Recognizing and Managing Breakthrough Pain in Complex Regional Pain Syndrome
By Howard L. Rosner, MD

Pain is a painful subject for most people; both for patients as well as the physicians and nurses who take care of them. All of us share a common cultural conviction that people who complain about pain are exaggerating their discomfort to gain attention, elicit sympathy, or to gain access to narcotic drugs. People in pain know better; they know that it hurts, but they also don't want to be known as "complainers" or "whiners" to their family, friends and health care providers. Our culture teaches us to "keep a stiff upper lip" and "grin and bear it", keeping our distress quiet and private. Ultimately, this leads to increased disability and depression, promoting dysfunction instead of a reasonably normal life. For those who suffer from CRPS, pain is a daily reality that must be recognized and addressed before a semblance of normalcy can return to life. Because pain cannot be assessed by purely objective criteria, the patient's subjective assessment is essential to accurate diagnosis and effective management.

Social and cultural factors play major roles in the self-assessment of pain, and behavioral patterning, set down in early childhood, can influence the patient's pain experience. While sensation threshold does not differ from culture to culture or among members of different communities, the translation of sensation into pain (or suffering) does differ widely from patient to patient.

Complex regional pain syndrome, or CRPS, is a chronic and progressive neurologic condition which can affect a single extremity or the entire body. It is called a syndrome because it presents as a myriad of symptoms, only some of which are needed for diagnosis, and can involve the skin, muscles, joints, and bones. First described in 1868, CRPS has been known by many names, including Reflex Sympathetic Dystrophy (RSD) and Causalgia. The syndrome usually develops in an injured extremity, and can be due to fractures, sprains, or even simple bumps. The extent of the injury is not a predisposing factor to develop the syndrome. Often it is triggered by a major injury, but in many cases, can be triggered by something innocuous or inconsequential. In some cases, no precipitating event at all can be identified. The primary symptom is pain, which may begin in one area or limb and then spread to other limbs. CRPS is characterized by various degrees of burning pain, excessive sweating, swelling and sensitivity to touch. Symptoms of RSD/CRPS may recede for years and then reappear with a new injury.

Two sub-types of CRPS have been described:

• Type 1 (formerly called RSD) - without major nerve injury
• Type 2 (formerly called causalgia) - with major nerve injury
  Both types express the same signs and symptoms; primary among them is pain.

Although pain is part of almost all diseases, it is the common condition of many people who have CRPS, and although some pain is to be expected, it doesn't have to be overwhelming. Pain in all its forms, sharp or dull, throbbing or steady, constant or intermittent, can be controlled. For that to happen, patients must tell their physician that they are in pain. To get fast, lasting relief from that pain, patients must also have to be able to describe that pain: quality, quantity, duration, factors that improve or worsen the problem, accompanying factors, and special characteristics.

Breakthrough Pain

Many people with CRPS experience intermittent flares of pain that occur even though they are taking pain killers on a fixed shedule. The term for this is "breakthrough pain" because the pain "breaks through" the regular pain medication cycle. Almost all people experiencing chronic pain and who are being treated medically should receive adequate medications for around-the-clock pain control at rest as well as medication specifically indicated for managing breakthrough cycles of pain. More medication than is needed to relieve rest pain may cause overmedication; hence, trying to control episodic or breakthrough pain with an increased dose of the around-the-clock medication can lead to excess sedation and other side effects at rest. On the other hand, a breakthrough occurring just before the next dose of medication is an indication of "end-of-dose" breakthrough. This should be managed by adjusting either the dose or schedule of the medication.

The characteristics of breakthrough pain vary from person to person and episode to episode, including its duration and possible exacerbating factors. Generally, breakthrough pain happens suddenly, often as a result of physical activity, and may last anywhere from seconds to hours. Most people who experience breakthrough pain can have several cycles per day.

Regardless of cause, the objective of pain treatment is three-fold: to reduce discomfort, decrease anxiety, and return the patient to previous levels of function. There are no easy formulas for achieving these objectives. The treatment of pain must always be individualized, because people exhibit a remarkably wide range of pain tolerance and responsiveness to drug therapy. Opiate analgesics are rarely used for mild pain, but they are frequently prescribed for moderate-to-severe pain.

Many people with CRPS suffer chronic pain and it is entirely appropriate to use sustained-release opiate analgesics to reduce this pain. The specific agent chosen is less important than the principle that maintaining a near-constant level of opiate in the blood stream is desirable when patients have deep and enduring pain.

Opiate analgesics are regarded as a mainstay of pain control in CRPS; however, drugs are not the only means of alleviating pain. Patients may also want to consider a number of other approaches to pain management, including hypnosis, biofeedback, electrical nerve stimulation, physical therapy, nerve blocks, and acupuncture. These are often labeled "alternative" therapy, as if one had to choose this treatment or that. The more recent and informed description of these treatment choices is "complementary" medicine, and should be used side-by-side with more conventional therapies.

Cognitive techniques, including relaxation training, hypnosis, guided imagery, and distraction techniques may also help relieve breakthrough pain for many people. Many patients benefit from neuromodulation: modifying pain conduction through the use of electric currents or medications directly administered to the central nervous system.

Many practitioners use the WHO (World Health Organization) pain ladder for guidance in selecting an appropriate medication to treat pain. Unfortunately, this ladder does not take into account neuropathic pain, the primary diagnosis of CRPS-related pain. Neuropathic pain may not completely respond to narcotic analgesics, so providers need to treat this form of pain with what are often termed "adjuvant" medications, which include tricyclic antidepressants, anti-seizure medications, and membrane stabilizers. Most patients, however, will be managed by some combination of adjuvant medications and opiates.

Practitioners should allow adequate time for gastrointestinal absorption of these drugs, a process that can take up to 90 minutes. In the case of many longer-acting opiates, there can be a four-hour lag from ingestion to activity. Therefore, follow-up doses of the scheduled medication should be taken well before drug levels in the blood drop to sub-therapeutic levels. The therapeutic goal of any pain-relief regimen is to achieve an adequate level of drug in the blood stream, a level high enough to assure relief of "background" pain when you are resting. If the patient experiences pain during activity, additional medications should be available to blunt this breakthrough pain. To manage both forms of pain, two forms of medication are needed: a long-acting drug, taken on a fixed schedule to eliminate background pain and a rapid-onset medication, used on an as needed basis for the breakthrough pain.

The ideal treatment for breakthrough pain should be easily administered, work rapidly, be non-toxic, and have a short, controlled duration of action. Traditionally, most treatments for breakthrough pain are opioids (potent painkillers). Getting a sufficient blood level for activity is very important; the route of administration of the medication and its chemical properties directly affects the speed of onset. Medications for breakthrough pain can be administered in many ways: by mouth (PO), by injection in the vein (IV), muscle (IM) or under the skin (SC), under the tongue (SL), by rectal suppository (PR), or absorbed across the mucous membranes of the mouth but not swallowed (oral transmucosal). Most people prefer oral medications, but these are not always the fastest in onset of action. Some patients may not be able to take an oral drug due to difficulty in swallowing, nausea, or other gastrointestinal problems. The newest delivery system in our armamentarium is the oral transmucosal lozenge. This delivery system provides extremely fast onset of action, and the dose delivered can be controlled both by the amount of medication in the lozenge and by the length of time the lozenge remains in the mouth. For breakthrough pain, rapid onset is highly desired. The speed of onset of the oral transmucosal lozenge is, in many cases, comparable to injectable breakthrough medications.

Unlike antibiotics, anti-inflammatories, and other medications, there is no specific dose of an opiate analgesic that should be given to treat pain. The ideal way to use opiates is to titrate them to the desired level of efficacy, on a case-by-case basis. With the important exceptions of meperidine, propoxyphene, and pentazocine, there are no peak doses for opiates. The major limiting factor in increasing opiate doses is the escalation of undesirable side effects (such as constipation, sedation, respiratory suppression, and confusion). When opiates are used for the treatment of pain, it is unlikely that addiction will become a major factor. Controversy exists among health care providers at all levels of expertise (including the pain management community) about maximum doses above which further dosing is inadvisable. For many practitioners, the opiate dose should be pushed to whatever level it takes to make the patient comfortable. For others, the concern over long-term damage to central nervous system receptors and other organ damage will limit the extent to which a dose will be escalated.

Modern medicine is capable of delivering a high degree of pain control to most patients without sacrificing their sense of self and their ability to think and function. In some patients, more invasive techniques may be needed, including spinal stimulators and infusion pumps. However, in the vast majority of cases, carefully considered titration of medications can result in a satisfactory outcome for both patient and doctor. The combination of carefully selected, properly dosed around-the-clock long-acting medication for baseline comfort at rest is ideally paired with an as-needed rapid onset medication for incident or breakthrough pain. This combination suits people's lifestyles; we are neither wholly sedentary nor active 24-hours per day. Pairing these two types of painkillers gives patients the opportunity to live more normal lives, blunting pain while maintaining dignity and comfort.

Howard L. Rosner, MD is Medical Director of The Pain Center at Cedars-Sinai Medical Center in Los Angeles, California.

Updated July 19, 2005