Mechanism of pain

Pain sensation is a dynamic process with highly organized neural and chemical circuits. Sensory information is transmitted to the central nervous system from afferent neurons, a process termed ‘nociception’. These incoming pain signals are processed within the dorsal horn of the spinal cord and result in reflexive actions, such as withdrawal from the source of injury. Reflexive actions facilitate a rapid response, while, concurrently, pain signals are transmitted to the brain to produce an emotional response and memory. The motivational responses to pain, which provoke a goal-directed action of avoidance, results from activity within the hypothalamus, periaqueductal grey area and thalamus, whereas the anterior cingulate cortex evaluates the hedonistic value of pleasure and of pain. Within the midbrain, the pain system interacts closely with the fear system at several locations, such as within the amygdala and periaqueductal grey, facilitating consolidation of memories that will be important for recognising potentially dangerous stimuli in the future and developing flexible responses of avoidance.

Pain signals are suppressed or amplified by coordinated neural connections between the brain and spinal cord. During sympathetic nervous system activation or the fight–flight–freeze response when animals may be scared, pain sensations are suppressed – a phenomenon referred to as ‘stress-induced analgesia’. Conversely, conditioned safety signals can increase pain sensation, through the release of peptides, such as cholecystokinin, in the cerebrospinal fluid, which can suppress pain control mechanisms, including opioid analgesic drugs, acupuncture and placebo effects. The regulation of pain sensation is discussed further below.

During the fight–flight–freeze response, suppression of pain serves an adaptive function, allowing the animal to escape from or resolve the conflict. The ‘gate control theory’ suggests that sensory inputs of pain are modulated through ascending and descending pathways in the central nervous system. Descending neural pathways potentiate or attenuate pain signals influencing the amount of neurotransmitter released by the incoming neurons or by changing the sensitivity of the ascending nerves in the spinal cord to these neurotransmitters. Analgesia is not just a response to pain but can also be classically conditioned to avoid painful sensation. When stimuli are perceived that are predictive of pain from past experience, descending signals may be sent to inhibit pain sensation (anti-nociception).

Conversely, safety signals can result in the release of peptides such as cholecystokinin in the cerebrospinal fluid surrounding the spinal cord, which suppress pain-controlling mechanisms (anti-analgesia). Thus administering painful physiotherapeutic interventions to an animal in the presence of a safety signal (most often the owner) may actually exacerbate the pain of the procedure. Hyperalgesia refers to exaggerated pain states with increased responsiveness to signals within the spinal cord. The pain threshold is lowered, and sensory nerve fibers release large quantities of neurotransmitter in the spinal cord in response to afferent signals. It may arise for many reasons, but chronic compression of pain fibers within the spinal cord due to a back lesion are a common cause in animals. In these cases the pain may be sensed as arising from the point of compression or the area served by the nerve. Neuropathic pain refers to a pain that arises as a result of nerve damage and can be extremely painful.

Causalgia is a particular form of hyperalgesia associated with nerve damage (neuropathy) particularly stretching. It is sensed as a burning pain following trauma local to the nerve. It is therefore an important differential in cases presenting with attempts at self-mutilation. A history of trauma to the region and exacerbation by warmth with remission in response to cooling of the affected area may help identify the problem, which often resolves within a year. Infection may also result in hyperalgesia, both with and without neuropathy. For example, it has been suggested that herpes virus infection of the trigeminal nerve in horses may be a cause of headshaking, a severe, involuntary tossing of the head by the ridden horse. It is also known that two types of glial cells, astrocytes and microglial cells, that act as immune cells within the central nervous system, specifically recognise and bind to bacteria and viruses, and when activated they release nitric oxide, prostaglandins, and proinflammatory cytokines, such as interleukin-1 and tumor necrosis factor. These chemicals excite neurons and are key mediators within the spinal cord of exaggerated pain states.

Phantom-limb pain is a common sequel to limb amputation in humans and usually develops several days following surgery. It is reportedly more common in individuals who experienced pain in the limb before amputation. An animal experiencing phantom limb pain might be expected to present with self-mutilation of the wound site and this must be differentiated from direct wound site problems such as irritation from sutures; alternatively, the animal may show a more general pain response. Pain sensation may be suppressed by competing motivational systems. For example, in poultry it has been found that expression of feeding and of pre-laying behaviour produces a degree of analgesia. While there are no scientific reports known to the authors of this being tested experimentally in a physiotherapeutic context, this is often applied in practice by feeding or distracting an animal during examination. It would also be interesting to examine the effects of enriched environments on rehabilitation, especially in horses that often undergo box rest in very barren environments. The processing of pain is also affected by background mood. For example, pain reports are lower in human subjects when stimuli are paired with positive or pleasant odours. Therapeutically, the creation of a relaxing environment for treatment is therefore to be advised for many reasons. Suppression of pain also occurs during and following intense aerobic activity, and is likely mediated by endogenous opioids. This may be one of the benefits of hydrotherapy.

However, not all interventions producing analgesia are necessarily positive and it is important to be aware that when an animal is faced with inescapable aversion, as might occur as a result of intense restraint during painful manipulation, learned helplessness may result. This results in emotional biasing of behaviour towards passivity, active inhibition of skeletal muscles and opioid-mediated analgesia. Thus, if an animal initially struggles and is then overzealously restrained, it may be harder to identify the source of pain.

Reference: Animal Physiotherapy: Assessment, Treatment and Rehabilitation of Animals

Edited by Catherine M. McGowan, Lesley Goff, Narelle Stubbs.