Osteoarthritis Pain Research Articles

Lisfranc injuries

Lisfranc injuries are rare but severe injuries of the foot. They range from ligament sprain to complex fracture dislocations. Etiologically, adistinction is made between indirect and direct force and between high-energy and low-energy trauma. Inadequate diagnostics (injuries overlooked or misinterpreted) can lead to painful posttraumatic osteoarthritis, chronic instability and deformity of the foot. Afracture, malalignment and unclear findings in conventional radiological diagnostics necessitate computed tomography imaging including 3D reconstruction. Lisfranc injuries are often associated with accompanying pathologies of the foot that also need to be addressed. Only stable non-displaced fractures can be treated conservatively. Depending on the injury pattern, surgical treatment is performed percutaneously, minimally invasive or open. The prognosis following Lisfranc injury is determined by the severity of damage and the quality of reconstruction.

Closed-Loop Infraslow Brain-Computer Interface can Modulate Cortical Activity and Connectivity in Individuals With Chronic Painful Knee Osteoarthritis: A Secondary Analysis of a Randomized Placebo-Controlled Clinical Trial.

Introduction. Chronic pain is a percept due to an imbalance in the activity between sensory-discriminative, motivational-affective, and descending pain-inhibitory brain regions. Evidence suggests that electroencephalography (EEG) infraslow fluctuation neurofeedback (ISF-NF) training can improve clinical outcomes. It is unknown whether such training can induce EEG activity and functional connectivity (FC) changes. A secondary data analysis of a feasibility clinical trial was conducted to determine whether EEG ISF-NF training can significantly alter EEG activity and FC between the targeted cortical regions in people with chronic painful knee osteoarthritis (OA). Methods. A parallel, two-arm, double-blind, randomized, sham-controlled clinical trial was conducted. People with chronic knee pain associated with OA were randomized to receive sham NF training or source-localized ratio ISF-NF training protocol to down-train ISF bands at the somatosensory (SSC), dorsal anterior cingulate (dACC), and uptrain pregenual anterior cingulate cortices (pgACC). Resting state EEG was recorded at baseline and immediate post-training. Results. The source localization mapping demonstrated a reduction (P = .04) in the ISF band activity at the left dorsolateral prefrontal cortex (LdlPFC) in the active NF group. Region of interest analysis yielded significant differences for ISF (P = .008), slow (P = .007), beta (P = .043), and gamma (P = .012) band activities at LdlPFC, dACC, and bilateral SSC. The FC between pgACC and left SSC in the delta band was negatively correlated with pain bothersomeness in the ISF-NF group. Conclusion. The EEG ISF-NF training can modulate EEG activity and connectivity in individuals with chronic painful knee osteoarthritis, and the observed EEG changes correlate with clinical pain measures.

Association of physical activity trajectories over 8 years and risk of knee replacement: data from the osteoarthritis initiative

BackgroundTo identify physical activity (PA) trajectories in adults with or at risk of knee osteoarthritis and to evaluate the association of PA trajectories with incident knee replacement (KR).MethodsThis study used data from the Osteoarthritis Initiative. The Physical Activity Scale for the Elderly and the KR were assessed annually from baseline to 9 years. Individuals were included if they did not undergo KR surgery at baseline and had data on PA at ≥ 1 visit before KR. Latent class growth mixture Modeling was used to identify the optimal trajectories of PA before KR. Log-binomial regression models were used to assess the association between PA trajectories and the risk of KR. Data analyses were conducted in all individuals and those with radiographic osteoarthritis (ROA) and significant knee pain (Western Ontario and McMaster Osteoarthritis Index pain score of ≥ 5 on a 0–20 scale) at baseline, respectively.ResultsOf 4731 participants (mean age 61.1 years, 58.5% female), four distinct and slightly declined PA trajectories were identified. Compared to individuals with a “Low” PA trajectory, those with “Medium-low”, “Medium-high”, or “High” PA trajectories were not significantly associated with the risk of KR (risk ratios: 0.97–1.19, all p > 0.05). Similar PA trajectories and associations with the risk of KR were observed in the subgroups of individuals with radiographic osteoarthritis and those with significant knee pain at baseline, respectively.ConclusionIn participants with or at risk of knee osteoarthritis, PA slightly declines over time and may play no role in the risk of KR.

Increased nerve growth factor expression and osteoclast density are associated with subchondral bone marrow lesions in osteoarthritic knees

ObjectivesSubchondral bone marrow lesions (BMLs) detected on magnetic resonance imaging in knee osteoarthritis (OA) are associated with knee pain, though the mechanisms remain unknown. Increased nerve growth factor (NGF) expression and osteoclast density in subchondral bone appear to be the key features associated with bone pain in knee OA. Therefore, we aimed to identify associations among NGF, osteoclasts, and BMLs in knee OA. MethodsTwenty tibial plateaus were obtained from patients undergoing total knee arthroplasty for medial knee OA with BMLs at the medial tibial plateau (MTP). Osteochondral tissue samples from the weight-bearing part of the MTP, with and without BML, and from the weight-bearing part of the lateral tibial plateau (LTP), without BML, were collected. NGF expression and density of osteoclasts were compared among the three osteochondral tissue types. ResultsMTP bone with BMLs exhibited significantly higher NGF expression in bone marrow space and osteochondral channel, and higher osteoclast density than MTP bone without BML and LTP bone. The mean differences in NGF-positive area in the bone marrow space and the percentage of NGF-positive channels between MTP bones with and without BML were 9.0% (95% confidence interval [CI]: 5.9–12.1%) and 23.1% (95% CI: 11.3–35.0%), respectively. The difference in osteoclast density between MTP bones with and without BML was 0.6 osteoclasts per mm (95% CI: 0.3–0.9 osteoclasts per mm). ConclusionsIncreased NGF expression and osteoclast density are associated with subchondral BMLs in knee OA, contribute to understanding the mechanisms underlying BML-related bone pain in knee OA.

Knee Joint Neural Sources and Pathways and Their Osteoarthritis Pathogenic Linkages and Pain Control Implications

Knee Joint Neural Sources and Pathways and Their Osteoarthritis Pathogenic Linkages and Pain Control Implications

Aspects of the use of modern injection disease-modifying therapy in real clinical practice in patients with osteoarthritis and (or) back pain

The results of a study on the effectiveness of the injectable chondroprotector Ambene® Bio in the treatment of patients with degenerative-dystrophic diseases of the spine and pain in the lower back are presented. The program involved 30 patients diagnosed with osteoarthritis and/ or spondyloarthritis, facet syndrome, osteochondrosis in the acute stage (severe symptoms: pain according to VAS 40–90 mm). All patients were prescribed the chondroprotector Ambene® Bio in the regimen of 2 ml every other day No. 10.Results. During treatment with the injectable chondroprotector Ambene® Bio for 20 days, it was possible to significantly reduce the manifestations of the target nosologies, restore the ability to move and self-care, improve the psycho-emotional state of patients, while reducing the need for NSAIDs.Conclusions. A short course of therapy with Ambene® Bio contributed to the effective treatment of study participants due to the synergism of the unique composition of biologically active substances. The study demonstrated a high safety profile and good tolerability of the therapy.

Gut Microbiome and Osteoarthritis: Insights From the Naturally Occurring Canine Model of Osteoarthritis.

The purpose of this study was to enhance the current knowledge of the relationship between the gut microbiome and osteoarthritis (OA) and associated pain using pet dogs as a clinically relevant translational model. Fecal samples were collected from 93 owned pet dogs. Dogs were designated as either clinically healthy or OA pain using validated methods. Metagenomic profiling was performed through shotgun sequencing using the Illumina NovaSeq platform. MetaPhlAn2 and HUMAnN2 were used to evaluate bacterial taxonomic and pathway relative abundance. Comparisons between healthy and OA-pain groups were performed individually for each taxa using nonparametric tests following Benjamini and Hochberg adjustment for multiple comparisons. Permutation analysis of variance was performed using Bray-Curtis distance matrices. All downstream analyses were completed in R. No significant differences between healthy and OA-pain dogs were observed for alpha and beta diversity. We found 13 taxa with nominally significant (P < 0.05) associations with OA case status, but none of the associations remained significant after adjustment for multiple comparisons. No differences in alpha or beta diversities or the Firmicutes to Bacteroidetes ratio were found regarding pain severity, mobility or activity level, age, or body composition score. Similar to recent studies in humans, the present study did not demonstrate a significant difference in the fecal microbial communities between dogs with OA pain and healthy control dogs. Future research in this naturally occurring model should expand on these data and relate the gut microbiome to gut permeability and circulating proinflammatory and anti-inflammatory molecules to better understand the influence of the gut microbiome on OA and OA pain.

Penerapan Kompres Rebusan Jahe Terhadap Penurunan Skala Nyeri Pada Lansia Osteoarthritis di Kelurahan Jebres

Background : Based on the WHO suevey around 529 million people around the world suffer from osteoartgritis. In Indonesia people who ferment arthritis disease numer 181,556. Osteoarthritis is a chronic, progressive joint disorder that typically occurs in middle to old age with reference to cartilage damage located in bone joints. In osteoarthritis a deterioration of the caetilage tissue in the joint region will result in pain and rigidity that lead to motion impairment. Non pharmalogical therapy is recommended with steaming giner stew. Objective The ginger stew therapy is for lowering the scale of pain in oldet osteoarthritis. Method : The research used was a descriptive study using case study methods. The subject pf the board’s diagnosis is two osteoarthritis respondens. Result : A case dtudy has shown that there has been a decline in the scare of pain in older osteoarthritis. Conclusion : The progression of the scales of pain before and after application of the ginger stew made 2 respondents had a decrease I the scale of the pain with a 2-3 scale

Application of the IASP Grading System to Identify Underlying Pain Mechanisms in Patients With Knee Osteoarthritis: A Prospective Cohort Study.

This study aimed to apply the International Association for the Study of Pain (IASP) grading system for identifying nociplastic pain in knee osteoarthritis (KOA) awaiting total knee arthroplasty (TKA) and propose criteria to fine-tune decision-making. In addition, the study aimed to characterize a "probable" versus "no or possible" nociplastic pain mechanism using biopsychosocial variables and compare both groups in their 1-year post-TKA response. A secondary analysis of baseline data of a longitudinal prospective study involving 197 patients with KOA awaiting total TKA in Belgium and the Netherlands was performed. Two approaches, one considering 4 and the other 3 pain locations (step 2 of the grading system), were presented. Linear mixed model analyses were performed to compare the probable and no or possible nociplastic pain mechanism groups for several preoperative biopsychosocial-related variables and 1-year postoperative pain. Also, a sensitivity analysis, comparing 3 pain mechanism groups, was performed. Thirty (15.22%-approach 4 pain locations) and 46 (23.35%-approach 3 pain locations) participants were categorized under probable nociplastic pain. Irrespective of the pain location approach or sensitivity analysis, the probable nociplastic pain group included more woman, was younger, exhibited worse results on various preoperative pain-related and psychological variables, and had more pain 1-year post-TKA compared with the other group. This study proposed additional criteria to fine-tune the grading system for nociplastic pain (except for discrete/regional/multifocal/widespread pain) and characterized a subgroup of patients with KOA with probable nociplastic pain. Future research is warranted for further validation.

Disease-modifying rdHSV-CA8* non-opioid analgesic gene therapy treats chronic osteoarthritis pain by activating Kv7 voltage-gated potassium channels.

Chronic pain is common in our population, and most of these patients are inadequately treated, making the development of safer analgesics a high priority. Knee osteoarthritis (OA) is a primary cause of chronic pain and disability worldwide, and lower extremity OA is a major contributor to loss of quality-adjusted life-years. In this study we tested the hypothesis that a novel JDNI8 replication-defective herpes simplex-1 viral vector (rdHSV) incorporating a modified carbonic anhydrase-8 transgene (CA8*) produces analgesia and treats monoiodoacetate-induced (MIA) chronic knee pain due to OA. We observed transduction of lumbar DRG sensory neurons with these viral constructs (vHCA8*) (~40% of advillin-positive cells and ~ 50% of TrkA-positive cells colocalized with V5-positive cells) using the intra-articular (IA) knee joint (KJ) route of administration. vHCA8* inhibited chronic mechanical OA knee pain induced by MIA was dose- and time-dependent. Mechanical thresholds returned to Baseline by D17 after IA KJ vHCA8* treatment, and exceeded Baseline (analgesia) through D65, whereas negative controls failed to reach Baseline responses. Weight-bearing and automated voluntary wheel running were improved by vHCA8*, but not negative controls. Kv7 voltage-gated potassium channel-specific inhibitor XE-991 reversed vHCA8*-induced analgesia. Using IHC, IA KJ of vHCA8* activated DRG Kv7 channels via dephosphorylation, but negative controls failed to impact Kv7 channels. XE-991 stimulated Kv7.2-7.5 and Kv7.3 phosphorylation using western blotting of differentiated SH-SY5Y cells, which was inhibited by vHCA8* but not by negative controls. The observed prolonged dose-dependent therapeutic effects of IA KJ administration of vHCA8* on MIA-induced chronic KJ pain due to OA is consistent with the specific activation of Kv7 channels in small DRG sensory neurons. Together, these data demonstrate for the first-time local IA KJ administration of vHCA8* produces opioid-independent analgesia in this MIA-induced OA chronic pain model, supporting further therapeutic development.

Intra-articular sprouting of nociceptors accompanies progressive osteoarthritis: comparative evidence in four murine models.

Knee joints are densely innervated by nociceptors. In human knees and rodent models, sprouting of nociceptors has been reported in late-stage osteoarthritis (OA). Here, we sought to describe progressive nociceptor remodeling in early and late-stage OA, using four distinct experimental mouse models. Sham surgery, destabilization of the medial meniscus (DMM), partial meniscectomy (PMX), or non-invasive anterior cruciate ligament rupture (ACLR) was performed in the right knee of 10-12-week old male C57BL/6 NaV1.8-tdTomato mice. Mice were euthanized (1) 4, 8 or 16 weeks after DMM or sham surgery; (2) 4 or 12 weeks after PMX or sham; (3) 1 or 4 weeks after ACLR injury or sham. Additionally, a cohort of naïve male wildtype mice was evaluated at age 6 and 24 months. Mid-joint cryosections were assessed qualitatively and quantitatively for NaV1.8+ or PGP9.5+ innervation. Cartilage damage, synovitis, and osteophytes were assessed. Progressive OA developed in the medial compartment after DMM, PMX, and ACLR. Synovitis and associated neo-innervation of the synovium by nociceptors peaked in early-stage OA. In the subchondral bone, channels containing sprouting nociceptors appeared early, and progressed with worsening joint damage. Two-year old mice developed primary OA in the medial and the lateral compartment, accompanied by nociceptor sprouting in the synovium and the subchondral bone. All four models showed increased nerve signal in osteophytes. These findings suggest that anatomical neuroplasticity of nociceptors is intrinsic to OA pathology. The detailed description of innervation of the OA joint and its relationship to joint damage might help in understanding OA pain.

The Effect of Probiotics on the Management of Pain and Inflammation in Osteoarthritis: A Systematic Review and Meta-Analysis of Clinical Studies.

Osteoarthritis (OA) is one of the most common musculoskeletal disorders. Recently, research has focused on the role of intestinal microbiome dysbiosis in OA. The aim of this study was to systematically review randomized intervention clinical studies investigating the effect of probiotics on the management of OA-related pain and inflammation. Pre-clinical studies and non-randomized trials were excluded. A literature search was conducted using MEDLINE, EMBASE, and Web of Science. Study quality was assessed with the Cochrane risk of bias (RoB2) tool and the Risk of Bias in N-of-1 Trials (RoBiNT) scale. RevMan was used for the meta-analysis. Outcome measures assessed self-reported pain, stiffness and impediment, and serum hs-CRP. Three studies, with 501 participants, were considered eligible for qualitative synthesis and meta-analysis. A significant reduction in symptoms across all outcomes measured, except stiffness, was evident with Lactobacillus casei Shirota. However, all other probiotics reviewed did not seem to have any effect on the measured outcomes. Pre-clinical evidence, along with the RCTs reviewed, suggests that probiotics of the Lactobacillus strains might be of use for managing pain and inflammation in OA. Considering the small number of studies included in the present review and the possible risk of bias, we conclude that further studies on the role of probiotics in humans with OA are warranted.

Blood pressure is associated with knee pain severity in middle-aged and elderly individuals with or at risks for osteoarthritis: data from the Osteoarthritis Initiative

BackgroundHypertension is a common comorbidity of osteoarthritis (OA). Joint pain is the main clinical manifestation of OA. Knowledge about the relationship between hypertension and OA pain is limited. This study aimed to investigate whether blood pressure parameters are associated with knee pain severity in individuals with or at risks for OA.MethodsOur sample consisted of 2598 subjects (60.7% female, aged 45–79 years) collected from the Osteoarthritis Initiative. Blood pressure parameters included blood pressure stage, systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure (PP). Radiographic evaluation using Kellgren-Lawrence system and pain severity evaluation using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Knee Injury and Osteoarthritis Outcome Score (KOOS), and Numeric Rating Scale (NRS) were performed for right knee. Linear regression was used to examine the relationship between blood pressure parameters and knee pain severity.ResultsFor the overall sample, blood pressure stage, SBP, and PP were positively correlated with WOMAC and NRS pain scores when adjusting for age, sex, and body mass index (BMI) (p ≤ 0.024) and were inversely correlated with KOOS score (p ≤ 0.004). After further adjusting for all covariates, PP remained a positive correlation with WOMAC score (p = 0.037) while other associations between blood pressure parameters and pain scores did not reach the statistical significance. In female, higher blood pressure stage, SBP, and PP were significantly associated with increased WOMAC and NRS scores and decreased KOOS score after adjustments of age and BMI (p ≤ 0.018). When adjusting for all covariates, the correlations of PP with WOMAC, KOOS and NRS scores remained significant (p = 0.008–0.049). In male sample, SBP was positively correlated with WOMAC score when adjusting for age and BMI (p = 0.050), but other associations between blood pressure parameters and pain scores were not statistically significant. No significant correlation was observed in male when further adjusting for other covariates.ConclusionsIncreased PP is a risk factor for knee pain and mainly affects females, which suggested that controlling PP may be beneficial in preventing or reducing knee pain in females with or at risks for OA.

Effectiveness of Platelet Rich Plasma Injection in Comparison with Dextrose Prolotherapy on Improving Pain and Function in Osteoarthritis of Knee: A Randomized Controlled Trial

Effectiveness of Platelet Rich Plasma Injection in Comparison with Dextrose Prolotherapy on Improving Pain and Function in Osteoarthritis of Knee: A Randomized Controlled Trial

First site-specific conjugation method for native goat IgG antibodies via glycan remodeling at the conserved Fc region.

Despite their triumph in treating human diseases, antibody therapies for animals have gained momentum more slowly. However, the first approvals of animal antibodies for osteoarthritic pain in cats and dogs may herald the dawn of a new era. For example, goats are vital to economies around the world for their milk, meat, and hide products. It is therefore imperative to develop therapies to safeguard goats-with antibodies at the forefront. Goat antibodies will be crucial in the development of therapeutic antibodies, for example, as tracers to study antibody distribution in vivo, reagents to develop other therapeutic antibodies, and therapeutic agents themselves (e.g., antibody-drug conjugates). Hamstringing this effort is a still-burgeoning understanding of goat antibodies and their derivatization. Historically, goat antibody conjugates were generated through stochastic chemical modifications, producing numerous attachment sites and modification ratios, thereby deleteriously impacting antigen binding. Site-specific methods exist but often require substantial engineering and have not been demonstrated with goat antibodies. Nevertheless, we present herein a novel method to site-specifically conjugate native goat antibodies: chemo-enzymatic remodeling of the native Fc N-glycan introduces a reactive azide handle, after which click chemistry with strained alkyne partners affords homogeneous conjugates labeled only on the Fc domain. This process is robust, and resulting conjugates retain their antigen binding and specificity. To our knowledge, our report is the first for site-specific conjugation of native goat antibodies. Furthermore, our approach should be applicable to other animal antibodies-even with limited structural information-with similar success.

Dual effects of dulaglutide on glycemic control and knee osteoarthritis pain in elderly patients with Type 2 diabetes.

Aim: This study aims to evaluate the dual benefits of dulaglutide in improving glycemic control and reducing knee OA pain.Patients & methods: Elderly T2DM patients diagnosed with bilateral knee OA on conventional OA treatment for at least 3 months were studied for their glycemic metrics, OA pain scores and NSAID consumption at baseline, 3 months and 6 months.Results: Significant improvements in glycemic control were observed, HbA1c decreased from 8.7% to 6.5% over 6 months. Pain scores, NSAID, body weight and BMI showed substantial reductions over time. Positive correlation (r=0.73, p<0.001) was found between glycemic control and pain reduction.Conclusion: Dulaglutide improves glycemic control, knee joint OA pain and weight management in elderly patients with T2DM.

Association between synovial tissue damage and pain in late-stage knee osteoarthritis: A cross-sectional study

ObjectiveTo identify the presence and distribution of histopathological features of synovial inflammation and tissue damage, and to test their associations with US imaging measures of synovitis and patient-reported measures of pain in knee osteoarthritis (OA). DesignIn the cross-sectional study of 122 patients undergoing surgery for painful late-stage (Kellgren-Lawrence Grade 3 or 4) knee OA, we compared ultrasound (US) measures of synovitis (n=118) and pain (Knee Injury and Osteoarthritis Outcome Score) to histopathological measures of inflammation vs. synovial tissue damage in synovial tissue biopsies. Associations of histopathological features with US measures of inflammation or pain were assessed using linear or logistic regression, while controlling for covariates. ResultsHistopathological features of inflammation were associated with higher odds of moderate/severe US synovitis (OR=1.34 [95%CI 1.04, 1.74), whereas features of synovial tissue damage were associated with lower odds of moderate/severe US synovitis (OR = 0.77 [95%CI 0.57, 1.03]). Worse histopathological scores for synovial tissue damage were associated with more pain (-1.47 [95%CI -2.88, -0.05]), even while adjusting for synovial inflammation (-1.61 [95%CI -3.12, -0.10]). ConclusionsSynovial tissue damage is associated with pain in late-stage knee OA, independent from inflammation and radiographic damage. These novel findings suggest that preventing synovial tissue damage may be an important goal of disease-modifying OA therapy.

Interventions to Improve Long-Term Adherence to Physical Rehabilitation: A Systematic Review.

To evaluate the impact of physical rehabilitation interventions, supplemented with one or more adherence-enhancing components, on outcomes among adults with hip or knee osteoarthritis or chronic lower back pain. Primary literature search from inception of each database to July 27, 2021, guided by relevant search terms and keywords to search titles and abstracts. All articles meeting eligibility criteria were included for data abstraction. MEDLINE, CINAHL Complete, and Embase. Randomized and nonrandomized trials evaluating adherence-focused intervention components conducted in addition to an index usual care or usual care-like physical rehabilitation program among adults with hip or knee osteoarthritis or chronic low back pain. Eligible studies included a comparator group of the same index physical rehabilitation intervention without the adjunctive adherence components. Included studies measured outcomes at least 3 months after the rehabilitation course. Of the 10 studies meeting inclusion criteria, 6 interventions were delivered concurrent to an index rehabilitation program and 4 were delivered sequentially. Of the 3 studies that reported a positive effect on long-term adherence, only 1 was a low risk of bias study. There is very limited evidence of a beneficial treatment effect of adjunct adherence interventions on long-term physical function, self-efficacy, or adverse events. We found inadequate evidence evaluating adherence-enhancing interventions for the specific promotion of long-term adherence to home rehabilitation programs. Future studies should consider testing interventions specifically built to target behavioral maintenance of home rehabilitation programs.

Evaluation of the effect of low-intensity pulsed ultrasound in pain and dysfunction for knee osteoarthritis: a double-blind, randomised controlled trial protocol

IntroductionOsteoarthritis (OA) is the most common joint disorder among musculoskeletal conditions. Non-surgical treatment is the standard therapy for knee OA (KOA). Ultrasound therapy is recommended for alleviating pain and dysfunction...

The State of Synthetic Cannabinoid Medications for the Treatment of Pain.

Synthetic cannabinoids are compounds made in the laboratory to structurally and functionally mimic phytocannabinoids from the Cannabis sativa L. plant, including delta-9-tetrahydrocannabinol (THC). Synthetic cannabinoids (SCs) can signal via the classical endogenous cannabinoid system (ECS) and the greater endocannabidiome network, highlighting their signalling complexity and far-reaching effects. Dronabinol and nabilone, which mimic THC signalling, have been approved by the Food and Drug Administration (FDA) for treating nausea associated with cancer chemotherapy and/or acquired immunodeficiency syndrome (AIDS). However, there is ongoing interest in these two drugs as potential analgesics for a variety of otherclinical conditions, including neuropathic pain, spasticity-related pain, andnociplastic pain syndromes including fibromyalgia, osteoarthritis, and postoperative pain, among others. In this review, we highlight the signalling mechanisms of FDA-approved synthetic cannabinoids, discuss key clinical trials that investigate their analgesic potential, and illustrate challenges faced when bringing synthetic cannabinoids to the clinic.