Evaluation of the practical clinical use of the Horse Grimace Scale translated into French.

OBJECTIVE: To assess the reliability of a French version of the Horse Grimace Scale (HGSfv). STUDY DESIGN: Prospective, randomized, clinical study. ANIMALS: The operated (OP) group included 13 horses undergoing elective surgery. The positive (PC) and negative control (NC) groups included seven colicking horses and eight exercising sport horses, respectively. METHODS: Photographs were extracted from videos of the horses' heads. Videos were taken before and immediately after surgery in OP, on arrival of the horse in PC, and at rest in their stalls in NC. Pictures were evaluated by three anaesthetists [Diplomates (DIPs)] and four riders (RIDs) using Horse Grimace Scale translated into French (HGSfv) at two points, 2 weeks apart (E1 and E2). Each evaluator gave each image a score (1-3) for six identified facial action units. The scores given by DIPs and RIDs were compared using a Wilcoxon test. Intra- and inter-evaluator reliability were assessed using Spearman correlation tests (rs) and intra-class coefficients (ICCs), respectively. RESULTS: RIDs and DIPs gave significantly higher scores in the PC group than in the NC group [RIDsE1PC 5.0 (4.2-9.8) versus RIDsE1NC 2.2 (0.0-6.5), p = 0.02; RIDsE2PC 5.2 (3.2-9.5) versus RIDsE2NC 2.0 (0.2-5.8), p < 0.01; DIPsE1PC 4.0 (1.3-6.3) versus DIPsE1NC 2.2 (1.0-4.7), p = 0.04; DIPsE2PC 2.7 (1.0-6.0) versus DIPsE2NC 1.0 (0.0-2.3), p = 0.03]. Scores given by RID or DIPs 2 weeks apart were highly correlated [rs (RIDsE1, RIDsE2) r = 0.86, p < 0.0001] and [rs (DIPsE1, DIPsE2) r = 0.81 p < 0.0001]. The ICC between RIDs and DIPs in E1 and E2 was 0.94 (0.92-0.95) and 0.91 (0.89-0.93), respectively. The specificity and sensitivity of the HGSfv was 94% and 43%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Using the HGSfv, knowledge of horses rather than specialization in veterinary anaesthesia and analgesia appears to differentiate horses with visceral pain from those assumed to be pain free.

Animal Model of Video-Assisted Cecum and Ileum Instrumentation for Equine Visceral Pain Study.

This study aimed to describe an animal model for studying equine visceral pain using minimally invasive and video-assisted cecum and ileum instrumentation. The access to the cecum and ileum was affected because of a previous typhlostomy. For video-assisted distention of the cecum and ileum, a distention device, which we developed using an endotracheal Rusch probe, was used, adapted, and coupled to a cuffometer to inflate and measure the pressure of the cuff attached to its distal portion. In a video-assisted manner, the distal portion of the device was introduced into the cecum and ileum, which contained the cuff in its distal portion, properly positioning it in the lumen. The cuff of the distension device was insufflated after the measurement of baseline physiological parameters of the animals and video-assisted confirmation of its right placement in the cecum and ileum lumen (M0). Was performed in one moment through two simultaneous cuff compressions and 1 minute of animal observation to evaluate the degree of abdominal discomfort manifestations (M1). To cease these stimuli, the cuff was deflated by disconnecting the extensor of the distension device attached to its proximal portion (M2). The procedure was easily performed in most cases. Slow and progressive insufflation allowed subjective adjustment of the intensity of the pain stimulus based on behavioral manifestations. Even with a low rate of complications, the model is feasible and reproducible for studies on visceral pain and the evaluation of analgesic effects.

Nrf2 mediates the antinociceptive activity of dexmedetomidine in an acute inflammatory visceral pain rat model by activating the NF-κB sensor.

Dexmedetomidine (DEX) is a highly selective α2 adrenoceptor agonist. In this study, we evaluated the antalgic effect of DEX on acetic acid-induced acute inflammatory visceral pain (AIVP) in rats. Additionally, we evaluated the role of Nrf2 signalling in antinociception. We administered acetic acid to male Sprague Dawley rats that were treated with DEX or saline. Twenty rats were randomly classified into the following groups: normal, model, vehicle, or DEX group. Both q-RT PCR and enzyme-linked immunosorbent assay data suggested that interleukin 1ß (IL-1ß), tumour necrosis factor α, and IL-6 were upregulated in the spinal cord. Western blotting and q-RT PCR analyses were performed to detect the protein and mRNA expression levels of Nrf2, Keap1, and HO-1 in the spinal cord. The DEX group exhibited a significant downregulation in Nrf2/Keap1/HO-1 signal activation compared with the model group. Furthermore, we used the Nrf2-/- knockout AIVP rat model to determine the role of Nrf2 in the antinociceptive effect of DEX. We observed that the Nrf2 knockout blocked the Keap1/Nrf2/HO-1 signal transduction and partially abated the antinociceptive and the anti-inflammatory effects of DEX. Moreover, our data also indicated that DEX treatment decreased the activation and expression of nuclear factor (NF)-κB. However, Nrf2 silencing restored the expression of NF-κB and its phosphorylated form to physiological levels. In summary, our results suggested that Nrf2 signalling plays an important role in the antinociceptive effect of DEX in the AIVP rat model and that Nrf2 exerts its function by enhancing the activation of the NF-κB sensor. SIGNIFICANCE OF THE STUDY: Currently, using the behavioural parameters is not adequate for the diagnosis of AIVP, and there are no studies that have investigated the role and the mechanism of DEX in ameliorating visceral pain. In this study, we demonstrated that acetic acid stimulation in rats induces AIVP. Additionally, the administration of DEX inhibited the acute inflammation response and decreased the visceromotor reaction (behavioural) to algesia. Further, DEX inhibited the Keap1/Nrf2 pathway, which was activated by acetic acid treatment. We suggest that suppressing the inflammatory response could partially regulate the antinociceptive effect of DEX through Nrf2-mediated NF-κB activation associated with AIVP.

Objective pain assessment in horses (2014-2018).

In recent decades, much effort has been invested in scientific studies of objective and reliable assessment of pain in horses. Various types of pain assessment tools have been described and (partly) validated for different types of pain in horses. Currently, composite pain scales and facial expression-based pain scales seem to be the most promising tools for pain assessment in horses and numerous studies have recently been published on the use of these pain scales in horses. Therefore, this narrative review mainly focusses on these two types of pain scales and on the studies that have appeared describing these type of pain scales in horses. The extent to which these pain scales have been validated (sensitivity, specificity, inter-observer reliability etc.) and their potential use for clinical pain states is discussed. Possible future directions for new studies and their possible aid in assessing pain in hospitalised and ridden horses are presented. In this way, improved pain scoring could improve criteria used to evaluate the clinical efficacy of new analgesic drugs and techniques, potentially benefiting equine welfare.

Monitoring acute equine visceral pain with the Equine Utrecht University Scale for Composite Pain Assessment (EQUUS-COMPASS) and the Equine Utrecht University Scale for Facial Assessment of Pain (EQUUS-FAP): A validation study.

This study presents the validation of two recently described pain scales, the Equine Utrecht University Scale for Composite Pain Assessment (EQUUS-COMPASS) and the Equine Utrecht University Scale for Facial Assessment of Pain (EQUUS-FAP), in horses with acute colic. A follow-up cohort study of 46 adult horses (n = 23 with acute colic; n = 23 healthy control horses) was performed for validation and refinement of the constructed scales. Both pain scales showed statistically significant differences between horses with colic and healthy control horses, and between horses with colic that could be treated conservatively and those that required surgical treatment or were euthanased. Sensitivity and specificity were good for both EQUUS-COMPASS (87% and 71%, respectively) and EQUUS-FAP (77% and 100%, respectively) and were not substantially influenced by applying weighting factors to the individual parameters.

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.

Monitoring acute equine visceral pain with the Equine Utrecht University Scale for Composite Pain Assessment (EQUUS-COMPASS) and the Equine Utrecht University Scale for Facial Assessment of Pain (EQUUS-FAP): A scale-construction study.

Although recognition of equine pain has been studied extensively over the past decades there is still need for improvement in objective identification of pain in horses with acute colic. This study describes scale construction and clinical applicability of the Equine Utrecht University Scale for Composite Pain Assessment (EQUUS-COMPASS) and the Equine Utrecht University Scale for Facial Assessment of Pain (EQUUS-FAP) in horses with acute colic. A cohort follow-up study was performed using 50 adult horses (n = 25 with acute colic, n = 25 controls). Composite pain scores were assessed by direct observations, Visual Analog Scale (VAS) scores were assessed from video clips. Colic patients were assessed at arrival, and on the first and second mornings after arrival. Both the EQUUS-COMPASS and EQUUS-FAP scores showed high inter-observer reliability (ICC = 0.98 for EQUUS-COMPASS, ICC = 0.93 for EQUUS-FAP, P <0.001), while a moderate inter-observer reliability for the VAS scores was found (ICC = 0.63, P <0.001). The cut-off value for differentiation between healthy and colic horses for the EQUUS-COMPASS was 5, and for differentiation between conservatively treated and surgically treated or euthanased patients it was 11. For the EQUUS-FAP, cut-off values were 4 and 6, respectively. Internal sensitivity and specificity were good for both EQUUS-COMPASS (sensitivity 95.8%, specificity 84.0%) and EQUUS-FAP (sensitivity 87.5%, specificity 88.0%). The use of the EQUUS-COMPASS and EQUUS-FAP enabled repeated and objective scoring of pain in horses with acute colic. A follow-up study with new patients and control animals will be performed to further validate the constructed scales that are described in this study.

Assessing experimental visceral pain in dairy cattle: A pilot, prospective, blinded, randomized, and controlled study focusing on spinal pain proteomics.

Few studies have verified the validity of behavioral and physiological methods of pain assessment in cattle. This prospective, blinded, randomized controlled experimental study aimed to validate different methods of pain assessment during acute and chronic (up to 21 d postintervention) conditions in dairy cattle, in response to 3 analgesic treatments for traumatic reticuloperitonitis. Cerebrospinal fluid (CSF) biomarkers and mechanical sensitization were measured as indicators of centralized pain. Proteomics in the CSF were examined to detect specific (to pain intensity) and sensitive (responsive to analgesia) markers. Recordings of spontaneous behavior with video analysis, telemetered motor activity, pain scales, electrodermal activity, and plasma cortisol concentration were quantified at regular intervals. Cows were assigned to group 1 (n=4, standard control receiving aspirin), group 2 (n=5, test group receiving preemptive tolfenamic acid), or group 3 (n=3, positive control receiving preemptive multimodal analgesia composed of epidural morphine, plus tolfenamic acid and butorphanol). Rescue analgesia was administered as needed. Generalized estimating equations tested group differences and the influence of rescue analgesia on the measurements. All 3 groups demonstrated a long-term decrease in a CSF protein identified as transthyretin. The decrease in transthyretin expression inversely correlated with the expected level of analgesia (group 1<2<3). Moreover, in group 1, CSF noradrenaline decreased long term, cows were hypersensitive to mechanical stimulation, and they demonstrated signs of discomfort with higher motor activity and "agitation while lying" recorded from video analysis. Decreased "feeding behavior," observer-reported pain scales, electrodermal activity, and plasma cortisol concentration were inconsistent to differentiate pain intensity between groups. In summary, changes in CSF biomarkers and mechanical sensitization reflected modulation of central pain in dairy cows. The spontaneous behavior "agitation while lying" was the only behavioral outcome validated for assessing acute and chronic pain in this visceral pain model.

Monitoring equine visceral pain with a composite pain scale score and correlation with survival after emergency gastrointestinal surgery.

Recognition and management of equine pain have been studied extensively in recent decades and this has led to significant advances. However, there is still room for improvement in the ability to identify and treat pain in horses that have undergone emergency gastrointestinal surgery. This study assessed the validity and clinical application of the composite pain scale (CPS) in horses after emergency gastrointestinal surgery. Composite pain scores were determined every 4h over 3 days following emergency gastrointestinal surgery in 48 horses. Inter-observer reliability was determined and another composite visceral pain score (numerical rating scale, NRS) was determined simultaneously with CPS scores. CPS scores had higher inter-observer reliability (r=0.87, K=0.84, P<0.001), compared to NRS scores (r=0.68, K=0.72, P<0.001). Horses that survived without complications had significantly lower CPS and NRS scores compared to horses that were euthanased or had to undergo re-laparotomy (P<0.001). Breed and the location in the intestinal tract (small or large intestine) did not influence pain scores. In conclusion, the use of the CPS improved objectivity of pain scoring in horses following emergency gastrointestinal surgery. High inter-observer reliability allows for comparisons between different observers. This will be of great benefit in larger veterinary hospitals where several attending clinicians are often involved in the care of each case.

Effect of maropitant, a neurokinin 1 receptor antagonist, on anesthetic requirements during noxious visceral stimulation of the ovary in dogs.

OBJECTIVE: To determine the anesthetic-sparing effect of maropitant, a neurokinin 1 receptor antagonist, during noxious visceral stimulation of the ovary and ovarian ligament in dogs. ANIMALS: Eight 1-year-old female dogs. PROCEDURES: Dogs were anesthetized with sevoflurane. Following instrumentation and stabilization, the right ovary and ovarian ligament were accessed by use of laparoscopy. The ovary was stimulated with a traction force of 6.61 N. The minimum alveolar concentration (MAC) was determined before and after 2 doses of maropitant. RESULTS: The sevoflurane MAC value was 2.12 ± 0.4% during stimulation without treatment (control). Administration of maropitant (1 mg/kg, IV, followed by 30 µg/kg/h, IV) decreased the sevoflurane MAC to 1.61 ± 0.4% (24% decrease). A higher maropitant dose (5 mg/kg, IV, followed by 150 µg/kg/h, IV) decreased the MAC to 1.48 ± 0.4% (30% decrease). CONCLUSIONS AND CLINICAL RELEVANCE: Maropitant decreased the anesthetic requirements during visceral stimulation of the ovary and ovarian ligament in dogs. Results suggest the potential role for neurokinin 1 receptor antagonists to manage ovarian and visceral pain.