Analgesic Potency Research Articles

EFFICACY OF SUBLINGUAL VERSUS ORAL PIROXICAM IN MANAGEMENT OF POST-SURGICAL PAIN, SWELLING AND TRISMUS AFTER LOWER 3RD MOLAR SURGERY- A RANDOMIZED CONTROL CLINICAL TRIAL

Background of the study: Third molar surgical removal is a common procedure in oral and maxillofacial surgery, causing moderate to severe pain, swelling, and trismus. Postoperative pain control improves patient recovery and oral function, with commonly used analgesics including Ibuprofen, Aceclofenac, Ketorolac, Tramadol, Paracetamol, Nalbuphine, Nimusulide, and Buprenorphine. Aim and Objective: The study compares oral and sub-lingual Piroxicam for managing post-surgical pain after extraction of impacted third molars, focusing on analgesia onset, pain intensity, swelling, and trismus degree. Materials and method: A randomized control trial was conducted on 30 patients who underwent surgical removal of mandibular impacted third molars. The patients were divided into two groups: Group I (Study) and Group II (Control). All patients underwent the procedure by a single surgeon. Post-operative medications were prescribed according to the study design, with Piroxicam 20mg administered sub-lingually (Group I) and 20mg orally (Group II). The parameters were assessed and measured for both groups, and the results and statistical analysis were compared. Result: The results revealed that the inter-group difference for the post-operative symptoms evaluated using a t-test for Equality of means by comparing the pre-op, POD 2, POD 7 values was statistically significant. Mean onset time taken and pain perception by Group I (Sub-lingual) in the first dose was 32.3 minutes and for Group II was 51.21 minutes which was established to be significantly (P<0.05) low for the sub-lingual group by statistical analysis. Conclusion: The study found that the sublingual route of administering Piroxicam had a faster onset of action and better analgesia postoperatively compared to the oral route. This is crucial for patients and surgeons to improve compliance and comfort post-operatively after impaction surgery, as potent analgesics are essential for effective pain management.

An LC-MS/MS method for the determination of W18 in urine samples

IntroductionSynthetic drugs pose one of the most significant drug problems worldwide. In this category, W18 emerges as a potent drug of abuse chemically related to fentanyl. W18 has an analgesic potency 10,000 times greater than morphine. Recent in-vitro studies reported no activity of W18 towards opioid receptors. However, its presence in seized drug samples indicates its use as a precursor in fentanyl synthesis. This emphasizes the need to develop methods for its detection in developing countries dealing with emerging new drugs.ObjectivesTo develop an analytical method for the determination of W18 in urine samples.MethodsStandards with W18 concentrations ranging from 5-500 ng/ml were prepared in negative urine along with deuterated internal standard. The samples were diluted with methanol, centrifuged and the supernatant was subjected to Liquid chromatography-tandem mass spectrometry (LC-MS-MS) with time of flight (QTOF) analysis. For chromatographic separation, a C18 column with 50 degrees oven temperature was used. The mobile phase consists of formic acid, water, and acetonitrile. The TOF MS was operated in positive ion mode and multiple reaction monitoring was used for quantification.ResultsThe retention time of W18 was obtained at 9.57 minutes. The parent ion with molecular weight 422.1 along with precursor ions Q1-273, Q2-111.0, Q3-150.0 g/mol were measured. The area of the standards ranges from 1 to 9.0 log 5 with R square of 0.99. The limit of detection (LOD) and quantitation were 5 and 20 ng/ml respectively. The recovery of W18 was estimated to be 96% from the from spiked urine standards.ConclusionsThe developed method is able to detect W18 presence in urine samples. This method has the potential to be used in clinical and research studies.Disclosure of InterestNone Declared

Evaluation of analgesic, antioxidant, and anti-inflammatory potential of Dianthus crinitus using mice as a research animal

In the past, natural resources were used as best therapeutic sources for different diseases. Among several herbal resources, certain plant families are known for their analgesic activities, such as Dianthus crinitus, which showed a good curative potential. The mentioned plant has been used traditionally for the healing of several illnesses such as pain, inflammation, injuries, etc. The current study, therefore, evaluated the analgesic and anti-antioxidant activities of ethanolic extracts of leaves, flowers, and seeds of Dianthus crinitus in mice. For analgesic activity, acetic acid and a hot plate thermal stimulation method were used to induce writhes in mice, followed by a tail emersion process. Results showed that the extract demonstrated analgesic potential in mice, signifying both peripheral and central modes of action. Furthermore, extract also significantly inhibited the rat paw edema triggered by carrageenan seaweed and dextran as revealed by neutrophil migration toward the peritoneal cavities of animals and enhanced vascular permeability. The data suggested that the extract exhibited a dose-dependent antioxidant action. These preliminary observations provided support for further exploration and justification for the potential development of a new class of analgesic and anti-inflammatory medicines from the constituents of Dianthus crinitus extract.

Pharmacodynamic effects following co-administration of cannabinoids and opioids: a scoping review of human experimental studies.

Cannabinoids are increasingly used in the management of chronic pain. Although analgesic potential has been demonstrated, cannabinoids interact with a range of bodily functions that are also influenced by chronic pain medications, including opioids. We performed a scoping review of literature on the pharmacodynamic effects following the co-administration of cannabinoids and opioids. We systematically searched EMBASE, PubMed, and PsycINFO for studies that experimentally investigated the co-effects of cannabinoids and opioids in human subjects. Available evidence was summarized by clinical population and organ system. A risk of bias assessment was performed. A total of 16 studies met the inclusion criteria. Study populations included patients with chronic non-cancer and cancer pain on long-term opioid regimens and healthy young adults without prior exposure to opioids who were subject to experimental nociceptive stimuli. Commonly administered cannabinoid agents included Δ9-tetrahydrocannabinol and/or cannabidiol. Co-administration of cannabinoids and opioids did not consistently improve pain outcomes; however, sleep and mood benefits were observed in chronic pain patients. Increased somnolence, memory and attention impairment, dizziness, gait disturbance, and nauseousness and vomiting were noted with co-administration of cannabinoids and opioids. Cardiorespiratory effects following co-administration appeared to vary according to duration of exposure, population type, and prior exposure to cannabinoids and opioids. The available evidence directly investigating the pharmacodynamic effects following co-administration of cannabinoids and opioids for non-analgesic outcomes is scarce and suffers from a lack of methodological reporting. As such, further research in this area with comprehensive methodologic reporting is warranted.

The clinical use of cannabinoids for pain

Cannabis has been used for medicinal purposes more than millennia., further research concerning the potential applications of medicinal cannabis has gained considerable momentum in the medical community. Among the several cannabinoids produced by cannabis leaves, the most notable compounds include Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), which act on the endocannabinoid system and play significant physiological roles, such as pain regulation. This manuscript reviews the current knowledge and provides medical evidence about the analgesic potential of medicinal cannabis for chronic pain management. The following databases were searched: MEDLINE, COCHRANE, SCIELO and LILACS. Only randomized controlled trials published within six years were selected. Nine articles met the inclusion criteria for the present review. All nine RCTs reported a significant difference in the reduction in pain intensity; however, only five of the studies reported a significant reduction in pain. The presence of mild-to-moderate adverse events was greater in the intervention groups than in the control group, but these adverse events were well tolerated. The difference in opioid use and other analgesic drugs between the intervention group and the placebo group was not statistically significant. Cannabis-derived compounds promote beneficial effects when administered into patients with chronic pain.

Evaluating The Analgesic Activity of Leaf, Stem Bark Extract And Isolated Nutraceuticals of <i>Caesalpinia Bonducella L (Roxb.)</i>

Evaluating The Analgesic Activity of Leaf, Stem Bark Extract And Isolated Nutraceuticals of <i>Caesalpinia Bonducella L (Roxb.)</i>

ANALGESIC AND ANTI-LITHIASIC EFFECTS OF MOROCCAN Citrus aurantium FLOWERS AND FRUIT AQUEOUS EXTRACTS

Citrus aurantium holds widespread use in Moroccan society as a remedy for various diseases, owing to its significant pharmacological properties. The objective of this study was to investigate the antioxidant activity, analgesic potential, and anti-lithiasis properties of the aqueous extracts of both the fruits and juice of Citrus aurantium. To achieve this, we employed various techniques: antioxidant activity was assessed using 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and reducing power assays (FRAP), while the antinociceptive effect of the plant was evaluated through writhing and hotplate tests on mice. The urolithiasis model was induced in rats through the administration of ethylene glycol and ammonium chloride, and assessments were made based on variations in body weight, kidney histopathology, and biochemical analysis using urea and creatinine. Our findings demonstrated significant antioxidant activity in both extracts (flowers and juice) of Citrus aurantium, represented by DPPH values of 5.42±0.20 and 2.87±0.42, and FRAP values of 4.23±0.05 and 1.67±0.13 in flowers and juice, respectively. The obtained results also showed that Citrus aurantium extracts significantly reduced the number of writhes and increased the latency time in response to a thermal stimulus compared to the control group (p≤0.001). Both extracts (flowers and juice) of Citrus aurantium exhibited a protective effect on the kidneys by preventing the formation of oxalo-calcium crystals. The histopathological study of the kidneys in the groups treated with Citrus aurantium revealed a marked reduction in abnormalities observed in rats treated with Ethylene Glycol. Additionally, urea and creatinine values were reduced compared to the control group (p≤0.001), signifying an important anti-urolithiasic activity. Overall, Citrus aurantium demonstrated potent antioxidant, analgesic and antilithic activities, suggesting its potential as a valuable natural source of bioactive compounds with various therapeutic applications. Keywords: Citrus aurantium; Uro-lithiasis; Histopathological examination; Biochemical parameters; Analgesic effect.

Anti-Inflammatory, Antipyretic, and Analgesic Potential of Chitin and Chitosan Derived from Cockroaches (Periplaneta americana) and Termites.

The chitin and chitosan biopolymers are extremely valuable because of their numerous industrial and pharmacological uses. Chitin and chitosan were extracted from the exoskeleton of Periplaneta americana (cockroaches) and termites using various acid and alkali techniques. The extraction process involves an initial demineralization step, during which integument dry powder was subjected to 500 mL (2.07 mol/L) of concentrated HCl at 100 degrees Celsius for 30 min, followed by meticulous rinsing with distilled water to restore the pH to its baseline. Deproteinization was conducted at 80 degrees Celsius using 500 mL (1 mol/L) of NaOH solution, which was repeated for 24 h. A total of 250 mL (0.06 mol/L) of NaOH was added at 100 degrees Celsius for 4 h to obtain chitosan, followed by extensive washing and subsequent drying. FTIR analysis was used to identify the functional groups in Periplaneta americana and termites. The crystallinity of these biopolymers, which have a face-centered cubic structure, was determined by X-ray diffraction analysis. This study assessed the analgesic properties of chitin and chitosan via an acetic-acid-induced writhing test in mice, revealing a significant reduction in writhing behavior following the chitin and chitosan extract. Notably, chitin exhibits the highest degree of analgesic activity compared to chitosan. Both chitin and chitosan show anti-inflammatory effects, with chitosan absorbing proton ions at sites of inflammation, while chitin effectively inhibits ear edema and elicits an analgesic response in mice. Furthermore, the present study revealed antipyretic activity, with termite chitin demonstrating the most significant effect at a concentration of 500 µL/mL, followed by chitosan and chitin at 100 µL/mL. These findings indicate the potential of using chitin and chitosan derived from termites and Periplaneta americana as natural anti-inflammatory compounds, implying prospective uses in anti-inflammatory, antipyretic, and analgesic capabilities.

Chemical composition, antioxidant, antimicrobial, and wound healing effects of Trachyspermum roxburghianum (DC.) H. Wolff essential oil: An in vivo and in silico approach

Ethnopharmacological relevanceTrachyspermum roxburghianum (DC.) H. Wolff, commonly known as ‘Ajamoda,’ is a neglected Indian spice highly used in Ayurveda and folklore remedies as an antimicrobial for chronic wounds and discharges, along with many other disease conditions. Aim of the studyThe objective of the study was to explore chemical composition and to investigate the antioxidant, antimicrobial, analgesic, and wound healing activities of T. roxburghianum fruit essential oil from India. Materials and methodsThe phytochemical characterization of the oil was determined through standard qualitative procedures and the gas chromatography-mass spectrometry (GC-MS) technique. The in vitro antioxidant aptitude was assessed by scavenging DPPH and ABTS radicals. The antimicrobial potential of the oil was investigated using the disc diffusion method, followed by the determination of minimum inhibitory concentration against Gram-positive and Gram-negative bacterial and fungal strains. The analgesic potential was evaluated using thermal and chemically induced pain models in Swiss albino mice. Wound healing was assessed in vivo, including determining wound contraction rates, histopathology, and hydroxyproline estimation, using the excision wound model in Swiss albino mice. ResultsGC-MS analysis identified 55 compounds with major terpenoids, including thymol (13.8%), limonene (11.5%), and others. Substantial radical-scavenging activity was exhibited by T. roxburghianum fruit essential oil (TREO) (IC50 94.41 ± 2.00 μg/mL in DPPH assay and 91.28 ± 1.94 μg/mL in ABTS assay). Microorganisms were inhibited with low MIC (2 μL/mL for the inhibition of Staphylococcus aureus and Bacillus subtilis; 4 μL/mL against Salmonella typhi and 16 μL/mL against Candida albicans). In the cytotoxicity study, no cytotoxicity was observed on the Monkey Normal Kidney Cell line (Vero). Significant antinociceptive effects were observed (25.47 ± 1.10 % of inhibition at 100 mg/kg and 44.31 ± 1.69 % at 200 mg/kg). A remarkable rate of wound closure and epithelization, along with a marked increase in hydroxyproline content, were observed for the oil during wound healing in mice. ConclusionsThe results suggested that oil could be utilized as a potential source of wound healing therapeutics.

An investigation on the role of oxytocin in chronic neuropathic pain in a Wistar rat model

Introduction Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side effect with ineffective preventative and curative treatment. Currently, only Duloxetine has been recommended as effective treatment for CIPN, which has shown individual-dependent, short-term analgesic effects, with limiting adverse effects and poor bioavailability. The neuropeptide, oxytocin, may offer significant analgesic and anxiolytic potential, as it exerts central and peripheral attenuating effects on nociception. However, it is unknown whether the intervention administered in a model of CIPN is an effective therapeutic alternative or adjuvant. Materials and Methods The intervention was divided into two phases. Phase 1 aimed to induce CIPN in adult Wistar rats using the chemotherapeutic agent Paclitaxel. Mechanical (electronic von Frey filament) and thermal (acetone evaporation test and Hargreaves test) hypersensitivity testing were used to evaluate changes due to the neuropathic induction. Phase 2 consisted of a 14-day intervention period with saline (o.g.), duloextine (o.g.), or oxytocin (i.n.) administered as treatment. Following the intervention, anxiety-like behaviour was assessed using the elevated plus maze (EPM) and light–dark box protocols. Analysis of peripheral plasma corticosterone, peripheral plasma oxytocin, and hypothalamic oxytocin concentrations were assessed using ELISA assays. Results The findings showed that we were able to successfully establish a model of chemotherapy-induced peripheral neuropathy during Phase 1, determined by the increase in mechanical and thermal nociceptive responses following Paclitaxel administration. Furthermore, the animals treated with oxytocin displayed a significant improvement in mechanical sensitivity over the intervention phase, indicative of an improvement in nociceptive sensitivity in the presence of neuropathic pain. Animals that received Paclitaxel and treated with oxytocin also displayed significantly greater explorative behaviour during the EPM, indicative of a reduced presence of anxiety-like behaviour. Conclusion Our results support the hypothesis that intranasally administered oxytocin may augment the analgesic and anxiolytic effects of duloxetine in a chemotherapy induced peripheral neuropathy model in a Wistar rat. Future studies should consider administering the treatments in combination to observe the potential synergistic effects.

Pyrazoles as Anti-inflammatory and Analgesic Agents: In-vivo and In-silico Studies.

Pyrazole is a well-known nucleus in the pharmacy field with a wide range of other activities in addition to anti-inflammatory and analgesic, i.e., anticonvulsant, antiviral, and anticancer activities. There are well-known marketed drugs having pyrazole moiety as celecoxib, and lonazolac as COX-II inhibitors. We aim to synthesize better anti-inflammatory than existing ones. Thiophene is also known for its analgesic and anti-inflammatory action. Thus, the fusion of both gives better anti-inflammatory agents. In the present studies, derivatives from two series of pyrazole were prepared by reacting substituted chalcone (3a-3f) derivatives prepared from 2-acetyl thiophene. They substituted aromatic aldehydes with phenyl hydrazine to form (5a-5f) and with 2, 4-dinitro phenyl hydrazine giving compounds (6a-6f) separately. Purified and characterized pyrazoles have been analyzed for in-vivo analgesic and anti-inflammatory activities by using standard methods. Compounds 5e, 5f, and 6d were proved to be potent analgesics and series (5a-5f) was found to have anti-inflammatory action, which was further validated using docking and ADME studies. The ADME profile of synthesized compounds was found to be satisfactory. The synthesized compounds can serve as lead for further drug designing.

Effects of Patient-Controlled Transcutaneous Electrical Acupoint Stimulation on Cancer Induced Bone Pain Relief in Patients with Non-Small Cell Lung Cancer: Study Protocol for a Randomized Controlled Trial.

Transcutaneous Electrical Acupoint Stimulation (TEAS) therapy opens up the possibility for individuals with Cancer-induced bone pain (CIBP) to receive a home-based, patient-controlled approach to pain management. The aim of this study is designed to evaluate the efficacy of patient-controlled TEAS (PC-TEAS) for relieving CIBP in patients with non-small cell lung cancer (NSCLC). This is a study protocol for a prospective, triple-blind, randomized controlled trial. We anticipate enrolling 188 participants with NSCLC bone metastases who are also using potent opioid analgesics from 4 Chinese medical centers. These participants will be randomly assigned in a 1:1 ratio to either the true PC-TEAS or the sham PC-TEAS group. All participants will receive standard adjuvant oncology therapy. The true group will undergo patient-controlled TEAS intervention as needed, while the sham group will follow the same treatment schedule but with non-conductive gel patches. Each treatment course will span 7 days, with a total of 4 courses administered. There will be 4 assessment time points: baseline, the conclusion of weeks 4, 8, and 12. The primary outcome of this investigation is the response rate of the average pain on the Brief Pain Inventory (BPI) scale at week 4 after treatment. Secondary outcomes include pain related indicators, quality of life scale, mood scales, and routine blood counts on the assessment days. Any adverse events will be promptly addressed and reported if they occur. We will manage trial data using the EDC platform, with a data monitoring committee providing regular quality oversight. PC-TEAS interventions offer an attempt to achieve home-based acupuncture treatment and the feasibility of achieving triple blinding in acupuncture research. This study is designed to provide more rigorous trial evidence for the adjuvant treatment of cancer-related pain by acupuncture and to explore a safe and effective integrative medicine scheme for CIBP. ClinicalTrials.gov NCT05730972, registered February 16, 2023.

Clinical Studies that Initiated the Use of Spinal Opioids for the Treatment of Pain: A New Approach to Historical Review.

Opioids administered into the spinal space by intrathecal or epidural routes can provide potent and prolonged selective analgesia. Compared to the systemic administration of opioids, spinal administration can bring about analgesia with fewer central and systemic adverse effects. For the past 40 years, spinal opioid analgesia has achieved great popularity in various fields of pain treatment. The aim of this work is to identify clinical studies that initiated the use of spinal opioids for the treatment of pain. To determine the historical role of each of the review's studies, we used the combination of two factors: the study priority in terms of the time of its publication and the degree of its acknowledgement in the form of citation impact. The date of publication was regarded as the primary factor, but only if the count of citations indicated a sufficient acknowledgement by the other authors. The citation impact was assessed as the initial citation count - for a period of five years after the year of article publication - and the total count. Analysis of the related data shows that the clinical studies initiating the use of spinal opioids for the treatment of pain belong to two groups of authors - Wang et al. and Behar et al. Both studies were published in 1979 and described delivery of morphine into the spinal space, although the techniques of administration were different: Wang et al. injected morphine intrathecally, Behar et al. administered morphine epidurally. The response to these studies was overwhelming - close to a dozen reports on this topic were published in 1979 and more than a hundred - in 1980-1981. The total citation response to the Wang et al. article reached 699, and that to Behar et al. - 518. Two earlier records (1900-1901) of the use of intrathecal morphine, by Nicolae Racoviceanu-Pitesti and Otojiro Kitagawa, found no following in medical literature for more than three quarters of a century.

Childhood trauma and the use of opioids and other prescription analgesics in adolescence and young adulthood: The HUNT Study.

Opioid and nonopioid analgesics are commonly prescribed to young people to alleviate pain. Even short-term prescriptions increase the risk of persistent use and future misuse of potent analgesics, such as opioids. Childhood trauma exposure has been found to be related to pain conditions and to using more prescription analgesics. This large, prospective cohort study aimed to investigate the association of a broad range of childhood trauma exposures with prescription rates for opioid and nonopioid analgesics in adolescence and young adulthood. Self-reported data on childhood trauma exposures from adolescents (aged 13-19 years) who participated in the Young-HUNT3 Study (2006-2008, n = 8199) were linked to data from the Norwegian Prescription Database (NorPD, 2004-2021). We found that exposure to childhood trauma was consistently associated with higher prescription rates for opioids throughout adolescence and young adulthood. The highest incidence rate ratio (IRR) in adolescence was observed for sexual abuse (IRR 1.63, confidence interval [CI] 1.19-2.23). In young adulthood, the highest IRR was observed for physical violence (2.66, CI 2.27-3.12). The same overall pattern was observed for nonopioid analgesics. The more frequent prescriptions of opioid and nonopioid analgesics to participants exposed to childhood trauma suggests a higher symptom load of pain causing them to seek professional help with pain relief. Receiving potent analgesics is not without risk, and the likelihood of misuse may be elevated among trauma-exposed individuals. A trauma-informed approach to pain could be vital for guiding clinicians to the most effective and least harmful treatment for each patient.

Hyaluronic acid from bluefin tuna by-product: Structural analysis and pharmacological activities

The fishing and aquaculture industries generate a huge amount of waste during processing and preservation operations, especially those of tuna. Recovering these by-products is a major economic and environmental challenge for manufacturers seeking to produce new active biomolecules of interest. A new hyaluronic acid was extracted from bluefin tuna's vitreous humour to assess its antioxidant and pharmacological activities. The characterization by infrared spectroscopy (FT-IR), nuclear magnetic resonance ((1D1H) and 2D (1H COSY, 1H/13C HSQC)) and size exclusion chromatography (SEC/MALS/DRI/VD) revealed that the extracted polysaccharide was a hyaluronic acid with high uronic acid content (55.8 %) and a weight average molecular weight of 888 kDa. This polymer possesses significant anti-radical activity and ferrous chelating capacity. In addition, pharmacological evaluation of its anti-inflammatory and analgesic potential, using preclinical models, in comparison with reference drugs (Dexamethasone, diclofenac, and acetylsalicylate of lysine), revealed promising anti-inflammatory activity as well as interesting peripheral and central antinociceptive activity. Therefore, our new hyaluronic acid compound may therefore serve as a potential drug candidate for the treatment of pain sensation and inflammation of various pathological origins.

Thermoresponsive Polymeric Hydromorphone Prodrug Provides Sustained Local Analgesia without Apparent Adverse Effects.

The extensive use of opioids for chronic pain management has contributed significantly to the current opioid epidemic. While many alternative nonopioid analgesics are available, opioids remain the most potent analgesics for moderate to severe pain management. In addition to the implementation of multimodal analgesia, there is a pressing need for the development of more effective and safer opioids. In this study, we developed a thermoresponsive N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-based hydromorphone (HMP) prodrug (ProGel-HMP, HMP content = 16.2 wt %, in base form). The aqueous solution of ProGel-HMP was free-flowing at 4 °C but became a hydrogel when the temperature was raised to ≥37 °C, allowing sustained local retention when administered in vivo. When tested in the destabilization of the medial meniscus (DMM) mouse model of osteoarthritis (OA), ProGel-HMP was retained after intra-articular injection in the OA knee joint for at least 2 weeks postinjection, with low extra-articular distribution. ProGel-HMP was not detected in the central nervous system (CNS). A single dose of ProGel-HMP produced rapid and sustained joint pain resolution for greater than 14 days when compared to saline and dose-equivalent HMP controls, likely mediated through peripheral μ-opioid receptors in the knee joint. Systemic analgesia effect was absent in the DMM mice treated with ProGel-HMP, as evident in the lack of difference in tail flick response between the ProGel-HMP-treated mice and the controls (i.e., Healthy, Saline, and Sham). Repeated dosing of ProGel-HMP did not induce tolerance. Collectively, these data support the further development of ProGel-HMP as a potent, safe, long-acting and nonaddictive analgesic for better clinical pain management.

Bakuchiol nanoemulsion loaded electrospun nanofibers for the treatment of burn wounds.

The present work aims to develop and evaluate the wound healing potential of bakuchiol nanoemulsion loaded electrospun scaffolds. Since oxidative stress and microbial burden leads the burn wounds to become chronic and fatal to patients, a phytoconstituent, bakuchiol (BAK), was screened on the basis of antioxidant and antimicrobial potential which also defined its dose. Furthermore, BAK was incorporated into a nanoemulsion to enhance its therapeutic efficacy, reduce its dosage frequency, and maximize its stability. The present study is inclined towards the collaborative interaction of natural products and novel drug delivery systems to develop safe and therapeutically efficient systems for burn wound healing. The optimized nanoemulsion showed excellent antioxidant and antimicrobial potential against wound susceptible pathogens, i.e., Candida albicans and Methicillin-resistant Staphylococcus aureus which was further loaded into gelatin based hydrogel and nanofibrous scaffold system. The mesh structure of scaffolds was chosen as a suitable carrier system for wound healing process not only because it offers resemblance to skin's anatomy but is also capable of providing uniform distribution of wound biomarkers across the skin. The prepared nanofibers were assessed for their analgesic, anti-inflammatory, and wound healing potential which was observed to be significantly better than its gel formulation.

Hyperlipidemia Increases Nalbuphine Brain Accumulation with Multiple Dosing without Affecting Its Analgesic Response-Its Respiratory Depression Potential Should Be Investigated in Future Studies.

Nalbuphine is associated with a significant risk of respiratory depression. Its central nervous system entry is hindered by P-glycoproteins, and lower P-glycoprotein activity is a risk factor for respiratory depression. We assessed the effect of hyperlipidemia on nalbuphine pharmacokinetics, brain and liver uptake, and analgesic response following single (2.5 mg/kg) and multiple (2.5 mg/kg/day for three days) doses in normolipidemic and hyperlipidemic rats. Trends of reduction and increase in nalbuphine Cmax and Vdss/F were observed, respectively, in hyperlipidemic rats. Negative correlations were observed between Cmax and serum lipoproteins. Serum-normalized brain and liver levels at 1 h post-dose were lower in hyperlipidemic rats, with brain and liver levels being negatively and positively correlated with TG and HDL, respectively. At steady state, marked nalbuphine accumulation was observed in hyperlipidemic rat brains (R = 1.6) compared with normolipidemic rats (R = 1.1). Nalbuphine analgesic response was not altered by hyperlipidemia at steady state. Caution should be exercised since greater brain accumulation in hyperlipidemic patients treated with nalbuphine could increase their risk of respiratory depression. Our study highlights an unexpected role of lipoproteins in drug absorption and tissue uptake. We also propose a model for reduced nalbuphine absorption based on interaction with intestinal HDL-3.

Ameliorative effects of Atriplex crassifolia (C.A.Mey) on pain and inflammation through modulation of inflammatory biomarkers and GC-MS-based metabolite profiling.

Atriplex crassifolia (A. crassifolia) is a locally occurring member of Chenopodiaceae family that has been used in folk medicine for the treatment of joint pain and inflammation. The present study was focused to determine the analgesic and anti-inflammatory potential of the plant. n-hexane (ACNH) and methanol (ACM) extracts of A. crassifolia were evaluated for in vitro anti-inflammatory potential using protein denaturation inhibition assay. In vivo anti-inflammatory potential was determined by oral administration of 250, 500, and 1000mg/kg/day of extracts against carrageenan and formalin-induced paw edema models. Inflammatory mediators such as TNF-α, IL-10, IL-1β, NF-kB, IL-4, and IL-6 were estimated in blood samples of animals subjected to formalin model of inflammation. Analgesic activity was determined using acetic acid-induced writhing and tail flick assay model. Phytochemical profiling was done by GC-mass spectrophotometer. The results of in vitro anti-inflammatory activity revealed that both ACNH and ACM displayed eminent inhibition of protein denaturation in concentration-dependent manner. In acute in vivo carrageenan-induced paw edema model, both extracts reduced inflammation at 5th and 6th hour of study (p < 0.05). A. crassifolia extracts exhibited significant inhibition against formalin-induced inflammation with maximum effect at 1000mg/kg. ACNH and ACM significantly augmented the inflammatory mediators (p < 0.05). Levels of TNF-α, IL-6, IL-1β, and NF-kB were reduced, while those of IL-4 and IL-10 were upregulated. ACNH displayed maximum analgesic effect at 1000mg/kg, while ACM showed potent activity at 500 and 1000mg/kg. The extracts restored the CBC, TLC and CRP toward normal. GC-MS analysis revealed the presence of compounds like n-hexadecanoic acid, Phytol, (9E,11E)-octadecadienoic acid, 2-hydroxy-1-(hydroxymethyl) ethyl ester, 1-hexacosene, vitamin E, campesterol, stigmasterol, gamma sitosterol in both extracts. These compounds have been reported to suppress inflammation by inhibiting inflammatory cytokines. The current study concludes that A. crassifolia possesses significant anti-nociceptive and anti-inflammatory potential owing to the presence of phytochemicals.

Uncontrolled pain: a call for better study design.

Studies assessing animal pain in veterinary research are often performed primarily for the benefit of animals. Frequently, the goal of these studies is to determine whether the analgesic effect of a novel treatment is clinically meaningful, and therefore has the capacity to improve the welfare of treated animals. To determine the treatment effect of a potential analgesic, control groups are necessary to allow comparison. There are negative control groups (where pain is unattenuated) and positive control groups (where pain is attenuated). Arising out of animal welfare concerns, there is growing reluctance to use negative control groups in pain studies. But for studies where pain is experimentally induced, the absence of a negative control group removes the opportunity to demonstrate that the study methods could differentiate a positive control intervention from doing nothing at all. For studies that are controlled by a single comparison group, the capacity to distinguish treatment effects from experimental noise is more difficult; especially considering that pain studies often involve small sample sizes, small and variable treatment effects, systematic error and use pain assessment measures that are unreliable. Due to these limitations, and with a focus on farm animals, we argue that many pain studies would be enhanced by the simultaneous inclusion of positive and negative control groups. This would help provide study-specific definitions of pain and pain attenuation, thereby permitting more reliable estimates of treatment effects. Adoption of our suggested refinements could improve animal welfare outcomes for millions of animals globally.