoperative analgesia provided effective analgesia, higher QoR and physical performance, and reduced postoperative opioid consumption. However, there was no effect on postoperative sleep quality.

Analgesic Effects of Methanol Leaf Extracts from Datura alba ness in Male Wistar Rats through Reduction of C-reactive Protein Levels

Introduction: The increasing interest in utilizing natural products from medicinal plants for pain management stems from their wide availability and minimal side effects. This study aims to evaluate the toxicity profile of Datura alba ness (DAN) extracts and assess their potential analgesic activity through preventive and therapeutic analgesia models in Wistar rats, as well as to investigate the possible mechanisms of action using molecular docking. Materials and Methods: Fresh leaves of DAN were collected from a garden in the Abua/Odua Local Government Area of Rivers State, Nigeria. The leaves were extracted using cold maceration to obtain ethanolic extracts of Datura alba ness (MEDAN). Twelve mice (19-30g) were used for toxicity study, while sixty Wistar rats (140-180g) were used for analgesic studies. Serum C-reactive protein levels were determined using ELISA methods, and molecular docking simulations were conducted using AutoDock and Discovery Studio Visualizer. Results: The results indicated that MEDAN was very safe, with an LD50 of 5000 mg/kg. The findings demonstrate that MEDAN significantly increased the pain threshold in male Wistar rats after three weeks of administration in a dose-dependent manner during the preemptive analgesia study, while pain thresholds increased within one hour but decreased over time in the therapeutic analgesia study. The combination of MEDAN with a standard drug (Flexicam) resulted in improved analgesic effects at the 500 mg/kg dose. Additionally, the study revealed that MEDAN significantly reduced serum C-reactive protein levels after three weeks of oral administration. Molecular docking studies indicated that stigmasterol, gamma-sitosterol, and cholest-5-en-3-ol, 24-propylidene-(3β) from MEDAN demonstrated binding affinity to C-reactive protein receptors, mimicking the effects of the reference drug, celecoxib. Conclusion: This study concludes that ethanolic extracts of Datura alba ness exhibited significant efficacy in pain reduction by lowering C-reactive protein levels. This effect was especially enhanced when the 500 mg/kg dose of MEDAN was combined with the standard drug, Flexicam. The findings provide a scientific basis supporting the traditional medicinal use of Datura alba ness for pain management.

The participation of monoamines in the realization of vasopressin analgesic effects during electrical stimulation of paws in rats

BACKGROUND: Arginine vasopressin has been implicated in the modulation of stress and pain. The influence of a synthetic analogue of arginine vasopressin, 1-deamino-8-D-arginine-vasopressin, оn pain sensitivity, stress reactivity, levels of monoamines and brain neurotrophic factor in a model of paw electrical stimulation in rats has not been studied. AIM: The aim was to evaluate the effect of a synthetic vasopressin analog, 1-deamino-8-D-arginine-vasopressin, on pain sensitivity and the content of norepinephrine, serotonin, dopamine, brain neurotrophic factor in the parietal cortex and spinal cord in electrocutaneous paw stimulation test in rats. MATERIALS AND METHODS: The study was conducted on male Wistar rats who were injected with 1-deamino-8-D-arginine-vasopressin intranasally once a day for 5 days in small (single 20 ng, course 100 ng) and large doses (single 2 ug, course 10 ug). The content of brain neurotrophic factor in the parietal cortex and spinal cord, and corticosterone in blood serum were determined using enzyme immunoassay. The levels of norepinephrine, serotonin, dopamine and their metabolites in the brain were evaluated using high-performance liquid chromatography. RESULTS: 1-Deamino-8-D-arginine-vasopressin in different doses reduced pain sensitivity in rats, more pronounced when administered in large doses. The peptide in small doses in the parietal cortex increased the content of dopamine and reduced the levels of 5-hydroxyindolacetic acid, a metabolite of serotonin; in the spinal cord, it reduced the content of 5-hydroxyindolacetic acid. 1-Deamino-8-D-arginine-vasopressin in high doses in the parietal cortex increased the content of dopamine and reduced the levels of 5-hydroxyindolacetic acid; in the spinal cord ― reduced the content of serotonin and 3,4-dihydroxyphenylacetic acid, a metabolite of dopamine; increased the levels of norepinephrine and homovanilic acid, a metabolite of dopamine. The peptide had no effect on corticosterone levels in the blood and brain neurotrophic factor levels in the brain in rats. CONCLUSIONS: The analgesic effects of 1-deamino-8-D-arginine-vasopressin were revealed with intranasal administration in different subendocrine doses. Regardless of the administered doses, dopamine and serotonin at the supraspinal level were involved in peptide-induced anesthesia; serotonin at the spinal cord level. More pronounced analgesia with the administration of 1-deamino-8-D-arginine-vasopressin in high doses was due to the additional involvement of dopamine and norepinephrine at the spinal cord level.

Is acetylsalicylic acid use in cats contraindicated or limited indicated?

Acetylsalic acid, (Aspirin®) is a nonsteroidal anti-inflammatory drug (NSAID) widely used in human and veterinary medicine, especially for its analgesic and antithrombotic effects, mainly in the prevention of cardiovascular complications and in the treatment of various diseases. Aspirin® can not be metabolized in cats because they do not have the enzyme glucuronyl transferase. For this reason, it has a long half-life and a narrow dose range. High dose administration in cats may cause serious toxicity in the liver. Acetylsalicylic acid is known to cause gastric ulcers associated with decreased prostaglandin levels. For these reasons, it is considered toxic to cats. But it also has antipyretic, analgesic, anti-inflammatory and antithrombotic properties. It is indicated for use alone or in combination with other antithrombotic drugs in the treatment and prophylaxis of thrombus formation resulting from cardiovascular diseases. This review aims to examine the indicated and contraindicated areas of use of Aspirin®, which is widely considered toxic in cats.

Discovery of ent-kaurane diterpenoid glucosides as potent analgesics from the leaves of Pieris formosa

To search for structurally novel analgesics from Ericaceae plants, the leaves of Pieris formosa collected at Yichang, Hubei, China, were phytochemically investigated for the first time. A total of fifteen ent-kaurane diterpene glucosides (1–15) including twelve new ones, named forminosides A–L (1–12), were isolated. Their structures were elucidated by comprehensive spectroscopic data analyses, quantum chemical calculations (13C NMR and ECD calculations and DP4+ analysis), and chemical methods. The absolute configures of 1–3, 5–8, 11, and 13 were further determined by single-crystal X-ray diffraction analysis. Forminoside A (1) represents the first 3α-(β-d-glucopyranosyloxy)-11,16-epoxy-ent-kaurane diterpenoid bearing a unique 12-oxa-pentacyclo[9.3.3.01,10.04,9.013,16]heptadecane core. Forminoside J (10) is the first 17-nor-ent-kaurane type diterpenoid from Ericaceae family, while forminoside L (12) represents the first example of 4,5-seco-ent-kaurane diterpenoid glycoside bearing an unusual α-hydroxyl-α,β-unsaturated ketone block. Notably, the structure of mollisside A was revised to 3β-(β-d-glucopyranosyloxy)-16β,17-dihydroxy-ent-kaurane based on the NMR and single-crystal X-ray diffraction data analysis of forminoside C (3). All the isolates 1–15 showed potent analgesic activity in the HOAc-induced writhing test in mice. Among them, compounds 1–3, 5–12, and 15 exhibited significant analgesic effects at a dose of 5.0 mg/kg with the inhibition rates over 50%. Compounds 1, 5, 7, and 9–12 still displayed significant analgesic effects with the inhibition rates exceeding 50% at a lower dose of 1.0 mg/kg. Forminosides J (10) and L (12) still showed significant analgesic potency even at a lower dose of 0.2 mg/kg, comparable to that of the positive control, morphine. This is first report of the analgesic activity of 11,16-epoxy-ent-kaurane diterpenoid. A preliminary structure–activity relationship was explored, providing new clues to design novel analgesics based on the ent-kaurane and related diterpenoids.

Multifunctional Analgesic Sutures from Microfluidic Spinning Technology.

Sutures are the most commonly used wound repair method after surgery. However, addressing delayed recovery and pain management remains a significant challenge. Here, microfibers are developed from microfluidic spinning with long-lasting analgesia capabilities for sutures. By using a solvent extraction manner, the polycaprolactone (PCL) microfibers encapsulated with ropivacaine (ROP), a well-known analgesic, can be continuously obtained from microfluidics. The intrinsic property of PCL and the advantage of microfluidic spinning technique impart the microfiber with highly controlled morphologies, mechanical strengths, as well as drug release. After exploring their biocompatibility both at in vitro and in vivo levels, the microfibers are directly applied to wound suture. The results demonstrate the lasting analgesic effect of the microfiber on mice with incision pain, highlighting its potential as promising suture for post-surgery treatments. It is anticipated that the multifunctional analgesic sutures produced through microfluidic spinning will pave the way for utilizing fibers as effective sutures in clinical incision wound treatment.

Paracetamol and ibuprofen fixed-dose combination for the management of acute mild-to-moderate pain in children: strengthening and enhancing of result of Nominal Group Technique through Delphi consensus

BackgroundParacetamol and ibuprofen are the most commonly used drugs for pain treatment in children and their combination has shown improved analgesic effect compared to treatment with either drug alone. Current literature lacks specific guidelines regarding the settings in which this combination should be adopted.MethodsThe survey, conducted with Delphi methodology, involved 75 hospital and outpatient pediatricians with clinical experience in the management of pain in children. Pediatricians involved were asked to validate or not the results of the previous NominalGroup Tecnique (NGT) consensus and thus specify the optimal clinical settings in which the paracetamol/ibuprofen fixed-dose combination could be adopted.ResultsThe results confirm the importance of the fixed-dose paracetamol and ibuprofen combination for the control of mild-to-moderate acute pain in children. Particularly, this association seems to be appropriate in case of headache, earache, odontalgia and musculoskeletal pain, and in specific settings such as post-operative and post-procedural pain. The broadening of the panel brought to slight variations in clinical management practices between hospital and outpatient specialists. Nonetheless, overall consensus supports the notion that the fixed dose combination is more efficacious than monotherapies and it is well tolerated. Moreover, experts unanimously agree on the usefulness of the combination for caregivers, leading to improved adherence and effectiveness.ConclusionsBoth the NGT consensus and the broader Delphi consensus confirm the usefulness of the paracetamol-ibuprofen fixed-dose combination in pediatric pain. This is attributed to its superior effectiveness compared to monotherapies, a good tolerability profile, and improved compliance and ease of use. Some pain settings related to chronic, inflammatory and rheumatological pathologies remain to be investigated to evaluate the use of this combination.

Quantitative Analysis, Anti-Inflammatory and Analgesic Effects of Ethanol Leaf Extract and Fractions of Microsorium scolopendria (Burm. f.) Copel. in Mice

Microsorium scolopendria, a fern was studied for phytochemicals, anti-inflammatory, and analgesic effects to add credence to its various folkloric applications. Phytochemicals were analyzed quantitatively, anti-inflammatory experiment was carried out with egg albumin- induced paw oedema and xylene-induced ear oedema models while analgesic effects were studied using formalin-induced paw licking, acetic acid-induced writhing and hot plate-induced pain models. The results revealed the presence of alkaloids, flavonoids, saponins, tannins, terpenoids, and phenols with alkaloids (14.6 %w/w) as the most predominant phytoconstituent. In anti-inflammatory experiments, M. scolopendria extract reduced oedema caused by egg albumin and xylene in a dose related manner and comparable to standard agents. Also, in analgesic experiments, the extract reduced pain induced by formalin, acetic acid, and hot plate. These reductions were statistically (p?0.05) significant. Considering the fractions in all experiments, butanol and ethyl acetate fractions were prominent in anti-inflammatory effect while ethyl acetate fraction was at top in reduction of pain. This study supports the use of M. scolopendria in ethnomedicinal practice.

Multimodal analgesics after adult cardiac surgery; a systematic review

Abstract Background Moderate to severe pain is frequently reported during the acute recovery phase following adult cardiac surgery. Multimodal analgesics are recommended for adult patients post cardiac surgery, but the optimal combination of multimodal analgesics is unknown. Purpose To synthesise the best available evidence about the effectiveness of multimodal analgesics on pain after adult cardiac surgery. Methods A systematic review was conducted according to the PRISMA-P statement and the published review protocol. Inclusion criteria were full-text papers or abstracts with adequate reporting, in any language, of randomised controlled trials (RCTs) in adult patients undergoing cardiac surgery that investigated the effect of multimodal postoperative analgesic regimens, compared to a control group. The highest mean level of patient self-reported pain intensity at rest, captured using a validated pain assessment tool, was the primary outcome measure. Results Of 3754 citations identified in the initial search to the 12th of December 2022, there were 1605 duplicates leaving 2149 citations for title and abstract screening, of which 2027 were irrelevant. There were 122 full-text papers assessed and 29 included in the review. Data were independently extracted by 2 reviewers in Covidence®. Participants (N = 2360), aged 59.5 + 8.2 years, were primarily male (N = 1561, 66.1%), weighing 78.1 +9.2 kilograms. Risk of bias was high and reporting quality was poor. Pain at rest reported in 18 (62%) studies was 3.5 (SD 1.2) in the control and 2.7 (SD 0.9) in the intervention groups respectively. Nurse-led versus patient-controlled analgesic administration was tested in 14 (48.3%) trials. All trials tested different analgesic combinations, none of which compared a combination of non-opioids, opioid agonist-antagonist agents, or full opioid agonists. Conclusions Poorly managed pain is associated with postoperative complications, unplanned readmissions, and the development of chronic pain. Robust RCTs are urgently needed to inform optimal combinations of multimodal analgesics to optimise patient recovery after adult cardiac surgery.Risk of Bias

Floral Elegance Meets Medicinal Marvels: Traditional Uses, Phytochemistry, and Pharmacology of the Genus Lagerstroemia L.

The genus Lagerstroemia L. (Lythraceae), known for its exquisite flowers and prolonged flowering period, is commonly employed in traditional medicinal systems across Asian countries, where it has always been consumed as tea or employed to address ailments such as diabetes, urinary disorders, coughs, fevers, inflammation, pain, and anesthesia. Its diverse uses may be attributed to its rich active ingredients. Currently, at least 364 biological compounds have been identified from Lagerstroemia extracts, encompassing various types such as terpenes, flavonoids, phenolic acids, alkaloids, and phenylpropanoids. Extensive in vitro and in vivo experiments have examined the pharmacological activities of different extracts, revealing their potential in various domains, including but not limited to antidiabetic, anti-obesity, antitumor, antimicrobial, antioxidant, anti-inflammatory, analgesic, and hepatoprotective effects. Additionally, 20 core components have been proven to be associated with antidiabetic and hypoglycemic effects of Lagerstroemia. Overall, Lagerstroemia exhibit substantial medicinal potential, and the alignment between its traditional applications and contemporary pharmacological findings present promising opportunities for further investigation, particularly in food and health products, drug development, herbal teas, and cosmetics. However, evidence-based pharmacological research has largely been confined to in vitro screening and animal model, lacking clinical trials and bioactive compound isolations. Consequently, future endeavors should adopt a more holistic approach.

A Pharmacokinetic Study of the Interaction Between Regorafenib and Paracetamol in Male Rats

Background: In clinical practice, the prevalent problem of polypharmacy could result in increased risks of drug–drug interactions. Regorafenib (REG) is commonly co-administered with paracetamol (PA) as a treatment protocol in cancer patients with pain therapy. Purpose: This study aimed to demonstrate the effect of paracetamol on the pharmacokinetic parameters of regorafenib and its metabolites following a single administration of both substances in rats. Additionally, the influence of REG and its metabolites on the pharmacokinetics of paracetamol was also determined. Methods: Twenty-four rats were divided randomly into three groups: REG group (IIREG, regorafenib 20 mg/kg, n = 8), PA group (IIIPA, paracetamol 100 mg/kg, n = 8), and REG+PA co-administration group (IREG+PA, REG 20 mg/kg and PA 100 mg/kg, n = 8). The concentrations of regorafenib, regorafenib-N-oxide (M-2), and N-desmethyl-regorafenib-N-oxide (M-5) were determined using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC–MS/MS). The plasma concentrations of PA and its glucuronide (GPA) and sulfate (SPA) metabolites were measured using the validated high-performance liquid chromatography method with ultraviolet detection (HPLC–UV). The pharmacokinetic parameters were calculated using a non-compartmental model. The statistical evaluation was performed in the SAS program. Results: After the administration of PA, the Cmax and AUC0–∞ of REG increased by 890% and 1140%, respectively; for M-2, they increased by 220% and 170%, and for M-5, by 2130% and 1730% (Cmax and AUC0–∞, respectively). A difference in the ratio of M-2/REG for AUC0–∞ and Cmax between the groups was observed, but not for M-5/REG. The AUC0–∞ for PA and GPA decreased by 20.7% and 51.1%, respectively, when PA was co-administered with REG. But the AUC0–∞ for SPA increased by 91.35% in the IREG+PA group. A difference in the ratio of GPA/PA for Cmax and for SPA/PA for AUC0–t and AUC0–∞ between the groups was observed. Conclusions: Paracetamol increased the plasma exposure of regorafenib, M-2, and M-5, which may exacerbate the drug’s side effects. In contrast, REG reduced paracetamol exposure and contributed to its faster elimination, which may reduce the analgesic and antipyretic effects of paracetamol. These findings suggest clinical relevance for oncology patients requiring analgesic treatment.

Thoracic Epidural and Analgesic Options After Failed Transversus Abdominus Plane Block With Liposomal Bupivacaine.

A 39 year-old female with a history of Roux-en-Y gastric bypass underwent emergent partial colectomy. Her postoperative analgesic management of a transversus abdominus plane block administered with a combination of bupivacaine and liposomal bupivacaine was ineffective. A bupivacaine thoracic epidural was then placed, which provided significant pain relief. This use of a bupivacaine thoracic epidural infusion following liposomal bupivacaine regional anesthesia demonstrated a case of effective analgesia without the development of local anesthetic systemic toxicity symptoms in a remote hospital setting, where certain laboratory analyses were not readily available.

A Biomimetic Nociceptor Based on a Vertical Multigate, Multichannel Neuromorphic Transistor.

Nociceptors, crucial sensory receptors within biological systems, are essential for survival in diverse and potentially hazardous environments. Efforts to replicate nociceptors through advanced electronic devices, such as memristors and neuromorphic transistors, have achieved limited success, capturing basic nociceptive functions while more advanced characteristics like various forms of central sensitization and analgesic effect remain out of reach. Here, we introduce a vertical multigate, multichannel electrolyte-gated transistor (Vm-EGT), designed to mimic nociceptors. Utilizing the hybrid mechanism combining electric-double-layer (EDL) with ion intercalation/deintercalation in EGTs, our approach successfully replicates peripheral sensitization and desensitization characteristics of nociceptors. The intricate multigate and multichannel design of the Vm-EGT enables the emulation of more advanced nociceptive functionalities, including central sensitization and analgesic effect. Furthermore, we demonstrate that by exploiting the inherent current-voltage relationship, the Vm-EGT can simulate these advanced nociceptive features and seamlessly transition between them. Integrating a Vm-EGT with a thermistor and a heating plate, we have developed an artificial thermal nociceptor that closely mirrors the sensory attributes of its biological counterpart. Our approach significantly advances the emulation of nociceptors, providing a basis for the development of sophisticated artificial sensory systems and intelligent robotics.

The effect of stretching intensity on pain sensitivity: A randomized crossover study on healthy adults.

Stretching exercises have effects on local and widespread pain sensitivity. A dose-response relationship may exist between the analgesic effect and the intensity of stretching, such that a higher intensity of stretching may generate a larger reduction in analgesic response, but this remains to be studied. This study aimed to examine the dose-response relationship between stretching intensity and the analgesic effect. A randomized, repeated-measures crossover study was performed to examine the effect of stretching to the first point of pain onset and stretching to the point of a sensation of stretching (discomfort). The primary outcome was regional and distant pressure pain thresholds. Thirty-one participants (n = 24 female) were available for analysis. We observed a 22.2% increase in regional pressure pain thresholds (93.2 kPa, p = 0.001) and a 15.0% increase in distant pressure pain thresholds (50.9 kPa, p = 0.012) following stretching to the point of stretch. We observed a 20.0% increase in regional pressure pain thresholds (90.3 kPa, p = 0.001) and a 15.1% increase in distant pressure pain thresholds (52.1 kPa, p = 0.004) following stretching to the point of pain. The results showed that local and widespread pain sensitivity decreased following acute stretching, regardless of stretching intensity. No differences in pain sensitivity were found between stretching to the point of stretch or stretching to the first onset of pain. Thus, the results showed no evidence of a dose-response relationship between stretching intensity and the analgesic effect. The study showed a significant acute hypoalgesic effect of stretching exercises regardless of stretching intensity. This may have appropriate clinical implications for patients with musculoskeletal and nociplastic pain.