Where Is the Evidence for Breakthrough Pain in Chronic Non-cancer Pain?

Takeaway Points:

• Chronic pain and breakthrough pain share several characteristics, making it difficult to differentiate among them
• There is relatively little knowledge about the prevalence and characteristics of breakthrough pain in patients with chronic non-cancer pain
• There have been few studies of the effectiveness of treatment of breakthrough pain in chronic non-cancer pain

Noting that “treatment of chronic non-cancer pain with opioid therapy has escalated in recent years, resulting in exploding therapeutic use and misuse of prescription opioids and multiple adverse drug events, inappropriate opioid therapy, and escalating costs of adherence monitoring,” the authors of “Breakthrough Pain in Chronic Non-Cancer Pain: Fact, Fiction, or Abuse,” published in the March/April issue of Pain Physician, undertook to evaluate “the available evidence of breakthrough pain in chronic non-cancer pain including its existence, prevalence, and managing symptoms,” to determine whether there is legitimate justification for the increased use of opioids to treat this form of pain.

According to the authors, it is not evidence for the proven efficacy of opioid therapy for chronic non-cancer pain that is driving the enormous increase in the use of these medications, but rather it is “conjecture (breakthrough pain in cancer pain) and personal philosophy of the undertreatment of pain and continuous total pain relief at any cost, multiple organizations promoting opioid use, guidelines, accreditation standards, advocacy efforts, and enormous publicity of pain as a fifth vital sign” that are the cause of this phenomenon.

The authors conducted a comprehensive literature search for clinical trial results published from 1996 to 2010. They also consulted “bibliographies from notable primary and review articles, abstracts from scientific meetings and peer-reviewed non-indexed journals.” They reported that the first obstacle to identifying the evidentiary basis for the use of long-term opioid therapy of breakthrough pain in the treatment of chronic non-cancer pain lies with the shifting definition breakthrough pain, which has been based almost completely on the experience of breakthrough pain as experienced as part of chronic cancer pain. Thus, “the literature for breakthrough pain in non-cancer pain, including its terminology, prevalence, relevance, characteristics, and treatment, has been scant.” Because many proposed definitions for chronic pain, chronic pain syndrome, and breakthrough pain share several characteristics, making it difficult to differentiate among them, “the definition of breakthrough pain varies based on the reviewers, their concepts, and requirements.”

Although several characteristics and definitions of cancer pain are still contested by various groups within the oncology community, there is widespread agreement on the parameters of cancer pain. However, “there is no unanimous agreement upon the assessment of breakthrough pain in cancer patients.” Likewise, the authors note that “there is no definition which is even accepted by some groups or arrived at by a consensus by a group of unbiased specialists for breakthrough pain in non-cancer pain.” The authors also identify several knowledge gaps in the prevalence of breakthrough pain (“very little is known about the prevalence and characteristics of breakthrough pain in the population with chronic non-cancer pain. An inherent issue regarding breakthrough pain is the subjective nature of chronic pain, and also the desire of patients to obtain 100% pain relief”), the impact of breakthrough pain on function and quality of life, assessment, and treatment and management.

The treatment of breakthrough pain in chronic non-cancer pain may be especially problematic. The authors claim that “the majority of attraction for the unlimited use of opioids with long-acting and short-acting combinations with emergence of breakthrough pain has been due in some measure to the campaign about the alleged undertreatment of pain even though the information has been very sparse and derived from mostly cancer pain and postoperative pain.” Indeed, according to the authors “there has not been any significant literature studying the effectiveness of treatment of breakthrough pain in chronic non-cancer pain.” This is concerning, given the known risks associated with opioid use, including “increased disability, medical costs, subsequent surgery, and continued or late opioid use in chronic pain.”

The authors concluded that “there is no significant evidence of any type of breakthrough pain in chronic non-cancer pain based on available literature, methodology utilized, and response to opioids in chronic non-cancer pain.” Despite the “escalating use and abuse of therapeutic opioids,” the scientific evidence for the effectiveness of opioids for chronic non-cancer pain remains unclear. Claiming breakthrough pain in chronic non-cancer pain to be “a hypothesis without any significant evidence” that can lead to “excessive use and abuse of opioids,” the authors recommend that patients should be “evaluated when they request medication for breakthrough pain or episodic pain and educated along with the application of principles of appropriate pain management therapy with repeat evaluations with investigations of all the causes and application of other modalities including functional interventional techniques and behavioral management.”