Search Results (233)

Background: Pain is a complex phenomenon characterized by unpleasant experiences with profound heterogeneity influenced by biological, psychological, and social factors. According to the National Health Interview Survey, 50.2 million U.S. adults (20.5%) experience pain on most days, with the annual cost of prescription medication for pain reaching approximately USD 17.8 billion. Theranostic pain nanomedicine therefore emerges as an attractive analgesic strategy with the potential for increased efficacy, reduced side-effects, and treatment personalization. Theranostic nanomedicine combines drug delivery and diagnostic features, allowing for real-time monitoring of analgesic efficacy in vivo using molecular imaging. However, clinical translation of these nanomedicines are challenging due to complex manufacturing methodologies, lack of standardized quality control, and potentially high costs. Quality by Design (QbD) can navigate these challenges and lead to the development of an optimal pain nanomedicine. Our lab previously reported a macrophage-targeted perfluorocarbon nanoemulsion (PFC NE) that demonstrated analgesic efficacy across multiple rodent pain models in both sexes. Here, we report PFC-free, biphasic nanoemulsions formulated with a biocompatible and non-immunogenic plant-based coconut oil loaded with a COX-2 inhibitor and a clinical-grade, indocyanine green (ICG) near-infrared fluorescent (NIRF) dye for parenteral theranostic analgesic nanomedicine. Methods: Critical process parameters and material attributes were identified through the FMECA (Failure, Modes, Effects, and Criticality Analysis) method and optimized using a 3 × 2 full-factorial design of experiments. We investigated the impact of the oil-to-surfactant ratio (w/w) with three different surfactant systems on the colloidal properties of NE. Small-scale (100 mL) batches were manufactured using sonication and microfluidization, and the final formulation was scaled up to 500 mL with microfluidization. The colloidal stability of NE was assessed using dynamic light scattering (DLS) and drug quantification was conducted through reverse-phase HPLC. An in vitro drug release study was conducted using the dialysis bag method, accompanied by HPLC quantification. The formulation was further evaluated for cell viability, cellular uptake, and COX-2 inhibition in the RAW 264.7 macrophage cell line. Results: Nanoemulsion droplet size increased with a higher oil-to-surfactant ratio (w/w) but was no significant impact by the type of surfactant system used. Thermal cycling and serum stability studies confirmed NE colloidal stability upon exposure to high and low temperatures and biological fluids. We also demonstrated the necessity of a solubilizer for long-term fluorescence stability of ICG. The nanoemulsion showed no cellular toxicity and effectively inhibited PGE2 in activated macrophages. Conclusions: To our knowledge, this is the first instance of a celecoxib-loaded theranostic platform developed using a plant-derived hydrocarbon oil, applying the QbD approach that demonstrated COX-2 inhibition. Full article

Background and Objectives: Implantation of cardiac implantable electronic devices (CIEDs) is increasingly performed in elderly and comorbid patients, for whom minimizing perioperative complications—including pain and systemic drug use—is critical. Traditional local infiltration often provides insufficient analgesia. The ultrasound-guided PECS II block, an interfascial regional technique, offers promising analgesic benefits in thoracic wall procedures but remains underutilized in cardiac electrophysiology. Materials and Methods: We conducted a prospective, controlled, non-randomized clinical study including 106 patients undergoing de novo CIED implantation. Patients were assigned to receive either a PECS II block (n = 53) or standard lidocaine-based local anesthesia (n = 53). Pain intensity was assessed using the numeric rating scale (NRS) intraoperatively and at 1, 6, and 12 h postoperatively. Secondary outcomes included the need for rescue analgesia, procedural duration, length of hospitalization, and patient satisfaction. Results: Patients in the PECS II group reported significantly lower NRS scores at all time points (mean intraoperative score: 2.1 ± 1.2 vs. 5.7 ± 1.6, p < 0.001; at 1 h: 2.5 ± 1.5 vs. 6.1 ± 1.7, p < 0.001). Rescue analgesia (metamizole sodium) was required in only four PECS II patients (7.5%) vs. 100% in the control group within 1 h. Hospital stay and procedural time were also modestly reduced in the PECS II group. Patient satisfaction scores were significantly higher in the intervention group. Conclusions: The ultrasound-guided PECS II block significantly reduces perioperative pain and the need for additional analgesia during CIED implantation, offering an effective, safe, and opioid-sparing alternative to conventional local infiltration. Its integration into clinical protocols for device implantation may enhance procedural comfort and recovery. Full article

Background: Few studies have examined exercise-based treatments for migraine and tension-type headache (TTH), and even fewer have focused on strength training and chronic headache, as these present greater challenges. Objectives: This study aimed to evaluate the effectiveness of a group-based neck and shoulder strength training intervention combined with postural correction for patients with chronic headache. Methods: This prospective, single-arm, uncontrolled pilot study with a pre–post design included patients with chronic migraine (n = 10) and TTH (n = 12) who participated in an 8-week group-based program consisting of neck and shoulder strength training three times per week, along with instructions for postural correction. The primary outcome was change in headache frequency. Secondary outcomes included changes in the intensity and duration of headache, number of days of analgesic use, and functionality. Results: In total, 22 patients completed the intervention and were included in the analysis. Headache frequency decreased at follow-up for the overall group (r = 0.531; p = 0.014). In-depth analysis showed that 45% of participants experienced an average reduction of 38% in headache frequency. Additionally, large to moderate effect sizes were observed for the secondary outcomes. Conclusions: This is the first study to introduce a group-based exercise program targeting the neck and shoulder muscles, combined with postural correction and standard pharmacological treatment, for patients with chronic primary headache. It was found to be a safe, well-tolerated, useful, and promising intervention for improving headache frequency, duration, and functionality. Full article

Background: Uvulopalatopharyngoplasty (UPPP) and expansion sphincter pharyngoplasty (ESP) are two standard surgical procedures for the treatment of snoring and obstructive sleep apnea. In a retrospective clinical trial, we compared the two surgical techniques regarding objective sleep parameters and patients’ reported outcomes. Materials and Methods: Patients treated with UPPP or ESP between January 2016 and February 2020 were included in this retrospective clinical trial. Pre- and postoperative AHI, BMI, and smoking habits were recorded. Subjective improvement was assessed by the ESS score and symptom relief reported by patients and their bed partners. Results: Between 2016 and 2020, 114 patients were included in the study, 74 patients suffered from OSA, and 30 patients had non-apnoeic snoring (AHI < 5/h). No preoperative sleeping studies were available in 10 patients (10/114; 9%). Based on the findings during drug-induced sedation endoscopy, most patients received an ESP (71/114, 62%), and 43 patients received a UPPP (43/114, 38%). Additionally, in 52/114 (46%), radio frequency ablation of the tongue base was performed if DISE revealed retrolingual collapse. ESP reduced AHI from 21.1 ± 10.8/h to 13.3 ± 12.1/h (p = 0.04), whereas UPPP caused a non-significant decrease in the AHI from 25.0 ± 13.8/h to 18.2 ± 14.6/h (p = 0.6). A minor secondary bleeding was observed in 32 patients, which was effectively treated with electrocautery or conservative therapy (32/114). This was more common in the ESP group (22/71; 31%) than in the UPPP group (10/43; 23%). Postoperative need for analgesics was higher in the ESP group than in the UPPP group. The ESS score showed no significant improvement after UPPP or ESP (p = 0.3), but subjective improvement in snoring was reported by 87/114 (76%) patients. Conclusion: AHI reduction was significantly higher in the ESP patient group than in the UPPP group. ESP patients had a slightly higher rate of minor secondary bleeding and postoperative need for analgesics than UPPP patients. Full article

Cannabis sativa L. is a phytochemically rich plant with therapeutic potential across various clinical domains, including pain, inflammation, and neurological disorders. Among its constituents, terpenes are gaining recognition for their capacity to modulate the pathophysiological processes underlying chronic pain syndromes. Traditionally valued for their aromatic qualities, terpenes such as myrcene, β-caryophyllene (BCP), limonene, pinene, linalool, and humulene have demonstrated a broad spectrum of biological activities. Beyond their observable analgesic, anti-inflammatory, and anxiolytic outcomes, these compounds exert their actions through distinct molecular mechanisms. These include the activation of cannabinoid receptor type 2 (CB₂), the modulation of transient receptor potential (TRP) and adenosine receptors, and the inhibition of pro-inflammatory signalling pathways such as Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Cyclooxygenase-2 (COX-2). This narrative review synthesizes the current preclinical and emerging clinical data on terpene-mediated analgesia, highlighting both monoterpenes and sesquiterpenes, and discusses their potential for synergistic interaction with cannabinoids, the so-called entourage effect. Although preclinical findings are promising, clinical translation is limited by methodological variability, the lack of standardized formulations, and insufficient pharmacokinetic characterization. Further human studies are essential to clarify their therapeutic potential. Full article

Background: Ginger contains gingerols, shagaols, paradols, gingerdiones, and terpenes, which have been shown to display anti-inflammatory properties and inhibit pain receptors. For this reason, ginger has been marketed as a natural analgesic. This study examined whether a specialized ginger extract obtained through supercritical CO₂ extraction and subsequent fermentation affects pain perception, functional capacity, and markers of inflammation. Methods: Thirty men and women (56.0 ± 9.0 years, 164.4 ± 14 cm, 86.5 ± 20.9 kg, 31.0 ± 7.5 kg/m²) with a history of mild to severe joint and muscle pain as well as inflammation participated in a placebo-controlled, randomized, parallel-arm study. Participants donated fasting blood, completed questionnaires, rated pain in the thighs to standardized pressure, and then completed squats/deep knee bends, while holding 30% of body mass, for 3 sets of 10 repetitions on days 0, 30, and 56 of supplementation. Participants repeated tests after 2 days of recovery following each testing session. Participants were matched by demographics and randomized to ingest 125 mg/d of a placebo or ginger (standardized to contain 10% total gingerols and no more than 3% total shogaols) for 58 days. Data were analyzed by a general linear model (GLM) analysis of variance with repeated measures, mean changes from the baseline with 95% confidence intervals, and chi-squared analysis. Results: There was evidence that ginger supplementation attenuated perceptions of muscle pain in the vastus medialis; improved ratings of pain, stiffness, and functional capacity; and affected several inflammatory markers (e.g., IL-6, INF-ϒ, TNF-α, and C-Reactive Protein concentrations), particularly following two days of recovery from resistance exercise. There was also evidence that ginger supplementation increased eosinophils and was associated with less frequent but not significantly different use of over-the-counter analgesics. Conclusions: Ginger supplementation (125 mg/d, providing 12.5 mg/d of gingerols) appears to have some favorable effects on perceptions of pain, functional capacity, and inflammatory markers in men and women experiencing mild to moderate muscle and joint pain. Registered clinical trial #ISRCTN74292348. Full article

Background/Objectives: Greater occipital nerve blockade (GONB) is a minimally invasive intervention used to treat primary headaches. However, the evidence regarding its role in craniofacial pain syndromes and its potential impact on analgesic use remains limited. Previous studies have reported that GONB is an effective method in patients with cranial neuralgia, but its efficacy is limited in persistent idiopathic facial pain (PIFP). Methods: This study was a retrospective cohort trial examining the medical records of 26 patients who applied to our Headache Clinic due to facial pain and cranial neuralgia between April 2023 and April 2025. Of these patients, 12 were trigeminal neuralgia (46%), 6 were occipital neuralgia (23%), 4 were trigeminal neuropathic pain (15%), and 4 were PIFP (15%) patients. In our study, the landmark-based GONB technique was used to determine the greatest tenderness to palpation (TTP) area. A standard 2.5 mL mixture of 30 mg 2% lidocaine and 4 mg dexamethasone was injected bilaterally as a single dose into the nerve region of all patients. After GONB, all patients were routinely contacted by phone or addressed face to face once a week for the first month and monthly thereafter, and medical changes were recorded with a standard-case follow-up form file. The case follow-up form allowed regular monitoring of parameters, such as the Visual Analog Scale (VAS), self-assessment scales for patients’ clinical responses, sensitivity to triggers, possible side effects, duration of effect, and the number of analgesics used. Results: A positive response with at least 50% overall improvement compared to the patient’s baseline level was found in 22 of 26 patients. Response to treatment was observed in 10 patients in the trigeminal neuralgia group (83%), 3 patients in the trigeminal neuropathic pain (75%) and PIFP groups (75%), and all in the occipital neuralgia group (100%). There was no statistically significant difference in response rates between the diagnostic groups. A significant difference was found in terms of response rates according to gender (p = 0.022). Accordingly, while response was observed in all 15 female patients, response was observed in 7 of 11 male patients (64%). Pre-GONB VAS values of those responding to treatment were found to be higher. Patients with positive responses to GONB had a significantly higher median value of the VAS total score (5; 95% CI: 1.83–4.52) in comparison to those with negative responses (8.32; 95% CI: 8.17–12.12) (p < 0.001). Post-GONB Intensity (VAS) and Post-GONB sensitivity to triggers decreased significantly (p < 0.001, p < 0.001). In those who responded, the decrease in analgesic use after GONB compared to before was statistically significant in the first and second months (p < 0.001, p < 0.003, respectively). Although the decrease continued in the third month, this difference did not reach statistical significance (p = 0.551). Conclusions: GONB reduces the duration, frequency, and intensity of headaches, and the need for acute analgesic use in CN and PIFP patients. Full article

Background/Objectives: Sternal pain after cardiac surgery results in considerable discomfort and may contribute to the development of chronic postoperative sternal pain syndrome. Parasternal intercostal plane blocks have been shown to improve postoperative sternal pain and can be an essential part of enhanced recovery after cardiac surgery (ERACS). This cohort study evaluated the postoperative impact of a single-shot deep parasternal intercostal plane block (PIPB) on the requirement of analgesic medication and pain sensation up to 48 h. Methods: This retrospective single-center analysis evaluates the postoperative acute pain in 157 patients undergoing off-pump coronary artery bypass (OPCAB) with median sternotomy. The additive analgesic effects of deep PIPB (38 patients) were compared to a group with standard therapy but without PIPB (119 patients). To strengthen the findings, a propensity score matching analysis was performed. Outcomes included the consumption of emergency pain agents (piritramide), the requirement of the total morphine equivalent (ME), time to extubation, and ICU length of stay. Furthermore, we examined pain sensation with evaluation by using the behavioral pain score (BPS) and numeric rating score (NRS) up to 48 h after extubation. Results: The deep PIPB reduced the piritramide administration 24 h and 48 h after OPCAB surgery. Moreover, the requirement of ME was 24 h and 48 h after bypass surgery also significantly decreased. The one-to-one propensity score matching confirmed our primary findings and showed a decreased requirement for intravenous agents. Additionally, we observed a reduced time for extubation and a decreased NRS rating. However, no significant changes were observed in ICU length of stay, incidence of nausea, and vomiting. Conclusions: Our data suggests that an ultrasound-guided single-shot deep PIPB can be a valuable tool for a multimodal analgesic protocol on patients undergoing OPCAB surgery. Full article

Cichorium intybus L. (common chicory) is a medicinal plant valued for health-promoting effects. Although analgesic properties are known for chicory sesquiterpenes, the effects of extracts need yet to be explored. This study aimed to evaluate for the first time the analgesic effect (against nociceptive pain) of the root extract from C. intybus var. foliosum. The target evaluation was preceded by toxicity tests in vivo and phytochemical standardization of root extracts prepared with different extraction methods—pectinase-assisted, pressure-assisted, and a combination of both—to choose the most effective one. The phytochemical profiling involved UHPLC-PDA-ESI-MS/MS and UHPLC-PDA analyses. The toxicity and the analgesic effects were tested in mice following the OECD 423 guideline and the hot-plate test, respectively. The highest recovery of bioactive compounds was achieved for the pressure-assisted extract: 642.5 mg sesquiterpene lactones, 187.1 mg phenolic acids, and 47.3 g inulin/100 g of dry matter. The extract showed no toxic effects at the oral dose of 2000 mg/kg body weight, including no histopathologic changes, in mice within two weeks (GHS Category 5/Uncategorized). The maximum analgesic effect (MAE) of the extract at 600 mg/kg was 6.75% for rearing and 13.7% for jumping, with the impact on the nocifensive reactions not differing significantly from those of paracetamol at 60 mg/kg. Despite the relatively low effects at 600 mg/kg, the verified safety and abundance of active compounds encourage further studies on the extract and its active fractions as potential approaches to complementary pain therapy, with special concern for their mechanisms of action. Full article

Background: CDK4/6 inhibitor plus ET is a standard treatment for advanced HR+ BC. This study evaluates the efficacy and safety of CDK4/6 inhibitors with concurrent RT (SBRT and non-SBRT) in terms of pain, analgesic therapy changes, toxicities, and net clinical benefit (NCB). Methods: BC patients with bone metastases treated with RT and CDK4/6 inhibitor in the prospective observational COMBART study were analyzed. Pain was measured with the NRS. The NCB was defined by pain reduction (NRS), toxicity, and treatment changes. Adverse events (AEs) were graded per CTCAE v5.0. Statistical tests included chi-square and t-test. Results: Forty patients were treated with CDK4/6 inhibitor (palbociclib 30.8%, ribociclib 51.3%, abemaciclib 17.9%) and RT (131 lesions; 100 SBRT, 31 non-SBRT). The mean NRS score dropped from 3.52 (pre-treatment) to 1.31 (post-treatment) (p < 0.001), with better outcomes for patients treated with moderate hypofractionation (58.6% vs. 39.9% pain relief, p = 0.016). Pain relief was independent of the type of CDK4/6 inhibitor used (p = NS). Analgesic reduction was most common with palbociclib (35.4%, p = 0.001). Eight toxicities (grade 1–2) were reported. The NCB was 0.6 overall, higher with non-SBRT (0.74 vs. 0.52). Conclusions: RT plus CDK4/6 inhibitor, especially with moderate hypofractionation, significantly reduced pain with manageable toxicity. Analgesic therapy can often continue without stopping CDK4/6 inhibitor. Full article

Celtis iguanaea, widely used in Brazilian folk medicine, is known for its analgesic and anti-inflammatory properties. This study evaluated the in vitro antioxidant capacity and the in vivo antinociceptive and anti-inflammatory mechanisms of the standardized spray-dried Celtis iguanaea hydroethanolic leaf extract (SDCi). Phytochemical analysis showed that SDCi contains 21.78 ± 0.82 mg/g polyphenols, 49.69 ± 0.57 mg/g flavonoids, and 518.81 ± 18.02 mg/g phytosterols. UFLC-DAD-MS identified iridoid glycosides, p-coumaric acid glycosides, flavones, and unsaturated fatty acids. Antioxidant assays revealed an IC₅₀ of 301.6 ± 38.8 µg/mL for DPPH scavenging and an electrochemical index of 6.1 μA/V. In vivo, SDCi (100–1000 mg/kg, p.o) did not impair locomotor function (rotarod test) but significantly reduced acetic acid-induced abdominal writhing and both phases of the formalin test at higher doses (300 and 1000 mg/kg). The antinociceptive effects were independent of α-2 adrenergic receptors. SDCi also increased latency in the hot-plate test and reduced paw edema in the carrageenan model, accompanied by decreased IL-1β and increased IL-10 levels. Histological analysis showed a 50% reduction in inflammatory cell infiltration. These findings support SDCi as an effective anti-inflammatory and antinociceptive phytopharmaceutical intermediate, with potential applications in managing pain and inflammation. Full article

Background: Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) is a severe complication associated with bisphosphonate therapy, commonly used in the treatment of osteoporosis and metastatic bone diseases. Low-Level Laser Therapy (LLLT) has been proposed as a potential treatment modality for BRONJ, with its anti-inflammatory, analgesic, and regenerative effects being of particular interest. This systematic review aims to critically assess the current evidence regarding the efficacy of LLLT in the management of BRONJ. Methods: This review was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A comprehensive search of electronic databases, including PubMed, Scopus, and Web of Science, was performed to identify relevant studies published up to September 2024. The systematic review protocol has been registered on the International Prospective Register of Systematic Reviews (PROSPERO) with the number 423003. All studies considered are observational. Studies were included if they investigated the application of LLLT in BRONJ treatment, reporting clinical outcomes such as pain reduction, lesion healing, and quality of life. The quality of the studies was assessed using the Cochrane Risk of Bias tool, and the data were synthesized descriptively. Results: A total of four studies met the inclusion criteria. The findings indicate that LLLT, particularly when used in conjunction with surgical debridement and pharmacological therapy, significantly may reduce pain and promote soft tissue healing in patients with BRONJ. However, the heterogeneity of study designs, laser parameters, and outcome measures limits the generalizability of these results. Furthermore, most studies were small-scale, with moderate to high risk of bias. Conclusions: The current evidence suggests that LLLT may be a beneficial adjunctive therapy in the treatment of BRONJ. However, conclusions are limited by the lack of randomized controlled trials and methodological heterogeneity, particularly for pain management and soft tissue regeneration. However, further high-quality randomized controlled trials with standardized laser protocols are necessary to establish its efficacy and optimize clinical application. Therefore, one of the limitations of this literature review with meta-analysis is that only four studies were considered and, moreover, they were observational. The results of the meta-analysis showed that there is not enough evidence to declare a statistical correlation; this result will surely be due to the small number of studies and heterogeneity. Full article

Impetigo is a highly contagious bacterial skin infection characterized by blistering and erosions that can lead to significant discomfort and complications. The standard treatment includes topical or systemic antibiotics, but severe cases may require advanced wound management strategies. Polylactic acid (PLA)-based membranes have demonstrated effectiveness in enhancing wound healing, modulating inflammation, and reducing pain. Clinical case: We present three cases of bullous impetigo with extensive erosions, managed using PLA membranes as an adjunct to systemic antibiotics. A significant improvement was shown after 7 days of treatment of a single application, and complete resolution was achieved after 30 days. Notably, pain was resolved within 48–72 h, highlighting the analgesic and protective properties of the membrane. Conclusions: These findings suggest that PLA membranes provide a viable adjunct to antibiotic therapy in bullous impetigo, accelerating healing, reducing discomfort, and improving long-term skin outcomes. Given the increasing concern over antibiotic resistance and the limitations of standard wound care, bioresorbable synthetic membranes represent a promising alternative in dermatological wound management. Full article

Background/Objectives: Pain management during minor surgical procedures in wound care across various etiologies is often underestimated in daily clinical practice. Pharmacotherapy remains the most effective and efficient method for pain reduction. However, growing concerns regarding the side effects of traditional analgesics and distressing psychosomatic experiences highlight the need for innovative non-pharmacological pain management strategies. The use of virtual reality (VR) has been suggested as a potential method to alleviate pain during medical procedures. The aim of this study was to assess the feasibility of virtual reality as a non-pharmacological approach to pain reduction during the debridement and dressing of hard-to-heal vascular wounds. Methods: This prospective observational study included a cohort of 100 patients who were consulted and treated at a specialized wound care clinic in the Podkarpacie region, Poland. Participant selection was based on predefined inclusion criteria. Patients were assigned to two groups: Group A, in which VR goggles were used, and Group B, in which standard care without VR was provided. All wounds were pre-treated with Lignocaine 2% gel for approximately 3–5 min before tissue debridement. Pain intensity was measured before the procedure, during the procedure, and 10 min after completion. A structured research questionnaire was used for data collection, consisting of two parts: sociodemographic data, functional assessment, wound characteristics, clinical scales, and the Numeric Rating Scale (NRS) for pain assessment before, during, and after the procedure. Results: A total of 100 participants voluntarily took part in the study, of whom 49.0% (n = 49) were male and 51.0% (n = 51) were female. The age of participants ranged from 43 to 89 years, with a mean age of 68.02 ± 10.0 years. A statistically significant difference in pain perception was observed between the pre-procedure and intra-procedure phases of wound debridement. The average pain increase in the Group with VR was lower than in the Group without VR (p = 0.006, effect size = 0.32). Conclusion: Pain occurrence and intensity during wound debridement are common challenges in clinical practice. The visual perception of a bleeding and treated wound may contribute to the psychogenic pain component. Virtual reality may serve as a simple adjunctive method to medical procedures by diverting attention away from surgical interventions. Further research, including psychological aspects of non-pharmacological pain management, is necessary in the context of wound care prevention and treatment. Full article

Background: Cannabidiol (CBD), a non-intoxicating phytocannabinoid, has garnered interest as a potential therapeutic agent for managing pain and inflammation associated with upper-quarter disorders, including temporomandibular disorders (TMDs), orofacial pain, myofascial dysfunction, and postoperative dental pain. Methods: This systematic review critically evaluated clinical, preclinical, and mechanistic studies on the efficacy and safety of CBD in the management of such conditions. A total of 10 studies, comprising randomized clinical trials and animal models, met the inclusion criteria and were assessed for methodological quality and risk of bias. Results: The findings suggest that CBD demonstrates analgesic, anti-inflammatory, and muscle-relaxant effects in chronic myofascial TMDs and bruxism, particularly when applied topically or intraorally. In contrast, studies on acute nociceptive pain (e.g., pulpitis, third molar surgery) yielded inconsistent results. Notably, CBD enhanced the effects of conventional analgesics such as opioids and NSAIDs in several preclinical models, indicating synergistic potential. However, substantial heterogeneity in CBD dosage, formulation, administration routes, and outcome measures limited comparability across studies. Adverse effects were minimal in clinical trials, yet underreported. Conclusions: While early evidence supports CBD’s potential as an adjunctive treatment for certain upper-quarter conditions, especially those involving chronic myofascial pain, further high-quality, condition-specific trials are required to establish standardized dosing, delivery methods, and long-term safety. Full article