Pruritus—The opiates, such as morphine and codeine, produce flushing and warming of the skin accompanied sometimes by sweating, urticaria, and itching. Although peripheral histamine release is an important contributor, all opioids can cause pruritus via a central (spinal cord and medullary) action on pruritoceptive neural circuits. When opioids are administered to the neuraxis by the spinal or epidural route, their usefulness may be limited by intense pruritus over the lips and torso. The incidence of opioid-induced pruritus via the neuraxial route is high, estimated at 70–100%. However, the κ agonist/partial μ antagonist nalbuphine and the selective κ agonist nalfurafine have been proven effective and have been approved for the management of itch in some countries.
h.
Immune—The opioids modulate the immune system by effects on lymphocyte proliferation, antibody production, angioneogenesis, and chemotaxis. In addition, leukocytes migrate to the site of tissue injury and release opioid peptides, which in turn help counter inflammatory pain. However, natural killer cell cytolytic activity and lymphocyte proliferative responses to mitogens are usually inhibited by opioids, which may play a role in tumor progression. Although the mechanisms involved are complex, activation of central opioid receptors could mediate a significant component of the changes observed in peripheral immune function. These effects are mediated by the sympathetic nervous system in the case of acute administration and by the hypothalamic-pituitary-adrenal system in the case of prolonged administration of opioids.
Successful management of pain is a challenging task that begins with assessment of and an attempt to understand the source and magnitude of the pain. Pain is an unpleasant sensory and emotional experience with many layers of complexity.
The amount of pain experienced by the patient is often measured by means of a pain numeric rating scale (NRS) or less frequently by marking a line on a 100-mm visual analog scale (VAS, which is more commonly used in research), as well as the verbal rating scale (VRS) with word descriptors ranging from no pain to excruciating pain. In each case, values indicate the magnitude of pain as mild (1–3), moderate (4–6), or severe (7–10). A similar scale can be used with children (Face, Legs, Activity, Cry, Consolability [FLACC] or Wong-Baker scales) and with patients who cannot speak; the Wong-Baker scale depicts five faces ranging from smiling (no pain) to crying (maximum pain). The Brief Pain Inventory is a series of questions regarding the severity of pain. Functional scales include the Oswestry Disability Index or the World Health Organization Disability Assessment Scale 2.0. There are specialized scales for patients with specific conditions including rheumatoid arthritis and dementia. More comprehensive questionnaires such as the McGill Pain Questionnaire address the multiple facets of pain including both the affective and sensory experience.
For a patient in severe pain, administration of an opioid analgesic is usually considered a primary part of the overall management plan. Determining the route of administration (oral, parenteral, neuraxial), duration of drug action, ceiling effect (maximal intrinsic activity), duration of therapy, potential for adverse effects, and the patient’s past experience with opioids, including their genetics, social history, and family history, all should be addressed. One of the principal errors made by physicians in this setting is failure to match the severity of a patient’s pain to his or her analgesic. Just as important is the principle that following delivery of the therapeutic plan, its effectiveness must be monitored and reevaluated and the plan modified if necessary.
Use of opioid drugs in acute situations should be contrasted with their use in chronic pain management, in which a multitude of other factors must be considered, including the development of tolerance, dependence, and the rarer cases of diversion or misuse.
Clinical Use of Opioid Analgesics
A. Analgesia