Pain

“Although the world is full of suffering, it is full also of the overcoming of it.” -Helen Keller

INTRODUCTION TO PAIN

Humans have always known and sought relief from pain. The act of relieving pain is probably as old as the medical profession itself. Today, pain’s impact on society is still great, and indeed, it is a primary reason patients seek medical attention.

The management of pain is not only important from a patient perspective but also from an economic perspective. Fifty million Americans are partially or totally disabled because of pain. With this staggering number, it isn’t all that shocking that the annual cost of pain to American society has been estimated to be in the billions of dollars. These numbers are only expected to grow as Americans work beyond 60 years of age and live well into their 80s.

It is truly unfortunate that pain often remains undertreated and continues to be a major problem in the community. In fact, in the Michigan pain study, 70% of chronic pain patients claimed to have pain despite treatment, with 22% believing that treatment worsened their pain.

TYPES OF PAIN

While an acceptable definition of pain remains an enigma, the current definition of pain has been described by The International Association for the Study of Pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage.” Because pain is so subjective, however, and can be described in so many ways, many healthcare providers define pain simply as whatever the patient says it is.

There are several ways to classify pain. One way is to distinguish it in regards to its onset and duration. Acute pain occurs suddenly and lasts for only a few hours to days. Once the underlying cause is addressed, acute pain typically subsides. In some instances, pain persists for months to years, leading to a chronic pain state. Chronic pain is usually associated with a long-term illness, such as arthritis, or it can even be one of the defining characteristics of the disease, such as with fibromyalgia.

While both acute and chronic pain can be debilitating, patients in chronic pain tend to be more susceptible to both physiological (poor posture) and psychological (depression and anxiety) consequences, which in turn can amplify the pain. In addition, chronic pain patients may be subject to dependence and tolerance to analgesics, insomnia or irregular sleep and intensified pain response from reactions to environmental changes.

Pain can be further classified by the kind of damage that causes it. The two main categories are nociceptive pain, or pain caused by tissue damage, and neuropathic pain, or pain caused by nerve damage. The most common type of pain is nociceptive pain, which can be further classified as either somatic or pain arising from injury to skin, bone, joint, muscle, or connective tissue or visceral, which is pain arising from internal organs. A third category is psychogenic pain, which is pain affected by psychological factors. This type of pain, while it most often has a physical origin, is increased by such factors as fear, depression, stress or anxiety.

NEUROPATHIC PAIN

Pain originating from nerve damage or simply neuropathic pain is distinctly different from nociceptive pain. It is pain sustained by abnormal processing of nerve transmissions. Nerves basically function like electrical cables transmitting signals, in this case pain signals, to and from the brain. When these nerves are damaged by diseases, such as diabetes, or trauma, it can interfere with the way these signals are transmitted, causing abnormal pain signals.

Some examples of neuropathic pain include:

-Complex Regional Pain Syndrome (CRPS): Complex Regional Pain Syndrome, once also known as Reflex Sympathetic Dystrophy (RSD), is a form of chronic neurological pain that most often affects a limb, such as an arm or leg. It usually develops after an injury, surgery, stroke or heart attack. This syndrome is often characterized by severe burning pain, pathological changes in the bone and skin, excessive sweating, tissue swelling and extreme sensitivity to touch. The most common characteristic of CRPS is the pain is out of proportion to the severity of the initial injury, if any. Occasionally, this pain syndrome may spread from its originating source to elsewhere in the body; for example, if the right arm is initially affected, the pain may spread into the left arm for no apparent reason.

Complex Regional Pain Syndrome can be further divided into CRPS Type I, which is also referred to as RSD, and CRPS Type II, which is also referred to as causalgia. While CRPS Type I cannot be identified according to a specific nerve injury, CRPS Type II has a distinct and major injury to a nerve.

-Diabetic Neuropathy: Diabetic neuropathy is characterized by nerve damage in the body secondary to noncontrolled high blood sugar levels from diabetes. About 80% of people with diabetes will eventually develop some type of nerve damage. Peripheral neuropathy is the most common complication seen in Type II diabetic patients. Predominant symptoms may include tingling, burning, prickling, numbness or pain. The feet tend to be affected far more often than the hands.

-Shingles/Postherpetic Neuralgia: Shingles (herpes zoster) is an outbreak of rash and/or blisters on the skin that is caused by the same virus responsible for causing chickenpox, the varicella-zoster virus. The first sign of shingles is often burning or tingling pain often located along a band, called a dermatome, spanning one side of the trunk around the waistline. The painful after effects of shingles, known as postherpetic neuralgia, can be described as a deep aching, burning, stabbing or an electrical shock-like feeling.

-Trigeminal Neuralgia: Trigeminal neuralgia is a nerve disorder characterized by a stabbing or electric shock-like pain in parts of the face. The trigeminal nerve carries signals from the face, eyes, sinuses and mouth to the brain in response to feelings of touch and pain. While trigeminal neuralgia often does not have a direct cause, in some cases it can be accredited to aging, multiple sclerosis or a tumor compressing the trigeminal nerve. Symptoms of this disorder include shooting or jabbing pain that may feel like an electrical shock with bouts of pain lasting for only a few seconds or episodes of several attacks lasting days, weeks, months or even longer.

ADDICTION AND OPIOID ABUSE HAVE INCREASED IN FREQUENCY OVER THE PAST 20 YEARS.

Addiction is far more than a craving. Addiction is frequently characterized by the presence of potentially maladaptive, drug-seeking behaviors. It also means there are troubling consequences that can often disrupt someone's personal life or job. Addiction means the individual has lost control over the use of the drug. Physical dependence and tolerance are not the same as addiction. Often times, however, these terms are used incorrectly to define the term addiction. Physical dependence is a normal physiologic consequence of chronic use of many psychotropic medications, or medications that have an altering effect on perception, emotion or behavior. It is defined as the development of unpleasant withdrawal symptoms if a person abruptly stops taking a drug. Likewise, tolerance is not indicative of addiction and can be defined as a normal physiologic response in which the body has become used to the drug and now the drug has less of an effect at a given dose. Both physical dependence and tolerance are normal and predictable physiologic events that commonly occur in people chronically using opioids, such as hydrocodone, oxycodone and morphine. Adding to the already difficult task of determining the presence of active addiction is a phenomenon called pseudoaddiction, which may mimic active addiction. This behavior occurs when a patient’s pain is not adequately controlled, and out of fear of not receiving adequate pain medication, the patient begins hoarding medication or asking for amounts that may seem out of proportion to their pain.

The goal of any physician practicing chronic pain management is to provide patients with reasonable pain relief while also maintaining their maximum level of function. Successful pain management, especially in the recovering addict, presents primary care physicians with unique challenges. Some of these challenges that physicians face include distinguishing between seeking pain relief and seeking drugs for the euphoric effects and identifying predictable effects of pain management, such as tolerance and physiologic dependence, that can easily be misinterpreted as drug seeking or relapse behavior.

Regardless of substance abuse history, there are several basic principles in pain management. The first and most important principle is to provide effective pain management, and there are several strategies available in accomplishing this. First, medications should be chosen based on their ability to successfully provide pain relief. There are multiple medications as well as different delivery routes that add to a physician’s arsenal. In addition to choosing the appropriate medications, a second strategy is to provide pain relief around the clock. This type of dosing approach allows for better suppression of pain and therefore will provide better comfort for patients.

Due to fear of legal repercussions for possibly overprescribing narcotics, there are many physicians who have developed “opiophobia,” or a fear of prescribing opioids in adequate amounts to relieve pain. Regardless, opioids are not the only option for providing pain relief. For example, when musculoskeletal or bone pain is present, first-line therapy consists of nonsteroidal anti-inflammatory drugs (NSAIDs) or corticosteroids. As for neuropathic pain, the first line treatment recommendation for continuous burning, electrical or other abnormal sensations, is tricyclic antidepressants, such as amitriptyline. For neuropathic pain characterized as sharp, stabbing, shooting, knifelike pain that often has a sudden onset, first line treatment includes the use of anticonvulsants, such as gabapentin. As stated previously, it is also vitally important to keep in mind that there are alternative delivery routes that can be utilized for the adequate relief of pain.

COMPOUNDING: A BRIEF HISTORY

Pharmacy compounding is the art and science of preparing personalized medications for patients. Compounded medications are “made from scratch” – individual ingredients are mixed together in the exact strength and dosage form required by the patient. This method allows the compounding pharmacist to work with the patient and the prescriber to customize a medication to meet the patient’s specific needs.

At one time, nearly all prescriptions were compounded. With the advent of mass drug manufacturing in the 1950s and 1960s, compounding rapidly declined. The pharmacist’s role as a preparer of medications quickly changed to that of a dispenser of manufactured dosage forms, and most pharmacists no longer were trained to compound medications. However, the “one-size-fits-all” nature of many mass-produced medications meant that some patients’ needs were not being met.

COMPOUNDING: INDIVIDUALIZING & OPTIMIZING MEDICATIONS FOR PAIN RELIEF

There is perhaps no other specialty that appreciates the problem-solving abilities of compounding more than that of pain management. By the time many chronic pain patients are seen by a pain management physician, they are unable to work due to excruciating pain, are depressed from being in constant pain and are treated like addicts by those who are unfamiliar with chronic pain conditions and its treatment. Often times, the pain management specialist is the chronic pain patient’s last hope for pain relief. By this time, they have tried multiple medications offering little relief. This is when the pain management physician must think outside of the box. Some of the problems chronic pain patients run into during treatment include acetaminophen toxicity caused by combination analgesics, frequent dosing intervals and unbearable side effects.

One problem physicians face when treating chronic pain patients is acetaminophen toxicity caused by combination analgesics. Long term use of acetaminophen at doses as low as three grams per day has been shown to cause liver damage. With this being said, consider the chronic pain patient who requires 120 mg of hydrocodone to achieve optimum pain relief. In order for the patient to receive 120 mg of hydrocodone, he would also have to ingest four grams of acetaminophen, well over the dose known to cause liver damage. It would be very upsetting for a patient who has tried multiple medications and finally found a medication that relieves pain and allows for normal daily functioning to have to switch medications because of acetaminophen toxicity. This is one example where compounding can offer a solution; an acetaminophen-free hydrocodone capsule can be prepared to offer the patient the same pain relief without the harmful liver effects.

Another problem faced by both pain management specialists and chronic pain patients is frequent dosing intervals. Because many manufactured drugs only come in a few select strengths, such as hydromorphone tablets in 2 mg, 4 mg and 8 mg strengths, a patient may have to take multiple tablets to achieve optimum pain control. In addition to this, hydromorphone is a relatively short-acting drug, requiring the patient to have to take the medication several times throughout the day, as well as disrupting sleep to take the medication. Compounding can offer a solution to this problem as well. A hydromorphone capsule can be prepared at the strength required by the patient in a sustained release formulation; this would eliminate the need to take multiple tablets to achieve optimum pain relief and less frequent dosing intervals. Overall, the patient’s compliance and quality of life are improved.

Because multiple classes of medications are often used to treat most chronic pain conditions, the likelihood of drug interactions and side effects is inevitable. For example, some patients are extremely sensitive to the gastrointestinal side effects associated with the use of oral nonsteroidal anti-inflammatory drugs (NSAIDs). This is no reason for a chronic pain patient not to reap the benefits this class of drugs has to offer. By preparing a topical cream/gel, medications are delivered through the skin and directly to the site of pain, bypassing the gastrointestinal tract; this type of drug delivery eliminates most side effects. Topical pain relief formulations offer numerous advantages to conventional oral medications; not only can multiple medications in varying combinations be combined into one convenient cream/gel, but the occurrence of side effects and drug interactions is decreased, if not completely eliminated.

TOPICAL PAIN RELIEF COMPOUNDS: TARGETED TREATMENT – RAPID RECOVERY

Because patients vary in size, symptoms and pain tolerance, commercially available medications often do not provide appropriate dosage strength for the adequate relief of pain. Through compounding, however, a physician and pharmacist can customize a pain relief formula to meet the patient’s specific needs. Development of topical gels/creams capable of supporting multiple classes of medications while enhancing penetration and subsequent delivery of drug entities across the skin barrier allow for a noninvasive, convenient and relatively adverse event free mechanism for accomplishing this tailored care. In fact, some doctors have found that multi-ingredient compounded topical pain relief formulations provide relief more quickly than their commercially prepared single-entity counterparts.

Delivery systems are specially designed to carry medications through the skin directly to the site of the patient's pain. Topical delivery has many advantages over traditional oral medications, including:

· Non-addictive

· Direct delivery to the site of the pain

· Minimal absorption into the bloodstream

· Fewer side effects, if any at all

· Reduced possibility of adverse drug interactions

· Reduced organ toxicity

· Decreased inflammation

· Measurable and identifiable pain relief

·Greater effectiveness and results

Another great advantage of compound formulations is that they can be easily adjusted according to the patient’s changing medical needs.

Compounded topical analgesics are extremely effective in relieving the pain that accompanies so many life-limiting and life-threatening diseases. In fact, some doctors believe that in order to help their patients heal, rather than just treat symptoms which provides the illusion of health, the prescribing of a compounded topical pain relief formulation is warranted.

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Read more on Topical Pain Relief Compounds

REFERENCES:

Vidrine, Eric (March/April 1998). Compounding for Pain Management. International Journal of Pharmaceutical Compounding. Vol 2 No 2, pp 104-105.

Baumann, Terry J. Pharmacotherapy: A Pathophysiologic Approach Sixth Ed. New York: McGraw-Hill, 2005. Pp 1089-1104.

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