Palmitoyl-glucosamine co-micronized with curcumin for maintenance of meloxicam-induced pain relief in dogs with osteoarthritis pain.

BACKGROUND: Osteoarthritis (OA) pain is the number one cause of chronic pain in dogs. Multimodal treatment, including combining safe and effective nutritional interventions with non-steroidal anti-inflammatory drugs (NSAIDs), is currently considered one of the most appropriate choices for managing OA pain. Palmitoyl-glucosamine is a feed material belonging to the ALIAmide family, whose parent molecule is the prohomeostatic lipid amide N-palmitoyl-ethanolamine. Curcumin is a promising plant antioxidant. The present study aimed at investigating whether 18-week dietary integration with palmitoyl-glucosamine co-micronized with curcumin was able to maintain pain relief in dogs with OA-associated chronic pain receiving meloxicam (1.5 mg/ml oral suspension) on a tapering regimen (progressive 25% decrease of the original 0.1 mg/kg/day dose, on a biweekly basis) during the first 8 weeks of treatment. Pain was assessed both by the owners and veterinary surgeons, with the first using both subjective evaluation and validated metrology instruments-i.e., Helsinki Chronic Pain Index (HCPI) and Canine Brief Pain Inventory (CBPI)-while the second rating the severity of lameness and pain on palpation on two previously used 5-point scales. RESULTS: A total of fifty-eight dogs with OA chronic pain entered the uncontrolled study. Pain on HCPI was considered severe at baseline (range 18-39). Based on owner's assessment, 90% of dogs who responded to meloxicam at the full-dose regimen could reduce meloxicam up to 25% of the original dose without experiencing pain worsening. Moreover, 75% of dogs was assessed as having no pain increase ten weeks after meloxicam withdrawal. A statistically significant decrease of pain severity as scored by HCPI (P < 0.0001) was observed two and ten weeks after meloxicam withdrawal compared to study entry (17.0 ± 1.05 and 15.1 ± 1.02, respectively, vs 29.0 ± 0.74; mean ± SEM). After meloxicam withdrawal, no statistically significant change in the CBPI scores was recorded. Pain on palpation and lameness significantly changed to less severe distributions along the study period (P < 0.0001). CONCLUSION: The findings appear to suggest that dietary integration with palmitoyl-glucosamine co-micronized with curcumin was able to maintain meloxicam-induced pain relief in dogs with severe OA chronic pain.

Pharmacokinetics and analgesic efficacy of intranasal administration of tramadol in dogs after ovariohysterectomy.

OBJECTIVE: To assess analgesic efficacy and the pharmacokinetics of intranasal (IN) tramadol in dogs following ovariohysterectomy. STUDY DESIGN: Randomized, blinded clinical study. ANIMALS: A total of 30 bitches undergoing elective ovariohysterectomy. METHODS: Dogs were randomly assigned to one of three experimental groups (10 dogs per group): IN tramadol 4 mg kg-1 (group T-IN), intravenous (IV) tramadol 4 mg kg-1 (group T-IV) and IV methadone 0.2 mg kg-1 (group M). Drugs were administered at extubation. At established time points (before surgery and up to 8 hours after drug administration) analgesia was assessed using the Italian version of the Glasgow Composite Measure Pain Scale Short Form and physiological variables were recorded. To determine the pharmacokinetics of IN tramadol, blood samples were collected at predetermined time points. Shapiro-Wilk test was used to assess whether data were normally distributed and consequently parametric or non parametric tests were applied. A p value < 0.05 was considered significant. RESULTS: No significant intergroup differences were observed in the dogs that were administered rescue analgesia and time of its administration. Excluding dogs that were administered rescue analgesia, no significant intergroup differences emerged in pain scores and physiological variables, except for a lower rectal temperature in group M compared with the tramadol groups. After IN administration, tramadol was rapidly absorbed into the systemic circulation, reaching its maximum concentration (range 74.74-200.29 ng mL-1) within 30-60 minutes, it then decreased rapidly and was detectable in plasma for up to 2 hours after treatment in all dogs. CONCLUSIONS AND CLINICAL RELEVANCE: IN tramadol administration appears to be as effective as IV tramadol and methadone treatments in pain management of dogs after elective ovariohysterectomy. Given its low concentrations and short detection time in plasma after the IN route, systemic tramadol action appears unlikely.

Cardiovascular effects and intraoperative pharmacokinetics of tramadol in sheep undergoing spinal surgery.

OBJECTIVE: To evaluate the pharmacokinetics of two doses of tramadol during isoflurane anaesthesia in sheep and their ability to prevent the cardiovascular response induced by surgical stimulation. STUDY DESIGN: Prospective randomized controlled study. ANIMALS: A total of 12 healthy sheep (mean weight, 47.5±7.9 kg) undergoing lumbar transpedicular intervertebral disk nucleotomy. METHODS: Sheep were sedated with medetomidine, anaesthesia was induced with propofol and maintained with isoflurane at 1.5 vol.%. Baseline heart rate and blood pressure were measured and sheep were randomly assigned an intravenous injection of tramadol (4 or 6 mg kg-1). Fentanyl was injected as rescue analgesic if cardiovascular parameters were increased more than 20% compared to baseline. If those variables were below 20% of baseline, the concentration of isoflurane was gradually decreased until parameters returned to the original value. Blood collections were performed at pre-assigned times, and concentrations of tramadol and O-desmethyltramadol (M1) assessed by high-performance liquid chromatography. RESULTS: Time from premedication to anaesthesia induction, anaesthesia time, propofol dose and intraoperative body temperature were similar between doses. Cardiovascular variables remained between ±20% of baseline value, and no statistical difference was observed between treatments. Regardless of the dose of tramadol administered, arterial blood pressure was statistically higher than baseline 10 minutes after tramadol administration, but it gradually returned to previous values. A two-compartment model and a non-compartment model described the pharmacokinetics of tramadol and M1, respectively. Plasma concentrations of tramadol rapidly decreased in the first 2 hours for both doses with an elimination half-life of more than 40 minutes. The M1 maximum concentration was similar for both doses, and it was detected in plasma after 35 minutes. CONCLUSIONS AND CLINICAL RELEVANCE: Both doses of tramadol provided adequate cardiovascular stability during spinal surgery in sheep. The pharmacokinetic variables may be used to plan the dosage regime during general anaesthesia.

Validation of the Italian version of the UNESP-Botucatu unidimensional composite pain scale for the assessment of postoperative pain in cattle.

OBJECTIVE: The aim of this study was to validate the Italian version of the UNESP-Botucatu Unidimensional Composite Pain Scale (UCPS-IV) for assessing postoperative pain in cattle. STUDY DESIGN: Video analysis and psychometric testing. ANIMALS: A total of 40 Nellore cattle, age 2-3 years, weighing 365±51 kg. METHODS: An English version of the scale was translated to Italian and back translated to English to ensure semantic equivalence. A total of four Italian observers and the researcher who developed the original scale (considered as the gold standard) analysed videos of 40 cattle previously subjected to orchiectomy (recorded for each cattle at four predetermined timepoints during the perioperative period) unaware of the videos' timepoint. They assigned a pain score [ranging from no pain (0) to severe pain (10)] using the Italian version of the scale and verified the need for analgesic treatment for each animal. The obtained scores were subjected to psychometric validity, responsiveness and reliability tests. RESULTS: The factor analysis of the scale resulted in a one-factor solution. Significant changes in pain scores in response to surgery and analgesics confirmed not only the content and construct validity, but also responsiveness. The agreement between the researcher who developed the original scale and the blinded observers and the correlation between the pain scores determined by the scale and those determined by three classical unidimensional pain scales confirmed criterion and concurrent validity. Internal consistency of the scale was excellent. Inter- and intrarater reliability ranged from moderate to good and from moderate to very good for all scale items, respectively, supporting reproducibility and stability. The cut-off point for rescue analgesia calculated by the receiver operating characteristic curve was > 3. CONCLUSIONS AND CLINICAL RELEVANCE: The results confirm that the UNESP-Botucatu UCPS-IV appears to be a valid and reliable tool for the assessment of postorchiectomy pain in the bovine species. The determination of a cut-off point for rescue analgesia is also helpful for guiding analgesic therapy.

Preliminary study on attitudes, opinions and knowledge of Italian veterinarians with regard to abdominal visceral pain in dogs.

OBJECTIVE: To determine the attitudes, opinions and knowledge of Italian veterinarians regarding abdominal visceral pain in canine practice. STUDY DESIGN: Prospective online survey. METHODS: An online questionnaire was created on a Google Form spreadsheet and the weblink was circulated to Italian veterinarians on several mailing lists. The questionnaire, which was available between November 2012 and July 2013, comprised 18 closed, semi-closed and open questions divided into five sections (aetiology, recognition and assessment, drug choices for canine visceral pain, general knowledge about pain management and desire for further education, and demographic information). RESULTS: A total of 527 responses to the questionnaire were completed. Pancreatitis (19%), gastroenteritis (17%) and gastrointestinal obstructions or foreign bodies (9%) were highlighted as the most frequent causes of abdominal visceral pain. Posture, gait and movement changes (32%) and physiological changes (31%) were commonly quoted for pain recognition and assessment. Most respondents (74%) did not use pain scoring systems. Pancreatitis and peritonitis were considered the most painful abdominal conditions. Opioids (40%), nonsteroidal anti-inflammatory drugs (21%) and tramadol (20%) were cited as drugs for the management of visceral pain. A large percentage of respondents (97%) believed that their knowledge regarding pain management required improvement. There is practitioner interest for more continuing education in the subject. Most respondents were women (66%), aged between 25 and 40 years (57%). Internal medicine (56%), surgery (34%) and anaesthesiology (29%) were the main three speciality areas of interest in this study. CONCLUSIONS AND CLINICAL RELEVANCE: This online survey represents the opinion of a small number of Italian veterinarians regarding the assessment and treatment of canine abdominal visceral pain. The results show that Italian veterinarians are aware of the main causes and clinical signs of canine visceral pain. Pain-scoring systems are not often used for the recognition and assessment of pain; however, according to these veterinarians, visceral pain is commonly diagnosed.

Corrigendum: One-carbon pathway metabolites are altered in the plasma of subjects with Down syndrome: relation to chromosomal dosage.

[This corrects the article DOI: 10.3389/fmed.2022.1006891.].

Tuberculosis case finding based on symptom screening among immigrants, refugees and asylum seekers in Rome.

BACKGROUND: In Italy the proportion of cases of tuberculosis in persons originating from high-prevalence countries has been increasing in the last decade. We designed a study to assess adherence to and yield of a tuberculosis screening programme based on symptom screening conducted at primary care centres for regular and irregular immigrants and refugees/asylum seekers. METHODS: Presence of symptoms suggestive of active tuberculosis was investigated by verbal screening in migrants presenting for any medical condition to 3 free primary care centres in the province of Rome. Individuals reporting at least one symptom were referred to a tuberculosis clinic for diagnostic workup. RESULTS: Among 2142 migrants enrolled, 254 (11.9%) reported at least one symptom suggestive of active tuberculosis and 176 were referred to the tuberculosis clinic. Of them, 80 (45.4%) did not present for diagnostic evaluation. Tuberculosis was diagnosed in 7 individuals representing 0.33% of those screened and 7.3% of those evaluated for tuberculosis. CONCLUSION: The overall yield of this intervention was in the range reported for other tuberculosis screening programmes for migrants, although we recorded an unsatisfactory adherence to diagnostic workup. Possible advantages of this intervention include low cost and reduced burden of medical procedures for the screened population. Further evaluation of this approach appears to be warranted.

Pain in Pets: Beyond Physiology.

Animals do not speak a language humans understand, making it easy to believe that they do not experience pain the way humans do. Despite data affirming that companion animals can and do experience pain much as do humans, there remains a gap between companion animal acute pain management knowledge and its execution. Companion animal pain is not simply a physiological issue. Veterinary clinicians can and should embrace the foundational principles of clinical bioethics-respect for autonomy, nonmaleficence, beneficence, and justice-translated from human medicine for the benefit of their patients. By reframing companion animal pain as a bioethical issue, as described in this paper, veterinarians affirm their commitment to closing the gap between what is known and what is done for painful companion animals. This takes pet pain beyond physiology.

Pharmacokinetics, efficacy, and safety of cannabidiol in dogs: an update of current knowledge.

In the last 5 years, interest has grown in using phytocannabinoids, particularly cannabidiol (CBD), in veterinary medicine to treat several pathologies, including pain, epilepsy, anxiety, nausea, anorexia, skin lesions, and even some types of cancer, among others. Indeed, due to a positive perception of CBD use, many pet owners are increasingly requesting this option to relieve their pets, and many veterinarians are exploring this possibility for their patients. Besides the widespread empiric use of CBD in pets, the research is trying to obtain proof of its efficacy and lack of adverse effects and to know its pharmacokinetics to define an appropriate posology. This review summarizes all data published so far about the canine pharmacokinetics, efficacy, and tolerability of CBD and cannabidiolic acid (CBDA). Despite a certain number of available pharmacokinetic studies, the kinetic profile of CBD has yet to be fully known, probably because of the very different experimental conditions. In terms of efficacy, most studies have tested CBD' ability to relieve osteoarthritic pain. In contrast, few studies have evaluated its role in epilepsy, behavioral disorders, and skin lesions. From obtained results, some evidence exists supporting the beneficial role of CBD. Nevertheless, the limited number of published studies and the occurrence of bias in almost all require caution in interpreting findings. From tolerability studies, CBD' side effects can be classified as mild or unremarkable. However, studies were prevalently focused on short- to medium-term treatment, while CBD is usually employed for long-term treatment. Further studies are warranted to define better whether CBD could be a valid adjunct in canine treatment.

Translation to Spanish and linguistic validation of the Canine Brief Pain Inventory.

Introduction: Pain scales for the assessment of chronic pain have been developed for dogs but they should be translated and linguistically validated to be used by owners with different native languages. The Canine Brief Pain Inventory (CBPI) is widely employed for this purpose but has not been translated into Spanish. Thus, the aim was to produce a validated translation of the Spanish CBPI. Methods: The original English version of the CBPI was analyzed and translated by two native linguists of the target language and both revised by a third native linguist to identify potential discrepancies and create a unified translation (reconciliation). Then, an independent linguist with native fluency in English and the target language drafted the back-translation. Finally, the research team confronted both the original and the back-translation to identify and solve relevant differences. Once the translated version was produced, a cognitive debriefing was performed to assess the questionnaire in the target population. Results: A total of 50 surveys were conducted to dog and cat owners of different ages, sex, and socio-economic characteristics. All respondents considered the survey to be clear and a final version of the Spanish CBPI has been produced.

Psychometric Testing and Validation of the Italian Version of the Helsinki Chronic Pain Index (I-HCPI) in Dogs with Pain Related to Osteoarthritis.

Pain assessment is of paramount importance for properly managing dogs with osteoarthritis (OA) pain. The aim of the present study was to develop and psychometrically validate the Italian version of the Helsinki Chronic Pain Index (I-HCPI). Owners of OA painful (n = 87) and healthy dogs (n = 40) were administered the I-HCPI once or twice after an eight-week meloxicam treatment. Sixty-nine owners of healthy and OA dogs also completed the Italian version of the Canine Brief Pain Inventory (I-CBPI). Pain on palpation on a 0-4 scale was assessed on all recruited dogs. Construct validity was tested both with hypothesis testing and principal component analysis, confirming the I-HCPI accurately measured chronic pain. Good convergent and criterion validity were shown through correlations with I-CBPI subscores and distribution among pain on palpation scores (p < 0.0001). The significant difference between the pre- and post-treatment I-HCPI scores (p < 0.0001) and Cohen's effect size (2.27) indicated excellent responsiveness. The I-HCPI was shown to be reliable through communalities (range 0.47-0.90) and Cronbach α (≥0.95). Discriminative ability and cut-off point, as tested through Receiver Operating Characteristic analysis, showed excellent diagnostic accuracy with a threshold value of 11 (specificity 0.98 and sensitivity 0.94). The I-HCPI was confirmed to be a valid, sensitive, reliable, and accurate tool to discriminate between dogs with and without pain.

4-(3-Phenyl-4-(3,4,5-trimethoxybenzoyl)-1H-pyrrol-1-yl)benzenesulfonamide, a Novel Carbonic Anhydrase and Wnt/ß-Catenin Signaling Pathway Dual-Targeting Inhibitor with Potent Activity against Multidrug Resistant Cancer Cells.

We synthesized new pyrrole and indole derivatives as human carbonic anhydrase (hCA) inhibitors with the potential to inhibit the Wnt/ß-catenin signaling pathway. The presence of both N1-(4-sulfonamidophenyl) and 3-(3,4,5-trimethoxyphenyl) substituents was essential for strong hCA inhibitors. The most potent hCA XII inhibitor 15 (Ki = 6.8 nM) suppressed the Wnt/ß-catenin signaling pathway and its target genes MYC, Fgf20, and Sall4 and exhibited the typical markers of apoptosis, cleaved poly(ADP-ribose)polymerase, and cleaved caspase-3. Compound 15 showed strong inhibition of viability in a panel of cancer cells, including colorectal cancer and triple-negative breast cancer cells, was effective against the NCI/ADR-RES DOX-resistant cell line, and restored the sensitivity to doxorubicin (DOX) in HT29/DX and MDCK/P-gp cells. Compound 15 is a novel dual-targeting compound with activity against hCA and Wnt/ß-catenin. It thus has a broad targeting spectrum and is an anticancer agent with specific potential in P-glycoprotein overexpressing cell lines.

Palmitoylethanolamide and Related ALIAmides for Small Animal Health: State of the Art.

ALIAmides are a family of fatty acid amides whose name comes from their mechanism of action, i.e., the Autacoid Local Injury Antagonism (ALIA). Actually, the ALIAmide parent molecule, palmitoylethanolamide (PEA), is locally produced on demand from a cell membrane precursor in order to control immune-inflammatory cell responses, avert chronic non-resolving inflammation, and limit the resulting clinical signs. ALIAmide sister compounds, such as Adelmidrol and palmitoylglucosamine, share mechanisms of action with PEA and may also increase endogenous levels of PEA. Provided that their respective bioavailability is properly addressed (e.g., through decreasing the particle size through micronization), exogenously administered ALIAmides thus mimic or sustain the prohomeostatic functions of endogenous PEA. The aim of the present paper is to review the main findings on the use of ALIAmides in small animals as a tribute to the man of vision who first believed in this "according-to-nature" approach, namely Francesco della Valle. After briefly presenting some key issues on the molecular targets, metabolism, and pharmacokinetics of PEA and related ALIAmides, here we will focus on the preclinical and clinical studies performed in dogs and cats. Although more data are still needed, ALIAmides may represent a novel and promising approach to small animal health.

Pharmacokinetics of cannabidiol following single oral and oral transmucosal administration in dogs.

Introduction: In the last few years, different formulations containing cannabidiol (CBD) were tested with regard to its efficacy on chronic pain, refractory epilepsy, anxiety, aggressive behavior and atopic dermatitis in dogs. CBD is generally administered orally, but its low bioavailability, probably due to a first-pass metabolism, represents a great limitation. The aim of this study was to evaluate if CBD bioavailability increases after oral transmucosal administration (OTM) compared to oral treatment. Methods: Twelve dogs diagnosed with mild chronic pain were enrolled in the study and treated once orally or OTM (6 dogs/group) with a pure CBD in oil formulation at a dosing rate of 1 mg/kg b.w. At prefixed time points, blood samples were collected to define CBD plasma concentrations vs. time profiles, and the main pharmacokinetics parameters were obtained by non-compartmental model. Results: CBD Cmax, Tmax, terminal half-life and AUC0 - t were 206.77 ± 167 and 200.33 ± 158.33 ng/mL, 2.17 ± 0.98 and 1.92 ± 1.11 h, 2.67 ± 0.53 and 2.62 ± 0.64 h, 647.51 ± 453.17, and 536.05 ± 370.21 h*ng/mL, following oral and OTM administration, respectively. No significant difference in pharmacokinetic parameters were observed between treatments. Discussion: The OTM administration did not increase cannabidiol bioavailability compared to oral treatment. The almost perfectly superimposable mean plasma concentrations of cannabidiol following the two treatments suggests that CBD is not able to be adsorbed by the oral mucosa or that its absorption is very scarce, and that CBD is swallowed and absorbed in the gastrointestinal tract.

Multilingual validation of the short form of the Unesp-Botucatu Feline Pain Scale (UFEPS-SF).

Background: Pain is the leading cause of animal suffering, hence the importance of validated tools to ensure its appropriate evaluation and treatment. We aimed to test the psychometric properties of the short form of the Unesp-Botucatu Feline Pain Scale (UFEPS-SF) in eight languages. Methods: The original scale was condensed from ten to four items. The content validation was performed by five specialists in veterinary anesthesia and analgesia. The English version of the scale was translated and back-translated into Chinese, French, German, Italian, Japanese, Portuguese and Spanish by fluent English and native speaker translators. Videos of the perioperative period of 30 cats submitted to ovariohysterectomy (preoperative, after surgery, after rescue analgesia and 24 h after surgery) were randomly evaluated twice (one-month interval) by one evaluator for each language unaware of the pain condition. After watching each video, the evaluators scored the unidimensional, UFEPS-SF and Glasgow composite multidimensional feline pain scales. Statistical analyses were carried out using R software for intra and interobserver reliability, principal component analysis, criteria concurrent and predictive validities, construct validity, item-total correlation, internal consistency, specificity, sensitivity, the definition of the intervention score for rescue analgesia and diagnostic uncertainty zone, according to the receiver operating characteristic (ROC) curve. Results: UFEPS-SF intra- and inter-observer reliability were ≥0.92 and 0.84, respectively, for all observers. According to the principal component analysis, UFEPS-SF is a unidimensional scale. Concurrent criterion validity was confirmed by the high correlation between UFEPS-SF and all other scales (≥0.9). The total score and all items of UFEPS-SF increased after surgery (pain), decreased to baseline after analgesia and were intermediate at 24 h after surgery (moderate pain), confirming responsiveness and construct validity. Item total correlation of each item (0.68-0.83) confirmed that the items contributed homogeneously to the total score. Internal consistency was excellent (≥0.9) for all items. Both specificity (baseline) and sensitivity (after surgery) based on the Youden index was 99% (97-100%). The suggestive cut-off score for the administration of analgesia according to the ROC curve was ≥4 out of 12. The diagnostic uncertainty zone ranged from 3 to 4. The area under the curve of 0.99 indicated excellent discriminatory capacity of UFEPS-SF. Conclusions: The UFEPS-SF and its items, assessed by experienced evaluators, demonstrated very good repeatability and reproducibility, content, criterion and construct validities, item-total correlation, internal consistency, excellent sensitivity and specificity and a cut-off point indicating the need for rescue analgesia in Chinese, French, English, German, Italian, Japanese, Portuguese and Spanish.

One-carbon pathway metabolites are altered in the plasma of subjects with Down syndrome: Relation to chromosomal dosage.

Introduction: Down syndrome (DS) is the most common chromosomal disorder and it is caused by trisomy of chromosome 21 (Hsa21). Subjects with DS show a large heterogeneity of phenotypes and the most constant clinical features present are typical facies and intellectual disability (ID). Several studies demonstrated that trisomy 21 causes an alteration in the metabolic profile, involving among all the one-carbon cycle. Methods: We performed enzyme-linked immunosorbent assays (ELISAs) to identify the concentration of 5 different intermediates of the one-carbon cycle in plasma samples obtained from a total of 164 subjects with DS compared to 54 euploid subjects. We investigated: tetrahydrofolate (THF; DS n = 108, control n = 41), 5-methyltetrahydrofolate (5-methyl-THF; DS n = 140, control n = 34), 5-formyltetrahydrofolate (5-formyl-THF; DS n = 80, control n = 21), S-adenosyl-homocysteine (SAH; DS n = 94, control n = 20) and S-adenosyl-methionine (SAM; DS n = 24, control n = 15). Results: Results highlight specific alterations of THF with a median concentration ratio DS/control of 2:3, a decrease of a necessary molecule perfectly consistent with a chromosomal dosage effect. Moreover, SAM and SAH show a ratio DS/control of 1.82:1 and 3.6:1, respectively. Discussion: The relevance of these results for the biology of intelligence and its impairment in trisomy 21 is discussed, leading to the final proposal of 5-methyl-THF as the best candidate for a clinical trial aimed at restoring the dysregulation of one-carbon cycle in trisomy 21, possibly improving cognitive skills of subjects with DS.

Chronic Pain in Dogs and Cats: Is There Place for Dietary Intervention with Micro-Palmitoylethanolamide?

The management of chronic pain is an integral challenge of small animal veterinary practitioners. Multiple pharmacological agents are usually employed to treat maladaptive pain including opiates, non-steroidal anti-inflammatory drugs, anticonvulsants, antidepressants, and others. In order to limit adverse effects and tolerance development, they are often combined with non-pharmacologic measures such as acupuncture and dietary interventions. Accumulating evidence suggests that non-neuronal cells such as mast cells and microglia play active roles in the pathogenesis of maladaptive pain. Accordingly, these cells are currently viewed as potential new targets for managing chronic pain. Palmitoylethanolamide is an endocannabinoid-like compound found in several food sources and considered a body's own analgesic. The receptor-dependent control of non-neuronal cells mediates the pain-relieving effect of palmitoylethanolamide. Accumulating evidence shows the anti-hyperalgesic effect of supplemented palmitoylethanolamide, especially in the micronized and co-micronized formulations (i.e., micro-palmitoylethanolamide), which allow for higher bioavailability. In the present paper, the role of non-neuronal cells in pain signaling is discussed and a large number of studies on the effect of palmitoylethanolamide in inflammatory and neuropathic chronic pain are reviewed. Overall, available evidence suggests that there is place for micro-palmitoylethanolamide in the dietary management of chronic pain in dogs and cats.

Intra-articular use of analgesic/antinflammatory drugs in dogs and horses.

Joint pain is a major cause of lameness in animals such as horses and dogs, and it may affect their athletic performance and quality of life. The intra-articular administration of analgesic/antinflammatory drugs is a common practice in veterinary medicine, for both lameness diagnosis and joint pain management. It is used either perioperatively, such as in animals undergoing arthroscopy/arthrotomy, and in osteoarthritic animals. However, evidence regarding efficacy and safety of each drug is limited, and controversies persist in these areas. In particular, it is often uncertain whether a defined treatment is effective by simply relieving the symptomatic pain associated with the joint disease, or whether it has a positive effect on the joint environment. Moreover, there is still much hesitation about treatments for joint diseases, related to the time of their application for the best outcome, and to any possible deleterious side effects. This article includes a review of the literature concerning the main analgesic/antinflammatory drugs used intra-articularly for managing acute and chronic joint pain/inflammation in dogs and horses. Three main issues for each class of drugs are considered, including clinical efficacy, pharmacokinetics, and local cytotoxic effects.

Initial Psychometric Testing and Validation of the Italian Version of the Canine Brief Pain Inventory in Dogs With Pain Related to Osteoarthritis.

The Canine Brief Pain Inventory (CBPI) is an owner-administered questionnaire, originally developed and validated in English, used to assess canine chronic pain in terms of severity and interference with daily life activities. The aim of the present study was to perform a preliminary validation of an Italian version of the CBPI. Translation was performed and the resulting questionnaire was administered to 45 native Italian speaking owners of dogs suffering from chronic pain due to radiographically confirmed osteoarthritis. Psychometric properties of the Italian CBPI including construct validity, convergent validity and reliability were evaluated. Construct validity was assessed by factor analysis and confirmed a two-factor model (i.e., pain severity and interference factors). The respective scores, that is, the pain severity score (PSS) and pain interference score (PIS), exhibited a substantial negative correlation with overall quality of life score. Pain severity and interference items showed a mean inter-item correlation of 0.90 and 0.80, respectively. For each question, communality ranged from 0.84 to 0.97, highlighting strong internal consistency and suggesting that PSS and PIS can be calculated by averaging the items contained within each factor. Cronbach's α was 0.97 and 0.96 for PSS and PIS, respectively. The present findings confirmed the main psychometric properties of the Italian version of the CBPI, providing clinicians and researchers with a useful metrology instrument to evaluate the severity of chronic pain and its interference with daily life activities in dogs with osteoarthritis owned by Italian speaking people. Further properties of the questionnaire need to be evaluated in future research and larger studies are warranted.

Hemp in Veterinary Medicine: From Feed to Drug.

Hemp (Cannabis sativa) is an angiosperm plant belonging to the Cannabaceae family. Its cultivation dates back to centuries. It has always been cultivated due to the possibility of exploiting almost all the parts of the plant: paper, fabrics, ropes, bio-compounds with excellent insulating capacity, fuel, biodegradable plastic, antibacterial detergents, and food products, such as flour, oils, seeds, herbal teas, and beer, are indeed obtained from hemp. Hemp flowers have also always been used for their curative effects, as well as for recreational purposes due to their psychotropic effects. Cannabis contains almost 500 chemical compounds, such as phytocannabinoids, terpenes, flavonoids, amino acids, fatty acids, vitamins, and macro-, and micro-elements, among others. When utilized as a food source, hemp shows excellent nutritional and health-promoting (nutraceutical) properties, mainly due to the high content in polyunsaturated fatty acids (especially those belonging to the ω-3 series), as well as in phenolic compounds, which seem effective in the prevention of common diseases such as gastrointestinal disorders, neurodegenerative diseases, cancer, and others. Moreover, hemp oil and other oils (i.e., olive oil and medium-chain triglyceride-MCT-oil) enriched in CBD, as well as extracts from hemp dried flowers (Cannabis extracts), are authorized in some countries for therapeutic purposes as a second-choice approach (when conventional therapies have failed) for a certain number of clinical conditions such as pain and inflammation, epilepsy, anxiety disorders, nausea, emesis, and anorexia, among others. The present review will synthetize the beneficial properties of hemp and hemp derivatives in animal nutrition and therapeutics.