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Oxidative stress is an inevitable process that occurs during life activities, and it can participate in the development of inflammation. Although great progress has been made according to research examining analgesic drugs and therapies, there remains a need to develop new analgesic drugs to fill certain gaps in both the experimental and clinical space. This review reports the research and preclinical progress of this class of analgesics by summarizing known nuclear factor E-2-related factor-2 (Nrf2) pathway-modulating substances. We searched and reported experiments that intervene in the Nrf2 pathway and its various upstream and downstream molecules for analgesic therapy. The medical literature database (PubMed) was searched for experimental studies examining the reduction of pain in animals through the Nrf2 pathway, the research methods were analyzed, and the pathways were classified and reported according to the pathway of these experimental interventions. Humans have identified a variety of substances that can fight pain by regulating the expression of Nrf2 and its upstream and downstream pathways. The Nrf2 pathway exerts anti-inflammatory activity by regulating oxidative stress, thereby playing a role in the fight against pain. [ABSTRACT FROM AUTHOR]

Introduction: Chronic pain is often managed using co-prescription of analgesics and adjuvants, with concomitant medication prescribed for comorbidities. Patients may have suboptimal response to some analgesics or be at risk of drug interactions or adverse drug reactions (ADRs) due to polypharmacy affecting CYP2D6 enzyme activity. The aim of the service improvement project was to determine the proportion of patients referred to a specialist pain service in the UK National Health Service (NHS) by general practitioners (GPs) who may be at risk of suboptimal analgesic response or ADRs due to CYP2D6 inhibition through polypharmacy. This was achieved by reviewing clinical prescribing information provided by GPs at time of referral. It was hoped that the findings could be used to aid clinical and prescribing decisions without conducting CYP2D6 genotyping or phenotyping. Methods: A review of letters from 250 patients referred to an NHS hospital pain service from GPs over a 3-month period was undertaken. Information about current and concomitant medications was analysed to identify the potential for CYP2D6 inhibition and adverse events. Results: Letters failed to provide information about current pain medication for 20 (8%) patients or non-pain concomitant medication for 54 (21.6%) patients. Of 176 patients, 52 (29.5%) patients with information about non-pain concomitant medication had been prescribed at least one known CYP2D6 inhibitor. A total of 35 (19.9%) patients were identified as being at risk of an adverse drug reaction and 33 (18.75%) patients at risk of suboptimal analgesic response due to co-administration of CYP2D6 inhibitors. Conclusion: The review revealed the need for improved detail in GP referral letters used to transfer care to UK NHS hospital pain clinics. There is a need to consider an individual's CYP2D6 phenotype when prescribing analgesic prodrugs to manage persistent pain. Caution is needed when patients are co-prescribed codeine or tramadol with selective serotonin reuptake inhibitors (SSRIs). [ABSTRACT FROM AUTHOR]

Background: Intraoperative remifentanil has been associated with postoperative hyperalgesia, higher visual analogic pain scores, and increased postoperative morphine consumption. However, this has not been investigated from patient's perspective by using a patient-reported outcomes (PROs) approach with a validated questionnaire.Methods: We joined the largest prospective observational study on postoperative pain, PAIN OUT Project (NCT02083835), and collected data for 2 years. We studied the effects of remifentanil (R+) vs nonremifentanil (R-) anesthesia on PROs regarding their pain management after elective thyroidectomy. We selected 5 primary PROs (worst pain experienced, time spent in severe pain, relief received by treatment, satisfaction about pain management, wish for more pain treatment) and five secondary PROs (drowsiness, itching, nausea, dizziness, waking up due to pain) from the validated International Pain Outcomes questionnaire.Results: The analysis included 317 patients, 208 in the R+ group (65.6%) and 109 in the R- group (34.4%), the latter receiving fentanyl as intraoperative opioid. Although the R+ group received more frequently intraoperative nonopioids (202/208, 97.1% vs 86/109, 78.9%; P < .0001) and opioids (184/208, 88.5% vs 38/109, 34.9%; P < .001), it reported higher worst pain (5.1±2.1 vs 4.3±2.1, P < .005), lower satisfaction (7.4±2.0 vs 8.1±2.1, P < .001), and worse results in 4 secondary PROs. A sensitivity analysis performed matching 67 couples of patients yielded similar results in primary PROs.Conclusions: Our study suggests that remifentanil-based anesthesia is associated with worse pain-related PROs in patients undergoing thyroidectomy despite more frequent intraoperative analgesic administration. This study adds further evidence to the growing literature about opioid- and remifentanil-induced hyperalgesia. [ABSTRACT FROM AUTHOR]

Background: Pain is an indication for total hip arthroplasty (THA) and it should be resolved post-surgery. Because patients' pain is typically treated pharmacologically we tested whether opioid use can be used as a surrogate for patient-reported pain and as an indicator for early surgical failure. Specifically, we evaluated whether the amount of opioids taken within the year after THA was associated with one and five years risk of revision surgery.Methods: A cohort of 9943 THAs (01/2001-12/2012) was evaluated. Post-operative opioid use was the exposure of interest and cumulative daily oral morphine equivalent (OME) amounts were calculated. Total OMEs/90-day periods were categorised into quartiles. Revisions within one and five years were the outcomes of interest.Results: Of the THAs, 2.0 % (N = 200) were revised within one year and 4.2 % (N = 413) within five years. After adjustments for gender, age, surgical indication, co-morbidities, and other analgesics, revision was associated with amount of OMEs in the second quarter after THA (days 91-180 after discharge). Patients on medium-high amounts of OME (400-1119 mg) had higher risk of one (hazard ratio (HR) = 2.22, 95 % CI 1.08-4.56) and five year (HR = 1.66, 95 % CI 1.08-2.56) revision than a patient not taking opioids. During the same period, patients taking the highest amounts of OMEs (≥1120 mg) had a 2.64 (95 % CI 1.03-6.74) times higher risk of one year and a 2.11 (95 % CI 1.13-3.96) times higher risk of five year revision.Conclusions: Opioid use 91-180 days post-surgery is associated with higher risk of revision surgery and therefore is an early and useful indicator for surgical failure. [ABSTRACT FROM AUTHOR]

Neuropathic pain (NP) is a challenging condition to treat, as the need for new drugs to treat NP is an unmet goal. We investigated the analgesic potential of a new sulfated disaccharide compound, named BIS014. Oral administration (p.o.) of this compound induced ameliorative effects in formalin-induced nociception and capsaicin-induced secondary mechanical hypersensitivity in mice, but also after partial sciatic nerve transection (spared nerve injury), chemotherapy (paclitaxel)-induced NP, and diabetic neuropathy induced by streptozotocin. Importantly, BIS014, at doses active on neuropathic hypersensitivity (60 mg/kg/p.o.), did not alter exploratory activity or motor coordination (in the rotarod test), unlike a standard dose of gabapentin (40 mg/kg/p.o.) which although inducing antiallodynic effects on the NP models, it also markedly decreased exploration and motor coordination. In docking and molecular dynamic simulation studies, BIS014 interacted with TRPV 1 , a receptor involved in pain transmission where it behaved as a partial agonist. Additionally, similar to capsaicin, BIS014 increased cytosolic Ca 2+ concentration ([Ca 2+ ] c ) in neuroblastoma cells expressing TRPV 1 receptors; these elevations were blocked by ruthenium red. BIS014 did not block capsaicin-elicited [Ca 2+ ] c transients, but inhibited the increase in the firing rate of action potentials in bradykinin-sensitized dorsal root ganglion neurons stimulated with capsaicin. Perspective: We report that the oral administration of a new sulfated disaccharide compound, named BIS014, decreases neuropathic pain from diverse etiology in mice. Unlike the comparator gabapentin, BIS014 does not induce sedation. Thus, BIS014 has the potential to become a new efficacious non-sedative oral medication for the treatment of neuropathic pain., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The use of analgesics can lead to cases of drug abuse and dependence. It can also cause pseudo-addiction in patients suffering from pain. What is the actual situation in patients suffering from severe sickle-cell disease, exposed to acute pain during vaso-occlusive crises? Evaluation of the use of analgesics, on the basis of Diagnostic and Statistical Manual of Mental Disorders criteria for substance abuse and dependence, makes it possible to differentiate the symptoms occurring only in a context of pain, in the aim of managing the pain, and thus describing pseudo-addiction, from symptoms also occurring when there is no pain, and more in favour of true addiction. Currently there is no data available in France on this problem, and no studies have been carried out in children or adolescents with sickle-cell disease. The purpose of the study is to evaluate the prevalence of problematic use of equimolar mixture of oxygen and nitrous oxide and other analgesic drugs in a population of subjects with severe sickle-cell disease in France. Methods/design: PHEDRE (Pharmacodépendance Et DREpanocytose-drug dependence and sickle-cell disease) is an observational, descriptive and transversal study. Patients under the age of 26 with sickle-cell disease are included in the study by the doctors looking after them in sickle-cell disease centres. The patients are then contacted by a trained researcher for a telephone interview, including an evaluation of the Diagnostic and Statistical Manual of Mental Disorders criteria for abuse and dependence to equimolar mixture of oxygen and nitrous oxide and for each of the analgesic drugs taken by the patient. The data are also completed using the subject’s medical record. Discussion: This study will make it possible to provide an initial quantitative and qualitative evaluation of problematic use of equimolar mixture of oxygen and nitrous oxide and analgesic drugs in the sickle-cell disease population. The results will be used firstly to provide additional data essential for monitoring the risk of overdose, abuse, dependence and misuse of these products, and to begin awareness-raising and to provide information for health care professionals, in order to significantly improve the management of sickle-cell disease-related pain. [ABSTRACT FROM AUTHOR]

Many children experience treatable moderate to severe pain following surgery. Increasingly, children undergo surgery as day cases, and, as such, parents are more likely to be responsible for managing pain post-operatively. Research in the United States and Finland has found parents fear the side effects of analgesics; think they are addictive; and that children should receive as little analgesia as possible. Little is known about parental attitudes in this context in the United Kingdom. This study set out to explore parental attitudes towards children’s pain and analgesic drugs to contribute to existing knowledge about parental attitudes elsewhere so that the information provided to parents can be tailored effectively. A convenience sample of parents (n = 108) at one hospital in South West London completed the Parental Pain Expression Perceptions and the Medication Attitudes Questionnaires. Although many parents have a good understanding of the ways in which children express pain, a substantial proportion of parents hold misconceptions regarding how children express pain and concerns in relation to analgesic drugs. This may impact on the quality of the pain management provided to children post-operatively and needs taking into account when preparing parents in this context. [ABSTRACT FROM AUTHOR]

New sensitive and rapid spectrophotometric methods for the determination of four analgesic drugs namely, nalbuphine (NALB), naltrexone (NALT), morphine (MORF) and tramadol (TRAM) in pharmaceutical formulations were developed and optimized. The proposed methods involve the addition of a measured excess of N-bromosuccinimide in acid medium followed by determination of unreacted NBS by reacting with either a fixed amount of methyl orange and measuring the absorbance at 508 nm (Method A), or orange G and measuring the absorbance at 478 nm (Method B). In both methods, the amount of NBS reacted corresponds to the amount of drugs. Under the optimum conditions, Beer's law limit, molar absorptivity and Sandell's sensitivity were calculated. The limits of detection and quantification were also reported for both methods. Statistical evaluation of the methods was examined by determining intra-day and inter-day precisions. The methods were successfully applied to the assay of drugs in their pharmaceutical formulations. No interference was observed from common additives and the validity of the methods was tested. [ABSTRACT FROM AUTHOR]

Aim Critically ill children can develop withdrawal syndrome after prolonged analgesia and sedation in a paediatric intensive care unit ( PICU), when treatment is stopped abruptly or reduced quickly. The aim of this study was to evaluate the incidence of withdrawal syndrome in patients after three or more days of analgesic or sedative drug therapy, using a validated scale. We also analysed the association between withdrawal syndrome and the patients' outcome and factors related to analgesia and sedation treatment. Methods This prospective observational study analysed 89 periods of weaning from analgesia and sedation in 60 children between October 2010 and October 2011. Of these, 65% were less than six months old and 45% were admitted to the PICU after heart surgery. Withdrawal syndrome was assessed using the Withdrawal Assessment Tool-1 ( WAT-1) scale. Results The incidence of withdrawal syndrome was 37%, and the only variable that predicted its presence was the highest administered dose of benzodiazepine. The duration of weaning, Sophia Observational Withdrawal Symptom scale score and nurse judgment were also associated with positive WAT-1 scores. Conclusion Withdrawal syndrome should be considered after three or more days of analgesic or sedative treatment. A high dose of benzodiazepine increases the risk of developing withdrawal symptoms. [ABSTRACT FROM AUTHOR]

A simple, rapid, accurate, precise and sensitive spectrophotometric method for the determination of four analgesic drugs namely, tramadol (TRAM), morphine (MORF), nalbuphine (NALB) and naltrexone (NALT) in bulk sample and in dosage forms is described. The method is based on oxidation of the studied drugs by potassium permanganate in acidic medium and determination of the unreacted oxidant by measuring the decrease in the absorbance of indigo carmine (IC) dye at 610 nm. Under the optimum conditions, Beer's law limit, molar absorptivity and Sandell's sensitivity were calculated. The limits of detection and quantification were also reported. Statistical evaluation of the method was examined by determining an intra-day and inter-day precisions. The method was successfully applied to the assay of drugs in their pharmaceutical formulations. No interference was observed from common additives and the validity of the method was tested. [ABSTRACT FROM AUTHOR]

Simple, reliable, sensitive, and accurate spectrofluorimetric and spectrophotometric methods were proposed for the determination of two selected analgesic drugs, namely tramadol and morphine, in pharmaceuticals and biological fluids. The proposed methods were based on the oxidation of the studied drugs by Cerium (Ce)IV in an acidic medium. The spectrofluorimetric method is based on measuring the relative fluorescence intensity of Ce(III) arising from Ce(IV) at 350 nm with an excitation wavelength at 250 nm. The spectrophotometric method involves on addition of a known excess of Ce(IV) to the studied drugs in an acid medium, followed by the determination of residual Ce(IV) by reacting with a fixed amount of methyl orange and measuring the absorbance at 510 nm. Different variables affecting the reaction conditions, such as the concentrations of Ce(IV), type and concentration of the acid medium, reaction time, temperature, and the diluting solvents, were carefully studied and optimized. [ABSTRACT FROM AUTHOR]

New sensitive and rapid spectrophotometric methods for the determination of four analgesic drugs namely, nalbuphine (NALB), naltrexone (NALT), morphine (MORF) and tramadol (TRAM) in pharmaceutical formulations and biological fluids were developed and optimized. The proposed methods involve the addition of a measured excess of bromate-bromide mixture in acid medium and subsequent estimation of the residual bromine by reacting with either a fixed amount of indigo carmine and measuring the absorbance at 610 nm, or amaranth and measuring the absorbance at 520 nm. In both methods, the amount of bromine reacted corresponds to the amount of drugs. Under the optimum conditions, Beer's law limit, molar absorptivity and Sandell's sensitivity were calculated. The limits of detection and quantification were also reported for both methods. Statistical evaluation of the methods was examined by determining an intra-day and inter-day precisions. The methods were successfully applied to the assay of drugs in their pharmaceutical formulations and biological fluids. No interference was observed from common additives and the validity of the methods was tested. [ABSTRACT FROM AUTHOR]

Aims The risk of hypoglycaemia with tramadol ( TRM) is not well described. Our aim was to analyze spontaneous reports of hypoglycaemia registered in the French Pharmacovigilance database and to compare these data with two other step-2 analgesic drugs. Methods Cases of hypoglycaemia associated with TRM, dextropropoxyphene ( DXP) and codeine ( COD) recorded between 1997 and November 2010 in the French pharmacovigilance database were compared. Results Seventy-two cases of hypoglycaemia associated with DXP and 43 with TRM were retained for evaluation (the single case reported with COD was not further considered). Most patients were elderly people with no significant difference in age between DXP- and TRM-treated patients (71.2 ± 21 vs. 69.4 ± 22.5 years). Hypoglycaemia occurred after a median of 4 and 5 days with DXP and TRM treatment, respectively. The mean lowest serum glucose concentration was 2.1 ± 0.9 mmol l−1 in the DXP group compared with 2.5 ± 1 mmol l−1 in the TRM group ( P = 0.072). At least, one risk factor of hypoglycaemia was found in most patients, with no significant difference between groups (58.3% in the DXP group and 58.1% in the TRM group). In particular, 31.9% patients from the DXP group had diabetes compared with 41.8 % from the TRM group ( P = 0.28) and 18% of DXP patients had renal insufficiency compared with 16.3% of TRM patients ( P = 0.8). Conclusions Our study confirms that TRM is associated with the occurrence of hypoglycaemia in elderly or predisposed patients, with characteristics similar to those previously reported with DXP. [ABSTRACT FROM AUTHOR]

Abstract: The effects of dragon’s blood and its components cochinchinenin A, cochinchinenin B, loureirin B as well as various combinations of the three components on capsaicin-induced TRPV1 receptor currents were studied in acutely dissociated DRG neurons using both voltage and current whole-cell patch clamp technique. The results indicated that dragon’s blood and its three components concentration-dependently reduce the peak amplitudes of capsaicin-induced TRPV1 receptor currents. There was no significant difference between the effects of dragon’s blood and the combination wherein the three components were present in respective mass fractions in dragon’s blood. The respective concentrations of the three components used alone were all higher than the total concentration of three components used in combination when the percentage inhibition of the peak amplitude was 50%. The proportion of three components was adjusted and the total concentration reduced, the resulting combination still inhibit the currents with a lower IC50 value, and inhibit capsaicin-induced membrane depolarization on current clamp. The combination of three components not only increase the capsaicin IC50 value, but also reduce the capsaicin maximal response. These result suggested that analgesic effect of dragon’s blood may be partly explained on the basis of silencing pain signaling pathways caused by the inhibition of dragon’s blood on capsaicin-induced TRPV1 receptor currents in DRG neurons and could be due to the synergistic effect of the three components. Antagonism of the capsaicin response by the combination of three components is not competitive. The analgesic effect of dragon’s blood was also confirmed using animal models. [Copyright &y& Elsevier]

BACKGROUND: Differently from the adult patients, in pediatric age it is more difficult to assess and treat efficaciously the pain and often this symptom is undertreated or not treated. In children, selection of appropriate pain assessment tools should consider age, cognitive level and the presence of eventual disability, type of pain and the situation in which it is occurring. Improved understanding of developmental neurobiology and paediatric analgesic drugs pharmaco-kinetics should facilitate a better management of childhood pain. AIM: The objective of this review is to discuss current practice and recent advances in pediatric pain management. METHODS: Using PubMed we conducted an extensive literature review on pediatric pain assessment and commonly used analgesic agents from January 2000 to January 2012. CONCLUSIONS: A multimodal analgesic regimen provides better pain control and functional outcome in children. Cooperation and communication between the anaesthesiologist, surgeon, and paediatrician are essential for successful anaesthesia and pain management. [ABSTRACT FROM AUTHOR]

Atogepant is a selective oral, small-molecule calcitonin gene-related peptide (CGRP) receptor antagonist that has been approved for preventive treatment of migraine. CGRP is a neuropeptide involved in vasodilation and cerebrovascular regulation. CGRP is the most potent vasoactive constituent of the cerebrovascular trigeminal neuronal system and has a key role in migraine. Medications targeting CGRP are being used as migraine preventive and abortive treatments., (Copyright 2022 Clarivate.)

Chronic pain, a common symptom of people with rheumatoid arthritis, usually behaves as persistent polyarthralgia pain and causes serious damage to patients' physical and mental health. Opioid analgesics can lead to a series of side effects like drug tolerance and addiction. Thus, seeking an alternative therapy and screening out the corresponding analgesic drugs is the key to solving the current dilemma. Traditional Chinese Medicine (TCM) therapy has been recognized internationally for its unique guiding theory and definite curative effect. In this study, we used the Apriori Algorithm to screen out potential analgesics from 311 cases that were treated with compounded medication prescription and collected from "Second Affiliated Hospital of Zhejiang Chinese Medical University" in Hangzhou, China. Data on 18 kinds of clinical symptoms and 16 kinds of Chinese herbs were extracted based on this data mining. We also found 17 association rules and screened out four potential analgesic drugs-"Jinyinhua," "Wugong," "Yiyiren," and "Qingfengteng," which were promised to help in the clinical treatment. Besides, combined with System Cluster Analysis, we provided several different herbal combinations for clinical references., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lai, Li, Yu, Huang, Zheng, Jiang, Wang, Wen, Chen, Wen and Jin.)

The application of endomorphins as clinical available analgesic drugs has been impeded by their relatively poor receptor selectivity compared with alkaloid analgesics, rapid degradation in vivo, inefficient to penetrate the blood-brain barrier (BBB), and undesirable or toxic effects, such as acute tolerance and physical dependence, respiratory depression, and inhibition of gastrointestinal motility. Extensive studies have been performed so far striving to conquer these problems. In this article we review and discuss conformational and topographical modifications of the peptide amide bond and amino acid side groups to attain the most appropriate receptor binding affinity and high receptor selectivity; diverse strategies such as insertion of unnatural amino acids, covalent or noncovalent constraints as well as cyclization of linear peptides to enhance the enzymatic stability; designing of peptidomimetic ligands, glycopeptides, and N-terminal amidinationed analogues (such as incorporating guanidine into endomorphins) to penetrate the BBB. Also, several pertinent examples of bivalent and/or multivalent (such as mixed µ-agonist/δ-antagonist profile) compounds are discussed based on the existing literature and current data intending to give an insight into the development of opioid peptides expressing low tendency to produce acute tolerance and physical dependence. © 2011 Wiley Periodicals, Inc. Med Res Rev, 32, No. 3, 536-580, 2012 [ABSTRACT FROM AUTHOR]

The in vitro effects of the injectable form of analgesic drugs, dexketoprofen trometamol, dexamethasone sodium phosphate, metamizole sodium, diclofenac sodium, thiocolchicoside, on the activity of purified human carbonic anhydrase I and II were evaluated. The effect of these drugs on erythrocyte hCA I and hCA II was compared to recombinant hCA I and hCA II expressed in Ecoli. IC50 values of the drugs that caused inhibition were determined by means of activity percentage diagrams. The IC50 concentrations of dexketoprofen trometamol and dexamethasone sodium phosphate on hCA I were 683 μM and 4250 μM and for hCA II 950 μM and 6200 μM respectively. Conversely, the enzyme activity was increased by diflofenac sodium. In addition, thiocolchicoside has not any affect on hCA I and hCA II. The effect of these drugs on erythrocyte hCA I and hCA II were consistent with the inhibition of recombinant enzymes. [ABSTRACT FROM AUTHOR]

Abstract: We developed an automated technique based on the detection of pain-related behaviours (like licking or biting) and small activities (mostly grooming) in the formalin pain test. By comparing automated and manual scoring, we determined that the interphase score was mostly independent of pain-related behaviours and it was used as an index of sedative events. The non-pain-related behaviours, still present during the second phase, were eliminated in order to visualize only pain-related behaviours. This new method, validated using classical analgesic (morphine) and sedative drugs (diazepam) could be used to discriminate sedative from analgesic effects of pharmacological treatments in the formalin test. [Copyright &y& Elsevier]

Background: No study has so far addressed whether differences do exist in the management of cancer-related pain in patients admitted to oncology and non-oncology settings.Patients and methods: A multicentre cross-sectional study in 48 Italian hospitals has enrolled 819 patients receiving analgesic therapy for cancer-related pain. Demographics and clinical and analgesic therapy information have been prospectively collected by standardized forms. Adequacy of pain management has been evaluated by the Pain Management Index (PMI).Results: Differences in the analgesic drug administration according to settings of care have been evident, non-opioids more frequently being administered in non-oncology units (19.6% versus 7.0%; P < 0.0001), while strong opioids are more frequently used in the oncology units (69.5% versus 51.9%; P < 0.0001). The number of patients receiving inadequate therapy (PMI < 0) has lowered in oncology compared with non-oncology units (11.3% versus 18.8%; P = 0.0024). Results of multiple logistic regression analysis have shown that the admission to non-oncology setting [odds ratio (OR) = 1.75, 95% confidence interval (CI) = 1.15–2.67; P = 0.0096] and the absence of metastatic disease (OR = 1.60, 95% CI = 1.04–2.44; P = 0.0317) were independent factors associated with an increased risk of receiving an inadequate analgesic therapy.Conclusion: Oncology wards provide the most adequate standard of analgesic therapy for cancer-related pain. [ABSTRACT FROM AUTHOR]

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Three ‘weak’ opioid analgesics are marketed in France and other European countries in association with paracetamol. • They are very largely used, but to our knowledge there is no large study comparing the reporting rate of adverse drug reactions (ADRs) between these different step 2 analgesic combinations to determine the safest one. WHAT THIS STUDY ADDS • The aim of this study was to compare reporting rate of ADRs with three step 2 combinations according to their consumption in France. • The results show that among these combinations, reporting rate and ‘seriousness’ of reported ADRs are the highest with tramadol/paracetamol (TRM+P) and the lowest with codeine/paracetamol. • The safety of TRM+P needs to be urgently investigated with more methodologically rigorous studies. AIMS Three ‘weak’ opioid analgesics in association with paracetamol are marketed in France as step 2 analgesics: dextropropoxyphene, tramadol and codeine. These combinations are involved in several adverse drug reactions (ADRs), but no data are available about their comparative reporting rate. The aim was to compare the reporting rate of ADRs between tramadol/paracetamol (TRM+P), codeine/paracetamol (COD+P) and dextropropoxyphene/paracetamol (DXP+P). METHODS All spontaneous reports submitted to the French Pharmacovigilance Database from 1 January 1987 to 31 December 2006 suspected to be induced by one of the three step 2 analgesic combinations (DXP+P, TRM+P, COD+P) were extracted. Their consumption for the same period was obtained from the French Drug Agency. The number of ADRs, serious ADRs and different organ classes of ADRs were compared according to their consumption. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each variable using DXP+P as reference. RESULTS The reporting rate of ADRs was calculated as 24.9/100 000 person-years for DXP+P, 44.5/100 000 person-years for TRM+P and 12.5/100 000 person-years for COD+P. The reporting rate (OR 0.56, 95% CI 0.50, 0.63) and ‘seriousness»’ (OR 0.65, 95% CI 0.53, 0.80) of ADRs were significantly higher with TRM+P than with DXP+P. However, hepatobiliary ADRs were significantly more frequent with the DXP+P combination (OR 2.62, 95% CI 1.59, 4.37). In contrast, the reporting rate (OR 1.99, 95% CI 1.82, 2.18) and ‘seriousness’ (OR 2.64, 95% CI 2.24, 3.11) of ADRs were significantly higher with DXP+P than with COD+P. CONCLUSIONS Among the three step 2 analgesic combinations, reporting rate and ‘seriousness’ of ADRs are the highest with TRM+P and the lowest with COD+P. Our study suggests that the safety profile of DXP+P is worst than that of COD+P. [ABSTRACT FROM AUTHOR]

Dextropropoxyphene is a weak opioid analgesic, widely used as a step 2 analgesic (according to WHO classification) in combination with peripheral analgesics, mainly paracetamol. Recent data have underlined its poor analgesic efficacy (in comparison with paracetamol), risks of serious adverse drug reactions (i.e. hepatic reactions, hallucinations, abuse, withdrawal symptoms, hypoglycaemia), possible lethality after overdose, its risk of accumulation in patients with renal failure or in elderly people and some pharmacokinetic insufficiencies (i.e. different half-lives for dextropropoxyphene and paracetamol). Taking into account these data, the drug committee of the Toulouse University Hospital (France) decided to withdraw dextropropoxyphene from the hospital formulary since 1 June 2005. The aim of our study was to investigate the consequences of this withdrawal by comparing use of analgesic drugs in Toulouse University Hospital before (2004) and after (2006) dextropropoxyphene withdrawal (using defined daily dose for 1000 hospitalization-days as the unit measure). Before withdrawal, dextropropoxyphene (in combination with paracetamol) was the second most used analgesic drug after paracetamol alone. After dextropropoxyphene withdrawal, total consumption of analgesic drugs decreased by 4.6% (2006 vs. 2004). There was a 28% decrease in consumption of step 2 analgesics [with an increase in oral tramadol and a slight decrease in codeine (in combination with paracetamol)]. During the same period, step 1 analgesic consumption increased by 11% (mainly paracetamol) and that of step 3 analgesics slightly decreased (−8%). These results show that dextropropoxyphene withdrawal was not associated with a marked switch in prescriptions towards other analgesic drugs. This paper underlines the interest of a hospital-based drug committee to promote rational drug use. Finally, the present data allow us to discuss putative misuse of dextropropoxyphene. [ABSTRACT FROM AUTHOR]

Abstract: Patients with Parkinson’s disease (PD) frequently experienced pain. Nevertheless, there are no epidemiological data about frequency of pain in PD. We compare pain prevalence using analgesic prescription in PD patients, in the general population and in two samples of painful patients: diabetics and osteoarthritis patients in France. Data were obtained from the French System of Health Insurance for the year 2005. Medications (antiparkinsonian, antidiabetics drugs and osteoarthritis drugs) were used for identification of PD, diabetic and osteoarthritis patients. We estimated the prevalence of analgesic drugs prescription (at least one analgesic drug) and the prevalence of chronic analgesic drugs prescription (more than 90 DDD of analgesic drug). The study included 11,466 PD patients. PD patients significantly received more prescription of analgesics than the general population (82% versus 77%,) and fewer than patients with osteoarthritis (82% versus 90%). No significant difference was found between PD and diabetic patients. The chronic prescription of analgesic drugs was more prevalent in PD patients (33%) than in the general population (20%) and in diabetic patients (26%) and similar to that in osteoarthritis patients. PD patients were more exposed than the general population and diabetics to opiates, acetaminophen, and adjuvant analgesics chronic use. [Copyright &y& Elsevier]

Abstract: Type 2 diabetes (noninsulin-dependent diabetes mellitus) develops from a pre-diabetic condition that is characterized by insulin resistance and glucose intolerance, and is exacerbated by obesity. In this study, we compared the ability of over-the-counter analgesic drugs (OTCAD) [acetaminophen (APAP); ibuprofen (IBU); naproxen (NAP); aspirin (ASA)], to protect against the development of a pre-diabetic state in mice fed a high fat diet. After 10 weeks on the high fat diet, mice had normal fasting blood glucose (FBG) levels, but exhibited impaired glucose tolerance. Treatment with 20mg OTCADs/kg body weight improved glucose tolerance, with the order of efficacy, APAP=ASA>IBU, while NAP proved ineffective. Mice fed the high fat diet also exhibited increases in weight gain associated with an increase in body fat. OTCADs prevented in part this increase in body fat, in the order of efficacy, APAP=IBU>NAP=ASA. In isolated liver mitochondria, OTCADs inhibited succinate-dependent H2O2 production, while in white adipose tissue, APAP inhibited NADPH-oxidase mediated H2O2 production and lipid peroxidation. Thus, OTCADs diminish pro-oxidant processes that might otherwise exacerbate inflammation and a pre-diabetic state. We conclude that OTCADs, especially APAP and IBU, may be valuable tools to delay or prevent the development of type 2 diabetes from a pre-diabetic condition. [Copyright &y& Elsevier]

Background: The hemicrania herpes zoster with trigeminal nerve affection is due to the virus reactivation of the chickenpox in patients with chickenpox history and risk or predisposing factors. Acute pain may be alleviated spontaneously, but the infection sequela may persist. Chronic pain, known as postherpetic neuralgia, may appear in 15% of patients. It affects trigeminal nerve in second and third branches, it is rare in the first one and, in general, it is not bilateral. Objective: To evaluate effectiveness of analgesic type non steroid anti-inflammatory, antidepressants and placebo, in a single patient with post-herpetic neuralgia of the first right branch of trigeminal nerve without reaction to treatment. Patient and method: Masculine of 34 years old, with positive HIV and hepatitis C. In a random clinical trial four drugs were studied by oral way; acetaminophen 250 mg, sertraline 25 mg; amitriptiline 12.5 mg and placebo c/24 h during four weeks each one. Statistical analysis; paired t Student Statistical package SPSS v 10. Microsoft Office 2003. Results: The pair placebo-amitriptilina, 1.3036 with confidence interval (CI) 95% (.8166-1.7905) t=5.365 gl=55 p=0.00, pair 5 amitriptiline-sertraline, 1.1429 CI 95% (1.5805-0.7053) t 5.234 gl=55 p=0.000. Conclusions: In this patient this kind of scheme may be considered efficient to reduce trigeminal neuralgia. Results benefit amitriptiline about clinical efficacy and statistical significance. [ABSTRACT FROM AUTHOR]

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Binary mixtures of dipyrone and pitophenone hydrochloride are assayed by zero-crossing second- and third-derivative spectrophotometry and by ratio-spectra first- and second-derivative spectrophotometry. In the first method, calibration plots are linear at 266.5 and 302.5 nm (dipyrone, second derivative), and 257 and 286 nm (pitophenone second derivative) and 242 and 278.3 nm (dipyrone third derivative), and 228.5 and 300 nm (pitophenone, third-derivative). By the second method, lines of regression are linear at 235 and 262 nm (dipyrone, first derivative), and 229.5 and 288.5 nm (pitophenone, first-derivative), and 249.7 and 268 nm (dipyrone, second derivative), and 280.5 and 300 nm (pitophenone, second-derivative). In all methods calibration curves follow the Beer''s law up to 40 μg/ml of each drug. LOD and LOQ values were calculated. The developed derivative spectrophotometric methods were applied to laboratory mixtures and to vials for these drugs. The procedures are simple, rapid, and did not require any preliminary separation or treatment of the samples. [Copyright &y& Elsevier]

Summary The use of herbal supplements in the US has increased dramatically in recent years. These products are not regulated by the Food and Drug Administration (FDA) with the same scrutiny as conventional drugs. Patients who use herbal supplements often do so in conjunction with conventional drugs. This article is a review of potential adverse interactions between some of the commonly used herbal supplements and analgesic drugs. Non-steroidal anti-inflammatory drugs (NSAIDs), particularly aspirin, have the potential to interact with herbal supplements that are known to possess antiplatelet activity (ginkgo, garlic, ginger, bilberry, dong quai, feverfew, ginseng, turmeric, meadowsweet and willow), with those containing coumarin (chamomile, motherworth, horse chestnut, fenugreek and red clover) and with tamarind, enhancing the risk of bleeding. Acetaminophen may also interact with ginkgo and possibly with at least some of the above herbs to increase the risk of bleeding. Further, the incidences of hepatotoxicity and nephrotoxicity may be augmented by acetaminophen when concomitantly used with the potentially hepatotoxic herbs Echinacea and kava, and with herbs containing salicylate (willow, meadowsweet), respectively. The concomitant use of opioid analgesics with the sedative herbal supplements, valerian, kava and chamomile, may lead to increased central nervous system (CNS) depression. The analgesic effect of opioids may also be inhibited by ginseng. It is suggested that health-care professionals should be more aware of the potential adverse interactions between herbal supplements and analgesic drugs, and take appropriate precautionary measures to avoid their possible occurrences. However, as most of the interaction information available is based on individual case reports, animal studies and in vitro data, further research is needed to confirm and assess the clinical significance of these potential interactions. [ABSTRACT FROM AUTHOR]

SummarySixty-two children were randomly allocated to receive, during inhalational anaesthesia with isoflurane and nitrous oxide, either 1.0 µ g.kg-1 remifentanil (n = 33) or saline (n = 29) just before the tunnelling phase of ventriculoperitoneal shunt insertion, in a double-blind study. The remifentanil group showed little stress response to tunnelling as indicated by median (interquartile range [range]) change in heart rate -5.2 (-11.4 to 9.8 [-19.4 to 30.4])%, mean arterial pressure -5.0 (-20.8 to 15.5 [-40.9 to 42.9])% or plasma norepinephrine -13.5 (-38.1 to -2.5 [-77.7 to 81.5])% compared with the saline group, in which the changes were 20.1 (11.5–36.1 [2.1–83.1])%, 42.7 (27.1–56.8 [3.2–73.5])% and 13.3 (0.8–70.0 [-45.2 to 337.5])%, respectively (p < 0.001 for all comparisons). These changes were consistent across most different age categories. The cardiovascular response in the saline group lasted for 8 (4–15 [0–39]) min. Tracheal extubation occurred after 3 (2–4 [1–8]) min in the remifentanil group and 3 (2–6␣[0–15]) min in the saline group (p = 0.29), with transfer to the recovery area and discharge to␣the ward, respectively, 4 (4–5 [1–10]) min and 9 (7–13 [2–32]) min in the remifentanil group and 7␣(4–8 [2–18]) min and 14 (10–19 [7–44]) min in the saline group (p = 0.06 and 0.01, respectively). Postoperatively there was some evidence of respiratory depression and increased oxygen requirements in all age categories, but this was similar in both groups. Overall, the maximum increase from baseline in transcutaneous carbon dioxide tension was 41.2 (11.3–66.7 [-2.0 to 141.7])% in the remifentanil group compared with 30.7 (20.5–55.1 [1.7–159])% in the saline group (p = 0.8), and the time taken for transcutaneous carbon dioxide tension to decrease to < 6.0 kPa was... [ABSTRACT FROM AUTHOR]

Paracetamol (PAC) is one of the most extensively used analgesics and antipyretic drugs to treat mild and moderate pain. P-aminophenol (PAP), the main hydrolytic degradation product of PAC, can be found in environmental water. Recently, CE has been developed for the detection of a wide variety of chemical substances. The purpose of this study is to develop a simple and fast method for the detection and separation of PAC and its main hydrolysis product PAP using CE and microchip electrophoresis with capacitively coupled contactless conductivity detection. The determination of these compounds using microchip electrophoresis with capacitively coupled contactless conductivity detection is being reported for the first time. The separation was run for all analytes using a BGE (20 mM β-alanine, pH 11) containing 14% (v/v) methanol. The RSDs obtained for migration time were less than 4%, and RSDs obtained for peak area were less than 7%. The detection limits (S/N = 3) that were achieved ranged from 0.3 to 0.6 mg/L without sample preconcentration. The presented method showed rapid analysis time (less than 1 min), high efficiency and precision, low cost, and a significant decrease in the consumption of reagents. The microchip system has proved to be an excellent analytical technique for fast and reliable environmental applications., (© 2022 Wiley-VCH GmbH.)

Tanezumab is a novel humanized IgG2 monoclonal antibody that works by selectively targeting, binding to and inhibiting nerve growth factor (NGF). NGF is upregulated in response to injury and inflammation, and preclinical data indicate it plays a role in pain signaling by inducing peripheral and central sensitization. Tanezumab potentially reduces sensitization and pain by blocking the interaction between NGF and the tropomyosin receptor kinase A (TrkA), and it has been studied extensively for the treatment of pain in patients with osteoarthritis (OA). In 2017, tanezumab was granted fast track designation in the U.S. for the treatment of chronic pain in patients with OA, as well as for the treatment of chronic low-back pain. This review discusses the mechanism of action, preclinical data and phase I, II and III studies of efficacy and safety of tanezumab in patients with OA., (Copyright 2022 Clarivate.)

Management of pain following spinal surgery is important not only for patient outcomes but also for improving costs, complication rates, and patient experiences. In this session, presenters reviewed current guidelines and recommendations, the use of perioperative epidurals, ways to reduce tissue injury, and characteristics of current medications used postoperatively for spinal surgery. [ABSTRACT FROM PUBLISHER]