Pain mechanisms and their implication for the management of pain in farm and companion animals

Over the last two decades there has been a dramatic increase in the literature relating to the mechanisms and management of pain in domestic animals. Understanding the mechanisms of pain is crucial for its effective management. This review highlights the current understanding of the neurophysiology of nociception and the plastic changes involved in chronic pain states. Additionally, we describe a range of novel molecules and pathways that offer opportunities for the development of mechanism-based analgesic therapies. Pain management in animals is limited by pain assessment which remains highly subjective, with clinicians relying on indirect measures of pain, using rating scales and (less frequently) quantifiable physiological and behavioural parameters. The need for a systematic approach which would assess different pain components is well justified. Species-specific issues on pain assessment and management in mammalian companion and farm animals are addressed in the later part of this review.     

Assessment and management of acute pain in cats

Abstract: Cats are popular pets, but until recently, their peri-operative and traumatic pain had been seriously underestimated and under-treated. The lack of treatment stems from difficulty in recognizing pain, lack of licensed analgesic drugs, fear of toxic side effects, and lack of information specific to cats. Fortunately, in the last decade, many advances have been made in feline analgesia. It is now obvious that because of the cat's unique metabolism, species-specific studies are essential. Opioids are the mainstay of any analgesic protocol for acute pain and can be used with few side effects. Other drugs that can be utilized include the α₂-agonists, local anesthetics, and non-steroidal anti-inflammatory drugs. Pain assessment in cats is challenging and developing, and validating pain scoring systems remains an important goal. The information in this article will help the critical care and emergency clinician formulate a safe and effective analgesic plan for feline patients.     

Clinical Analgesia in Reptiles

Reptile pain and analgesia is only beginning to be understood in veterinary research and clinical medicine. The diversity of the class Reptilia also makes it difficult to extrapolate analgesic efficacy across species. Many veterinary clinicians argue that the administration of analgesic medication is risky to the patient and may mask behavioral signs of pain, which are considered evolutionarily adaptive for survival. However, veterinarians have an ethical obligation to treat painful conditions in all animals, including reptiles, because effective pain management reduces stress-induced disruption to homeostatic mechanisms and also decreases morbidity and mortality associated with trauma or surgery. Nevertheless, several obstacles limit successful analgesic use, including subjectivity of pain assessment, inadequate knowledge regarding analgesic efficacy across species, pharmacokinetics of analgesic drugs, and the unknown relationship between risks and benefits for this class of drugs. The objective of this review is to provide a current perspective on the practical application of analgesic medication in commonly maintained pet reptile species.     

Long‐term use of non‐steroidal anti‐inflammatory drugs in cats with chronic kidney disease: from controversy to optimism

This is the first of a series of capsule reviews published by the World Small Animal Veterinary Association ‐ Global Pain Council (WSAVA‐GPC). Each of these short articles provides a brisk assessment of the scientific evidence in specific aspects of pain management, including analgesic techniques, recommendations and controversies surrounding their use. In this first capsule review, the scientific evidence available on the long‐term use of non‐steroidal anti‐inflammatory drugs in cats with concomitant chronic pain and chronic kidney disease is discussed.     

Characteristics of pain and response to analgesic treatment in dogs and cats examined at a veterinary teaching hospital emergency service

OBJECTIVE: To estimate the prevalence and characteristics of pain in dogs and cats examined by an emergency service at a veterinary teaching hospital and evaluate the response of dogs and cats with signs of pain to analgesic treatment. DESIGN: Cross-sectional study. ANIMALS: 317 dogs and 112 cats. PROCEDURE: A questionnaire was used to categorize the characteristics of pain. The location, cause, and signs of pain were determined by obtaining a thorough history and conducting a physical examination. Pain was categorized by type (superficial somatic, deep somatic, or visceral), mechanism (inflammatory, neuropathic, or both), severity (mild, moderate, or severe), and duration. Evidence for primary or secondary hypersensitivity and hyposensitivity to manipulation was determined. The response to single or multiple analgesic drug administration was assessed. RESULTS: 179 (56%) dogs and 60 (54%) cats had signs of pain. In most of these dogs and cats, pain was classified as acute (< 24 hours' duration) and of moderate severity and was associated with primary hypersensitivity. Most dogs had deep somatic pain; most cats had visceral pain. Inflammation was the most common mechanism. One hundred nineteen (66%) dogs and 41 (68%) cats were treated with analgesic drugs. Analgesic treatment was considered effective in 73 (61%) dogs and 31 (76%) cats. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that moderate to severe acute somatic pain caused by inflammation is common in dogs and cats examined by an emergency service and that a combination of multiple analgesic drugs is more effective than any single analgesic drug in the treatment of pain in these dogs and cats.     

Anesthesia and pain control

Successful anesthetic management of the critically ill patient requires familiarity with the pharmacologic properties of a variety of anesthetic drugs. An understanding of the altered physiology present in the critically ill allows an anesthetic regimen to be selected that prevents an anesthetic-induced decompensation. Pain should never go untreated because of a fear of causing excessive physiologic depression. There are numerous options available to control pain. A technique suitable in one instance may be unsuitable in another; for example, an animal that has a significant degree of respiratory compromise may not tolerate the additional respiratory insult associated with narcotic use. A local anesthetic technique may be preferred in this situation. Often a local technique is all that is necessary to control postoperative pain. Furthermore, if pain is controlled for the first 4 to 6 h post-insult, often no further analgesic drugs need to be administered.     

非甾体抗炎药在猫临床疼痛管理中的应用

疼痛是猫常见且多发的问题,诱发原因很多。近几年,随着国内外兽医对宠物猫的慢性疼痛问题以及临床中疼痛管理日益重视,疼痛管理已成为临床兽医必须面对的重要课题之一。非甾体抗炎药因其解热、抗炎和镇痛的特性而逐渐被广泛应用于动物医学。国内有关非甾体类抗炎药在猫临床疼痛管理中的应用少见报道。主要就国外发表的一些关于猫长期使用非甾体抗炎药的相关文献进行综述,以期为非甾体抗炎药在猫临床疼痛管理中的进一步应用提供参考。     

Postoperative pain and perioperative analgesic administration in dogs: practices, attitudes and beliefs of Queensland veterinarians

Objective The aim of this study was to describe the practices, attitudes and beliefs of Queensland veterinarians in relation to postoperative pain and perioperative analgesia in dogs. Methods One veterinarian from each of the 50 randomly selected Queensland veterinary practices was enrolled after selection by convenience sampling. Results The study response rate was 94.3%. Demeanour, vocalisation and heart rate were the most common postoperative pain assessment tools used, even though the most sensitive tools were considered to be demeanour, heart rate and respiratory rate. Only 20% of respondents used formalised pain scoring systems. Preoperative analgesic administration was always used by 72% of respondents. There was marked variability in the frequency with which analgesia was administered perioperatively for ovariohysterectomy. Only 24% of veterinarians discharged animals with ongoing analgesia even though 38% agreed that pain is still present 7 days postoperatively. Multimodal analgesia was used by 82% of respondents. Epidural and local anaesthetic analgesic techniques were not being utilised by any respondents. Conclusions These results indicate that management of postoperative pain in dogs in Queensland is frequently suboptimal and, at times, is not consistent with the veterinarian's attitudes and beliefs. Continuing education into analgesic use and pain evaluation may be effective in addressing this.     

Pharmacological options for intra-operative and early postoperative analgesia: an update

The motto of the 2011 Global Year Against Acute Pain was 'Anticipate, Assess, Alleviate'. Recent advances in acute pain management include novel applications of widely used drugs, new techniques, as well as further development in our knowledge of pain scoring in veterinary patients. The concept of preventive analgesia is introduced here and serves to strengthen the widely accepted practice of pre-emptive, multimodal analgesia.     

Analgesia and sedation in the critically ill

Objective: To summarize the challenges to recognizing pain in critically ill patients, the rationale for treatment even in the absence of signs of pain, and the therapeutic options available in the intensive care environment. Etiology: Pain is one of many stressors challenging the critically ill patient, and may in turn be multifactorial in nature. Common causes include local and systemic inflammation, injuries, diagnostic and therapeutic procedures, immobilization, and thrombosis. Diagnosis: Critically ill animals with pain may not demonstrate overt behavioral or physiologic signs of distress. Therefore, pain must be assumed to be present for animals whose condition puts them at risk. Therapy: Currently available analgesic and sedative drugs and methods of delivery are described. Several useful analgesics and sedatives may be co‐administered as fluid additives to provide continuous therapy. Prognosis: There is growing evidence that the neuroendocrine stress response to severe injury or illness may become sufficiently intense to contribute to morbidity and mortality. Many therapeutic analgesic and sedation options provide good control of pain and stress, and in some circumstances this may improve the outcome of critical illness.     

Analgesia.

Critical to reducing patient morbidity as well as heightened ethical awareness, alleviation of pain in animals has become integral to medical case management and surgical procedures. Pharmacotherapy is directed at peripheral nociceptors, primary and secondary spinal neurons, and pain-processing areas in the CNS. Accordingly, three primary pharmacologic strategies have evolved: drugs that bind to and activate opioid receptors, drugs that bind to and activate alpha 2 receptors, and drugs that reduce de novo prostaglandin synthesis. In horses, the two predominant types of pain encountered are musculoskeletal and visceral pain. Several factors must be considered when devising a therapeutic strategy, including the etiology of the painful event, desired duration of therapy (acute vs chronic), desire for sedation, and potential side effects and toxicity. Opioids and alpha 2 agonists are particularly effective for visceral pain associated with colic. Butorphanol remains the only commercially available opioid and provides superior visceral analgesia compared with pentazocine or flunixin meglumine but not compared with the alpha 2 agonists. The behavioral changes such the sedative effects of alpha 2 agonists and the increased locomotion and CNS excitability seen with some opioids are important considerations when these agents are used as analgesics. NSAIDs may be considered for visceral pain therapy also, especially pain associated with an inflammatory component or endotoxemia. In particular, flunixin meglumine and ketoprofen provide prolonged analgesia and suppress the effects of endotoxin. Long-term therapy of musculoskeletal diseases usually necessitates chronic NSAID use. Although many NSAIDs are now available in approved equine formulations, there remain some important differences among NSAIDs for the practitioner to consider when choosing an analgesic. NSAIDs differ in their ability to ameliorate pyrexia, affect platelet function, alleviate pain, and reduce inflammation. For ease of administration, those available for oral use include phenylbutazone, meclofenamic acid, flunixin meglumine, and naproxen. All are potentially ulcerogenic, and poor tolerance to one may necessitate switching to another with a better toleration profile or to drug from a different analgesic class.     

Clinical pain management techniques for cats

Although pain management is an emerging and popular topic in veterinary medicine, use of analgesics in cats has received little attention relative to their canine counterparts. Some of the difficulty lies in assessment of whether or not a cat is in pain. Simple observation of a cat in a cage relies upon overt expression of pain, and is often inaccurate. Pain scales have been developed that allow a semiquantitative evaluation of the degree of pain an animal may be experiencing. However, treating pain based upon observation of the painful state is less effective than anticipating and preemptively treating pain. This article reviews specific methods for preemptively treating and alleviating pain in the cat. The traditional approach to pain management involves drug administration. Specific categories of agents used in cats include opioids, nonsteroidal anti-inflammatories, or alpha-2 agonists. Other modalities of pain management, which are also reviewed, include use of local anesthetic drugs for local and regional analgesia, as well as acupuncture.     

Comparison of the analgesic effects of xylazine in sheep via three different administration routes

OBJECTIVE: To examine the influence of administration route on the analgesic effects of identical doses of xylazine in sheep. A prospective, linear, randomised laboratory study. PROCEDURE: The analgesic response to the administration of 2.5 mg of the alpha2 agonist xylazine either intravenously, intramuscularly or subcutaneously was assessed using an analgesia testing method based upon a learned response to a painful electrical stimulus. RESULTS: Intravenous administration achieved the most rapid onset and highest peak analgesic values of all administration methods, but was characterised by a shorter duration of action (25 min). Intramuscular and subcutaneous administration resulted in a longer duration of action (40 min) and a greater total analgesic response. CONCLUSION: For the routine management of acute pain, intramuscular administration provided the best combination of onset, duration and total analgesic response of the routes examined. The absence of adverse side effects, such as sedation, normally associated with the administration of alpha2 agonists should also encourage the use of this method as a simple and effective means of providing significant analgesia in the sheep.     

Application of a Composite Pain Scale to Objectively Monitor Horses with Somatic and Visceral Pain under Hospital Conditions

Pain recognition and management in animals has advanced considerably in the last decade and currently animal welfare is receiving increasing public interest. However, the comprehensive assessment of pain has been inadequately addressed in horses and till recently composite pain scales (CPSs) have hardly been validated for use in patients. We investigated the reliability and clinical applicability of a CPS, originally developed under experimental conditions for assessing pain in horses with various acute soft-tissue and orthopedic conditions before and after general anesthesia and/or (non)elective surgery. These clinical cases (n = 94) were scored by means of the CPS twice daily. Horses without painful conditions and horses admitted for nonpainful diagnostic procedures under general anesthesia were compared with those that were admitted with either acute or chronic surgical and nonsurgical painful conditions of both visceral and somatic origin. Scores of observer 1 were compared with observer 2 to study inter-observer reliability. Composite pain scores showed low baseline values in healthy animals with nonpainful conditions and were not affected when general anesthesia was the only intervention. Inter-observer reliability was very high (n = 23 horses; weighted kappa correlation coefficient, κ = 0.81). Horses with painful conditions responding well to analgesic treatment could be discriminated from horses that had to be euthanized on humane grounds because of painful nonresponsive conditions. We found the CPS to be a promising tool that has the potential to provide a good basis for direct day-to-day assessment of pain status in equine patients with various painful conditions in the future.     

Avian analgesia.

Understanding behavioral indicators of pain and other assessment techniques can help one to recognize pain in birds and prompt us to treat birds with analgesics. An analgesic plan needs to include several modalities to help reduce pain in the avian patient. Analgesic therapy should be directed at treating the disease/injury in the periphery, and the changes that occur in the central nervous system (CNS). Both opioid and nonsteroidal anti-inflammatory drug (NSAID) therapeutics can be selected to provide analgesia for the avian patient.     

Analgesia for the pregnant, lactating and neonatal to pediatric cat and dog

Objective: Very little information on the approach to analgesia in pregnant, nursing or very young animals is available in the veterinary literature. A review of the human and veterinary literature on the various analgesics available for use in this group of patients is presented. The unique physiological characteristics that must be considered when selecting analgesics is discussed. Etiology: As with mature cats and dogs, the origin and severity of pain in this group of animals may be similar; however, differences do exist. Diagnosis: The diagnosis and assessment of pain in pregnant and nursing animals is based on the problem at hand and is similar to other mature animals. The diagnosis in the very young, however, may be more challenging, but should be suspected based on history and clinical signs. Response to analgesic therapy is advised in all animals to confirm the presence and degree of pain. Therapy: Various analgesics and analgesic modalities are discussed with emphasis placed on preference and caution for each group. Prognosis: Management of pain is extremely important in all animals, but especially the very young, where a permanent hyperalgesic response to pain may exist with inadequate therapy. Inappropriate analgesic selection in pregnant and nursing bitches or queens may result in congenital abnormalities of the fetus or neonate. Inadequate analgesia in nursing bitches or queens may cause aggressive behavior toward the young.     

Current attitudes to,and use of,peri-operative analgesia in dogs and cats by veterinarians in New Zealand

AIM: To investigate the attitudes of veterinary practitioners in New Zealand to pain and analgesia, and their use of analgesic drugs, in dogs and cats.

METHODS: A questionnaire posted to 1,200 practising veterinarians was used to gather information about the use of analgesia in dogs and cats, assessment of pain, attitudes to pain relief, analgesic drugs and procedures used, factors affecting choice of analgesic agent, and veterinary demographics, continuing education and staffing.

RESULTS: Three hundred and twenty questionnaires with useable data were returned, a response rate of 28%. Male and female veterinarians were evenly represented. The analgesic agents most commonly used were morphine (opioids) and carprofen (a non-steroidal anti-inflammatory drug; NSAID). Use of peri-operative pain relief ranged from 50% for castration of cats to 91% for fracture repair in dogs. For most procedures, female veterinarians scored pain at a significantly higher level than their male colleagues. Fifty-eight percent of respondents considered their knowledge in the area of assessment and treatment of pain was adequate.

CONCLUSIONS: This survey was considered representative of veterinarians working in companion animal practice in New Zealand. Results indicated a relatively high use of peri-operative analgesia, including both pre-emptive and multi-modal analge- sia, in cats and dogs, although there was still some disparity between the perception of how painful a procedure was and the consequent use of pain relief.

CLINICAL RELEVANCE: The establishment of current attitudes and practices indicates to practising veterinarians how their own use of analgesics compares with that of their colleagues. It also provides information to educators on potential areas of focus, given that 42% of respondents felt their knowledge in the area of assessment and treatment of pain was inadequate.     

Intra‐articular opioid analgesia is effective in reducing pain and inflammation in an equine LPS induced synovitis model

Reasons for performing study: Intra‐articular administration of morphine as a local analgesic and anti‐inflammatory drug is widely used in human medicine. In equids, little is known about its clinical analgesic and anti‐inflammatory efficacy. Objectives: To use an inflammatory orthopaedic pain model to investigate the analgesic and anti‐inflammatory effects of intra‐articularly administered morphine as a new treatment modality in horses with acute arthritis. Methods: In a crossover study design, synovitis was induced in the left or right talocrural joint by means of intra‐articular injection of 0.5 ng lipopolyssacharide (LPS). The effect of 120 mg morphine, intra‐articularly administered at 1 h after induction of synovitis, was evaluated using both physiological and behavioural pain variables. Synovial fluid was sampled at 0, 4, 8, 28 and 52 h after induction of synovitis and analysed for total protein concentration, leucocyte count and for prostaglandin E₂, bradykinin and substance P concentrations by ELISA. Ranges of motion of metatarsophalangeal and talocrural joints were measured as kinematic variables with the horses walking and trotting on a treadmill under sound and lame conditions. Clinical lameness scores and several behavioural variables related to the perception of pain were obtained. Results: LPS injection caused marked transient synovitis, resulting in increased concentrations of inflammatory synovial fluid markers, clinical lameness, joint effusion and several behavioural changes, such as increased time spent recumbent, decreased limb loading at rest and decreased time spent eating silage. Intra‐articular morphine resulted in a significant decrease in synovial white blood cell count, prostaglandin E₂ and bradykinin levels and improvement in clinical lameness, kinematic and behavioural parameters, compared to placebo treatment. Conclusions: Intra‐articular morphine offers potent analgesic and anti‐inflammatory effects in horses suffering from acute synovitis. Potential relevance: Local administration of opioids may be useful for horses with acute inflammatory joint pain and offers possibilities for multimodal analgesic therapies without opioid‐related systemic side effects.     

Development of a scale to evaluate postoperative pain in dogs

OBJECTIVE: To design and evaluate a scale for measurement of postoperative pain in dogs. DESIGN: Randomized, blinded, prospective study, with positive- and negative-control groups. ANIMALS: 36 dogs undergoing general anesthesia for ovariohysterectomy and 12 dogs undergoing general anesthesia without surgery. PROCEDURE: A pain assessment scale was developed for dogs, which incorporated physiologic data (heart and respiratory rates) and behavioral responses (response to palpation, activity, mental status, posture, and vocalization). This pain scale was then applied to a study in which dogs were allocated to 2 groups, depending on the type of medication administered (acepromazine maleate only or acepromazine and butorphanol) before induction of general anesthesia. The 36 dogs that had ovariohysterectomy were allocated to 3 groups, members of which received butorphanol, carprofen, or no analgesic after surgery. Dogs were scored for signs of pain and videotaped at 0, 1, 2, 4, 6, 8, 12, and 18 hours after surgery by an assessor who was blinded to the groups. Results were analyzed for significant differences in pain scores for single categories and total pain scores among groups. Video segments were scrambled and then scored by a second external assessor to test the repeatability of the results, using the pain assessment scale. RESULTS: Mean total pain scores were significantly different between the group of dogs that underwent general anesthesia only and each group of dogs that underwent general anesthesia and surgery. Pain scores for the analgesic-treatment groups reflected the known onset and duration of action of the analgesic used. Agreement between the internal and external assessors was excellent and indicated high precision between the 2 assessors for the population of dogs as a whole. CLINICAL IMPLICATIONS: Behavioral and physiologic measurements can be used reliably to evaluate degree of pain in dogs during the postoperative period and their response to analgesics.     

Pain management in cats--past, present and future. Part 1. The cat is unique

Cats are popular pets but until recently their perioperative and traumatic pain was seriously underestimated and under treated. There are several causes of this under treatment. First, it may be difficult to detect pain in cats, because they do not demonstrate overt pain-associated behaviour. Secondly, there are relatively few analgesic drugs with market authorization for cats. Thirdly, cats have an unfortunate reputation for toxicity from analgesic drugs, particularly opioid-induced mania and classical non steroidal anti inflammatory drug toxicity. Fourthly, cats are deficient in some metabolic pathways used to metabolise analgesic drugs in other species; this may lead to genuine toxicity or to lack of effect. Recently, understanding of feline behaviour and physiology has improved, leading to better clinical management of this enigmatic species. Behavioural methods are proving to be the best means of assessing pain, and knowledge of unique feline physiology has enabled rational treatment protocols to be developed specifically for cats.