Analgesic Effect Research Articles

Analgesic Effectiveness of Liposomal Bupivacaine versus Plain Local Anesthetics for Abdominal Fascial Plane Blocks: A Systematic Review and Meta-analysis of Randomized Trials.

Liposomal bupivacaine is reported to prolong the duration of analgesia when used for abdominal fascial plane blocks compared to plain local anesthetics; however, evidence from randomized trials is mixed. This meta-analysis aims to compare the analgesic effectiveness of liposomal bupivacaine to plain local anesthetics in adults receiving abdominal fascial plane blocks. Randomized trials comparing liposomal bupivacaine and plain (nonliposomal) local anesthetics in abdominal fascial plane blocks were sought. The primary outcome was area under the curve rest pain between 24 to 72 h postoperatively. Secondary outcomes included rest pain at individual timepoints (1, 6, 12, 24, 48, and 72 h); analgesic consumption at 0 to 24, 25 to 48, and 49 to 72 h; time to analgesic request; hospital stay duration; and opioid-related side effects. Data were pooled using the Hartung-Knapp-Sidik-Jonkman random effects method. Sixteen trials encompassing 1,287 patients (liposomal bupivacaine, 667; plain local anesthetics, 620) were included. The liposomal bupivacaine group received liposomal bupivacaine mixed with plain bupivacaine in 10 studies, liposomal bupivacaine alone in 5 studies, and both preparations in 1 three-armed study. No difference was observed between the two groups for area under the curve pain scores, with a standardized mean difference (95% CI) of -0.21 cm.h (-0.43 to 0.01; P = 0.058; I2 = 48%). Results were robust to subgroup analysis based on (1) potential conflict of interest and (2) mixing of plain local anesthetics with liposomal bupivacaine. The two groups were not different for any of the day 2 or day 3 secondary outcomes. This systematic review and meta-analysis suggests similar analgesic effectiveness between liposomal bupivacaine and plain local anesthetics when used for fascial plane block of the abdominal wall. The authors' analysis does not support an evidence-based preference for liposomal bupivacaine compared to plain local anesthetics for abdominal fascial plane blocks.

Use and Clinical Relevancy of Pericapsular Nerve Block (PENG) in Total Hip Arthroplasty: A Systematic Review and Meta-analysis.

Ultrasound-guided pericapsular nerve group (PENG) block is an emerging regional anesthesia technique that may provide analgesia for patients undergoing total hip arthroplasties (THA). There are clinical studies comparing this fascial plane block to other established methods; however, evidence on the actual efficacy of this block for THA continues to evolve. Available clinical studies conducted over the past 4 years were reviewed to evaluate the analgesic efficacy and effectiveness of PENG block in patients undergoing THAs. A meta-analysis of randomized controlled trials (RCTs) in patients undergoing THA, where PENG block was compared to no block, placebo/sham block (injection with saline), or other analgesic techniques including suprainguinal fascia iliaca block (FIB), or periarticular infiltration (PAI) was performed. Our primary outcome was opioid consumption during the first 24 hours. Secondary outcomes were postoperative rest and dynamic pain scores at 6-12, 24 and 48 hours, block performance time, sensory-motor assessment, quadriceps weakness, the incidence of postoperative falls, first analgesic request, block and opioid-related complications, surgical complications, patient satisfaction scores, postanesthesia care unit length of stay, hospital length of stay, and functional and quality of life outcomes. We included 12 RCTs with a total of 705 patients. Data showed that PENG block decreased 24-hour oral morphine milligram equivalent consumption by a mean difference (MD) of 3.75mg (95% CI: -5.96,-1.54; P =0.0009). No statistically significant differences in rest or dynamic pain were found, except for a modest MD reduction in dynamic pain score of 0.55 points (95% CI: -0.98, -0.12; P =0.01), measured 24 hours after surgery in favor of PENG block. Our systematic review and meta-analysis suggest that PENG block provides better analgesia, measured as MME use, in the first 24 hours after THA, with no real impact on postoperative VAS scores. Despite statistical significance, the high heterogeneity across RCTs implies that PENG's benefits may not surpass the minimal clinically important difference threshold for us to recommend PENG as best practice in THA.

Neuroprotective effects of chlorogenic acid against oxidative stress in rats subjected to lithium-pilocarpine-induced status epilepticus.

Epilepsy is a condition marked by sudden, self-sustained, and recurring brain events, showcasing unique electro-clinical and neuropathological phenomena that can alter the structure and functioning of the brain, resulting in diverse manifestations. Antiepileptic drugs (AEDs) can be very effective in 30% of patients in controlling seizures. Several factors contribute to this: drug resistance, individual variability, side effects, complexity of epilepsy, incomplete understanding, comorbidities, drug interactions, and no adherence to treatment. Therefore, research into new AEDs is important for several reasons such as improved efficacy, reduced side effects, expanded treatment options, treatment for drug-resistant epilepsy, improved safety profiles, targeted therapies, and innovation and progress. Animal models serve as crucial biological tools for comprehending neuronal damage and aiding in the discovery of more effective new AEDs. The utilization of antioxidant agents that act on the central nervous system may serve as a supplementary approach in the secondary prevention of epilepsy, both in laboratory animals and potentially in humans. Chlorogenic acid (CGA) is a significant compound, widely prevalent in numerous medicinal and food plants, exhibiting an extensive spectrum of biological activities such as neuroprotection, antioxidant, anti-inflammatory, and analgesic effects, among others. In this research, we assessed the neuroprotective effects of commercially available CGA in Wistar rats submitted to lithium-pilocarpine-induced status epilepticus (SE) model. After 72-h induction of SE, rats received thiopental and were treated for three consecutive days (1st, 2nd, and 3rd doses). Next, brains were collected and studied histologically for viable cells in the hippocampus with staining for cresyl-violet (Nissl staining) and for degenerating cells with Fluoro-Jade C (FJC) staining. Moreover, to evaluate oxidative stress, the presence of malondialdehyde (MDA) and superoxide dismutase (SOD) was quantified. Rats administered with CGA (30 mg/kg) demonstrated a significant decrease of 59% in the number of hippocampal cell loss in the CA3, and of 48% in the hilus layers after SE. A significant reduction of 75% in the cell loss in the CA3, shown by FJC+ staining, was also observed with the administration of CGA (30 mg/kg). Furthermore, significant decreases of 49% in MDA production and 72% in the activity of SOD were seen, when compared to animals subjected to SE that received vehicle. This study introduces a novel finding: the administration of CGA at a dosage of 30 mg/kg effectively reduced oxidative stress induced by lithium-pilocarpine, with its effects lasting until the peak of neural damage 72 h following the onset of SE. Overall, the research and development of new AEDs are essential for advancing epilepsy treatment, improving patient outcomes, and ultimately enhancing the quality of life for individuals living with epilepsy.

Effect of Preemptive Systemic Patient-controlled Analgesia in Evisceration

Purpose: To investigate the effect of preemptive systemic analgesia using patient-controlled analgesia (PCA) on postoperative pain after evisceration.Methods: Of the patients who underwent evisceration under general anesthesia in our hospital, 55 who were able to evaluate pain using a numeral rating scale (NRS) were included. The patients were divided into two groups: group 1 used PCA after surgery, and group 2 used PCA preemptively before surgery. We compared the two groups in terms of the NRS pain scores on the day of surgery and 1, 2, and 3 days after surgery, and according to whether additional analgesics were used.Results: The 55 patients included 17 in group 1 and 38 in group 2. The NRS at 3, 5, and 7 hours on the day of surgery tended to be lower in group 2, but not significantly (<i>p</i> > 0.05). The NRS on days 1 and 2 after surgery was significantly lower in group 2 (<i>p</i> = 0.014 and <i>p</i> = 0.027, respectively), and the NRS on day 3 after surgery was also lower, although not significantly (<i>p</i> = 0.059). Significantly fewer cases required additional analgesics in group 2 compared to group 1 on the day of surgery and 1, 2, and 3 days after surgery (<i>p</i> = 0.001, <i>p</i> < 0.001, <i>p</i> < 0.001, and <i>p</i> = 0.008, respectively).Conclusions: Using preemptive systemic PCA in evisceration significantly reduced the postoperative pain, and PCA itself was an effective administration method due to the high rate of pain control without the need for additional analgesics.

Retro superior costotransverse ligament space block as an effective analgesia after laparoscopic gastrectomy: a case report

Retro superior costotransverse ligament space block as an effective analgesia after laparoscopic gastrectomy: a case report

Comparing the Effectiveness of Oral Celecoxib with Oral Tramadol as Pre-Emptive Analgesia in Ambulatory Surgery

Nociception pathway is thought to be pre-emptively inhibited in hope to reduce acute pain in an anticipated procedural related tissue injury intraoperatively or postoperatively when pre-emptive analgesics are administered preoperatively. High intensity of pain is expected after surgical removal of the third molar which is associated with jaw swelling and limited opening of the jaw. We compared the pre-emptive analgesia effect of oral celecoxib and oral tramadol in elective ambulatory dental surgery under general anaesthesia. Informed consents were obtained from 84 patients with American Society of Anesthesiologists (ASA) physical status I or II and aged between 18 to 56 years. They were randomised to receive either oral celecoxib 200 mg (Group A) or oral tramadol 50 mg (Group B) one hour before induction of anaesthesia. Intraoperative and postoperative fentanyl consumption were compared. Numeric Rating Scale (NRS), ranging from 1 to 10, was used to assess postoperative pain scores. Group A showed a significant reduction in fentanyl consumption intraoperatively compared to Group B (p=0.047). Both groups of patients experienced mild pain at various times assessed postoperatively ranging between 0-2 NRS scores. Comparison between the groups did not detect significant reduction in pain scores and postoperative fentanyl consumption. We concluded that neither medication was found to be effective as pre-emptive analgesia, however, intraoperative fentanyl consumption was reduced by pre-emptive administration of oral celecoxib.

The boon and bane of nitrous oxide.

Nitrous oxide (N2O) has been known since the end of the eighteenth century. Today, N2O plays a huge role as a greenhouse gas and an ozone-depleting stratospheric molecule. The main sources of anthropogenic N2O emissions are agriculture, fuel combustion, wastewater treatment, and various industrial processes. By contrast, the contribution of medical N2O to the greenhouse effect appears to be small. The recreational and medical uses of N2O gradually diverged over time. N2O has analgesic and anesthetic effects, making it widely used in modern dentistry and surgery. New research has also begun studying N2O's antidepressant actions. N-methyl-D-aspartate (NMDA) antagonism and opioid effects are believed to be the main underlying biochemical mechanisms. At this point, numerous questions remain open and, in particular, the conduct of larger clinical trials will be essential to confirm N2O's use as a rapid-acting antidepressant. The N2O concentration delivered, the duration of a single inhalation, as well as the number of inhalations ultimately required, deserve to be better understood. Finally, the non-medical use of N2O has gained significant attention in recent years. Sudden deaths directly attributed to N2O are primarily due to asphyxia. Heavy, chronic N2O use may result in vitamin B12 deficiency, which, among other things, may cause megaloblastic anemia, venous thrombosis, myeloneuropathy, and skin pigmentation. Helpful biochemical tests include homocysteine and methylmalonic acid. The centerpiece of treatment is complete cessation of N2O use together with parenteral administration of vitamin B12.

Nephroprotective effects of coriander (Coriandrum sativum) leaves aqueous extracts in aristolochic acid-intoxicated zebrafish embryos.

Coriander is a notable medicinal plant known for its diverse properties, including anti-inflammatory, antioxidant, anticancer, analgesic, and anti-diabetic effects. Despite its recognized health benefits, research on its nephroprotective properties is limited. This study aimed to investigate the potential nephroprotective properties of an aqueous extract derived from coriander leaves using an aristolochic acid-intoxicated zebrafish model. To assess kidney abnormalities induced by aristolochic acid (AA), we utilized the transgenic line Tg(wt1b:egfp), which expresses green fluorescent protein (GFP) in the kidney. Our previous report indicated that AA exposure leads to acute renal failure in zebrafish characterized by kidney malformation and impaired renal function. However, pretreatment of coriander extract (CE) can mitigate kidney malformations induced by AA. In addition, CE pretreatment reduces the accumulation of red blood cells in the glomerular region. To verify the nephroprotective effects of CE, we analyzed renal function by measuring the glomerular filtration rate in zebrafish embryos. Results indicate that CE partially mitigates renal function impairment caused by AA exposure, suggesting its potential to attenuate AA-induced renal failure. Mechanistically, pretreatment with CE reduces the expression of proinflammatory and proapoptotic genes induced by AA. This suggests that CE likely alleviates acute renal failure by reducing inflammation and apoptosis. As a result, we regard zebrafish as a valuable model for screening natural compounds that have the potential to alleviate AA-induced nephrotoxicity.

Effects of aloe vera on burn injuries: A systematic review and meta-analysis of randomized controlled trials.

Burn injuries cause severe pain, infection risks, psychological distress, financial burdens, and mortality, necessitating effective care. Aloe vera, a traditional burn remedy, shows wound healing potential, but its analgesic effects and efficacy with varying burn severity are uncertain. This study aims to investigate aloe vera's impact on wound healing, pain management, and infection prevention in burn patients. A systematic search on PubMed, Embase, and CENTRAL was performed on 9th October 2023 for randomized controlled trials (RCTs). The risk of bias was examined using the Cochrane risk-of-bias tool (version 2), and the meta-analysis was carried out using a random-effects model. The primary outcome was wound healing time, with secondary outcomes examining pain severity and wound infection. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the quality of evidence for each outcome. Nine RCTs were included in the current study, of which six provided data on the primary outcome. Aloe vera significantly reduced mean wound healing time compared to other topicals [mean difference (MD) -3.76 days; 95% confidence interval (CI) -5.69 to -1.84]. Additionally, the meta-analysis of the secondary outcomes found no significant differences in pain reduction (MD -0.76 points; 95% CI -1.53 to 0.01) and wound infection risk (risk ratio 1.10; 95% CI 0.34 to 3.59) between aloe vera and control groups. In conclusion, aloe vera expedites wound healing in second-degree burn patients without increased infection risk compared to other antimicrobial agents. The analgesic effects on burn injuries remain uncertain.

Vagal tone, pain sensitivity and exercise-induced hypoalgesia: The effect of physical activity level.

Vagal activity has analgesic effects that are attributed to exercise-induced hypoalgesia (EIH). High vagal tone and low pain sensitivity are reported in individuals who routinely exercise yet, their association is unclear. Furthermore, it is unknown if the heightened vagal tone following high physical activity predicts and intensifies EIH. Fifty-one healthy participants (27 low-moderately physically active; 27 females) underwent a resting-state electrocardiogram followed by heart rate variability analysis. Pain measurements, including pressure (PPT) and heat (HPT) pain thresholds, ratings of tonic heat pain (THP) and conditioned pain modulation (CPM) paradigm, were conducted pre- and post-exercise on a cycle ergometer. The highly active group demonstrated higher vagal tone compared to the low-moderately active (root mean square of successive differences between R-R intervals: 63.96.92 vs. 34.78 ms, p = 0.018; percentage of successive R-R intervals that exceed 50 ms: 24.41 vs. 11.52%, p = 0.012). Based on repeated-measure ANOVA, the highly active group showed higher PPT at pre-exercise, compared to the low-moderately active group (382 kPa vs. 327 kPa; p = 0.007). Post-exercise, both groups demonstrated EIH, increased HPT (p = 0.013) and decreased THP ratings (p < 0.001). Linear regression revealed that only in the low-moderately active group, higher vagal tone was associated with more efficient pre-exercise CPM and a greater reduction in THP ratings post-exercise (p ≤ 0.01). Highly active individuals demonstrate greater vagal tone and lower pain sensitivity but no greater EIH. Vagal tone moderates pain inhibition efficiency and EIH only in low-moderately active individuals. These findings suggest that physical activity level moderates the vagal-pain association via the endogenous analgesia system. Highly physically active individuals exhibit greater vagal tone and reduced sensitivity to experimental pain, yet they do not benefit more from exercise-induced hypoalgesia (EIH) compared to low-moderately active individuals. Moreover, low-moderately active individuals with greater vagal tone exhibited more efficient endogenous pain inhibition and greater EIH, suggestive of the moderation effect of physical activity level on vagal-pain associations.

Analgesic, Anti-Inflammatory, and Chondroprotective Activities of Siraitia grosvenorii Residual Extract

Inflammation is crucial to osteoarthritis (OA) pathogenesis. The aim of this study was to evaluate Siraitia grosvenorii residue extract (NHGRE) obtained by extracting S. grosvenorii fruits with water as a potential food supplement for treating arthritis based on its analgesic, anti-inflammatory, and chondroprotective effects and the remaining residue with 70% ethanol. We observed the analgesic activity of NHGRE based on the acetic acid-induced writhing response in mice, examined its anti-inflammatory efficacy against carrageenan-induced paw oedema in mice, and investigated its effect on inflammatory cytokine expression in interleukin (IL)-1β-induced SW1353 cells. Furthermore, we determined its effects on cartilage protection in interleukin-1β (IL-1β)-treated SW1353 cells. NHGRE at 200 mg/kg significantly reduced the acetic acid-induced writhing response and prevented oedema formation in the carrageenan-induced paw oedema model. In IL-1β-induced SW1353 cells, NHGRE at 400 µg/mL reduced the expression of inflammation mediators such as tumour necrosis factor (TNF)-α (55.3%), IL-6 (35.4%), and prostaglandin E2 (PGE2) (36.9%) and down-regulated the expression of matrix metalloproteinase (MMP)-1 (38.6%), MMP-3 (29.3%), and MMP-13 (44.8%). Additionally, it restored degraded collagen II levels in chondrocytes. NHGRE plays a protective role in chondrocytes by regulating Nuclear factor kappa B (NF-κB) activation. Overall, NHGRE may be a useful therapeutic agent for OA by controlling pain, oedema formation, and inflammation-related mechanisms.

Cannabinoids for Acute Pain Management: Approaches and Rationale.

Acute pain management remains a challenge and postoperative pain isoften undermanaged despite many available treatmentoptions, also including cannabinoids. In the light of the opioid epidemic, there has been growing interest in alternative care bundles for pain management, including cannabinoids as potential treatment to decrease opioid prescribing. Despite the lack of solid evidence on the efficacy of cannabinoids, their use among patients with pain, including those using opioids, is currently increasing. This use is supported by data suggesting that cannabinoids could potentially contribute to a better pain management and to a reduction in opioid doses while maintaining effective analgesia with minimum side effects. The scientific basis for supporting the use of cannabis is extensive, although it does not necessarily translate into relevant clinical outcomes. The use of cannabinoids in acute pain did not alwaysconsistently show statistically significant results in improving acute pain. Large randomized, controlled trials evaluating diverse cannabis extracts are needed in different clinical pain populations to determine safety and efficacy.

Evaluating the Efficacy of the Erector Spinae Plane Block as a Supplementary Approach to Cardiac Anesthesia during Off-Pump Coronary Bypass Graft Surgery via Median Sternotomy: A Randomized Clinical Trial

Background: Pain control after off-pump coronary artery bypass graft (OPCAB) facilitates mobilization and improves outcomes. The efficacy of the erector spinae plane block (ESPB) after cardiac surgery remains controversial. Methods: We aimed to investigate the analgesic effects of ESPB after OPCAB. Precisely 56 patients receiving OPCAB were randomly divided into ESPB and control groups. The primary outcome was visual analog scale (VAS) pain scores at 6, 12, 24, and 48 h postoperatively. Secondary outcomes were the dose of rescue analgesics in terms of oral morphine milligram equivalents, the dose of antiemetics, the length of intubation time, and the length of stay in the intensive care unit (ICU). Results: The VAS scores were similar at all time points in both groups. The incidence of severe pain (VAS score &gt; 7) was significantly lower in the ESPB group (50% vs. 15.4%; p = 0.008). The dose of rescue analgesics was also lower in the ESPB group (19.04 ± 18.76, 9.83 ± 12.84, p = 0.044) compared with the control group. The other secondary outcomes did not differ significantly between the two groups. Conclusions: ESPB provides analgesic efficacy by reducing the incidence of severe pain and opioid use after OPCAB.

Actions of remimazolam on inhibitory transmission of rat spinal dorsal horn neurons

Remimazolam is an ultra-short benzodiazepine that acts on the benzodiazepine site of γ-aminobutyric acid (GABA) receptors in the brain and induces sedation. Although GABA receptors are found localized in the spinal dorsal horn, no previous studies have reported the analgesic effects or investigated the cellular mechanisms of remimazolam on the spinal dorsal horn. Behavioral measures, immunohistochemistry, and in vitro whole-cell patch-clamp recordings of dorsal horn neurons were used to assess synaptic transmission. Intrathecal injection of remimazolam induced behavioral analgesia in inflammatory pain-induced mechanical allodynia (six rats/dose; p < 0.05). Immunohistochemical staining revealed that remimazolam suppressed spinal phosphorylated extracellular signal-regulated kinase activation (five rats/group, p < 0.05). In vitro whole-cell patch-clamp analysis demonstrated that remimazolam increased the frequency of GABAergic miniature inhibitory post-synaptic currents, prolonged the decay time (six rats; p < 0.05), and enhanced GABA currents induced by exogenous GABA (seven rats; p < 0.01). However, remimazolam did not affect miniature excitatory post-synaptic currents or amplitude of monosynaptic excitatory post-synaptic currents evoked by Aδ- and C-fiber stimulation (seven rats; p > 0.05). This study suggests that remimazolam induces analgesia by enhancing GABAergic inhibitory transmission in the spinal dorsal horn, suggesting its potential utility as a spinal analgesic for inflammatory pain.

Effect of Immediate Kangaroo Mother Care on Pain in Sick Low Birth Weight Neonates During Heel Prick in Mother–Newborn Intensive Care Unit

Introduction: In the Mother-Newborn Intensive Care Unit(M–NICU), sick, low birth weight(LBW) neonates are cared for along with their mothers with facilities of level-II newborn care and postnatal care for mothers. Babies weighing 1–1.8 kg are admitted and Kangaroo Mother Care (KMC) is started after birth without waiting for stabilization. This is immediate Kangaroo Mother Care (iKMC). There are studies on analgesic effect of KMC, but no studies on analgesic effect of iKMC in sick neonates; therefore, the present study was planned. Aims and objectives: To compare pain score and recovery time from pain following heel prick in sick LBW neonates weighing 1–1.8 kg in iKMC and under radiant warmer. Materials and methods: In the M-NICU, neonates are in iKMC for 12–18 hours. If iKMC is not possible, the baby is placed under radiant-warmer. LBW neonates are screened for hypoglycemia at 2, 6, 12, 24, 48-hour intervals by heel prick. Pain scoring was done by the Premature Infant Pain Profile (PIPP) score and the recovery time (time for heart rate to return to baseline) noted following heel prick in iKMC and under radiant warmer. Results: 75 babies enrolled, 150 episodes of glucose estimation in iKMC and 150 in radiant warmer included. Mean(SD) baby weight(Kg) was 1512.93(171.10). Mean(SD) gestational age(Weeks) was 33.77(2.54). In the iKMC group, mean pain score(SD) was 7.59(2.27) and median(IQR) was 8.00(2.75). In the radiant warmer group, mean pain score(SD) was 14.41(2.04) and median(IQR) was 15.00(3.00). Mean recovery time(seconds)(SD) was 33.3(20.22) in the iKMC group and 92.43(49.68) in the radiant warmer group. The difference was statistically significant( P = &lt;0.001). Conclusion: In sick LBW neonates, painful procedures must be done in KMC, whenever possible.

Evaluation of analgesic activity of ethanol and ethyl acetate extracts from basil leaves (Ocimum x africanum L.) in acetic acid-induced rat models

Analgesics are medications that alleviate pain without impairing consciousness, with certain plants, such as basil (Ocimum x africanum L.), showing potential as natural pain relievers. This research investigated the analgesic effects of ethanol and ethyl acetate extracts from basil leaves on acetic acid-induced pain in rats. The study utilized percolation extraction methods with 96% ethanol and ethyl acetate solvents. Twenty-eight male white rats were divided into seven groups: one normal control group without treatment or induction, one negative control group receiving 0.5% CMC-Na, two groups treated with ethanol extracts of basil leaves at doses of 400 mg/kg BW and 800 mg/kg BW, two groups treated with ethyl acetate extracts at the same doses, and one positive control group administered 50 mg/kg BW diclofenac sodium. Thirty minutes post-treatment, 1% acetic acid was injected intraperitoneally, and writhing responses were observed over 60 minutes. The data on percentage protection from writhing were analyzed using One-way ANOVA followed by the LSD test. The findings revealed that both the ethanol and ethyl acetate extracts at an 800 mg/kg BW dosage closely matched the analgesic effectiveness of the diclofenac sodium group.

Role of L-, N- and T-type Calcium Channels in Achieving Maximum Analgesic and Minimum Toxic Effect of Tramadol

The aim of the study was to investigate the effects of lacidipine, amlodipine and benidipine on the analgesic activity and toxicity of tramadol. Rats (n=6/each group) were divided into five groups as control(CG), tramadol(TRD), lacidipine+tramadol(LTRD), amlodipine+tramadol(ATRD) and benidipine+tramadol(BTRD). Tramadol was administered once at a dose of 50 mg/kg and lacidipine, amlodipin, benidipin were administered at a dose of 4 mg/kg orally, once a day for 10 days. After the animals were sacrificed malondialdehyde(MDA) and total glutathione(tGSH) levels were measured in brain, heart, liver and kidney tissues. Troponin I(Tp I), alanine aminotransferase(ALT), aspartate aminotransferase(AST), blood urea nitrogen(BUN), and creatinine levels were determined in serum. Paw pain thresholds were measured 1 hour before and after drug administration. Analgesic effect of tramadol was increased the most by benidipine, while amlodipine and lacidipine increased it equally. Lacidipine failed to suppress MDA increase and tGSH decrease in brain tissue. Benidipine suppressed MDA increase and tGSH decrease in brain tissue better than amlodipine. All three drugs suppressed cardiac tissue oxidative stress and the release of TP I into the circulation. Lacidipine and amlodipine could not prevent tramadol-induced oxidative stress in liver and kidney tissues, whereas benidipine prevented excessive MDA increase and tGSH decrease. Benidipine significantly suppressed the increase of ALT, AST, BUN, and creatinine. Analgesic activity was 35.1% in TRD, 43.7% in LTRD 50.4% in ATRD and 67,5% in BTRD. Study results show that benidipine and tramadol co-treatment is better than co-treatment with lacidipine or amlodipine in achieving minimal toxic effects and maximum analgesia.

Nanodelivery Approaches of Phytoactives for Skin Cancers: Current and Future Perspectives.

In recent years, there has been an increase in skin cancers due to external factors, especially environmental factors, and studies on treatment alternatives have gained importance. Nanomaterials are common, from sunscreen formulas to formulations designed to treat skin cancers at various stages. Using bioactives has multiple effects in treating skin cancers, which provides many advantages. In this regard, many phytochemicals gain importance with their antioxidant, anti-proliferative, anti-inflammatory, antiangiogenic, and analgesic effects. Their delivery with nanocarriers is on the agenda for phytochemicals to gain the targeted stability, effectiveness, and toxicity/safety properties. This review presents types of skin cancers, phytochemicals effective in skin cancers, and their nanocarrier-loaded studies from an up-to-date perspective.

Two doses of subcutaneous methadone for postoperative analgesia in dogs undergoing tibial plateau levelling osteotomies.

To evaluate analgesia, sedation and adverse effects of two doses of subcutaneous methadone in dogs undergoing tibial plateau levelling osteotomy. Seventeen client-owned dogs undergoing unilateral tibial plateau levelling osteotomy were randomly allocated to receive either 0.25 mg/kg methadone (eight dogs) or 0.5 mg/kg methadone (nine dogs). All dogs were premedicated with methadone and 2 to 6 mcg/kg dexmedetomidine subcutaneously. They were induced and maintained on a standard protocol. All animals received a second dose of methadone subcutaneously 4 hours after premedication and a 4.4 mg/kg dose of carprofen subcutaneously at 8 hours after premedication. During surgery, blood pressure, heart rate and temperature were assessed every 5 minutes. Postoperatively, sedation scores, temperature, heart rate and Glasgow composite modified pain score - short form were assessed for 12 hours postoperatively. One of 17 (5.9%) dogs had intraoperative hypotension, nine of 17 dogs had intra-operative bradyarrhythmias and 17 of 17 dogs had intra-operative hypothermia. No dogs required intra-operative rescue. Composite modified pain score - short form scores were below the threshold for intervention in 16 of 17 (94.1%) animals. Only one of 17 (5.9%) dogs required rescue analgesia. Median sedation score was 0 by the T8 time point. Adverse events were rare in both groups with only vocalisation and hypothermia reported commonly postoperatively. Two doses of methadone at either 0.25 or 0.5 mg/kg administered via subcutaneous injections pre-operatively and 4 hours later, along with 4.4 mg/kg carprofen subcutaneously 8 hours after the first methadone dose appear to provide sufficient pain control for up to 12 hours in dogs undergoing tibial plateau levelling osteotomy.

Comparison of Thoracoscopy-Guided Thoracic Paravertebral Block and Ultrasound-Guided Thoracic Paravertebral Block in Postoperative Analgesia of Thoracoscopic Lung Cancer Radical Surgery: A Randomized Controlled Trial.

Ultrasound-guided thoracic paravertebral block (UTPB) is widely used for postoperative analgesia in thoracic surgery. However, it has many disadvantages. Thoracoscopy-guided thoracic paravertebral block (TTPB) is a new technique for thoracic paravertebral block (TPB). In this study, we compared the use of TTPB and UTPB for pain management after thoracoscopic radical surgery for lung cancer. In total, 80 patients were randomly divided 1:1 into the UTPB group and the TTPB group. The surgical time of TPB, the success rate of the first puncture, block segment range, visual analog scale (VAS) scores at 2, 6, 12, 24, and 48h post operation, and the incidence of postoperative adverse reactions were compared between the two groups. The surgical time of TPB was significantly shorter in the TTPB group than in the UTPB group (2.2 ± 0.3 vs. 5.7 ± 1.7min, t = - 12.411, P < 0.001). The success rate of the first puncture and the sensory block segment were significantly higher in the TTPB group than in the UTPB group (100% vs. 76.9%, χ2 = 8.309, P < 0.001; 6.5 ± 1.2 vs. 5.1 ± 1.3 levels, t = - 5.306, P < 0.001, respectively). The VAS scores were significantly higher during rest and coughing at 48h post operation than at 2, 6, 12, and 24h post operation in the TTPB group. The VAS scores were significantly lower during rest and coughing at 12 and 24h post operation in the TTPB group than in the UTPB group (rest: 2.5 ± 0.4 vs. 3.4 ± 0.6, t = 7.325, P < 0.001; 2.5 ± 0.5 vs. 3.5 ± 0.6, t = 7.885, P < 0.001; coughing: 3.4 ± 0.6 vs. 4.2 ± 0.7, t = 5.057, P < 0.001; 3.4 ± 0.6 vs. 4.2 ± 0.8, t = 4.625, P < 0.001, respectively). No significant difference was observed in terms of postoperative adverse reactions between the two groups. Compared with UTPB, TTPB shows advantages, such as simpler and more convenient surgery, shorter surgical time, a higher success rate of the first puncture, wider block segments, and superior analgesic effect. TTPB can effectively reduce postoperative pain due to thoracoscopic lung cancer radical surgery. https://www.chictr.org.cn , identifier ChiCTR2300072005, prospectively registered on 31/05/2023.