Propellant Free Pressurized Spray System of Etodolac to Manage Acute Pain Conditions: In Vitro and In Vivo Evaluation.

This study aimed to develop a propellant-free topical spray formulation of Etodolac (BCS-II), a potent NSAID, which could be beneficial in the medical field for the effective treatment of pain and inflammation conditions. The developed novel propellant-free spray formulation is user-friendly, cost-effective, propellant-free, eco-friendly, enhances the penetration of Etodolac through the skin, and has a quick onset of action. Various formulations were developed by adjusting the concentrations of different components, including lecithin, buffering agents, film-forming agents, plasticizers, and permeation enhancers. The prepared propellant-free spray formulations were then extensively characterized and evaluated through various in vitro, ex vivo, and in vivo parameters. The optimized formulation exhibits an average shot weight of 0.24 ± 0.30 ml and an average drug content or content uniformity of 87.3 ± 1.01% per spray. Additionally, the optimized formulation exhibits an evaporation time of 3 ± 0.24 min. The skin permeation study demonstrated that the permeability coefficients of the optimized spray formulation were 21.42 cm/h for rat skin, 13.64 cm/h for mice skin, and 18.97 cm/h for the Strat-M membrane. When assessing its potential for drug deposition using rat skin, mice skin, and the Strat-M membrane, the enhancement ratios for the optimized formulation were 1.88, 2.46, and 1.92, respectively against pure drug solution. The findings from our study suggest that the propellant-free Etodolac spray is a reliable and safe topical formulation. It demonstrates enhanced skin deposition, and improved effectiveness, and is free from any skin irritation concerns.

Transcutaneous electrical nerve stimulation for reducing postoperative acute pain after hip fracture surgery: a double-blinded randomized clinical trial.

OBJECTIVE: The aim of this study was to assess the effects of two different applications of transcutaneous electrical nerve stimulation (TENS) on the reduction of postoperative acute pain after hip fracture surgery. PATIENTS AND METHODS: In this study, 120 patients undergoing hip surgery were divided into three groups. The first group received patient-controlled analgesia (PCA) with epidural fentanyl and additional medications. The second group received lumbar plexus and sciatic nerve transcutaneous electrical nerve stimulation (LS-TENS) along with the same medication protocol as the first group. The third group received the same medication protocol as the first group, as well as surgical wound transcutaneous electrical nerve stimulation (SW-TENS). Pain levels were measured using a Visual Analog Scale (VAS) score, and the number of opioid analgesics used by each patient was recorded. VAS score and the total consumption of opioid analgesics were meticulously documented. RESULTS: VAS scores were higher in the control group than in the SW-TENS group at 30 min (1.58±2.49 vs. 0.70±2.15, p<0.05) and in the SW-TENS group than in the LS- TENS group at 24 h postoperatively (2.33±1.29 vs. 1.63±1.05, p<0.05). The 48-h total analgesic consumption level of the control group was higher than that of the LS-TENS group (p<0.05). CONCLUSIONS: The findings of this study indicate that TENS application to the surgical wound, lumbar plexus, and sciatic nerve using anatomical landmarks can significantly reduce postoperative pain, as demonstrated by the higher VAS scores, higher total analgesic consumption and high additional analgesic need in the control group after hip fracture surgery. CLINICALTRIALS: gov ID: NCT02642796.

Gastrointestinal adverse effects associated with the use of intravenous oliceridine compared with intravenous hydromorphone or fentanyl in acute pain management utilizing adjusted indirect treatment comparison methods.

Background: In the absence of head-to-head comparative data from randomized controlled trials, indirect treatment comparisons (ITCs) may be used to compare the relative effects of treatments versus a common comparator (either placebo or active treatment). For acute pain management, the effects of oliceridine have been compared in clinical trials to morphine but not to fentanyl or hydromorphone. Aim: To assess the comparative safety (specifically differences in the incidence of nausea, vomiting and opioid-induced respiratory depression [OIRD]) between oliceridine and relevant comparators (fentanyl and hydromorphone) through ITC analysis. Methods: A systematic literature review identified randomized clinical trials with oliceridine versus morphine and morphine versus fentanyl or hydromorphone. The ITC utilized the common active comparator, morphine, for the analysis. Results: A total of six randomized controlled trials (oliceridine - 2; hydromorphone - 3; fentanyl - 1) were identified for data to be used in the ITC analyses. The oliceridine data were reported in two studies (plastic surgery and orthopedic surgery) and were also reported in a pooled analysis. The ITC focused on nausea and vomiting due to limited data for OIRD. When oliceridine was compared with hydromorphone in the ITC analysis, oliceridine significantly reduced the incidence of nausea and/or vomiting requiring antiemetics compared with hydromorphone (both orthopedic surgery and pooled data), while results in plastic surgery were not statistically significant. When oliceridine was compared with hydromorphone utilizing data from Hong, the ITC only showed a trend toward reduced risk of nausea and vomiting with oliceridine that was not statistically significant across all three comparisons (orthopedic surgery, plastic surgery and combined). An ITC comparing oliceridine with a study of fentanyl utilizing the oliceridine orthopedic surgery data and combined orthopedic and plastic surgery data showed a trend toward reduced risk that was not statistically significant. Conclusion: In ITC analyses, oliceridine significantly reduced the incidence of nausea and/or vomiting or the need for antiemetics in orthopedic surgery compared with hydromorphone and a non-significant trend toward reduced risk versus fentanyl.

Prescription Opioid Decision-making and Use Behaviors in Adolescents With Acute Pain: A Qualitative Study.

OBJECTIVES: Understanding adolescent perspectives on prescribed opioids in the context of medical care for acute pain is needed to prevent opioid-related adverse outcomes. We explored factors that may influence opioid decision-making and use behaviors among adolescents prescribed opioids for acute pain. METHODS: We conducted semistructured interviews with 19 adolescents (63% females, ages 12 to 17) prescribed opioids upon discharge from surgery or intensive care unit admission. Interview transcripts were coded using inductive thematic analysis. RESULTS: Five themes were identified: "Opioid use to reduce extreme pain and facilitate acute recovery"; "Familiarity with risks and negative effects of opioids"; "Assessment of opioid risk based on individual characteristics and use behaviors"; "Careful balance of risks, benefits, and symptoms when taking opioids"; "Importance of trusted adults for adolescent opioid management". Adolescents commonly believe opioids are only appropriate for severe pain that cannot be managed with other strategies. Most (but not all) adolescents were aware of addiction and other potential opioid harms and generally disapproved of misuse. However, a few adolescents would consider taking unprescribed opioids for severe pain. Adolescents wanted to be well informed for opioid decision-making, considering guidance from trusted adults. DISCUSSION: Adolescents often demonstrated active and sound participation in shared opioid decision-making, influenced by complex integration of inputs and self-reflection. Conversely, potential factors that could contribute to risky behaviors included low personal risk perceptions, uncertainty about what constitutes opioid misuse, and avoidance of prescribed opioids despite extreme pain. Future studies may explore associations of adolescents' opioid decision-making with longer-term pain and opioid-related outcomes.

Co-crystal of Tramadol-Celecoxib Versus Tramadol or Placebo for Acute Moderate-to-Severe Pain After Oral Surgery: Randomized, Double-Blind, Phase 3 Trial (STARDOM1).

INTRODUCTION: Co-crystal of tramadol-celecoxib (CTC) is the first analgesic co-crystal for acute pain. This completed phase 3 multicenter, double-blind trial assessed the efficacy and safety/tolerability of CTC in comparison with that of tramadol in the setting of moderate-to-severe pain up to 72 h after elective third molar extraction requiring bone removal. METHODS: Adults (n = 726) were assigned randomly to five groups (2:2:2:2:1): orally administered twice-daily CTC 100 mg (44 mg rac-tramadol hydrochloride/56 mg celecoxib; n = 164), 150 mg (66/84 mg; n = 160) or 200 mg (88/112 mg; n = 160); tramadol 100 mg four times daily (n = 159); or placebo four times daily (n = 83). Participants in CTC groups also received twice-daily placebo. The full analysis set included all participants who underwent randomization. The primary endpoint was the sum of pain intensity differences over 0 to 4 h (SPID0-4; visual analog scale). Key secondary endpoints included 4-h 50% responder and rescue medication use rates. Safety endpoints included adverse events (AEs), laboratory measures, and Opioid-Related Symptom Distress Scale (OR-SDS) score. RESULTS: All CTC doses were superior to placebo (P < 0.001) for primary and key secondary endpoints. All were superior to tramadol for SPID0-4 (analysis of covariance least squares mean differences [95% confidence interval]: - 37.1 [- 56.5, - 17.6], - 40.2 [- 59.7, - 20.6], and - 41.7 [- 61.2, - 22.2] for 100, 150, and 200 mg CTC, respectively; P < 0.001) and 4-h 50% responder rate. Four-hour 50% responder rates were 32.9% (CTC 100 mg), 33.8% (CTC 150 mg), 40.6% (CTC 200 mg), 20.1% (tramadol), and 7.2% (placebo). Rescue medication use was lower in the 100-mg (P = 0.013) and 200-mg (P = 0.003) CTC groups versus tramadol group. AE incidence and OR-SDS scores were highest for tramadol alone. CONCLUSIONS: CTC demonstrated superior pain relief compared with tramadol or placebo, as well as an improved benefit/risk profile versus tramadol. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02982161; EudraCT number, 2016-000592-24.

Dexmedetomidine Prevents Chronic Incisional Pain After Brain Tumor Resection: A Secondary Analysis of the Randomized Control Trial.

BACKGROUND: Dexmedetomidine was reported to reduce postoperative acute pain after neurosurgery. However, the efficacy of dexmedetomidine for preventing chronic incisional pain is uncertain. METHODS: This article is a secondary analysis of a randomized, double-blind, placebo-controlled trial. Eligible patients were randomly allocated to either the dexmedetomidine group or the placebo group. Patients assigned to the dexmedetomidine group were given a 0.6 µg kg -1 dexmedetomidine bolus followed by a 0.4 µg kg -1 h -1 maintenance dose until dural closure; placebo patients were given comparable amounts of normal saline. The primary end point was the incidence of incisional pain at 3 months after craniotomy evaluated by numerical rating scale scores and defined as any score >0. The secondary end points were postoperative acute pain scores, sleep quality, and Short-Form McGill Pain Questionnaire (SF-MPQ-2) at 3 months after craniotomy. RESULTS: From January 2021 to December 2021, a total of 252 patients were included in the final analysis: the dexmedetomidine group (n = 128) and the placebo group (n = 124). The incidence of chronic incisional pain was 23.4% (30 of 128) in the dexmedetomidine group versus 42.7% (53 of 124) in the placebo group (risk ratio, 0.55; 95% confidence interval, 0.38-0.80; P = .001). The overall severity of chronic incisional pain was mild in both groups. Patients in the dexmedetomidine group had lower acute pain severity on movement than those in the placebo group for the first 3 days after surgery (all adjusted P < .01). Sleep quality did not differ between groups. However, the SF-MPQ-2 total sensory ( P = .01) and neuropathic pain descriptor ( P = .023) scores in the dexmedetomidine group were lower than those in the placebo group. CONCLUSIONS: Prophylactic intraoperative dexmedetomidine infusion reduces the incidence of chronic incisional pain as well as acute pain score after elective brain tumor resections.

Cryoanalgesia: Review with Respect to Peripheral Nerve.

BACKGROUND: Cryoanalgesia is a tool being used by interventional radiology to treat chronic pain. Within a certain cold temperature range, peripheral nerve function is interrupted and recovers, without neuroma formation. Cryoanalgesia has most often been applied to the intercostal nerve. Cryoanalgesia has applications to peripheral nerve surgery, yet is poorly understood by reconstructive microsurgeons. METHODS: Histopathology of nerve injury was reviewed to understand cold applied to peripheral nerve. Literature review was performed utilizing the PubMed and MEDLINE databases to identify comparative studies of the efficacy of intraoperative cryoanalgesia versus thoracic epidural anesthesia following thoracotomy. Data were analyzed using Fisher's exact and analysis of variance tests. A similar approach was used for pudendal cryoanalgesia. RESULTS: Application of inclusion and exclusion criteria resulted in 16 comparative clinical studies of intercostal nerve for this review. For thoracotomy, nine studies compared cryoanalgesia with pharmaceutical analgesia, with seven demonstrating significant reduction in postoperative opioid use or postoperative acute pain scores. In these nine studies, there was no association between the number of nerves treated and the reduction in acute postoperative pain. One study compared cryoanalgesia with local anesthetic and demonstrated a significant reduction in acute pain with cryoanalgesia. Three studies compared cryoanalgesia with epidural analgesia and demonstrated no significant difference in postoperative pain or postoperative opioid use. Interventional radiology targets pudendal nerves using computed tomography imaging with positive outcomes for the patient with pain of pudendal nerve origin. CONCLUSION: Cryoanalgesia is a term used for the treatment of peripheral nerve problems that would benefit from a proverbial reset of peripheral nerve function. It does not ablate the nerve. Intraoperative cryoanalgesia to intercostal nerves is a safe and effective means of postoperative analgesia following thoracotomy. For pudendal nerve injury, where an intrapelvic surgical approach may be difficult, cryoanalgesia may provide sufficient clinical relief, thereby preserving pudendal nerve function.

Dosing of Cannabinoids Associated with an Opioid-Sparing Effect: A Systematic Review of Longitudinal Studies.

OBJECTIVE: To assess cannabinoid dosing that could be associated with a reduction in opioid use. DESIGN: Systematic review conducted according to the PRISMA statement. DATA SOURCES: PubMed, Embase, Web of Science, and PsycINFO were searched up to December 10, 2022. REVIEW/ANALYSIS METHODS: We included randomized controlled trials (RCT) and longitudinal observational studies assessing cannabinoids effect on opioid use in patients with acute or chronic pain. Two reviewers independently assessed the studies for inclusion and extracted the data. Tetrahydrocannabinol (THC), Cannabidiol (CBD), and other cannabinoids with dosing were the exposures. Change in opioid doses and opioid discontinuation were the outcomes. RESULTS: Fifteen studies (including seven RCTs) were included. Eight studies (six observational and two RCTs) were conducted among patients with chronic pain including three with cancer-related pain. Seven studies involved patients with acute pain (five RCTs).In chronic non-cancer pain patients, two observational studies that assessed THC and CBD in combination (average daily dose 17mg/15mg), and one that assessed a CBD-rich extract (31.4 mg/day), showed a significant reduction in opioid use. Of the three studies conducted on patients with cancer, only the observational study that assessed nabilone (average 1.7 mg/day) showed a significant reduction in opioid use. In patients with acute pain, only two observational studies that assessed dronabinol (5mg and 5-10 mg/day for four days) showed a significant reduction in opioid use. CONCLUSION: The opioid-sparing effect of cannabinoids remains uncertain based on current evidence. However, attention could be paid to cannabinoid doses associated with opioid reduction in included observational studies.

Trajectory of pain threshold and its association with acute pain after thoracic surgery: a prospective observational study.

BACKGROUND: Postoperative analgesic management is an ongoing challenge. The pain threshold (PT) is an objective index that reflects the body's sensitivity to pain and can be used for quantitative pain assessment. We hypothesized that the PT is correlated with postoperative pain and can thus be used to guide postoperative pain management. METHODS: This study involved 93 patients who underwent thoracoscopic surgery from December 2019 to February 2020. The PT was measured with transcutaneous electrical stimulation before surgery (T0) and at 1 h (T1), 6 h (T6), and 24 h (T24) after surgery. The visual analogue scale (VAS) score was used to evaluate the severity of postoperative pain at the same time. The PT variation (PTV) after surgery was calculated as the ratio of the postoperative PT to preoperative PT. RESULTS: The postoperative PT was higher than the preoperative PT and showed a downward trend within 24 h after surgery; the PTV also showed a downward trend within 24 h after surgery. PT-T1 was negatively correlated with VAS-T1 at rest and during motion (rest: VAS-T1r = - 0.274, P = 0.008; motion: VAS-T1r = - 0.298, P = 0.004). PTV-T1 was negatively correlated with VAS-T1 during motion (r = - 0.213, P = 0.04). Lower VAS-T1 scores (< 4) at rest and during motion were associated with higher PT-T1 (rest: t = 2.452, P = 0.016; motion: t = 2.138, P = 0.035). The intraoperative sufentanil dose was associated with a postoperative increase in PTV-T1. Increased rescue analgesic administration was associated with PTV elevation. However, the incidence of dizziness in patients with moderate PTV-T24 was lower than that in patients with high or low PTV-T24 (χ2 = 8.297, P = 0.015). CONCLUSIONS: The postoperative PT was higher than the preoperative PT and showed a downward trend within 24 h after surgery; PTV also showed a downward trend within 24 h after surgery. The PT and PTV were negatively correlated with the pain intensity at rest and during motion and were associated with perioperative analgesic consumption and the incidence of adverse events.

Impact of mandated drug monitoring on opioid use during highly conformal radiotherapy for oropharynx cancer.

BACKGROUND: Prescription drug monitoring programs (PDMPs) have proliferated due to increasing opioid-related deaths. We evaluated acute opioid use changes for 64 patients treated with highly conformal radiotherapy (RT) following a state-mandated PDMP. METHODS: Patients receiving proton therapy (PT) (n=40), intensity-modulated RT (IMRT) (n=14), or both (n=10) were divided into preintervention (n=26) and postintervention cohorts (n=38); records were reviewed retrospectively under an institutional review board (IRB)-approved tracking protocol. Dosages prescribed during acute therapy (during RT-3 months post-RT) and patient-reported pain (Defense and Veterans Pain Rating Scale) were endpoints. Dosages were treated as responses in Chi-square tests (three-level ordinal response). RESULTS: Overall, 72% (n=46) received opioids; of which 22% (n=10) of all patients and 10% (n=2) of opioid-naive patients continued analgesic management 3 months post-RT. Median total doses were 975 and 1,025 morphine milligram equivalents (MME) in pre- and postintervention groups, with no significant differences in MME prescribed (P=0.8) or uncontrolled pain (P=0.3). Statistically significant factors were tonsil primaries (P<0.01) and alcohol use (P=0.02). Uncontrolled pain episodes during and post-RT did not vary per cohort (P=0.19). CONCLUSIONS: PDMP use was not associated with management changes in patient-reported acute pain during RT (IMRT or PT). Following highly conformal RT, few patients remained on narcotics 3 months post-RT.

A pilot randomized, placebo-controlled, double-blind study of omega-3 fatty acids to prevent paclitaxel-associated acute pain syndrome in breast cancer patients: Alliance A22_Pilot2.

PURPOSE: Paclitaxel is associated with an acute pain syndrome (P-APS- and chronic chemotherapy-induced peripheral neuropathy (CIPN). P-APS is associated with higher risk of CIPN. Omega-3 fatty acids have well-established anti-inflammatory and neuroprotective properties. The primary purpose of this pilot study was to assess whether omega-3 fatty acids could decrease P-APS and thus CIPN. METHODS: Patients scheduled to receive weekly paclitaxel for breast cancer were randomized to receive 4 g of omega-3 acid ethyl esters (Lovaza) or placebo, beginning 1 week prior and continued until paclitaxel was stopped. Patients completed acute pain questionnaires at baseline, daily after each treatment, and 1 month after completion of therapy. RESULTS: Sixty patients (49 evaluable) were randomized to treatment versus placebo. Seventeen (68.0%) patients receiving the omega-3 fatty acids intervention experienced P-APS, compared to 15 (62.5%) of those receiving placebo during the first week of treatment (p = 0.77). Over the full 12-week study, 21 (84.0%) patients receiving the omega-3 fatty acid intervention experienced P-APS, compared to 21 (87.5%) of those receiving placebo (p = 1.0). Secondary outcomes suggested that those in the intervention arm used more over-the-counter analgesics (OR: 1.65, 95% CI: 0.72-3.78, p = 0.23), used more opiates (OR: 2.06, 95% CI: 0.55-7.75, p = 0.28), and experienced higher levels of CIPN (12.8, 95% CI: 7.6-19.4 vs. 8.4, 95% CI: 4.6-13.2, p = 0.21). CONCLUSIONS: The results of this pilot study do not support further study of the use of omega-3 fatty acids for the prevention of the P-APS and CIPN. TRIAL REGISTRATION: Number: NCT01821833.

Effect of Analgesic Low-Dose Ketamine Infusions on the Cardiovascular Response: A Retrospective Analysis.

BACKGROUND: Low-dose ketamine infusion (LDKI) has shown effectiveness for treating acute pain associated with surgical and nonsurgical (traumatic, neuropathic, and acute cancer-related) origin as an adjuvant to opioids. The increasing use of LDKI as an opioid-sparing agent in multimodal analgesia requires a better understanding of its effects on the cardiovascular response, a known dose-dependent side effect of ketamine administration. We investigated the cardiovascular response of acute pain patients treated with LDKI. OBJECTIVES: The aim of the present study was to evaluate the effect of LDKI in hemodynamic variables (blood pressure [BP] and heart rate [HR]) during LDKI analgesia for up to 48 hours of treatment in an acute pain setting. Secondary objectives were to evaluate psychomimetic effects. STUDY DESIGN: Retrospective unicentric cohort design. SETTING: The study was conducted at an academic university hospital. METHODS: We conducted a single-center retrospective cohort analysis of adult patients who underwent LDKI to treat surgical and nonsurgical acute pain. We obtained data from the Hospital San Vicente Fundación Health Documentation System database and evaluated the medical records of 318 patients with surgical and nonsurgical pain. Patients received a 0.1 mg/kg/h ketamine infusion as part of a multimodal analgesic plan. Baseline systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and HR values were compared with those measured after 24 and 48 hours of treatment. Pain level and psychomimetic effects were measured at 24 and 48 hours. Cardiovascular complications and treatment duration were also recorded. Patients with a history of psychiatric, cardiovascular, or cognitive disease were excluded from the study. This study was registered in the clinicaltrials.gov database (identifier: NCT03979105). RESULTS: No statistical differences in SBP, DBP, MAP, or HR were observed when baseline and post-LDKI treatment values were compared (P < 0.05). When comparing hemodynamic variables after exposure to LDKI in patients with and without hypertension, we did not observe statistically significant differences in mean HR, systolic arterial pressure, diastolic arterial pressure, or MAP values at 24 and 48 hours. The frequency of severe pain was reduced from 72% on day 0 to 4.4% on day 1 and 6.2% on day 2 post-LDKI. Observed psychomimetic effects were confusion 4.39%, hallucinations 2.51%, and nightmares 1.25%. No major cardiovascular events were observed. LIMITATIONS: This study was limited by its retrospective design, the lack of a comparative matching cohort, and the good general condition of the majority of patients included in the study. CONCLUSIONS: LDKI (0.1 mg/kg/h) was not associated with significant changes in baseline BP or HR. Our results suggest that as an adjuvant in multimodal analgesia for surgical and nonsurgical acute pain, LDKI has a low impact on the cardiovascular response. KEY WORDS: Ketamine, adverse effects, tachycardia, hypertension, postoperative pain, chronic postsurgical pain.

Comparison of the effects of one-level and bi-level pre-incisional erector spinae plane block on postoperative acute pain in video-assisted thoracoscopic surgery; a prospective, randomized, double-blind trial.

BACKGROUND: This prospective, randomized, double-blind trial aimed to compare the postoperative analgesic efficacy of One-Level pre-incisional erector spinae plane block (ESPB) and Bi-Level pre-incisional ESPB in patients undergoing video-assisted thoracic surgery (VATS). METHODS: This pilot trial was conducted between April 2022 and February 2023 with sixty patients. The patients were randomly divided into two groups. In One-Level ESPB Group (n = 30) block was performed at the thoracal(T)5 level with the 30 ml 0.25% bupivacaine. In the Bi-Level ESPB Group (n = 30) block was performed at T4 and T6 levels by using 15 ml of 0.25% bupivacaine for each level. In the postoperative period, 50 mg dexketoprofen every 12 h and 1 g paracetamol every 8 h were given intravenously (IV). Patient-controlled analgesia (PCA) prepared with morphine was applied to the patients. 0.5 mg/kg of tramadol was administered via IV for rescue analgesia. Visual analog scale (VAS) scores were recorded in the postoperative 1st, 2nd, 4th, 12th, 24th, and 48th -hours. The need for additional analgesics and side effects were recorded. In two groups, patients' demographics and postoperative hemodynamic data were recorded. RESULTS: VAS scores at resting were statistically significantly higher at the 1st (p: 0.002) and 4th -hour (p: 0.001) in the One-Level ESPB. When the groups were evaluated in terms of VAS coughing scores, the 4th -hour (p: 0.001) VAS coughing scores results were found to be statistically significantly higher in the One-Level ESPB group. In terms of VAS values evaluated during follow-up, the rates of VAS coughing score > 3 values were found to be statistically significantly lower in the Bi-Level ESPB group (p: 0.011). There was no statistically significant difference between the groups in terms of side effects, morphine consumption, and additional analgesic use (p > 0.05). CONCLUSIONS: Adequate analgesia was achieved in the early postoperative period in the group treated with Bi-Level ESPB with similar morphine consumption and side effects. This may be an advantage, especially in the early postoperative period when the pain is quite intense.

Acute Pain in Perspective.

KEY TAKEAWAYS: Acute pain is a common and nearly universal experience that usually has a sudden onset and is limited in duration. It is a normal physiologic response to a noxious stimulus that can become pathologic if untreated or not treated effectively. Acute pain has a limited duration (<1 month) and often is caused by injury, trauma, or medical treatments such as surgery. Primary care practitioners (PCPs) who encounter patients with acute pain can help preserve function and quality of life and prevent progression to chronic pain by implementing appropriate management strategies. PCPs in rural settings may bear greater responsibility for acute pain management because of the lack of accessible specialists. All current guidelines support using a multimodal approach to pain management and reserving use of opioids for patients with severe pain that cannot be managed with other agents. There are several new agents and formulations recently approved or in development for the treatment of acute pain. The recently approved co-crystal formulation of celecoxib and tramadol hydrochloride provides an additional option for acute pain management and utilizes a single-medication multimodal approach.

Similar functional roles of the Orexin-1 and Orexin-2 receptors within the dentate gyrus area of the hippocampus in the stress-induced antinociceptive responses in the acute pain model in the rat.

Studies establish that the brain's Orexin system is involved in pain modulation. Orexin-1 and orexin-2 receptors (OX1 and OX2r, respectively) are essential in responsiveness to stressful stimuli. Some evidence indicates that the hippocampus's dentate gyrus (DG) potentially modulates pain and stress. The present study examined the involvement of OX1 and OX2 receptors within the DG in response to acute pain after exposure to forced swim stress (FSS). Five to seven days post-stereotaxic surgery, the baseline tail-flick latency (TFL) was taken from the animal, then rats unilaterally received through an implanted cannula either different doses of OX1r antagonist (SB334867; 1, 3, 10, and 30 nmol), OX2r antagonist (TCS OX2 29; 1, 3, 10 and 30 nmol), or vehicle (0.5 µl solution of 12% DMSO). After 5 min, rats were exposed to the FSS for six minutes. Subsequently, the tail-flick test was conducted, and the TFLs were measured at the 60-min time set intervals. Results indicated that FSS produces antinociceptive responses in the tail-flick test. Two-way ANOVA analysis showed that Microinjection of OX1r and OX2r antagonists into the DG region of the brain reduced FSS-induced analgesia in the tail-flick test. The decrement effects of these two antagonists were almost the same. Additionally, results showed that the role of both receptors was the same in modulating stress-induced analgesia (SIA). These findings show that the orexin system in the hippocampal DG region might be partially involved in the SIA in acute pain.

Low-Level Laser Therapy for Acute Pain: A Comprehensive Review.

PURPOSE OF REVIEW: An analysis of data conducted in 2015 by the National Health Interview Survey (NHIS) found that an estimated 25.3 million adults (11.2%) have experienced pain every day for the preceding 3 months, and nearly 40 million adults (17.6%) have experienced a severe level of pain. RECENT FINDINGS: Multiple reviews have analyzed the current management of acute pain; however, much of the current literature only focuses on pharmacological methods of analgesia, such as opiates, ketamine, or non-steroidal anti-inflammatory drugs (NSAIDs). Publications that discuss non-pharmacological options often criticize the limitations of available research for these therapies, making further exploration of this type of treatment necessary. The present investigation aims to summarize current knowledge on the use of low-level laser therapy (LLLT), a cold laser non-pharmacological approach, in managing acute pain and to discuss important clinical findings and considerations when it comes to utilizing this treatment option in patients.

Impact of different doses of remifentanil on chronic postsurgical pain after video-assisted thoracic surgery: A propensity score analysis.

A remifentanil infusion dose of >0.2 µg/kg/min is associated with hyperalgesia, leading to acute postsurgical pain; however, its contribution to the development of chronic postsurgical pain after video-assisted thoracic surgery remains unclear. This study aimed to evaluate the impact of different remifentanil doses on chronic postsurgical pain after video-assisted thoracic surgery. This study included inpatients aged ≥ 55 years who underwent video-assisted thoracic surgery under general anesthesia between April 2016 and December 2018. An inverse probability of treatment weighted using stabilized inverse propensity scores was adopted to minimize bias. After adjustments based on patient data, the outcomes of interest were compared with intraoperative covariates using a generalized estimating equation. The primary study outcome was chronic postsurgical pain 1 year after surgery, defined as a pain score ≥1 on a numerical rating scale. Of the 262 eligible patients, 258 with a mean age of 71.2 years were included in this analysis. Chronic postsurgical pain occurred in 23.6% of patients. The generalized estimating equation revealed that a remifentanil infusion dose >0.2 µg/kg/min was associated with chronic postsurgical pain at 1 year after surgery (odds ratio [OR] 1.52; 95% confidence interval [CI] 1.03-2.27), while remifentanil infusion doses >0.15 µg/kg/min (OR 1.12; 95% CI 0.79-1.59) and >0.175 µg/kg/min (OR 1.17; 95% CI 0.83-1.64) were not associated with our primary outcome. Remifentanil infusions >0.2 µg/kg/min were associated with chronic postsurgical pain 1 year after video-assisted thoracic surgery.

Patient-controlled analgesia for the management of adults with acute trauma in the emergency department: A systematic review and meta-analysis.

BACKGROUND: Patient-controlled analgesia (PCA) has potential as a form of analgesia for trauma patients in the emergency department (ED). The objective of this review was to evaluate the effectiveness and safety of PCA for the management of adults with acute traumatic pain in the ED. The hypothesis was that PCA can effectively treat acute trauma pain in adults in the ED, with minimal adverse outcomes and better patient satisfaction compared with non-PCA modalities. METHODS: MEDLINE (PubMed), Embase, SCOPUS, ClinicalTrials.gov , and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched from inception date to December 13, 2022. Randomized controlled trials involving adults presenting to the ED with acute traumatic pain who received intravenous (IV) analgesia via PCA compared with other modalities were included. The Cochrane Risk of Bias tool and the Grading of Recommendation, Assessment, Development, and Evaluation approach were used to assess the quality of included studies. RESULTS: A total of 1,368 publications were screened, with 3 studies involving 382 patients meeting the eligibility criteria. All three studies compared PCA IV morphine with clinician-titrated IV morphine boluses. For the primary outcome of pain relief, the pooled estimate was in favor of PCA with a standard mean difference of -0.36 (95% confidence interval, -0.87 to 0.16). There were mixed results concerning patient satisfaction. Adverse event rates were low overall. The evidence from all three studies was graded as low-quality because of a high risk of bias from lack of blinding. CONCLUSION: This study did not demonstrate a significant improvement in pain relief or patient satisfaction using PCA for trauma in the ED. Clinicians wishing to use PCA to treat acute trauma pain in adult patients in the ED are advised to consider the available resources in their own practice settings and to implement protocols for monitoring and responding to potential adverse events. LEVEL OF EVIDENCE: Systematic Review/Meta-Analyses; Level III.