The Tragedy of Uncontrolled Chronic Pain

Acute pain is a predictable response to an insult associated with surgery, trauma, or acute illness. It usually decreases over a period of over a period of few minutes, hours, days or weeks. In contrast, chronic pain is pain associated with a chronic medical condition or extending beyond the period of tissue injury and normal healing. Chronic pain is variously defined as pain lasting more than a month, more than three months or more than six months. Chronic pain may be due to cancer (usually referred to as cancer pain), injury to nerves (usually referred to as neuropathic pain) or conditions other than cancer or neuropathy (usually referred to as chronic non-cancer pain, chronic nonmalignant pain, or simply chronic pain).

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. Painful musculoskeletal conditions such as low back pain, osteoarthritis and myofascial pain affect over 50 million Americans and it is the leading causes of disability in individuals of working age. 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 and celecoxib), 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, painful diabetic neuropathy and painful HIV-neuropathy are examples of neuropathic pain syndromes.

With few available treatment options, neuropathic pain represents an area of significant unmet medical need. Many patients have suboptimal relief with monotherapy and treatment is frequently multimodal, involving use of two or more drugs from different pharmacologic classes.

Postherpetic neuralgia (PHN) is a chronic, debilitating neuropathic pain syndrome that occurs as a complication of shingles or herpes zoster infection. In some patients with shingles, the pain persists after the healing of the acute lesions and a chronic pain state develops. 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. Only four drugs are approved to treat PHN (Lyrica®, Cymbalta®, Lidoderm® and Qutenza®) and seldom is pain relief complete.

Diabetes affects approximately 20 million individuals in the United States and about one-fifth of them suffer from painful diabetic neuropathy, which is a distal, symmetrical neuropathy usually involving the feet and legs initially and later the hands. A limited number of treatment options are available for the treatment of painful diabetic neuropathy and only two drugs Lyrica® and Cymbalta® have been approved by the FDA for the treatment of this condition.

HIV infection and HIV medications are both associated with the development of neuropathy which usually manifests as distal, symmetrical, predominantly sensory, polyneuropathy. Painful HIV-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 and walking. Painful HIV-neuropathy is also a toxicity of antiretroviral therapy and as such it limits patients’ ability to remain on antiviral regimens containing these life saving compounds. It has been documented that painful HIV-neuropathy can lead to patient refusal to take anti-retroviral therapy, with potentially life threatening consequences. At this time, no drug is approved for painful HIV neuropathy in the United States.