Study on Analgesic Effects of Combined Thoracic Paravertebral Block Anesthesia or Erector Spinae Plane Block with Ultrasound Guided Transversus Abdominis Plane Block in Endoscopic Esophagectomy: A Clinical Anatomical Approach

SUMMARY: The application effect of transversus abdominis plane block (TAPB) combined with thoracic paravertebral block (TPVB) or erector spinae plane block (ESP) under ultrasound guidance in endoscopic radical resection of esophageal cancer under general anesthesia was studied. From March 2021 to February 2022, patients who underwent endoscopic radical resection of esophageal cancer in our hospital were selected as the research object, and 90 patients were selected as the samples. Patients were divided into groupA and group B according to the difference of blocking schemes. Group A received ESP and Group B received TPVB. The dosage of sufentanil, nerve block time, awakening time and extubation time of the two groups were counted. The postoperative pain, sedation effect, sleep satisfaction and analgesia satisfaction of the two groups were compared, and the complications of the two groups were observed. The nerve block time and extubation time in group A were shorter than those in group B (P0.05). At T2, T3 and T4, the visual analogue scale (VAS) scores of group A at rest and cough were significantly lower than those of group B (P0.05). The satisfaction of sleep and analgesia in group A was higher than that in group B (P0.05). The analgesic effect of ultrasound-guided TAPB combined with ESP is better than that of ultrasound-guided TAPB combined with TPVB, and it can shorten the time of nerve block and extubation, which is worth popularizing.

Se estudió el efecto de la aplicación del bloqueo del plano transverso del abdomen (TAPB) combinado con el bloqueo paravertebral torácico (TPVB) o el bloqueo del plano del erector de la columna (ESP) bajo guía ecográfica en la resección radical endoscópica del cáncer de esófago bajo anestesia general. Desde marzo de 2021 hasta febrero de 2022, en nuestro hospital, se seleccionaron como objeto de investigación pacientes sometidos a resección radical endoscópica de cáncer de esófago, y como muestra se seleccionaron 90 pacientes. Los pacientes se dividieron en el grupo A y el grupo B según la diferencia de esquemas de bloqueo. El grupo A recibió ESP y el grupo B recibió TPVB. Se contaron la dosis de sufentanilo, el tiempo de bloqueo nervioso, el tiempo de despertar y el tiempo de extubación de los dos grupos. Se compararon el dolor posoperatorio, el efecto de la sedación, la satisfacción del sueño y la satisfacción de la analgesia de los dos grupos y se observaron las complicaciones de los dos grupos. El tiempo de bloqueo nervioso y el tiempo de extubación en el grupo A fueron más cortos que los del grupo B (P0,05). En T2, T3 y T4, las puntuaciones de la escala visual analógica (EVA) del grupo A en repo- so y tos fueron significativamente más bajas que las del grupo B (P 0,05). La satisfacción del sueño y la analgesia en el grupo A fue mayor que en el grupo B (P0,05). El efecto analgésico de la TAPB guiada por ecografía combinada con ESP es mejor que el de la TAPB guiada por ecografía combinada con TPVB, y puede acortar el tiempo de bloqueo nervioso y extubación, lo que vale la pena popularizar.

Anestesia libre de opioides en cirugía bariátrica laparoscópica

Introducción: La anestesia libre de opioides surge de las alternativas farmacológicas que permiten otra opción anestésica en el arsenal del anestesiólogo. Objetivo: Evaluar la efectividad y seguridad de una técnica anestésica libre de opioides en el paciente intervenido con cirugía bariátrica laparoscópica. Métodos: Se realizó un estudio observacional analítico, prospectivo y longitudinal en 23 pacientes operados con anestesia general multimodal libre de opioides. Pacientes mayores de 18 años con un índice de masa corporal mayor o igual a 35 kg/m2, con estado físico ASA II y III. Se evaluó la analgesia posoperatoria e intraoperatoria como una necesidad de la analgesia de rescate en el tiempo de recuperación y los efectos adversos. Resultados: Se demostró que la edad promedio fue 38,19 ± 8,73 con un predominio en el sexo femenino, los pacientes fueron clasificados como ASA II y obesos grados III. Hubo una estabilidad hemodinámica intraoperatoria. El 82,6 % de los pacientes no presentaron dolor posoperatorio en las primeras 24 h. No se presentaron pacientes con dolor severo. Requirieron analgesia de rescate cinco pacientes (21,7 %) en posoperatorio, y las complicaciones fueron escasas sin repercusión clínica. El tiempo promedio para la extubación fue de 6,7 ± 0,8 min y la recuperación total de 29,6 ± 0,8 min. Conclusiones: La técnica multimodal libre de opioides resultó segura y efectiva, con un adecuado estado de analgesia perioperatoria y escasas complicaciones en los pacientes intervenido con cirugía bariátrica laparoscópica.

Introduction: Opioid-free anesthesia arises from pharmacological alternatives that allow another anesthetic option in the anesthesiologist's arsenal. Objective: To evaluate the effectiveness and safety of an opioid-free anesthetic technique in patients undergoing laparoscopic bariatric surgery. Methods: An analytical, prospective and longitudinal observational study was carried out in 23 patients operated on with opioid-free multimodal general anesthesia. The patients studied were over 18 years of age, with a body mass index greater than or equal to 35 kg/m2, ASA physical status II and III. Postoperative and intraoperative analgesia were evaluated as a need for rescue analgesia in recovery time and adverse effects. Results: It was shown that the average age was 38.19 ± 8.73 with a predominance in the female sex, the patients were classified as ASA II and grade III obese. There was intraoperative hemodynamic stability. 82.6% of patients did not experience postoperative pain in the first 24 hours. There were no patients with severe pain. Five patients (21.7%) required rescue analgesia postoperatively, and complications were rare without clinical repercussions. The average time for extubation was 6.7 ± 0.8 min and total recovery was 29.6 ± 0.8 min. Conclusions: The opioid-free multimodal technique was safe and effective, with adequate state of perioperative analgesia and few complications in patients undergoing laparoscopic bariatric surgery.

The essential oil from Kelussia odoratissima Mozaff. fruits exerting potent analgesic and anti-inflammatory effects / El aceite esencial de frutos de Kelussia odoratissima Mozaff. ejerce potentes efectos analgésicos y antiinflamatorios

Kelussia odoratissima fruits are utilized in Persian traditional medicine as a painkiller and to prevent inflammation-based disorders. Considering the higher content of essential oil in the fruits, the oil's anti-inflammatory and analgesic activities were investigated via the paw edema triggered in mice and the writhing test and hot plate technique, respectively. It was observed that the 100, and 200 mg/Kg doses of the oil revealed an analgesic impact (p<0.001) considering the increment in the reaction time needed for the hot plate approach. Furthermore, 100 and 200 mg/Kg doses of the oil caused a reduction in the frequency of writhes in the mice (p<0.01 and p<0.001, respectively). Using all examined doses of theoil (25, 50, and 100 mg/Kg) caused inflammatory reduction (p<0.001). The findings indicated that the oil possess significant activities against acute inflammation. It had both peripheral and central pain-killing impacts. The main components 3-n-butylphthalide (28.3%) and germacrene D (17.3%) can be considered as the responsible compounds to manage the inflammation and pain.

Las frutas de Kelussia odoratissima se utilizan en la medicina tradicional persa como analgésico y para prevenir los trastornos basados en la inflamación. Teniendo en cuenta el mayor contenido de aceite esencial en las frutas, se investigaron las actividades antiinflamatorias y analgésicas del aceite a través del edema de la pata desencadenado en ratones y la prueba de contorsiones y la técnica del plato caliente, respectivamente. Se observó que las dosis de 100 y 200 mg / kg del aceite revelaron un impacto analgésico (p<0,001) considerando el incremento en el tiempo de reacción necesario para el enfoque de placa caliente. Además, dosis de 100 y 200 mg / kg del aceite provocaron una reducción en la frecuencia de retorcimientos en los ratones (p<0,01 y p<0,001, respectivamente). El uso de todas las dosis examinadas del aceite (25, 50 y 100 mg/kg) provocó una reducción inflamatoria (p<0,001). Los hallazgos indicaron que el aceite posee actividades significativas contra la inflamación aguda. Tiene impactos analgésicos tanto periféricos como centrales. Los principales componentes 3-n-butilftalida (28,3%) y germacreno D (17,3%) pueden considerarse como los compuestos responsables del manejo de la inflamación y el dolor.

Application of Natural Ingredients of Traditional Chinese Medicine in Pain Management： A Review / 中国实验方剂学杂志

Pain is one of the most prevalent health problems. Current medications for pain are mainly anticonvulsants， tricyclic antidepressants， and opioidergic drugs. However， their therapeutic effectiveness is limited during application， and some even have severe side effects. In recent years， research on natural ingredients from Chinese herbal medicine has been extensively conducted for their analgesic activities. A series of natural ingredients represented by alkaloids， coumarins， flavonoids， and terpenoids have shown great analgesic activity， and further studies on their analgesic mechanism have found that most natural products have multi-target analgesic mechanisms. It can exert analgesic effects by blocking ion channels， regulating related receptors， or inducing anti-inflammatory or antioxidant effects. In addition， many traditional Chinese medicine （TCM） formulas have shown great analgesic ability after clinical application and have multiple complex analgesic mechanisms. The drug cloud （dCloud） theory can better describe the mechanisms， and it can represent the complete therapeutic spectrum of multi-target analgesics from two dimensions， namely the "direct efficacy" that directly inhibits pain signals and the "background efficacy" that targets the root causes of pain. The authors summarized the research progress of natural ingredients with analgesic effects found in Chinese herbal medicine so far， as well as the analgesic efficacy and potential mechanisms of TCM formulas with great analgesic effects in clinical applications， so as to provide a new basis for searching for new analgesic drugs from TCM.

Advances in medicinal research on tetrodotoxin / 药学实践杂志

Tetrodotoxin (TTX) is a neurotoxin found in puffer fish and other marine organisms. It has been used as an inhibitor of voltage-gated sodium channels (VGSCs), which could selectively bind to the α-subunit on the outer vestibule of VGSCs, preventing sodium ions from entering the channel, resulting in pharmacological activities. As a typical sodium channel blocker, TTX shows a significant analgesic effect. TTX could selectively block Na+ channels without affecting other ion channels, therefore it could reduce the probability of adverse reactions caused by commonly used antiarrhythmic drugs. In addition, TTX has a significant role in detoxification and prevention of renal failure, so TTX has great potential as a medicine. The structure and physicochemical properties, mechanism of action, pharmacological activities and preparations of tetrodotoxin have been reviewed in this paper, so as to provide a general support for the evaluation of its druggability and application in the field of pharmacy.

Efficacy and safety of ropivacaine combined with alfentanil for analgesia after knee arthroscopic surgery / 中国药房

OBJECTIVE To explore the efficacy and safety of intra-articular injection of ropivacaine combined with alfentanil for postoperative analgesia in patients who underwent knee arthroscopic surgery. METHODS A total of 60 patients who underwent knee arthroscopic surgery were collected from the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture from March to September in 2022， and then divided into trial group and control group with random number table method， with 30 cases in each group. The control group received intra-articular injection of 0.25% ropivacaine 50 mg， and the trial group received intra-articular injection of 0.25% ropivacaine 50 mg+alfentanil 0.15 μg/kg.The first postoperative remedial analgesia time， the total amount of postoperative remedial drugs， numerical rating scale at rest （NRS-R） scores， numerical rating scale at movement （NRS-M） scores， heart rate， mean arterial blood pressure， and pulse oxygen saturation during exercise at different monitoring time points after surgery， the incidence of adverse drug reactions such as hypotension， respiratory depression， nausea， and vomiting after surgery were compared between 2 groups. RESULTS Compared with the control group， the first postoperative remedial analgesia time was significantly longer in the trial group， and the total amount of postoperative remedial drugs was significantly reduced （P＜0.001）. The trial group had lower NRS-R and NRS-M scores at each monitoring time point， with statistically significant differences （P＜0.001）， and there was an interactive effect between time and groups （P＜0.001）. The changes in heart rate， mean arterial blood pressure， and pulse oxygen saturation of patients in the trial group were relatively small， with no statistically significant differences （P＞0.05）， and there was no interactive effect between time and groups （P＞0.05）. There was no statistical significance in the incidence of adverse drug reactions between 2 groups， such as postoperative hypotension， respiratory depression， nausea， vomiting （P＞0.05）. CONCLUSIONS The intra- articular injection of ropivacaine combined with alfentanil shows good efficacy and safety for post-knee arthroscopic analgesia， and significantly prolongs the analgesic duration of ropivacaine.

(+)/(-)-Yanhusamides A-C, three pairs of unprecedented benzylisoquinoline-pyrrole hetero-dimeric alkaloid enantiomers from Corydalis yanhusuo

A chemical investigation on the aqueous extract of Corydalis yanhusuo tubers led to the isolation and structural elucidation of three pairs of trace enantiomeric hetero-dimeric alkaloids, (+)/(-)-yanhusamides A-C ( 1- 3), featuring an unprecedented 3,8-diazatricylco[5.2.2.02,6]undecane-8,10-diene bridged system. Their structures were exhaustively characterized by X-ray diffraction, comprehensive spectroscopic data analysis, and computational methods. Guided by the hypothetical biosynthetic pathway for 1- 3, a gram-scale biomimetic synthesis of (±)- 1 was achieved in 3 steps using photoenolization/Diels-Alder (PEDA) [4+2] cycloaddition. Compounds 1‒3 exhibited potent inhibition of NO production induced by LPS in RAW264.7 macrophages. The in vivo assay showed that oral administration of 30 mg/kg of (±)- 1 attenuated the severity of rat adjuvant-induced arthritis (AIA). Additionally, (±)- 1 induced a dose-dependent antinociceptive effect in the acetic acid-induced mice writhing assay.

Bispecific sigma-1 receptor antagonism and mu-opioid receptor partial agonism: WLB-73502, an analgesic with improved efficacy and safety profile compared to strong opioids

Opioids are the most effective painkillers, but their benefit-risk balance often hinder their therapeutic use. WLB-73502 is a dual, bispecific compound that binds sigma-1 (S1R) and mu-opioid (MOR) receptors. WLB-73502 is an antagonist at the S1R. It behaved as a partial MOR agonist at the G-protein pathway and produced no/unsignificant β-arrestin-2 recruitment, thus demonstrating low intrinsic efficacy on MOR at both signalling pathways. Despite its partial MOR agonism, WLB-73502 exerted full antinociceptive efficacy, with potency superior to morphine and similar to oxycodone against nociceptive, inflammatory and osteoarthritis pain, and superior to both morphine and oxycodone against neuropathic pain. WLB-73502 crosses the blood-brain barrier and binds brain S1R and MOR to an extent consistent with its antinociceptive effect. Contrary to morphine and oxycodone, tolerance to its antinociceptive effect did not develop after repeated 4-week administration. Also, contrary to opioid comparators, WLB-73502 did not inhibit gastrointestinal transit or respiratory function in rats at doses inducing full efficacy, and it was devoid of proemetic effect (retching and vomiting) in ferrets at potentially effective doses. WLB-73502 benefits from its bivalent S1R antagonist and partial MOR agonist nature to provide an improved antinociceptive and safety profile respect to strong opioid therapy.

Immediate analgesic effect of electroacupuncture combined with diclofenac sodium on acute gouty arthritis: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the immediate analgesic effect of electroacupuncture (EA) combined with diclofenac sodium on acute gouty arthritis (AGA).@*METHODS@#A total of 90 patients with AGA were randomly divided into a low-dose medication (LM) group (30 cases, 1 case was eliminated, 1 case dropped off), a conventional medication (CM) group (30 cases, 1 case dropped off) and a combination of acupuncture and medication (AM) group (30 cases ). The LM group was given oral administration of 50 mg diclofenac sodium sustained-release capsule; the CM group was given oral administration of 100 mg diclofenac sodium sustained-release capsule; on the basis of the treatment of LM group, the AM group was treated with electroacupuncture at ashi points, Dadu (SP 2), Taichong (LR 3), Taibai (SP 3), Neiting (ST 44), Sanyinjiao (SP 6), Zusanli (ST 36) and Yinlingquan (SP 9) on the affected side, and Taichong (LR 3) and Zusanli (ST 36), Sanyinjiao (SP 6) and Yinlingquan (SP 9) were connected to electroacupuncture respectively, continuous wave, 2 Hz in frequency. The visual analogue scale (VAS) scores of pain before treatment and after 10 min, 2 h, 4 h and 6 h of treatment completion, joint tenderness and swelling scores before treatment and after 10 min and 6 h of treatment completion were compared, and the rate of diclofenac sodium addition within 24 h after treatment completion was recorded among the three groups.@*RESULTS@#After 10 min of treatment completion, the scores of VAS, joint tenderness and joint swelling in the AM group were lower than those before treatment (P<0.05), and the VAS score in the AM group was lower than that in the other two groups (P<0.05). After 2, 4 and 6 h of treatment completion, the VAS scores of the three groups were lower than those before treatment (P<0.05), and the scores in the AM group were lower than those in the LM group (P<0.05). After 6 h of treatment completion, the joint tenderness scores of the three groups and the joint swelling scores of the AM group and the CM group were lower than those before treatment (P<0.05), and the joint tenderness and swelling scores of the AM group were lower than those of the LM group (P<0.05). The rate of diclofenac sodium addition was 3.3 % (1/30) and 3.4 % (1/29) in the AM group and the CM group, respectively, which were lower than 17.9% (5/28) in the LM group (P<0.05).@*CONCLUSION@#Electroacupuncture combined with diclofenac sodium have a good immediate analgesic effect in the treatment of AGA, and have the advantages of small dosage of analgesic drugs and less adverse reactions.

“Liquid seal to detoxification – drying and puffing” of two stage processing technology design and pharmacodynamic study of aconite (Aconiti Lateralis Radix Praeparata) processed by microwave / 药学学报

Establish a production line with controllable process and high intelligence, contribute to improve the quality and production efficiency of aconite processed by microwave, and promote the transformation and application of aconite processed by microwave. According to the principle of aconite detoxification and the characteristics of industrial microwave equipment, an industrial production line of aconite processed by microwave was established with diester alkaloids and monoester alkaloids as indicators, and pilot production was carried out. At the same time, the content of active constituents and efficacy were compared with that of the main processed products, such as Shengfupian, Baifupian and Heishunpian. The results showed that the industrial production of aconite processed by microwave can be divided into two stages: "Liquid seal to detoxification - drying and puffing". The content of monoester alkaloids in 10 batches of aconite processed by microwave was 0.071%-0.166% and the content of diester alkaloids was 0.004%-0.016%, which met the relevant requirements of the Chinese Pharmacopoeia in 2020. Compared with Heishunpian and Baifupian, the retention rate of the effective components of aconite processed by microwave was higher. Pharmacological experiments showed that aconite processed by microwave not only retained the anti-inflammatory and analgesic activities of Heishunpian and Baifupian, but also significantly increased the levels of leukocytes and lymphocytes in mice with liver cancer chemotherapy, enhanced the CD4/CD8 ratio in spleen cells of mice (P < 0.05), thus regulating the body's immunity. However, this effect of Baifupian was weak, while Heishunpian and Shengfupian had no such effect. Through the above research, this study established microwave processing line with controllable process and high intelligence, as well produced the aconite processed by microwave with low toxicity and stable quality. It laid a foundation for the industrialized continuous production and clinical positioning of aconite by microwave processed, and provided scientific support for the development and application of microwave technology in the field of traditional Chinese medicine. All animal experiments in this study were reviewed and approved by the Experimental Animal Ethics Committee of Chengdu University of Traditional Chinese Medicine before being carried out (Approval No. 2020-28).

Exploration and Assessment on the Agronomic Requirement of Taverniera abyssinica A. Rich: A Critically Endangered Medicinal Plant of Ethiopia

We determined the distribution and abundance of Taverniera abyssinica A. Rich in the Shewa floristic region, Ethiopia. We also carried out a mesh-house experiment to know whether T. abyssinica is able to survive and grow in any soil. From the nine potential locations we made exploration, T. abyssinca populations were found only in the two, Lemen and Mojo. The abundance of mature individuals was estimated to be more than 600/hectare. The one-way ANOVA results indicated that soil does not have a significant (p>0.05) effect on seedlings survival rate. However, it was found to have significant (p<0.05) effects on seedlings growth, root nodulation, and root arbuscular mycorrhizal fungi colonization. Seedlings grown on the soil collected from Lemen and Mojo produced significantly (p<0.05) more number of leaves and grew better than those grown on Addis Ababa (where the species was never reported to grow) soil. The root fresh weight of seedlings grown on Addis Ababa soil was found to be significantly (p<0.05) and 38.89% and 54.17% lower than the root fresh weight of seedlings grown on Lemen and Mojo soils respectively. We report that T. abyssinica is N-fixer and arbuscular mycorrhizal. Seedlings grown on the Addis Ababa soil were not colonized by arbuscular mycorrhizal fungi while those grown on Lemen and Mojo soils were. Although the estimated abundance of mature T. abyssinica individuals was high, there is continued exploitation of the species and habitat loss is imminent. Therefore, integrated conservation program by way of ex situ conservation, in situ conservation, and cultivation should be implemented. Taverniera abyssinica could be cultivated in areas with leptosol and degraded vertisol soils with slightly acidic to basic pH. Arbuscular mycorrhizal fungi could play key role in future conservation and cultivation efforts of the species.

Preclinical evaluation of analgesic activity of hydroalcoholic extract of Costus pictus leaves in Wistar albino rats

Background: Pain is the most common symptom in various pathological conditions requiring appropriate treatment with analgesics. Use of analgesics is limited by various adverse drug effects. The present study was aimed to evaluate the analgesic activity of hydroalcoholic extract of Costus pictus leaves in Wistar albino rats. Aim and Objective: The objective of this study is to evaluate the analgesic activity of hydroalcoholic extract of C. pictus leaves in Wistar albino rats. Materials and Methods: The study was conducted on 30 Wistar albino rats and was divided into five groups each of six rats. Group-I (Sterile water-equivalent volume/po), Group-II Morphine (5 mg/kg/ip), Group-III CPHAE (200 mg/kg/po), Group-IV CPHAE (400 mg/kg/po), and Group-V Diclofenac (12.5 mg/kg/po). All the rats were administered respective drugs before starting of 30 min of experiment. Central analgesic (Tail clip and hot plate) and peripheral analgesic (Writhing test) methods were used to evaluate the analgesic activity. The data were recorded and analyzed with SPSS software. Results: Group-II, III, IV and V showed significant analgesic activity compared to Group-I in both central and peripheral animal models. Group-II showed significant effect compared to Group-III and IV in the central analgesic activity. Group-V showed significant effect compared to Group-III and IV in peripheral analgesic activity. Group-IV showed significant effect compared to Group-III. Conclusion: High dose of (400 mg/kg) C. pictus plant extract showed significant analgesic activity in the central and peripheral animal models compared to low dose.

Evaluation of analgesic properties of petroleum ether extract of Zingiber officinale

Background: Herbal remedies and alternative therapies have been employed in the treatment of pain from time immemorial. Ginger is a widely used spice with a lot of medicinal properties, and it is especially soothing to the gastro-intestinal system. Most of the analgesics used in modern medicine have side effects to either gastro-intestinal tract or nervous system. Ginger has neither. Scientific evaluation of the analgesic properties of Zingiber officinale is needed. Aim and Objective: The aim of the study was to evaluate the analgesic effect of three doses of orally administered petroleum ether extract of Z. officinale and to compare with morphine. When tested for analgesic activity, to find out the difference in reaction time at various time intervals for each dose of the extract, and their significance. Materials and Methods: Petroleum ether extract of Z. officinale rhizomes was used. Wistar strain albino rats (150-200 g) and Swiss albino mice (20-25 g) housed under standard laboratory conditions were used. The central analgesic activities of the extract were evaluated by the tail clip method and hot plate method. Statistical analysis was done by one-way analysis of variance to compare the means in the experimental groups. Results: In tail clip method, pain was mechanically induced pain and the pain threshold was measured in terms of mice’ reaction time in seconds. All doses of the extract of Z. officinale were capable of increasing the reaction time in mice during the various time periods. Maximum analgesic activity was shown by 800 mg/kg of the extract at 90 minutes. In hot plate test, maximum analgesic activity was shown by 800 mg/kg of the extract at 180 min. At 30 and 60 min, 800 mg/kg of the extract was as effective as the standard drug, morphine. Conclusions: The study revealed that Z. officinale has significant analgesic properties especially in higher doses.

The Effect of Intravenous Ketamine After Spinal Anesthesia on the Duration of Postoperative Analgesia and Analgesic Requirement

Objective: To evaluate the impact of ketamine following spinal anesthesia on the duration of postoperative analgesia and the need for analgesics. Methods: This was a prospective, randomized, double-blinded placebo-controlled study done over a period of two years. A total of 60 participants undergoing elective surgeries under spinal anesthesia were randomized into two groups. After 10 min of spinal anesthesia and achieving the required level of sensory and motor blockade, both groups were given Inj. Midazolam 1 mg intravenously, followed by Inj. Ketamine 0.25 mg/kg, volume made up to 10 mL with normal saline, given intravenously for Group K and Inj. Normal Saline 10 mL was given intravenously for Group N. Hemodynamic monitoring was done intraoperatively, and the postoperative visual analog score (VAS), sedation score, the mean time for the first rescue analgesia, and the total dose of postoperative analgesic required in 24 h were tabulated. Results: There was no statistical difference between the two groups in terms of age, weight, ASA grade, and duration of surgery. In Group K, the VAS scores were significantly lower and patients were comfortable when compared to Group N (P value <.01). The mean time to first rescue analgesia was longer in Group K (6.4 ± 1.69 h) when compared to Group N (2.9 ± 1.01 h), and the total dose of postoperative analgesia (Tramadol) required in 24 h was also significantly less in Group K (143.33 ± 56.83 mg) when compared to Group N (236 ± 49.01 mg). Changes in hemodynamic parameters (heart rate and mean arterial pressure (MAP)) were statistically and clinically not significant in both the intraoperative and postoperative periods between the groups. Conclusion: Patients in Group K were more comfortable, had a longer duration of postoperative analgesia, and required less dose of rescue analgesia in the postoperative period. Ketamine is a safe drug that is readily available, and it decreases the use of opioids and opioid-related side effects. Therefore, ketamine can serve effectively as an adjunctive analgesic drug.

Looking beyond the obvious: Role of non?invasive electroanalgesia in management of cancer pain

Pain is considered as one of the most debilitating symptoms of cancer and its treatment. Owing to the limited efficacy of traditional pharmacological interventions to address cancer pain in its entirety, an avenue exists for exploration into nonpharmacological therapies. Analgesia using non?invasive electrotherapeutic modalities such as transcutaneous electrical nerve stimulation (TENS) and scrambler therapy emerges as a viable option to address cancer pain. The inability of these modalities to find a place within the recommended clinical guidelines has possibly resulted in the paucity of application of the same within the clinical setup. This perspective article aims at stimulating a discussion surrounding the inclusion of non?invasive neuromodulatory treatment techniques such as TENS and scrambler therapy to combat cancer pain and explore the benefits and pitfalls of using these techniques as an adjunct to the pre?existing treatment strategies. It is envisioned that this opinion piece will open a dialogue about a possible home for non?invasive electroanalgesia within the clinical treatment pathway for cancer pain.

Opioids for Pediatric Pain Management

Objectives: To study the efficacy and adverse effects of opioids in management of pain in children. Methods: A descriptive study was conducted in children aged below 15 years with moderate to severe pain, and response to opioids and adverse effects were assessed at 24, 48 and 72 hours after administration. Results: 100 children (68% males) with median (IQR) age of 6.5 (3.5,10) years were studied. 81% (n=81) children with moderate pain and 78.9% (n=15) with severe pain responded to opioids in 72 hours. Among children with severe pain of non-malignant origin, 80% (n=8) responded in 48 hours compared to 11.1% (n=1) with malignancy and this difference was statistically significant at 24 hours (P=0.005). Of children with severe pain 73.7% (n=14) developed adverse reactions compared to 30.9% (n=25) with moderate pain. Conclusions: Children with moderatesevere pain, either of malignant or non-malignant origin could be managed effectively with opioids without severe adverse effects.

Oral administration of eucalyptol reduces cell migration and pain-like behavior in zymosan-induced arthritis mice

Abstract Rheumatoid arthritis (RA) is an inflammatory disease that utilizes nonbiologic and biologic drugs for appropriate disease management. However, high cost, adverse effects, reduced effectiveness, and risk of infection have stimulated the search for safer and more efficacious therapeutic strategies. In the present study, we aimed to evaluate the anti-inflammatory and analgesic properties of eucalyptol in an experimental model of arthritis. Mice were administered zymosan or saline intra-articularly. One hour before the zymosan administration, the mice were treated with oral eucalyptol (200-400 mg/kg) and vehicle. Cell influx, neutrophils, lymphocytes, and monocytes were measured in joint exudates. Joint pain was assessed using paw-pressure tests. Orally administered eucalyptol (200 and 400 mg/kg) significantly reduced cell influx, as well as neutrophils, lymphocytes, and monocytes, when compared with the control. Eucalyptol at a dose of 400 mg/kg significantly reversed joint pain and demonstrated analgesic activity (60%); however, 200 mg/kg failed to alter joint pain. These results indicate that oral eucalyptol promotes anti-inflammatory and analgesic activity in mice subjected to zymosan-induced arthritis.

Phytochemical investigation on Vitex negundo leaves and their anti-inflammatory and analgesic activities

Abstract The phytochemical investigation on Vitex negundo leaves has led to the isolation of one new iridoid glucoside (8α-hydroxy-4-carboxyl-5ßH-9ßH-iridoid-1α-O-(6'-O-(6,7-dihydrofoliamenthonyl)-ß-ᴅ-glucopyranoside, 3), together with three known compounds, namely agnuside (1), 6'-O-E-caffeoylmussaenosidic acid (2), and 3,5-dicaffeoylquinic acid (4). The HPLC analytical study was also performed to quantify the content of agnuside (1) in dried leaves. The results indicated the very high content of 1 (3.04 ± 0.02%). The method was also validated by various parameters, including linearity (R2= 0.9999), precision (intra-day RSD ≤ 2.50%, inter-day RSD= 0.76%), and accuracy (recovery rates 96.58-101.86%). The animal testing data showed that the extract did not reduce pain at the doses of 9.6 and 28.8 g /kg (leaf weight/body weight) in the hot plates and pain measuring models but showed the pain reduction in the acetic acid-induced pain model. The extract at the dose of 5.6 g/kg (leaf weight/body weight) also had effects on the acute inflammation in the carrageenin-induced edema model. The extract at the dose 9.6 and 28.8 g/kg (leaf weight/body weight) also showed significant chronic anti-inflammation, comparable to methylprednisolone at the dose 10 mg/kg on the mouse peritoneal

Analgesic, antipyretic, anti-inflammatory, and hepatoprotective activities of Pulicaria crispa (Forssk. ) Oliv. (Asteraceae)

Abstract Some plants of the genus Pulicaria have been used in traditional medicines for treating back pain and inflammation. They possess various bioactivities such as antipyretic, analgesic, and hepatoprotective. This study aimed to investigate the potential analgesic, antipyretic, anti- inflammatory, and hepatoprotective activities of Pulicaria crispa (P. crispa) extract (PCE). Analgesic activity was evaluated using the hot plate and acetic acid-induced writhing tests. Antipyretic and anti-inflammatory activities were evaluated using rectal temperature and carrageenan-induced hind paw edema methods, respectively. CCl4-intoxication was used for hepatoprotective activity. Also, liver histopathology was assessed. PCE, at 500 mg/kg, exhibited significant analgesic, antipyretic, and anti-inflammatory effects. The increased serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and bilirubin of CCl4-exposed rats reflects their liver injury. PCE significantly decreased the elevated liver markers. The hepatoprotective effect of PCE was confirmed, as it successfully reversed the altered levels of total protein, malondialdehyde (MDA), and non-protein sulfhydryls (NP-SH) in the liver tissues of CCl4-exposed rats. Histopathological studies confirmed the hepatoprotective nature of PCE. Pretreatment of rats with PCE reduced the severity of CCl4-induced liver damage. These findings concluded that PCE possesses analgesic, antipyretic, anti-inflammatory, and hepatoprotective activities.