Pain negatively affects quality of life, delays recovery and induces behavioral changes that affect owner-companion animal bond. Pain causes unnecessary fear, anxiety, and stress in affected animals and may lead to sympathetic nervous system activation, and alter food intake and metabolism.¹ For these reasons, the management of animal pain is a significant ethical and economic component in the modern practice of veterinary medicine.² Pain is now considered as the 4th vital sign, and its assessment should be incorporated into the clinical evaluation of all patients. We, as veterinarians, need to be prepared to appropriately assess and treat pain in order to mitigate animal suffering to the best of our ability.¹

The more we investigate pain, the more we learn how complex it is. The pathophysiology of pain is approached in a simplified manner in order to understand its clinical presentation and therapy. The pain processing occurs via four main steps, transduction, transmission, modulation and perception.^3,4

Transduction occurs via activation of peripheral nociceptors. These are present in the skin, muscles, joints and viscera. The activation of nociceptors results in the opening of membrane ion channels resulting in membrane depolarization and generation of an action potential. Therefore, a mechanical, chemical, electrical, or thermal stimulation may generate an action potential at the nociceptor level (periphery).

Transmission occurs when this impulse travels from the primary afferent fiber (1st order neuron) to the dorsal horn of the spinal cord (grey matter).

Modulation occurs at the level of the dorsal horn of the spinal cord where the nociceptive message travels via 2nd order neuron to the cerebral cortex (3rd order neuron). During the modulation process, the nociceptive message may be amplified or inhibited depending on the nature of the neurotransmitters. Therefore, these changes could be excitatory (e.g., glutamate, substance P), inhibitory (e.g., GABA) or modulatory (e.g., noradrenaline, serotonin, opioids).

Mechanisms of pain inhibition:

 Local inhibitory pathway (afferent fibers) known as the `gate control theory`

 Descending inhibitory system

Perception occurs when there is `translation` of the stimulus into perceived pain.

Additionally, the difference between acute and chronic pain needs to be clear.

Acute pain is also known as adaptive pain. It occurs when inflammation and nociception prevail such as in postoperative pain. It is generally associated with potential or actual tissue damage and serves to avoid or minimize damage during healing. It is usually self-limiting.¹

Within the acute pain umbrella, nociceptive and inflammatory pain may occur.

Nociceptive pain is a process where the peripheral primary afferent neurones are activated by a noxious stimulus which can be chemical, mechanical, or thermal. The intensity and duration are proportional to the stimulus and usually produces a protective response such as withdrawal (e.g., pinching of the skin, hot surface).^3,4

Inflammatory pain occurs when there is actual tissue injury or immune cell activation. These result in the release of inflammatory mediators from cells and consequent chemical changes in the tissues around the nociceptors which amplify the nociceptive input to the spinal cord. This occurs by facilitation or direct nociceptor activation.^3,4

Chronic pain is also known as maladaptive pain. It is characterized by neuropathic or functional pain, such that the degree of pain does not necessarily correlate with the pathology observed or perceived by the individual. It is not associated with healing. It persists beyond the expected course of an acute disease process and it has no clear end-point.¹

Neuropathic pain is associated to a primary lesion or dysfunction of the nervous system. This results in complexes mechanisms including sensitisation of neural connective tissues, ectopic excitability, cross-excitation, gliopathy, and neuro-immune interations.^5,6

Examples include nerve compression, infiltration by cancers, amputations, intervertebral disk disease, nerve damage during dental extractions, osteoarthritis, among others. In humans, neuropathic chronic pain is generally considered to cause more severe and long-lasting pain, and to be less responsive to analgesics. In addition, it causes greater dysfunction and poorer indices of quality of life when compared with other types of chronic pain.

In some cases, acute inflammatory pain can persist and become pathologic and maladaptive especially when neuropathic pain (e.g., limb amputation) is involved or pain was not addressed properly at the time of initial injury. Thus the importance of appropriate analgesic management in the perioperative period. Pre-emptive and multimodal analgesia should always be considered.

Central sensitisation is the increased responsiveness of nociceptive neurons in the central nervous system to their normal or subthreshold afferent input. It is expressed as pain hypersensitivity and sustained cerebral nociceptive inputs. These processes translate clinically to hyperalgesia (i.e., increased pain from a stimulus that normally provokes pain) and allodynia (i.e., pain due to a stimulus that does not normally provoke pain).⁷

References

1.  Mathews K, Kronen PW, Lascelles D, et al. Guidelines for recognition, assessment and treatment of pain: WSAVA Global Pain Council members and co-authors of this document. J Small Anim Pract. 2014:55:E10–68.

2.  Greene SA. Chronic pain: pathophysiology and treatment implications. Top Companion Anim Med. 2010;25:5–9.

3.  Klinck M, Troncy E. The physiology and pathophysiology of pain. In: Duke-Novakovski T, Vries M, Seymour C, eds. BSAVA Manual of Canine and Feline Anaesthesia and Analgesia. 3rd ed. Gloucester, UK: BSAVA; 2016.

4.  Meintjes RA. An overview of the physiology of pain for the veterinarian. Vet J. 2012;193:344–348.

5.  Grubb T. Chronic neuropathic pain in veterinary patients. Top Companion Anim Med. 2010;25:45–52.

6.  Woolf CJ, Mannion RJ. Neuropathic pain: Aetiology, symptoms, mechanisms and management. Lancet. 1999;353:1959–1964.

7.  Merskey H, Bogduk N, eds. Classification of Chronic Pain: Descriptions of Chronic Pain Syndromes and Definitions of Pain Terms. 2nd ed. Seattle, WA: IASP Press; 1994.