Development

Responses to somatic stimuli begin at an early age. Reflex responses to stimuli begin around 7.5 weeks postconception in the perioral skin and continue to develop in the palms of the hands before finally reaching the limbs by about 13 to 14 weeks. Peripheral pain receptors are in place systemically by around 20 weeks postconception (Stevens, 1999). By 21 weeks, there is dendritic arborization. At around 22 weeks postconception, nerve tracts in the spinal cord to the brain stem and connections with the thalamocortical fibers are in place. But it is not until 32 weeks that the descending, inhibitory fibers are complete. These fibers aid in blunting full pain response and experience. Therefore, a lack of neurotransmitters in the descending tract suggests a lack of complete neuromodulating mechanisms in the preterm infant, making the infant more sensitive to pain than older children and adults (Anand et al., 2006).

Nociception is the most common pain pathway. Nociceptors are sensory receptors that are located throughout the body and are activated by physical, chemical, or heat stimuli. First, painful sensory stimuli are introduced; these can be actual tissue damage, muscle spasms, or even anticipated tissue damage.

Most pain originates from damage to body tissues. A stimulus is introduced, perceived by the nociceptors, then sent through the spinal cord and into the brain for interpretation. A stimulus is transmitted first through tiny afferent nerve fibers in the spinal cord. The fibers that are most responsible for pain are the afferent A-delta and C-fibers (Adriaensen, Gybels, Handwerker, & Van Hees, 1983). These fibers are the first-order neurons and they begin the pain-perception process. A-delta fibers are found primarily in the skin and muscle, and C-fibers are found in muscle, periosteum, and visceral organs. A-delta fibers are myelinated fibers that produce rapid sharp, pricking, and piercing sensations. This pain is usually localized. In contrast, C-fibers are unmyelinated (or poorly so), and conduct temperature, chemical, or strong physical signals. Pain elicited from the C-fibers is a dull, aching, or burning pain that is more diffuse. Of note, there are other fibers responsible for sensation related to pain, such as A-alpha and A-beta fibers. A-alpha and A-beta fibers transmit nonpainful sensations such as pressure, soft touch, and vibration. These nonpainful sensations can be either beneficial or detrimental to pain management by either contributing to stimulation overload or by helping to block painful messages.

The stimuli then travel through to the spinal cord, to the dorsal root ganglia, through to the dorsal horn, and up to the thalamus. This begins the involvement of the second-order neurons. The tract from the dorsal horn to the thalamus is called the spinothalamic tract and it is divided into two pathways: the lateral pathway called the neospinothalamic (NST) tract and the medial pathway called the paleospinothalamic (PST) tract. The NST tract transmits pain directly to the sensory cortex, where it is interpreted. The PST tract synapses in other parts of the brain, such as the limbic system and the reticular formation, which are areas of the brain responsible for emotion and circadian rhythm. A-beta fibers make synapses in the spinal dorsal horn close to synapses of the A-delta and C-fibers. This dorsal horn connection means that input from touch fibers can enter the spinal cord and synapse or communicate with cells carrying nociceptive input. This is an important reason that techniques, such as massage, light touch, acupuncture/acupressure, and other alternative measures, work to aid in pain management.

Pain stimuli may be influenced by neuroregulators. Neuroregulators are chemicals that inhibit, enable, or even enhance painful stimuli. There are two types: neurotransmitters and neuromodulators. Neurotransmitters, such as epinephrine, norepinephrine, acetylcholine, and dopamine, work to either slow or accelerate postsynaptic nerve activity. Neuromodulators are endogenous opiates and help in pain relief. They consist of large amino acid peptides, such as alpha-endorphins, beta-endorphins, and enkephalins, which act similarly to morphine with increased potency. Endorphins are produced in the anterior pituitary gland and hypothalamus. They are larger peptides and longer acting than enkephalins. Enkephalins are more diffuse throughout the brain and dorsal horn. Several types of endorphins and enkephalins have been identified and each acts on a highly specific opiate receptor in the central nervous system (CNS).

Once the pain signal reaches the brain, it is processed at three levels: the thalamus, midbrain, and cortex. These areas work together to interpret and respond to stimuli. The thalamus relays sensory data from the NST and PST tracts. The midbrain alerts the cortex to be aware of incoming stimuli. Lastly, the cortex discriminates and interprets the stimuli. This demonstrates that the painful stimuli must pass through many areas of the brain, which sometimes includes behavioral and emotional centers. All of this happens in a matter of seconds (Figure 1.1).

Almost all painful stimuli cause some degree of tissue damage (e.g., heel lancing, venipuncture, catheterization, difficult adhesive tape removal). This damage leads to a release of chemicals, such as noradrenaline, bradykinin, histamine, prostaglandins, purines, cytokines, 5-HT, leukotrienes, nerve growth factor, and neuropeptides, which sensitize the receptors. This sensitization occurs to make sure the body is aware of the painful stimuli and can act to stop the stimuli and begin repair. These chemicals can also lead to a decrease in the nociception threshold, ectopic discharges, and accumulation of sodium (Na) channels, especially with repeated exposure to pain (Devor, 1994).

Pain is processed in four main ways: transduction, transmission, modulation, and perception (Box 1.1).

FIGURE 1.1.

Noceptive stimulus received at the periphery → travels through the dorsal horn of the spinal cord to the dorsal root ganglia → thalamus → through the spinothalamic tracts (paleospinothalamic [PST] and neospinothalamic [NST]) → NST goes to the sensory cortex → PST goes to limbic system and reticular formation.

Pain Theories

Most information known about pain is related to the adult pain experience. One prominent pain theory is the gate control theory introduced in 1965 by Melzack and Wall. This theory explores the fact that pain is more than just a physiologic response; other variables, such as behavioral and emotional responses, influence perception of pain. Because neonates lack the context to apply the stimuli, this gate is more likely to be open for painful messages to reach the brain. Let us further describe this theory. The gating process occurs in the spinal cord. A-delta and C-fibers send pain impulses from the periphery. These impulses travel to the dorsal horns of the spinal cord, specifically to the substantia gelatinesa. The cells of the substantia gelatinesa either stop or allow pain signals to be transmitted to the T-cells. When T-cell activity is inhibited, the gate is closed and pain signals have a reduced chance of reaching the brain. When the gate is open, pain signals travel directly to the brain (Melzack & Wall, 1965).

Similar “gating” mechanisms exist in the nerve fiber descending from the thalamus and cerebral cortex. These are the areas of the brain that control thoughts and emotions. When pain occurs, a person’s thoughts and emotions can modify the perception of pain. Neonates, unfortunately, lack language abilities, life experience, and control over thoughts and emotions to assist in this gating process. Neonates benefit from comfort measures that help to reduce pain by reducing agitation, promoting sleep, and decreasing a feeling of disorganization (AAP and Canadian Paediatric Society, 2006). Other theories have been proposed against the gate control theory, some arguing a more dynamic and less linear path of pain interpretation.

Another theory related to pain that has significant bearing on the neonate is the theory of wind-up. Wind-up is a phenomenon in which repeated exposure to the same noxious stimulus leads to an exaggerated response and this response continues even after the noxious stimulus is withdrawn (McMahon, Koltzenburg, Tracey, & Turk, 2013). With repeated moderateto severe pain, N-methyL-D-aspartate (NMDA) receptors are activated, which produces a wind-up effect, changing intracellular calcium ion concentrations and creating synaptic buildup of excitatory amino acids. Pain intensity, duration, and surface distribution become greater than expected for a particular stimulus (Coderre, Katz, Vaccarino, & Melzack, 1993).

Types of Pain (Nociceptive, Neuropathic, Somatic, Visceral, Acute, Chronic)

One of the ways to describe pain is from its source. Pain can originate from several different locations and manifest in many different ways. Nociceptive pain is perceived by afferent nerve fibers (as described in Figure 1.1). This refers to a stimulus activating the nociceptors in body tissue, and then traveling through the spinal cord and brain for interpretation and action. Nociceptors are so named because of their affinity to transmit noxious stimuli (Sherrington, 1906). They perceive all potential risks to body tissues, including thermal, mechanical, and chemical risks. Neuropathic pain is perceived by deafferent nerve fibers. The IASP defines neuropathic pain as “pain caused by a lesion or disease of the somatosensory system” (Merskey, Lindblom, Mumford, Nathan, & Sunderland, 1994). This is basically pain not caused by a painful stimulus, but by a dysfunction or defect in the neurological system resulting in pain. This is rare in neonates, but may occur with traumatic brain injury from delivery, meningitis, or some other encephalopathic condition.

Pain can also be described as somatic or visceral. Somatic pain affects the skin, bone, muscle, blood vessels, and connective tissue. Visceral pain affects the vital organs and the linings of body cavities. An example of somatic pain would be a venipuncture. An example of visceral pain would be insertion of a chest or gastrointestinal tube.

Acute pain is temporary pain that is expected to last no longer than 6 months. Examples of this would be procedural pain or pain from an acute injury. Chronic pain is pain that lasts or is expected to last longer than 6 months. Chronic pain is rare in neonates. Examples of chronic pain would be pain from incurable neurodegenerative diseases or cancer. In the APS’s latest statement they indicate the significance of chronic pain in the pediatric population and stress the importance of improving patient functioning and quality of life. The APS also recommends the use of psychological interventions, such as relaxation techniques and parent interventions, for all children with chronic pain.