Mirogabalin: a novel gabapentinoid or another false dawn?

PURPOSE OF REVIEW: Mirogabalin is a novel gabapentinoid medication for the treatment of neuropathic pain. The purpose of this review is to discuss current evidence for its use. Gabapentinoids are widely prescribed for neuropathic pain. Mirogabalin offers theoretical advantages over traditional gabapentinoids due to its specificity for the α2δ-1 subunit of voltage-gated calcium channels. It is theorised that this specificity may reduce adverse drug reactions by minimising binding to the α2δ-2 subunit which is responsible for many of the gabapentinoid side effects. RECENT FINDINGS: Mirogabalin's slower dissociation from the α2δ-1 compared with α2δ-2, and its higher potency may also impart an efficacy benefit over traditional gabapentinoids. These theoretical advantages of mirogabalin remain inconclusive in clinical practice, with mixed evidence regarding mirogabalin versus traditional gabapentinoids. Some studies suggest a reduced side effect profile yet, others fail to demonstrate significant differences. Regarding efficacy, mirogabalin may be superior to placebo for several neuropathic pain syndromes, but evidence of widespread benefit over traditional gabapentinoids is currently lacking. SUMMARY: Mirogabalin offers theoretical promise, but large, independent studies are required to further assess its performance versus traditional gabapentinoids.

Ketamine for Pain in Hospice Patients - A Transdermal Gel Applied to the Painful Site.

The author has been using ketamine to treat hospice patients for several years, with varying degrees of success, and reports being most successful with the transdermal-gel form. He has also had success with ketamine administered as a nasal spray. In addition to providing general comments on the use of ketamine in this context, he presents four brief case reports demonstrating the use of ketamine and other medications in treating pain associated with various types of cancer.

Novel phenylpiperazine derivatives as potent transient receptor potential vanilloid 1 antagonists.

Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel, which is considered a highly validated target for pain perception. Repeated activation with agonists to desensitize receptors or use the antagonists can both exert analgesic effects. In this work, two series of novel phenylpiperazine derivatives were designed, synthesized, and evaluated for the in vitro receptor inhibitory activity and in vivo analgesic activity. Among them, L-21 containing sulfonylurea group was identified with potent TRPV1 antagonistic activity and analgesic activity in various pain models. At the same time, L-21 exhibited low risk of hyperthermia side effect. These results indicated that L-21 is a promising candidate for further development of novel TRPV1 antagonist to treat pain.

Enhancing Emergency Department Pain Management for Older Adults with the Hip Fracture Fast-Track (HFFT) Protocol in a Middle-Income Country.

Purpose: This study aimed to evaluate the impact of the Hip Fracture Fast-Track (HFFT) protocol, designed specifically for older patients at our hospital, which commenced on January 1, 2022, on the management of emergency department (ED) pain in older adults with hip fractures. Patients and Methods: Retrospective pre- and post-study data from electronic health records (EHR) at our hospital, using the International Classification of Diseases (ICD)-10 codes S72.0, S72.1, S72.8, and S72.9, were utilized. The study included patients aged 65 years or older who presented to the ED with low-energy, non-pathologic isolated hip fractures or proximal femur fractures. The pre-HFFT period included patients from January 1, 2020, to December 31, 2021, and the post-HFFT period included patients from January 1, 2022, to October 31, 2023. Data were compared for the proportion of patients undergoing pain evaluation in the ED, before discharge, time to first analgesia, number of patients receiving pain relief in the ED, and the use of fascia iliaca compartment blocks (FICBs) and pericapsular nerve group blocks (PENGBs). Results: The final analysis involved 258 patients, with 116 in the pre-protocol group and 142 in the post-protocol group. The rate of analgesic use increased significantly in the post-HFFT group (78 [67.24%] vs 111 [78.17%], P = 0.049). The rate of pain score screening at triage increased from 51.72% before the HFFT protocol to 86.62% post-HFFT protocol (p < 0.001). Compared with the pre-HFFT protocol, the post-HFFT protocol exhibited a higher rate of FICB (0% vs 14.08%, p < 0.001) and PENGB (0% vs 5.63%, p = 0.009) administration. Conclusion: The HFFT protocol's implementation was associated with improved ED pain evaluation and analgesic administration in older adults with hip fractures. These findings indicate that tailored protocols, such as the HFFT, hold promise for enhancing emergency care for this vulnerable population.

Efficacy of intrauterine device procedural analgesics.

ABSTRACT: Nearly half of all pregnancies worldwide are unintended. Intrauterine devices are an effective, long-acting form of pregnancy prevention that require minimal maintenance, and also can be used in patients with menorrhagia. However, they are underused because of pain associated with their insertion. Topical and local anesthesia are good options for reducing procedural pain in select patients. IUD placement falls within the scope of practice for physician associates/assistants (PAs) practicing in family medicine, internal medicine, and women's health. PAs should be aware of these additional analgesia options available to patients in order to increase use of effective contraception.

Repurposing of the analgesic Neurotropin for MASLD/MASH treatment.

BACKGROUND: The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) has increased in recent decades. Approximately 25% of patients with MASLD progress to metabolic dysfunction-associated steatohepatitis, which is characterized by hepatic steatosis plus hepatocyte damage, inflammation, and fibrosis. We previously reported that Neurotropin (NTP), a drug used for relieving pain in Japan and China, inhibits lipid accumulation in hepatocytes by preventing mitochondrial dysfunction. We hypothesized that inhibiting hepatic steatosis and inflammation by NTP can be an effective strategy for treating MASLD and tested this hypothesis in a MASLD mouse model. METHODS: Six-week-old C57BL/6NJ male mice were fed a normal diet and normal drinking water or a high-fat diet with high fructose/glucose water for 12 weeks. During the last 6 weeks, the mice were also given high-dose NTP, low-dose NTP, or control treatment. Histologic, biochemical, and functional tests were conducted. MitoPlex, a new proteomic platform, was used to measure mitochondrial proteins, as mitochondrial dysfunction was previously reported to be associated with MASLD progression. RESULTS: NTP inhibited the development of hepatic steatosis, injury, inflammation, and fibrosis induced by feeding a high-fat diet plus high fructose/glucose in drinking water. NTP also inhibited HSC activation. MitoPlex analysis revealed that NTP upregulated the expression of mitochondrial proteins related to oxidative phosphorylation, the tricarboxylic acid cycle, mitochondrial dynamics, and fatty acid transport. CONCLUSIONS: Our results indicate that NTP prevents the development of hepatic steatosis, injury, and inflammation by preserving mitochondrial function in the liver and inhibits liver fibrosis by suppressing HSC activation. Thus, repurposing NTP may be a beneficial option for treating MASLD/metabolic dysfunction-associated steatohepatitis.

Molecular Transformers: Adaptive Multitarget Ligands for Esterase-Induced Transition from Analgesics to Anesthetics.

Multitarget strategies are essential in addressing complex diseases, yet developing multitarget-directed ligands (MTDLs) is particularly challenging when aiming to engage multiple therapeutic targets across different tissues. Here, we present a molecular transformer strategy, enhancing traditional MTDLs. By utilizing esterase-driven hydrolysis, this approach mimics the adaptive nature of transformers for enabling molecules to modify their pharmacological effects in response to the biological milieu. By virtual screening and biological evaluation, we identified KGP-25, a novel compound initially targeting the voltage-gated sodium channel 1.8 (Nav1.8) in the peripheral nervous system (PNS) for analgesia, and later the γ-aminobutyric acid subtype A receptor (GABAA) in the central nervous system (CNS) for general anesthesia. Our findings confirm KGP-25's dual efficacy in cellular and animal models, effectively reducing opioid-related side effects. This study validates the molecular transformer approach in drug design and highlights its potential to overcome the limitations of conventional MTDLs, paving new avenues in innovative therapeutic strategies.

Preoperative psychological factors influence analgesic consumption and self-reported pain intensity following breast cancer surgery.

BACKGROUND: Psychological factors such as anxiety and mood appear to influence acute postoperative pain; however, there is conflicting evidence on the relationship between preoperative psychological parameters and the severity of postoperative pain. In the context of the stressful setting of initial surgery for breast cancer, we conducted a prospective observational study of patients who were scheduled to undergo initial breast cancer surgery. METHODS: The objectives were to examine the potential associations between predefined preoperative psychological parameters and (i) Self-reported pain scores at discharge from the postoperative acute care unit, (ii) Cumulative perioperative opioid consumption at four hours postoperatively and (iii) Self-reported pain as measured during the first seven days after surgery. Patients completed the following questionnaires during the three hours prior to surgery: the Spielberger State Trait Anxiety Inventory (STAI State and Trait), the Pain Catastrophizing Scale (PCS), the Cohen Stress Questionnaire (CSQ), the Hospital Anxiety and Depression Scale (HADS A and D), and the short-form McGill Pain Questionnaire. Postoperative pain experience was assessed using patient self-reports of pain (SF Magill Pain questionnaire on discharge from the postanaesthesia care unit and a pain diary for seven days postoperatively) and records of analgesic consumption. RESULTS: Pre- to postoperative self-reported pain was significantly different with respect to the STAI State, Cohen score and PCS for both low and high values (p < 0.001), but only patients categorized as having low STAI Trait, HADS A, and HADS D values achieved significant differences (p < 0.001). A significant positive correlation was demonstrated between preoperative state anxiety (STAI) and the most severe pain reported during the first seven days postoperatively (r = 0.271, p = 0.013). Patients who were categorized preoperatively as having a "high value" for each of the psychological parameters studied (HADS A and D, STAI State and Trait and PCS) tended to have greater perioperative opioid consumption (up to four hours postoperatively); this trend was statistically significant for HADS D and HADS A only. Using a linear regression model, state anxiety was found to be a significant predictor of postoperative pain based on self-reports during the first seven postoperative days (standardized ß = 0.271, t = 2.286, p = 0.025). CONCLUSION: Preoperative state anxiety, in particular, is associated with the severity of postoperative pain experienced by women undergoing initial breast cancer surgery. Formal preoperative assessment of anxiety may be warranted in this setting with a view to optimize perioperative analgesia and wellbeing.

Exploring the safety of lycorine in the central nervous system and its impact on pain-like behaviors in mice.

Alkaloid analgesics have been associated with adverse effects on the central nervous system (CNS). Therefore, it is crucial to characterize the effects of alkaloid analgesics. Plants rich in lycorine, an alkaloid, have shown promise as analgesics. However, the exploration of their CNS side effects, and analgesic effectiveness remains incomplete. The aim of the present study was to investigate the CNS safety profiles of lycorine and its potential analgesic efficacy. Lycorine (3, 10, and 30 mg/kg, intraperitoneal) did not affect motor coordination, and doses of 3 and 10 mg/kg of lycorine did not lead to any impairment in spontaneous locomotor activity. However, the highest dose (30 mg/kg) demonstrated a significant impairment in rearing behavior and an increase in immobility. The safety doses were subsequently used to assess the analgesic efficacy of lycorine in a mouse model of inflammatory pain. Lycorine (1, 3, and 10 mg/kg, intraperitoneal) demonstrated a dose-dependent reduction in pain-like behaviors in formalin-induced mice. In the in vitro study, lycorine regulated immune cells, suggesting its involvement as a cellular mechanism underlying the suppression of pain-like behaviors observed in the formalin model. Overall, our findings delineate the CNS safety range of lycorine in mice and suggest its potential use as an analgesic.

Protocol for a pragmatic trial of Cannabidiol (CBD) to improve chronic pain symptoms among United States Veterans.

BACKGROUND: Chronic pain affects over 100 million Americans, with a disproportionately high number being Veterans. Chronic pain is often difficult to treat and responds variably to medications, with many providing minimal relief or having adverse side effects that preclude use. Cannabidiol (CBD) has emerged as a potential treatment for chronic pain, yet research in this area remains limited, with few studies examining CBD's analgesic potential. Because Veterans have a high need for improved pain care, we designed a clinical trial to investigate CBD's effectiveness in managing chronic pain symptoms among Veterans. We aim to determine whether CBD oral solution compared to placebo study medication is associated with greater improvement in the Patient Global Impression of Change (PGIC). METHODS: We designed a randomized, double-blind, placebo-controlled, pragmatic clinical trial with 468 participants. Participants will be randomly assigned in a 1:1 ratio to receive either placebo or a CBD oral solution over a 4-week period. The trial is remote via a smartphone app and by shipping study materials, including study medication, to participants. We will compare the difference in PGIC between the CBD and placebo group after four weeks and impacts on secondary outcomes (e.g., pain severity, pain interference, anxiety, suicide ideation, and sleep disturbance). DISCUSSION: Once complete, this trial will be among the largest to date investigating the efficacy of CBD for chronic pain. Findings from this clinical trial will contribute to a greater knowledge of CBD's analgesic potential and guide further research. Given the relative availability of CBD, our findings will help elucidate the potential of an accessible option for helping to manage chronic pain among Veterans. TRIAL REGISTRATION: This protocol is registered at clinicaltrials.gov under study number NCT06213233.

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

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

A New Application for Cenicriviroc, a Dual CCR2/CCR5 Antagonist, in the Treatment of Painful Diabetic Neuropathy in a Mouse Model.

The ligands of chemokine receptors 2 and 5 (CCR2 and CCR5, respectively) are associated with the pathomechanism of neuropathic pain development, but their role in painful diabetic neuropathy remains unclear. Therefore, the aim of our study was to examine the function of these factors in the hypersensitivity accompanying diabetes. Additionally, we analyzed the analgesic effect of cenicriviroc (CVC), a dual CCR2/CCR5 antagonist, and its influence on the effectiveness of morphine. An increasing number of experimental studies have shown that targeting more than one molecular target is advantageous compared with the coadministration of individual pharmacophores in terms of their analgesic effect. The advantage of using bifunctional compounds is that they gain simultaneous access to two receptors at the same dose, positively affecting their pharmacokinetics and pharmacodynamics and consequently leading to improved analgesia. Experiments were performed on male and female Swiss albino mice with a streptozotocin (STZ, 200 mg/kg, i.p.) model of diabetic neuropathy. We found that the blood glucose level increased, and the mechanical and thermal hypersensitivity developed on the 7th day after STZ administration. In male mice, we observed increased mRNA levels of Ccl2, Ccl5, and Ccl7, while in female mice, we observed additional increases in Ccl8 and Ccl12 levels. We have demonstrated for the first time that a single administration of cenicriviroc relieves pain to a similar extent in male and female mice. Moreover, repeated coadministration of cenicriviroc with morphine delays the development of opioid tolerance, while the best and longest-lasting analgesic effect is achieved by repeated administration of cenicriviroc alone, which reduces pain hypersensitivity in STZ-exposed mice, and unlike morphine, no tolerance to the analgesic effects of CVC is observed until Day 15 of treatment. Based on these results, we suggest that targeting CCR2 and CCR5 with CVC is a potent therapeutic option for novel pain treatments in diabetic neuropathy patients.

The dual amylin and calcitonin receptor agonist KBP-336 elicits a unique combination of weight loss, antinociception and bone protection - a novel disease-modifying osteoarthritis drug.

BACKGROUND: Despite the extensive research to provide a disease-modifying osteoarthritis drug (DMOAD), there is still no approved DMOAD. Dual amylin and calcitonin receptor agonists (DACRA) can provide metabolic benefits along with antinociceptive and potential structural preserving effects. In these studies, we tested a DACRA named KBP-336 on a metabolic model of OA in meniscectomised (MNX) rats. METHODS: We evaluated KBP-336's effect on pain-like symptoms in Sprague Dawley (SD) rats on high-fat diet (HFD) that underwent meniscectomy using the von Frey test to measure the 50% paw withdrawal threshold (PWT) and analyzed using one-way ANOVA. Short in vivo studies and in vitro cell receptor expression systems were used to illustrate receptor pharmacology. RESULTS: After 30 weeks on HFD, including an 8-week treatment, female MNX animals receiving KBP-336 4.5 nmol/Kg/72 h had lower body weight and smaller adipose tissues than their vehicle-treated counterparts. After 20 weeks on HFD, including an 8-week treatment, male rats receiving KBP-336 had lower body weight than the vehicle group. In both the female and male rats, the MNX groups on KBP-336 treatment had a higher PWT than the vehicle-treated MNX group. Aiming to identify the receptor influencing pain alleviation, KBP-336 was compared to the long-acting human calcitonin (hCTA). Single-dose studies on 12-week-old male rats showed that hCTA lowers CTX-I without affecting food intake, confirming its calcitonin receptor selectivity. On the metabolic OA model with 18 weeks of HFD, including 6-week treatment, hCTA at 100 nmol/Kg/24 h and KBP-336 at 0.5, 1.5, and 4.5 nmol/Kg/72 h produced significantly higher PWT in MNX animals compared to MNX animals on vehicle treatment. hCTA and KBP-336 at 0.5 nmol/Kg did not affect body weight and fat tissues. CONCLUSION: Overall, KBP-336 improved the pain observed in the metabolic OA model. Calcitonin receptor activation proved to be essential in this antinociceptive effect.

Optimizing medication guidance support for patients with cancer pain: development and evaluation of a pharmaceutical care system for healthcare professionals.

BACKGROUND: Effective management of cancer pain critically depends on timely medication administration and adherence to precise medication guidelines. In the context of limited time and a busy healthcare environment, tailoring the optimal medication schedule for each patient with cancer pain presents a significant challenge for physicians and clinical pharmacists. METHODS: To address this challenge, we conducted a comprehensive analysis of healthcare professionals' needs in guiding cancer pain medication. By developing core features based on key user needs and continuously updating them, we have created the Universal Medication Schedule System (UMSS). We invited 20 physicians and pharmacists specializing in oncology or cancer pain to trial the system and assessed UMSS usage through distributed questionnaires. RESULTS: We identified five key needs of healthcare professionals in cancer pain medication guidance. Based on these needs, we (1) constructed a comprehensive drug information database, including basic information for 1135 drugs, 130,590 drug interaction data entries, and 1409 individual medication timing constraints, and (2) developed a web-based system that provides essential reference information such as drug interactions and dietary restrictions. It can create medication schedules and provide medication education tailored to the patient's daily routine. Participating evaluators unanimously agreed (100%) that the system aids in accurately assessing the risks of polypharmacy and quickly scheduling medication regimens. CONCLUSION: UMSS, by offering personalized medication schedule support, assists healthcare professionals in better managing patients' medication treatment plans. However, further improvements are needed in the automation of database updates and maintenance, as well as in integrating it with electronic health records.

Analysis of Two Treatment Modalities for Post-surgical Pain after Hemorrhoidectomy.

Background: This non-randomized study aimed to compare the efficacy of two pharmacological treatments, "around-the-clock" analgesic treatment (ACAT) and "on-demand" analgesic treatment (ODAT), for managing postoperative pain following hemorrhoidectomy. Material and Methods: The study, conducted from July 2016 to December 2020, included 5335 hemorrhoidectomy patients. Participants were divided into ACAT (3767) and ODAT (1568) groups. The study was registered at clinicaltrials.gov (NCT04953182). Results: Patients had a mean age of 47.47 years, with 59.98% males. Postoperatively, 14.13% reported severe pain, 36.49% moderate, 34.28% mild, and 15.09% no pain. ACAT group's maximum pain was 3.04 (VAS), ODAT 4.95 (p; average pain was 0.79 (ACAT) and 1.45 (ODAT). Discharge pain was 0.42 (ACAT) and 0.63 (ODAT) VAS. The ACAT group consistently reported lower levels of pain across all measured instances. Higher BMI and younger age were pain risk factors (p=.049, p .001 respectively). ACAT administration resulted in reduced opioid usage, with meperidine showing a 68.38% decrease, morphine 43.57% less, tramadol 46.82% less, oxycodone reduced by 38.74%, and codeine by 53.40%. Additionally, the use of non-opioid analgesics was notably lower in the ACAT group, ranging from 16% to 59% less compared to the ODAT group. Conclusion: Hemorrhoidectomy induces moderate postoperative pain, with only 14% experiencing severe pain. A fixed schedule multimodal pain regimen, regardless of procedure and anesthesia type, reduces pain from moderate to mild post-hemorrhoidectomy. This approach also decreases opioid and non-opioid analgesic requirements. Higher BMI and younger age are identified as risk factors for elevated postoperative pain.

[Medication overuse headache]. / Kopfschmerz bei Medikamentenübergebrauch.

Medication overuse headache (MOH) is a globally prevalent and debilitating condition that results from excessive use of acute therapies and can significantly affect quality of life, despite the fact that simple information about the causes and consequences of the condition can help prevent or stop MOH. In recent years, many new insights have been gained into headaches caused by medication overuse. In addition, the diagnostic criteria and guideline recommendations have changed considerably. This article provides a comprehensive overview of the clinic, definition/classification, epidemiology, risk factors, pathophysiology, controversies, prevention, and treatment of MOH.

Knowledge and attitude towards the use of pain medications according to WHO cancer pain analgesic ladder in tertiary care hospitals of Pakistan.

To assess the knowledge and attitude of practicing physicians and surgeons towards the use of pain medication according to the World Health Organisation cancer pain analgesic ladder, the current study was conducted at tertiary care hospitals of the four provinces of Pakistan. Professionals having experience of treating cancer patients for >2 years were included. Data was collected using a self-administered questionnaire sent to each participant using Google Forms. Of the 630 physicians approached, 133(21%) responded. Of them, 74(55.64%) participants were familiar with the World Health Organisation analgesic ladder. There was a significant difference in the frequency of using the ladder based on age (p<0.05). Most participants 31(23%) reported the nonavailability of the recommended drugs as the reason for not following the analgesic ladder. There is a strong need to educate physicians and surgeons about the World Health Organisation analgesic ladder, and to make strategies to improve opioid availability in Pakistan.

A novel cinnamic and caffeic acid-conjugated peptide analogs with anticonvulsant and analgesic potency: Comparative analyses of trans/cis isomers.

The novel cinnamic acid (CA) (H4-CA, H5-CA, and H7-CA) and caffeic acid (KA) (H4-KA, H5-KA, and H7-KA) hemorphin analogs have recently been synthesized and their trans isomers have been tested for antiseizure and antinociceptive activity. In the present study, the cis forms of these compounds were tested and compared with their trans isomers in seizure and nociception tests in mice. The cis-H5-CA and H7-CA compounds showed efficacy against psychomotor seizures, whereas the trans isomers were ineffective. Both the cis and trans KA isomers were ineffective in the 6-Hz test. In the maximal electroshock (MES) test, the cis isomers showed superior antiseizure activity to the trans forms of CA and KA conjugates, respectively. The suppression of seizure propagation by cis-H5-CA and the cis-H5-KA was reversed by a kappa opioid receptor (KOR) antagonist. Naloxone and naltrindole were not effective. The cis-isomers of CA conjugates and cis-H7-KA produced significantly stronger antinociceptive effects than their trans-isomers. The cis-H5-CA antinociception was blocked by naloxone in the acute phase and by naloxone and KOR antagonists in the inflammatory phase of the formalin test. The antinociception of the KA conjugates was not abolished by opioid receptor blockade. None of the tested conjugates affected the thermal nociceptive threshold. The results of the docking analysis also suggest a model-specific mechanism related to the activity of the cis-isomers of CA and KA conjugates in relation to opioid receptors. Our findings pave the way for the further development of novel opioid-related antiseizure and antinociceptive therapeutics.

Statistical physical modeling insights for urinary analgesic drug adsorption on carbon nanomaterial derivative.

The presence of phenazopyridine in water is an environmental problem that can cause damage to human health and the environment. However, few studies have reported the adsorption of this emerging contaminant from aqueous matrices. Furthermore, existing research explored only conventional modeling to describe the adsorption phenomenon without understanding the behavior at the molecular level. Herein, the statistical physical modeling of phenazopyridine adsorption into graphene oxide is reported. Steric, energetic, and thermodynamic interpretations were used to describe the phenomenon that controls drug adsorption. The equilibrium data were fitted by mono, double, and multi-layer models, considering factors such as the numbers of phenazopyridine molecules by adsorption sites, density of receptor sites, and half saturation concentration. Furthermore, the statistical physical approach also calculated the thermodynamic parameters (free enthalpy, internal energy, Gibbs free energy, and entropy). The maximum adsorption capacity at the equilibrium was reached at 298 K (510.94 mg g-1). The results showed the physical meaning of adsorption, indicating that the adsorption occurs in multiple layers. The temperature affected the density of receptor sites and half saturation concentration. At the same time, the adsorbed species assumes different positions on the adsorbent surface as a function of the increase in the temperature. Meanwhile, the thermodynamic functions revealed increased entropy with the temperature and the equilibrium concentration.

Glucagon-like peptide-1 (GLP-1) receptor agonists for headache and pain disorders: a systematic review.

BACKGROUND: Glucagon-like peptide-1 (GLP-1) plays a crucial role in metabolic disorders by enhancing insulin secretion, inhibiting glucagon release, and slowing gastric emptying, thereby improving glycemic control. In recent years, GLP-1 role in neuronal pathways has expanded its therapeutic potential. We aim to comprehensively evaluate the relevance of GLP-1 in headache and pain disorders. METHODS: A systematic literature search was conducted on PubMed and Embase (Ovid) databases using the search terms "GLP-1" and "pain". Animal and human studies published in English language were included. Abstracts, reviews, and articles on other disorders than "pain" were excluded. RESULTS: The search strategy identified 833 hits, of which 42 studies were included in the final review. The studies were categorized into four groups: inflammatory pain and osteoarthritis, headaches, neuropathic pain and diabetic neuropathy, and visceral pain and irritable bowel syndrome. GLP-1 receptor (GLP-1R) agonists, like liraglutide, have shown analgesic effects by modulating pain hypersensitivity in animal models of inflammatory and neuropathic pain. GLP-1 is involved in migraine mechanisms and GLP-1R agonists are beneficial in individuals with idiopathic intracranial hypertension. Additionally, GLP-1R agonists reduce visceral hypersensitivity and ameliorate symptoms in patients with irritable bowel syndrome. CONCLUSIONS: The therapeutic scope of GLP-1R agonists is expanding beyond traditional metabolic targets, highlighting its potential for headache and pain disorders. Engineering bimodal molecules that integrate GLP-1R agonism with specific pain-related mechanisms may offer innovative therapeutic options.