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Strong opioids are the cornerstone in the treatment of cancer-related pain. This study aims to compare analgesic effectiveness of different strong opioids for the treatment of cancer-related pain. PubMed and Embase were searched for RCTs that compared strong opioids for treatment of cancer-related pain against one another. A network meta-analysis was conducted and the related Surface Under the Cumulative RAnking (SUCRA)-based treatment ranks were calculated. Primary outcome was pain intensity (numerical rating scale (NRS)) and/or the percentage of patients with ≥50% pain reduction, after 1 and 2–4 weeks. Sixteen RCTs (1813 patients) were included. Methadone showed, with a high certainty of evidence, increased ORs for treatment success at 1 week, compared with morphine, buprenorphine, fentanyl, and oxycodone, range 3.230–36.833. Methadone had the highest likelihood to be the treatment of preference (ToP) (SUCRA 0.9720). For fentanyl, ORs were lower, however significant and with high certainty. After 2–4 weeks, methadone again showed the highest likelihood for ToP, however, with moderate certainty and nonsignificant ORs. The combination of morphine/methadone, compared with morphine, buprenorphine, fentanyl, hydromorphone, methadone, and oxycodone achieved a treatment effect of mean NRS difference after 2–4 weeks between −1.100 and −1.528 and had the highest likelihood for ToP. The results suggest that methadone possibly deserves further promotion as first-line treatment for the treatment of cancer-related pain. [ABSTRACT FROM AUTHOR]

Background Methods Conclusion Peripheral nerve blocks effectively alleviate postoperative pain. Animal studies and human research suggest that opioid tolerance may reduce the effectiveness of local analgesics. The reduced effectiveness has been observed in opioid‐tolerant humans and animals undergoing spinal and infiltration anaesthesia with both lidocaine and bupivacaine. However, the impact on peripheral nerve blocks in humans has not been evaluated. This study aims to assess the onset time and duration of a radial nerve block in opioid‐tolerant individuals compared to opioid‐naive individuals. We hypothesise that peripheral nerve blocks may be less effective in producing sensory and motor blockades in opioid‐tolerant individuals compared to their opioid‐naive counterparts.Twenty opioid‐tolerant individuals will be matched by sex and age with opioid‐naïve counterparts. Participants will receive an ultrasound‐guided radial nerve block. The primary outcome is the difference in the duration of sensory nerve blockade between the two groups. The secondary outcomes include the onset time of sensory blockade, onset time of motor blockade, and difference in duration of motor nerve blockade.This study will compare the effectiveness of a peripheral nerve block between opioid‐tolerant and opioid‐naïve individuals. Any found differences could support a specific postoperative protocol for opioid‐tolerant individuals regarding the use of peripheral nerve blocks. [ABSTRACT FROM AUTHOR]

Aims: Bone cancer produces severe pain that is treated with opioids, but serious side effects limit opioid utilization. There is therefore a need to develop effective and safe non‐opioid alternatives. The lipid mediator, Resolvin D1 (RvD1), could be a prospective candidate for cancer pain treatment. To assess RvD1 and other potential candidates, appropriate animal models that recapitulate clinical features must be used. Although several preclinical models of cancer pain have been developed, the influence of sex on the development of cancer pain and the effectiveness of RvD1 have not been studied. Results: Using a mouse model of fibrosarcoma growth in and around the calcaneus bone, we demonstrated that the mechanical hyperalgesia in the tumor‐bearing hind paw develops independently of sex, except that it developed a little sooner in female mice. A single intravenous injection of RvD1 (0.001–10 μg/kg) decreased hyperalgesia in both sexes with similar potency (ED50 = 0.0015 μg/kg) and efficacy. Repeated daily administration of 10 μg/kg RvD1 prolonged the analgesic effect and completely abolished hyperalgesia. This was also independent of sex. Conclusion: In this preclinical mouse model of bone cancer pain, the development of pain and the analgesic effectiveness of RvD1 are not influenced by sex. [ABSTRACT FROM AUTHOR]

Introduction: Most patients undergoing the Nuss procedure reported moderate to severe pain after surgery. This study aimed to investigate the efficacy and safety of ultrasound-guided serratus anterior plane block (SAPB) combined with transversus thoracic muscle plane (TTMP) block for relieving acute pain in patients undergoing the Nuss procedure. Methods: The enrolled patients in our study were allocated to either receive combined nerve blocks with ropivacaine (NB group) or saline (CON group). The primary outcome of this study was postoperative pain at 2, 4, 8, 16, 24, 36, and 48 h during rest and movement (coughing). Secondary outcomes included intraoperative dosage of remifentanil, the time to extubation and the length of stay in the post-anesthesia care unit (PACU), the total acetaminophen and codeine tablet consumption, time to first bowel movement, time to first flatus, opioid-related adverse events, and the length of hospital stay. Results: Patients in the NB group had significantly lower Numerical Rating Scale (NRS) pain scores compared with the CON group. The NB group required significantly less postoperative acetaminophen consumption and lower dosages of perioperative sufentanyl and remifentanil compared with the CON group. The length of stay in the PACU and time to extubation were significantly increased in the CON group compared with the NE group. Time to first bowel movement and time to first flatus were earlier in the NB group. But there were no significant differences between the groups in terms of the length of hospital stay and codeine tablet consumption. Conclusion: Ultrasound-guided SAPB and TTMP blocks in patients undergoing the Nuss procedure could provide effective analgesia. Trial Registration: This study was registered in the Chinese Clinical Trial Registry (ChiCTR2000038506). [ABSTRACT FROM AUTHOR]

Alkaloid analgesics have been associated with adverse effects on the central nervous system (CNS). Therefore, it is crucial to characterize the effects of alkaloid analgesics. Plants rich in lycorine, an alkaloid, have shown promise as analgesics. However, the exploration of their CNS side effects, and analgesic effectiveness remains incomplete. The aim of the present study was to investigate the CNS safety profiles of lycorine and its potential analgesic efficacy. Lycorine (3, 10, and 30 mg/kg, intraperitoneal) did not affect motor coordination, and doses of 3 and 10 mg/kg of lycorine did not lead to any impairment in spontaneous locomotor activity. However, the highest dose (30 mg/kg) demonstrated a significant impairment in rearing behavior and an increase in immobility. The safety doses were subsequently used to assess the analgesic efficacy of lycorine in a mouse model of inflammatory pain. Lycorine (1, 3, and 10 mg/kg, intraperitoneal) demonstrated a dose-dependent reduction in pain-like behaviors in formalin-induced mice. In the in vitro study, lycorine regulated immune cells, suggesting its involvement as a cellular mechanism underlying the suppression of pain-like behaviors observed in the formalin model. Overall, our findings delineate the CNS safety range of lycorine in mice and suggest its potential use as an analgesic. [ABSTRACT FROM AUTHOR]

Background: The pleiotropic effects of the melanocortin system show promise in overcoming limitations associated with large variations in opioid analgesic effectiveness observed in equine practice. Of particular interest is variation in the melanocortin-1-receptor (MC1R) gene, which dictates pigment type expression through its epistatic interaction with the agouti signalling protein (ASIP) gene. MC1R has previously been implicated in opioid efficacy in other species; however, this relationship is yet to be explored in horses. In this study, analgesic effectiveness was scored (1-3) based on noted response to dura penetration during the performance of cerebrospinal fluid centisis after sedation and tested for association with known genetic regions responsible for pigmentation variation in horses. Results: The chestnut phenotype was statistically significant (P < 0.05) in lowering analgesic effectiveness when compared to the bay base coat colour. The 11bp indel in ASIP known to cause the black base coat colour was not significant (P>0.05); however, six single nucleotide polymorphisms (SNPs) within the genomic region encoding the ASIP gene and one within MC1R were identified as being nominally significant (P<0.05) in association with opioid analgesic effectiveness. This included the location of the known e MC1R variant resulting in the chestnut coat colour. Conclusions: The current study provides promising evidence for important links between pigmentation genes and opioid effectiveness in horses. The application of an easily identifiable phenotype indicating variable sensitivity presents a promising opportunity for accessible precision medicine in the use of analgesics and warrants further investigation. [ABSTRACT FROM AUTHOR]

Pericapsular nerve group (PENG) block and periarticular injection (PAI) provide motor-sparing analgesia following hip surgery. We hypothesized that PAI offers non-inferior pain relief compared with PENG block in patients undergoing primary total hip arthroplasty (THA). In this randomized trial, 66 patients who underwent primary THA under spinal anesthesia were assigned to the PENG or PAI groups. The primary endpoint was the resting pain score 24 h postoperatively. The secondary endpoints included pain scores at rest and during movement at 6 and 48 h postoperatively, quadriceps strength at 24 h postoperatively, and opioid consumption at 24 and 48 h postoperatively. The mean difference in pain scores at rest between the two groups was 0.30 (95% confidence interval [CI], −0.78 to 1.39) at 24 h postoperatively. The upper 95% CI was lower than the non-inferiority margin, indicating non-inferior performance. No significant between-group differences were observed in the pain scores at 6 and 48 h postoperatively. Additionally, no significant differences in quadriceps strength and opioid consumption were observed between the two groups. The PAI and PENG blocks provided comparable postoperative analgesia during the first 48 h after primary THA. Further investigation is required to determine the optimal PAI technique and local anesthetic mixture. [ABSTRACT FROM AUTHOR]

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Breast cancer is the most common cancer among women and tumour resection carries a high prevalence of chronic persistent postsurgical pain (CPSP). Perioperative i.v. lidocaine infusion has been proposed as protective against CPSP; however, evidence of its benefits is conflicting. This review evaluates the effectiveness of perioperative lidocaine infusions for breast cancer surgery. Randomised trials comparing perioperative lidocaine infusions with parenteral analgesia in breast cancer surgery patients were sought. The two co-primary outcomes were the odds of CPSP at 3 and 6 months after operation. Secondary outcomes included rest pain at 1, 6, 12, and 24 h; analgesic consumption at 0–24 and 25–48 h; quality of recovery; opioid-related side-effects; and lidocaine infusion side-effects. Hartung–Knapp–Sidik–Jonkman (HKSJ) random effects modelling was used. Thirteen trials (1039 patients; lidocaine: 518, control: 521) were included. Compared with control, perioperative lidocaine infusion did not decrease the odds of developing CPSP at 3 and 6 months. Lidocaine infusion improved postoperative pain at 1 h by a mean difference (95% confidence interval) of −0.65 cm (−0.73 to −0.57 cm) (P <0.0001); however, this difference was not clinically important (1.1 cm threshold). Similarly, lidocaine infusion reduced oral morphine consumption by 7.06 mg (−13.19 to −0.93) (P =0.029) over the first 24 h only; however, this difference was not clinically important (30 mg threshold). The groups were not different for any of the remaining outcomes. Our results provide moderate-quality evidence that perioperative lidocaine infusion does not reduce CPSP in patients undergoing breast cancer surgery. Routine use of lidocaine infusions for perioperative analgesia and CPSP prevention is not supported in this population. PROSPERO CRD42023420888. [ABSTRACT FROM AUTHOR]

Background: The efficacy of the erector spinae plane (ESP) block in mitigating postoperative pain has been shown for a range of thoracic and abdominal procedures. However, there is a paucity of literature investigating its impact on postoperative analgesia as well as its influence on weaning and subsequent recovery in comparison to thoracic epidural analgesia (TEA) in median sternotomy-based approach for open-cardiac surgeries and hence the study. Methods: Irrespective of gender or age, 74 adult patients scheduled to undergo open cardiac surgery were enrolled and randomly allocated into two groups: the Group TEA (thoracic epidural block) and the Group ESP (bilateral Erector Spinae Plane block). The following variables were analysed prospectively and compared among the groups with regard to pain control, as determined by the VAS Scale both at rest (VASR) and during spirometry (VASS), time to extubation, quantity and frequency of rescue analgesia delivered, day of first ambulation, length of stay in the intensive care unit (ICU), and any adverse cardiac events (ACE), respiratory events (ARE), or other events, if pertinent. Results: Clinical and demographic variables were similar in both groups. Both groups had overall good pain control, as determined by the VAS scale both at rest (VASR) and with spirometry (VASS) with Group ESP demonstrating superior pain regulation compared to Group TEA during the post-extubation period at 6, 9, and 12 h, respectively (P > 0.05). Although statistically insignificant, the postoperative mean rescue analgesic doses utilised in both groups were comparable, but there was a higher frequency requirement in Group TEA. The hemodynamic and respiratory profiles were comparable, except for a few arrhythmias in Group TEA. With comparable results, early recovery, fast-track extubation, and intensive care unit (ICU) stay were achieved. Conclusions: The ESP block has been found to have optimal analgesic effects during open cardiac surgery, resulting in a decreased need for additional analgesic doses and eliminating the possibility of a coagulation emergency. Consequently, it presents itself as a safer alternative to the potentially invasive thoracic epidural analgesia (TEA). [ABSTRACT FROM AUTHOR]

Background Depressive symptoms are common in knee osteoarthritis (OA), exacerbate knee pain severity and may influence outcomes of oral analgesic treatments. The aim was to assess whether oral analgesic effectiveness in knee OA varies by fluctuations in depressive symptoms. Methods The sample included Osteoarthritis Initiative (OAI) participants not treated with oral analgesics at enrolment (n  = 1477), with radiographic disease at the first follow-up visit (defined as the index date). Oral analgesic treatment and depressive symptoms, assessed with the Center for Epidemiological Studies Depression [(CES-D) score ≥16] Scale, were measured over three annual visits. Knee pain severity was measured at visits adjacent to treatment and modifier using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale (rescaled range = 0–100). Structural nested mean models (SNMMs) estimated causal mean differences in knee pain severity comparing treatment versus no treatment. Results The average causal effects of treated versus not treated for observations without depressive symptoms showed negligible differences in knee pain severity. However, causal mean differences in knee pain severity comparing treatment versus no treatment among observations with depressive symptoms increased over time from −0.10 [95% confidence interval (CI): −9.94, 9.74] to −16.67 (95% CI: −26.33, −7.01). Accordingly, the difference in average causal effects regarding oral analgesic treatment for knee pain severity between person-time with and without depressive symptoms was largest (−16.53; 95% CI: −26.75, −6.31) at the last time point. Cumulative treatment for 2 or 3 years did not yield larger causal mean differences. Conclusions Knee OA patients with persistent depressive symptoms and chronic pain may derive more analgesic treatment benefit than those without depressive symptoms and less pain. [ABSTRACT FROM AUTHOR]

Gabapentinoid (GABA) prescribing has substantially increased while opioid prescribing has decreased since the 2016 Centers for Disease Control and Prevention Guidelines restricted opioid prescribing for chronic pain. The shift to GABA assumes equal analgesic effectiveness to opioids, but no comparative analgesic effectiveness data exist to support this assumption. We compared GABA to opioids by assessing changes in pain interfering with activities (activity-limiting pain) over time in patients with chronic pain. We used 2017 to 2019 data from a 20% national sample of Medicare beneficiaries diagnosed with chronic pain who initiated a GABA or opioid prescription for ≥30 continuous days and received home health care in the study year. The main outcome was the difference in reduction in pain score from pre- to post-prescription assessments between the 2 groups. Within a 60-day window before-and-after drug initiation, our sample comprised 3208 GABA users and 2846 opioid users. Reduction in post-prescription scores of pain-related interference with activities to less-than-daily pain was 48.1% in the GABA group and 41.7% in the opioid group; this remained significant (odds ratio = 1.29, 95% confidence interval: 1.17-1.43, P < 0.0001) after adjustment for patient demographics and comorbidities. The adjusted difference in reduced pain-related interference score between the 2 groups was −0.10 points on a 0 to 4 scale (P = 0.01). Gabapentinoid use had greater odds of less-than-daily pain post-prescription, in a dose-dependent manner. Thus, GABA use was associated with a larger reduction in chronic pain than opioids, with a larger effect at higher GABA dosage. Future research is needed on functional outcomes in patients with chronic pain prescribed GABA or opioids. [ABSTRACT FROM AUTHOR]

Transplantation surgery continues to evolve and improve through advancements in transplant technique and technology. With the increased availability of ultrasound machines as well as the continued development of Enhanced Recovery after Surgery (ERAS) protocols, regional anesthesia has become an essential component of providing analgesia and minimizing opioid use perioperatively. Many centers currently utilize peripheral and neuraxial blocks during transplantation surgery, but these techniques are far from standardized practices. The utilization of these procedures is often dependent on transplantation centers' historical methods and perioperative cultures. To date, no formal guidelines or recommendations exist which address the use of regional anesthesia in transplantation surgery. In response, the Society for the Advancement of Transplant Anesthesia (SATA) identified experts in both transplantation surgery and regional anesthesia to review available literature concerning these topics. The goal of this task force was to provide an overview of these publications to help guide transplantation anesthesiologists in utilizing regional anesthesia. The literature search encompassed most transplantation surgeries currently performed and the multitude of associated regional anesthetic techniques. Outcomes analyzed included analgesic effectiveness of the blocks, reduction in other analgesic modalities—particularly opioid use, improvement in patient hemodynamics, as well as associated complications. The findings summarized in this systemic review support the use of regional anesthesia for postoperative pain control after transplantation surgeries. Part 1 of the manuscript focused on regional anesthesia performed in thoracic transplantation surgeries, and part 2 in abdominal transplantations. Specifically, regional anesthesia in liver, kidney, pancreas, intestinal, and uterus transplants or applicable surgeries are discussed. [ABSTRACT FROM AUTHOR]

Postoperative pain is a typical example of acute pain. Several inflammatory, visceral, neuropathic pain mechanism account for pain in postoperative period. More than 80 millions of patients undergo surgeries which is associated with considerable post operative discomfort. To assess the analgesic effectiveness of epidural butorphanol and epidural tramadol for postoperative pain relief in lower limb surgeries and duration of analgesia, this study was done with a profile of 60 patients of ASA physical status I and II, aged between 18 to 65 years, belonging to both genders undergoing routine orthopedic lower limb surgeries under combined spinal epidural anaesthesia were enrolled in the study, after getting approval from Institutional Ethical Committee and written informed consent from the patients was taken. These patients were assigned to one of the groups for statistical purpose into group B and group T. Every alternate patient received injection butorphanol or injection tramadol epidurally in the post operative period when the VAS score for pain crossed scale of 4. The parameters observed were intensity of pain using Visual analogue scale, sedation scores, duration of analgesia, number of epidural top ups required, hemodynamic parameters and any adverse effects up to 24 hours postoperatively. In our observation, we found that the patients in the tramadol group (group T) experienced longer duration of analgesia 7.4 ± 2.58 hours as compared to butorphanol group where duration of analgesia was 5.7 ± 0.758 hours with a significant p value of 0.002. Tramadol group patients required lesser number of epidural top ups. The total drug consumption in the post operative period was lesser in group T as compared to group B which was statistically significant (p value 0.001). The VAS scores of the two groups noted in the post operative period showed a statistically significant difference with lower VAS scores in the butorphanol group as compared to tramadol group indicating better pain relief with epidural butorphanol. The sedation scores were also compared between the two groups in the post operative period where higher sedation scores were obtained for butorphanol group as compared to tramadol group. Conclusion: Both Epidural butorphanol and epidural tramadol provided very good post operative analgesia in patients undergoing lower limb orthopaedic surgeries. Epidural butorphanol showed better pain relief to patients in the form of low VAS scores though with relatively more sedation scores. However, epidural tramadol due to its longer duration of analgesia needed top ups at relatively longer intervals albeit with relatively lesser pain relief and lesser sedation than epidural butorphanol. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate the effect of locally diclofenac application on postoperative pain, sequalae, and adverse effects following mandibular third molar (MTM) surgery. Methods: A randomized, crossover, double-blind, controlled trial was conducted in 20 patients who required surgical removal of bilateral symmetrical impacted MTM at two separate appointments. The 40 MTMs were randomly allocated to two groups. One side was assigned 0.1% w/v diclofenac sodium as the diclofenac group. The contralateral side was assigned phosphate-buffered saline (PBS) as the control group. Postoperative pain intensity was measured by visual analogue scale (VAS), where the time when the first pain emerged, the time to first rescue medication, pain at 6 and 24 h after surgery, and the total number of analgesics consumed were recorded. Postoperative swelling and trismus were assessed on postoperative days 2 and 7. The differences of continuous outcomes between two groups were analyzed by paired t-test or Wilcoxon signed-rank test. Results: VAS scores were significantly lower when the first pain emerged and 6 h after surgery in diclofenac group (p < 0.05). The onset of pain in the diclofenac group was significantly longer than in the control group (p < 0.05). Two patients reported mild nausea and dizziness in the diclofenac group. Conclusion: This study demonstrates the analgesic effectiveness of 0.1% local application of diclofenac within 6 h postoperative with few side effects. Clinical relevance: Locally diclofenac application is an alternative of postoperative analgesic in MTM surgery which provides pain-free periods within 6 h. [ABSTRACT FROM AUTHOR]

Background: Transversus abdominis plane (TAP) block delivers excellent analgesia with few side effects. Previous research suggests that the efficacy and duration of the block can be increased by adding adjuvants such as dexmedetomidine to the local anesthetics. Aims and Objectives: To compare the post-operative analgesic effectiveness of 0.25% levobupivacaine and 0.25% levobupivacaine with dexmedetomidine 1 µg/kg in US-guided TAP block in infraumbilical surgery patients. Materials and Methods: Ultrasound-guided TAP block was given to sixty patients. Patients consented for infraumbilical surgery, and patients were randomly assigned to two groups: Group L received 20 mL of 0.25% levobupivacaine alone and Group LD received 20 mL of 0.25% levobupivacaine with dexmedetomidine 1 µg/kg. The efficacy of analgesia was measured in terms of degree and duration of analgesia; the post-operative pain was evaluated using a visual analog scale (VAS). The Chi-square test and Student's t-test were used for statistical analysis. Results: Result shows that there is no statistically significant difference in gender, age group, weight, height, BMI, and type of surgery between groups, with a P=0.40, 0.83, 0.37, 0.59, and 0.93, respectively. In addition, there is no statistically significant difference in the duration of surgery between the groups (P=0.63). However, it was observed statistically significant differences in the onset of analgesia requirement, duration of effect of analgesia, and the total anesthesia consumption between the experimental groups with a P=0.001, 0.001, and 0.001, respectively. No significant difference in VAS was observed initially but was significant in later hours. Conclusion: Adding dexmedetomidine to 0.25% levobupivacaine enhanced the efficacy of the block and duration of post-operative analgesia compared to 0.25% levobupivacaine alone. [ABSTRACT FROM AUTHOR]

Objective: Challenging differential diagnosis. Background: Thoracic epidural analgesia is a commonly applied technique for perioperative pain management in major thoraco-abdominal surgery, but is complicated by high failure rates. The epidural electrical stimulation test (EEST) or "Tsui test" is a safe and effective method whereby low electrical current is used to confirm correct epidural catheter position and decrease the variability in analgesic effectiveness of the neuraxial technique. Case Report: We present the case of a 61-year-old woman with no prior cardiac or pulmonary comorbidities who was scheduled to undergo a ventral and parastomal hernia repair with component separation. The patient was offered a low thoracic epidural for perioperative analgesia. Technical aspects of the siting of the epidural catheter were uneventful and a confirmatory Tsui test was planned. At the initiation of electrical stimulation via the epidural catheter to confirm optimal catheter positioning, the patient experienced symptomatic bradycardia and hemodynamic instability that persisted despite terminating the electrical stimulation, and required pharmacologic intervention. Conclusions: This report describes a rare case of vasovagal pre-syncope associated with the EEST or Tsui test. Although vasovagal reactions can be commonly associated with neuraxial procedures due to augmented venous return or severe emotional stress, we raise the possibility that through direct electrical stimulation in the epidural space, the EEST may have the potential to trigger such a physiologic response. [ABSTRACT FROM AUTHOR]

Study Design: This is a basic science, animal research study. Objective: This study aims to explore, in rodent models, the effectiveness of systemic nonsteroidal anti-inflammatory drugs in reducing recombinant human bone morphogenetic protein-2 (rhBMP-2) induced neuroinflammation. Summary of Background Data: rhBMP-2 is increasingly used to augment fusion in lumbar interbody fusion surgeries, although it can cause complications including postoperative radiculitis. Materials and Methods: Eighteen 8-week-old Sprague-Dawley rats underwent Hargreaves testing to measure the baseline thermal withdrawal threshold before undergoing surgical intervention. The L5 nerve root was exposed and wrapped with an Absorbable Collagen Sponge containing rhBMP-2. Rats were randomized into 3 groups: (1) Low dose (LD), (2) high dose (HD) diclofenac sodium, and (3) saline, receiving daily injection treatment. Hargreaves testing was performed postoperatively on days 5 and 7. Seroma volumes were measured by aspiration and the nerve root was then harvested for hematoxylin and eosin, immunohistochemistry, Luxol Fast Blue staining, and real-time quantitative polymerase chain reaction. The Student t test was used to evaluate the statistical significance among groups. Results: The intervention groups showed reduced seroma volume, and a general reduction of inflammatory markers (MMP12, MAPK6, GFAP, CD68, and IL18) compared with controls, with the reduction in MMP12 being statistically significant (P = 0.02). Hematoxylin and eosin and immunohistochemistry of the nerve roots showed the highest macrophage density in the saline controls and the lowest in the HD group. Luxol Fast Blue staining showed the greatest extent of demyelination in the LD and saline groups. Lastly, Hargreaves testing, a functional measure of neuroinflammation, of the HD group demonstrated a minimal change in thermal withdrawal latency. In contrast, the thermal withdrawal latency of the LD and saline groups showed a statistically significant decrease of 35.2% and 28.0%, respectively (P < 0.05). Conclusion: This is the first proof-of-concept study indicating that diclofenac sodium is effective in alleviating rhBMP-2--induced neuroinflammation. This can potentially impact the clinical management of rhBMP-2--induced radiculitis. It also presents a viable rodent model for evaluating the effectiveness of analgesics in reducing rhBMP-2--induced inflammation. [ABSTRACT FROM AUTHOR]

Objective: to find perioperative analgesic effectiveness of low dose Ketamine in radical nephrectomy operations and comparing its anodyne potency with Nalbuphine Hcl (Nalbin). Study Design: Quasi-experimental study. Place and Duration of Study: Armed forces institute of urology from Sep 2016 to June 2019. Methodology: The 60 randomly selected surgical patients for radical nephrectomy were divided into two groups in a random manner. The Anaesthetic technique used in both groups (K and N) was standard along with 10 mg injection Nalbin given to both groups at induction. Group-K (n=30) patients had IV Ketamine bolus 0.3 mg /kg followed by 0.1 mg/kg/h infusion at induction till completion of surgery. Group-N (n=30) received a similar volume of saline in bolus as well as an infusion. The pain score (VAS) at different intervals and total Nalbin consumed in 12 hours were recorded for each group. Patient satisfaction and complications were recorded during this period. Results: The effective intraoperative analgesia was achieved with an infusion of low dose Ketamine which continued till completion of surgery as seen in group K which has reduced Nalbin requirement 8.8± 3.5 mg (Group N 25±5 mg). There was a statistically significant reduction in overall pain scores and Nalbin demand (P≤0.05) in the Ketamine group (p≤0.00, 0.036, 0.286, 0.257, 0.253 respectively). Patient satisfaction was better in the Ketamine group but few patients in this group had delayed recovery. Conclusion: Intraoperative low-dose Ketamine infusion provides good postoperative analgesia while reducing the need for opioid analgesics, which must be considered for better management of postoperative analgesia. [ABSTRACT FROM AUTHOR]

Background: Ultrasound-guided supra-inguinal fascia iliaca block (FIB) provides effective analgesia after total hip arthroplasty (THA) but is complicated by high rates of motor block. The erector spinae plane block (ESPB) is a promising motor-sparing technique. In this study, we tested the analgesic superiority of the FIB over ESPB and associated motor impairment. Methods: In this randomized, observer-blinded clinical trial, patients scheduled for THA under spinal anesthesia were randomly assigned to preoperatively receive either the ultrasound-guided FIB or ESPB. The primary outcome was morphine consumption 24 h after surgery. The secondary outcomes were pain scores, assessment of sensory and motor block, incidence of postoperative nausea and vomiting and other complications, and development of chronic post-surgical pain. Results: A total of 60 patients completed the study. No statistically significant differences in morphine consumption at 24 h (P = 0.676) or pain scores were seen at any time point. The FIB produced more reliable sensory block in the femoral nerve (P = 0.001) and lateral femoral cutaneous nerve (P = 0.018) distributions. However, quadriceps motor strength was better preserved in the ESPB group than in the FIB group (P = 0.002). No differences in hip adduction motor strength (P = 0.253), side effects, or incidence of chronic pain were seen between the groups. Conclusions: ESPBs may be a promising alternative to FIBs for postoperative analgesia after THA. The ESPB and FIB offer similar opioid-sparing benefits in the first 24 h after surgery; however, ESPBs result in less quadriceps motor impairment. [ABSTRACT FROM AUTHOR]

Transplantation surgery continues to evolve and improve through advancements in transplant technique and technology. With the increased availability of ultrasound machines as well as the continued development of enhanced recovery after surgery (ERAS) protocols, regional anesthesia has become an essential component of providing analgesia and minimizing opioid use perioperatively. Many centers currently utilize peripheral and neuraxial blocks during transplantation surgery, but these techniques are far from standardized practices. The utilization of these procedures is often dependent on transplantation centers' historical methods and perioperative cultures. To date, no formal guidelines or recommendations exist which address the use of regional anesthesia in transplantation surgery. In response, the Society for the Advancement of Transplant Anesthesia (SATA) identified experts in both transplantation surgery and regional anesthesia to review available literature concerning these topics. The goal of this task force was to provide an overview of these publications to help guide transplantation anesthesiologists in utilizing regional anesthesia. The literature search encompassed most transplantation surgeries currently performed and the multitude of associated regional anesthetic techniques. Outcomes analyzed included analgesic effectiveness of the blocks, reduction in other analgesic modalities—particularly opioid use, improvement in patient hemodynamics, as well as associated complications. The findings summarized in this systemic review support the use of regional anesthesia for postoperative pain control after transplantation surgeries. Part 1 of the manuscript focuses on regional anesthesia performed in thoracic transplantation surgeries, and part 2 in abdominal transplantations. [ABSTRACT FROM AUTHOR]

Neuropathic pain is a debilitating condition that affects millions of people worldwide. Numerous studies indicate that this type of pain is a chronic condition with a complex mechanism that tends to worsen over time, leading to a significant deterioration in patients' quality of life and issues like depression, disability, and disturbed sleep. Presently used analgesics are not effective enough in neuropathy treatment and may cause many side effects due to the high doses needed. In recent years, many researchers have pointed to the important role of chemokines not only in the development and maintenance of neuropathy but also in the effectiveness of analgesic drugs. Currently, approximately 50 chemokines are known to act through 20 different seven-transmembrane G-protein-coupled receptors located on the surface of neuronal, glial, and immune cells. Data from recent years clearly indicate that more chemokines than initially thought (CCL1/2/3/5/7/8/9/11, CXCL3/9/10/12/13/14/17; XCL1, CX3CL1) have pronociceptive properties; therefore, blocking their action by using neutralizing antibodies, inhibiting their synthesis, or blocking their receptors brings neuropathic pain relief. Several of them (CCL1/2/3/7/9/XCL1) have been shown to be able to reduce opioid drug effectiveness in neuropathy, and neutralizing antibodies against them can restore morphine and/or buprenorphine analgesia. The latest research provides irrefutable evidence that chemokine receptors are promising targets for pharmacotherapy; chemokine receptor antagonists can relieve pain of different etiologies, and most of them are able to enhance opioid analgesia, for example, the blockade of CCR1 (J113863), CCR2 (RS504393), CCR3 (SB328437), CCR4 (C021), CCR5 (maraviroc/AZD5672/TAK-220), CXCR2 (NVPCXCR220/SB225002), CXCR3 (NBI-74330/AMG487), CXCR4 (AMD3100/AMD3465), and XCR1 (vMIP-II). Recent research has shown that multitarget antagonists of chemokine receptors, such as CCR2/5 (cenicriviroc), CXCR1/2 (reparixin), and CCR2/CCR5/CCR8 (RAP-103), are also very effective painkillers. A multidirectional strategy based on the modulation of neuronal–glial–immune interactions by changing the activity of the chemokine family can significantly improve the quality of life of patients suffering from neuropathic pain. However, members of the chemokine family are still underestimated pharmacological targets for pain treatment. In this article, we review the literature and provide new insights into the role of chemokines and their receptors in neuropathic pain. [ABSTRACT FROM AUTHOR]

Aims and Objectives: Different regional anesthetic techniques have been described and are frequently used in breast cancer surgeries to provide efficient pain management and reduce the use of opioids. This study's main goal was to use pain scores to compare the postoperative analgesic effectiveness of pectoral nerve (PECS 1) block with serratus anterior plane (SAP) block, thoracic paravertebral (TPV) block, and erector spinae plane (ESP) block. Comparing the needs for intraoperative analgesia and postoperative anesthesia was one of the secondary goals. Methods: After institutional ethical committee approval and after prospectively registering this trial with the Clinical Trials Registry of India, 25 patients were randomized and enrolled in each group (Group 1 - PECS 1 and SAP block, Group 2 - TPV group, and Group 3 - ESP group). Standard general anesthesia was administered to all the patients and the blocks, as per randomization were performed before anesthesia induction. Results: The demographic characteristics, intraoperative opioid and sevoflurane consumption, and requirement of rescue analgesia were comparable between the three groups. Pain scores at 0 and 6 h were significantly less in the TPV group when compared to the ESP group and PECS 1 with the SAP group (P = 0.005 and P = 0.006, respectively). Pain scores at 12 and 24 h were comparable between three groups. Conclusion: TPV block provides significantly better pain scores at 0 and 6 h, with comparable pain scores at 12 and 24 h, compared to PECS 1 with SAP block and ESP block with comparable adverse events. [ABSTRACT FROM AUTHOR]

Neuropathic pain remains a clinical challenge due to its complex and not yet fully understood pathomechanism, which result in limited analgesic effectiveness of the management offered, particularly for patients with acute, refractory neuropathic pain states. In addition to the introduction of several modern therapeutic approaches, such as neuromodulation or novel anti-neuropathic drugs, significant efforts have been made in the repurposing of well-known substances such as phenytoin. Although its main mechanism of action occurs at sodium channels in excitable and non-excitable cells and is well documented, how the drug affects the disturbed neuropathic interactions at the spinal cord level and how it influences morphine-induced analgesia have not been clarified, both being crucial from a clinical perspective. We demonstrated that single and repeated systemic administrations of phenytoin decreased tactile and thermal hypersensitivity in an animal model of neuropathic pain. Importantly, we observed an increase in the antinociceptive effect on thermal stimuli with repeated administrations of phenytoin. This is the first study to report that phenytoin improves morphine-induced antinociceptive effects and influences microglia/macrophage activity at the spinal cord and dorsal root ganglion levels in a neuropathic pain model. Our findings support the hypothesis that phenytoin may represent an effective strategy for neuropathic pain management in clinical practice, particularly when combination with opioids is needed. [ABSTRACT FROM AUTHOR]

Labor pain is among the most severe types of physical pain that women may experience during their lifetime. Thus, pain relief is an essential part of medical care during childbirth. Epidural analgesia is considered to be the most efficient method of pain relief during labor. Nevertheless, patient preferences, contraindications, limited availability, and technical failure may require the use of alternative pain reliving methods during labor including systemic pharmacologic agents, and nonpharmacologic methods. Nonpharmacologic methods for pain alleviation during vaginal birth have become popular over the years, either as a complement to pharmacologic agents or at times as the principal therapy. Methods such as relaxation techniques (ie, yoga, hypnosis, and music), manual techniques (ie, massage, reflexology, and shiatsu), acupuncture, birthing ball, and transcutaneous electrical nerve stimulation are considered safe, although the evidence supporting their effectiveness for pain relief is not as robust as it is for pharmacologic agents. Systemic pharmacologic agents are mostly administered by inhalation (nitrous oxide) or through the parenteral route. These agents include opioids such as meperidine, nalbuphine, tramadol, butorphanol, morphine, and remifentanil, and non-opioid agents such as parenteral acetaminophen and nonsteroidal anti-inflammatory drugs. Systemic pharmacologic agents suggest a diverse armamentarium of medication for pain management during labor. Their efficacy in treating pain associated with labor varies, and some continue to be used even though they have not been proven effective for pain relief. In addition, the maternal and perinatal side effects differ markedly among these agents. There is a relative abundance of data regarding the effectiveness of analgesic drugs compared with epidural, but the data regarding comparisons among the different types of alternative analgesic agents are scarce, and there is no consistency regarding the drug of choice for women who do not receive epidural pain management. This review aims to present the available data regarding the effectiveness of the different methods of relieving pain during labor other than epidural. The data presented are mainly based on recent level I evidence regarding pharmacologic and nonpharmacologic methods for pain relief during labor. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Pain is an unpleasant sensory and emotional experience and is considered the fifth vital sign. Opioid-free anesthesia (OFA) is a technique where no intraoperative systemic, neuraxial, or intracavitary opioids are administered during the anesthesia. The prescription misuse/ overuse has generated an opioid crisis which has led to the need for OFA. In this study, we will investigate the 24-h postsurgical analgesia and analgesic consumption with the use of OFA versus opioid anesthesia (tramadol) in patients undergoing abdominal surgery under general anesthesia. METHODOLOGY: Sixty patients of the American Society of Anesthesiologists Grade I-II scheduled for various abdominal surgeries were randomly assigned into two groups, with 30 patients in each group. Group A (opioid-free group): received IV lignocaine (2 mg/kg), IV magnesium sulfate (20 mg/kg), and V paracetamol (15 mg/kg) in 100 ml NS. Group B (opioid group): received IV tramadol (2 mg/kg) in 100 ml NS. Hemodynamic parameters, postoperative analgesic consumption, duration of analgesia, and any adverse effects were recorded. RESULTS: A very significant difference was observed between the study groups for mean values of mean arterial pressure at the last stages of surgery, with hemodynamics more stable in the opioid-free group (P < 0.01). In terms of mean values of minimum alveolar concentration throughout the surgery, the opioid group showed more anesthetic-sparing effect (P < 0.05). In terms of postoperative pain scores between the groups, the opioid-free group experienced less pain (P < 0.01). There was no difference between the groups in postoperative analgesic consumption and duration of analgesia. More side effects were noted in the opioid group. CONCLUSION: This study concludes that avoiding opioid use by preemptive administration of intravenous paracetamol, lignocaine, and magnesium sulfate provides safe, effective, and satisfactory analgesia in patients undergoing various abdominal surgeries under general anesthesia. [ABSTRACT FROM AUTHOR]

Background: Nasal backing and the actual surgical trauma are responsible for mild to severe postoperative pain following nose operations. Aim: To evaluate analgesic effectiveness of nebulized ketamine against nebulized dexmedetomidine for patients undergoing nose operations. Patients and methods: 105 adult patients for elective nose operations were divided into three groups. Patients in each group were given the drug via nebulization 15 minutes before to surgery; in the case of group D, patients received 50 µg of dexmedetomidine (0.5 ml + normal saline 0.9% up to 3 ml), group K, 50 mg of ketamine (1 ml + normal saline 0.9% up to 3 ml), and group C, 0.9% (3 ml) of normal saline. Hemodynamics, intraoperative opioids, the first-time analgesia was requested, the total amount of postoperative rescue analgesia administered, and side effects were all included in the outcome measures. Version 20 of SPSS was used to code and analyses the data that had been gathered. Results: There was statistically significant (p< 0.05) reduction in intraoperative fentanyl needs in D group < K group < C group and also significant decrease in postoperative ketoprofen needs. The first time to rescue analgesia was delayed (p< 0.05) in D group > K group > C group. Postoperative complications were lower in D and K groups < C group (p< 0.05). Conclusion: Preemptive nebulization of dexmedetomidine produces extremely good analgesia in nasal surgeries, when compared with other groups it can effectively reduce the intra- and postoperative opioid consumption. [ABSTRACT FROM AUTHOR]

Adequate pain management is essential for ethical and scientific reasons in animal experiments and should completely cover the period of expected pain without the need for frequent re-application. However, current depot formulations of Buprenorphine are only available in the USA and have limited duration of action. Recently, a new microparticulate Buprenorphine formulation (BUP-Depot) for sustained release has been developed as a potential future alternative to standard formulations available in Europe. Pharmacokinetics indicate a possible effectiveness for about 72 h. Here, we investigated whether the administration of the BUP-Depot ensures continuous and sufficient analgesia in two mouse fracture models (femoral osteotomy) and could, therefore, serve as a potent alternative to the application of Tramadol via the drinking water. Both protocols were examined for analgesic effectiveness, side effects on experimental readout, and effects on fracture healing outcomes in male and female C57BL/6N mice. The BUP-Depot provided effective analgesia for 72 h, comparable to the effectiveness of Tramadol in the drinking water. Fracture healing outcome was not different between analgesic regimes. The availability of a Buprenorphine depot formulation for rodents in Europe would be a beneficial addition for extended pain relief in mice, thereby increasing animal welfare. [ABSTRACT FROM AUTHOR]

Objectives: Epidural anesthesia, once considered a gold standard, has significant complications: hypotension, urinary retention, and catastrophic neurological damage in rare cases. While paravertebral analgesia can provide similar analgesic effectiveness to epidural analgesia, it is associated with fewer side effects. To compare the perioperative and postoperative effects of epidural (ED) and ultrasound-guided paravertebral block (PVB) applications in thoracotomy surgeries. Methods: Fifty-two patients underwent elective thoracotomy; Group 1 (ED, n = 23) and Group 2 (PVB, n = 29) were evaluated. A comparison of hemodynamic parameters and complications preoperatively and postoperatively, postoperative analgesia requirements, visual analog scale (VAS) pain scores within 24 hours at specified times, the amount of analgesic used, the time to mobilize, the time to discharge, and the VAS values measured at three months was made. Results: There was no difference between the study groups regarding demographic and ASA values, most comorbid chronic diseases, obesity, and smoking. The number of attempts, the postoperative 2nd hour VAS score, and the doses of paracetamol and tramadol used was significantly higher in Group 1 than in Group 2 (p = 0.002, p = 0.002, p = 0.012, and p = 0.022, respectively). There was no statistical difference between the groups in terms of postoperative 6, 12, 24 hours, and 3 months VAS scores, first mobilization and discharge, time to remove the thorax tube, intensive care (PACU) need, and perioperative and postoperative complications (p > 0.05). Conclusions: Ultrasound-guided PVB can be considered a safe and effective alternative to ED in thoracotomy surgery. [ABSTRACT FROM AUTHOR]

Intravenous (IV) lidocaine is a proven analgesic therapy but has not been evaluated in extensive procedures such as cytoreductive surgery (CRS). Our aim was to assess the effectiveness and safety of IV lidocaine in this setting. This is a retrospective hybrid case-cohort study investigating analgesic effectiveness and complications of perioperative IV lidocaine at 1.5 mg/kg/h for 48 h compared to thoracic epidural anaesthesia (TEA) among patients undergoing CRS in a high-volume centre. Sixty patients were included, 20 received IV lidocaine and 40 underwent TEA. Pain scores were low (median ≤2) and similar in both groups (p = 0.88). At 72 h, the lidocaine group had a lower median pain score (p = 0.03). Overall opioid consumption in the first 48 h was lower in the lidocaine compared to the TEA group (median 0 (IQR 0–9.5) mg vs. 45.4 (0–62.4) MME respectively, p = 0.001). Opioid consumption was also lower in the lidocaine compared to the TEA group during the whole 5-day period (median 1 (IQR 1–13.5) mg vs. 112 (36.6–137.85) MME respectively, p = 0.000). The incidence of PONV was significantly lower in the lidocaine group (27.5% vs 5%, p = 0.047) with no difference in other complications or length of in-hospital stay. Intravenous lidocaine infusion may be a safe and effective analgesic approach in CRS and is associated with a significant reduction of opioid use and PONV compared to opioid-containing TEA. [ABSTRACT FROM AUTHOR]

Aim and Objective: To compare the analgesic effectiveness of the patient-controlled inhaled nitrous oxide (Entonox®) with intravenous opioids (pethidine/midazolam) in reducing pain during minor gynecological operative procedures, including manual vacuum aspiration (MVA), fractional curettage and dilatation and curettage. Materials and Methods: Patients undergoing minor gynecological procedures from August 2021 to December 2022 were randomized to receive nitrous oxide or intravenous pethidine (50–75 micrograms) plus midazolam (2 mg). Pain scores during and post-procedure, satisfaction level, and side effects were assessed and compared. Results: A total of 106 patients met the inclusion criteria, including 53 in the pethidine/midazolam group and 53 in the nitrous oxide group. Baseline characteristics were comparable (p-value > 0.05). Pain scores during, immediately and 30 min after procedures were not significantly different in two groups (4.94 ± 3.15, 2.74 ± 2.57, 1.58 ± 2.13 vs. 5.47 ± 2.80, 2.98 ± 2.70, 1.64 ± 2.70; p-value: 0.174, 0.634, 0.889, for pethidine/midazolam vs. nitrous oxide group, respectively. Satisfaction scores were comparable in both groups (p-value > 0.05). However, the rate of side effects was significantly lower in the nitrous oxide group (3.8% vs. 28.3%; p-value 0.001). Additionally, the discharge scores showed a significantly faster recovery time in the nitrous oxide group at 60 and 90 min after the procedure; median (IQR): 10 (9–10) vs. 9 (8–10) and 10 (10–10) vs. 10 (8.5–10); p-value 0.002 and 0.029, respectively). Conclusions: Nitrous oxide is as effective as pethidine/midazolam for pain relief in minor gynecological operative procedures but associated with significantly lower side effects and significantly faster recovery time. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is one of the most common metabolic diseases in which one of the most serious complications is the diabetic foot ulcer (DFU). The aim of the study was to compare the efficacy of two physical therapeutic methods: topical oxygen therapy and topical ozone therapy in the treatment of DFU with the calculation of the financial costs for both applied physical methods. The study included 85 patients, 47 male (55.2%) and 38 female (44.7%) in age range between 40 and 90 years (mean age: 67.82 ± 12.42 years) with hard to heal diabetic foot ulcers. The mean diabetic foot ulcer duration was 3.6 ± 1.23 years. Patients were randomized into two study groups not significantly different in terms of age, body mass index (BMI) value, and baseline ulcer surface area value, who underwent topical oxygen therapy (group I) and topical ozone therapy (group II), respectively. Both the groups underwent a total of 30 daily treatments lasting 30 minutes, in 2 sessions of 15 treatments with a 14-day break between sessions. Progress in wound healing was evaluated by computerized planimetry and the pain intensity was assessed with use of a VAS scale. After the treatment, the ulcer area in group I decreased by an average of 33.25 ± 10.97% and by an average of 28.67 ± 14.47% in group II p = 0.030 . On the other hand, the intensity of pain ailments after the treatment was statistically significantly decreased in group I by an average of 57.13 ± 16.24% while in group II by an average of 40.21 ± 14.53% (p < 0.001). After application of topical oxygen therapy and topical ozone therapy in the treatment of diabetic foot ulcers a statistically significant reduction in the surface area of treated ulcers in objective planimetric assessment was observed, with local oxygen therapy showing only a slight advantage in this regard. Both compared methods also caused a statistically significant reduction in the pain intensity, while local oxygen therapy shows statistically significantly better analgesic effectiveness. Due to the calculated moderate cost, both applied methods appeared to be cost-effective. [ABSTRACT FROM AUTHOR]

Background/Aim. Children with burns are submitted to multiple painful and anxiety-related procedures during the change of wound dressing, treatment, and rehabilitation. The objective of analgesic treatments for procedural pain is the safe and efficient management of pain and emotional stress, which requires a careful, balanced, and systematic approach. The aim of this study was to determine the effectiveness of analgesic and/or local anesthetic in relieving the intensity of procedural pain. Methods. The study included 120 pediatric patients with second-degree burns who were allocated into four groups of 30 children (control group, groups I, II, and III). During the change of wound dressings, children in the control group did not receive any analgesics, while in the remaining three groups, 30 minutes prior to the change of wound dressing, oral nonsteroidal antiinflammatory drug (group I), local anesthetic (group II), or both medications (group III) were administered. Results. The average visual analog scale (VAS) score for assessing pain was statistically significantly higher in the control group on all tested days compared with children in the other three treated groups. On the first test day (24 hrs after sustaining the burn injuries), all children had high VAS scores, and according to the receiver operating characteristics (ROC) analysis, the boundary value was 89.50/100. There was a remarkable difference in the VAS score between the groups on the fifth day of dressing change with the boundary value of 57.50/100 and on the seventh day when the boundary value was 43.50/100. Children who experienced the lowest intensity pain during dressing changes of burn wounds for all test days were those from the group who received both systemic analgesic and local anesthetic. Conclusion. The study confirmed the importance of introducing the complex polymodal protocol in treating procedural pain in seconddegree burns. The protocol should include analgesics as well as anesthetics since they both contribute to achieving the best results in pain reduction and treatment outcomes. [ABSTRACT FROM AUTHOR]

Summary: Anterior cruciate ligament reconstruction can cause moderate to severe acute postoperative pain. Despite advances in our understanding of knee innervation, consensus regarding the most effective regional anaesthesia techniques for this surgical population is lacking. This network meta‐analysis compared effectiveness of regional anaesthesia techniques used to provide analgesia for anterior cruciate ligament reconstruction. Randomised trials examining regional anaesthesia techniques for analgesia following anterior cruciate ligament reconstruction were sought. The primary outcome was opioid consumption during the first 24 h postoperatively. Secondary outcomes were: rest pain at 0, 6, 12 and 24 h; area under the curve of pain over 24 h; and opioid‐related adverse effects and functional recovery. Network meta‐analysis was conducted using a frequentist approach. A total of 57 trials (4069 patients) investigating femoral nerve block, sciatic nerve block, adductor canal block, local anaesthetic infiltration, graft‐donor site infiltration and systemic analgesia alone (control) were included. For opioid consumption, all regional anaesthesia techniques were superior to systemic analgesia alone, but differences between regional techniques were not significant. Single‐injection femoral nerve block combined with sciatic nerve block had the highest p value probability for reducing postoperative opioid consumption and area under the curve for pain severity over 24 h (78% and 90%, respectively). Continuous femoral nerve block had the highest probability (87%) of reducing opioid‐related adverse effects, while local infiltration analgesia had the highest probability (88%) of optimising functional recovery. In contrast, systemic analgesia, local infiltration analgesia and adductor canal block were each poor performers across all analgesic outcomes. Regional anaesthesia techniques that target both the femoral and sciatic nerve distributions, namely a combination of single‐injection nerve blocks, provide the most consistent analgesic benefits for anterior cruciate ligament reconstruction compared with all other techniques but will most likely impair postoperative function. Importantly, adductor canal block, local infiltration analgesia and systemic analgesia alone each perform poorly for acute pain management following anterior cruciate ligament reconstruction. [ABSTRACT FROM AUTHOR]

Introduction: The optimal pain management strategy after lung transplantation is unknown. This study compared analgesic outcomes of intercostal nerve blockade by cryoanalgesia (Cryo) versus thoracic epidural analgesia (TEA). Methods: Seventy-two patients who underwent bilateral lung transplantation via clamshell incision at our center from 2016 to 2018 were managed with TEA (N = 43) or Cryo (N = 29). We evaluated analgesic-specific complications, opioid use in oral morphine equivalents (OME), and pain scores (0–10) through postoperative day 7. Adjusted linear regression was used to assess for non-inferiority of Cryo to TEA. Results: The overall mean pain scores (Cryo 3.2 vs TEA 3.8, P = 0.21), maximum mean pain scores (Cryo 4.7 vs TEA 5.5, P = 0.16), and the total opioid use (Cryo 484 vs TEA 705 OME, P = 0.12) were similar in both groups, while the utilization of postoperative opioid-sparing analgesia, measured as use of lidocaine patches, was lower in the Cryo group (Cryo 21% vs TEA 84%, P < 0.001). Analgesic outcomes remained similar between the cohorts after adjustment for pertinent patient and analgesic characteristics (P = 0.26), as well as after exclusion of Cryo patients requiring rescue TEA (P = 0.32). There were no Cryo complications, with four patients requiring subsequent TEA for pain control. Two TEA patients experienced hemodynamic instability following a test TEA bolus requiring code measures. Additionally, TEA placement was delayed beyond postoperative day 1 in 33% owing to need for anticoagulation or clinical instability. Conclusions: In lung transplantation, Cryo was found to be safe with analgesic effectiveness similar to TEA. Cryo may be advantageous in this complex patient population, as it can be used in all clinical scenarios and eliminates risks and delays associated with TEA. [ABSTRACT FROM AUTHOR]

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. WLB-73502 is a bispecific sigma-1 antagonist and partial mu-opioid agonist (low intrinsic efficacy at G i/o -protein activation and undetectable β -arrestin-2 recruitment) with improved antinociceptive and safety profile respect to strong opioids. [Display omitted] [ABSTRACT FROM AUTHOR]

• Amaranthus blitum L. is native to Mediterranean but now found around all over the world. • The analgesic and hypoglycaemic activity has never been investigated before for this plant. • Eleven druggable compounds were isolated from the methanolic extract of the plant. • In-vivo study showed the promising result as both analgesic and hypoglycaemic candidate. • Glycidyl oleate had the best affinity for cyclooxygenase enzyme-2 inhibitor in silico analysis. • 2,2-di‑tert-butylphenol showed the best docking score in molecular docking studies against sulfonyl urea protein. Amaranthus blitum L. is a worldwide weed that originated in the Mediterranean region and now grows from the tropics to temperate zones, from Asian to southern African countries. It is commonly consumed as a cooked vegetable item. Amaranthus blitum L., on the other hand, has never been extensively investigated for its medicinal properties like analgesic and hypoglycemic potentials. Hence, using an in vivo and in silico method, assess the analgesic and hypoglycemic efficacy of Amaranthus blitum L. methanolic extract and its key phytoconstituents is the primary aim of this study. The acetic acid-induced writhing test and the hot plate test protocol were employed to assess the in vivo analgesic effectiveness of Amaranthus blitum L. methanolic extract (ABME) in Swiss albino mice of either sex. In a Stretozotocin (STZ) induced anti-diabetic test, the hypoglycemic activity was investigated. Admet-SAR web server and PyMOL (Version 1.7.4) software package were used to perform in silico activity of the isolated compounds and ADME analysis. The research employed methanolic extracts (ME) at dosages of 250 mg/kg and 500 mg/kg to assess analgesic and hypoglycemic effects. ME (250 mg/kg) and ME (500 mg/kg) showed substantial outcomes in the acetic acid-induced writhing test, with 39.48 ± 5.66% and 51.20 ± 3.78%, respectively. ME at a dosage of 500 mg/kg caused the highest latency time increase of 16.92 ± 0.94s in the hot plate test. In the context of in silico assessment, eleven chemicals fit Lipinski's five-condition criteria. The best docking score was for glycidyl oleate which is 6.3 kcal/mol against cyclooxygenase-2 enzyme (PDB ID: 5KIR) among these safe chemicals, which was practically identical to Celecoxib's (8.5 kcal/mol). In streptozotocin induced hypoglycemic test, significant decrease in plasma glucose level was observed for 500 mg/kg of methanolic extract. In silico study showed best docking score of 2,2-di‑tert-butylphenol with − 6.4 kcal/mol against sulfonylurea protein (PDB ID: 6JB3), compared to glibenclamide (− 9.4 kcal/mol). Our research demonstrates that phytoconstituents of Amaranthus blitum L. are very potential analgesic and hypoglycemic candidates. These compounds might be employed to develop an effective analgesic and anti-diabetic medication from a natural resource using advanced technologies. [ABSTRACT FROM AUTHOR]

Background: The comparative benefits and harms of opioids for musculoskeletal pain in the emergency department (ED) are uncertain.Purpose: To evaluate the comparative effectiveness and harms of opioids for musculoskeletal pain in the ED setting.Data Sources: Electronic databases and registries from inception to 7 February 2022.Study Selection: Randomized controlled trials of any opioid analgesic compared with placebo or a nonopioid analgesic administered or prescribed to adults in or on discharge from the ED.Data Extraction: Pain and disability were rated on a scale of 0 to 100 and pooled using a random-effects model. Certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework.Data Synthesis: Forty-two articles were included (n = 6128). In the ED, opioids were statistically but not clinically more effective in reducing pain in the short term (about 2 hours) than placebo and paracetamol (acetaminophen) but were not clinically or statistically more effective than nonsteroidal anti-inflammatory drugs (NSAIDs) or local or systemic anesthetics. Opioids may carry higher risk for harms than placebo, paracetamol, or NSAIDs, although evidence is very uncertain. There was no evidence of difference in harms associated with local or systemic anesthetics.Limitations: Low or very low GRADE ratings for some outcomes, unexplained heterogeneity, and little information on long-term outcomes.Conclusion: The risk-benefit balance of opioids versus placebo, paracetamol, NSAIDs, and local or systemic anesthetics is uncertain. Opioids may have equivalent pain outcomes compared with NSAIDs, but evidence on comparisons of harms is very uncertain and heterogeneous. Although factors such as route of administration or dosage may explain some heterogeneity, more work is needed to identify which subgroups will have a more favorable benefit-risk balance for one analgesic over another. Longer-term pain management once dose thresholds are reached is also uncertain.Primary Funding Source: None. (PROSPERO: CRD42021275293). [ABSTRACT FROM AUTHOR]

Dehorning is a zootechnical practice that causes severe pain in cattle. Although there are several studies evaluating the effects of analgesics in calf dehorning, none of them used validated pain assessment instruments. We evaluated the analgesic effectiveness of meloxicam administered before dehorning, compared to a control group, using the Unesp-Botucatu, numerical, simple descriptive, and visual analogue scales for pain assessment before and 4, 8, and 24 hours after the dehorning in 44 female calves. All calves received 0.04 mg/kg of xylazine IM 20 minutes before dehorning and local anesthetic block with 2% lidocaine with a vasoconstrictor. Calves were divided into two groups: without (GX; n = 22) or with 0.5 mg/kg of meloxicam (GXM; n = 22) administered intravenously before the procedure. Dehorning was performed through the section of the base of the horn bud, followed by thermocautery disbudding. For comparisons over time, mixed linear or generalized mixed linear model were used. The interaction between groups and study phases was used as fixed effects and each calf as a random effect. Bonferroni post hoc test was used. There was an increase in the pain scores at 4h compared to baseline in both groups (GX and GXM) for the four scales. The scores at 4h were higher in GX compared to GXM for all scales. Meloxicam reduced, but did not eliminate, behavioral expressions of pain in calves submitted to hot-iron dehorning. Therefore, it should be included in the analgesic protocol to improve welfare in calves undergoing dehorning. [ABSTRACT FROM AUTHOR]

Spinal opioids have mixed efficacy and their adverse effects force treatment cessation of postoperative pain. Consequently, there is an ongoing search for new therapeutic strategies. Here, we evaluated the analgesic efficacy of intrathecal UCM707, an anandamide reuptake inhibitor, and morphine combination. Firstly, we assessed the effects of morphine (1, 5 and 10 μg), UCM707 (75 μg) and its combination in the hot plate. Then, morphine + UCM707 at sub-effective doses was evaluated in a rat post-incisional pain model. In addition, μ-, CB1r-, CB2r- and TRPV1-antagonists were pre-administered before the combination. Activation of μ-opioid and CB1r, and Cnr1, Cnr2, Oprm1 and TRPV 1 expressions were evaluated in the lumbar sacra and periaqueductal grey by [35 S]-GTPγS binding autoradiography and qPCR studies. In the hot plate, morphine (1 μg) and UCM707 (75 μg) induced a more robust analgesic effect than each drug alone. Morphine plus UCM707 did not modify μ-opioid nor CB1 receptor function in the PAG or LS. Cnr1 and TRPV1 expression increased in the lumbar sacra (LS). Morphine plus UCM707 significantly reduced post-incisional pain at 1 and 4 days after surgery. Cnr1, Cnr2 and TRPV1 expressions increased in the LS. Blockade of μ-opioid receptor reduced combination effects on days 1 and 4. CB1r- and CB2r-antagonism reduced morphine + UCM707 effects on days 1 and 4, respectively. CB1r and TRPV1-antagonism improved their antinociceptive effects on day 4. These results revealed a synergistic/additive analgesic effect of UCM707 and morphine combination controlling postincisional pain. CB1r, CB2r and TRPV1 contribute differently as central sensitization occurs. • Intrathecal UCM707 has synergistic/additive analgesic effects with morphine. • μ-opioid, cannabinoid and TPRV1 receptors contribute to UCM707 + morphine effects. • UCM707 may be acting as a co-adjuvant drug with opioids for relief of POP. [ABSTRACT FROM AUTHOR]

Several opioids have pharmacogenetic and drug-drug interactions which may compromise their analgesic effectiveness, but are not routinely implemented into supportive pain management. We hypothesized that CYP2D6 phenotypes and concomitant use of CYP2D6 substrates or inhibitors would correlate with opioid analgesic outcomes. An observational cross-sectional study was conducted with 263 adult chronic non cancer pain (CNCP) patients from a real-world pain unit under long-term CYP2D6-related opioid treatment (tramadol, hydromorphone, tapentadol or oxycodone). Metabolizer phenotype (ultrarapid [UM], normal [NM], intermediate [IM] or poor [PM]) was determined by the CYP2D6 genotype. The socio-demographic (sex, age, employment status), clinical (pain intensity and relief, neuropathic component, quality of life, disability, anxiety and depression), pharmacological (opioid doses and concomitant pharmacotherapy) and safety (adverse events) variables were recorded. The whole population (66 % female, 65 (14) years old, 70 % retired and 63 % attended for low back pain) were classified as PM (5 %), IM (32 %), NM (56 %) and UM (6 %). Multiple linear and logistic regressions showed higher pain intensity and neuropathic component at younger ages when using any CYP2D6 substrate (p = 0.022) or inhibitor (p = 0.030) drug, respectively, with poorer pain relief when CYP2D6 inhibitors (p=0.030) were present. The concomitant use of CYP2D6 substrates or inhibitors during opioid therapy for CNCP may result in lack of analgesic effectiveness. This aspect could be relevant for pharmacological decision making during CNCP management. [Display omitted] • Concomitant use of opioids and CYP2D6 drugs compromise the analgesic effectiveness. • Younger chronic pain patients using concomitant CYP2D6 drugs have worse pain relief. • Extreme CYP2D6 metabolizers under analgesia show disability, depression and anxiety. [ABSTRACT FROM AUTHOR]

The majority of intrauterine devices (IUDs) inserted in China are tailless, requiring intrauterine manipulations for removal and causing pain. This study aimed to investigate the analgesic efficacy of lidocaine injection into a novel disposable injectable cervical dilator for IUD removal procedures. A double-blinded, placebo-controlled, randomized clinical trial was conducted with women aged 18–65 years old requesting outpatient IUD removal. The study randomly assigned participants to either lidocaine (injecting 5 ml of 2% lidocaine into the injectable cervical dilator) or placebo (injecting 5 ml of normal saline into the device) group. All participants received a standardized paracervical block. The primary outcome was pain reported during IUD removal on a 100 mm Visual Analog Scale (VAS). Intention-to-treat were conducted to evaluate the analgesic effectiveness of injecting lidocaine into the injectable cervical dilators. We enrolled seventy-four eligible participants (37 in lidocaine group and 37 in placebo group). The results showed that the median intraoperative VAS score in the lidocaine group was lower than the placebo group (30.0 mm [IQR 20.0–46.0, n = 37] vs 46.0 mm [IQR 30.0–55.0, n = 37], p = 0.01. In subgroup analyses, among participants with IUD removal and without uterine manipulation and additional procedures, there was no statistically significant disparity observed in intraoperative VAS scores between the lidocaine and placebo group (15.0 mm [IQR 10.0–27.5, n = 8] vs 20.0 mm [IQR 20.0–40.0, n = 6]), p = 0.28). Among participants with an IUD removal necessitating intrauterine manipulations and without additional procedures, showing lower intraoperative VAS scores in lidocaine group (25.0 mm [IQR 15.0–40.5, n = 17]) compared to placebo group (46.0 mm [IQR 38.5–50.0, n = 23]), p < 0.01. Among participants with additional procedures in addition to IUD removal, there was no statistically significant disparity observed in intraoperative VAS scores between the lidocaine and placebo group (41.0 mm [IQR 32.5–57.5, n = 12] vs 45.0 mm [IQR 22.5–69.0, n = 8]), p = 0.97). Injecting lidocaine into the novel disposable injectable cervical dilator for cervix dilation can significantly reduce pain during an IUD removal, particularly in patients necessitating intrauterine manipulations during IUD removal. When we have to perform intrauterine manipulations to remove an IUD, surgical pain and narrow cervical canal undoubtedly affect the implementation of the procedure. Injecting lidocaine into the injectable cervical dilator can achieve local anesthesia while dilating the cervix, and might reduce the choice of general anesthesia for IUD removal. [ABSTRACT FROM AUTHOR]

Muña and llantén are plants from the Andean region of Bolivia, traditionally their leaves are used as an infusion due to their analgesic and gastroprotective properties. Objective: to evaluate the analgesic and gastroprotective activity of extracts and infusion of muña (Minthostachys mollis) and llantén (Plantago major) leaves, using biological tests in Rattus norvegicus. Methods: an experimental, prospective, longitudinal study was conducted in which the analgesic and gastroprotective activity was evaluated in 30 Rattus norvegicus divided into six lots: control, standard, problem I, II, III, IV, to which abdominal convulsions were induced with glacial acetic acid and gastric ulcers with absolute ethanol. Results: the infusion of muña and llantén presented 81.4% analgesic activity and an effectiveness percentage above 100%, 60% gastroprotective activity and 100% effectiveness in relation to the number of lesions. Similarly, 69.6% gastroprotective activity and 95.9% effectiveness with respect to the degree of injury. These percentages described were higher in comparison to the percentages of muña extract, llantén extract, combined extracts. The ANOVA one-factor Kruskal-Wallis test revealed a statistically significant difference (p<0.05 (p=0.013 number of convulsions); 95% CI) in analgesic activity and a non-significant difference in gastroprotective activity (p>0.05 (p=0.167 number of lesions and p=0.384 degree of injury); 95% CI). Conclusions: the infusion of muña and llantén has better analgesic and gastroprotective activity compared to the extracts. [ABSTRACT FROM AUTHOR]

Opiates have a long history of medical use as effective analgesics associated with well‐described side effects, including euphoria, respiratory depression, constipation, bradycardia, and histamine release, among others. The search for opiate analogs that retain effective analgesic qualities without detrimental side effects has yielded numerous compounds, including buprenorphine. Early studies of buprenorphine demonstrated analgesic effectiveness with a favorable safety profile, leading to the approval of formulations for use in humans. Since then, advances in receptor theory and molecular cloning of opioid receptors have led to a deeper understanding of buprenorphine pharmacology. More recent studies of receptor affinity and intrinsic activity have shown that buprenorphine is a μ‐ and κ‐opioid receptor agonist, a nociceptin orphanin peptide agonist, and a δ‐opioid receptor antagonist. Buprenorphine appears to have a primary spinal analgesic mechanism with complex supraspinal actions. It is considered a full agonist for pain but a partial agonist for other clinical endpoints such as respiratory depression. In feline medicine, buprenorphine is approved as low‐ and high‐concentration injectable solutions, in addition to the most recently introduced long‐acting transdermal formulation. Several investigational and compounded formulations have also been evaluated. There are contrasting differentiable features that include pharmacokinetics, onsets‐ and durations‐of‐action, routes of administration, and formulation constituents. Available buprenorphine formulations allow clinicians to select a formulation based on the anticipated duration of pain associated with various surgical procedures, and to provide interventions as needed. In light of the newly approved transdermal buprenorphine solution in cats and progress in buprenorphine pharmacology, the objective of this review is to examine the history and pharmacology of buprenorphine relative to full opioid agonists, where appropriate, integrating these insights into advances within feline medicine. [ABSTRACT FROM AUTHOR]

Introduction and aim. The purpose of this study was to compare different Computerized-Controlled Local Anesthetic Delivery (CCLAD) systems to one another in addition to the conventional syringe. Material and method. The CCLAD systems chosen for this study are the Quicksleeper, SleeperOne, and The Wand. These are discussed in categorical objectives, including the following: duration of anesthesia, analgesic effect, locality; anxiolytic effect; advantages and disadvantages; comfort and safety of use; limitations. Analysis of the literature. The research found that many factors influence the effectiveness of dental injections, and the CCLAD systems are designed to reduce the ones that cause negative experiences. The injection systems are unique in their descriptions but show many similarities. Conclusion. The research concluded that each device has its advantages and disadvantages and that its efficiency depends on outlying factors, independent of the injection system used. [ABSTRACT FROM AUTHOR]

Abstract Background Effective postoperative analgesia is needed to prevent the negative effects of postoperative pain on patient outcomes. To compare the effectiveness of hydromorphone hydrochloride and sufentanil, combined with flurbiprofen axetil, for postoperative analgesia in pediatric patients. Methods This prospective randomized controlled trial included 222 pediatric patients scheduled for repair of a structural congenital malformation under general anesthesia. Patients were randomized into 3 groups: hydromorphone hydrochloride 0.1 mg/kg (H1), hydromorphone hydrochloride 0.2 mg/kg; (H2) or sufentanil 1.5 µg/kg (S). Analgesics were diluted in 0.9% saline to 100 ml and infused continuously at a basic flow rate of 2 mL per h. The primary outcome measure was the Face, Legs, Activity, Cry, and Consolability (FLACC) pain score. Secondary outcomes included heart rate (HR), respiration rate (RR), SpO2, Ramsay sedation scores, scores on the Paediatric Anaesthesia Emergence Delirium (PAED) scale, adverse reactions, parent satisfaction with analgesia. Results The FLACC score was significantly lower in H1 and H2 groups compared to S. The Ramsay sedation score was significantly higher in H1 and H2 groups compared to S. Recovery time was shorter in H1 group compared to patients H2 group or S group. There were no significant differences in the PAED scale, HR, RR, SpO2, adverse reactions, satisfaction of parents with analgesia, or length and cost of hospital stay. Conclusions Hydromorphone hydrochloride is a more effective analgesic than sufentanil for postoperative pain in pediatric patients following surgical repair of a structural congenital malformation, however, hydromorphone hydrochloride and sufentanil had similar safety profiles in this patient population. Trial registration Chinese Clinical Trial Register ChiCTR-INR-17013935). Clinical trial registry URL: Date of registration: December 14, 2017.

Aims: The aim of this study was to evaluate the analgesic effectiveness and adverse reactions of ketorolac in comparison with other drugs when administered postoperatively after third molar surgery. Methods: PubMed and Google Scholar were utilized to search for articles comparing the efficacy and safety of ketorolac and other analgesic agents after third molar surgery. Data from papers with a lower risk of bias were recorded. The overall evaluation of analgesia onset, general and subgroup evaluation of the number of patients requiring rescue analgesic medication, general and subgroup assessment of the study medication (satisfaction on the study drugs), and the overall estimation of adverse effects were performed using the Review Manager Software 5.3 to analyse the data and obtain the meta‐analysis plot. Results: The subgroup evaluation of the study medication showed that patients who received ketorolac 30 mg were more satisfied than those who were given parecoxib 1 mg (odds ratio [OR] = 8.57, 95% confidence interval [CI] = 3.66–20.08, P =.00001), parecoxib 2 mg (OR = 7.17, 95% CI = 2.88–17.86, P =.0001), parecoxib 5 mg (OR = 3.03, 95% CI = 1.69–5.41, P =.0002), and parecoxib 10 mg (OR = 2.42, 95% CI = 1.36–4.32, P =.003). Moreover, patients who received ketorolac reported fewer adverse reactions compared with those who had received opioid analgesics (OR = 0.14, 95% CI = 0.32–1.76, P =.0001). Conclusions: The data from this study demonstrates that the postoperative administration of ketorolac 30 mg presents better results on patient satisfaction when compared to parecoxib 1 mg to 10 mg, and presents a similar satisfaction to parecoxib 20 mg following third molar removal. [ABSTRACT FROM AUTHOR]

Introduction: Calotropis procera is a shrub had been used traditionally for the treatment of many diseases including analgesic, anti-inflammatory, hepatic and other diseases. The flower of the plant has not been investigated for its analgesic activity. The present study aims High Pressure Thin Layer Chromatography (HPTLC) and Gas Chromatography-Mass Spectrometry (GC-MS) analysis of Ethanolic Extract of Calotropis procera to evaluate the analgesic effects of Calotropis procera as well as assessment of analgesic activity in animal models. Methods: The ethanolic extracts were prepared using a rotary evaporator and the maceration procedure. The phytocompounds characterization was done by GC-MS and HPTLC. The hot plate method, acetic acid-induced writhing test, and tail-flick test were used to determine the analgesic activity of various doses (100, 200, 300 mg/kg body weight) of the Ethanolic Extract of Calotropis procera flower (EECP). Conclusion: The extract has shown showed significant analgesic activity in the all experiments at a dose of 300 mg/kg. We found that even at low doses, analgesic effectiveness could be achieved via central and peripheral mediated action. The ethanol extract's HPTLC and GC-MS analysis revealed number of compounds with potent analgesic and antioxidant activity. [ABSTRACT FROM AUTHOR]