Merck Manual

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Professional Version

Pain Perception in Animals


Sandra Allweiler

, DVM, DACVAA, Department of Clinical Sciences, Carlson College of Veterinary Medicine, Oregon State University

Reviewed/Revised Mar 2023 | Modified Jun 2023

Based on current knowledge, all vertebrates, and some invertebrates, experience pain in response to actual or potential tissue damage. Many types of pain are encountered, with the most common types being acute, chronic, cancer-related, and neuropathic.

  • Acute pain is sudden in onset and can be severe. However, it disappears when the stimulus is removed or in a short period of time, and it tends to be self-limiting. Acute pain has a biological function, because it serves as a warning of dysfunction while leading to protective behavioral changes. Acute pain is a symptom of disease.

  • Chronic pain, unlike acute pain, lasts for several weeks to months and persists beyond the expected healing time. Chronic pain does not serve a biological function and imposes severe detrimental stress. Chronic pain, in and of itself, is a disease of altered neuroprocessing.

  • Cancer-related pain, or "cancer pain" is the result of primary tumor growth, metastatic disease, or the adverse effects of chemotherapy and radiation treatment. Cancer pain can be acute, chronic, or intermittent and is related to the disease itself or the treatment.

  • Neuropathic pain originates from injury or post-injury damage to the central or peripheral nervous systems, such as trauma (eg, amputation or crushing injury), vascular injury (eg, thromboembolic disease), endocrinopathy (eg, diabetes mellitus), or infection (eg, postherpetic neuralgia), possibly associated with motor, sensory, or autonomic deficits.

Five processes comprise the physiology of pain: transduction, transmission, modulation, projection, and perception.

Transduction is the conversion of stimuli into an action potential or nerve signal at the level of the specialized receptors or free nerve endings. Signaling transduction can only be initiated by a mechanical, thermal, or chemical stimulus.

Transmission is the propagation of the action potential by primary afferent neurons. There are two major fibers transmitting to the spinal cord. A-delta fibers have a small diameter and a thin myelin sheath and transmit immediate sharp pain. The unmyelinated C-fibers are small and transmit longer-lasting dull or burning pain sensations more slowly, carrying signals from multiple or repeated stimulation of nociceptors. The spinal cord's dorsal horn is divided into laminae (layers), with lamina I at the tip of the dorsal horn. A-delta and C-fibers mainly terminate in laminae I and II, but C fibers often communicate in deeper laminae as well via interneurons.

Modulation is the process of augmenting or suppressing nociceptive information.

Projection is the process of transporting nociceptive information to the brain, from the spinal cord to the brain stem and thalamus and then to the cortex.

Activity in spinal nociceptive pathways is strongly influenced by descending antinociceptive systems that originate in the brain stem. Endogenous antinociceptive neurotransmitters (eg, endorphin, enkephalin, dynorphin, serotonin, and norepinephrine) inhibit the transmission of nociceptive information in the spinal cord and brain.

The neuroanatomic components of the nociceptive/pain pathways and pain-suppressing systems can change in response to sustained sensory input. Peripheral sensitization of nociceptors and central sensitization of nociceptive pathways in the dorsal horn of the spinal cord and brain can develop as a result of extensive tissue trauma or nerve injury. The process of peripheral and central sensitization has been termed “wind-up” and refers to the neuroanatomic changes (plasticity) that result in heightened or exaggerated pain states.

Additionally, these exaggerated pain states often do not respond to conventional analgesic treatment. The efficacy of opioids is especially limited, likely because of a downregulation of opioid receptors, a phenomenon that has been reported in the dorsal root ganglion and the dorsal horn. Thus, changes in the CNS in response to repeated and sustained nociceptive input (ie, pain) complicate the clinical management of pain.


  • Muir WW 3rd, Woolf CJ. Mechanisms of pain and their therapeutic implications. J Am Vet Med Assoc. 2001;219(10):1346–1356. doi:10.2460/javma.2001.219.1346

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