2. Spinal modulation that results in augmentation of pain pathways is a consequence of neuronal plasticity. The phenomenon of “wind-up” is an example of central plasticity that results from repetitive C-fiber stimulation of wide-dynamic range (WDR) neurons in the dorsal horn.

B. A multimodal approach to pain therapy should target all four elements of the pain processing pathway.

FIGURE 56-2. Efferent pathways involved in nociceptive regulation.

IV. CHEMICAL MEDIATORS OF TRANSDUCTION AND TRANSMISSION (Table 56-2 and Fig. 56-5)

A. Pain receptors include the NMDA (N-methyl-d-aspartate), AMPA (α-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid), kainite, and metabotropic receptors (Fig. 56-6).

B. Repetitive C-fiber stimulation of WDR neurons in the dorsal horn at intervals of 0.5 to 1.0 Hz may precipitate the occurrence of “wind-up” and central sensitization and secondary hyperalgesia (Fig. 56-7).

V. THE SURGICAL STRESS RESPONSE. Although similar, postoperative pain and the surgical stress response are not the same. Surgical stress causes release of cytokines and precipitates adverse neuroendocrine and sympathoadrenal responses (increased secretion of the catabolic hormones [cortisol, glucagon, growth hormone, and catecholamines] and decreased secretion of the anabolic hormones [insulin and testosterone]) (Table 56-3).

TABLE 56-1 PRIMARY AFFERENT NERVES

FIGURE 56-3. Pain sensitization.

FIGURE 56-4. The four elements of pain processing are transduction, transmission, modulation and perception. CCK = cholecystokinin; 5HT = 5-hydroxytryptamine (serotonin); NE = norepinephrine; NMDA = N-methyl-d-aspartate; NO = nitric oxide; NSAID = nonsteroidal anti-inflammatory drug.

VI. PREEMPTIVE ANALGESIA. The goal of preemptive analgesia is to prevent NMDA receptor activation in the dorsal horn, which causes “wind-up,” facilitation, central sensitization expansion of receptive fields, and long-term potentiation, all of which may lead to a chronic pain state.

VII. STRATEGIES FOR ACUTE PAIN MANAGEMENT. The majority of postoperative pain is nociceptive in character. Evidence suggests that women experience more pain after surgery than men and therefore require more morphine to achieve a similar level of pain relief.

VIII. ASSESSMENT OF ACUTE PAIN (Fig. 56-8). Common features of pain are usually reviewed during the assessment for acute pain (Table 56-4).

TABLE 56-2 ALGOGENIC SUBSTANCES

TNF = tissue necrosis factor.

IX. OPIOID ANALGESICS. Opioid analgesics are the mainstay for the treatment of acute postoperative pain, and morphine is the “gold standard” (Table 56-5).

A. Hydromorphone is a semisynthetic opioid that has four to six times the potency of morphine, making it the ideal drug for long-term subcutaneous administration in opioid-tolerant patients.

B. Fentanyl is available for intravenous (IV), subcutaneous, transdermal, transmucosal, and neuraxial administration.

FIGURE 56-5. Schematic of the neurochemistry of somatosensory processing at peripheral sensory nervy endings.

FIGURE 56-6. Schematic representation of peripheral and spinal mechanism involved in neuroplasticity. AAMPA = α-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid; NK = neurokinin; NMDA = N-methyl-d-aspartate.

FIGURE 56-7. Primary nociceptive transmission in the spinal cord. NMDA (N-methyl-d-aspartate) antagonists have an antihyperalgesic rather than an analgesic effect in the spinal cord. AMPA = α-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid; CGRP = calcitonin gene-related peptide; NK = neurokinin; NMDA = N-methyl-d-aspartate.

TABLE 56-3 CONSEQUENCES OF POORLY MANAGED ACUTE PAIN

FIGURE 56-8. Linear visual analogue scale and FACES pain assessment tool.

TABLE 56-4 FEATURES OF PAIN COMMONLY ADDRESSED DURING ASSESSMENT

Onset of pain

Temporal pattern of pain

Site of pain

Radiation of pain

Intensity (severity) of pain

Exacerbating features (what makes the pain start or get worse?)

Relieving factors (what prevents the pain or makes it better?)

Response to analgesics (including attitudes and concerns about opioids)

Response to other interventions

Associated physical symptoms

Associated psychological symptoms

Interference with activities of daily living

TABLE 56-5 OPIOID EQUIANALGESIC DOSING

C. Sufentanil. The high intrinsic potency of sufentanil makes it an excellent choice for epidural analgesia in opioid-dependent patients.

D. Methadone is well absorbed from the gastrointestinal (GI) tract. With repetitive dosing, methadone can accumulate. Opioid rotation is a useful technique to restore analgesic sensitivity in highly tolerant patients, and methadone is a common choice for opioid rotation.

X. NONOPIOID ANALGESIC ADJUNCTS (Table 56-6). Nonsteroidal anti-inflammatory drugs (NSAIDs) have been proven effective in the treatment of postoperative pain. In addition, they are opioid sparing and can significantly decrease the incidence of opioid-related side effects such as postoperative nausea and vomiting and sedation. Platelet dysfunction, GI ulceration, and an increased risk of nephrotoxicity are several reasons why the nonselective NSAIDs may be avoided in the perioperative period.

A. NMDA receptor antagonists (ketamine, dextromethorphan) may be analgesic adjuncts.

B. α₂-Adrenergic agonists (clonidine, dexmedetomidine) may be administered perioperatively to provide analgesia, sedation, and anxiolysis.

C. Gabapentin and pregabalin are effective analgesics not only for the treatment of neuropathic pain syndromes but also for the treatment of postoperative pain. When these drugs are combined with an NSAID, the combination has been shown to be synergistic in attenuating the hyperalgesia associated with peripheral inflammation.

TABLE 56-6 ADULT DOSING GUIDELINES FOR NONOPIOID ANALGESICS

COX = cyclooxygenase; IV = intravenous; PO = by mouth.

TABLE 56-7 USUAL INTRAVENOUS OPIOID PATIENT-CONTROLLED ANALGESIA REGIMENS FOR OPIOID-NAÏVE ADULT PATIENT

D. Lidocaine has been shown to be analgesic, antihyperalgesic, and anti-inflammatory after IV administration.

E. Glucocorticoids possess analgesic, anti-inflammatory, and antiemetic effects.

XI. METHODS OF ANALGESIA

A. Patient-controlled analgesia (PCA) is any technique of pain management that allows patients to administer their own analgesia on demand.

1. The five variables associated with all modes of PCA include bolus dose, incremental (demand) dose, lockout interval, background infusion rate, and 1- and 4-hour limits (Table 56-7).

2. Risk Factors for Use of Opioid Patient-controlled Analgesia (Table 56-8)

TABLE 56-8 RELATIVE RISK FACTORS ASSOCIATED WITH PATIENT-CONTROLLED ANALGESIA

Pulmonary disease

Obstructive sleep apnea

Renal or hepatic dysfunction

Congestive heart failure

Closed head injury

Altered mental status

Lactating mothers

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