Search Results (397)

Gap junctions (GJs) are channels that enable exchange of ions and small molecules between cells, and have been implicated in the development and maintenance of neuropathic pain. Injury-induced glial activation in sensory ganglia is associated with increased coupling by GJs, which in turn enhances neuronal excitability, contributing to pain signaling. Tonabersat (TON) was suggested to act as a GJ blocker with analgesic actions, but these claims have been disputed. Here we examined whether TON blocks GJs and whether it influences pain behavior in a mouse pain model. Gap junctional coupling was assayed by the dye coupling method in mouse liver and trigeminal ganglia. Pain behavior was tested in a mouse model of chemotherapy-induced pain, using von Frey filaments (tactile sensitivity), the acetone method (cold sensitivity) and hot plate (heat sensitivity). Intracellular dye injection showed that TON and the GJ blocker carbenoxolone (both 50 µM) inhibited gap junctional coupling by 70% and 82%, respectively. In the trigeminal ganglia, TON and carbenoxolone inhibited gap junctional coupling by 74 and 77%, respectively. TON selectively reduced heat and cold hypersensitivity, but not mechanical threshold. Carbenoxolone reduced all hypersensitivity types. No sex differences were observed. We conclude that both TON and carbenoxolone reduced coupling, indicating their potential to influence GJ-mediated coupling. In behavioral tests TON showed a selective effect for thermal hypersensitivity, but the underlying mechanism is unclear. Carbenoxolone produced a somewhat greater reduction in coupling compared with TON. These findings suggest that GJs play a role in pain pathways and highlight the need to explore whether other pain-relieving drugs act by blocking GJs. Full article

Background/Objectives: Symptomatic irreversible pulpitis (SIP) is conventionally treated with pulp tissue removal via root canal treatment, pulpectomy, or pulpotomy. This case series introduces the Pulpitis Restorative Protocol (PRP), a novel method used to treat SIP without pulp removal, relieve pain, and maintain a positive pulp sensibility response. Methods: In this retrospective case series (March 2022–March 2025), 17 SIP patients (plus 10 reversible pulpitis [RP] control cases) were treated with the PRP utilizing a bioactive glutaraldehyde (GA)-resin-modified glass ionomer (RMGI) solid matrix. Follow-up to 36 months (average 17.37 ± 9.61 months) included clinical examination, cold sensibility testing, and radiographs. Results: Treatment was successful in 15/17 SIP cases, an 88.2% success rate, and 9/10 RP cases, a 90.0% success rate. Overall, a total of 24 of 27 cases were successful, a rate of 88.89%. Success criteria were the absence of pain, no soft-tissue abnormality, a positive cold test response, and no radiographic apical lesions. No failures occurred in the first year; two cases failed in the second year and one in the third year. The PRP provided favorable pain relief: 74.1% of patients reported minimal post-operative pain (0–1/10 VAS) the evening of treatment, and 96.3% of patients reported no pain at 24 h without analgesics. All 24 successful cases maintained a positive pulp sensibility response at their final visit. Radiographs were stable in 24 cases. In vitro experiments showed that the GA-RMGI solid matrix exhibits contact-independent bactericidal activity. Conclusions: The PRP provides a promising approach to SIP management, offering a conservative, cost-effective, and efficient alternative to conventional endodontic treatments alongside favorable pain relief. Its clinical significance warrants further verification in various clinical settings and randomized clinical trials. Full article

Fibromyalgia is a chronic nociplastic pain disorder characterized by widespread pain and affective disturbances, in which oxidative stress and neuroinflammation are now recognized as central pathogenic mechanisms. However, current therapies provide only limited symptomatic relief. This study compared the therapeutic and molecular effects of dimethyl fumarate (DMF), an activator of nuclear factor erythroid 2-related factor 2 (NRF2), and cobalt protoporphyrin IX (CoPP), an inducer of heme oxygenase-1 (HO-1), in a reserpine-induced mouse model of fibromyalgia-like pain. Male and female C57BL/6J mice received repeated reserpine administration to induce mechanical allodynia, thermal hyperalgesia, cold allodynia, and depressive-like behaviors. Therapeutic efficacy was evaluated by behavioral testing and molecular analyses of the periaqueductal gray (PAG), anterior cingulate cortex (ACC), and spinal cord (SC). DMF produced a faster antinociceptive response than CoPP, although both compounds ultimately reversed nociceptive hypersensitivity and depressive-like behaviors in male and female mice. These behavioral alterations were associated with increased NLRP3 expression and activated AKT signaling, together with region-specific redox dysregulation involving differential regulation of NADPH oxidases and endogenous antioxidant defenses. Both treatments differentially modulated region-specific redox alterations, enhanced selected antioxidant defenses, and attenuated inflammatory and nociception-related signaling. These findings identify region-specific redox dysregulation as a prominent feature of fibromyalgia-like pathology, providing new mechanistic insight into the molecular basis of nociplastic pain. Collectively, these results demonstrate that DMF and CoPP treatments remodel region-specific redox networks while inhibiting both sensory and affective manifestations of fibromyalgia-like pain, supporting endogenous antioxidant pathways as promising mechanism-based therapeutic targets for fibromyalgia. Full article

Species belonging to the genus Seseli have long been known to be used as herbal remedies in traditional medicine for various purposes such as colds, inflammation, pain, and gastrointestinal disorders. Therefore, in this study, the flower parts of Seseli transcaucasicum (Schischk.) Pimenov & Sdobnina were extracted using methanol and acetone to investigate their phytochemical composition and antioxidant, antimicrobial, and cytotoxic activities. For this purpose, total phenolic content (TPC), DPPH free radical scavenging activity (RSA), phenolic component (PCs) profile, volatile component composition, antimicrobial effect, and cytotoxic potential on the HT29 human colorectal adenocarcinoma cell line were evaluated. When the results were examined, HPLC analysis of phenolic components revealed that both extracts contained particularly high levels of rosmarinic acid, catechin, and quercetin. Among these, rosmarinic acid was detected in the highest amount, with 15.195 mg/g in the methanol extract and 14.929 mg/g in the acetone extract. The volatile components of this plant were determined by GC-MS, and a total of 29 volatile compounds were identified. Among these, β-pinene (220.792 mg/kg), Δ3-carotene (81.898 mg/kg), α-sedrene (63.331 mg/kg), elixen (44.535 mg/kg), sabinene (40.822 mg/kg), and D-limonene (38.422 mg/kg) were identified as the most dominant compounds. It was observed that the methanol extract had a higher total phenolic content (77.389 ± 1.389 mg gallic acid equivalent/g extract) and higher free radical scavenging activity (40.933 ± 0.067 mg trolox equivalent/g extract) compared to the acetone extract. Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans strains were used to determine the antimicrobial activities of plant extracts, and moderate inhibitory effects were observed against these microorganisms. The highest antimicrobial activity was determined by the 16 mm inhibition zone created against S. aureus by the methanol extract at a concentration of 100 mg/mL. The cytotoxic activity of the plant was determined by measuring its dose-dependent antiproliferative effect on HT29 cells. When the difference between solvents was examined, it was observed that the acetone extract at a concentration of 500 µg/mL reduced cell viability by 18.03%, while the methanol extract at the same concentration reduced viability by 30.56%. According to the results, S. transcaucasicum is rich in phenolic and terpenic compounds and exhibits antioxidant, antimicrobial, and cytotoxic effects. Therefore, this plant species is considered a promising resource for the development of naturally occurring biologically active compounds. Full article

Background and Objectives: Free flap reconstruction is the gold standard for complex head and neck defects following oncological ablation. While surgical techniques have improved flap success rates, donor site sensory morbidity remains relatively understudied. The radial forearm free flap (RFFF) and fibula free flap (FFF) are the two most commonly used free flaps for head and neck reconstruction and sensory abnormalities at their donor sites represent a significant but underrecognized source of postoperative morbidity. Materials and Methods: The aim of this study is to systematically review and synthesize the existing evidence on the prevalence, characteristics and assessment methods of sensory abnormalities and pain at the donor sites of RFFF and FFF harvests. A systematic review was conducted according to PRISMA 2020 guidance. PubMed/MEDLINE, Scopus, Web of Science, the Cochrane Library, and Google Scholar were searched from inception to 1 October 2025, with additional gray-literature and reference-list screening. Primary studies reporting sensory abnormalities, donor-site pain, neuropathic pain, or cold intolerance after RFFF and/or FFF harvest were included; prior reviews were used for citation tracking and contextual comparison only. Risk of bias was assessed with study-design-specific Joanna Briggs Institute (JBI) checklists, and the level of evidence was classified using the Oxford Centre for Evidence-Based Medicine (OCEBM) framework. Descriptive prevalence summaries and exploratory random-effects pooled estimates were calculated when numerators and denominators could be extracted. Results: From 1247 initially identified records, 73 studies met the inclusion criteria (36 RFFF-specific, 35 FFF-specific, and 2 addressing both flap types). Most studies were observational, and sensory outcomes were frequently secondary endpoints. For RFFF, reported sensory abnormalities ranged from 0% to 100% across extractable studies (median 31.3%; IQR 13.1–55.0%), reflecting differences in definitions, follow-up, and testing; the exploratory pooled prevalence was 34.4% (95% CI 23.6–47.1%; I2 = 88.4%). General donor-site pain ranged from 0% to 36.8% (median 12.0%; pooled 16.0%, 95% CI 9.9–24.8%), whereas Douleur Neuropathique en 4 Questions (DN4)-defined neuropathic pain was 18% in the largest dedicated RFFF study and 18% in a smaller pain-focused study. Cold intolerance ranged from 0% to 40.0% (median 16.2%). For FFF, sensory abnormalities ranged from 0% to 76.3% (median 21.4%; IQR 8.2–46.8%; pooled 24.0%, 95% CI 16.5–33.6%; I2 = 88.6%). General pain ranged from 0% to 72.7% (median 17.5%; pooled 18.8%, 95% CI 13.9–24.9%), and DN4-defined neuropathic pain was 21% in the only dedicated FFF study. Objective testing (quantitative sensory testing [QST], Semmes-Weinstein monofilaments, two-point discrimination, or standardized neurological examination) was used inconsistently, and no included study systematically used nerve conduction studies or electromyography (EMG). Conclusions: Sensory abnormalities and pain after RFFF and FFF harvest appear common, but available estimates remain uncertain because of heterogeneous definitions, follow-up intervals, assessment instruments, and predominantly Level 2b-4 evidence. The literature shows a persistent gap between patient-reported symptoms and objective sensory testing. Future prospective studies would benefit from standardized neuropathic pain screening, structured neurological examination, and QST; however, current data do not support strong causal inferences or a validated treatment algorithm. Full article

Background: Cancer-related pain involves complex peripheral and central mechanisms. Quantitative sensory testing (QST) assesses somatosensory function and provides insights into pain mechanisms. However, longitudinal evidence in oncological populations remains limited. This study investigated longitudinal changes in somatosensory function and their relationship with pain intensity and pain trajectory groups in a Portuguese cancer cohort. Methods: This longitudinal study was conducted within the international PAINLESS project and included participants from the Portuguese clinical unit. A total of 56 cancer patients were assessed at diagnosis (baseline, T0), before treatment, and at 6-month follow-up (T6). Pain intensity was measured using the Numeric Rating Scale (NRS), and somatosensory function was assessed using standardized thermal QST, including heat pain threshold (HPT), cold detection threshold (CDT), cold pain threshold (CPT), temporal summation of pain (TSP), and conditioned pain modulation (CPM). Non-parametric analyses evaluated longitudinal changes, correlations between pain and QST measures, differences according to clinically relevant pain (NRS < 4 vs. ≥ 4), and differences across clinically meaningful pain trajectory groups. Results: Thermal sensory thresholds changed significantly, with decreased HPT (p = 0.025) and increased CDT (p < 0.001) and CPT (p = 0.005). At T0, pain intensity was negatively correlated with CDT (r_s = − 0.371, p = 0.009), whereas at T6 it was positively correlated with CPT (r_s = 0.401, p = 0.006). Longitudinal changes in pain intensity were also associated with changes in CPT (r_s = 0.337, p = 0.029). Trajectory analysis demonstrated significant baseline CDT differences across pain trajectory groups (p = 0.028), with higher CDT values in the pain increase group than in the persistent pain group (adjusted p = 0.035). No significant longitudinal changes were observed in central pain modulatory measures (TSP and CPM). Conclusions: Altered thermal sensory processing, particularly cold-related measures, was associated with pain intensity and trajectories during the first six months after diagnosis. While central pain modulation remained stable, CDT and CPT showed consistent relationships with clinically relevant pain outcomes. These findings support the potential utility of thermal QST for characterizing sensory profiles and pain trajectory groups in cancer-related pain; being important, further longitudinal studies are needed to determine the predictive value of these measures. Full article

Diabetic painful neuropathy (DPN) is a common complication of diabetes. Despite ongoing efforts, the underlying biological mechanisms of DPN remain poorly understood. Hyperglycemia-mediated oxidative stress can affect cell barrier properties, triggering low-grade inflammation. Previous studies have reported increased histone deacetylase (HDAC) activity and altered expression of tight junction proteins in diabetes, which may link to nerve damage. This study examined the effects of the HDAC inhibitor FK228 on cell barrier-mediated changes in the spinal cord and dorsal root ganglia (DRG) of type 2 diabetic mice. Diabetic mice were treated with FK228 (1 mg/kg, twice a week for 3 weeks). Behavioral assessment of cold hypersensitivity was assessed at the end of the treatment regimen. In vitro studies were conducted using ND7/23 immortalized DRG cells. The expression of tight junction proteins (occludin, claudin-1, and zona occludens-1 or ZO-1) and a number of stress-related cellular markers, including HDAC2, growth-associated protein (GAP) 43, epidermal growth factor receptor (EGFR), and nuclear factor erythroid 2-related factor (Nrf2), were evaluated in DRG, spinal cord tissue, and cultured ND7/23 DRG cells following treatment. FK228 treatment demonstrated changes in cold pain sensitivity as well as the expression of tight junction proteins and stress related markers in both in vivo and in vitro models of diabetic neuropathy. These findings indicate that HDAC inhibition by FK228 may support the maintenance of tight junction protein expression and alter cellular stress responses in the spinal cord and DRG, suggesting a possible role of FK228 in mitigating DPN. Full article

Objectives: This prospective observational study aimed to compare the efficacy of a novel bioceramic intracanal medicament (Bio-C Temp) with a conventional calcium hydroxide-based medicament (UltraCal XS) in reducing postoperative spontaneous pain and percussion sensitivity in patients with symptomatic irreversible pulpitis (SIP) with apical periodontitis (AP). Methods: Thirty-seven systemically healthy patients diagnosed with SIP with AP were included. The selected teeth were vital, single-rooted, single-canal maxillary or mandibular teeth presenting with prolonged moderate to severe pain in response to cold testing (Visual Analog Scale [VAS] ≥ 50 mm), moderate to severe percussion pain (VAS ≥ 50 mm), and a periapical index (PAI) score ≤ 2. Patients were randomly allocated to receive either Bio-C Temp (n = 19) or UltraCal XS (n = 18) as the intracanal medicament. Postoperative pain, percussion sensitivity, and analgesic consumption were recorded at 6, 12, and 24 h, and 3, 5, and 7 days. Data were analyzed using R statistical software (version 4.5.0). Statistical significance was set at p < 0.05. Results: Both groups demonstrated a significant reduction in postoperative pain and percussion sensitivity compared with preoperative levels (p < 0.05). By the end of the 7th day, the UltraCal XS group showed significantly lower spontaneous pain (p < 0.001) and percussion sensitivity (p < 0.001) than the Bio-C Temp group. Complete spontaneous pain relief was reported in 65% of the UltraCal XS group and 31% of the Bio-C Temp. However, no patient in either group achieved complete resolution of percussion sensitivity. Conclusions: UltraCal XS provided superior short-term postoperative pain relief and greater reduction in percussion sensitivity compared with the bioseramic medicament. Neither medicament fully resolved percussion sensitivity within 7 days. Full article

Background: Cracked teeth may present with variable and atypical symptoms, sometimes mimicking non-odontogenic orofacial pain conditions, making diagnosis challenging, particularly when cracks appear limited to enamel. Case presentation: A 36-year-old woman presented with intermittent pain in a mandibular molar radiating to the ipsilateral temporal region. Clinical examination identified a crack line on the lingual surface of the mandibular first molar. Pulp sensibility testing (cold test and electric pulp test), occlusal loading tests, and cone-beam computed tomography (CBCT) were performed. CBCT was used primarily to exclude vertical root fracture and periapical pathology, and no radiographic abnormalities were identified. Differential diagnosis was conducted using structured diagnostic frameworks, including the International Classification of Orofacial Pain and the International Classification of Headache Disorders (3rd edition). Diagnostic local anaesthesia eliminated both biting pain and referred pain, supporting an odontogenic source. Collectively, the findings suggested that the enamel crack was the most likely source of odontogenic pain, although a definitive causal relationship could not be established. Because pulp sensibility remained normal, conservative management was selected. Crack sealing with a methyl methacrylate-based adhesive resin resulted in complete symptom resolution that was maintained throughout a 3-year follow-up period without the need for root canal treatment. Conclusions: Although the diagnosis remained probabilistic, the structured diagnostic approach, together with the favourable clinical response after crack sealing, supported the enamel crack as the most likely source of odontogenic pain. Full article

Musculoskeletal disorders (MSDs) represent a critical global challenge to workforce productivity. In Thailand, these disorders are particularly prevalent in labor-intensive industries such as ice manufacturing, where workers face significant ergonomic hazards. Addressing this gap, the present study aimed to assess the occupational health, safety, and ergonomic risks facing workers in ice production facilities. This cross-sectional descriptive study investigated production workers who were employees in two of eight ice manufacturing plants in Surat Thani, Thailand, using the Rapid Entire Body Assessment (REBA) method. A structured occupational health and safety risk assessment questionnaire and the REBA evaluation form were used to collect data. All participants were male, averaging 30.4 (±8.5) years old. Regular pain areas included the upper/lower back, hips/thighs, shoulders, wrists, and ankles. Ergonomic assessments showed high overall risk due to heavy lifting, repetitive tasks, and cold environments. Based on REBA scores, 13.04% were in the very-high-risk group (score ≥ 11) and 65.22% in the high-risk group (score 8–10). Most production workers in ice plants faced high ergonomic risks, especially from postures affecting the upper and lower back. Training should be provided to promote awareness of risky postures and proper lifting techniques. Mechanical aids and back-support equipment are also recommended to help prevent musculoskeletal injuries. Full article

Objective: To determine whether contrast therapy improves recovery after climbing-specific forearm fatigue in amateur climbers. Methods: In a randomized repeated-measures trial, 40 climbers were allocated to passive recovery (n = 20) or Game Ready contrast therapy (n = 20). Both groups completed a fixed-task intermittent fingerboard protocol on a 20 mm edge using a half-crimp grip, with 7 s of work and 3 s of rest for five sets; the load was not individualized to climbing-specific maximal finger-flexor force. The intervention group received bilateral forearm treatment consisting of alternating 1 min cold (3 °C) and heat (45 °C) phases combined with pneumatic compression ranging from 15 to 75 mmHg. Sessions lasted 20 min and were administered immediately after post-fatigue testing, at 24 h and 48 h, and then three times weekly on alternate days for 8 weeks, for a total of 27 sessions. Outcomes were assessed at baseline, immediately after fatigue, at 24 h and 48 h, and after 8 weeks. Outcomes included perfusion, reactive hyperemia, stiffness, pressure pain threshold, grip strength, perceived recovery, creatine kinase, and interleukin-6. Results: Immediate post-fatigue responses were comparable. Contrast therapy produced greater 24 h and 48 h resting perfusion responses (+7.28 percentage points, 95% CI 6.58 to 7.98; +7.62, 95% CI 6.94 to 8.31; both adjusted p < 0.001). At week 8, peak hyperemic perfusion improved more with contrast therapy (+6.21 PU, 95% CI 5.62 to 6.79; p < 0.001). Recovery favored contrast therapy for stiffness at 48 h (−71.7 N/m, 95% CI −75.6 to −67.8), pressure pain threshold at week 8 (+8.1 N/cm², 95% CI 7.3 to 8.8), and grip strength at 48 h (+7.8 kgf, 95% CI 7.3 to 8.3; all p < 0.001). CK and IL-6 differences were transient, and no serious adverse events or intervention-related discontinuations were recorded. Conclusions: Contrast therapy was associated with more favorable cutaneous perfusion, post-occlusive reactive hyperemia-derived, and neuromechanical recovery outcomes, whereas biochemical differences were limited and time-dependent. The vascular findings do not establish improved endothelial function or nitric-oxide-mediated vasodilation because these mechanisms were not directly assessed. Trial registration: ISRCTN49499065 on 23 June 2025. Full article

Background/Objectives: Paclitaxel is a chemotherapy drug used to treat various tumours, but its use is often limited by an acute and chronic pain syndrome that is poorly managed. Naringin and its aglycone, naringenin, exhibit antioxidant, antitumour, anti-inflammatory, and antinociceptive effects, making them potential alternative treatments. However, their low water solubility limits their oral bioavailability in humans. Micronisation in a supercritical medium reduces particle size and enhances the dissolution of compounds, offering a possible solution. In this study, we investigated whether micronising naringin and naringenin via supercritical technology could improve their dissolution and oral efficacy against paclitaxel-induced pain syndrome. Methods: Micronisation was performed using supercritical CO₂. Molecular docking was used to analyse the binding of naringin and naringenin to TRPV1, a key target for pain relief. Swiss mice were used in capsaicin (TRPV1 agonist)-induced nociception and paclitaxel-caused acute and chronic pain models. We assessed mechanical, cold, and heat sensitivity, potential adverse effects, and TRPV1 mRNA expression. Results: Micronisation improved the apparent dissolution profile of molecules. Docking results showed that naringin and naringenin bind to TRPV1. Both micronised compounds reduced capsaicin-induced nociception without affecting locomotion or body temperature. Micronised naringin and naringenin alleviated mechanical and cold allodynia, as well as thermal hyperalgesia in both acute and chronic paclitaxel-induced pain, outperforming their conventional forms. They also downregulated TRPV1 mRNA expression in the mice’s sciatic nerve. Conclusions: Taken together, these results show that supercritical micronisation improved the apparent dissolution and oral antinociceptive efficacy of naringin and naringenin, emphasising their potential as promising alternatives for managing paclitaxel-induced pain, with TRPV1 being a probable contributor to the observed antinociceptive effects. Full article

The role of the catechol-O-methyltransferase (COMT) Val158Met rs4680 polymorphism in altered pain processing in headaches is controversial. The aim of this study was to investigate the influence of the Val158Met rs4680 polymorphism in conditioned pain modulation (CPM) in women with migraine. A case-control study including 70 women with chronic migraine, 70 with episodic migraine and 70 pain-free women was conducted. Pressure pain thresholds (PPTs) at the temporalis muscle, lateral epicondyle, and tibialis anterior were bilaterally assessed. Heat (HPT) and cold (CPT) pain thresholds at the frontalis muscle were also assessed. Subsequently, CPM was evaluated immediately after a one-minute cold-pressor test paradigm on changes obtained in PPTs, HPT and CPT. Thus, after amplifying Val158Met polymorphism by polymerase chain reaction, genotype frequencies (Val/Val, Val/Met, or Met/Met) and allele distributions were identified. The distribution of Val158Met genotypes (p = 0.097) was not significantly different among women with episodic migraine, chronic migraine and pain-free controls. The results revealed significant group*time*Val 158Met interactions for PPTs at the temporalis (Wilk’s λ = 0.917, F [4, 193] = 4.377, p = 0.002, n²p = 0.083, 1 − β = 0.930) and lateral epicondyle (Wilk’s λ = 0.892, F [4, 193] = 5.870, p < 0.001, n²p = 0.108, 1 − β = 0.982), as well as CPT (Wilk’s λ = 0.872, F [4, 193] = 7.111, p < 0.001, n²p = 0.128, 1 − β = 0.995) or HPT (Wilk’s λ = 0.921, F [4, 193] = 4.133, p = 0.003, n²p = 0.079, β − 1 = 0.914), but not for the PPT at tibialis anterior (Wilk’s λ = 0.983, F [4, 193] = 0.834, p = 0.505, n²p = 0.017, 1 − β = 0.263). Women with chronic migraine with the Met/Met genotype exhibited reduced CPM indexes for PPT, CPT, or HPT at the temporalis (trigeminal area) than those with the Val/Val genotype. This study showed that CPM deficit is higher in women with migraine with the Met/Met genotype, but this association is mostly present in the symptomatic (trigeminal) area in the chronic form of the disease. No association of the Met/Met genotype with CPM was seen in healthy controls. Full article

Ocimum gratissimum L. subsp., commonly known as African basil, is a native African medicinal plant that has been used for generations to address various health issues. These include colds, flu, diabetes, diarrhoea, pain and swelling, psychological disorders, malaria, inflammation, and infections caused by fungi and bacteria. In addition, African basil is abundant in vitamins and minerals and is mostly used to add flavour to dishes and soups in West African households. Studies have identified multiple bioactive compounds in this plant, such as alkaloids, polyphenols, triterpenes, steroids, fatty acids, esters, alcohols, essential oils, ketones, and aldehydes. Key bioactive constituents, essential oils like thymol and eugenol, are responsible for the pharmacological effects of Ocimum gratissimum. The diverse bioactive compounds give the plant a wide range of therapeutic properties, including antioxidant, cognitive-enhancing, antimicrobial, anti-inflammatory, analgesic, anticancer, antihypertensive, hepatoprotective, and organoleptic effects. Notable mechanisms of action include the PI3K/Akt, NRF-2, and NF-κB signalling pathways, free radical scavenging, and modulation of pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α. This review paper aimed to compile recent studies on the phytochemistry, medicinal uses, therapeutic activities, and molecular mechanisms of action of Ocimum gratissimum. Further studies are needed to better understand the effects of Ocimum gratissimum at the pathological and molecular levels. Full article

Recently, an anti-inflammatory effect of no-ozone cold plasma (NCP) has been reported, but the direct use of NCP for treating muscle inflammation is very difficult since NCP is a form of gas. In this study, we tested whether the anti-inflammatory effect of the NCP could be delivered through conductive metal needles to reduce muscle inflammation. C2C12 mouse muscle cells were treated with TNFα to induce muscle inflammation and then treated with NCP and a conductive metal needle separately or in combination. The effects of NCP and a needle were monitored by performing RT-PCR and Western blot analysis. As a result, NCP effectively suppressed the TNFα-mediated expression of the TNFα, IL1β, and FasL genes, but this effect weakened as the distance between the cells and the NCP increased. On the other hand, treatment of cells with a plasma-needle (PN) had an anti-inflammatory effect regardless of distance, and the anti-inflammatory effect of the PN was maintained under conditions where the gas flow of NCP was not delivered to the cells. It is believed that the PN-mediated activation of media plays a pivotal role in the anti-inflammatory effect of the PN. Finally, this study also showed that electroacupuncture can inhibit TNFα-induced inflammatory gene expression in a manner like a PN. Taken together, the results of this study demonstrate that the anti-inflammatory effect of NCP can be delivered through metal needles, suggesting that PN may be useful for treating inflammatory muscle pain. Full article