Cancer Pain Management in the 21st Century

Cancer Pain Management in the 21st Century

Cancer causes pain as it invades bone, compresses nerves, produces obstructive symptoms in the pulmonary, gastrointestinal, and genitourinary systems, and distends involved visceral organs. This manuscript reviews progress in cancer pain management during the past 2 decades. Since the 1980s, we have seen (1) genuine advances in research on the biology of pain, (2) new approaches to the treatment of cancer pain, and (3) important changes in the health-care system to ensure that pain is appropriately assessed and managed. Currently, clinicians have the appropriate diagnostic and therapeutic tools to ensure that the vast majority of patients with cancer pain can be comfortable during their illness. Nevertheless, too many patients with terminal malignancies continue to die in pain in nations around the globe. An effective strategy to make alleviating pain a major health-care priority remains the primary challenge to effectively palliating patients with cancer pain.

Cancer has long been known to be painful as it invades bone, compresses nerves, produces obstructive symptoms in the pulmonary, gastrointestinal, and genitourinary systems, and distends involved visceral organs. Currently, the vast majority of patients with advanced systemic cancers are unable to be cured. However, health-care providers can reassure patients that their pain can be well controlled during the course of their illness. This article reviews progress in cancer pain management during the past 2 decades. Advances have come in three general areas: (1) improved understanding of the biology of pain, (2) novel therapeutic approaches, and (3) changes in the health-care system designed to ensure that pain is appropriately managed.

Cancer Pain Management Circa 1986

Two decades ago, basic information on the biology of pain was changing rapidly. The original theory proposed by Rene Descartes in 1664 described pain as a reflex that traveled through a single channel to the brain. This was challenged by the gate-control theory postulated by Melzack and Wall in 1965.[1] This novel framework conceived of pain as a dynamic and interlocking series of biologic mechanisms, prompting research on central sensitization and central nervous system plasticity.[2] Opioid receptors were discovered in the late 1970s, suggesting that endogenous opioids existed and that these acted centrally in the nervous system. Further studies described activation and sensitization of nociceptors and mechanoreceptors, effects of endogenous agents (epinephrine, serotonin, bradykinin, and prostaglandins), deafferentation pain states, and alterations in the autonomic nervous system with sensitization of perivascular receptors.

Advances in Drug Therapy

In the 1980s, the available opioid agonists included morphine, meperidine, methadone, levorphanol, oxycodone, heroin, hydromorphone, oxymorphone, and codeine as well as the mixed agonist-antagonists pentazocine, nalbuphine, butorphanol, and buprenorphine. Adjuvant agents, such as phenytoin, carbamazepine, and tricyclic antidepressants for neuropathic pain, corticosteroids for epidural cord compressions, nonsteroidal anti-inflammatory agents, and cocaine (Brompton's cocktail) were prescribed for severe pain.

In addition, novel methods of drug administration were being studied. These included continuous intravenous and subcutaneous infusions of opioids as well as continuous epidural and intrathecal morphine infusions, which placed opioids adjacent to the recently described opioid receptors. In addition, anesthetic approaches (trigger point injections, blocks of peripheral and autonomic nerves), epidural and intrathecal local anesthetics, neurolytic blocks, and neurosurgical approaches (dorsal rhizotomy, dorsal root entry zone lesions, cordotomy of midline myelotomy, and placement of neurostimulators) had been described. Also, computed tomographic (CT) scans became available, allowing clinicians to better visualize lesions causing pain.[2,3]

Need for Education and Drug Access

Despite the expanding scientific base, more accurate diagnostic tools, and a broad range of available therapeutic approaches, however, a high percentage of patients with cancer in the 1980s were dying with severe pain. Medical students and house staff were not trained in the evaluation of treatment of cancer pain, and there were no institutional guidelines to ensure that pain was appropriately assessed or treated. In developing nations, these problems were compounded by a lack of opioid availability.

In 1986, the World Health Organization (WHO) published a monograph titled Cancer Pain Relief in an attempt to promote education and opioid availability. The principles of cancer pain management were simplified using the "three-step analgesic ladder" (Figure 1).[4] This suggested that physicians begin therapy with aspirin or acetaminophen and then escalate to codeine and, if necessary, to morphine. Other key concepts in this monograph included using oral medications whenever possible, dosing around the clock rather than waiting for severe pain, and making modifications to each patient's regimen to maximize relief.

Although innovative at its inception, the three-step analgesic ladder has subsequently been criticized as being too simplistic and not including interventional modalities to cancer pain management. At the time, however, it fulfilled the global need to promote an uncomplicated therapeutic approach and to emphasize the use of an individual patient's pain rating to adjust medications. The WHO also maintained that all cancer programs should provide pain and palliative care services.


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