Pain Inhibition Research Articles

The Role and Potential Mechanism of Complement Factor D in Fibromyalgia Development.

Fibromyalgia (FM) is a syndrome characterized by chronic musculoskeletal pain. Its clinical symptoms include both somatic and psychiatric symptoms, making the treatment of FM extremely challenging. The cause of FM is still unknown, and some patients do not improve their symptoms even after long-term active treatment. Thus, the development of new targeted therapies is important to reduce pain and improve quality of life for FM patients. In this study, we screened genes and secreted factors that play key roles in FM through bioinformatics and big data analysis. Furthermore, we performed CCK-8, qRT-PCR, glucose, ATP and lactate content testing, dual luciferase reporter gene assay to investigate the potential mechanism of complement factor D in fibromyalgia development. In bioinformatics and big data analysis, we identified CFD was negatively correlated with the pro-inflammatory factor IL-6 and positively correlated with the anti-inflammatory factor IL-4, which suggested that CFD may be an anti-inflammatory factor. Through cellular assays, we verified that CFD reversed the decrease in IL-4 expression and the increase in IL-6 expression in BV2 cells caused by ATP. In summary, based on bioinformatic methods and big data mining we obtained a new target CFD for FM, and further experiments verified that CFD has significant inhibition of ATP-induced neuropathic pain. These findings provide a new theoretical basis for the clinical translation of CFD.

MicroRNA-138: an emerging regulator of skeletal development, homeostasis, and disease.

Noncoding microRNAs are powerful epigenetic regulators of cellular processes by their ability to target and suppress expression of numerous protein-coding mRNAs. This multitargeting function is a unique and complex feature of microRNAs. It is now well-described that microRNAs play important roles in regulating the development and homeostasis of many cell/tissue types, including those that make up the skeletal system. In this review, we focus on microRNA-138 (miR-138) and its effects on regulating bone and cartilage cell differentiation and function. In addition to its reported role as a tumor suppressor, miR-138 appears to function as an inhibitor of osteoblast differentiation. This review provides additional information on studies that have attempted to alter miR-138 expression in vivo as a means to dampen ectopic calcification or alter bone mass. However, a review of the published literature on miR-138 in cartilage reveals a number of contradictory and inconclusive findings with respect to regulating chondrogenesis and chondrocyte catabolism. This highlights the need for more research in understanding the role of miR-138 in cartilage biology and disease. Interestingly, a number of studies in other systems have reported miR-138-mediated effects in dampening inflammation and pain responses. Future studies will reveal if a multifunctional role of miR-138 involving suppression of ectopic bone, inflammation, and pain will be beneficial in skeletal conditions such as osteoarthritis and heterotopic ossification.

Physical activity, sitting time, and thermal quantitative sensory testing responses in African Americans.

Prior research suggests that African Americans (AAs) have more frequent, intense, and debilitating pain and functional disability compared with non-Hispanic Whites (NHWs). Potential contributing factors to this disparity are physical activity and sedentary behavior, given that AAs are less physically active, and physical activity is associated with antinociception (whereas sedentary behavior is linked to pronociception). However, impact of these factors on pain processing has largely been unexplored in AAs, especially before chronic pain onset. This study examined relationships between physical activity, sedentary behavior (sitting time), and laboratory measures of pain and pain modulation in adult AAs. These included heat pain threshold and tolerance, temporal summation of pain (TSP, a marker of central sensitization), and conditioned pain modulation (CPM, a marker of descending pain inhibition). Multiple regressions were conducted to examine the effects of physical activity and sitting time on heat threshold and tolerance. Multilevel models were conducted to assess the relationship between physical activity, sitting time, and temporal summation of pain. Additional multilevel models were conducted to assess the relationship between physical activity, sitting time, and conditioned pain modulation. Higher level of physical activity, but not sitting time, was associated with reduced TSP slopes. Neither physical activity nor sitting time was associated with CPM slopes. No significant relationships between physical activity or sitting time and heat pain threshold or tolerance were detected. These findings suggest that physical activity is associated with reduced TSP, an effect which may be driven by reduced spinal hyperexcitability in more active individuals. Thus, structural and individual interventions designed to increase physical activity in healthy, young AAs may be able to promote antinociceptive processes (ie, reduced TSP/reduced pain facilitation) potentially protective against chronic pain.

Comparative study of intravenous flurbiprofen and acetaminophen for preventing pain after third molar surgery: A retrospective cohort study

ObjectiveIn the general management of postoperative pain after third molar surgery under intravenous (IV) sedation, a nonsteroidal anti-inflammatory drug (NSAID) or acetaminophen is usually prescribed. However, there is no concrete evidence regarding whether an NSAID or acetaminophen is more effective. In this study, we assessed the efficacy of a single dose of IV NSAIDs (50 mg flurbiprofen axetil) compared with that of a single dose of 1000mg acetaminophen in reducing pain when administered after impacted mandibular third molar surgery. MethodsIn this retrospective observational cohort study, we collected data from medical records of patients who underwent single mandibular molar surgery in a hospitalization setting under IV sedation from 2017 to 2021. We defined patients who received IV flurbiprofen axetil after surgery as the FLB group and those who received IV acetaminophen as the AA group. The primary study outcome was the maximum postoperative pain score during the first 5–15 h post-surgery. The secondary outcome was pain suppression time (the time of initial adjuvant analgesic dose [60 mg loxoprofen]) and the number of doses within 17 h post-surgery. ResultsThe FLB group had significantly lower pain levels at 1, 2, and 3 h postoperatively than the AA group. In addition, the FLB group showed significantly lower adjunct analgesic consumption. ConclusionsIV NSAID administration after impacted mandibular third molar surgery provided more effective pain control than IV acetaminophen. This information can be used by clinicians, especially those working with patients with post-surgical pain, to improve patient care and recovery.

Naturally Inspired Molecules for Neuropathic Pain Inhibition—Effect of Mirogabalin and Cebranopadol on Mechanical and Thermal Nociceptive Threshold in Mice

Background: Neuropathic pain is drug-resistant to available analgesics and therefore novel treatment options for this debilitating clinical condition are urgently needed. Recently, two drug candidates, namely mirogabalin and cebranopadol have become a subject of interest because of their potential utility as analgesics for chronic pain treatment. However, they have not been investigated thoroughly in some types of neuropathic pain, both in humans and experimental animals. Methods: This study used the von Frey test, the hot plate test and the two-plate thermal place preference test supported by image analysis and machine learning to assess the effect of intraperitoneal mirogabalin and subcutaneous cebranopadol on mechanical and thermal nociceptive threshold in mouse models of neuropathic pain induced by streptozotocin, paclitaxel and oxaliplatin. Results: Mirogabalin and cebranopadol effectively attenuated tactile allodynia in models of neuropathic pain induced by streptozotocin and paclitaxel. Cebranopadol was more effective than mirogabalin in this respect. Both drugs also elevated the heat nociceptive threshold in mice. In the oxaliplatin model, cebranopadol and mirogabalin reduced cold-exacerbated pain. Conclusions: Since mirogabalin and cebranopadol are effective in animal models of neuropathic pain, they seem to be promising novel therapies for various types of neuropathic pain in patients, in particular those who are resistant to available analgesics.

Unveiling the mechanisms of neuropathic pain suppression: perineural resiniferatoxin targets Trpv1 and beyond

Neuropathic pain arises from damage or disorders affecting the somatosensory system. In rats, L5 nerve injury induces thermal and mechanical hypersensitivity/hyperalgesia. Recently, we demonstrated that applying resiniferatoxin (RTX) directly on uninjured L3 and L4 nerves alleviated thermal and mechanical hypersensitivity resulting from L5 nerve injury. Herein, using immunohistochemistry, Western blot, and qRT-PCR techniques, we reveal that perineural application of RTX (0.002%) on the L4 nerve substantially downregulated the expression of its receptor (Trpv1) and three different voltage-gated ion channels (Nav1.9, Kv4.3, and Cav2.2). These channels are found primarily in small-sized neurons and show significant colocalization with Trpv1 in the dorsal root ganglion (DRG). However, RTX treatment did not affect the expression of Kv1.1, Piezo2 (found in large-sized neurons without colocalization with Trpv1), and Kir4.1 (localized in satellite cells) in the ipsilateral DRGs. Furthermore, RTX application on L3 and L4 nerves reduced the activation of c-fos in the spinal neurons induced by heat stimulation. Subsequently, we investigated whether applying RTX to the L3 and L4 nerves 3 weeks before the L5 nerve injury could prevent the onset of neuropathic pain. Both 0.002 and 0.004% concentrations of RTX produced significant analgesic effects, while complete prevention of thermal and mechanical hypersensitivity required a concentration of 0.008%. Importantly, this preventive effect on neuropathic manifestations was not associated with nerve degeneration, as microscopic examination revealed no morphological changes. Overall, this study underscores the mechanisms and the significance of perineural RTX treatment applied to adjacent uninjured nerves in entirely preventing nerve injury-induced neuropathic pain in humans and animals.

Sex differences in descending control of nociception (DCN) responses after chronic orofacial pain induction in rats and the contribution of kappa opioid receptors

Descending control of nociception (DCN), a measure of efficiency of descending pain inhibition, can be assessed in animals by the combined application of test and conditioning noxious stimuli. Evidence from pre-clinical and clinical studies indicates that this mechanism of pain control may differ between sexes and might be impaired in many chronic pain states. However, little is known about sex differences in DCN efficiency in models of acute and chronic orofacial pain. Herein, we first evaluated DCN responses in male and female rats by the applying formalin into the upper lip or capsaicin into the forepaw as the conditioning stimulus, followed by mechanical stimulation (Randall-Selitto) of the hind paw as the test stimulus. The same protocol (i.e., capsaicin in the forepaw followed by mechanical stimulation of the hind paw) was evaluated in male and female rats on day 3 after intraoral incision and on day 15 and 30 after chronic constriction injury of the infraorbital nerve (CCI-ION). Additionally, we assessed the effect of the kappa opioid receptor (KOR) antagonist Norbinaltorphimine (nor-BNI) on DCN responses of female nerve-injured rats. This study shows that naïve female rats exhibit less efficient DCN compared to males. Postoperative pain did not alter DCN responses in female and male rats, but CCI-ION induced loss of DCN responses in females but not in males. Systemic pretreatment with nor-BNI prevented the loss of DCN induced by CCI-ION in female rats. The results reveal sex differences in DCN responses and female-specific impairment of DCN following chronic orofacial pain. Moreover, the findings suggest that, at least for females, blocking KOR could be a promising therapeutic approach to prevent maladaptive changes in chronic orofacial pain.

Nifedipine versus magnesium sulfate in the management of preterm labour- A randomised controlled trial

Preterm labour is the leading cause of perinatal morbidity and mortality worldwide. Preterm birth accounts for 75% of neonatal deaths and 50% of long-term morbidity including respiratory disease and neuro-developmental impairment. The use of tocolysis in women in preterm labour aims to inhibit uterine contractions and reduce perinatal morbidity and mortality associated with early delivery.To study the effect and compare the efficacy of Nifedipine and Magnesium sulphate in management of preterm labour.: This randomized controlled trial was performed on 80 women with preterm labor between 28 and 37 weeks of gestation who were randomly assigned to receive either MgSO4 or nifedipine. All patients were checked for successful prolongation of pregnancy who had not been delivered at 48 hours [primary tocolytics effects] and more than 7 days [secondary tocolytics effects] after beginning the treatment and side effects of tocolysis.: From 80 patients, 40 received nifedipine and 40 received MgSO4. There were no differences in suppression of labor pain in 24 hours, 48 hours and 7 days between the two groups. Even though there were no statistically significant differences in one-minute and five-minute Apgar scores, neonatal respiratory distress syndrome between the groups neonates of MgSO4 group had more NICU admission which is significant (p value 0.049).: Oral nifedipine is as effective as magnesium sulfate with regard to inhibition of preterm labor.

Influence of the descending pain-inhibiting serotonergic pathway on the antihyperalgesic effect of gabapentin in neuropathic pain model rats

Gabapentinoids are used worldwide as first-line agents for the treatment of neuropathic pain. Accumulating evidence indicates that one of the antihyperalgesic mechanisms of gabapentinoids is through activation of the noradrenergic pathway of the descending pain inhibition system. However, the involvement of the serotonin pathway is unclear. We investigated the effects of gabapentin (GBP) on the serotonergic pathway of the descending inhibitory system using the spinal nerve ligation (SNL) rat model. As in previous reports, administration of GBP to SNL rats improved paw withdrawal thresholds (PWT). Intrathecally administered serotonin receptor antagonists abolished GBP's amelioration in PWT. GBP did not ameliorate PWT in noradrenaline-depleted SNL rats by DSP-4. However, GBP ameliorated PWT in serotonin-depleted SNL rats by para-chlorophenylalanine, which was not inhibited by intrathecal administration of a serotonin receptor antagonist. Immunohistochemical analysis of serotonin in the spinal dorsal horn revealed a slight, albeit statistically insignificant, increase in 5-HT levels in SNL rats compared to naive rats. However, no apparent changes were observed before or after GBP administration in naive and SNL rats. In conclusion, the involvement of the serotonergic pathway in the antihyperalgesic effects of GBP on the spinal cord is secondary, although it cooperates with the noradrenergic system to produce analgesia.

Conditioned pain modulation and psychological factors in young adults with recurrent or chronic neck pain.

Controversy exists with the presence of alterations in descending pain inhibition mechanisms in patients with non-specific neck pain (NSNP). The aim of the present study was to evaluate the status of conditioned pain modulation CPM, remote pressure pain thresholds (PPT), and psychological factors in a specific subgroup of patients with NSNP such as young adult students. In addition, possible associations between CPM, psychological factors, and pain characteristics were analyzed. Thirty students with recurrent or chronic NSNP and 30 pain-free students were included in this cross-sectional study. The following measures were assessed: CPM, remote PPT, psychological factors (depression, anxiety, pain catastrophizing, and kinesiophobia), pain characteristics (duration, intensity, severity of chronic pain, interference with daily life), and central sensitization inventory (CSI). No significant differences were found in the efficacy of CPM between students with chronic or recurrent NSNP and pain-free students (β coefficient = -0.67; 95% CI = -1.54, 0.20). However, students with pain showed a significantly higher remote PPT (mean difference = -1.94; 95% CI = -2.71, -1.18). and a greater presence of anxious (mean difference = 6; 95% CI = 2, 9) and depressive symptoms (mean difference = 8.57; 95% CI = 3.97, 13.16). In addition, significant moderate or strong correlations were found between CPM and pain intensity (partial r = 0.41), pain catastrophizing and mean pain intensity (r = 0.37), grade (r = 0.50), and interference of pain (r = 0.57), kinesiophobia and disability (r = 0.38), and depression and CSI (r = 0.39). Young adult students with chronic or recurrent NSNP present remote hyperalgesia and symptoms of depression and anxiety but not dysfunctional CPM.

Longitudinal changes in human supraspinal processing after RIII-feedback training to improve descending pain inhibition

The human body has the ability to influence its sensation of pain by modifying the transfer of nociceptive information at the spinal level. This modulation, known as descending pain inhibition, is known to originate supraspinally and can be activated by a variety of ways including positive mental imagery. However, its exact mechanisms remain unknown. We investigated, using a longitudinal fMRI design, the brain activity leading up and in response to painful electrical stimulation when applying positive mental imagery before and after undergoing a previously established RIII-feedback paradigm. Time course analysis of the time preceding painful stimulation shows increased haemodynamic activity during the application of the strategy in the PFC, ACC, insula, thalamus, and hypothalamus. Time course analysis of the reaction to painful stimulation shows decreased reaction post-training in brainstem and thalamus, as well as the insula and dorsolateral PFC. Our work suggests that feedback training increases activity in areas involved in pain inhibition, while simultaneously decreasing the reaction to painful stimuli in brain areas related to pain processing, which points to an activation of decreased spinal nociception. We further suggest that the insula and the thalamus may play a more important role in pain modulation than previously assumed.

Effects of virtual reality on psychophysical measures of pain: superiority to imagination and nonimmersive conditions.

Virtual reality (VR) has been shown to be effective in pain management. However, to date, little is known about the mechanisms by which immersive experiences influence pain processing. The aim of this study was to investigate the direct effects of an immersive VR environment on the perception of experimental pain in individuals with chronic pain and pain-free controls. The immersion in a VR landscape was compared with mental imagery and a nonimmersive control condition. Using a randomized within-crossover design, pressure pain detection and tolerance thresholds, spatial and temporal summation (SSP, TSP), and conditioned pain modulation (CPM) were measured in 28 individuals with chronic pain and 31 pain-free controls using phasic cuff pressure on the legs. Direct comparison between the groups showed that although individuals with pain had significantly lower pain thresholds, reduced CPM effects, and increased TSP, the VR condition had the same pain-inhibitory effect on pain thresholds as in pain-free controls. Conditioned pain modulation effects were reduced by all conditions compared with baseline. There were no significant differences between conditions and baseline for TSP and SSP. Overall, pain modulatory effects were largest for VR and smallest for imagery. These results demonstrate that immersion in a VR environment has an increasing effect on pain thresholds, reduces pain inhibition in a CPM paradigm, and has no effects on TSP. This applies for participants with chronic pain and pain-free controls. These VR effects exceeded the effects of mental imagery on the nonimmersive control condition. This indicates that VR effectively modulates pain perception in both patients and controls irrespective of differences in pain perception.

Prospective, randomized single-blind, multicenter comparison of the analgesic efficacy of flurbiprofen/ thiocolchicoside and ibuprofen in myalgia complaints in SARS-CoV-2 patients

Introduction: Myalgia is a common symptom in patients with COVID-19. NSAIDs perform pain suppression mechanisms by suppressing prostaglandin synthesis through inhibition of cyclooxygenase enzyme (COX). Thiocolchicoside activates GABA and Glycine receptors at the spinal level and exerts a myorelaxant effect. The aim of this study is to compare the analgesic efficacy of two drugs, the active ingredients of which are ibuprofen and flurbiprofen/ thiocolchicoside. Method: The study was designed according to a multicenter, prospective, randomized, controlled clinical trial model. A power analysis was performed based on the study of Derosa et al. including patients with myalgia complaints(11). By accepting 80% power and 5% type-1 error, the number of patients to be included in each group was calculated as at least 68. We planned to include 100 patients in each group, taking into account data losses and patients who may drop out of the study during follow-up (n=200). Results: According to the results of the study, the difference between baseline and 2nd day NRS and the difference between baseline and 3rd day NRS were found to be statistically significantly higher in the group using ibuprofen 800 mg retard TB (P<0.05). Conclusion: In the treatment and follow-up of patients with COVID-19 and myalgia complaints, ibuprofen 800 mg retard tb can be preferred primarily because its effectiveness is superior and no side effects are observed.

P011 How Sex and Age moderate the effect of Sleep Loss on Pain Perception: A Systematic Review and Meta-analysis

Abstract Females tend to exhibit increased sensitivity to pain and are more susceptible to developing chronic pain conditions. Sleep disturbances are comorbid with chronic pain and exacerbate pain symptoms. Sleep disturbances have been found to affect pain perception distinctly, but whether these effects are consistent in men and women is unclear. This systematic review investigated how sex and age moderate the sleep-pain interaction under various forms of sleep disturbances. We searched EBSCO, MEDLINE, Psych INFO, Science Direct, and Web of Science from January 2001 to November 2022. A total of 38 studies with 978 participants were included in the review. The meta-regression was conducted based on the predicted value of effect size and its estimated standard error at a significance level of 0.05. The results showed that sex moderated the effect of sleep disturbance on pain facilitation (SMD=.13; 95%CI:.004 to .022; p=.009) and pain inhibition (SMD=.033; 95%CI:.011 to .054; p=.005). Females exhibited increased pain facilitation and decreased pain inhibition, whereas males showed the opposite direction of effect. Further, age moderated the effects of total sleep deprivation (SMD=-.194; 95%CI -.328 to -.060; p=.008) on pain sensitivity and fragmented sleep (SMD=-.110; 95%CI: -.148 to -.072; p<.001) on pain threshold. Although the moderating effects of sex and age on the sleep-pain interaction were relatively small, these findings highlight the importance of considering these factors in future sleep-pain studies.

Hydrogel fibers that enable optogenetic pain inhibition during locomotion.

Hydrogel fibers that enable optogenetic pain inhibition during locomotion.

The Inhibition of Neuropathic Pain Incited by Nerve Injury and Accompanying Mood Disorders by New Heme Oxygenase-1 Inducers: Mechanisms Implicated.

Neuropathic pain is a type of pain that persists for a long time and becomes pathological. Additionally, the anxiodepressive disorders derived from neuropathic pain are difficult to palliate with the current treatments and need to be resolved. Then, using male mice with neuropathic pain provoked by chronic constriction of the sciatic nerve (CCI), we analyzed and compared the analgesic actions produced by three new heme oxygenase 1 (HO-1) inducers, 1m, 1b, and 1a, with those performed by dimethyl fumarate (DMF). Their impact on the anxiety- and depressive-like comportments and the expression of the inflammasome NLRP3, Nrf2, and some antioxidant enzymes in the dorsal root ganglia (DRG) and amygdala (AMG) were also investigated. Results revealed that the administration of 1m, 1b, and DMF given orally for four days inhibited the allodynia and hyperalgesia caused by CCI, while 1a merely reduced the mechanical allodynia. However, in the first two days of treatment, the antiallodynic effects produced by 1m were higher than those of 1a and DMF, and its antihyperalgesic actions were greater than those produced by 1b, 1a, and DMF, revealing that 1m was the most effective compound. At four days of treatment, all drugs exerted anxiolytic and antidepressant effects, decreased the NLRP3 levels, and increased/normalized the Nrf2, HO-1, and superoxide dismutase 1 levels in DRG and AMG. Data indicated that the dual modulation of the antioxidant and inflammatory pathways produced by these compounds, especially 1m, is a new promising therapeutic approach for neuropathic pain and related emotional illnesses.

Anti-inflammatory and Antinociceptive Activity of Terminalia avicennioides Guill. & Perr. Stem Bark Extract is Distinct from the Antioxidant Effect Mediated by Its Phenolic-rich Fraction

Background: Terminalia avicennioides stem bark has been used in the management of pain and inflammatory disorders in northern Nigeria. This study evaluated the antinociceptive and anti-inflammatory properties of T. avicennioides stem bark extract and its fractions. The correlation of these effects to the presence and concentration of phenolics was also ascertained.
 Study Design: Experimental Design.
 Place and Duration of Study: Department of Pharmacology and Toxicology, National Institute for Pharmaceutical Research and Development, Idu, Abuja, Nigeria. The study was conducted from October to December 2022.
 Methods: A 70%v/v ethanol extract of T. avicennioides stem bark was prepared. Aqueous and ethyl acetate fractions (AF, EF) and sub-fractions (EF1 – EF4) were also prepared. The antioxidant capacity of the extract and fractions were determined using DPPH radical scavenging test, while xylene-induced topical ear edema and formalin test were used to assess antinociceptive and anti-inflammatory activity. The ethyl acetate sub-fractions were further assessed using the egg albumin–induced inflammation. The extract and fractions were characterized by High-Performance Liquid Chromatography (HPLC), and phenolic content was quantified as gallic acid equivalent (GAE)/mg of extract or fraction.
 Results: The ethyl acetate and aqueous fractions showed higher antioxidant capacity compared to the parent ethanol extract. T. avicennioides ethanol extract significantly inhibited pain (p<0.001) and inflammatory responses (p<0.05) and these effects were more significant compared to those produced by the fractions. Fractions AF and EF exhibited similar activity, although EF produced better inhibition of pain and topical edema. The subfraction EF2 also showed anti-inflammatory activity but this effect was insignificant (p>0.05). The HPLC profiles of the extract and fractions showed peaks corresponding to caffeic acid, chlorogenic acid, and gallic acid. The EF and AF revealed higher peak areas corresponding to gallic acid and rutin respectively. This correlated with a comparatively high gallic acid content and antioxidant effect of the ethyl acetate fraction (GAE: 1.32/mg, IC50 = 0.036 mg/ml), relative to the extract (GAE: 0.88/mg, IC50 = 0.052 mg/ml).
 Conclusion: The constituents responsible for the antinociceptive and anti-inflammatory activity of T. avicennioides extract appear distinct from antioxidative principles in phenolics-rich fractions.

Managing Temporomandibular Joint Osteoarthritis by Dental Stem Cell Secretome

The potential therapeutic role of the Dental Pulp Stem Cells Secretome (SECR) in a rat model of experimentally induced Temporomandibular Joint (TMJ) Osteoarthritis (OA) was evaluated. Proteomic profiling of the human SECR under specific oxygen tension (5% O2) and stimulation with Tumor Necrosis Factor-alpha (TNF-α) was performed. SECR and respective cell lysates (CL) samples were collected and subjected to SDS-PAGE, followed by LC-MS/MS analysis. The identified proteins were analyzed with Bioinformatic tools. The anti-inflammatory properties of SECR were assessed via an in vitro murine macrophages model, and were further validated in vivo, in a rat model of chemically-induced TMJ-OA by weekly recording of the head withdrawal threshold, the food intake, and the weight change, and radiographically and histologically at 4- and 8-weeks post-treatment. SECR analysis revealed the presence of 50 proteins that were enriched and/or statistically significantly upregulated compared to CL, while many of those proteins were involved in pathways related to “extracellular matrix organization” and “immune system”. SECR application in vitro led to a significant downregulation on the expression of pro-inflammatory genes (MMP-13, MMP-9, MMP-3 and MCP-1), while maintaining an increased expression of IL-10 and IL-6. SECR application in vivo had a significant positive effect on all the clinical parameters, resulting in improved food intake, weight, and pain suppression. Radiographically, SECR application had a significant positive effect on trabecular bone thickness and bone density compared to the saline-treated group. Histological analysis indicated that SECR administration reduced inflammation, enhanced ECM and subchondral bone repair and regeneration, thus alleviating TMJ degeneration.Graphical

Various Extraction Techniques of Curcumin-A Comprehensive Review.

Curcumin, the active component of the rhizome of Curcuma longa, is a safe substance whose applications are extensively used in medicinal, biological, pharmacological activities, and food cosmetic additives. In the field of medicine, curcuminoids have a greater impact; they have been associated with the suppression of neuropathic pain, depression, angiogenesis, tumorigenesis, diabetes, and diseases of the liver, skin, and pulmonary systems, as well as cardiovascular and nervous systems. These are in high demand and have high market potential and inflated costs. For the aforementioned uses, as well as for basic research, it is crucial to get pure curcumin from plant sources. There is a need for effective extraction and purification techniques that adhere to standards for process efficiency, environmental friendliness, and safety. Scope: This account offers an accurate and thorough explanation of the many techniques used to extract and purify curcumin from plant sources, as well as a look at its various roles in the pharmaceutical, cosmetic, medical, and other industries. Curcumin's prospective and commercial roles are also discussed. Key findings: Curcuminoids have been extracted and purified by using a broad range of techniques that are utilized extensively across the world. Extraction of curcuminoids includes both traditional and contemporary approaches, of which a handful include Soxhlet extraction, maceration, solvent extraction, ultrasound-assisted extraction, microwave-assisted extraction, enzyme-assisted extraction, and supercritical liquid extraction. The other process called purification can be performed alone or in combination with techniques. The use of column chromatography and semipreparative high-performance liquid chromatography are examples of traditional purification procedures, and other innovative methods include high-speed counter-current chromatography and supercritical fluid chromatography.

Cold pressed Pinus halepensis Mill. seed oil for potential health applications: Analgesic, anti-inflammatory effects, and assessment of inflammatory mediators by RT-qPCR in skin wound healing

Ethnopharmacological relevancePinus halepensis Mill. seed (Pinaceae), commonly known as “Zgougou,” is widely consumed in the Mediterranean region and has long been used to treat diseases including bronchitis, rheumatism, infection, and inflammation. Aim of the studyThe present study was focused on the investigation of some pharmacological activities, such as analgesic, anti-inflammatory, and wound healing effects, of cold-pressed oil of Pinus halepensis Mill. seed (COPHS). Materials and methodsThe fixed oil of Pinus halepensis seed was extracted by a cold pressing process. The analgesic activity of COPHS was examined by acetic acid and formalin-induced contortion and pain tests. The anti-inflammatory effects were evaluated in carrageenan and formalin induced paw and ear edema models. Wound healing potential was assessed on an experimental skin wound, and the expression levels of inflammation mediators were determined by RT-qPCR in skin wound healing. ResultsThe results showed analgesic efficacy through significant inhibition of abdominal cramps (59.15%) and pain (75.91%). In addition, this oil exerted an anti-inflammatory effect by inhibiting ear (62.25%) and paw (70.00%) edema. The COPHS stimulated wound contraction in experimental skin wound healing with a contraction rate of 89.23% with notable reduction of TNF-α and NF-kB expression levels in the treated groups. ConclusionsThis study provided for the first time the pharmacological profile, particularly the analgesic, anti-inflammatory, and healing effects, of fixed oil extracted by cold pressing from the seed of Pinus halepensis Mill.