Analgesic Profile Research Articles

Antinociceptive Profile of ARN19702, (2-Ethylsulfonylphenyl)-[(2S)-4-(6-fluoro-1,3-benzothiazol-2-yl)-2-methylpiperazin-1-yl]methanone, a Novel Orally Active N-Acylethanolamine Acid Amidase Inhibitor, in Animal Models.

N-Acylethanolamine acid amidase (NAAA) is an N-terminal cysteine hydrolase that stops the physiologic actions of palmitoylethanolamide, an endogenous lipid messenger that activates the transcription factor, peroxisome proliferator-activated receptor-α We have previously reported that the compound ARN19702 [(2-ethylsulfonylphenyl)-[(2S)-4-(6-fluoro-1,3-benzothiazol-2-yl)-2-methylpiperazin-1-yl]methanone] is an orally active, reversible NAAA inhibitor (IC50 on human NAAA = 230 nM) that produces remarkable protective effects against multiple sclerosis in mice. In the present study, we assessed the profile of ARN19702 in mouse and rat models of acute and neuropathic pain. Oral administration in male mice attenuated in a dose-dependent manner the spontaneous nocifensive response elicited by intraplantar formalin injection and the hypersensitivity caused by intraplantar carrageenan injection, paw incision, or sciatic nerve ligation. In male rats, ARN19702 reduced nociception associated with paclitaxel-induced neuropathy without development of subacute antinociceptive tolerance. Finally, ARN19702 (30 mg/kg, oral) did not produce place preference or alter exploratory motor behavior in male mice. The findings support the conclusion that NAAA is a suitable molecular target for the discovery of efficacious analgesic drugs devoid of rewarding potential. SIGNIFICANCE STATEMENT: This study evaluated the pharmacological profile of the orally bioavailable N-acylethanolamine acid amidase (NAAA) inhibitor (2-ethylsulfonylphenyl)-[(2S)-4-(6-fluoro-1,3-benzothiazol-2-yl)-2-methylpiperazin-1-yl]methanone (ARN19702) in mouse and rat models of neurogenic and inflammatory pain. The compound's potential rewarding and sedative effects were also examined. It is concluded that ARN19702 exhibits a broad analgesic profile that can be generalized across rodent species. The findings point to NAAA as a control node in the processing of neuropathic and inflammatory pain and to ARN19702 as a lead to uncover novel pain therapeutics devoid of addictive potential .

English

BACKGROUND Middle ear surgeries done under local anaesthesia require adequate patient sedation and analgesia to prevent patient anxiety and movement during surgical procedures. This study was undertaken to compare dexmedetomidine and propofol for their sedative and analgesic properties, safety profile, adverse events and recovery profile in patients undergoing middle ear surgery under monitored anaesthesia care. METHODS This is a prospective observational study. 96 patients of both sexes, of American society of anaesthesiologist (ASA) grade I or II, between 18 - 60 years of age were randomly divided into two groups; group D and group P consisting of 48 patients each. Patients in group D received a loading dose of injection dexmedetomidine 1 µg / kg I.V. over 10 minutes followed by an infusion at a rate of 0.5 µg / kg / hr. Patients in group P received a loading dose of injection propofol 75 µg / kg / min. I.V. over 10 min followed by an infusion at a rate of 50 µg / kg / min. Time taken to achieve the modified Aldrete score of 10 was compared between both the groups. Before discharge from post anaesthesia care unit (PACU), patient’s satisfaction with sedation & surgeon satisfaction was recorded on Likert scale. Time to rescue analgesia was compared. RESULTS The Bi-Spectral Index values in intra-operative period were on the lower side in the group D as compared to the corresponding values in the group P, but P values were statistically insignificant suggesting that both dexmedetomidine and propofol produced similar sedation. Time to rescue analgesia was greater for group D. CONCLUSIONS Having similar sedation effect, dexmedetomidine was better than propofol for sedation in patients undergoing middle ear surgery under monitored anaesthesia care. KEYWORDS Dexmedetomidine, Propofol, Monitored Anaesthesia Care, Bi-spectral Index

Tricyclic Triazoles as σ1 Receptor Antagonists for Treating Pain.

The synthesis and pharmacological activity of a new series of 5a,7,8,8a-tetrahydro-4H,6H-pyrrolo[3,4-b][1,2,3]triazolo[1,5-d][1,4]oxazine derivatives as potent sigma-1 receptor (σ1R) ligands are reported. A lead optimization program aimed at improving the aqueous solubility of parent racemic nonpolar derivatives led to the identification of several σ1R antagonists with a good absorption, distribution, metabolism, and excretion in vitro profile, no off-target affinities, and characterized by a low basic pKa (around 5) that correlates with high exposure levels in rodents. Two compounds displaying a differential brain-to-plasma ratio distribution profile, 12lR and 12qS, exhibited a good analgesic profile and were selected as preclinical candidates for the treatment of pain.

Physiologically based pharmacokinetic/pharmacodynamic model for the prediction of morphine brain disposition and analgesia in adults and children.

Morphine is a widely used opioid analgesic, which shows large differences in clinical response in children, even when aiming for equivalent plasma drug concentrations. Age-dependent brain disposition of morphine could contribute to this variability, as developmental increase in blood-brain barrier (BBB) P-glycoprotein (Pgp) expression has been reported. In addition, age-related pharmacodynamics might also explain the variability in effect. To assess the influence of these processes on morphine effectiveness, a multi-compartment brain physiologically based pharmacokinetic/pharmacodynamic (PB-PK/PD) model was developed in R (Version 3.6.2). Active Pgp-mediated morphine transport was measured in MDCKII-Pgp cells grown on transwell filters and translated by an in vitro-in vivo extrapolation approach, which included developmental Pgp expression. Passive BBB permeability of morphine and its active metabolite morphine-6-glucuronide (M6G) and their pharmacodynamic parameters were derived from experiments reported in literature. Model simulations after single dose morphine were compared with measured and published concentrations of morphine and M6G in plasma, brain extracellular fluid (ECF) and cerebrospinal fluid (CSF), as well as published drug responses in children (1 day- 16 years) and adults. Visual predictive checks indicated acceptable overlays between simulated and measured morphine and M6G concentration-time profiles and prediction errors were between 1 and -1. Incorporation of active Pgp-mediated BBB transport into the PB-PK/PD model resulted in a 1.3-fold reduced brain exposure in adults, indicating only a modest contribution on brain disposition. Analgesic effect-time profiles could be described reasonably well for older children and adults, but were largely underpredicted for neonates. In summary, an age-appropriate morphine PB-PK/PD model was developed for the prediction of brain pharmacokinetics and analgesic effects. In the neonatal population, pharmacodynamic characteristics, but not brain drug disposition, appear to be altered compared to adults and older children, which may explain the reported differences in analgesic effect.

Behavioral Battery for Testing Candidate Analgesics in Mice. I. Validation with Positive and Negative Controls

This study evaluated a battery of pain-stimulated, pain-depressed, and pain-independent behaviors for preclinical pharmacological assessment of candidate analgesics in mice. Intraperitoneal injection of dilute lactic acid (IP acid) served as an acute visceral noxious stimulus to produce four pain-related behaviors in male and female ICR mice: stimulation of 1) stretching, 2) facial grimace, 3) depression of rearing, and 4) depression of nesting. Additionally, nesting and locomotion in the absence of the noxious stimulus were used to assess pain-independent drug effects. These six behaviors were used to compare effects of two mechanistically distinct but clinically effective positive controls (ketoprofen and oxycodone) and two negative controls that are not clinically approved as analgesics but produce either general motor depression (diazepam) or motor stimulation (amphetamine). We predicted that analgesics would alleviate all IP acid effects at doses that did not alter pain-independent behaviors, whereas negative controls would not. Consistent with this prediction, ketoprofen (0.1-32 mg/kg) produced the expected analgesic profile, whereas oxycodone (0.32-3.2 mg/kg) alleviated all IP acid effects except depression of rearing at doses lower than those that altered pain-independent behaviors. For the negative controls, diazepam (1-10 mg/kg) failed to block IP acid-induced depression of either rearing or nesting and only decreased IP acid-stimulated behaviors at doses that also decreased pain-independent behaviors. Amphetamine (0.32-3.2 mg/kg) alleviated all IP acid effects but only at doses that also stimulated locomotion. These results support utility of this model as a framework to evaluate candidate-analgesic effects in a battery of complementary pain-stimulated, pain-depressed, and pain-independent behavioral endpoints. SIGNIFICANCE STATEMENT: Preclinical assays of pain and analgesia often yield false-positive effects with candidate analgesics. This study used two positive-control analgesics (ketoprofen, oxycodone) and two active negative controls (diazepam, amphetamine) to validate a strategy for distinguishing analgesics from nonanalgesics by profiling drug effects in a battery of complementary pain-stimulated, pain-depressed, and pain-independent behaviors in male and female mice.

A combination of infraclavicular and suprascapular nerve blocks for total shoulder arthroplasty: A case series

Shoulder arthroplasty is associated with significant post-operative pain. Interscalene plexus block is the gold standard for pain management in patients undergoing this surgery, however, alternatives are currently being developed. We hypothesized that a combination of anterior suprascapular nerve block and lateral sagittal infraclavicular block would provide effective post-operative analgesia. Primary aims for this study were to document numeric rating scale (NRS) pain score and use of oral morphine equivalents (OMEq) during the first 24hours after surgery. Secondary aim was to determine the incidence of hemidiaphragmatic paralysis. Twenty patients (ASA physical status I-III) scheduled for shoulder arthroplasty were studied. Four mL ropivacaine 0.5% was administered for the suprascapular nerve block and 15mL ropivacaine 0.75% for the infraclavicular block. Surgery was performed under general anaesthesia. Paracetamol and prolonged-release oxycodone were prescribed as post-operative analgesics. Morphine and oxycodone were prescribed as rescue pain medication. Diaphragm status was assessed by ultrasound. Median NRS (0-10) at 1, 3, 6, 8 and 24hours post-operatively were 1, 0, 0, 0 and 3, respectively. NRS at rest during the first 24 post-operative hours was 4 (2.5-4.5 [0-5]), median (IQR [range]). Maximum NRS was 6.5 (5-8 [0-10]) median (IQR [range]). Total OMEq during the first 24 post-operative hours was 52.5mg (30-60 [26.4-121.5]) median (IQR [range]). Hemidiaphragmatic paralysis was diagnosed in one patient (5%). The combination of suprascapular and infraclavicular nerve block shows an encouraging post-operative analgesic profile and a low risk for hemidiaphragmatic paralysis after total shoulder arthroplasty.

Serratus Anterior Plane Block and Erector Spinae Plane Block Versus Thoracic Epidural Analgesia for Perioperative Thoracotomy Pain Control: A Randomized Controlled Study

This study was designed to evaluate the safety and efficacy of erector spinae plane block and serratus anterior plane block versus thoracic epidural in perioperative pain control for patients with cancer undergoing lung surgeries. Single blinded, randomized, controlled trial. The study was carried out at the National Cancer Institute in Cairo, Egypt. Fifty-one patients with cancer. Patients were allocated randomly into three groups: thoracic epidural analgesia (TEA) group, serratus anterior plane block (SAPB) group, and erector spinae plane block (ESPB) group. Outcome measures were 24 hours postoperative visual analog scale (VAS), intraoperative rescue fentanyl consumption, perioperative heart rate, mean blood pressure (mean arterial pressure [MAP]), and total postoperative morphine consumption. VAS scores at rest were significantly lower in the TEA group at the postanesthesia care unit and 24 hours. VAS scores with cough were significantly higher in the SAPB group at eight and 24 hours. The first time to receive morphine was significantly longer in the TEA group. No patients in the TEA group required postoperative morphine, whereas 88.2% and 47.1% required morphine in the SAPB and ESPB groups, respectively, p < 0.001. In the TEA group, intraoperative MAP values were lower than the other two groups, p < 0.05. Erector spinae plane block can be used as an effective and safe alternative to thoracic epidural analgesia and shows superior analgesic profile to serratus anterior plane block for patients with lung cancer undergoing posterolateral thoracotomy.

Analgesic and opioid medication profile of european adult spinal deformity patients: Minimum 5 years follow-up study

Analgesic and opioid medication profile of european adult spinal deformity patients: Minimum 5 years follow-up study

The protective effect of dietary supplementation of Salmonella-specific bacteriophages in post-weaning piglets challenged with Salmonella typhimurium.

Opioids are considered the gold standard to manage acute or chronic or mild to severe pain. Tramadol is a widely prescribed analgesic drug for dogs and cats; it has a synthetic partial agonism on μ-opioid receptors and inhibits the reuptake of norepinephrine and serotonin. However, the biotransformation and resultant metabolites differ between species and depend on cytochrome P450 interactions. Dogs mainly produce the inactive N-desmethyl tramadol metabolite, whereas cats exhibit an improved antinociceptive effect owing to rapid active O-desmethyltramadol metabolite production and a longer elimination half-life. Tapentadol, a novel opioid with dual action on μ-receptors and noradrenaline reuptake inhibitory activity, is a promising option in dogs, as it is less reliant on metabolic activation and is unaffected by cytochrome polymorphisms. Although scientific evidence on the analgesic activity of tapentadol in both species remains limited, experimental studies indicate potential benefits in animals. This review summarizes and compares the pharmacology, pharmacokinetics, and therapeutic efficacy of tramadol and tapentadol in dogs and cats with different pain conditions. According to the available data, tramadol seems a more suitable therapeutic option for cats and should preferably be used as a component of multimodal analgesia in both species, particularly dogs. Tapentadol might possess a superior analgesic profile in small animals, but additional studies are required to comprehensively evaluate the activity of this opioid to manage pain in dogs and cats.

Postoperative Analgesic Efficacy of Nalbuphine vs Dexmedetomidine as Adjuvants to Ropivacaine in Ultrasound Guided Transversus Abdominis Plane Block for Abdominal Hysterectomies: A Randomised Clinical Study

Introduction: Transversus Abdominis Plane (TAP) block has been practised as an effective alternative to systemic analgesics to achieve adequate postoperative analgesia, with minimal systemic side effects. Dexmedetomidine, an alpha-2 agonist and nalbuphine, an opioid, have been studied as adjuvants to local anaesthetics to improve the analgesic profile of regional anaesthetic blocks. Aim: To compare the duration and quality of postoperative analgesia of dexmedetomidine and nalbuphine when used as adjuvants to ropivacaine for TAP block. Materials and Methods: This was a randomised double blinded study conducted on 60 patients undergoing total abdominal hysterectomies under spinal anaesthesia. Patients were randomly distributed into two groups of 30 patients each, to receive either 39 mL of 0.2% ropivacaine+50 μg dexmedetomidine (1 mL) (group D) or 39 mL of 0.2% ropivacaine+10 mg nalbuphine (1 mL) (group N), for bilateral TAP block. Postoperative pain scores, time for first rescue analgesic request and incidence of side effects were compared. Results: Duration of postoperative analgesia was similar in both groups (409.14±48.92 minutes in group D vs 419.03±54.11 minutes in group N) (p-value=0.462). Postoperative pain scores and total amount of rescue analgesic requirement (105.17±42.98 vs 106.45±46.08) was also similar in both the groups (p=0.912). In Nalbuphine group, 16.7% reported pruritis (p-value=0.02) and 13.3% reported nausea (p-value=0.213). However, in group D only one patient reported nausea two hours postoperatively. Conclusion: Nalbuphine when compared to dexmedetomidine, as an additive to ropivacaine for TAP block, provides similar postoperative analgesic duration and efficacy, but increases the incidence of pruritus and nausea.

A Comparison of Local Infiltration Analgesia and PECS II Block for Analgesia in Mastectomy with Axillary Dissection—A Randomised Equivalence Study

Objective: Various analgesic techniques can be used for a mastectomy with axillary dissection with varying degrees of efficacy. In our institution, local anaesthesia infiltration (LIA) is commonly performed by surgeons. In this study, we hypothesise that the relatively novel PECS II block is equivalent to the analgesic profile of LIA. Methodology: In this single center, prospective, randomised control trial, 40 patients undergoing unilateral mastectomy with axillary dissection were randomly assigned to receive either 30 ml 0.5% ropivacaine before skin via LIA by a specialist breast surgeon during surgery or 30 ml 0.5% ropivacaine via PECS II block, before skin incision. Fentanyl was used as rescue analgesia intraoperatively, and all patients received morphine via patient-controlled analgesia (PCA) device postoperatively. The primary outcome was the difference in total morphine consumption in 24 hours between the 2 groups after surgery with equivalency set at ±1 mg. Secondary outcomes included time to rescue analgesia after block administration, post-operative pain score over 24 hours, adverse effects encountered, total intraoperative opioid usage, effect on operative time, block performance time as well as block and surgery related complications. Results: Unadjusted mean PCA morphine consumption over 24 hours post-operatively comparing local infiltration analgesia (LIA) to that of PECS II at 95% confidence interval was -1.22 mg (95% CI: -3.77, 1.33). Total IV Fentanyl use comparing LIA to PECS II was 2.53 ± 0.98 mcg/kg and 1.96 ± 0.57 mcg, P = 0.035. There were no other significant differences in the secondary outcome. Conclusion: We conclude there is a lack of equivalence between that of LIA and PECS II block, with the PECS II block providing superior analgesia.

OPTIMIZED SCHEME OF DIAZEPAM USAGE DURING CORONARY ARTERY STENTING

During invasive procedures in the X-ray operating room, sedation and analgesia have been used throughout its history. For sedation and anxiolytic effects, benzodiazepines, namely diazepam, were one of the drugs of choice. However, when using this drug, undesirable side effects have been identified, such as drowsiness, fatigue, amnesia, headache, tremors, cognitive impairments, and others.Objective. To establish the optimal scheme of analgosedation using diazepam for coronary artery stenting.Materials and research methods. The study included 60 patients with coronary artery disease who underwent a planned stenting of the coronary arteries. Analgosedation (AS) during stenting of the coronary arteries was performed routinely, and the patients were evenly divided into two study groups. The comparison group consisted of patients who underwent analgosedation based on diazepam and fentanyl. Patients in this group of AC were administered 10 mg of diazepam and 100 μg of fentanyl for induction, and repeated administration of drugs at the same dosage to maintain anesthesia during surgery. The study group consisted of patients with balanced usage of diazepam, namely, at the induction stage, we slowly intravenously injected 5 mg of diazepam solution and fentanyl solution at a dose of 1.5 mg / kg and 1.5 mg / kg / h to maintain the level analgesia. Intraoperatively, to maintain the level of sedation III on the RAMSEY scale (surface sedation), we used propofol solution.Conclusions. During the main stage, when sampling blood gases, we noted a difference in the level of oxygen, which was 6% higher in the study group (p = 0.044) and carbon dioxide, which was 11% higher (p = 0.018). This indicates the best rates of gas exchange in the balanced anesthesia group. During AS, based on the balanced usage of a combination of fentanyl and propofol solution, was better analgesic profile and fewer episodes of excessive sedation.

Dexmedetomidine versus clonidine adjuvants to levobupivacaine for ultrasound-guided transversus abdominis plane block in paediatric laparoscopic orchiopexy: Randomized, double-blind study.

Laparoscopic surgeries are associated with less postoperative pain and adverse events compared to open procedures. But, it still reduces the quality of life in children. Transversus abdominis plane (TAP) block is used to reduce pain. We hypothesized that dexmedetomidine or clonidine could improve the analgesic profile of levobupivacaine to the same extent during TAP block in children. Ninety children were randomly allocated in a randomized double-blind trial to receive bilateral TAP block with levobupivacaine plus normal saline (group B, n=30), or dexmedetomidine (group D, n=30) or clonidine (group C, n=30). Primary outcome was the modified Children's Hospital of Eastern Ontario Pain Scale score. Secondary outcomes included time to initial analgesic request, number of analgesic claims, total analgesic consumption, parents' satisfaction, sedation score and complications. Children of group D showed reduced pain scores compared to other groups. They represented the longest period of analgesia (565.00±71.5min) with p<0.001, and fewer patients required two doses of analgesia during the first postoperative day. The cumulative amount of backup analgesia was significantly different between these groups (p=0.026). Higher parents' satisfaction scores were recorded in groups D and C compared to group B. Sedation among the study groups revealed significant differences (p=0.035), but no severe complications were recorded. Adding dexmedetomidine to levobupivacaine can extend the time of analgesia and reduce the use of postoperative backup analgesics with minimal sedation effects when used in TAP block in paediatrics undergoing laparoscopic orchiopexy. Clonidine can be used as an alternative adjuvant to local anaesthetics with good postoperative analgesic profiles. Clonidine can alternate dexmedetomidine during TAP block with local anesthetics for pediatrics laparoscopies. Both can lead to better postoperative analgesic profiles. Clonidine may be preferred, especially in our developing regions, because of its easy availability and lower cost than that of dexmedetomidine.

Comparative randomized study of continuous serratus anterior plane block versus continuous paravertebral block in post-mastectomy pain

BackgroundMany analgesic methods have been used to control post-mastectomy pain. Both thoracic paravertebral and serratus anterior blocks are recent regional techniques with promising results. The aim of this study was to compare safety and analgesic efficacy of both techniques in controlling post-mastectomy pain.MethodsThe study was conducted from January 1, 2019, till January 10, 2019, on 60 female patients ASA class ≤ 2 undergoing modified radical mastectomy. After induction of balanced general anesthesia patients received either continuous thoracic paravertebral block (group P) or continuous serratus anterior block (group S). Twenty milliliters of levobupivacaine 0.25% were injected in each technique under ultrasound guidance followed by continuous infusion of 5 ml/h levobupivacaine 0.125% through a 22-gage catheter. IV morphine was given postoperatively by patient-controlled analgesia. In both groups, we measured time to first dose morphine, total 24 and 48 h morphine consumption, vital signs, visual analog scale, and side effects of each technique.ResultsThe demographic data (age, body mass index, and duration of surgery) were comparable in both groups. The time for first dose of morphine was significantly longer in group P (368 ± 36 min) than group S (270 ± 37.65 min) with P value < 0.001. Total morphine consumption in milligram at both 24 and 48 h were significantly less in group P (8.1 ± 0.8, and 11.5 ± 1 respectively) than in group S (10.1 ± 1.3 and 14.2 ± 1.4), with limited side effects in both groups.ConclusionBoth continuous paravertebral and serratus anterior plane blocks are safe good alternatives to control post-mastectomy pain. However continuous paravertebral block provides better analgesic profile.

Patients use fewer analgesics following supervised exercise therapy and patient education: an observational study of 16 499 patients with knee or hip osteoarthritis

ObjectivesTo investigate changes in analgesic use before and after supervised exercise therapy and patient education in patients with knee or hip osteoarthritis (OA).MethodsWe recruited 16 499 of 25 933 eligible...

Multi-Criteria Decision Analysis to Develop an Efficacy-Safety Profile of Parenteral Analgesics Used in the Treatment of Postoperative Pain.

BackgroundIdentifying the optimal treatment in an acute postoperative setting remains a challenge. Multiple analgesic options are available, but comparing outcomes is limited by a lack of head-to-head trials. In addition, decisions based on efficacy only do not take drug safety into account. In such cases, multi-criteria decision analysis (MCDA) can be utilized to quantify and compare the efficacy and safety data of various drugs.MethodologyThe efficacy-safety profiles of eight parenteral, postoperative analgesics (acetaminophen, diclofenac, ketorolac, metamizole, morphine, nefopam, parecoxib, tramadol) widely used in Europe were evaluated using an MCDA model that included 17 criteria: three for efficacy and 14 for safety. Each drug was scored on each criterion on a scale from 0 (worst) to 100 (best), according to published data and the judgment of an expert panel. A weighting process was then applied to standardize the impact of each criterion and adjust drugs’ preference scores accordingly, normalizing them on the 0–100 scale. Sensitivity analyses were also performed, including a model in which analgesic profiles were compared when opioid sparing effect was set at a zero value for all drugs.ResultsIn the primary model, efficacy and safety had relative weightings of 64% and 36%, respectively. Efficacy and safety criteria with the highest values were pain relief (relative weight, 29%) and gastrointestinal effects (12%). Parecoxib received the highest overall score (93), followed by diclofenac (80), and ketorolac (75). Morphine scored the lowest (57), due to the lack of an opioid sparing effect. When opioid sparing was given a zero rating, parecoxib remained the highest scoring analgesic (93), followed by diclofenac (80), metamizole (76), and morphine (76). Parecoxib remained the most preferred analgesic in several other sensitivity analyses.ConclusionThis MCDA-based assessment suggests that parecoxib has the most favorable efficacy-safety profile among the assessed postoperative analgesics.

The effectiveness of percutaneous injections of ozonotherapy in low back pain.

Lumbar pain is one of the main reasons for medical consultation, causing the disruption of daily routines due to its disabling nature, thus resulting in social and personal damage. Among the complementary treatments, ozonotherapy offers analgesia to most patients, with reports of complications. However, great questions about its clinical effectiveness have not been answered yet, and there have been reports of serious complications. To describe the use of ozonotherapy in the treatment of lumbar pain, focusing on its favorable and unfavorable effects, and its analog profile. A cross-sectional bibliographic research was performed with scientific articles obtained from the Pubmed, LILACS and Scopus database, using the following descriptors: "Ozone", "Therapy", "Lumbar pain", "complication", "Disk herniation", "Guideline", "Protocol", "Standards", "Criteria". The researched literature corroborates that, in clinical practice, there is safety in the use of oxygen-ozone therapy through percutaneous injections for the treatment of lumbar pain, especially when compared to surgeries and use of medicines, provided that strict criteria are followed. The procedure is effective and has a favorable analgesic profile. However, it is necessary to produce a medical guideline that will help in its strict and systematic control.

Peripheral truncal blocks-Overview and assessment

By implementation of sonography for regional anesthesia, truncal blocks became more relevant in the daily practice of anesthesia and pain therapy. Due to visualized needle guidance ultrasound supports more safety and helps to avoid complications during needle placement. Additionally, complex punctures are possible that were associated with higher risk using landmarks alone. Next to the blocking of specific nerve structures, interfascial and compartment blocks have also become established, whereby the visualization of individual nerves and plexus structures is not of relevance. The present review article describes published and clinically established puncture techniques with respect to the indications and procedures. The clinical value is reported according to the scientific evidence and the analgesic profile. Moreover, the authors explain potential risks, complications and dosing of local anesthetic agents.

Overview of Neurological Mechanism of Pain Profile Used for Animal "Pain-Like" Behavioral Study with Proposed Analgesic Pathways.

Pain is the most common sensation installed in us naturally which plays a vital role in defending us against severe harm. This neurological mechanism pathway has been one of the most complex and comprehensive topics but there has never been an elaborate justification of the types of analgesics that used to reduce the pain sensation through which specific pathways. Of course, there have been some answers to curbing of pain which is a lifesaver in numerous situations—chronic and acute pain conditions alike. This has been explored by scientists using pain-like behavioral study methodologies in non-anesthetized animals since decades ago to characterize the analgesic profile such as centrally or peripherally acting drugs and allowing for the development of analgesics. However, widely the methodology is being practiced such as the tail flick/Hargreaves test and Von Frey/Randall–Selitto tests which are stimulus-evoked nociception studies, and there has rarely been a complete review of all these methodologies, their benefits and its downside coupled with the mechanism of the action that is involved. Thus, this review solely focused on the complete protocol that is being adapted in each behavioral study methods induced by different phlogogenic agents, the different assessment methods used for phasic, tonic and inflammatory pain studies and the proposed mechanism of action underlying each behavioral study methodology for analgesic drug profiling. It is our belief that this review could significantly provide a concise idea and improve our scientists’ understanding towards pain management in future research.

Sex Bias and Genotype Influence on Opioid Safety Profile in Chronic Low Back Pain.

The use of opioids to relieve pain is a challenge because of the high variability in dose requirements and tolerance profiles. Among potential modulators are the individual's genetic background and being female. Our aim was to evaluate sex bias and genotype-related influence on opioid titration safety, in chronic low back pain (CLBP), the most frequent chronic noncancer pain. A 3-year prospective study was developed in opioid-naive CLBP patients. Data were self-reported by patients (pain [Visual Analogy Scale], adverse events [AEs], and health care resource utilization) and physicians (analgesic prescription, morphine equivalent daily dose, and suspected adverse drug reactions [ADRs]). Outcomes were analyzed as patients with AEs (case) or without (control) together with patients' sex and genotype. Gene variants in OPRM1 (rs1799971), COMT (rs4680), ABCB1 (rs1045642), UGT2B7 (rs12233719 and rs7438135), KCNJ6 (rs2070995 and rs6517442), and CYP3A5*3 (rs776746) were assessed. The hospital ethics committee approved the study, and statistical analyses were performed with R, v.3.2.4. A total of 179 patients were included (64% female, mean pain intensity 73±16 mm), and 90% of them presented at least 1 AE (median of 3 (1 to 6) AEs/patient) with a rate of 5 AEs: 1 ADR without differences due to sex. However, there is a significant delay in referral of female patients (a mean of 6 years) to the Pain Unit, being significantly 3 to 5 times more likely to present sleep or psychiatric disorders. Meanwhile male individuals showed more sexual and reproductive system disorders. Genotypes influenced skin (COMT, G472A-GG) and gastrointestinal (ABCB1, C3435T-CC) related problems. Sex bias affects female patients resulting in a CLBP diagnostic delay and a different analgesic safety profile. Moreover, the individual's genetic background might be useful to predict certain AEs in opioid-naive patients under an opioid titration procedure. Addressing sex in necessary to resolve inequalities in health care access.