Thoracotomy Patients Under General Anesthesia: A Comparison on Intra-Operative Anesthetic and Analgesic Requirements, When Combined with Either Epidural Analgesia or Continuous Unilateral Paravertebral Analgesia.

BACKGROUND AND OBJECTIVE: Regional analgesia is effective for post-thoracotomy pain. The primary objective of the study is to compare the intraoperative requirement of isoflurane and fentanyl between general anaesthesia (GA) with epidural analgesia and GA with paravertebral analgesia. METHODS AND MATERIAL: A prospective observational comparative study was conducted on 56 patients undergoing open thoracotomy procedures. The patients were divided into two groups of 28 by assigning the study participants alternatively to each group: Group GAE - received thoracic epidural catheterization with GA, and Group GAP - received ultrasound guided thoracic paravertebral catheterization on the operative side with GA. Intraoperative requirement of isoflurane, fentanyl, postoperative analgesia, stress response, need of rescue analgesics and adverse effects were observed and analysed. RESULTS: 25 patients in each group were included in the data analysis. The intraoperative requirement of isoflurane (32.28 ± 1.88 vs 48.31 ± 4.34 ml; p < 0.0001) and fentanyl (128.87 ± 25.12 vs 157 ± 30.92 µg; p = 0.0009) were significantly less in the GAE group than in the GAP group. VAS scores and need of rescue analgesics and blood glucose levels were not statistically significant during the postoperative period (p > 0.05). The incidence of adverse effects was comparable except for hypotension and urinary retention which were significantly higher in the GAE group. CONCLUSION: GA with epidural analgesia resulted in significant reduction in the intraoperative consumption of isoflurane and fentanyl in comparison to GA with paravertebral analgesia. However, both the techniques were equally effective in the postoperative period.

Low-dose short infusion ketamine as adjunct to morphine for acute long bone fracture in the emergency department: a randomized controlled trial.

BACKGROUND: Ketamine is recognized as an alternative for pain management; however, concerns about emergent adverse reactions have limited its widespread adoption. This study aimed to assess the efficacy of a short infusion of low-dose ketamine (LDK) compared to intravenous morphine (MOR) as adjunctive analgesia for acute long bone fracture pain. METHODS: This single-blinded, randomized controlled trial was conducted in a single emergency department. Patients with acute long bone fractures and numerical rating scale (NRS) pain scores ≥ 6 following an initial dose of intravenous morphine were assigned to receive either a LDK (0.3 mg/kg) over 15 min or intravenous MOR at a dose of 0.1 mg/kg administered over 5 min. Throughout a 120-min observation period, patients were regularly evaluated for pain level (0-10), side effects, and the need for additional rescue analgesia. RESULTS: A total of 58 subjects participated, with 27 in the MOR group and 31 in the LDK group. Demographic variables and baseline NRS scores were comparable between the MOR (8.3 ± 1.3) and LDK (8.9 ± 1.2) groups. At 30 min, the LDK group showed a significantly greater mean reduction in NRS scores (3.1 ± 2.03) compared to the MOR group (1.8 ± 1.59) (p = 0.009). Similarly, at 60 min, there were significant differences in mean NRS score reductions (LDK 3.5 ± 2.17; MOR mean reduction = 2.4, ± 1.84) with a p-value of 0.04. No significant differences were observed at other time intervals. The incidence of dizziness was higher in the LDK group at 19.4% (p = 0.026). CONCLUSION: Short infusion low-dose ketamine, as an adjunct to morphine, is effective in reducing pain during the initial 30 to 60 min and demonstrated comparability to intravenous morphine alone in reducing pain over the subsequent 60 min for acute long bone fractures. However, it was associated with a higher incidence of dizziness. TRIAL REGISTRATION: NMRR17318438970 (2 May 2018; www.nmrr.gov.my ).

Anti-Nociceptive Effects of Sphingomyelinase and Methyl-Beta-Cyclodextrin in the Icilin-Induced Mouse Pain Model.

The thermo- and pain-sensitive Transient Receptor Potential Melastatin 3 and 8 (TRPM3 and TRPM8) ion channels are functionally associated in the lipid rafts of the plasma membrane. We have already described that cholesterol and sphingomyelin depletion, or inhibition of sphingolipid biosynthesis decreased the TRPM8 but not the TRPM3 channel opening on cultured sensory neurons. We aimed to test the effects of lipid raft disruptors on channel activation on TRPM3- and TRPM8-expressing HEK293T cells in vitro, as well as their potential analgesic actions in TRPM3 and TRPM8 channel activation involving acute pain models in mice. CHO cell viability was examined after lipid raft disruptor treatments and their effects on channel activation on channel expressing HEK293T cells by measurement of cytoplasmic Ca2+ concentration were monitored. The effects of treatments were investigated in Pregnenolone-Sulphate-CIM-0216-evoked and icilin-induced acute nocifensive pain models in mice. Cholesterol depletion decreased CHO cell viability. Sphingomyelinase and methyl-beta-cyclodextrin reduced the duration of icilin-evoked nocifensive behavior, while lipid raft disruptors did not inhibit the activity of recombinant TRPM3 and TRPM8. We conclude that depletion of sphingomyelin or cholesterol from rafts can modulate the function of native TRPM8 receptors. Furthermore, sphingolipid cleavage provided superiority over cholesterol depletion, and this method can open novel possibilities in the management of different pain conditions.

Mechanisms and Preventative Strategies for Persistent Pain following Knee and Hip Joint Replacement Surgery: A Narrative Review.

Chronic postsurgical pain (CPSP) following total knee arthroplasty (TKA) and total hip arthroplasty (THA) is a prevalent complication of joint replacement surgery which has the potential to decrease patient satisfaction, increase financial burden, and lead to long-term disability. The identification of risk factors for CPSP following TKA and THA is challenging but essential for targeted preventative therapy. Recent meta-analyses and individual studies highlight associations between elevated state anxiety, depression scores, preoperative pain, diabetes, sleep disturbances, and various other factors with an increased risk of CPSP, with differences observed in prevalence between TKA and THA. While the etiology of CPSP is not fully understood, several factors such as chronic inflammation and preoperative central sensitization have been identified. Other potential mechanisms include genetic factors (e.g., catechol-O-methyltransferase (COMT) and potassium inwardly rectifying channel subfamily J member 6 (KCNJ6) genes), lipid markers, and psychological risk factors (anxiety and depression). With regards to therapeutics and prevention, multimodal pharmacological analgesia, emphasizing nonopioid analgesics like acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs), has gained prominence over epidural analgesia. Nerve blocks and local infiltrative anesthesia have shown mixed results in preventing CPSP. Ketamine, an N-methyl-D-aspartate (NMDA)-receptor antagonist, exhibits antihyperalgesic properties, but its efficacy in reducing CPSP is inconclusive. Lidocaine, an amide-type local anesthetic, shows tentative positive effects on CPSP. Selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) have mixed results, while gabapentinoids, like gabapentin and pregabalin, present hopeful data but require further research, especially in the context of TKA and THA, to justify their use for CPSP prevention.

Neuropathic pain in cats: Mechanisms and multimodal management.

PRACTICAL RELEVANCE: Chronic pain is a significant welfare concern in cats, and neuropathic pain, which arises from aberrant processing of sensory signals within the nervous system, is a subcategory of this type of pain. To comprehend this condition and how multimodal pharmacotherapy plays a central role in alleviating discomfort, it is crucial to delve into the anatomy of nociception and pain perception. In addition, there is an intricate interplay between emotional health and chronic pain in cats, and understanding and addressing the emotional factors that contribute to pain perception, and vice versa, is essential for comprehensive care.Clinical approach:Neuropathic pain is suspected if there is abnormal sensation in the area of the distribution of pain, together with a positive response to trial treatment with drugs effective for neuropathic pain. Ideally, this clinical suspicion would be supported by confirmation of a lesion at this neurolocalisation using diagnostic modalities such as MRI and neuroelectrophysiology. Alternatively, there may be a history of known trauma at that site. A variety of therapies, including analgesic, anti-inflammatory and adjuvant drugs, and neuromodulation (eg, TENS or acupuncture), can be employed to address different facets of pain pathways.Aim:This review article, aimed at primary care/ general practitioners, focuses on the identification and management of neuropathic pain in cats. Three case vignettes are included and a structured treatment algorithm is presented to guide veterinarians in tailoring interventions.Evidence base:The review draws on current literature, where available, along with the author's extensive experience and research.

Utilizing experimental design and desirability function in optimizing RP-HPLC method for simultaneous determination of some skeletal muscle relaxants and analgesics.

An experimental design and response surface methodologies using Plackett-Burman and Box-Behnken designs were applied for selecting and optimizing the most appropriate parameters which significantly affect the separation and quantitative estimation of five skeletal muscle relaxants and four analgesic drugs (baclofen, methocarbamol, dantrolene sodium, orphenadrine citrate, cyclobenzaprine hydrochloride, ketoprofen, etoricoxib, ibuprofen, and mefenamic acid) with a relatively short duration of analysis in a single run. For the separation of the nine drugs, an INERTSIL ODS-V3-5 µm C18 column (250 × 4.6 mm I.D.) was used with the optimum mobile phase conditions (45.15 mM ammonium acetate buffer pH 5.56 adjusted with acetic acid, acetonitrile, and methanol in a ratio of 30.5:29.5:40, v/v/v with a flow rate of 1.5 mL/min) and UV-detection at 220 nm. The optimized method was successfully subjected to the validation steps as described in ICH guidelines for linearity, precision, accuracy, robustness, and sensitivity. The optimized and validated method was effectively applied to determine the content of the studied drugs in their pharmaceutical preparations and to expand its applicability to the counterfeit estimation of etoricoxib in different brands of tablet dosage forms.

Cannabis medicine for chronic pain.

In the last decade, patients with chronic pain have expressed increasing interest in cannabis-derived products for adjuvant therapy when treatment is deemed refractory to conventional analgesics. At present, clinical evidence to support this treatment approach appears to be sparse. Not because clinical studies as such are lacking, but rather as a result of methodological bias in relation to study design, patient populations, and treatment protocols. In this review, research in cannabis medicine for relief of chronic pain is reviewed, mainly with reference to published meta-analytic studies.

Evaluation of the effects of pregabalin and dexamethasone coadministration on preemptive multimodal analgesia and anxiety in third molar surgeries: a triple-blind randomized clinical trial.

OBJECTIVE: To evaluate the efficacy of pregabalin and dexamethasone coadministration in preemptive analgesia and anxiety control in lower third molar surgery. MATERIALS AND METHODS: A triple-blind, split-mouth clinical trial conducted with patients divided into two groups: control group, receiving placebo and dexamethasone, and test group, receiving pregabalin and dexamethasone preoperatively. The evaluated variables were pain, measured by the Visual Analog Scale (VAS), anxiety assessed through the State-Trait Anxiety Inventory (STAI) questionnaires, hemodynamic parameters [Blood Pressure (BP), Heart Rate (HR), Oxygen Saturation (SpO2)], and sedation assessed by the Ramsay scale. RESULTS: A total of 31 patients were included. The test group exhibited a significant reduction in pain at 2,4,6,8,12,16,24, and 48 h after surgery and in the consumption of rescue analgesics. Anxiety, evaluated by STAI and VAS, showed a significant decrease in the test group (p < 0.001). Additionally, there was a significant decrease in BP at most of the assessed time points (p < 0.05) and a significant reduction in HR at two different time intervals (p = 0.003 and p = 0.009), indicating a positive effect in the test group. There was no significant difference in SpO2 between the groups. Sedation assessment revealed a significant difference at all time points favoring the test group (p < 0.05). There were no significant postoperative adverse effects. CONCLUSIONS: Pregabalin coadministered with dexamethasone demonstrated significant efficacy in controlling postoperative pain and anxiety, as well as a sedative effect. CLINICAL RELEVANCE: The coadministration of pregabalin with dexamethasone may presents potential advantages in both pain modulation and psychological well-being of individuals undergoing third molar surgeries. TRIAL REGISTRATION: Brazilian Clinical Trials Registry (REBEC), No. RBR-378h6t6.

The Potential Antinociceptive Effect and Mechanism of Cannabis sativa L. Extract on Paclitaxel-Induced Neuropathic Pain in Rats Uncovered by Multi-Omics Analysis.

Cannabis sativa L. (hemp) is a herbaceous plant rich in cannabinoids with a long history of use in pain treatment. The most well-characterized cannabinoids, cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC), garnered much attention in chemotherapy-induced peripheral neuropathy (CIPN) treatment. However, few studies have investigated the biological benefits and mechanism of hemp extract on CIPN. In the present study, hemp extract (JG) rich in cannabinoids was extracted by supercritical fluid carbon dioxide extraction (SFCE). The antinociceptive efficacy was evaluated using a paclitaxel-induced peripheral neuropathy (PIPN) rat model based on behavioral tests. Further omics-based approaches were applied to explore the potential mechanisms. The results showed that JG decreased mechanical allodynia, thermal hyperalgesia, and inflammatory cytokines in PIPN rats significantly. Transcriptome analysis identified seven key genes significantly regulated by JG in PIPN model rats, mainly related to the neuroactive ligand-receptor interaction pathway, PPAR signaling pathway, and cAMP signaling pathway. In metabolomic analysis, a total of 39 significantly altered metabolites were identified, mainly correlated with pentose and glucuronate interconversions and the glycerophospholipid metabolism pathway. Gut microbiota analysis suggested that increased community Lachnoclostridium and Lachnospiraceae_UCG-006 in PIPN rats can be reversed significantly by JG. In conclusion, hemp extract exhibited antinociceptive effects on PIPN. The analgesic mechanism was probably related to the regulation of inflammation, neuroactive ligand-receptor interaction pathway, sphingolipid metabolism, etc. This study provides novel insights into the functional interactions of Cannabis sativa L. extract on PIPN.

The Analgesic Potential of Litsea Species: A Systematic Review.

Various plant species from the Litsea genus have been claimed to be beneficial for pain relief. The PRISMA approach was adopted to identify studies that reported analgesic properties of plants from the Litsea genus. Out of 450 records returned, 19 primary studies revealed the analgesic potential of nine Litsea species including (1) Litsea cubeba, (2) Litsea elliptibacea, (3) Litsea japonica, (4) Litsea glutinosa, (5) Litsea glaucescens, (6) Litsea guatemalensis, (7) Litsea lancifolia, (8) Litsea liyuyingi and (9) Litsea monopetala. Six of the species, 1, 3, 4, 7, 8 and 9, demonstrated peripheral antinociceptive properties as they inhibited acetic-acid-induced writhing in animal models. Species 1, 3, 4, 8 and 9 further showed effects via the central analgesic route at the spinal level by increasing the latencies of heat stimulated-nocifensive responses in the tail flick assay. The hot plate assay also revealed the efficacies of 4 and 9 at the supraspinal level. Species 6 was reported to ameliorate hyperalgesia induced via partial sciatic nerve ligation (PSNL). The antinociceptive effects of 1 and 3 were attributed to the regulatory effects of their bioactive compounds on inflammatory mediators. As for 2 and 5, their analgesic effect may be a result of their activity with the 5-hydroxytryptamine 1A receptor (5-HT1AR) which disrupted the pain-stimulating actions of 5-HT. Antinociceptive activities were documented for various major compounds of the Litsea plants. Overall, the findings suggested Litsea species as good sources of antinociceptive compounds that can be further developed to complement or substitute prescription drugs for pain management.

Analgesia for the treatment of acute pancreatitis: a protocol for a systematic review and network meta-analysis.

INTRODUCTION: Gastrointestinal hospitalisations in the USA cause over US$130 billion in expenditures, and acute pancreatitis is a leading cause of these hospitalisations. Adequate pain control is one of the primary treatment goals for acute pancreatitis. Though opioids are commonly used for analgesia in these patients, there have been concerns about short-term and long-term side effects of using opioids. Recently, non-opioid medications have been studied to treat pain in patients with acute pancreatitis. This systematic review and network meta-analysis aims to assess the comparative efficacy of analgesic medication for non-severe, acute pancreatitis. METHODS AND ANALYSIS: We will search multiple electronic databases for randomised controlled trials that study pain management in patients with non-severe, acute pancreatitis. The intervention will be any analgesic for acute pancreatitis in the hospital setting. The comparison group will be patients who received a placebo or other active interventions for pain management. The primary outcomes of interest include pain scores and the need for supplementary analgesia. The secondary outcomes will be serious adverse events, local complications, progression to severe pancreatitis, transfer to the intensive care unit, length of hospitalisation, time to start enteral feeds, 30-day all-cause mortality and Quality of Life Scale scores. If sufficient homogeneity exists among included studies, the findings will be pooled using a traditional pairwise and network meta-analysis. The risk of bias in randomised control trials will be evaluated using the Cochrane Risk of Bias Tool 2.0. The Grading of Recommendations, Assessment, Development, and Evaluation approach will be used to report the certainty of evidence. ETHICS AND DISSEMINATION: This systematic review will not involve direct contact with human subjects. The findings of this review will be published in a peer-reviewed journal. They will give healthcare providers a better awareness of the optimal analgesic medication for pain treatment in non-severe, acute pancreatitis.

[Pharmacological pain management in cancer patients]. / Medikamentöse Schmerztherapie bei Patienten mit Tumorerkrankungen.

Pharmacological pain therapy in cancer patients is based on guideline recommendations, which, however, do not fully coincide in all aspects due to varying weighting of evidence. The present article discusses current issues including the decreasing significance of the World Health Organization (WHO) analgesic ladder, with its distinction between step 2 and 3 being increasingly questioned. Risks of nonopioid analgesics such as paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs), particularly in older populations, are discussed. Paracetamol may potentially reduce the effectiveness of immunotherapies. Aspects of administering analgesics via a feeding tube are considered. Recommendations for the treatment of episodic pain, transitioning between different opioids, and some relevant interactions are also discussed.

Ecocebo: How the interaction between environment and drug effects may improve pharmacotherapy outcomes.

This narrative review describes the research on the effects of the association between environmental context and medications, suggesting the benefit of specific design interventions in adjunction to pharmacotherapy. The literature on Evidence-Based Design (EBD) studies and Neuro-Architecture show how contact with light, nature, and specific physical features of urban and interior architecture may enhance the effects of analgesic, anxiolytics, and antidepressant drugs. This interaction mirrors those already known between psychedelics, drugs of abuse, and setting. Considering that the physical feature of space is a component of the complex placebo configuration, the aim is to highlight those elements of built or natural space that may help to improve drug response in terms of efficacy, tolerability, safety, and compliance. Ecocebo, the integration of design approaches such as EBD and Neuro-Architecture may thus contribute to a more efficient, cost-sensitive, and sustainable pharmacotherapy.

The Effect of Depth of Anesthesia on Postoperative Pain in Laparoscopic Sleeve Gastrectomy: A Randomized Controlled Trial.

BACKGROUND: Patients with obesity are more sensitive to pain and more likely to have acute postoperative pain (APP). Studies have shown that the depth of anesthesia may affect the incidence of APP. The purpose of the study was to look into the connection between APP and depth of anesthesia in patients with obesity undergoing laparoscopic sleeve gastrectomy. METHODS: This is a prospective, double-blinded randomized clinical trial, 90 patients undergoing laparoscopic sleeve gastrectomy were randomly divided into two groups: the light anesthesia group (Bispectral Index of 50, BIS 50) and the deep anesthesia group (BIS 35). The degree of pain was evaluated by the visual analogue scale (VAS) at 0, 12, 24, 48, and 72 h after surgery. The use of analgesics, grade of postoperative nausea and vomiting (PONV), and the Quality of Recovery-15 (QoR-15) score were recorded. RESULTS: The VAS scores at rest or coughing at 0, 12, and 24 h after surgery in the BIS 35 group were lower than those in the BIS 50 group (P < 0.05). Fewer patients in the deep anesthesia group needed analgesia during the recovery period, and patient satisfaction was higher on the 3rd day after surgery (P < 0.015, P < 0.032, respectively). CONCLUSIONS: For patients with obesity, maintaining a deeper depth of anesthesia during surgery is beneficial to reduce APP causes less need for additional analgesic drugs, and improves patient satisfaction.

Pharmacokinetic profile of oral and subcutaneous administration of paracetamol in the koala (Phascolarctos cinereus) and prediction of its analgesic efficacy.

The pharmacokinetic profile of paracetamol in koalas is described when administered orally at 15 mg/kg; followed by the same dose, administered every 12 hours (hrs), repeated five times. After the initial oral administration, the median (range) maximal plasma concentration (Cmax), the time Cmax was reached (Tmax) and elimination half-life (t1/2) were 16.93 µg/mL (13.66 to 20.25 µg/mL); 4 hrs (4 to 8 hrs) and 5.54 hrs (4.66 to 7.67 hrs), respectively. When paracetamol was administered orally at 15 mg/mL every 12 hrs, the trough total plasma concentration range remained comparable to the therapeutic range in humans i.e. 4 to 20 µg/mL that is known to provide some analgesia. However, there is a smaller proportion of free drug (i.e. not bound to plasma proteins; and the active form) available in koala plasma (approximately 40% unbound) compared to human plasma (approximately 80% unbound). Consequently, even when there are similar total drug plasma concentrations in both koala and human plasma, the therapeutic efficacy may be reduced in koalas compared to humans. The initial oral dose and subsequent twice daily doses resulted in no obvious adverse effects in any koala. Haematology, plasma electrolyte and biochemical analyte values remained within their reference ranges eight hrs after the last dose but there was a significant change in alanine transaminase (ALT) levels (an increase), and in total protein (a decrease) (both p = 0.03). A dose of 15 mg/kg was also administered as a subcutaneous injection, diluted 50:50 with saline, to two koalas. As the oral formulation and the subcutaneous administration resulted in comparable absorption, the study focused on the oral profile. Based on these results there is an argument to recommend a slight increase in the oral paracetamol dose for the koala, however further investigation is required to confirm whether repeated administration of a slightly higher dose may be associated with more severe or additional significant changes in haematology, electrolytes or biochemical analytes. However, a preferable recommendation would be to administer this dosage of paracetamol in combination with another analgesic such as tramadol, as a subcutaneous injection, to improve efficacy.

Technical guideline for intra-prepontine cisternal drug delivery via spinal puncture through subarachnoid catheterization. / ç»è„ŠæŸ±æ¤Žé—´éš™ç©¿åˆºè››ç½‘è†œä¸‹è ”è„‘æ¡¥å‰æ± ç½®ç®¡è¯ç‰©è¾“æ³¨æŠ€æœ¯åº”ç”¨æŒ‡å—.

OBJECTIVES: The distribution characteristics of intrathecal drugs and the limitation of current catheterization techniques make traditional intrathecal analgesic treatment nearly useless for refractory craniofacial pain, such as trigemina neuralgia. This technical guideline aims to promote the widespread and standardize the application of intra-prepontine cisternal drug delivery via spinal puncture and catheterization. METHODS: A modified Delphi approach was used to work for this guideline. On the issues related to the intra-prepontine cisternal targeted drug delivery technique, the working group consulted 10 experts from the field with 3 rounds of email feedback and 3 rounds of conference discussion. RESULTS: For the efficacy and safety of the intra-prepontine cisternal targeted drug delivery technique, a consensus was formed on 7 topics (with an agreement rate of more than 80%), including the principles of the technique, indications and contraindications, patient preparation, surgical specifications for intra-prepontine cisternal catheter placement, analgesic dosage coordination, analgesic management, and prevention and treatment of complications. CONCLUSIONS: Utilizing the intra-prepontine cisternal drug infusion system to manage refractory craniofacial pain could provide advantages in terms of minimally invasive, secure, and effective treatment. This application can not only alleviate the suffering of individuals experiencing the prolonged pain but also support the maintenance of quality of life and dignity in their final moments, justifiing its widespread dissemination and standardized adoption in domestic and international professional fields.

A comparative study on prophylactic efficacy of cinnarizine and amitriptyline in childhood migraine: a randomized double-blind clinical trial.

BACKGROUND: Pediatric migraine prophylaxis is indicated when headaches are frequent and/or disabling. We aimed to conduct a study to compare the efficacy of cinnarizine and amitriptyline in pediatric migraine prophylaxis. METHODS: In a randomized, double-blind trial, patients aged 4-17 years with migraine who were eligible for prophylaxis enrolled. The primary outcome was a reduction response rate of ≥50% with p < 0.005 with respect to headache characteristics. The secondary outcome was migraine disability assessment. We evaluated patients every four weeks for three months: T1: week 4, T2: week 8 and T3: week 12. The safety profile was also assessed. RESULTS: Thirty patients were randomly assigned to each group. However, 43 patients completed the trial. Headache frequency decreased in amitriptyline group more effectively in T1 (p = 0.004). Amitriptyline was more successful in reducing the headache duration in all three periods (p < 0.005). There was no significant difference in severity improvement and reducing disability score between the two groups (p > 0.005). No serious adverse events were observed. CONCLUSIONS: Both medications are effective in ameliorating migraine headaches and related disabilities. However, amitriptyline appears be a preferable option over cinnarizine, given its faster onset of action, efficacy in reducing headache duration and longer-lasting effects.Trial Registration: The study was registered with the Iranian Registry of Clinical Trials (IRCT) under the code IRCT-20191112045413N1.

Effectiveness of Gel from Andaliman Fruit (Zanthoxylum acanthopodium DC.) Extract on Wound Inflammation.

<b>Background and Objective:</b> Pain is caused by damaged tissue on the outside or inside of an organ and it is regulated by chemicals. Synthetic drugs are used to ease pain because they are analgesics in the field of medicine. Traditional medicine is known to help people all over the world, in both rich and developing nations. The Andaliman fruit, or <i>Zanthoxylum acanthopodium</i> DC., comes from a spice plant that grows naturally in Toba Regency, North Sumatra, Indonesia. This study aims to determine the formulation of the nanoherbal analgesic spray gel preparation of Andaliman fruit (<i>Zanthoxylum acanthopodium</i> DC.) in terms of its effectiveness as a pain reliever. <b>Materials and Methods:</b> There were three amounts of spray gel made, namely 5, 10 and 15% and tests were done to see how well they worked. <i>Staphylococcus aureus</i> bacteria were used in the bacterial blocking test. To test how well painkillers worked, five groups of mice were used. Using a hot iron, tests for anti-inflammatory activity and wound healing were done. The tissue was then watched for 14 days and analysed using Hematoxylin and Eosin (H&E) stains. <b>Results:</b> The 15% concentration reduces pain and the time it takes for the body to respond to it. The clear zone size is the same as (K⁺) and it can lower the number of inflammatory cells and help wounds heal by adding fibroblast and collagen cells. These findings are supported by significant data results (p<0.05, p = 0.018). <b>Conclusion:</b> Finally, analgesic gel spray made from the Andaliman fruit at a 15% concentration can help with pain and also be antibacterial, reduce inflammation and help wounds heal.</p>.