2024 ISFM and AAFP consensus guidelines on the long-term use of NSAIDs in cats.

PRACTICAL RELEVANCE: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used and are effective for the management of pain in cats. These Guidelines will support veterinarians in decision-making around prescribing NSAIDs in situations of chronic pain, to minimise adverse effects and optimise pain management. Information is provided on mechanism of action, indications for use, screening prior to prescription, use in the presence of comorbidities, monitoring of efficacy, and avoidance and management of adverse effects. CLINICAL CHALLENGES: The cat's unique metabolism should be considered when prescribing any medications, including NSAIDs. Chronic pain may be challenging to detect in this species and comorbidities, particularly chronic kidney disease, are common in senior cats. Management of chronic pain may be complicated by prescription of other drugs with the potential for interactions with NSAIDs. EVIDENCE BASE: These Guidelines have been created by a panel of experts brought together by the International Society of Feline Medicine (ISFM) and American Association of Feline Practitioners (AAFP). Information is based on the available literature, expert opinion and the panel members' experience.

Quantitative sensory testing in canine musculoskeletal pain: Findings from a systematic review, meta-analysis feasibility assessment, and limitations.

Quantitative sensory testing (QST) allows the study of pain mechanisms, patient phenotyping, and response to therapy. The goals of this study were to conduct a systematic review of the use of QST in dogs with musculoskeletal disease including osteoarthritis (OA), and to assess, by means of a meta-analysis, the ability of QST to differentiate affected dogs from healthy controls. The study protocol was registered; three bibliographic databases were screened. Studies involving QST in healthy dogs and those with musculoskeletal disease were included. Data were extracted using a standardized form. Assessment of quality and risk of bias were performed using the CAMARADES critical assessment tool. Twenty-nine articles met the inclusion criteria [systematic review (n = 11); meta-analysis (n = 28)]. In the systematic review, ten studies performed static QST: mechanical [punctate tactile (n = 6); mechanical pressure (n = 5)]; thermal [cold (n = 3); hot (n = 4)]; electrical (n = 1); and one study performed dynamic QST [conditioned pain modulation (n = 1)]. Most studies were of good scientific quality and showed low to moderate risk of bias. A meta-analysis was not possible due to numerous and severe issues of heterogeneity of data among studies. Methods to reduce risk of bias and use of reporting guidelines are some of the most needed improvements in QST research in dogs. Standardization of QST methodology is urgently needed in future studies to allow for data synthesis and a clear understanding of the sensory phenotype of dogs with and without chronic pain including OA.

Spatial working memory in a disappearing object task is impaired in female but not male dogs with chronic osteoarthritis.

Chronic pain in humans is associated with impaired working memory but it is not known whether this is the case in long-lived companion animals, such as dogs, who are especially vulnerable to developing age-related chronic pain conditions. Pain-related impairment of cognitive function could have detrimental effects on an animal's ability to engage with its owners and environment or to respond to training or novel situations, which may in turn affect its quality of life. This study compared the performance of 20 dogs with chronic pain from osteoarthritis and 21 healthy control dogs in a disappearing object task of spatial working memory. Female neutered osteoarthritic dogs, but not male neutered osteoarthritic dogs, were found to have lower predicted probabilities of successfully performing the task compared to control dogs of the same sex. In addition, as memory retention interval in the task increased, osteoarthritic dogs showed a steeper decline in working memory performance than control dogs. This suggests that the effects of osteoarthritis, and potentially other pain-related conditions, on cognitive function are more clearly revealed in tasks that present a greater cognitive load. Our finding that chronic pain from osteoarthritis may be associated with impaired working memory in dogs parallels results from studies of human chronic pain disorders. That female dogs may be particularly prone to these effects warrants further investigation.

Comparing inpatient management of chronic pelvic pain flares before and after the COVID-19 pandemic.

Abstract: Patients with chronic pelvic pain (CPP) may experience pain exacerbations requiring hospital admissions. Due to the effects of backlogged elective surgeries and outpatient gynaecology appointments resulting from the COVID-19 pandemic, we hypothesised that there would be an increased number of women admitted with CPP flares. We conducted a retrospective review of all acute gynaecology admissions at the Royal Infirmary of Edinburgh from July to December 2018 (pre-COVID) and 2021 (post-COVID lockdown). We collected information on the proportion of emergency admissions due to CPP, inpatient investigations and subsequent management. Average total indicative hospital inpatient costs for women with CPP were calculated using NHS National Cost Collection data guidance. There was no significant difference in the number of emergency admissions due to pelvic pain before (153/507) and after (160/461) the COVID-19 pandemic. As high as 33 and 31% had a background history of CPP, respectively. Across both timepoints, investigations in women with CPP had low diagnostic yield: <25% had abnormal imaging findings and 0% had positive vaginal swab cultures. Women with CPP received significantly more inpatient morphine, pain team reviews and were more likely to be discharged with strong opioids. Total yearly inpatient costs were £170,104 and £179,156 in 2018 and 2021, respectively. Overall, emergency admission rates for managing CPP flares was similar before and after the COVID-19 pandemic. Inpatient resource use for women with CPP remains high, investigations have low diagnostic yield and frequent instigation of opiates on discharge may risk dependence. Improved community care of CPP is needed to reduce emergency gynaecology resource utilisation. Lay summary: Existing treatments for chronic pelvic pain (CPP) and endometriosis focus on surgery or hormone medication, but these are often ineffective or associated with unacceptable side-effects. As a result, women continue to experience chronic pain and often have 'flares' of worsening pain that may lead to hospital admission. The COVID-19 pandemic resulted in backlogged gynaecology clinics and surgeries. The aim of this study was to compare the management of emergency pelvic pain admissions for women with CPP before and after COVID-19. We also aimed to better understand their in-hospital management and estimate their hospital length of stay costs. We did not find an increase in CPP patients admitted for pelvic pain flares after the COVID-19 lockdown. Women with CPP often undergo multiple hospital tests and are often prescribed with strong pain medications which can cause long-term problems. Efforts are needed to improve long-term pain management for women with CPP.

A case report of CBD and THC as analgesic therapy in a cat with chronic osteoarthritic pain.

A 10-year-old mixed breed male cat presented with clinical signs related to chronic orthopaedic pain. Upon physical examination, pain was noted, based on the feline Musculoskeletal Pain Index (FMPI). An analgesic treatment with a full spectrum cannabis oil (1.8% CBD and 0.8% THC) was proposed for 30 days (0,5 mg/kg based on CBD). The FMPI scale score decreased more than 50%. This case reported a satisfactory outcome for the patient and the owner, although this medication could increase ALT. Given the paucity of literature published to date on the treatment of veterinary species with cannabis-based medications, further clinical and pharmacokinetic studies are necessary to study the safety and efficacy of its use.

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.

Effects of low-level laser therapy on impaired mobility in dogs with naturally occurring osteoarthritis.

BACKGROUND: Osteoarthritis is common in the aging dog and is associated with chronic pain and impaired mobility. The main objective of this study was to determine whether low-level laser therapy (LLLT) would increase physical activity in dogs with osteoarthritis. METHODS: Twenty-three dogs with osteoarthritis were instrumented with an accelerometer 48 h before the first LLLT session (baseline), to record daily activity. Each dog underwent six consecutive weekly laser treatments. The scores of the Canine Brief Pain Inventory and the Liverpool Osteoarthritis in Dogs' were recorded for clinical purposes, as a tool to titrate the analgesic therapy of each individual dog, before LLLT (as baseline) and then weekly for 6 weeks. RESULTS: The number of daily activities increased during week 2 (161,674; SD, 103,666) and remained higher than baseline (93,481; SD, 107,878) until week 6 (179,309; SD, 126,044; p < 0.001). Daily step count increased from week 1 (4472; SD, 3427) compared to baseline (1109; SD, 1061) and remained higher than the baseline until the end of week 6 (8416; SD, 3166; p < 0.001). Average energy expenditure during the study period was 179 [range, 2-536] kcal/day; there were no statistically significant differences in this variable between weeks of treatment. Systemic analgesics therapy was decreased in 50% of the dogs during the study period. CONCLUSIONS: Laser therapy may advance the management of osteoarthritis by increasing the level of activity of dogs, therefore improving their quality of life.

Evidence-Based Complementary and Alternative Canine Orthopedic Medicine.

The use of complementary and alternative veterinary medicine (CAVM) continues to become more widespread, especially for the management of chronic pain conditions such as canine osteoarthritis. Many patients have comorbidities that preclude traditional medical options, have not adequately responded to conventional therapies, or have owners interested in pursuing a complementary approach. Evidence-based CAVM can serve as a safe and effective adjunct to manage chronic pain conditions. There is growing evidence in the veterinary literature for the use of acupuncture and some herbal supplements in the multimodal management of canine osteoarthritis. The majority of evidence supporting chiropractic is limited to equine and human literature.

Identification of canine osteoarthritis using an owner-reported questionnaire and treatment monitoring using functional mobility tests.

OBJECTIVES: To investigate the diagnostic value of an owner-completed canine osteoarthritis screening checklist to help identify previously undiagnosed osteoarthritis cases, and assess their response to carprofen treatment by monitoring pain and functional mobility. MATERIALS AND METHODS: Dogs (n=500) whose owners reported ≥1 positive response to the osteoarthritis checklist were examined to identify dogs with previously undiagnosed osteoarthritis. Eligible dogs (n=133) were evaluated for pain and video mobility analysis by Helsinki Chronic Pain Index and visual analogue scale scores, respectively, following carprofen treatment, administered for 30 days (n=95) or up to 120 days (n=38). Dogs were filmed at clinics performing activities (walking, jogging, sitting/lying, walking up and down stairs), and scored at days 0, 30 and 120 using visual analogue scale by an independent blinded expert. RESULTS: A diagnosis of osteoarthritis was confirmed by a veterinarian in 38% (188 of 500) of dogs. Balance of sensitivity and specificity across the original group of nine screening questions was optimised to approximately 88 and 71%, respectively, after elimination of three questions. Pain measured by Helsinki Chronic Pain Index and functional mobility improved over time in response to treatment with carprofen. Mean ability scores for activities significantly improved between days 0 and 30 for walking, jogging, sitting/lying and walking down stairs, and days 0 and 120 for sitting/lying and walking up stairs. CLINICAL SIGNIFICANCE: More osteoarthritis cases were identified in study dogs than previous prevalence estimates, indicating the screening checklist's potential to help identify for further evaluation cases that could otherwise remain undiagnosed. Improvements in function were demonstrated after carprofen treatment.

Cannabidiol-based natural health products for companion animals: Recent advances in the management of anxiety, pain, and inflammation.

Recent advances in cannabidiol (CBD) use in canines and felines for anxiety management, pain management, and anti-inflammatory effects were reviewed using a literature search conducted with the following keywords: CBD, anxiety, inflammation, pain, dogs, cats, and companion animals. For decades, research on CBD has been hindered due to the status of cannabis (C. sativa L.) as an illicit drug. Limited safety data show that CBD is well-tolerated in dogs, with insufficient information on the safety profile of CBD in cats. Upon oral supplementation of CBD, elevation in liver enzymes was observed for both dogs and cats, and pharmacokinetics of CBD are different in the two species. There is a significant gap in the literature on the therapeutic use of CBD in cats, with no feline data on anxiety, pain, and inflammation management. There is evidence that chronic osteoarthritic pain in dogs can be reduced by supplementation with CBD. Furthermore, experiments are required to better understand whether CBD has an influence on noise-induced fear and anxiolytic response. Preliminary evidence exists to support the analgesic properties of CBD in treating chronic canine osteoarthritis; however, there are inter- and intra-species differences in pharmacokinetics, tolerance, dosage, and safety of CBD. Therefore, to validate the anxiety management, pain management, and anti-inflammatory efficacy of CBD, it is essential to conduct systematic, randomized, and controlled trials. Further, the safety and efficacious dose of CBD in companion animals warrants investigation.

Chronic pain and gait analysis in dogs with degenerative hip joint disease treated with repeated intra-articular injections of platelet-rich plasma or allogeneic adipose-derived stem cells.

This prospective, comparative, randomized, horizontal, and double-blind clinical study investigated the clinical efficacy of leucocyte-poor platelet-rich plasma (PRP, n=8) or allogeneic adipose-derived stem cells (ADSC, n=8) in dogs with bilateral degenerative hip joint disease (DHJD). Sixteen dogs were treated with two intra-articular injections of PRP or ADSCs, within a 30-day interval. The Canine Brief Pain Inventory (CBPI), the Helsinki Chronic Pain Index (HCPI), and Visual Analogue Scales for pain (VAS-pain) and locomotion (VAS-loc) were assessed by the dog owners. Analysis-of-gait using a force plate, response to palpation (VAS-palp), and the descriptive numerical scale for pain (DNS) were measured by a veterinarian. The assessments were performed before (baseline), 30 and 60 days after the first treatment. Data were analyzed using the unpaired t test, paired Wilcoxon test, Fisher's exact test, and Mann-Whitney and Friedman tests (P<0.05). Compared with baseline HCPI, CBPI, VAS-pain, and VAS-palp scores reduced 41%, 52%, 51%, and 48% (P=0.0001-0.03) at 60 days in the ADSC group. In PRP-treated dogs, CBPI, VAS-loc, and DNS scores decreased by 43%, 43%, and 33% at 60 days, respectively (P=0.0003-0.011). Based on CBPI data, the rate of success at 60 days was 75% and 25% in the ADSC and PRP groups (P=0.13), respectively. Both therapies were apparently safe and effective to reduce chronic pain in dogs with bilateral DHJD during a 60-day period. However, a trend towards greater improvement was provided by the ADSC treatment.

Novel approach to modeling high-frequency activity data to assess therapeutic effects of analgesics in chronic pain conditions.

Osteoarthritis (OA) is a chronic condition often associated with pain, affecting approximately fourteen percent of the population, and increasing in prevalence. A globally aging population have made treating OA-associated pain as well as maintaining mobility and activity a public health priority. OA affects all mammals, and the use of spontaneous animal models is one promising approach for improving translational pain research and the development of effective treatment strategies. Accelerometers are a common tool for collecting high-frequency activity data on animals to study the effects of treatment on pain related activity patterns. There has recently been increasing interest in their use to understand treatment effects in human pain conditions. However, activity patterns vary widely across subjects; furthermore, the effects of treatment may manifest in higher or lower activity counts or in subtler ways like changes in the frequency of certain types of activities. We use a zero inflated Poisson hidden semi-Markov model to characterize activity patterns and subsequently derive estimators of the treatment effect in terms of changes in activity levels or frequency of activity type. We demonstrate the application of our model, and its advance over traditional analysis methods, using data from a naturally occurring feline OA-associated pain model.

Multimodal analgesia in a Southern White Rhinoceros (Ceratotherium simum) with pentosan polysulfate, gabapentin, amantadine and phenylbutazone to manage chronic pain.

A 38-year-old white rhinoceros bull (Ceratotherium simum) was treated with phenylbutazone over a period of four years for chronic osteoarthritic and neuropathic pain of the thoracic limbs. Initially the lameness was sporadic and responded well to phenylbutazone (4 mg/kg PO SID). The lameness increased in severity during the winter months. Four years after treatment was initiated, there was an increase in the severity and incidence of the lameness. Analgesia was augmented by the addition of non-conventional analgesic drugs. Pentosan polysulfate was administered IM at 3 mg/kg once a week for two treatments and thereafter monthly when possible. Gabapentin was used at 8 mg/kg but produced ataxia and anorexia. The dose was reduced to 4-5 mg/kg PO SID. Amantadine (3 mg/kg PO BID) was added to the multimodal analgesia and produced a significant improvement in the clinical lameness. Chronic inflammation was monitored using both automated and manual fibrinogen methods. Eventually the rhinoceros was euthanized on humane grounds when treatment was unable to produce suitable clinical relief.

Objective assessment of chronic pain in donkeys using the donkey chronic pain scale (DCPS): A scale-construction study.

Assessment of chronic pain is very important for monitoring and improving welfare and quality of life in donkeys. Freedom from disease and pain is one of the 'five freedoms' underlying animal welfare. The aim of the current study was to develop a pain scale for assessment of chronic pain in donkeys (Donkey Chronic Pain Scale; DCPS), including behavioural and facial expression-related parameters. The scale was applied to 77 donkeys (38 donkeys diagnosed with chronic health problems by means of clinical examination and additional diagnostic procedures and 39 healthy control animals). Animals were assessed twice daily for three consecutive days by two observers that were not masked to the condition of the animals but were unaware of the analgesic treatment regimens. Both composite, facial expression-based and combined DCPS pain scales showed excellent inter-observer reliability (Cronbach's alpha = 0.98, 0.96 and 0.98 respectively; P < 0.001). Individual composite and facial expression-based pain scores and the resulting combined DCPS showed significant differences between donkeys with chronic conditions and control donkeys at all time points (P < 0.001). A DCPS cut-off of 6 showed good sensitivity and specificity (92% and 82.5% respectively) for presence of a chronic painful condition. Facial expression-related parameters separately showed low sensitivity. In conclusion, it is possible to use a composite pain scale for assessment of chronic pain in donkeys, based on behavioural and facial expression-based parameters. Further studies are needed to validate this pain scale before it can be used in veterinary practice.

EEG individual power profiles correlate with tension along spine in horses.

Assessing chronic pain is a challenge given its subjective dimension. In humans, resting state electroencephalography (EEG) is a promising tool although the results of various studies are contradictory. Spontaneous chronic pain is understudied in animals but could be of the highest interest for a comparative study. Riding horses show a very high prevalence of back disorders thought to be associated with chronic pain. Moreover, horses with known back problems show cognitive alterations, such as a lower attentional engagement. Therefore, we hypothesized that the individual EEG power profiles resting state (i.e. quiet standing) of different horses could reflect the state of their back, that we measured using static sEMG, a tool first promoted to assess lower back pain in human patients. Results show that 1) EEG profiles are highly stable at the intra-individual level, 2) horses with elevated back tension showed resting state EEG profiles characterized by more fast (beta and gamma) and less slow (theta and alpha) waves. The proportion of theta waves was particularly negatively correlated with muscular tension along the spine. Moreover, elevated back tension was positively correlated with the frequency of stereotypic behaviours (an "addictive- like" repetitive behavior) performed by the horses in their stall. Resting state quantitative EEG appears therefore as a very promising tool that may allow to assess individual subjective chronic pain experience, beyond more objective measures of tension. These results open new lines of research for a multi-species comparative approach and might reveal very important in the context of animal welfare.

Treatment of canine osteoarthritis with allogeneic platelet-rich plasma: review of five cases.

Background: Osteoarthritis (OA) is a major cause of chronic pain and lameness in dogs. Platelet-rich plasma (PRP) is a concentrate of growth and differentiation factors from the blood, which can be used in regenerative medicine strategies. Aim: The main aim of this study was to evaluate the effect of allogeneic PRP on the treatment of canine OA. Methods: Five dogs from several breeds, between 6 and 12 years old, and from both genders were studied. Clinical and imageological examinations diagnosed OA in the knee, tibiotarsal, elbow, and intercarpal joints. These dogs were refractory to medical therapy and to physical rehabilitation protocols that included shockwave therapy, laser therapy, electrostimulation, hydrotherapy, and diathermy.Animals were treated with allogeneic PRP obtained from the blood of the five dogs, which was processed in a pool. Echoguided intra-articular PRP injection was administered under sedation and after aseptic field preparation. Lameness at walk and trot (five grades) and pain (five scores) were evaluated before treatment and 30, 60, and 90 days post-treatment. Results: All animals presented improvements at 30 and 60 days in both parameters. Four dogs showed a decrease of three grades of lameness after 90 days and there was complete absence of lameness in 2 days. Pain was reduced from severe and moderate to mild in all the dogs after 30 days, and among them, three revealed no pain after 90 days. Conclusion: This study sheds light on the applicability and safety of a single administration of allogeneic PRP in osteoarthritic dogs.

Preliminary clinical experience of low-level laser therapy for the treatment of canine osteoarthritis-associated pain: A retrospective investigation on 17 dogs.

Background: Osteoarthritis (OA) is common in dogs and causes chronic pain that affects the quality of life and may not respond to analgesics. Objective: The objective of this study was to determine whether low-level laser therapy (LLLT) would improve the quality of life and help reducing systemic analgesics, in dogs with OA. Methods: Seventeen client-owned dogs diagnosed with OA and associated pain were included. The diagnosis of OA was confirmed by orthopedic and radiographic examination. Pain was evaluated in each dog with the canine brief pain inventory (CBPI), compiled by the dog owners, as well as with a visual analog scale (VAS) and the colorado state canine chronic pain scale, used by the clinician. The LLLT was performed weekly in each study dog, for a total period of 6 weeks. The CBPI was then repeated at 2, 4, 6, and 8 weeks after the first laser session, whereas the VAS was reassessed at weeks 2 and 6. The dogs were observed for the occurrence of laser-related side effects. Results: Both CBPI and VAS were significantly reduced after the first laser session (9.2 ± 3.8 and 5.2 ± 1.1, respectively) compared to pretreatment values (11.8 ± 3.6 and 7.6 ± 0.9, respectively; and p = 0.018 and p < 0.001, respectively) and continued to decrease over time until the end of the therapy. Based on these results and improved function, as assessed by the orthopedic surgeon, the pharmacological analgesic therapy was reduced by the clinician at week 2 in 13 of 17 dogs. Laser-related side effects were not observed. Conclusion: This retrospective report provides a basis for future investigations, needed to clarify whether laser therapy may be beneficial to treat canine OA-associated pain. The preliminary findings are promising and suggest that LLLT may help reducing the analgesic administration and improving client satisfaction and the quality of life of dogs with OA.

Proteomic profiling of proteins in the dorsal horn of the spinal cord in dairy cows with chronic lameness.

Chronic lameness affects bovine welfare and has a negative economic impact in dairy industry. Moreover, due to the translational gap between traditional pain models and new drugs development for treating chronic pain states, naturally occurring painful diseases could be a potential translational tool for chronic pain research. We therefore employed liquid chromatography tandem mass spectrometry (LC-MS/MS) to stablish the proteomic profile of the spinal cord samples from lumbar segments (L2-L4) of chronic lame dairy cows. Data were validated and quantified through software tool (Scaffold® v 4.0) using output data from two search engines (SEQUEST® and X-Tandem®). Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) analysis was performed to detect proteins interactions. LC-MS/MS identified a total amount of 177 proteins; of which 129 proteins were able to be quantified. Lame cows showed a strong upregulation of interacting proteins with chaperone and stress functions such as Hsp70 (p < 0.006), Hsc70 (p < 0.0079), Hsp90 (p < 0.015), STIP (p > 0.0018) and Grp78 (p <0.0068), and interacting proteins associated to glycolytic pathway such as; γ-enolase (p < 0.0095), α-enolase (p < 0.013) and hexokinase-1 (p < 0.028). It was not possible to establish a clear network of interaction in several upregulated proteins in lame cows. Non-interacting proteins were mainly associated to redox process and cytoskeletal organization. The most relevant down regulated protein in lame cows was myelin basic protein (MBP) (p < 0.02). Chronic inflammatory lameness in cows is associated to increased expression of stress proteins with chaperone, metabolism, redox and structural functions. A state of endoplasmic reticulum stress and unfolded protein response (UPR) might explain the changes in protein expression in lame cows; however, further studies need to be performed in order to confirm these findings.

Measurement of chronic pain in companion animals: Priorities for future research and development based on discussions from the Pain in Animals Workshop (PAW) 2017.

The estimation of long-standing pain in companion animals through the measurement of different dimensions impacted by pain is a fundamental requirement if pain management, and pain therapeutic development, are to advance. Although pain management in veterinary medicine has advanced considerably in the last 20 years, there is much critical work to do in the area of measurement of chronic pain. To date, most work has centered on musculoskeletal pain, and has been focused around the measurement of limb use and the development of owner-completed questionnaires, or clinical metrology instruments (CMI). Recent areas of research have extended to developing measures of activity, sensory function (quantitative sensory testing; nociceptive withdrawal reflexes), and quality of life (QoL). Across all these areas, more data on validity are needed, and studies should be extended to other painful disease states. By necessity, assessing measurement tools requires testing in field studies, which incur considerable time and expense. Facilitating these studies could be optimized with a collaborative (industry, academia and private practice) approach, and the utility of the information produced from all field studies would be enhanced by full and transparent reporting and data sharing, including data already generated by industry in the form of studies submitted to the regulatory authorities.

Assessment of potential neuropathic changes in cattle after cautery disbudding.

Disbudding of calves is a standard husbandry procedure to reduce the risk of injuries to other cattle and to workers. Whereas acute pain resulting from disbudding has been studied extensively, little is known about chronic pain as a potential long-term consequence. The goal of the present study was to investigate possible morphological changes in the cornual nerve as a function of disbudding. Samples were collected from 17 randomly selected bulls and from 21 calves from a prospective clinical study. Among the calves, 13 were disbudded and 8 were sham-disbudded. Out of the disbudded calves, 4 showed signs of chronic pain. In all the animals, the infraorbital nerve was used as a methodological check. Morphological analysis included measuring minimal diameters of the axons present in both the cornual and infraorbital nerves. Sympathetic fibers were identified as based on the presence of Tyroxine hydroxylase (TH). TH-negative fibers were considered afferents. Trigeminal ganglia from the calves were immunostained for glial fibrillary acidic protein (GFAP) and Activating transcription factor 3 (ATF3). R. cornualis and N. infraorbitalis differed in terms of axon diameters and proportion of TH-positive fibers. Weak evidence (p > .091) of a difference in axon diameters between control and disbudded calves was found in R. cornualis, but the proportion of TH-positive fibers was alike in both groups. Average glial envelope and the percentages of ATF3-positive neurons revealed no difference between calves with and without signs of pain. Thus, available evidence is insufficient to support neuropathic changes as a result of disbudding in calves.