diagnosis of pain in small companion animals

It is now widely accepted that animals are able to experience pain in a similar way to humans. Acute and/or chronic pain is associated not only with many surgical procedures, but also with various medical diseases, where pain may increase morbidity and mortality. Moreover, some types of pain (e.g., neuropathic pain) can be considered as an illness in themselves. Recognizing pain and assessing its intensity are both essential for its effective management: If pain is not recognised, then it is unlikely to be treated. Two major problems account for the difficulties in pain diagnosis in veterinary patients: (1) animals are not able to verbalise and cannot refer to the state of pain they are experiencing and (2) almost all animal species tend instinctively to mask signs of pain and weakness. Therefore, pain recognition in a diseased animal may be challenging. However, practitioners can rely on different strategies, which can be put in place to reveal the presence of pain in their patients. A presumptive diagnosis, a clinical exam, the evaluation of psychomotor changes and pain expressions, the attribution of pain scores and the response to therapy are all tools which, especially when used in combination, can help the veterinary practitioner recognise a subject suffering from pain and allow a correct approach to therapy. This review summarizes the current available information regarding the methodology that could be applied in small companion animals for a correct diagnosis of pain, offering veterinarians with some "easy to use" tools to apply in their daily practice

medical abdominal visceral pain in dogs

Abdominal visceral pain of medical origin is one of the most frequent reasons for request of medical treatment in humans. Its control is of paramount importance not only for ethical reasons, but also because, if untreated, pain can cause a stress response leading to alterations concerning many organs and apparatuses. Causes of acute or chronic medical visceral pain in men are numerous, with pain originating from various regions of the body. Considering the similarities with regard to the nervous system between humans and other mammals, it is very likely that pathological conditions that cause visceral pain in men are painful in animals as well. Despite this, in veterinary practice medical visceral pain is rarely considered and poorly treated, often for the difficulty in its identification and for a lack of specific guidelines addressing this specific topic. Moreover, no detailed and specific information on this subject are available in the current literature. The present review lists the main pathologies likely responsible of medical abdominal visceral pain in the canine species, trying to summarize, for each considered condition, the available information regarding the pathogenesis and the management of pain

Pain and Suffering in Invertebrates: An Insight on Cephalopods

Invertebrates are a broad group of animals that includes more than 90% of the estimated 10 million species in the world. Some species are abundantly used by man in scientific research and for human consumption. However, the current legislation is still very lacking about the protection toward conditions of pain, suffering, distress or lasting harm that these animals may suffer as a result of experimental practices, fishing and cooking. The purpose of this paper is to summarize what has already been stated by other Authors regarding the possibility that invertebrates (with a specific emphasis on cephalopods) can experience pain and suffering. The results of studies that show the existence, in these animals, of a number of elements that can be associated with the ability to feel pain and not only nociception are highlighted. Objective indicators (such as changes in physiological parameters) and behavioral attitudes of cephalopods that might be related to pain will be addressed as well

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

IntroductionIn 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.MethodsTwelve 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.ResultsCBD 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.DiscussionThe 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

RET/PTC3 translocation in a rare hemorrhagic brain metastasis of papillary thyroid cancer post Chernobyl radiation affects vessels ultrastructure

Abstract Background Slow progression and good prognosis are the usual characteristics of papillary thyroid carcinoma (PTC). The presence of brain metastases (0.4–1.2%) is suggestive of a worse prognosis. RET/PTC rearrangements were particularly prevalent in PTCs developed after Chernobyl nuclear accident. Case description A 50-year-old woman born in Slovakia, exposed to radiation resulting from the accident at the Chernobyl nuclear power plant, affected since 2017 by papillary thyroid cancer and in therapy at our hospital, experimented cerebral hemorrhagic metastasis. Biopsy analyses revealed a RET/PTC3 rearrangement, so our aim was to find possible morphological relation between hemorrhagic metastasis and RET/PTC3 translocation. Results Immunohistochemical analysis showed diffuse and intense positivity for VEGF in endothelial cells of the neoplasm’ vascular network. Transmission electron microscopy images showed vessels with unorganized pattern and uneven diameters. In particular, metastasis endothelial cells (MECs) showed irregular shape and size, thickened cytoplasm and swelling of endoplasmic reticulum. MECs organized in irregular monolayers or multiple layers, surrounded by a thickened but unstructured extracellular matrix. Absence of strong junctional complexes among MECs resulted in a further weakened vessels wall. Conclusion RET/PTC3 translocation causes VEGF overexpression via STAT3 signaling cascade and the increased amount of VEGF adds to the greater amount of VEGFRs expressed by MECs. Our ultrastructural investigation show that this condition creates a massive growth of altered vessels prone to bleeding. The clinical significance of our study consists in alert oncologist and surgeons on possible arising of hemorrhagic brain metastases in patients with PTC and RET/PTC3 translocation exposed to ionizing radiation as people living in areas caught up in Chernobyl or Fukushima disasters

Penile metastasis from primary cholangiocarcinoma: the first case report

BACKGROUND: Metastatic penile carcinoma derived from cholangiocarcinoma (CCA) has not been previously reported in the literature. Common metastatic sites for CCA include the regional lymph nodes and adjacent organs. CCAs are not highly vascularised tumours, making hematogenous metastases uncommon. Hematogenous CCA metastases commonly occur at distant organs such as the lungs, adrenal glands, and bones. Median survival for patients with metastatic disease is generally less than 1 year. CASE PRESENTATION: A 74-year-old Caucasian man consulted us after having undergone penile ultrasonography for pain and increased thickness at the base of the penis after self-examination. The patient presented with a history of hepatitis C-related cirrhosis and intrahepatic CCA, diagnosed 3 years previously. A biopsy of the corpora cavernosa on both sides revealed a carcinoma harbouring the same histological and immunophenotypical features as the primary hepatic lesion. CONCLUSIONS: To date, there is no case of penile or urogenital system metastasis from CCA described in the literature. Therefore, this article represents the first case report of penile metastasis from CCA

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

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

Pharmacokinetic profiles of meloxicam in turtles (Trachemys scripta scripta) after single oral, intracoelomic and intramuscular administrations

Meloxicam is an anti-inflammatory and analgesic drug used to treat many pathological conditions in turtles. With the aim to fill the lack of data about its pharmacokinetic in this species, eighteen turtles (Trachemys scripta scripta) were divided in three groups and treated with a single dose of meloxicam (0.2 mg/kg) by intramuscular, intracoelomic and oral route, respectively. At scheduled time points, blood samples were collected and meloxicam concentrations were determined by HPLC. Pharmacokinetic parameters were calculated from the obtained concentration-time curves. After intramuscular treatment, a plasma peak of meloxicam equal to 1590.03 +/- 1845.32 ng/mL (mean +/- SD) and a T-max of 1.17 +/- 0.45 h were reached, indicating a quick absorption of the drug. The intracoelomic administration brought to the largest AUC (12621.04 +/- 6203.79 h*ng/mL) and to a C-max and a T-max equal to 1154.52 +/- 662.78 ng/mL and 2.82 +/- 1.39 h, respectively. Following oral treatment, the plasma concentrations of meloxicam were very low indicating a scarce absorption. Further studies are warranted to determine the effective plasma concentration of meloxicam in turtles and, consequently, the dosage regimen

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