Drugs For Pain Management Research Articles

Smart pain relief: Harnessing conservative Q learning for personalized and dynamic pain management

Pain represents a multifaceted sensory and emotional experience often linked to tissue damage, bearing substantial healthcare costs and profound effects on patient well-being. Within intensive care units, effective pain management is paramount. However, determining suitable dosages of primary pain management drugs like morphine remains challenging due to their reliance on diverse patient-specific factors, including cardiovascular responses and pain intensity. To date, only a singular effort has explored personalized pain treatment recommendations through reinforcement learning. Regrettably, this pioneering study faced limitations stemming from incomplete patient state observations, a restricted action space, and the use of Deep Q-Networks, known for their sample inefficiency and lack of clinical interpretability. In our work, we introduced a Conservative Q-learning-based system for pain recommendation, enriching it with expanded state and action spaces. Additionally, we developed a comprehensive pipeline for both qualitative and quantitative evaluations, focusing on assessing the trained model’s performance. Our findings indicate a slight performance improvement over the clinician’s policy, offering a more clinically sensible and understandable approach compared to the current state-of-the-art methodologies.

Topical nonsteroidal anti-inflammatory drugs for management of pain after PRK: systematic review and network meta-analysis.

Topical nonsteroidal anti-inflammatory drugs (NSAIDs) for management of pain in patients after photorefractive keratectomy (PRK). Pain after PRK is a major concern for both patients and surgeons. Although evidence supports the use of NSAIDs postoperatively, no consensus exists regarding the preferred regimen. The study aimed to compare the efficacy and safety of different topical NSAIDs. This study was prospectively registered with PROSPERO (ID: CRD42023417651). A systematic search of electronic databases was performed, for randomized controlled trials reporting topical NSAIDs' outcomes of corneal re-epithelization, rescue analgesics intake, and pain in days 0 to 3 after PRK (postoperative days [PODs] 0 to 3). Studies were graded for risk of bias. Data were extracted, and standardized mean differences (SMDs) were evaluated in a network meta-analysis in accordance with the Cochrane's guidelines, to which a frequentist approach model was fitted. Transitivity was assessed using the net split method. Treatment effectiveness was ranked using forest plots based on comparison with placebo. P-scores (P) and league tables were used to examine combined direct and indirect comparisons. Of 1540 studies identified, 27 were included. These encompassed 2286 patients across 11 countries, evaluating 7 distinct topical NSAIDs. At POD0, ketorolac (P 0.764), flurbiprofen (P 0.763), and bromfenac (P 0.717) were the most efficient drugs overall and displayed significantly lower pain scores than placebo. Other than that, flurbiprofen held the highest rank for reported pain throughout, significantly outperforming placebo on POD1 (P 0.874, SMD -1.19, 95% CI -1.86 to -0.52), POD2 (P 0.882, SMD -1.05, 95% CI -1.82 to -0.27), and POD3 (P 0.939, SMD -1.14, 95% CI -2.1 to -0.18). Other NSAIDs were significantly better than placebo only on POD1 and POD0. Rescue analgesic intake analysis favored indomethacin (P 0.834, SMD -0.8, 95% CI -1.33 to -0.27), ketorolac, and diclofenac. Compared with placebo, re-epithelization was slowed to different significances with all NSAIDs but flurbiprofen (P 0.991, SMD -0.7, 95% CI -1.38 to -0.03). Flurbiprofen was favorable in pain scores on typically painful postoperative days and re-epithelization times. However, analgesics intake, a more objective outcome, suggested superiority of other NSAIDs. Inconsistencies may be explained by the small sample size. For clinical interpretation, NSAID effect sizes should be taken into consideration.

Impact of opioids on hospital stay and mortality in patients undergoing abdominal surgeries

PurposePostoperative pain management is a critical aspect of surgical care, significantly influencing patient recovery and outcomes. This study aims to evaluate the impact of opioid use on hospital stay and mortality rates among patients undergoing abdominal surgeries in Brazil, where healthcare disparities may affect postoperative outcomes.MethodsThis observational cross-sectional study was conducted at the University Hospital Onofre Lopes in Natal, Brazil. We included 385 patients aged 18 years or older who underwent abdominal surgery in 2023. Data were collected from medical records, focusing on analgesic therapy, opioid types, dosages, and patient demographics. Statistical analyses were performed using JAMOVI software.ResultsOpioid consumption was prevalent among the cohort, with 89.6% of patients receiving opioids postoperatively. Tramadol was the most frequently administered opioid, followed by nalbuphine and morphine. Patients treated with morphine had a significantly extended median hospital stay (15.5 days) compared to those receiving tramadol or nalbuphine (2 days). Morphine use was also associated with a higher mortality rate, with these patients being 16 times more likely to die compared to those on weaker opioids. Older age and extended hospital stays were additional risk factors for increased mortality.ConclusionOpioids were used extensively in this cohort as the main analgesic drug for postoperative pain management after abdominal surgeries. Use was associated with prolonged hospital stay and higher probability of death.

Comparison Of Ketorolac Versus Ibuprofen For Postoperative Pain Management In Total Abdominal Hystrectomy Surgeries

Background - Postoperative pain management is crucial for ensuring patient comfort and promoting faster recovery. Pharmacological interventions, such as NSAIDs, play an essential role in reducing pain intensity while minimizing opioid-related side effects. Ketorolac, a potent NSAID, and ibuprofen are both commonly used for pain relief. This study focuses on comparing the efficacy of these two drugs for pain management in total abdominal hysterectomy surgeries. Aim -To assess and compare the effects of intravenous ketorolac and intravenous ibuprofen on postoperative pain management in total abdominal hysterectomy patients. Materials and Methods: A randomized single-blind study was conducted on 30 patients, divided into two groups (Group K: ketorolac, Group I: ibuprofen). Various parameters, including VAS pain scores, sedation, time for rescue analgesia, and the number of rescue analgesics, were compared. Participants: 30 patients undergoing total abdominal hysterectomy, randomized into two groups (Group K: ketorolac, Group I: ibuprofen). Inclusion Criteria: Patients between 18 and 65 years of age undergoing elective surgery, ASA grade I or II. Exclusion Criteria: Patients with NSAID hypersensitivity, coagulation disorders, bronchial asthma, hepatic or renal failure, and peptic ulcers. Methodology: Patients received lumbar subarachnoid block, followed by either 30 mg of ketorolac or 800 mg of ibuprofen postoperatively. Rescue analgesics were provided if needed. Results: The postoperative pain scores were significantly lower in the ibuprofen group. Time for first rescue analgesia and the total number of rescue analgesics required were also lower in the ibuprofen group

Establishing Geriatric Opiate Use Patterns in Trauma.

Introduction: There is evidence that providers often overprescribe opiates in the postoperative period. Despite an ever-growing geriatric population, there is little research detailing current opiate usage in older patients after trauma. This population presents a unique set of challenges for pain management and prescription drug dependence due to sensitivity, a narrow therapeutic window, and high rates of pre-existing polypharmacy.Objective: Assess the use of narcotics in geriatric trauma patients with various injury patterns to establish a reference point for future intervention for reduction in narcotic dependence.Methods: We created a database of trauma patients' age ≥65 years admitted to a single level 1 trauma center in the Southeastern United States during the 2019 calendar year. Information gathered included patient factors, injury patterns, operative intervention, pain medications prescribed during hospitalization and at discharge, total and average daily morphine milligram equivalents (MME) inpatient and outpatient, and requests/prescriptions for narcotics at follow-up.Results: In 2019, there were 475 patients aged ≥65 admitted to our level 1 trauma center for acute traumatic injuries. 219 of those patients required operative intervention. Average total inpatient MME for this cohort was 169.0 with average daily MME of 22.89. The average total prescribed MME upon discharge was 79.27. There were 29 patients documented to request narcotic prescription refill at time of clinic follow-up, 27 of whom were prescribed a narcotic medication at follow-up.Conclusion: This dataset establishes a reference point for opiate use in geriatric trauma patients to facilitate further research for mitigation of risk in this population.

Effectiveness of the Use of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) for Postoperative Pain Management in Patients Undergoing Major Surgical Operations at Manokwari Hospital

Postoperative pain is a common complication in patients undergoing major surgical operations, interfering with comfort and recovery and increasing the risk of further complications. This study aimed to evaluate the effectiveness of NSAIDs in managing postoperative pain at Manokwari Regional Hospital. Utilizing qualitative research methods, data was collected through observation and literature study and analyzed via data reduction, data presentation, and conclusion drawing. The findings indicate that NSAIDs effectively alleviate postoperative pain by inhibiting cyclooxygenase (COX) enzymes responsible for prostaglandin production. However, their use is limited by potential systemic side effects, including gastrointestinal disorders, kidney impairment, increased blood pressure, heart attack, and heart failure. Consequently, topical NSAID formulations are recommended to mitigate these risks. The study suggests that while NSAIDs are effective, clinicians should consider their side effects and prefer topical alternatives. Future research should explore the efficacy and safety of topical NSAIDs and alternative pain management strategies to enhance clinical practice.

The Analgesic Potential of Litsea Species: A Systematic Review.

Various plant species from the Litsea genus have been claimed to be beneficial for pain relief. The PRISMA approach was adopted to identify studies that reported analgesic properties of plants from the Litsea genus. Out of 450 records returned, 19 primary studies revealed the analgesic potential of nine Litsea species including (1) Litsea cubeba, (2) Litsea elliptibacea, (3) Litsea japonica, (4) Litsea glutinosa, (5) Litsea glaucescens, (6) Litsea guatemalensis, (7) Litsea lancifolia, (8) Litsea liyuyingi and (9) Litsea monopetala. Six of the species, 1, 3, 4, 7, 8 and 9, demonstrated peripheral antinociceptive properties as they inhibited acetic-acid-induced writhing in animal models. Species 1, 3, 4, 8 and 9 further showed effects via the central analgesic route at the spinal level by increasing the latencies of heat stimulated-nocifensive responses in the tail flick assay. The hot plate assay also revealed the efficacies of 4 and 9 at the supraspinal level. Species 6 was reported to ameliorate hyperalgesia induced via partial sciatic nerve ligation (PSNL). The antinociceptive effects of 1 and 3 were attributed to the regulatory effects of their bioactive compounds on inflammatory mediators. As for 2 and 5, their analgesic effect may be a result of their activity with the 5-hydroxytryptamine 1A receptor (5-HT1AR) which disrupted the pain-stimulating actions of 5-HT. Antinociceptive activities were documented for various major compounds of the Litsea plants. Overall, the findings suggested Litsea species as good sources of antinociceptive compounds that can be further developed to complement or substitute prescription drugs for pain management.

Opioid use and disposal at 2 weeks post-surgery: Brief communication regarding excess opioids and disposal habits.

To measure the number of unused prescription opioids and disposal habits of patients following orthopedic shoulder surgery. A prospective observational study. Academic orthopedic sports medicine department. Sixty-seven patients undergoing shoulder surgery. Nine-question opioid use questionnaire. Responses to an opioid use questionnaire were collected at 2 weeks post-surgery. Outcomes of interest included the amount of initial opioid prescription used and the disposal of excess opioids. Sixty-seven patients completed the opioid use questionnaire. Forty-six (68.7 percent) patients reported having excess opioids at 2 weeks. Of the 46 patients with excess opioids, 57 percent disposed of the excess, and 43 percent planned to keep their opioids. Two-thirds of the patients reported having excess opioids, highlighting the issue of an overabundance of unused prescription opioids in America. Utilization of opioid-free pain management strategies and drug disposal kits should be explored to reduce the number of unused and improperly disposed opioids.

TRPV1 analgesics disturb core body temperature via a biased allosteric mechanism involving conformations distinct from that for nociception

Efforts on developing transient receptor potential vanilloid 1 (TRPV1) drugs for pain management have been hampered by deleterious hypo- or hyperthermia caused by TRPV1 agonists/antagonists. Here, we compared the effects of four antagonists on TRPV1 polymodal gating and core body temperature (CBT) in Trpv1+/+, Trpv1-/-, and Trpv1T634A/T634A. Neither the effect on proton gating nor drug administration route, hair coverage, CBT rhythmic fluctuations, or inflammation had any influence on the differential actions of TRPV1 drugs on CBT. We identified the S4-S5 linker region exposed to the vanilloid pocket of TRPV1 to be critical for hyperthermia associated with certain TRPV1 antagonists. PSFL2874, a TRPV1 antagonist we discovered, is effective against inflammatory pain but devoid of binding to the S4-S5 linker and inducing CBT changes. These findings implicate that biased allosteric mechanisms exist for TRPV1 coupling to nociception and CBT regulation, opening avenues for the development of non-opioid analgesics without affecting CBT.

Trends in Opioid and Nonsteroidal Anti-Inflammatory Drug Use for Patients with Kidney Stones in United States Emergency Departments from 2015 to 2021.

Introduction: Renal colic is frequently treated with opioids; however, narcotic analgesic use can lead to dependence and abuse. We evaluated use trends of opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) for pain management of kidney stones in United States emergency departments (EDs) from 2015 to 2021. Methods: Kidney stone encounters were identified using National Hospital Ambulatory Medical Care Survey data. We applied a multistage survey weighting procedure to account for selection probability, nonresponse, and population weights. Medication use trends were estimated through logistic regressions on the timing of the encounter, adjusted for selected demographic and clinical characteristics. Results: Between 2015 and 2021, there were an estimated 9,433,291 kidney stone encounters in United States EDs. Opioid use decreased significantly (annual odds ratio [OR]: 0.87, p = 0.003), and there was no significant trend in NSAID use. At discharge, male patients were more likely than females (OR: 1.93, p = 0.001) to receive opioids, and Black patients were less likely than White patients (OR: 0.34, p = 0.010) to receive opioids. Regional variation was also observed, with higher odds of discharge prescriptions in the West (OR: 3.15, p = 0.003) and Midwest (OR: 2.49, p = 0.010), compared with the Northeast. Thirty-five percent of patients received opioids that were stronger than morphine. Conclusion: These results suggest improved opioid stewardship from ED physicians in response to the national opioid epidemic. However, regional variation as well as disparities in discharge prescriptions for Black and female patients underscore opportunities for continued efforts.

Post-Amputation Pain: Combined Analyses of Randomized Controlled Trials Evaluating Opioids and Gabapentinoids versus Placebo.

An estimated 185,000 patients per year undergo an extremity amputation in the United States (over 500 amputations/day). Prolonged postoperative opioid use, defined as the presence of a filled opioid prescription between 90 and 180 days following the operative amputation procedure, affects nearly 50% of amputees. Moreover, the use of preoperative benzodiazepines, muscle relaxants, anticonvulsants, and antidepressants is strongly linked to prolonged opioid use suggesting new therapeutic strategies are needed. The goal of this study was to better understand how well post-amputation pain is currently treated by selected pharmacologic agents and the success rates of these existing agents. The available literature on PubMed was screened for articles that used randomized-controlled trial (RCT) study designs and gabapentinoids (eg, gabapentin or pregabalin) or opioids (eg, morphine). Two morphine-related RCTs using at least 50% pain reduction responder criteria were combined and qualitatively compared with two gabapentin trials that were previously combined to understand the potential benefits of these drugs in post-amputation pain management compared with placebo. All 4 trials included measured post-amputation pain over a 4- to 6-week acute period. The combined opioid analysis demonstrated a treatment effect that favored morphine (P=0.02) over placebo and indicated the number needed to treat (NNT) of 3.9 (95% CI: 2.5, 9.3) patients. Similarly, the previously combined analysis of gabapentin trials favored gabapentin over placebo and indicated an estimated NNT of 8.9 (95% CI: 5.3, 27.8). Patients undergoing limb amputation have a clear unmet need for more adequate chronic pain control. Given that post-amputation pain is often diagnosed as a chronic condition, persisting for at least 90 days, our data highlight the need for larger sample sizes and longer-term controlled trials to better understand the advantages and disadvantages of chronic use of gabapentinoids and opioids/opioid combination drugs in this patient population.

Role of Pregabalin in Pre-Operative and Post-Operative Pain Management of Lower Limb Orthopedic Surgeries.

Post-operative pain after orthopedic surgery has remained a challenging problem, which prolongs hospital stay and early rehabilitation. Pregabalin comes under the class of gabapentinoids that have been used in postoperative pain in arthroplasty and spine surgeries but studies regarding its role as pre-emptive analgesia in orthopedic limb surgeries are very few. To compare the efficacy of pre-operative pregabalin with a placebo drug in early post-operative pain management for lower limb orthopedics surgeries. A randomized double blinded prospective study was undertaken. Sixty patients were enrolled with age between 18 and 70 years and were divided into 2 groups. Group A - received 150 mg of oral pregabalin capsule, and Group B - received matched color empty capsules. Standard spinal anesthesia was given. Breakthrough analgesia was given with an injection of tramadol 50 mg intravenous. Assessment of pain was done with a Visual Analog Scale (VAS) at 6, 12, 24, and 48 h. In comparison to Group B, Group A had a significantly lower postoperative VAS score and required much less breakthrough analgesia within the 1st 24 h after surgery. In orthopedic lower limb fracture surgeries, pre-emptive pregabalin of 150 mg provides adequate postoperative analgesia with relatively few unfavorable side effects.

Repurposing antihypertensive drugs for pain disorders: a drug-target mendelian randomization study.

Addressing the rising prevalence of pain disorders and limitations of current analgesics, our study explores repurposing antihypertensive drugs for pain management, inspired by the link between hypertension and pain. We leverage a drug-target Mendelian Randomization (MR) approach to explore their dual benefits and establish causal connections. A comprehensive compilation of antihypertensive drug classes was undertaken through British National Formulary, with their target genes identified using the DrugBank database. Relevant single nucleotide polymorphisms (SNPs) associated with these targets were selected from published genomic studies on systolic blood pressure (SBP) as genetic instruments. These SNPs were validated through MR against acute coronary artery disease (CAD) to ensure genes not linked to CAD were excluded from acting as proxies for antihypertensive drugs. An MR analysis of 29 pain-related outcomes was conducted using the FinnGen R10 database employing the selected and validated genetic instruments. We utilized the Inverse Variance Weighted (IVW) method for primary analysis, applying Bonferroni correction to control type I error. IVW's multiplicative random effects (MRE) addressed heterogeneity, and MR-PRESSO managed pleiotropy, ensuring accurate causal inference. Our analysis differentiates strong and suggestive evidence in linking antihypertensive drugs to pain disorder risks. Strong evidence was found for adrenergic neuron blockers increasing migraine without aura risk, loop diuretics reducing panniculitis, and vasodilator antihypertensives lowering limb pain risk. Suggestive evidence suggests alpha-adrenoceptor blockers might increase migraine risk, while beta-adrenoceptor blockers could lower radiculopathy risk. Adrenergic neuron blockers also show a potential protective effect against coxarthrosis (hip osteoarthritis) and increased femgenpain risk (pain and other conditions related to female genital organs and menstrual cycle). Additionally, suggestive links were found between vasodilator antihypertensives and reduced radiculopathy risk, and both alpha-adrenoceptor blockers and renin inhibitors possibly decreasing dorsalgianas risk (unspecified dorsalgia). These findings highlight the intricate effects of antihypertensive drugs on pain disorders, underlining the need for further research. The findings indicate that antihypertensive medications may exert varied effects on pain management, suggesting a repurposing potential for treating specific pain disorders. The results advocate for further research to confirm these associations and to explore underlying mechanisms, to optimize pain management practices.

Detection of 41 Drugs and Metabolites in Urine with Internal Hydrolysis Control by Liquid Chromatography-Tandem Mass Spectrometry.

Regular monitoring of pain management and substance use disorder patients through urine drug screening is important for assessing patient compliance with prescribed drugs and abstinence fromnon-prescribed drugs. Sample analysis is commonly performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) as multiple drugs and metabolites can be monitored from one sample. However, challenges faced indeveloping an LC-MS/MS method for multiple analytes in urine include variability in matrix and concentration from sample to sample and variable chemistry of many pain management drugs and associated metabolites affecting accuracy and precision of results. We describe here an LC-MS/MS method for analysis of 41 drugs and metabolites commonly prescribed for pain management patients. The developed method uses enzymatic hydrolysis followed by cation exchange solid phase extraction. Resorufin-glucuronide is used as an internal hydrolysis control to monitor hydrolysis in each patient sample and minimize false negatives. Analysis was performed using an Agilent 6470 mass spectrometer in dynamic multiple reaction monitoring mode.

Time-Dependent Differences in the Effects of Oleic Acid and Oleyl Alcohol on the Human Skin Barrier.

Oleic acid and oleyl alcohol are commonly used permeation and penetration enhancers to facilitate topical drug delivery. Here, we aimed to better understand the mechanism of their enhancing effects in terms of their interactions with the human skin barrier using diclofenac diethylamine (DIC-DEA), a nonsteroidal anti-inflammatory drug for topical pain management. Oleic acid promoted DIC-DEA permeation through ex vivo human skin more rapidly than oleyl alcohol (both applied at 0.75%) due to fluidization of stratum corneum lipids as revealed by infrared spectroscopy. After 12 h, the effect of these enhancers on DIC-DEA permeation leveled off, fluidization was no longer evident, and skin permeabilization was mainly due to the formation of fluid enhancer-rich domains. Contrary to oleyl alcohol, oleic acid adversely affected two indicators of the skin barrier integrity, transepidermal water loss and skin electrical impedance. The content of oleyl alcohol in the stratum corneum was lower than that of oleic acid (even 12 h after the enhancers were removed from the skin surface), but it caused higher DIC-DEA retention in both epidermis and dermis compared to oleic acid. The effects of oleyl alcohol and oleic acid on DIC-DEA permeation and retention in the skin were similar after a single and repeated application (4 doses every 12 h). Thus, oleyl alcohol offers several advantages over oleic acid for topical drug delivery.

Ketorolac-induced anaphylaxis following oral administration: a case series.

Ketorolac is a commonly used non-steroidal anti-inflammatory drug for reducing pain and inflammation. Anaphylaxis is a medical emergency that occurs after exposure to an allergen, with a varied clinical presentation requiring prompt and appropriate measures to prevent or manage it. Although uncommon, ketorolac can cause anaphylaxis requiring immediate medical care. The authors present two cases of anaphylaxis in females induced after oral intake of ketorolac with successful outcomes. The cases involve two adult women who experienced an allergic reaction to ketorolac. The first woman, aged 36, and the second woman, aged 26, on her second postpartum day, both developed similar types of symptoms like periorbital swelling, itching, and difficulty breathing after taking oral ketorolac. The second woman had a history of allergic rashes. They received immediate treatment with epinephrine, oxygen therapy, intravenous fluids, and other medications. They showed a rapid improvement and were discharged after observation. Anaphylactic reactions to ketorolac, a commonly used pain management drug, have been reported. Symptoms include swelling, difficulty breathing, and hypotension. Treatment involves medications like epinephrine, hydrocortisone, and pheniramine. A detailed medical history, laboratory investigations, appropriate medication, oxygen therapy, and follow-up care are important in managing anaphylactic reactions, which can be life-threatening. Although rare, ketorolac can cause anaphylactic reactions in patients with or without a history of drug allergy. Immediate recognition and management are essential, along with a detailed medical history and follow-up care.

Anesthesia and pain management drugs used in Libyan hospitals and clinics

Background: Pain management can pose multiple challenges in the acute care setting for hospitalists and front-line prescribers. The drugs used for the relief of pain in the surgical can divided into potent and mild analgesics. Objectives: Identifying the most important analgesics used in some Libyan hospitals and health centers. Method: This study is a documentary survey and a description of the reality of the use of some narcotic drugs in Libyan hospitals. It has been conducted in seven Libyan cities (zwarah, al-jmail, Sabratha, al-zawia, Tripoli, misratah and benghazi) during the period of (2. 10. 2022 to 10. 12. 2022). The participants have been divided into two main groups (Patients and specialists group) in a total number of 115 participants (Male and Females). Results: all the participants from the 1st group (Patients group) confirmed that they have taken one of the pain management drugs as one of the treatment plan prescribed by the physicians. The statistical analysis revealed that the most common drug of the pain management was paracetamol (58%) followed by Tramadul (30%) and finally Voltarine (12%). Discussion and conclusion: Pain and its treatment are major public health issues that we face as a society today. Patients with chronic pain present a special challenge. When they have pre-existing pain and undergo an operative procedure, it becomes important to differentiate pre-existing chronic pain from new acute postoperative pain.

Efficacy of Novel Oral Non-Steroid Anti-Inflammatory Drugs for Pain Management After Total Knee Arthroplasty

Background. Total knee arthroplasty (TKA) typically associated with moderate to severe post-operative pain that resolves quite slowly. Therefore, injectable forms of non-steroid anti-inflammatory drugs became the key element of multi-modal analgesia in early post-operative period.
 Aim of the study to evaluate the effectiveness and safety of ketorolac vs. ketoprofen for relief of postoperative pain in patients after TKA.
 Methods. 100 end-stage osteoarthritic patients (mean age 66,6 years, 80 women and 20 men) that consecutively admitted for primary uncomplicated TKA were randomized in two groups. Ketorol Express (10 mg oral, 4 times per day) used for post-op pain management in the first (49 patients) while Ketonal (100 mg oral, twice a day) in the second (51 patients). The outcomes assessed by numeral rating scale (NRS), visual analog scale (VAS), pain diaries, comorbidities, peri-operative characteristics, knee function (Oxford Knee Score 12), adverse effects, drug tolerance and usability, overall satisfaction of treatment. Both groups had no significant gender, age, clinical, radiological, functional or intra-operative differences.
 Results. The NRS and VAS ratings showed the similar tendency in both groups: the next day after surgery the pain increased up to moderate, followed by 2 times reduction at day four. There were no differences in average, minimal and maximal pain both in rest and movement as well as amount of daily moderate to severe pain and speed of analgesic effect after oral drug intake. The similar number of patients needed additional analgesics in both groups: on average 3,57 and 4,41 injections correspondently. However, in ketorolac group at day 3 4 the percentage of such patients was significantly lower: by 30% at day 3 (p0,05) and 50% at day 4 (p0,05). Reported side effects were comparable in both groups but the high level of overall satisfaction was two times more in the patients who took ketorolac.
 Conclusion. Oral administration both of ketorolac and ketoprofen proved to be highly effective for pain management after TKA with appropriate tolerance therefore could be used instead of injections since early post-op period.

Pharmacoepidemiology and pharmacoeconomics of pain management in caesarean section in a chronological aspect

Background. For pain management during caesarean section, the correct choice of anesthesia and adequate analgesia are of great importance.
 Aim. To study pain management methods for caesarean section, to develop their pharmacoepidemiological and pharmacoeconomic characteristics in a chronological aspect.
 Material and methods. A retrospective pharmacoepidemiological and pharmacoeconomic analysis of 1025 birth histories of women after caesarean section with a detailed assessment of the use of local anesthetics, central deprecating agents, opioid and non-opioid analgesics in 20072009 (523) and 20162017 (502) was carried out. Frequency of use, total consumption and cost of drug therapy during and after surgery were analyzed. The significance of differences in relative indicators was assessed by Pearson (2).
 Results. In the first time period, regional methods of anesthesia were used in 98.5% of cases: epidural anesthesia in 428 (82%) cases, spinal anesthesia in 87 (16.5%) cases (p=0.001). In the second period, regional methods of anesthesia were used in 97.5% of cases: epidural anesthesia in 157 (31%) cases, spinal anesthesia in 334 (66.5%) cases (p=0.001). Intraoperatively, in the second period, trimeperidine for spinal anesthesia, fentanyl for epidural anesthesia (p=0.001; p=0.001) were prescribed 2 times more often; intraoperative consumption of opioid analgesics was greater than in the first period. After surgery in the first period with epidural anesthesia more often than in the second, trimeperidine (45%), ropivacaine (96%); for spinal and epidural anesthesi paracetamol, ketorolac (p=0.001), were prescribed. Spinal anesthesia in both periods was characterized by a greater consumption of adjuvants than epidural anesthesia. In the first period, 12 drugs for pain management from 5 pharmacotherapeutic groups were used, in the second 10 drugs from 5 groups. The cost of epidural anesthesia was 4 times higher in the first period, and 7 times higher in the second.
 Conclusion. Between 2007 and 2017, there was a transition from epidural to spinal anesthesia, and opioid analgesics were more often added to local anesthetics to manage pain during surgery in the second period; the cost of epidural anesthesia was high due to the price of ropivacaine.

Insulin-like Growth Factor-1 (IGF-1) Related Drugs in Pain Management.

Objective. The aim of this review is to explore the role of IGF-1 and IGF-1R inhibitors in pain-related conditions and assess the effectiveness of IGF-1-related drugs in pain management. Specifically, this paper investigates the potential involvement of IGF-1 in nociception, nerve regeneration, and the development of neuropathic pain. Methods. We conducted a search of the PUBMED/MEDLINE database, Scopus, and the Cochrane Library for all reports published in English on IGF-1 in pain management from origination through November 2022. The resulting 545 articles were screened, and 18 articles were found to be relevant after reading abstracts. After further examination of the full text of these articles, ten were included in the analysis and discussion. The levels of clinical evidence and implications for recommendations of all the included human studies were graded. Results. The search yielded 545 articles, of which 316 articles were deemed irrelevant by reading the titles. There were 18 articles deemed relevant after reading abstracts, of which 8 of the reports were excluded due to lack of IGF-1-related drug treatment after reviewing the full text of the articles. All ten articles were retrieved for analysis and discussion. We found that IGF-1 may have several positive effects on pain management, including promoting the resolution of hyperalgesia, preventing chemotherapy-induced neuropathy, reversing neuronal hyperactivity, and elevating the nociceptive threshold. On the other hand, IGF-1R inhibitors may alleviate pain in mice with injury of the sciatic nerve, bone cancer pain, and endometriosis-induced hyperalgesia. While one study showed marked improvement in thyroid-associated ophthalmopathy in humans treated with IGF-1R inhibitor, two other studies did not find any benefits from IGF-1 treatment. Conclusions. This review highlights the potential of IGF-1 and IGF-1R inhibitors in pain management, but further research is needed to fully understand their efficacy and potential side effects.