How Is Pain Classified?

Pain is generally an adaptive response to tissue injury, but can become its own maladaptive disease state. As such, pain may be classified as either adaptive or maladaptive.

Nociceptive and inflammatory pain are two types of adaptive pain responsible for detecting tissue damage and aiding in healing and prevention of continued tissue injury, respectively. Nociception involves the perception of hot, cold, or sharp sensations in response to chemical, thermal, or mechanical injury.

Inflammatory pain is an immune-mediated response to injury from infection or tissue trauma. The infiltration of immune cells and inflammatory mediators encourages healing, but the discomfort associated with this infiltration dissuades the person from exposing the tissue to continued injury.

Neuropathic pain and dysfunctional pain (sometimes referenced with the misnomer “functional pain”) are maladaptive pain states that include ongoing pain without an ongoing noxious stimulus. When present, inflammation is usually absent or minimal; although in maladaptive pain, it occurs as a result of altered neural processing, rather than the cause of the pain itself.

What Mechanisms Underlie Each Type of Pain?

Nociception occurs via receptors termed nociceptors. They are free nerve endings that are present through most tissues of the body and respond to noxious stimuli. Mechanical stimuli are carried towards the central nervous system via the faster A∂ fibers, and chemical and thermal stimuli are carried via the slower C fibers. Pain perception can then be modulated by descending pathways that affect the perception of pain by the central nervous system.

Inflammatory pain occurs through an interplay of tissue injury and a cascade of inflammatory mediators to produce the associated redness, swelling, and hyperalgesia. Ions, bradykinins, and other mediators are released from damaged cells. These, along with cytokines, prostaglandins, neurotrophic growth factors, and neurogenic factors, such as the neuropeptides substance P and calcitonin gene-related peptide (CGRP), act as either sensitizing agents that increase the sensation of pain, or act to directly stimulate nociceptors and cause pain spontaneously.

Neuropathic pain generally occurs with direct injury to nerves, either peripherally or centrally. Patients will describe neuropathic pain in a variety of ways that range from dysesthesia (hyperalgesia and allodynia) to paresthesia (tingling, numbness). Itching and burning are commonly described by patients.

Dysfunctional pain encompasses a variety of pain syndromes including fibromyalgia, “functional abdominal pain,” irritable bowel syndrome, headaches, and other syndromes where there is substantial pain without an ongoing noxious stimulus. The term “Amplified Pain Syndrome” is sometimes used to describe this collection of pathologic pain syndromes defined by a predisposition of the body to a heightened pain experience in the absence of a known noxious stimulus.

What Nonopioid Strategies Are Used to Treat the Different Pain Types?

Generally, an appropriate strategy for perioperative pain control includes a multimodal approach that consists of pharmacologic and nonpharmacologic techniques that target various levels of the pain pathway.

Regional and neuraxial anesthesia are safe and effective for the management of postoperative pain in children that targets either the dorsal root ganglia or peripheral nerves, and should be performed whenever possible, particularly for children with chronic pain. This may include caudal/epidural blocks, paravertebral blocks, plexus blocks (brachial, lumbar), or peripheral nerve blocks. Continuous catheters have been demonstrated to be safe, and to improve pain recovery in children, and should be used when children undergo procedures associated with significant and prolonged pain.

Antinociceptive agents include nonsteroidal antiinflammatory medications (NSAIDs), such as ibuprofen and ketorolac, acetaminophen, and glucocorticoids (e.g., dexamethasone) (Figure 55.1). Nonsteroidal antiinflammatory agents prevent the synthesis of prostaglandins via inhibition of cyclooxygenase in the central nervous system and the periphery in addition to their antiplatelet and antiinflammatory effects. Acetaminophen works similarly to NSAIDs, but without the antiplatelet and antiinflammatory effects. Both of these types of medications may have an additive analgesic effect. Dexamethasone has been shown to improve pain control, reduce opiate requirements, and prolong the effect of regional anesthetic techniques.

Figure 55.1 The arachidonic acid pathway.

Illustration by Adam C. Adler, MD

Neuropathic agents include gabapentinoids, such as gabapentin and pregabalin, the voltage-gated sodium channel blocker lidocaine, alpha-2 agonists, such as dexmedetomidine and clonidine, as well as the NMDA-antagonist ketamine.

Gabapentin reduces calcium currents by decreasing spontaneous firing at voltage-gated calcium channels in the central nervous system. While its ability to prevent neuropathic pain is debatable, gabapentin is effective in the treatment of various forms of neuropathic pain. For this reason, it is commonly used as an adjunct in surgeries with a higher likelihood of neurologic injury, such as spinal fusion surgeries, and can be given prophylactically in patients with a neuropathy who present for surgery.

Dexmedetomidine and clonidine act at alpha-2 receptors in the substantia gelatinosa of the dorsal horn of the spine, and work to inhibit the perception of somatic pain via inhibitory pathways. Generally administered systemically as part of a multimodal approach to analgesia, clonidine can be administered as part of a regional or neuraxial technique to strengthen or prolong the analgesia provided. Particularly useful in children is the fact that both clonidine and dexmedetomidine can serve as useful premedication when administered orally or intra-nasally.

Ketamine is a noncompetitive NMDA antagonist that has been shown to prevent hyperalgesia and decrease perioperative pain intensity. This seems to happen through its prevention of sensitization to pain via NMDA antagonism in the central nervous system. It also works to decrease release of glutamate, an excitatory neurotransmitter involved in pain sensation, at nerve terminals.

The evidence for its opiate-sparing effect is mixed, partly due to the heterogeneity of available studies; but it does seem to decrease opiate requirements in patients with chronic pain.

Lidocaine works at the level of neurons to block sodium channels and increase the depolarization threshold. This mechanism underlies its ability to decrease the propagation of pain signals, as well as its antiarrhythmic property to increase the threshold for spontaneous electrical activity and signal propagation within the cardiac conduction tissue. Studies have shown efficacy in the treatment of pain in adults and children. One concern specific to pediatrics is the potential for accumulation of monoethylglycineexylidide (MEGX), a lidocaine metabolite with a longer half-life. MEGX poses the greatest risk to neonates and children with renal dysfunction.

Other agents, such as the tricyclic antidepressants (TCA) and selective serotonin norepinephrine reuptake inhibitors (SNRI) (amitriptyline and duloxetine), as well as mixed-mechanism analgesic tramadol (opiate + SNRI) fit into the category of neuropathic agents.