Chronic Pain In Dogs Research Articles

How does chronic pain impact the lives of dogs: an investigation of factors that are associated with pain using the Animal Welfare Assessment Grid.

Chronic pain can profoundly affect the wellbeing of dogs and our understanding is limited regarding the multidimensional impact it has on dog quality of life. This study aimed to assess the factors that are significant and predictive of behavior problems in dogs using the Animal Welfare Assessment Grid (AWAG) to further understand what factors influence their welfare. Seventy six AWAG assessments were undertaken across 46 dogs that clinicians diagnosed as having musculoskeletal conditions that caused chronic pain. Wilcoxon-rank sum tests were used to assess the difference in scores between dogs with behavior disorders and a cohort of healthy dogs (n = 143). All physical factors besides body condition, and all psychological, environmental, and procedural factors were significantly different between healthy dogs and dogs with chronic pain, evidencing how chronic pain impacts all domains of a dog's life. Spearman Rank Correlation Coefficient (RS) revealed several significant strong positive correlations such as the association between the severity of clinical symptoms with poorer mobility and the frequency at which the dog experienced fearful stimuli. Logistic regression showed that fears and anxieties frequency, the dog's reaction to stressors, engagement with enrichment, and social interactions were significant predictors of chronic pain in dogs. This highlights that typical signs of musculoskeletal disorders such as gait changes, stiffness, lameness might manifest after behavioral changes such as increased fearfulness, prolonged recovery from a stressful event, a reduced interested in social interactions, toys or play. Owners only seeking veterinary attention when the presence of physical signs of disease are evident may result in a delayed veterinary attention resulting in reduced welfare. Regular veterinary assessments combined with use of the AWAG can proactively identify these behavioral indicators and result in prompt treatment and improved quality of life.

Translation and linguistic validation into Spanish of the Owner-Reported Outcome Measure "Liverpool Osteoarthritis in Dogs".

Assessing chronic pain in dogs has been greatly favoured by the development of Owner-Reported Outcome Measures. Among them, the Liverpool Osteoarthritis in Dogs (LOAD) has been widely used for this purpose. Most of these tools have been written in English and its use by non English natives requires not only translation but also linguistic validation for use by veterinarians and owners. For its use, the LOAD has not undergone translation into Spanish and the objective was to generate a linguistically validated Spanish translation of the LOAD. Following the World Health Organisation and the International Society for Pharmacoeconomics and Outcomes Research published guidelines, the original LOAD English version underwent analysis and translation by two native linguists proficient in the target language. Both translations were then reviewed by a third native linguist to identify potential disparities and establish a cohesive translation (reconciliation). Subsequently, an independent linguist, fluent in both English and the target language, conducted the back translation. Finally, the research team compared the original and back translated versions to pinpoint and resolve any significant differences. Following the creation of the translated version, a cognitive debriefing was conducted to assess the questionnaire within the target population. A total of 89 surveys were distributed to dog owners of varying ages, genders, and socioeconomic backgrounds. Although there were some suggestions and comments, and some adjustments were made, all respondents found the survey to be clear, achieving a linguistic validation of the Spanish LOAD.

Acute and chronic pain in dogs and cats

Pain is a common condition of dogs and cats that is managed by veterinary surgeons with variable degrees of success. The complex pathophysiology of different types of pain is a significant reason why they can be challenging to manage. It is important to consider the goals and outcomes of any intervention(s) for both acute and chronic pain, but the cornerstone of the management of both is regular objective assessment with a validated scoring system. The feasibility of any interventions should also be considered with both the owner and animal in mind. Consideration of relevant legislation must be made when prescribing pharmacological therapies. Effectively managing acute pain may reduce the incidence of chronic pain in dogs and cats.

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

BackgroundOsteoarthritis (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.ResultsA 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).ConclusionThe 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.

Understanding and managing pain in the arthritic synovial joint: an update

Osteoarthritis is a very common cause of chronic pain in dogs and cats. Great progress has been made in the last 2–3 decades in unravelling the molecular mediators of joint pain. Now we are starting to see the benefits of this research in terms of new targets to block joint pain and new medicines reaching our pharmacy shelves. This review summarises the progress that has been made in understanding why and how arthritic joints cause pain. This will help readers understand novel medicines and provide insight into the others that might follow in the future.

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

Simple SummaryChronic pain is being increasingly recognized and addressed in small animal practice. The recent recognition that inability to communicate does not negate the possibility to experience pain requires veterinarians to actively recognize, assess and manage animal pain. In order to successfully treat pain while limiting side effects, a combination of different therapeutic weapons (e.g., analgesic drugs, acupuncture, physiotherapy and dietary interventions) is currently preferred. In this perspective, the endocannabinoid-like palmitoylethanolamide represents a promising option, since it is naturally occurring in food sources and animal tissues, addresses the mechanisms of chronic pain (i.e., immune cell hyperactivity) and is presently used in complementary feeds for dogs and cats in highly absorbable micronized formulations (i.e., micro-palmitoylethanolamide). In the present paper, the role of immune non-neuronal cells in chronic pain is reviewed. Moreover, the function of body-own palmitoylethanolamide in controlling pain through non-neuronal cell modulation is discussed. Finally, data on pain-relieving effects provided by dietary supplementation with micro-palmitoylethanolamide are presented. The critical mass of data here reviewed might help veterinary practitioners in the process of evidence-based decision-making regarding the management of chronic pain in cats and dogs.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.

A survey study on the recognition and treatment of pain in dogs and cats by Slovenian veterinarians

ObjectiveTo obtain information on pain management in dogs and cats by Slovenian veterinarians, and to compare it with reports from other countries. Study designProspective online survey. MethodsThe questions were uploaded using open source survey software and pertained to demographic data, self-evaluation of acquired and current knowledge, attitude towards pain and evaluation of actual knowledge, assessment of chronic and acute pain and pain due to surgery or medical conditions, and the use of analgesics. Descriptive statistics were used to summarize frequency distribution. Wilcoxon signed rank test, Mann-Whitney U test and Spearman’s rho were applied where appropriate. ResultsThe response rate was 11%. From 680 registered members of the Veterinary Chamber of Slovenia, 73 veterinarians completed the survey. Most of the respondents were women (71.2%) working in small (60.3%) or mixed (21.9%) animal practices. A more recent year of graduation was positively correlated to the self-reporting of knowledge acquired during undergraduate studies (rs = 0.339, p = 0.003) and to current knowledge about the topic (rs = 0.293, p = 0.012). Cats were assigned higher scores than dogs for signs of acute (p < 0.001) pain. Female respondents assigned higher scores than male respondents for chronic pain in dogs. Dogs were assigned higher pain scores than cats for surgical procedures and medical conditions. The most frequently used non-steroidal anti-inflammatory drugs (NSAIDs) in dogs and cats were meloxicam and carprofen, and butorphanol was the most commonly used opioid. The choice of NSAID was influenced by perceived effectiveness, experience with use and anti-inflammatory effect. Opioid use was influenced by experience with use and perceived effectiveness. Conclusions and clinical relevanceSlovenian veterinarians acknowledged the importance of pain management as reported for other European countries. However, the use of multimodal analgesia is limited, and inadequacies remain in the pain management of cats.

Variations in gene expression levels with severity of synovitis in dogs with naturally occurring stifle osteoarthritis.

Osteoarthritis (OA) is one of the major causes of chronic pain in dogs. However, the pathogenesis of OA has not been fully understood in dogs. The objective of this study was to comprehensively investigate the mRNA expression levels of proinflammatory cytokines, inflammatory mediators, nerve growth factor and its receptor, and matrix metalloproteinases in the synovium of dogs with spontaneous OA as well as to elucidate their relationships with the severity of synovitis. Dogs that were diagnosed with stifle OA on the basis of radiographic findings were included, and the degree of synovitis was observed using stifle arthroscopy. The dogs were assigned to two different groups depending on their synovitis scores: the low-grade group (score of 1 or 2; n = 8) and high-grade group (score of 3 to 5; n = 18). The dogs showing no evidence of orthopedic disease were included in the control group (n = 6). Synovial tissue samples were collected from the sites at which synovitis scores were assessed using arthroscopy. Total RNA was extracted from the collected synovial tissue, and cDNA was synthesized. Subsequently, RT-qPCR were performed using canine-specific primer sets for IL1B, IL6, CXCL8, TNF, TGFB1, PTGS2, PTGES, MMP3, MMP13, NGF, NTRK1, and PTGER4. Expression levels of IL1B, IL6, CXCL8, and MMP13 were significantly higher in the high-grade group than in the control group. In addition, expression levels of IL1B, CXCL8, TNF, and PTGS2 were significantly higher in the high-grade group than in the low-grade group. Expression levels of IL1B, IL6, CXCL8, TNF, PTGS2, and PTGER4 showed significant positive correlation with synovitis score. In conclusion, all mRNA expression levels in the synovial membrane varied according to the degree of synovitis in dogs with spontaneous OA. Thus, this study may partially elucidate the pathogenesis of synovitis in dogs with spontaneous OA.

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.

Serum cannabidiol, tetrahydrocannabinol (THC), and their native acid derivatives after transdermal application of a low-THC Cannabis sativa extract in beagles.

Cannabinoids hold promise for treating health problems related to inflammation and chronic pain in dogs, in particular cannabidiol (CBD), and its native acid derivative cannabidiolic acid (CBDA). Information regarding systemic delivery of cannabinoids through transdermal routes is sparse. The purpose of this study was to determine pharmacokinetics of transdermal administration of a low-THC Cannabis sativa extract in healthy dogs. Six purpose-bred research beagles were treated with a transdermal CBD-CBDA-rich extract, and serum concentrations of CBD, CBDA, tetrahydrocannabinol (THC), and its acid derivative tetrahydrocannabinolic acid (THCA) were examined prior to and at the end of weeks 1 and 2. A 4mg/kg dose of total cannabinoids twice daily resulted in appx 10ng/ml of CBD, 21-32ng/ml of CBDA, trace amounts of THCA, and unquantifiable amounts of THC in serum at the end of weeks 1 and 2 of treatment. Results showed that CBDA and THCA were absorbed better systemically than CBD or THC.

Correlation of Artemin and GFRα3 With Osteoarthritis Pain: Early Evidence From Naturally Occurring Osteoarthritis-Associated Chronic Pain in Dogs.

Arthritis, including osteoarthritis (OA) and other musculoskeletal-associated pain, is a worldwide problem, however, effective drug options are limited. Several receptors, neurotransmitters, and endogenous mediators have been identified in rodent models, but the relevance of these molecules in disease-associated pain is not always clear. Artemin, a neurotrophic factor, and its receptor, glial-derived neurotrophic factor (GDNF) family receptor alpha-3 (GFRα3), have been identified as involved in pain in rodents. Their role in OA-associated pain is unknown. To explore a possible association, we analyzed tissue from naturally occurring OA in dogs to characterize the correlation with chronic pain. We used behavioral assessment, objective measures of limb use, and molecular tools to identify whether artemin and GFRα3 might be associated with OA pain. Our results using banked tissue from well-phenotyped dogs indicates that artemin/GFRα3 may play an important, and hitherto unrecognized, role in chronic OA-associated pain. Elevated serum levels of artemin from osteoarthritic humans compared to healthy individuals suggest translational relevance. Our data provide compelling evidence that the artemin/GFRα3 signaling pathway may be important in OA pain in both non-humans and humans and may ultimately lead to novel therapeutics.

Investigating the Probability of Response Bias in Owner-Perceived Pain Assessment in Dogs With Osteoarthritis

Owners’ ability to recognize signs of chronic pain in dogs undergoing pharmacologic and nonpharmacologic pain interventions during a period of physical rehabilitation is not known. This study aimed to compare dogs with and without chronic pain, and to assess the relationship between explanatory factors, including the probability of owners’ response bias induced by pharmacologic and nonpharmacologic pain intervention, and chronic pain in dogs with osteoarthritis (OA). Seventy-one dogs with OA were included in this observational study. Owner-perceived pain interference was measured by Canine Brief Pain Inventory (CBPI) and owner-perceived pain behavior was assessed using Helsinki Chronic Pain Index. A dichotomous variable of Helsinki Chronic Pain Index was used in regression analysis to investigate the association between chronic pain and explanatory factors (body condition, anti-inflammatory medication, animal physiotherapy consultation once or more and owners’ perception of pain interfering). Seventy-five percent of the dogs had ongoing anti-inflammatory medication, 51% of were overweight and 45% had a physiotherapy consultation. Higher levels of overt pain behaviors were reported in items addressing activities. Body condition, physiotherapy consultation and medication were not associated with chronic pain. Odds ratio (OR) and 95% confidence intervals of OR for the CBPI were 1.74 (1.23-2.47) and significantly associated with chronic pain. The adjusted OR of the CBPI did not differ from the crude OR. Owner-perceived pain behavior was not confounded by the dogs’ medication. Results indicated that CBPI was not mediated by the medication. The CBPI pain interference score was not associated with response bias and may be used as clinical outcome measure of chronic pain and pain-related disability in dogs with OA along a period of physical rehabilitation comprising pharmacologic and nonpharmacologic pain interventions.

Initial psychometric testing and validation of the French version of the Canine Brief Pain Inventory

ObjectiveThe Canine Brief Pain Inventory (CBPI) is an owner-completed questionnaire quantifying the severity and impact of chronic pain in dogs. The English version of the CBPI was adapted into French and the objective of this study was to validate this French version of the CBPI. Study designProspective clinical study. AnimalsA group of 32 dogs with a medical history, clinical signs and radiographic evidence consistent with osteoarthritis. MethodsOwners of dogs with osteoarthritis who were native French speakers completed a single administration of the translated questionnaire. The psychometric properties were evaluated including construct validity (by factor analysis), reliability (internal consistency) and convergent validity. ResultsFactor analysis on the responses from this cohort confirmed a two-factor questionnaire: the Pain Severity (PS) factor and the Pain Interference (PI) factor. The mean inter-item correlation for PS and PI questions was 0.74 and 0.53, respectively. These findings reveal strong internal consistency, suggesting that the questions contained within each factor measure the same concept and can be pooled to generate the PS score (PSS) and PI score (PIS). Cronbach’s α was 0.91 and 0.87 for PSS and PIS, respectively. There was strong negative correlation between PSS and PIS with the overall quality of life score (r = –0.62 and r = –0.79, respectively, with p < 0.001 for both), consistent with the hypothesis that increases in PS and PS with function are highly correlated with a corresponding decrease in overall quality of life. Conclusions and clinical relevanceInitial validation of this French version of the CBPI represents an important step in the expanded use of validated owner-completed outcome assessment instruments for use by researchers and clinicians who seek reliable methods to quantify the severity and impact of chronic pain in dogs with osteoarthritis.

Anti‐nerve growth factor monoclonal antibodies for the control of pain in dogs and cats

Nerve growth factor (NGF) is essential for the survival of sensory and sympathetic neurons during development. However, in the adult, NGF and its interaction with tropomyosin receptor kinase A receptor (TrkA) has been found to play a critical role in nociception and nervous system plasticity in pain conditions. Thus, various monoclonal antibody (mAb) therapies targeting this pathway have been investigated in the development of new pharmacotherapies for chronic pain. Although none of the mAbs against NGF are yet approved for use in humans, they look very promising for the effective control of pain. Recently, species-specific anti-NGF mAbs for the management of osteoarthritis (OA)-associated pain in dogs and cats has been developed, and early clinical trials have been conducted. Anti-NGF therapy looks to be both very effective and very promising as a novel therapy against chronic pain in dogs and cats. This review outlines the mechanism of action of NGF, the role of NGF in osteoarthritis, research in rodent OA models and the current status of the development of anti-NGF mAbs in humans. Furthermore, we describe and discuss the recent development of species-specific anti-NGF mAbs for the treatment of OA-associated pain in veterinary medicine.

Owner assessment of the outcome of tibial plateau levelling osteotomy without meniscal evaluation for treatment of naturally occurring cranial cruciate ligament rupture: 130 cases (2009 to 2013).

To evaluate long-term surgical outcome and chronic pain in dogs suffering from naturally occurring cranial cruciate ligament rupture treated by tibial plateau levelling osteotomy without meniscal evaluation. In this retrospective clinical study, data from surgical records of dogs with cranial cruciate ligament rupture that underwent tibial plateau levelling osteotomy without meniscal evaluation between August 2009 and November 2013 were reviewed. An owner questionnaire was used to evaluate the long-term outcome and the prevalence of chronic pain. 107 dogs were included in this study. The long-term follow-up ranged from 1 to 4·5 years (mean 2·5 years). Four dogs developed acute lameness 4 to 21 months after surgery after having shown improvement. Dog behavior was assessed to be normal in 93% of cases and the level of activity was estimated to be normal for 88% of cases. Persistent lameness was reported after surgery in 6% of dogs and might have resulted from undiagnosed meniscal lesions. Considering the low incidence of persistent lameness after surgery and the limits of diagnosis and treatment, the need for routine meniscal examination during tibial plateau levelling osteotomy is questionable.

Veterinarians' attitudes towards chronic pain

A PAPER summarised on p 428 of this issue of Veterinary Record on the attitudes of veterinary surgeons to chronic pain in dogs (Bell and others 2014) poses some interesting...

Veterinarians' attitudes to chronic pain in dogs

Veterinary surgeons in the UK were invited to complete an internet survey concerning their attitudes to chronic pain in dogs. UK veterinary surgeons numbering 215 completed surveys in full along...

Guidelines for recognition, assessment and treatment of pain: WSAVA Global Pain Council members and co-authors of this document:.

Karol Mathews DVM DVSc DACVECC (Canada) Peter W Kronen Dr Vet Med, DVM DECVAA (Switzerland) Duncan Lascelles BSc BVSc PhD DSAS DECVS DACVS MRCVS (USA) Andrea Nolan MVB DVA PhD DECVAA DECVPT MRCVS (UK) Sheilah Robertson BVMS (Hons) PhD DACVAA DECVAA DECAWBM (WSEL) DACAW MRCVS (USA) Paulo VM Steagall MV MS PhD DACVAA (Brazil/Canada) Bonnie Wright DVM DACVAA (USA) Kazuto Yamashita DVM MS PhD DJCVS (Japan)

Therapeutic options for the treatment of chronic pain in dogs

Chronic pain is a widely recognised problem in humans and is being increasingly recognised as a significant problem in dogs. Whilst a large number of therapies are described and utilised to treat chronic pain in dogs, there is a severe shortage of evidence to guide practitioners in selection of treatments. Until more evidence becomes available, practitioners should adopt a cautious approach, utilising licensed treatments first when possible. Non-pharmacological therapies should be incorporated into the chronic pain management plan whenever possible. Given the probable prevalence of chronic pain in dogs there is an urgent need for research to identify effective treatments.

The Challenges of Assessing Osteoarthritis and Postoperative Pain in Dogs

The challenge of measuring pain in veterinary medicine is compounded by the lack of fully validated, reliable methods to measure and assess pain in nonverbal patients. In human medicine, there are numerous, validated pain assessment tools (PATs) for assessing various, specific types of pain. The advances in human medicine pain management and numerous validated pain scales should serve as incentives and templates to facilitate similar advances in the development of validated PATs for use in dogs (and other species). The limited number of canine PATs constrains our ability to adequately and reliably assess pain. Improving the ability to quantify osteoarthritis and postoperative pain in dogs would enhance the development of analgesics for animals, advance the management of animal pain, facilitate the use of animal pain models in preclinical trials for human analgesics, and provide insight into the quantification of pain responses in humans who lack the ability to adequately communicate. This review describes the need for practical, valid, and reliable PATs for use in veterinary patients and discusses some currently available PATs commonly used to evaluate acute and chronic pain in dogs.