Chronic pain is typically classified as nociceptive (visceral or somatic) or neuropathic, depending on the underlying pathophysiology suggested by the pain. Nociceptive pain involves ongoing activation of pain-sensitive neurons by stimulation of specialized nociceptors from tissue irritation or injury. The visceral/somatic distinction depends on the structures involved. Visceral nociceptive pain stems from injury to the viscera or related structures. It may present as the localized ache of organ capsule damage or the poorly localized cramping of obstructed hollow viscera. Somatic nociceptive pain is related to ongoing damage in somatic tissues, such as the bones, joints, and muscles. It is usually described as throbbing, aching, stabbing, or pressure. Somatic pain syndromes are generally perceived to be highly responsive to opioid therapy.
Neuropathic pain is related to abnormal somatosensory processes that directly affect the peripheral or central nervous system. These processes either stimulate the pain system or damage nonnociceptive pathways to shift the balance between painful and nonpainful inputs to the central nervous system. Neuropathic pain does not require specific peripheral pain receptor stimulation, although it can be made worse by such stimulation.
Some types of neuropathic injury can produce aching, stabbing, or throbbing pain, but these syndromes often have an unfamiliar quality or sensory distortion. Burning, shooting, and tingling are suggestive of nerve involvement, but not sufficient for the diagnosis. Areas of abnormal sensations are often found on examination, including hypesthesia (a numbness or lessening of feeling), paresthesias (spontaneous abnormal nonpainful sensations such as tingling), dysesthesias (spontaneous abnormal painful sensations such as burning, tingling, or electrical sensations), hyperalgesia (increased perception of painful stimuli), hyperpathia (exaggerated pain response), and allodynia (pain induced by nonpainful stimuli).
Pain can be constant, paroxysmal, or a combination of both. Evidence of neural damage on examination or on electrophysiologic study supports the diagnosis but is not required, because damage to the nervous system can be quite focal and not easily detected.
Cancer can cause neuropathic pain by direct invasion, irritation, or external pressure on peripheral neural structures. In addition, antineoplastic therapies, such as surgery, chemotherapy, and radiation, can damage peripheral nerves and lead to neuropathic pain. In most cases, however, nerve injury occurs in tandem with damage to other structures, and the pain has a mixed pathophysiology, with both somatic and neuropathic components. Given this complexity, all patients must undergo a careful assessment that characterizes the pain, identifies potential etiologies, and clarifies the specific pain syndrome. This assessment then guides the selection of analgesic therapies from among a large number of alternatives.
Opioids are the mainstay of the treatment of moderate-to-severe cancer pain, including cancer-related neuropathic pain. In most cases, opioid therapy should be maximized before alternative strategies for neuropathic pain therapy are instituted.
If the first opioid selected yields intolerable side effects without satisfactory analgesia, trials of an alternative opioid (opioid rotation) are often considered. Pain that is poorly responsive to an opioid might also be addressed through trials of alternative systemic therapy (adjuvant analgesics), anesthesiologic and neurosurgical techniques, physical therapy and other physiatric modalities, or psychological interventions.
Adjuvant analgesics are drugs that often have been developed for primary indications other than pain but produce analgesic effects in specific circumstances. Although they are usually classified according to their primary roles, many potentially have powerful effects as neuroactive analgesic medications.
General Principles of Adjuvant Analgesic UseTo appropriately administer adjuvant analgesics, the clinician should become familiar with the approved indications, unapproved but accepted indications, probable mild side effects, potentially serious adverse effects, and specific dosing guidelines for pain management. Knowledge of the pharmacokinetics and usual time-to-effect relationship of specific medications is also useful. Because few adjuvant analgesics have been studied in the medically ill, the information used to develop dosing guidelines for cancer pain is usually extrapolated from other patient populations.
The large variability in mode of action and individual response to most adjuvant analgesics, including those in the same class, supports the utility of sequential trials to identify the most useful drug. In the absence of controlled trials, drug selection usually reflects the clinician’s best judgment about the risks associated with the therapy, the likelihood of analgesia, and the possibility of secondary beneficial effects on symptoms other than pain.
Important principles that help ensure an adequate trial of an adjuvant medication include the following:
- Choose each medication carefully for both intended effect and side effects. Antidepressant analgesics are appropriate for patients with pain complicated by depressed mood. The sedative side effects of some medications may help patients who have trouble sleeping.
- Ensure that patients have realistic expectations, especially concerning the slow onset of effect, the need for long-term use, the probable development of side effects, and the possibility of tolerance to effects over time.
- Begin the use of drugs with known bothersome side effects at a low dose and increase the dose slowly to allow patients to become tolerant to side effects. Doses of drugs with fewer side effects can be increased more rapidly or started at a therapeutic level.
- Increase the dose of each medication until the desired effect is achieved, side effects become unmanageable, or high therapeutic drug levels are obtained before calling the trial a failure.
- Different classes of drugs can be used concomitantly. To achieve the maximum level of symptom control, the concomitant use of drugs from several classes is frequently necessary.
- Be persistent, encouraging, and supportive as treatments are implemented.