Chronic Pain, the Brain, and Behavior
What is pain?
Pain, simply defined, is an aversive sensory experience. In general, it can be broadly categorized as either nociceptive or neuropathic. Nociceptive pain is caused by a noxious stimulus, associated with actual, or in response to potential, tissue damage, and is processed by an otherwise normally functioning somatosensory system. Neuropathic pain, in contrast, is a maladaptive process caused by a broad range of conditions that can affect any organ or tissue that possesses nerve endings. However, it specifically is considered chronic in conditions involving the musculoskeletal system and can be both stimulus-dependent or spontaneous.1
Acute pain is typically pain that lasts a short period of time and subsides after the inflammatory and healing processes have completed. With acute injuries, changes in the neurological response to such stimuli are considered protective, and are expected to subside once the healing has occurred.2
Compared to acute pain, chronic pain is more complex in nearly all respects. Chronic pain can occur with or without an initial acute injury, can become progressively worse, can occur intermittently, and outlasts the usual inflammatory healing process. With acute pain, nociceptors in the peripheral nerves are activated in response to injury or inflammation. These nerves send pain signals through the dorsal root ganglia to the spinal cord and central nervous system, and these signals typically stop once the initial sensory experience or stimulus responsible for the pain is resolved.3 However, with chronic pain, repeated stimulation of the sensory nerves over time can cause changes to the way these signals are processed. Under normal conditions, the stimulus diminishes as healing progresses and the pain sensation lessens; with persistent chronic pain, however, secondary mechanisms both at the periphery and within the central nervous system (CNS) are activated, which can diminish normal functioning.4
Chemical, mechanical, and thermal receptors, along with leukocytes that generate analgesic mediators to counteract inflammatory pain, help determine the intensity, location and duration of the sensory event and activate the sensory nerve signals in the peripheral nervous system (PNS).4 These signals are then transmitted from the PNS to the CNS. With chronic pain, peripheral sensitization occurs, in which a persistent increase in levels of the biochemical mediators causes persistent increase in the pain signals transmitted through the PNS. In turn, this PNS sensitization leads to CNS sensitization, in which the biochemistry of the sensory neurons is altered, fundamentally changing how pain signals are processed, resulting in a heightened perception of pain.5
Pain can inhibit normal behaviors and precipitate abnormal behaviors, and can greatly interfere with the quality of life for both companion animals and their owners.6,7,8 With human patients, the intrusive and subjective nature of pain, and specifically chronic pain states, are well documented. Pain is always subjective to the individual and can be described in terms of how it affects the individual across sensory, emotional, and cognitive dimensions.9 However, both acute and chronic pain can be easily overlooked in companion animals because they are masters at hiding pain and, unlike their human counterparts, are unable to self-report their pain. While pain management has become an essential part of veterinary medicine, it is equally essential for training and behavior professionals to understand pain, its origins and mechanisms, as well as its role in behavior. Research has shown that chronic pain is correlated with emotional and cognitive changes, and furthermore, that chronic pain can fundamentally change the brain on both a structural and functional level, contributing to the development of or increase in emotional and cognitive issues in both humans and animals.10 Understanding the relationship between physical pain and behavior issues in companion animals is fundamentally important in providing the most informed and functional behavior modification plans.
What’s the brain got to do with it, anyway?
Numerous human studies have demonstrated the complex nature of chronic pain, including alterations in brain regions involved with and responsible for cognitive and emotional functions.9 In humans, chronic pain states have a high comorbidity with other psychiatric disorders like anxiety and depression.11 Understanding the mechanisms of not only how chronic pain develops and progresses, but also how it can affect the behavior of companion animals, is important in helping to develop collaborative behavioral modification plans.
Studies of humans and other animals have suggested that regions involved with processing emotions, like the amygdala, as well as those that mediate marked changes in emotional, motivational, and reward-related centers of the brain are associated with the progression of chronic pain, and cause emotional disorders in patients with chronic pain conditions. Brain regions involved with pain processing are similar to those involved with mood disorders.
The mPFC, located in the frontal lobe, is an important region responsible for decision-making, regulation of emotional response, and processing of fear. The mPFC is a critical region that is involved with the emotional and cognitive processing of pain and the persistence of pain memory and the inability to eliminate pain memory after the initial injury has healed — turning acute pain into a chronic problem.10
The hippocampus and important part of the limbic system, located in the medial temporal lobe, is responsible for episodic memories and remembering contexts,12 and because of its extensive nerve connectivity to other brain regions, it also helps regulate and is involved with emotion and cognition. Changes in the hippocampus are associated with increased risk for depressive disorders in humans; additionally, research has shown that changes in hippocampal neurogenesis, the process by which neurons are formed, are associated with the development of chronic pain, as well as responsible for cognitive deficits and associated emotional disorders, like depression and anxiety, that accompany chronic pain states.10
Understanding this particular brain region is of critical importance for behavior professionals. In order for contextual learning to occur, animals must have both a representation of the context and also encoding of the context elements. Once encoded, context elements can themselves be associated with events, like the occurrence of an aversive shock. During normal context conditioning, animals will first encode a representation of the context, then associate that representation with the unconditioned stimulus. These two learning processes are referred to as context encoding and context conditioning.12 These processes, contextual learning, episodic memories, and associations, are made possible by the hippocampus.
Recent studies have shown that molecular and cellular changes in the hippocampus of animals with chronic or persistent pain states led to marked behavior changes, including an increase in anxiety behaviors, and an inability to extinguish contextual fear denoting deficits in both learning and memory.13 Changes in this brain region with chronic pain are so closely associated with anxiety, depression, and other emotional and cognitive difficulties that some researchers hypothesize that chronic pain itself can be redefined in terms of states of continual learning through context conditioning and extinction, through which aversive emotional associations are continuously formed with otherwise insignificant events due to the persistent and chronic presence of pain.13
The amygdala, a critical part of the limbic system located in the frontal portion of the temporal lobe, is important in the regulation of drives, especially fear, and is primarily involved in motivation, fear, and avoidance behaviors.14 The amygdala is responsible for adding emotional and affective context to sensory information, which is then used to regulate fear and pain responses. Changes in amygdala activation are present with chronic pain states, illustrating the important role the amygdala plays in the emotional affective aspects of chronic pain.10 Recent animal research has shown that two pathways in the brain converge at the amygdala and are responsible for regulating the anxiety that accompanies chronic pain states,15 highlighting the important relationship between emotions and pain.
Chronic pain can be associated with changes in the brain function and structure, unlike acute pain. Research has demonstrated that the brain starts to process pain differently if it has been processing pain over a long time.16 Chronic pain states have been associated with brain activity in areas that are normally considered to control or regulate emotion, motivation, and behavior, making it vitally important for behavior professionals to understand and investigate the potential role of chronic pain in behavior cases.
Pain-related behavior changes
Medical issues, particularly those involving chronic pain, may contribute to behavior issues or increase existing behavior problems in companion canines.17 Chronic pain conditions are well-recognized in humans and often have well-defined diagnostic criteria. These same criteria are all but impossible to apply to companion canines, as they require detailed descriptions of the individual’s pain experience or identification of symptoms that are difficult to recognize in animals.2 While veterinarians are able to identify some pain responses, it is often the case that addressing physical symptoms of pain occurs well after the disease has progressed, and in some cases, well after pain-related behavior changes have surfaced.
In a 2012 study, owners presented veterinarians with at least one specific behavior concern during consultation, with a total of over 50 behavior concerns identified by owners across all visits. Only 10 of these behavior concerns were addressed by veterinarians, it is also of note that none of the veterinarians sought to facilitate or implement a plan to manage the behavior problem outside of the clinic/hospital setting.17 This is concerning given that behavior changes are often the first sign of an underlying clinical problem like those involved in chronic pain states.18
Pain-related behavior changes can take on many forms, and owners can report their occurrence suddenly or gradually. They can manifest as changes in attitude, mentation, or demeanor; as development or increase in fearful, anxious, stressed, or avoidant behaviors; or as an increase in hyperarousal, hyperactivity, or hypervigilant behaviors.19,20 Some of the most common pain-related behavior changes are seen as changes in demeanor, including fear and aggression, toward owners or other pets in the home, as well as acute or gradual appearance of or increase in guarding behaviors toward owners or other pets, such as growling when approached.20 Research has shown definite links between chronic pain states in humans and fundamental changes in brain activity as it relates to behavior changes. Specifically, researchers found that, in people with chronic pain, a region of the cortex associated with emotional regulation fails to deactivate normally, leading chronic pain sufferers to also have a high incidence of anxious or depressed behaviors, as well as a marked difficulty in making simple decisions.11 Chronic pain in itself is a disease of altered neuroprocessing, and imposes severe detrimental stress on the brain and pain processing systems as changes develop in response to sustained sensory input.21
While behavior changes can occur suddenly or gradually, it is important to understand the potential for these changes to be in response to chronic pain. Companion animals experiencing severe acute or chronic pain are often found to be anxious and restless and can become increasingly protective, unmanageable or aggressive, while others can become submissive or depressed.22 In a recent study of companion canines presenting with severe noise sensitivity in which owners report at least one sign of fear, anxiety, or phobia behaviors, the relationship between noise sensitivity and chronic pain was investigated.19 Researchers found that in cases with chronic pain, the age of onset of noise sensitivity and associated behaviors was approximately four years earlier, and all cases responded well to behavior treatment once the underlying chronic musculoskeletal pain had been identified, suggesting the noise sensitivity developed as a pain-related behavior.19
Chronic pain–related behavior changes are not unique to older or aging companion animals, and with developmental orthopedic diseases, such as cranial cruciate ligament disease, hip dysplasia, elbow dysplasia and luxating/dislocating patella disease, recognized earlier and earlier in juvenile companion canines, it is important for behavior professionals to understand the potential role of chronic pain in behavior changes and work with both owners and veterinary professionals to create more holistic behavior management plans.
Chronic pain–related behavior changes are also not unique to companion canines. Recent research investigating the relationship of chronic pain and behavior issues in felines found that declawing surgeries that resulted in development of chronic back pain increased the incidence of unwanted behaviors in felines.23 The research found that declawing surgeries in which third phalanx (P3) fragments were left had long-term impacts on gait and weight-bearing displacement in limbs, which led to chronic back pain. This pain was associated with an increase in aggressive behavior, inappropriate elimination, excessive grooming, and biting when compared to felines without chronic back pain as a result of P3 fragments.23 When dealing with our feline friends, it is important for behavior professionals to understand that changes in behavior associated with chronic pain can be even more subtle than with canines, and that feline behavior changes are often mistakenly attributed to age.24
For felines, common signs of chronic pain can include both an increase or decrease in normal grooming activity, inappropriate elimination — urination and/or defecation — increase in hiding behaviors, or more marked emotional changes like increase in fear or aggression. For felines, many common medical conditions can result in chronic pain states, including osteoarthritis, typical urological issues such as stones and crystals, and even diabetes, as well as many other disorders that may have few overt clinical signs but cause chronic pain states.24
Often, owners notice signs of pain at home that cannot be seen by veterinarians in the clinic which makes it vital for owners with companion animals suffering from chronic pain conditions to have behavior support outside the scope of the veterinary office.8 Behavior changes due to chronic pain can be highly individual, and can range from subtle nonspecific changes to more overt changes, ranging from reduced general activity and reduced sociability to increased incidence of anxious or aggressive behavior; behavior displays may be intermittent and dependent on the severity of pain at the time the behavior is displayed.25
The complex nature of chronic pain and the relationship between chronic pain and behavior means behavior professionals need to be knowledgeable across multiple fields, take a more holistic approach to behavior, look at behavior as a function of the body process as a whole, and take a more multi-dimensional approach to behavior assessments and behavior management plans.
What behavior professionals can do
As behavior professionals, first and foremost we must be open to working with owners as well as veterinarians to assess and identify behavior changes that may be associated with or in response to underlying medical conditions and chronic pain states. Not only should we be taking extensive medical histories with behavior evaluations, but we should also become familiar with other signs of potential chronic pain conditions and be mindful of changes in activity, changes or abnormalities in gait, and indications of stiffness or lameness that may be indicative of common chronic pain diseases of the musculoskeletal system. Learning to identify these physical changes along with addressing behavior changes can potentially help owners identify chronic pain diseases earlier in their progression. Recognizing chronic pain can be challenging, particularly because even owners and veterinarians may not realize that behavioral changes can be a potential sign of chronic pain.
As behavior professionals, we can also include pain-focused assessments like the Canine Brief Pain Inventory (CBPI) which is a helpful tool used to quantify the severity of musculoskeletal diseases like osteoarthritis or other chronic pain conditions. The psychological/behavioral portion of the CSU Acute Pain Scale is another valuable tool. For any effective behavior management plan, detailed information on normal behavior, as well as behavior changes as described by the owner, is necessary; however, a detailed knowledge and understanding of the canine’s overall physical health and health changes must be considered equally. Often this requires a collective approach, with input and collaboration with the current veterinarian and/or a veterinary rehabilitation professional.
Another possible assessment tool to include would be the Helsinki Chronic Pain Index, which can be a helpful tool for behavior evaluations. This assessment helps owners identify changes in overall behavior in terms of changes in attitude and mood, as well as identifying potential behaviors associated with chronic pain states like frequency of vocalizations or displays of discomfort, and willingness to engage or play with owners. This measure also easily helps owners identify potential functional deficits that may be indicative of musculoskeletal diseases or chronic pain, like changes in mobility and exercise.
Behavior professionals can bridge this gap by seeking out area veterinary rehab professionals or veterinary orthopedists to refer potential behavior cases for medical assessment, and to offer necessary in-home behavior support for owners of canines suffering from chronic pain diseases. Generally, the most common musculoskeletal disease associated with chronic pain in companion canines is osteoarthritis (OA) which is typically diagnosed in the late stages when veterinary treatment can only help to decrease pain.26 In behavior cases where OA or a related chronic pain condition in suspected, having open communication with veterinary professionals can help facilitate much-needed medical intervention, and potentially help to slow the progression of OA when treatment is sought early. In these cases, using the University of Liverpool Osteoarthritis in Dog (LOAD) questionnaire and having owners present this to veterinarians may help identify behavior changes as a symptom of chronic OA pain earlier. The LOAD questionnaire is an owner assessment used to measure canine disorders like OA, as wells as the potential severity of symptoms, and can be a very helpful tool for owners to present to veterinarians where behavior changes may be a function of underlying chronic medical condition.
Another helpful tool for behavior professionals who may suspect underlying chronic pain disease is the Canine Arthritis Management Suspicion of Chronic Pain Form which can be filled out with the help of the owner and given to the veterinarian. This simple form can be included in all behavior evaluations, and addresses four key areas in identifying potential chronic pain associated with musculoskeletal disease, including changes in overall physical capabilities of the canine, as well as identifying gait changes or abnormal gait patterns, changes in posture, and behavior changes. This simple form, along with a detailed behavior history, can help owners have more informed conversations with veterinarians about potential medical causes of behavior changes.
While veterinarians should become familiar with potential behavior changes that are characteristic of diseases with a chronic pain component, it is equally important for behavior professionals to be versed in potential medical issues, particularly chronic pain conditions that can manifest as behavioral changes. Behavior professionals should be open to working with veterinarians and veterinary rehab professionals to provide guidance in helping owners manage chronic pain-related behaviors in the home, as well as help to develop multidisciplinary approaches in behavior plans, even in young companion animals where chronic pain conditions are suspected.
To bridge this gap, it is important for behavior professionals to understand both pain and its progression, as well as the complexities of pain-related changes in the brain and how pain-related behaviors manifest, as well as work with owners and veterinarians to better identify these behavior changes as function of chronic pain to develop more comprehensive treatment plans. Behavior professionals can also work with owners to better identify, understand, and manage pain-related behavior changes in companion animals where chronic pain diseases have been diagnosed. Behavior professionals can seek out these veterinary practices and offer services for chronic pain patients, helping to foster a collaborative relationship for better overall care. Behavior professionals can help bridge the gap between veterinary treatment and behavior management for owners with animals suffering from underlying chronic pain or where chronic pain is suspected, highlighting the importance of approaching and managing disease and chronic pain, as well as behavior, from a multimodal and multidisciplinary perspective.
- Moore, S.A. (2016) Managing neuropathic pain in dogs. Frontiers in Veterinary Science, 3:17.
- MacFarlane, P.D., Tute, A. S., & Alderson, B. (2014) Therapeutic options for the treatment of chronic pain in dogs. Journal of Small Animal Practice 55:3, pp. 127–134.
- Johnston, S.A. (1997) Osteoarthritis. Veterinary Clinics of North America: Small Animal Practice, 27 (4).
- Voscopoulos, C., & Lema, M. (2010) When does acute pain become chronic? British Journal of Anaesthesia 105, i69–i85.
- Woolf, C.J. (2011) Central sensitization: Implications for the diagnosis and treatment of pain. Pain 152(Supplement), S2–S15.
- Downing, R. (2011) Managing chronic maladaptive pain. NAVC Clinician’s Brief, August 2011.
- Downing, R. (2013) Options for treating pet pain continue to expand. Veterinary Practice News.
- Davis, K.N. et al, (2019) Qualitative study of owner perceptions of chronic pain in their dogs. Journal of the American Veterinary Medical Association 254:1, pp. 88–92.
- Crofford L.J. (2015) Chronic pain: Where the body meets the brain. Transactions of the American Clinical and Climatological Association 126, pp. 167–183.
- Yang, S., & Chang, M.C. (2019). Chronic pain: Structural and functional changes in brain structures and associated negative affective states. International Journal of Molecular Sciences, 20:13, p. 3130.
- Northwestern University. (2008) Chronic pain harms the brain. Science Daily, 6 Feb 2008.
- Maren, S., Phan, K.L., & Liberzon, I. (2013) The contextual brain: implications for fear conditioning, extinction and psychopathology. Nature Reviews Neuroscience, 14:6, pp. 417–428.
- Mutso, A.A., et al (2012) Abnormalities in hippocampal functioning with persistent pain. Journal of Neuroscience 32:17, pp. 5747–5756.
- Goddard, G.V. (1964) Functions of the amygdala. Psychological Bulletin 62:2, pp. 89–109.
- Cai, Y-Q et al (2018) Brain circuits mediating opposing effects on emotion and pain. Journal of Neuroscience 38:28, pp. 6340-6349.
- Ahmed, A. (2013) Brain activity shifts as pain becomes chronic. Pain Research Forum, Oct. 2013.
- Becker, M. (2015) Fear-Free tip: Know who’s training your patients. DVM360.
- Roshier, A.L., & McBride, E.A. (2012) Veterinarians’ perceptions of behaviour support in small-animal practice. Veterinary Record 172:10, pp. 267–267.
- Lopes Fagundes, A.L., et al. (2018) Noise sensitivities in dogs: an exploration of signs in dogs with and without musculoskeletal pain using qualitative content analysis. Frontiers in Veterinary Science 5:17
- Balakrishnan, A. & Benasutti, E. (2019) Pain assessment in dogs and cats. Today’s Veterinary Practice.
- Allweiler, S. (2019) Pain perception. In: Merck Veterinary Manual.
- Wiese, A.J. (2018) Canine and feline pain scales. Clinician’s Brief, Oct. 2018.
- Martell-Moran, N.K., Solano, M., & Townsend, H.G. (2017) Pain and adverse behavior in declawed cats. Journal of Feline Medicine and Surgery 20:4, pp. 280–288.
- Gottlieb, A. (2018) Me-oww. Managing chronic feline pain. Today’s Veterinary Nurse.
- Belshaw, Z., & Yeates, J. (2018) Assessment of quality of life and chronic pain in dogs. The Veterinary Journal 239, pp. 59–64.
- University of Missouri-Columbia. (2009) Early detection of osteoarthritis in dogs could open doors for a cure. Science Daily, 11 Jun 2009.
Nicole Ribeiro, MBM is a United States Veteran, animal trainer and behavior specialist, and co-owner of Massachusetts based adASTRA Canine Co. She has a masters degree in psychology and behavioral medicine with research focusing on learned helplessness in aggression cases, and specializes in holistic behavior modification plans helping owners and their pets build positive bonds for life. She is currently owned by two senior rescues dogs, Zed and Charlie who are enjoying a life of leisure and travel, an adolescent rescue cat named Huckleberry, two senior dumpy frogs, and a rescued tortoise named Oscar. For the coming year she is focusing on developing a senior dog wellness program to help older dogs and their owners live their best life.