The Tragedy of Uncontrolled Pain

Acute Pain
Acute pain is usually a consequence of an identifiable insult, such as surgery or other trauma, or a consequence of a disease, e.g., kidney stones, mechanical low back pain, etc. According to the National Center for Health Statistics, 71 million Americans undergo inpatient or outpatient surgery each year. In addition, about 95 million visits are made annually to the ER, according to the National Hospital Ambulatory Care Survey. Of these ER visits, more than 20% require analgesic treatment. Recent studies have shown that more than 60% of patients who undergo surgery experience moderate to severe pain despite analgesic treatment.

The treatment of post-surgical pain has not improved in the U.S. in recent years. In a survey of patients who had surgery, 77% of patients experienced significant post-operative pain. Of these, 80% characterized their pain as moderate or severe. Several factors may contribute to inadequate post-operative pain management, including the shortcomings of current injectable pain medications. Poorly managed pain can lengthen hospital stays and increase the number of re-admissions to hospital. Severe pain can interfere with breathing, digestion, recovery, rehabilitation and discharge.

Chronic Pain
Chronic pain is a major health problem that afflicts a significant number of patients, resulting in personal suffering, reduced productivity and substantial health care costs. According to the Institute of Medicine, musculoskeletal conditions such as low back pain, osteoarthritis and myofascial pain are the leading causes of disability in individuals of working age. In October 2002, the Center for Disease Control (CDC) issued revised estimates of the number of adults with arthritis and chronic joint symptoms at 70 million, a substantial increase over the previous estimate. Total disability expenditures among working adults cost the economy over $200 billion dollars a year and social security disability insurance benefits are far outstripping the increase in the working population insured for disability.

Although treatment for chronic pain is frequently initiated with non-narcotics (such as acetaminophen, ibuprofen, celecoxib and rofecoxib), many patients fail to get adequate pain relief with such agents. Consequently, narcotic (opioid) analgesics are frequently used either alone or in combination with non-narcotics when non-narcotics alone prove to be inadequate. Results from published clinical trials support the safety and efficacy of opioid analgesics in carefully selected patients with chronic pain. Many pain experts familiar with opioid use in chronic pain believe that except in individuals who have a previous history of substance abuse, addiction is not a common observation in patients who take opioids to control chronic pain. This shift in attitudes, while not universally embraced, has fundamentally changed the treatment landscape for patients with chronic pain.

An important goal of analgesic therapy is to achieve continuous relief of chronic pain. Regular administration of an analgesic is generally required to ensure that the next dose is given before the effects of the previous dose have worn off. Continuous suppression of pain through the use of around the clock opioid analgesics is now recommended in chronic pain treatment guidelines. Conventional (so called “immediate-release” or “short acting”) opioid analgesics have been demonstrated to provide short-lived plasma levels, usually requiring dosing every 4-6 hours in chronic pain. Sustained release formulations are the standard of care in chronic pain. A sustained release opioid analgesic may result in fewer interruptions in sleep, reduced dependence on caregivers, improved compliance, enhanced quality of life outcomes, and increased control over the management of their pain. In addition, such a formulation may provide more constant plasma concentrations and clinical effects, less frequent peak to trough fluctuations and fewer side effects, compared with short acting opioids.

Cancer Pain
Pain is one of the most feared consequences of cancer and often adversely affects quality of life. During their illness, approximately 70% of patients with cancer will suffer pain. The occurrence of pain is related to both the extent of the disease and the sites of metastatic involvement, with bony metastases generally being among the most painful. Cancer pain may be caused by direct invasion of bone, nerve, or other organs by the expanding tumor mass. Cancer pain can be separated into nociceptive pain, neuropathic pain, mixed pain and pain of unknown origin. Nociceptive pain is caused by tissue damage created by pressure, infiltration or destruction by an identifiable somatic or visceral lesion. Neuropathic pain is caused by pressure, invasion, or destruction of peripheral or central nervous tissues. In many instances, cancer pain is a combination of nociceptive and neuropathic processes. Despite anti-cancer therapy, most patients will require analgesics. Effective pain management is thus an essential part of the care of patients with cancer pain. Opioid analgesics are the most commonly used drugs for cancer pain. Sustained release formulations are the standard of care, with short acting (“immediate release”) formulations being used for the treatment of any breakthrough pain.

Neuropathic Pain
Neuropathic pain (pain caused by injury to nerves), is a commonly occurring complaint among patients with wide variety of conditions. It may be caused by drugs, radiation therapy, surgery, infection, tumor infiltration of peripheral nerve, and diseases. Neuropathic pain can be unrelenting and is characterized by burning, aching or itching with superimposed lancinating pains. Postherpetic neuralgia and painful HIV-associated neuropathy are examples of neuropathic pain syndromes.

Postherpetic neuralgia (PHN) is a chronic, debilitating neuropathic pain syndrome that occurs as a complication of shingles or herpes zoster infection. The pain of PHN is unrelenting and is often described as burning, stabbing or aching. In addition to persistent pain, patients with PHN experience episodic pain due to abnormal sensations from normal daily activities such as putting on a shirt or contact with a cool gentle breeze.

Painful HIV-associated neuropathy is characterized by steady pain, stabbing pain and mechanical allodynia. Patients experience sensations ranging in intensity from bothersome to excruciating from normal daily activities, such as putting on socks. Painful HIV-associated neuropathy can limit patient’s ability to remain on life saving antiviral regimens. At this time, no drug is approved for painful HIV-associated neuropathy.