Background: Chrysin is a natural flavonoid that exhibits various pharmacological activities including pain relief. However, the effects of chrysin on changes of metabolic profiles during pain remain unclear. The aim of this study was to analyze the biomarkers related to pain in serum and to evaluate the analgesic properties of chrysin in a rat model of pain. Methods: Male Wister rats were divided into four groups (n = 5). Pain was induced by injecting 50 μL of formalin into the hind paw. Chrysin and diclofenac (10 mg/kg, intraperitoneal injection) was administered to the intact and pain groups. All injections were given 30 minutes before pain induction. Immediately, the behavioral test was performed.Then the serum sample was separated for 1 HNMR-based metabolite analysis. Results: Chrysin treatment alleviated the paw licking events, flinching response, and pain score. The integrated analyses further revealed three major metabolic changes including glycine-serine-threonine, taurine-hypotaurine, and arginine by comparing the serums from intact operated rats, pain rats, and pain rats treated with chrysin, and suggested that chrysin may improve pain by regulating the biosynthesis of these metabolic pathways. Conclusions These findings provide insights into metabolic pathways involved in pain and the analgesic effects of chrysin and may help to identify potential targets for the anti-pain properties of chrysin.

Chronic pain is a universal problem that directly evolves the central nervous system, altering both its structure and function. This review discusses neuroplastic alterations in critical areas in the brain like the anterior cingulate cortex, insula, prefrontal cortex, primary (S1) and secondary (S2) somatosensory cortices, and thalamus. These regions exhibit gray matter decrease and changes in connectivity during chronic pain. Several cortical networks, mainly the central executive network, the default mode network, and the salience network exhibit neuroplasticity which reallocates cognitive and emotional resources to pain processing. Thus, it was reported that sensitivity to pain enhances emotional suffering, indicating that altered connectivity and functional reorganization of these networks support maladaptive pain processing and underpin chronic pain persistence. Neuroplasticity-focused treatments such as brain stimulation, neuro-feedback, and exercise-based therapies constitute potential interventions for preventing such negative changes. Further, innovative neuroimaging biomarkers are effective in demonstrating precise neural changes and in providing information about the diagnosis of chronic pain syndromes. This review highlights neuro-plastic changes in chronically painful patients and acknowledges the brain’s plasticity as a target for chronic pain treatment. It, also, points to the diagnostic strategies and practical interventions that address these alterations.

Background: Obesity and chronic pain are related in both directions, according to earlier observational research.This research aimed to analyze the causal association between obesity and chronic pain at the genetic level, as well as to assess whether common factors mediate this relationship. Methods: This study used bidirectional two sample Mendelian randomization (MR) technique to analyze the association between obesity and chronic pain. Obesity's summary genome-wide association data were obtained from European ancestry groups, as measured by body mass index (BMI), waist-to-hip ratio, waist circumference (WC), and hip circumference (HC), genome-wide association study data for chronic pain also came from the UK population, including chronic pain at three different sites (back, hip, and headache), chronic widespread pain (CWP), and multisite chronic pain (MCP). Secondly, a two-step MR and multivariate MR investigation was performed to evaluate the mediating effects of several proposed confounders. Results: The authors discovered a link between chronic pain and obesity. More specifically, a sensitivity analysis was done to confirm the associations between greater BMI, WC, and HC with an increased risk of CWP and MCP.Importantly, the intermediate MR results suggest that education levels and smoking initiation may mediate the causal relationship between BMI on CWP, with a mediation effect of 23.08% and 15.38%, respectively. Conclusions The authors’ findings demonstrate that the importance of education and smoking in understanding chronic pain’s pathogenesis, which is important for the primary prevention and prognosis of chronic pain.

Background: This study investigates whether intramuscular electrical stimulation (IMES) with inverse electrode placement (IEP) or conventional electrode placement (CEP) more effectively modulates pain. The current study’s aim was to compare the effects of IMES using IEP and CEP, and sham-IMES on the pressure pain threshold (PPT), EMG activity, upper trapezius (UT) muscle length and pain severity among adults with UT myofascial trigger points (MTrPs). Methods: Thirty-six male adults with UT-MTrPs were allocated into three groups. IEP, CEP and sham groups were respectively treated with a single IMES session using IEP, CEP, and sham-IMES. Pain intensity, PPT, EMG activity (root mean square, RMS) and UT muscle length were measured on day one before the treatment, day one post treatment and at a day three follow-up to determine the immediate and short-term effectiveness of IMES. Results: IMES using both IEP and CEP methods produced significant higher changes in UT-PPT (median, interquartile-interval, IEP group: 3.25, 2.56–3.50 and CEP group: 2.75, 1.75–3.00, vs. sham group: 1.07, 0.89–1.71 kg/cm 2 ), RMS (IEP: 0.31, 0.26–0.35 and CEP: 0.36, 0.23–0.38, vs. sham: 0.21, 0.16–0.25 mV), and UT muscle length (IEP: 9.50, 8–12.75 and CEP: 8, 7–10, vs. 1.5. 1–2.75 degrees) and UT-pain severity (IEP: 3.00, 2.25–4 and CEP: 3, 3–3, vs. sham: 2, 2–2.75 points on VAS) compared to the score change in sham-IMES at day three follow up. Conclusions Pain modulation can be effectively achieved using IMES regardless of electrode placement method, with different electrode configurations.

Background: To relieve acute and inflammatory pain, preparations of plant and animal origin have been used. The present work aimed to study the analgesic and anti-inflammatory effectiveness of a combined preparation based on viper venom and essential oil. Determining effective routes of exposure, optimal doses, the duration of action of the preparation, and possible mechanisms of their action were the areas of interest. Methods: Experiments were carried out on murine. Essential oil content was determined by gas chromatography– mass spectrometry equipment. The formalin, carrageenan, and hot plate tests were used. Certain methods for determining side effects were used as well. To determine the participation of cannabinoid and opioid receptors in the antinociceptive action of combined preparation, SR144528 and naloxone were used. Results: The treatment of the ointment version of the preparation reduced inflammatory pain by more than 68% and decreased the volume of inflammatory edema by up to 36%. The involvement of cannabinoid receptors in the analgesic mechanism of the ointment was approximately 73%, and, for the opioid receptors, about 64%. Physiologically significant side effects were not observed. Conclusions The active components of the ointment are principally different in their mechanism of action and make it possible to relieve pain and inflammation both through the blockade of pain receptors of afferent nociceptive neurons (venom) as well as via cannabinoid and opioid receptors (essential oil).

Background: Breast cancer is a common malignant tumor that has a high tendency to metastasis to the bone, leading to cancer-induced bone pain (CIBP). Ghrelin can not only stimulate appetite and regulate energy balance, but also alleviate CIBP by inducing NPY expression. Octanoic acid (OA), a type of medium chain fatty acids, provides an energy substrate and promotes acylation of ghrelin. However, it remains to be elucidated whether an OA-rich diet can alleviate CIBP by activating the acyl-ghrelin/NPY pathway. Methods: First, thirty-six Sprague–Dawley rats were randomly divided into the sham, CIBP, CIBP + OA (20), CIBP + OA (40), CIBP + OA (60) and CIBP + OA (80) groups to investigate the effects of diets with different ratios of OA on CIBP and the acyl-ghrelin/NPY pathway. Next, a ghrelin O-acyltransferase (GOAT) inhibitor was exogenously administered to investigate whether an OA-rich diet alleviated CIBP through increasing the level of acyl-ghrelin and activating the acyl-ghrelin/NPY pathway. Results: An OA-rich diet significantly alleviated nociceptive behaviors and increased the levels of acyl-ghrelin and NPY in a dose-dependent manner in cancer-bearing rats. With the exogenous administration of the GOAT inhibitor, the beneficial effects of an OA-rich diet on the acyl-ghrelin/NPY pathway and its pain-relieving effects were attenuated. Conclusions An OA-rich diet could alleviate CIBP through increasing the level of acyl-ghrelin and activating the acylghrelin/NPY pathway.

Background: Bone cancer pain (BCP) is not adequately addressed by current treatment methods, making the exploration of effective management strategies a topic of significant interest. Bone marrow mesenchymal stem cells (BMSCs) seem to be a potential way for managing BCP, yet little is known about the mechanisms underlying the efficacy of this potential treatment. Methods: We established the male C57BL/6 mice BCP models. Behavioral tests, X-ray, bone histology, western blotting, and immunofluorescence were used to verify the analgesic effect of BMSCs. Results: Intramedullary injection of Lewis lung carcinoma cells into the femur successfully generated the mice BCP models. The number of c-Fos-positive neurons and phosphorylated mitogen-activated protein kinase (MAPK) proteins in the spinal dorsal horn of the BCP mice increased. Intrathecal injection of BMSCs temporarily improved the BCP mice’s mechanical and thermal hyperalgesia without affecting motor function. This effect may be related to inhibiting spinal microglia and p-p38 MAPK activation. The analgesic effect of BMSCs may be related to the homing effect mediated by CXCR4. Conclusions Intrathecal injection of BMSCs can temporarily inhibit mechanical and thermal hyperalgesia in BCP mice without affecting motor function. This effect may be related to the inhibition of p-p38 protein expression and the inhibition of microglia but not to p-ERK and p-JNK.