CHAPTER 26 Pain Assessment and Management

Recognition and treatment of pain in neonates is an emerging science and is controversial. To effectively treat pain in neonates, the maturity and function of many different body systems must be considered (Figure 26-1). Choosing appropriate drug therapy requires consideration of course, cause, and severity of pain and the duration and side effects of the chosen analgesic therapy (Box 26-1). In addition, other medications, concurrent medical problems and medications, and the patient’s physical status should be considered when choosing analgesics. Few clinical studies have been conducted investigating pain in neonatal dogs and cats. All too often, pain in neonates and juvenile animals is undertreated.

Figure 26-1 Timeline of maturation.

Physiology and Pathophysiology of Pain in Neonates

Pathophysiology of Pain

The physiology and pathophysiology of pain in neonates is similar to other advanced mammals. Peripheral nociceptors (free nerve endings of primary afferent sensory nerve fibers) transduce mechanical, chemical, and thermal energy (noxious input) into electrical impulses. There are two types of nociceptors (A-mechano-heat receptors and C mechano-heat receptors).

Nociceptive impulses are transmitted to the central nervous system (CNS) by primary afferent sensory nerve fibers. There are two main types of fibers: A-delta and C fibers. The A-delta fibers are comparably large diameter, myelinated axons that conduct impulses rapidly and are associated with “first pain.” The C fibers are smaller diameter, unmyelinated axons, with slower conduction velocities, which reinforce the immediate response of A-delta fibers. C fibers mediate second pain.

Primary sensory afferent nerve fibers synapse in the grey matter of the spinal cord dorsal horn, which is organized into layers (laminae). A-delta fibers terminate in lamina I (most important) and lamina V. The C fibers terminate in lamina II. The dorsal horn is the site of modulation of nociceptive input. The primary sensory afferent nerve fibers may form direct or indirect connections with one of three functional populations of dorsal horn neurons (interneurons, propriospinal neurons, and projection neurons). Interneurons are either excitatory or inhibitory and act as relays participating in local processing. Propriospinal neurons extend over multiple spinal segments and involve segmental reflex activity. Projection neurons participate in ascending transmission of nociceptive impulses and extend axons beyond the spinal cord to terminate in supraspinal centers (such as the midbrain or cortex). There are three types of projection neurons: nociceptive specific, wide dynamic range, and complex neurons. Communication in the dorsal horn between primary afferent fibers and dorsal horn neurons occurs by chemical signaling, mediated by excitatory or inhibitory amino acids and peptides produced, stored, and released in the nerve terminals. Glutamate and aspartate are the most important excitatory mediators. Other excitatory neurotransmitters are substance P, neurotensin, vasoactive peptides, calcitonin gene-related peptide, and cholecystokinin.

Projection neurons transmit nociceptive input to supraspinal centers via tracts that ascend in white matter of the spinal cord: spinothalamic, spinoreticular, spinomesencephalic, spinocervical, and spinohypothalamic tracts. The spinothalamic tract originates from nociceptive specific and wide dynamic range neurons in laminae I, V, VI, and VII and terminates in lateral and medial nuclei of the thalamus and is believed to be the most important with regard to nociception. The spinothalamic tract is only faintly myelinated at birth. Myelination occurs in the external tracts more quickly than in the deeper tracts, with full myelination occurring between 3 and 6 weeks of age. Myelinated fibers in grey matter laminae are present at birth. Diameter increases and myelination of these fibers continues during the neonatal period, with full myelination and density occurring at 5 weeks of age.

Nociceptive impulses are subjected to modulation and integration before reaching their ultimate destination, the cerebral cortex. Other supraspinal structures that process and modulate nociceptive input include the reticular formation, periaqueductal grey matter, limbic system, and the thalamus. The thalamus is the major relay station for all sensory input en route to the cerebral cortex. It is especially important for integrating nociceptive impulses and is composed of numerous complex nuclei: the lateral thalamic nuclei are involved in sensory discriminative aspects of pain, while the medial thalamic nuclei are involved in motivational affective aspects of pain. The cerebral cortex is the site where the physiologic process of nociception is integrated and ultimately perceived (Figure 26-2). Several discrete cortical regions are preferentially activated by noxious stimulation: first and second somatosensory cortices, anterior insular cortex, and anterior cingulate. Neurotransmitters in the thalamocortical region are excitatory (glutamate and aspartate) and inhibitory (gamma-aminobutyric acid [GABA], glycine, monoamines, acetylcholine, and histamine). Differences between the integration of nociceptive impulses in neonates compared with adults are unknown.

Figure 26-2 Pathophysiology of pain.

Descending inhibitory pathways modulate sensory input and are especially important for nociceptive transmission. The descending inhibitory modulatory system has four tiers, with inhibitory influences located in the following regions: cortical and thalamic structures, periaqueductal grey matter of the midbrain, rostral medulla, and spinal cord dorsal horn. Antinociceptive effects in these regions are mediated by GABA, glycine, serotonin, norepinephrine, and endogenous opioids (enkephalins, endorphins, and dynorphins). This system ensures that the physiologic pain response generated is appropriate for the noxious stimulus initiated.

Physiologic Changes and Responses to Pain

There are two important aspects to the pain experience in animals: the sensory component and the affective (the emotional) component. In addition, there is a secondary pain affect, or the consequences associated with chronic pain and homeostatic responses. Pain sensation is more intense in humans than other somatic sensations, which would seem to be an evolutionary adaptation. Additional characteristics of pain include quality (e.g., sharp or piercing, dull, throbbing), persistence, temporal summation, spatial spread of sensation at high pain levels, and unique qualities of the sensation that are intrinsically dependent on the location and degree of tissue injury.

An animal’s ability to sense noxious stimuli is present at birth, but the actual sensation of pain in animals is not assessable except by behavioral interpretation. Extrapolation of reports of pain from human studies may result in anthropomorphizing and an increase in assignment of pain in animals. Confounding this is the heightened response to what may be considered a nonpainful or mildly painful stimulus in neonates (learning). The nervous system is plastic, and extensive studies of pain in neonatal animals as a model for human neonatal pain show a heightened sensitivity to tissue injury that can result in neural reorganization by formation of new primary afferents, increased innervation of wounded tissue, and hyperexcitability of dorsal root ganglia. The long-term result of this neural reorganization is hypersensitivity to sensory input and behavioral modification.