Pain-relieving Drugs Research Articles

The Effect of Evogliptin Tartrate on Controlling Inflammatory Pain.

Background: Evogliptin tartrate inhibits dipeptidyl peptidase-4 (DPP-4), boosting glucagon-like peptide 1 (GLP-1) secretion and improving insulin release and glucose tolerance, while also exerting anti-inflammatory effects. We investigated its anti-inflammatory and analgesic effects. Methods: Forty male Sprague Dawley rats were divided into (N = 10 in each): (1) naïve, (2) complete Freund's adjuvant (CFA) inflammation + evogliptin tartrate (once for 10 mg/kg) (CFAE), (3) CFA + vehicle (same volume with normal saline with evogliptin tartrate/once) (CFAV), and (4) CFA + indomethacin (5 mg/mL/kg/1 time) (CFAI) groups. CFA was injected subcutaneously into rat plantar regions, and medications (evogliptin tartrate, vehicle, and indomethacin) were administered orally for 5 days. Post treatment, blood from the heart and plantar inflammatory tissue were collected to assess inflammatory cytokines. Evogliptin tartrate effects on controlling inflammation and pain were evaluated by measuring rat plantar paw thickness, paw withdrawal threshold, dorsal root ganglion (DRG) resting membrane potential, DRG action potential firing, and cytokine (TNF-α and IL-1β) levels. Results: Compared with the naïve group, plantar paw thickness, cytokine (TNF-α and IL-1β) levels, DRG resting membrane potential, and DRG action potential firing increased, whereas the paw withdrawal threshold decreased in all CFA groups. However, CFAE and CFAI rats showed recovery. The degree of CFAE recovery resembled that observed in the CFAI group. Conclusions: Evogliptin tartrate mirrored the anti-inflammatory pain relief of indomethacin. We aim to broaden its use as an anti-inflammatory drug or pain relief drug.

Abdominal pain syndrome in patients with irritable bowel syndrome: features of selection of therapy

Irritable bowel syndrome (IBS) is an important social problem, since it is often diagnosed in people of young working age, significantly affects the quality of life of patients and causes economic damage to society. IBS is a chronic functional bowel disease, the main manifestation of which is pain combined with changes in bowel movements, frequency and character of stool. The mechanism of formation of abdominal pain syndrome is due to a disruption in the interaction along the brain-gut axis, which leads to changes in the regulation of intestinal motor function and the development of visceral hypersensitivity (VH). Abdominal pain as a manifestation of IBS is primarily associated with spasm of intestinal smooth muscles. The first-line drugs for pain relief are antispasmodics, which reduce the tone and contractility of intestinal smooth muscles, effectively coping with abdominal pain. The domestic pharmaceutical market is represented by different groups of muscle relaxants, among which calcium channel blockers are of particular relevance for patients with IBS. Representative of the latter is the drug Otilonium bromide, which is widely used throughout the world, is effective and safe, well tolerated and superior to placebo in reducing symptoms and preventing relapse of pain in patients with IBS. The effectiveness of otilonium bromide is due to a triple mechanism of action: blockade of calcium channels (relief of spasm), antagonism of tachykinone NK2 receptors (effect on HHV) and inhibition of acetylcholine muscarinic receptors (M3-ChR) (reduction of intestinal secretion). This article presents a short review of the literature on the causes and mechanism of development of pain in IBS, as well as the possibilities of its relief, primarily with the use of smooth muscle relaxants, namely otilonium bromide.

Unraveling the parameters and biological mechanisms of CO2 laser therapy for acute pain relief.

Acute pain-related pathology is a significant challenge in clinical practice, and the limitations of traditional pain-relief drugs have made it necessary to explore alternative approaches. Photobiomodulation (PBM) therapy using CO2 laser has emerged as a promising option. In this study, we aimed to identify the optimal parameters of CO2 laser irradiation for acute pain relief through in vivo and in vitro experiments. First, we validated the laser intensity used in this study through bone marrow mesenchymal stem cells (BMSCs) experiments to ensure it will not adversely affect stem cell viability and morphology. Then we conducted a detailed evaluation of the duty cycle and frequency of CO2 laser by the hot plate and formalin test. Results showed a duty cycle of 3% and a frequency of 25 kHz produced the best outcomes. Additionally, we investigated the potential mechanisms underlying the effects of CO2 laser by immunohistochemical staining, and found evidence to suggest that the opioid receptor may be involved in its analgesic effect. In conclusion, this study provides insights into the optimal parameters and underlying mechanisms of CO2 laser therapy for effective pain relief, thereby paving the way for future clinical applications.

Dual-pocket inhibition of Nav channels by the antiepileptic drug lamotrigine

Voltage-gated sodium (Nav) channels govern membrane excitability, thus setting the foundation for various physiological and neuronal processes. Nav channels serve as the primary targets for several classes of widely used and investigational drugs, including local anesthetics, antiepileptic drugs, antiarrhythmics, and analgesics. In this study, we present cryogenic electron microscopy (cryo-EM) structures of human Nav1.7 bound to two clinical drugs, riluzole (RLZ) and lamotrigine (LTG), at resolutions of 2.9 Å and 2.7 Å, respectively. A 3D EM reconstruction of ligand-free Nav1.7 was also obtained at 2.1 Å resolution. RLZ resides in the central cavity of the pore domain and is coordinated by residues from repeats III and IV. Whereas one LTG molecule also binds to the central cavity, the other is found beneath the intracellular gate, known as site BIG. Therefore, LTG, similar to lacosamide and cannabidiol, blocks Nav channels via a dual-pocket mechanism. These structures, complemented with docking and mutational analyses, also explain the structure-activity relationships of the LTG-related linear 6,6 series that have been developed for improved efficacy and subtype specificity on different Nav channels. Our findings reveal the molecular basis for these drugs' mechanism of action and will aid the development of novel antiepileptic and pain-relieving drugs.

EFFICACY AND PHARMACOECONOMICS STUDY OF SPINAL CORD STIMULATION (SCS) CONDUCTED AT THE PAIN THERAPY HUB, SAN GIULIANO HOSPITAL ASL NAPOLI 2

EFFICACY AND PHARMACOECONOMICS STUDY OF SPINAL CORD STIMULATION (SCS) CONDUCTED AT THE PAIN THERAPY HUB, SAN GIULIANO HOSPITAL ASL NAPOLI 2

Knowledge and Practice Regarding Self-Medication of Analgesic Drugs of the Students of Nursing Institute, Naogaon

This was a cross-sectional type of descriptive study that was carried out with a view to assessing knowledge and practice regarding self-medication of analgesic drugs of the students of the Nursing Institute, Naogaon. The sample size was 175 which were selected purposively. The mean age was 19.34±0.95 years. Here, 56.0% knew self-medication practice is a bad habit for a nursing student, 92.0% of respondents said that pain-relieving drugs are dangerous without anti-acid drugs, 60.0% told that self-medication practice is completely unethical, most 85.7% told that purchase of medicine needs a prescription, 67.43% respondents took medicine without doctor`s advice. This study provides some important information which might help the concerned people to take appropriate measures and might be the basis for further in-depth study on this issue.’’

Temperature-Sensitive Hydrogels as Carriers for Modulated Delivery of Acetaminophen.

The purposes of this study are the polymerization of temperature-sensitive copolymers based on N-isopropyl acrylamide and 10 mol % of 2-hydroxypropylmethacrylate, characterisations of their thermal, morphological and swelling properties, as well as the analysis of potential application in drug-delivery systems. Acetaminophen, the representative of non-steroidal anti-inflammatory drugs, was used as a model drug in this study. It is a common pain relief drug, which is also used for fever treatment. However, oral administration comes with certain health risks, mainly the overdose and frequent administration of up to four times a day. The goal of applying temperature-sensitive hydrogel is to enable extended administration once a day, depending on the body temperature. The swelling behavior of the obtained poly(N-isopropyl acrylamide-co-2-hydroxypropylmethacrylate) (p(NIPA/HPMA)) hydrogels and their temperature-sensitivity, kinetics and order of swelling processes at 18 and 38 °C were analyzed. The thermal properties of these hydrogels were observed by the DSC method, and the obtained thermograms showed both melting and glass transitions. The drug delivery system of p(NIPA/HPMA) hydrogels with loaded acetaminophen was analyzed using scanning electron microscopy and Fourier transform infrared spectroscopy methods. Structural analysis of FTIR spectra indicates that non-covalent intermolecular interactions of the type of hydrogen bonds were formed among functional groups of acetaminophen and side-chains of p(NIPA/HPMA) hydrogels. The surface structure of p(NIPA/HPMA) hydrogels after drug loading indicates the acetaminophen presence into the pores of the hydrogel network, and their loading efficiency was higher than 92%. Qualitative and quantitative analysis of acetaminophen, determined by the high-pressure liquid chromatography method, showed that about 90-99% of the loaded amount was released from p(NIPA/HPMA) hydrogels within 24 h. Kinetic parameters of the acetaminophen release under simulated gastrointestinal conditions were determined. Based on obtained results, the drug delivery system of temperature-sensitive p(NIPA/HPMA) hydrogels with loaded acetaminophen could be suitable for additional investigation for modulated drug administration, e.g., for extended drug administration.

Role of genetics and lifestyle in dysmenorrhea

The aim of this systematic review was to identify the current state of knowledge on the association between susceptibility genes associated with this disorder and the lifestyle of patients (including diet, habits and stress levels). It also highlighted the advances made in this field of study, from a constructive point of view, and pointed out the perspectives for research into this disorder. Dysmenorrhoea, as a primary and secondary disorder, is one of the main causes of partial or total disability in the life cycle of women, both in reproductive age and later. It is recognised as a painful and disabling disorder which, depending on the cultural context, may or may not be cured by medical care, physiotherapy and the use of pain-relieving drugs, from an unknown aetiology (primary dysmenorrhoea) or concomitantly to surgical intervention (secondary dysmenorrhoea). Lifestyle, habits and diet have been identified as related to the intensity of pain and the disability it causes (active or passive use of cigarettes, consumption of alcohol, etc.), and genes related to the interpretation of pain generated by the patient from the morphology of the hypothalamus and the associative function of pain (BNDF Val66Met polymorphism) have been identified, as well as alterations in cytokines (in primary dysmenorrhoea), prostaglandins and an influence of the Cyp1A1 gene (in passive smokers). The study perspective is usually non-integrative and limited to the site studied, as well as to professional, laboratory, imaging (gynaecological and genetic) and/or molecular resources, which can only in a few cases be of an integral approach. Limitations are compounded by the fact that not all the populations studied are usually educated about menstruation, which also limits compatibility and comparability among studies.

EuroAPI to boost pain relief drug supply for France

EuroAPI to boost pain relief drug supply for France

Capsaicin derived from endemic chili landraces combats Shigella pathogen: Insights on intracellular inhibition mechanism

Ethnic tribals in northeast India have been growing and maintaining local chili landraces for ages. These chilies are known for their characteristic pungency and immense therapeutic properties. Capsaicin, a significant chili metabolite, is recognized as a natural drug for pain relief, diabetic neuropathy, psoriasis, arthritis, etc. In this study, we tried to observe the influence of locality factors on the pungency and bioactive features of Capsicum annuum L. landraces. We also checked the gastro-protective ability of these chilies, especially in the cure of shigellosis. Phytometabolite characterization and estimation were done through spectrophotometric methods. Preparative and analytical HPLC techniques were employed for extracting and purifying capsaicin-enriched fractions. Shigella flexneri growth retardation was determined through the broth dilution method. Gentamicin protection assay and ELISA were done to assess the intracellular invasion and IL-1β inflammasome production by S.flexneri. The correlation analyses postulated that phenols, flavonoids, chlorophylls, β-carotene, and capsaicin synthase upregulation strongly influenced capsaicin biosynthesis in chili cultivars. Correspondingly, the inhibitory efficacy of the HPLC-purified Balijuri-derived capsaicin was more effective than the Raja-derived capsaicin in inhibiting intracellular Shigella growth. Reduced levels of pro-inflammatory cytokine (IL1β) in capsaicin-treated Shigella-infected cells probably reduced inflammation-mediated intestinal damage, limiting bacterial spread. This investigation advocates the unique potential of local chilies in curing deadly ‘shigellosis’ with mechanistic evidence. Our observation justifies the traditional healing practices of the ethnic people of NE India.

Success of the pain relief drug injections in management of the bertolloti syndrome: case report and review of the literature

Introduction: Low back pain accompanied by the lumbosacral transitional vertebra (LSTV) is called the Bertolotti syndrome. This report discussed a case treated with combined corticosteroid and local anesthetic injections based on the literature. Case report: A 35-year-old female patient was admitted to the hospital suffering from low back pain. On neurological exam, her left sacroiliac joint was painful on palpation. Her muscle strength was full, but the left patella reflex was hypoactive. X-ray images revealed “Castellvi Type IIa” LSTV on the left side; therefore, it was considered that the patient might have Bertolotti Syndrome. Because şhedid not accept surgical intervention, “betamethasone dipropionate+betamethasone sodium” and “bupivacaine hydrochloride” were injected into her bilateral sacroiliac joints, bilateral L3-4, and L4-5 facets, and left LSVT joint under fluoroscopy. Her low back pain vanished immediately after the procedure, and she was discharged from the hospital with a full recovery. With an interval of about six months, she was hospitalized 5 more times with complaints of recurrent low back pain, and at each hospitalization, "local anesthetic" (LA) alone or "local anesthetic+corticosteroid" (LA+S) combination was injected into the primary trigger zones. During long-term follow-up, she continued his daily life without any problems. Discussion: This case report showed that sequential LA and LA+S administrations could be curative for patients with Bertolotti syndrome who do not accept surgical treatment, or who cannot undergo surgical intervention. Thus, it was concluded that it would be beneficial to conduct studies with larger samples to obtain more precise information about this method.

Efficacy of surgical treatment on polypharmacy of elderly patients with lumbar spinal canal stenosis: retrospective exploratory research

BackgroundPolypharmacy is a growing public health problem occurring in all healthcare settings worldwide. Elderly patients with lumbar spinal canal stenosis (LSS) who manifest low back and neuropathic pain and have a high frequency of comorbidity are predicted to take many drugs. However, no studies have reported polypharmacy in elderly patients with LSS. Thus, we aimed to review the polypharmacy among elderly LSS patients with elective surgeries and examine how the surgical treatment reduces the polypharmacy.MethodsWe retrospectively enrolled all the patients aged ≥ 65 years who underwent spinal surgery for LSS between April 2020 and March 2021. The prescribed drugs of participants were directly checked by pharmacists in the outpatient department preoperatively and 6-month and 1-year postoperatively. The baseline characteristics were collected beside the patient-based outcomes including Roland–Morris Disability Questionnaire, Zurich Claudication Questionnaire, and Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ). The cutoff number of drugs for polypharmacy was defined as 6. The prescription drugs were divided into 9 categories: drugs for neuropsychiatric, cardiovascular, respiratory, digestive, endocrine metabolic, and urinary renal diseases; blood products; pain relief medication; and others.ResultsA total of 102 cases were finally analyzed, with a follow-up rate of 78.0%. Of the participants, the preoperative polypharmacy prevalence was 66.7%. The number of drugs 6-month and 1-year postoperatively was significantly less than the preoperative one. The proportions of polypharmacy at 6 months and 1 year after surgery significantly decreased to 57.8% and 55.9%, respectively. When the prescribed drugs were divided into 9 categories, the number of drugs for pain relief and digestive diseases was significantly reduced after surgery. The multi-variable analysis revealed that a higher score in the psychological disorder of JOABPEQ was associated with 3 or more drugs decreased 1-year postoperatively (OR, 2.5; 95% CI: 1.0–6.1).ConclusionPolypharmacy prevalence was high among elderly LSS patients indicated for lumbar spinal surgery. Additionally, our data showed that lumbar spinal surgery was effective in reducing polypharmacy among elderly LSS patients. Finally, the multi-variable analysis indicated that better psychological condition was associated with the reduction of prescribed drugs after lumbar spinal surgery.

Workplace Context to Prevent Substance Misuse in the United States: Associations Between workplace Policies and Employee Substance Use Disorders

Workplace policies are important because employee rates of alcohol and drug misuse can be associated with work-related risk factors in the United States. To explore the associations, this study analyzed the 2010–2014 National Survey on Drug Use and Health datasets. The overall sample size was 130,726, and the SUD outcome variables included alcohol, marijuana, pain reliever, and illicit drug use disorders. 20% of participants reported no substance use policies in their workplace. Significant associations were identified between all four measured SUD outcome variables, the presence of specific substance use workplace policies, and individual employment sectors. Specifically, comprehensive policies out of six policies were significantly associated with decreased SUDs in nearly every employment sector. The results of this study suggest that workplace substance use policies are important to prevent the development of employee SUDs and comprehensive policies in place can be most effective.

A Cross Sectional Study to Analyze Drug Utilization Pattern of Pain Clinic in a Tertiary Care Hospital of Central India

Background: Pain is associated with increased prevalence of chronic diseases which adversely affects the quality of life of patients. This also leads to increased demand of drugs for chronic pain relief. Drug utilization pattern studies of pain clinic are therefore important to ascertain rational use of medicines in healthcare system.The study aims to evaluate drug utilization pattern in pain clinic of a tertiary care teaching hospital.
 Methods: A cross sectional study was done by analyzing prescriptions of patients at pain clinic of MYH Hospital of Indore, MP, India, for a period of 3 months from November 2021 to January 2022. Total 260 prescriptions were analyzed on the basis of WHO core prescribing indicators, FDC (Fixed Dose Combinations) & NLEM (National List of Essential Medicines) list by using descriptive statistics.
 Results: Study results showed that analgesics were most commonly prescribed in the age grou p 41-60 years. Lower back pain (28.8%) was the most common indication for prescribing analgesics in pain clinic with a female preponderance of 57.7%. Out of total 639 drugs, Fixed Dose Combinations (FDC)(76.2%) were more than single drugs (24.8%). 59.3% of drugs were concomitant medications. 80% (220) FDCs were generic and Gabapentin+Nortryptiline (31.8%) was the commonest FDC. Pregabalin was the most commonly prescribed single drug preparation. Average number of drugs per encounter were 2.45 and generic prescribing was 85.7%. Total 46% of medicines were prescribed from NLEM.
 Conclusion: We found that FDC, generic prescribing and concomitant medications use was higher in our study. The study guides for rational prescribing of analgesics to maximize pain relief and minimize adverse effects associated with it.

Management of stenosing flexor tenosynovitis in primary care.

Management of stenosing flexor tenosynovitis in primary care.

Efficacy of oral mefenamic acid versus paracetamol as a prophylactic analgesic for needle pain in children receiving vaccination: a three-arm, parallel, triple-blind, placebo-controlled MAP VaC randomized controlled trial

Background: Needle pain due to routine vaccination is an important factor contributing to low vaccine adherence and immunization coverage. Prophylactic oral analgesics can address this important issue of needle pain related to vaccination. Paracetamol and mefenamic acid are commonly used nonsteroidal anti-inflammatory drugs for pain relief, but there is little published literature on whether the same can be used for needle pain related to vaccination. Objectives: This study was planned to compare the efficacy of oral mefenamic acid and paracetamol over placebo as a prophylactic analgesic during vaccination and prophylactic antipyretic during the post-vaccination period. Designs: Three-arm, triple-blind, randomized controlled trial. Methods: This study was conducted at the outpatient department of a tertiary-level medical college in South India from January 2021 to June 2022. In this three-arm interventional trial, each arm had either a single dose of placebo or mefenamic acid (4 mg/kg/dose) or paracetamol (10 mg/kg/dose). These medicines were administered orally 30 min before vaccination to reduce needle pain. Main outcome and measures: Outcome was measured with the change of FLACC (Face, Leg, Activity, Cry, Consolability) scoring at the time of vaccination, subsequently at 15 and 30 min of vaccination in all three groups. Appearance of fever, grade of fever, and need for antipyretics 24 h after vaccination were also noted. Results: There was a significant difference in FLACC scores at the time of administration ( p = 0.010) and at 15 min ( p = 0.014) with mefenamic acid compared to placebo. Although the paracetamol group showed a difference when compared to the placebo, it was not significant at the time of administration ( p = 0.401), at 15 min ( p = 0.451), or 30 min ( p = 0.892) post-vaccination. The appearance of fever, grade of fever, and use of antipyretic up to 24 h post-vaccination had no significant difference among any of the three groups. Conclusion: Mefenamic acid was more potent than placebo for pre-vaccination pain prophylaxis in children. There was no difference in the appearance of fever and its grade among the three groups. The promising results from this trial warrant further large-scale studies to recommend a single oral dose of mefenamic acid to tackle needle pain related to vaccination in children to improve vaccine adherence and coverage. Trial registration: CTRI (Clinical trials registry-India) (CTRI/2021/01/030239). [Date of Commencement: 13 Jan 2021, Date of last recruitment: 30 June 2022 (now closed for new participants)]

Structures of the entire human opioid receptor family

Opioids are effective analgesics, but their use is beset by serious side effects, including addiction and respiratory depression, which contribute to the ongoing opioid crisis. The human opioid system contains four opioid receptors (μOR, δOR, κOR, and NOPR) and a set of related endogenous opioid peptides (EOPs), which show distinct selectivity toward their respective opioid receptors (ORs). Despite being key to the development of safer analgesics, the mechanisms of molecular recognition and selectivity of EOPs to ORs remain unclear. Here, we systematically characterize the binding of EOPs to ORs and present five structures of EOP-OR-Gi complexes, including β-endorphin- and endomorphin-bound μOR, deltorphin-bound δOR, dynorphin-bound κOR, and nociceptin-bound NOPR. These structures, supported by biochemical results, uncover the specific recognition and selectivity of opioid peptides and the conserved mechanism of opioid receptor activation. These results provide a structural framework to facilitate rational design of safer opioid drugs for pain relief.

Research progress of Chinese medicine in the treatment of HyCoSy diagnosis of infertility

Infertility is defined as having sex without contraception for more than 12 months without becoming pregnant. The incidence of infertility is high. Once the disease occurs, it will not only affect the physical and mental health of women, but also affect the harmony of their families. Fallopian tube obstruction is the main factor causing infertility. In the past, X-ray hysterosalpingography was used to evaluate the patency of fallopian tube. In recent years, contrast-enhanced ultrasound technology has become more and more mature. It has the advantages of safety, accuracy, non-invasive, and reproducibility in evaluating fallopian tube patency, and is conducive to real-time observation of uterine cavity morphology, which has been widely used in the diagnosis and treatment of infertility. To evaluate the efficacy of Hysterosalpingo contrast sonography (Hysterosalpingo contrast sonography, hysterosalpingo contrast sonography, hysterosalpingo contrast sonography, hysterosalpingo contrast sonography, The improvement of adverse reactions such as pain caused by HyCoSy) in the diagnosis of infertility, and whether there are significant differences in the benefits brought by Hycosy compared with single moxa salt pack hot compress and conventional drugs for pain relief. This article reviews the research progress of Chinese and western medicine related to HyCoSy in the diagnosis of infertility in recent years, so as to provide some reference for clinicians.

Destruction of Narcotic Drugs and Psychotropic Substances as a Stage of Circulation of Medicines

Introduction. Destruction is one of the stages of the circulation of medicines. Special importance is attached to this stage in relation to drugs related to narcotic drugs and psychotropic substances. The activities of pharmacy and medical organizations in relation to the turnover of these funds are strictly regulated.Aim. The purpose of the study was to study the procedure for the destruction of narcotic drugs and psychotropic substances included in Lists II and III of the List, as a stage of the circulation of medicines, to identify trends in the appointment of individual drugs for pain relief based on the generalization of archival data of the commission on destruction established on the basis of the Perm State Pharmaceutical Academy.Materials and methods. Archival materials of the destruction commission for 2012–2021 were used in the execution of the work. Each archive folder for a certain month of the year included the following documents: an order for the commission on destruction and appendices, a set of documents and acts of destruction for each institution that provided medicines. Statistical and empirical methods were used, such as observation, description, study, generalization and grouping, comparison, proof.Results and discussion. Data on prescribing drugs to cancer patients and data on drugs submitted for destruction correlate. Therefore, the range and quantity of medicines transferred for destruction by medical institutions allows us to see trends in their appointment and use in medical practice.Conclusion. Optimization of activities related to the turnover of controlled substances can be ensured by building a clear algorithm of actions in a medical organization for each type of work and services specified in the license, including the type of work – destruction. The procedure for the destruction of narcotic and psychotropic drugs, which is accompanied by verification of accompanying documents and objects at the meetings of the commission, allows monitoring the use and accounting of drugs in medical institutions.

Sugar-free chewing gum versus conventional analgesic drugs for pain relief with fixed orthodontic appliances. A systematic review and meta-analysis.

To compare the effect of chewing sugar-free gum towards alleviating self-reported orthodontic treatment (OT) pain compared with conventional analgesic drugs (CADs). An unrestricted search of indexed databases and manual searching was performed up to September 2021. Randomised controlled trials (RCTs) comparing the impact of chewing gum and CADs on relieving self-reported orthodontic pain were included. Data screening, extraction and risk of bias (RoB) assessment were performed by two authors. Meta-analyses were performed using a random-effects model. The quality of available evidence was assessed using the Grades of Recommendation, Assessment, Development and Evaluation approach. Nine RCTs were included. Eight RCTs used the Visual Analogue Scale for self-reported pain assessment, while one RCT used the Numeric Rating Scale. Five RCTs had a high RoB and four RCTs had a moderate RoB. Power analysis for sample size estimation was performed in six RCTs. Separate meta-analyses were performed by pooling quantitative data from five RCTs that compared self-reported orthodontic pain between chewing gum and ibuprofen groups for the following timepoints: baseline; immediately; 2 hours; 6 hours; bedtime; 24 hours; 2 days; 3 days; 5 days; and 7 days after the placement of orthodontic appliances. None of the timepoints individually indicated a difference in self-reported pain scores between chewing sugar-free gum and ibuprofen groups. The overall level of evidence was very low. Chewing sugar-free gum is a potentially useful alternative to CADs towards pain alleviation during fixed OT.