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11 Articles in Volume 11, Issue #8
Pain Following Combat Trauma In the 21st Century: A New Look at an Old Problem
Part 2: Fibromyalgia: Practical Approaches To Diagnosis and Treatment
Advances in Regenerative Medicine: High-density Platelet-rich Plasma and Stem Cell Prolotherapy For Musculoskeletal Pain
Implant Technologies for Severe Pain: Why, When, and the Outcomes
Value of EMG in Patients With Non-Migrainous, Persistent Head Pain
Drug Interactions Among HIV Patients Receiving Concurrent Antiretroviral and Pain Therapy
Etiology of Chronic Pain and Mental Illness: The Biopsychosocial Component
Insights Into Patients’ Views About Topical Opioids: Observations From a Small Clinical Study
Teenage Boy With Multiple Pain Disorders
The Bench Delivers and It Matters
Renewing Opioid Prescriptions Over the Phone

Insights Into Patients’ Views About Topical Opioids: Observations From a Small Clinical Study

Central pain patients report that topical opioids are quite effective in controlling troublesome symptoms. They are inexpensive, have low abuse potential, and are easy to use with only a few side effects.

Topical opioids have been increasingly used since the discovery that opioid receptors exist in peripheral tissue.1,2 Practical Pain Management has previously reported on the use of topical opioids and has received a great number of requests to further expand on this modality of treatment.3

In my practice, I often have noted that patients with intractable, central pain have a robust desire to use topical opioids and carisoprodol (Soma), but not other topical agents. In an effort to better understand this observation, I recently conducted a study involving 37 patients with central pain. The study’s purpose was to identify how and why these patients use topical opioids.

This article describes my definition of central pain, the method and results from my study, and the conclusions I have drawn from the results. Although I recognize that the study is small and relies on patients’ self-reports, I do believe that the results provide an interesting insight into the fundamental question of which treatments patients with central pain find helpful.

Defining Central Pain
Table 1 (page 32) describes my criteria for diagnosis of central pain, which I recommend be used to evaluate all patients with chronic pain. It is important to classify all these patients as having peripheral pain, central pain, or a combination of both conditions. The hallmarks of central pain are that it is constant (“24/7”) and does not respond or responds poorly to peripheral treatment measures such as a local anesthetics, corticosteroid injections, needling, acupuncture, electromagnetic administration, or prolotherapy.

Patients with central pain give a history of allodynia and hyperalgesia and display evidence of excess sympathetic discharge such as tachycardia and vasoconstriction (cold extremities). Insomnia is almost always present.

Why Are Topical Opioids Helpful in Central Pain?
Although the reason for topical opioid effectiveness in central pain is somewhat unclear, it obviously has something to do with the lack of the inhibition of descending pain signals that is a component of central pain.4-6 Simply put, the controlling mechanism that prevents excess descending electric signals to emanate from the brain is impaired. At various stages in the transformation of peripheral to central pain, microglial activation, excess neuroinflammation, release of toxic amino acids, central nervous system cell death, and reformations take place.5 Allodynia, which is a painful response to normal stimuli such as touching bed clothes, and hyperalgesia, which is extra, unexpected pain from a stimulus such as simple pressure, will periodically or continually occur. After central pain is established, sympathetic discharge resulting in tachycardia, hypertension, vasoconstriction, mydriasis, diaphoresis, and hyperreflexia may occur. In my experience, patients with these symptoms claim that topical application of opioids and carisoprodol are about the only topical medications that offer them relief.

Topical Formulations
In my practice, with trial and error, I have observed that topical formulations of carisoprodol and the opioids morphine, oxycodone, and hydromorphone are consistently effective in patients with central pain (Table 2).

However, I also have observed that methadone, hydrocodone, oxymorphone, fentanyl, and meperidine have been inconsistent or noneffective as topical agents in central pain. No other muscle relaxant except carisoprodol has been consistently effective in my hands. Fentanyl is interesting in that it is the only opioid that appears capable of being placed on the skin and entering the bloodstream in significant amounts.

Any number of bases can be used in which to dissolve the opioids, and compounding pharmacists all seem to have their favorite.

A Word About Carisoprodol
Because of the prevalence for abuse and misuse, carisoprodol has gained a negative reputation in pain management. In my experience, carisoprodol is the most abused or misused compound when taken orally. Why the lust to overuse carisoprodol by pain patients is uncertain, but it must have some special “feel” or “relief” in central pain patients. Studies and clinical observations give the idea that it is part benzodiazepine and part opioid. Whatever the reason for its oral, systemic appeal, it is a most effective topical treatment in patients with central pain. Abuse opportunities are almost entirely removed when carisoprodol is mixed in a cream base for topical use.

Pain Study
In order to determine if my observation was correct that my patients with central pain find topical opioids and carisoprodol to be effective treatments, I provided a written questionnaire to 37 central pain patients during the week beginning Aug. 22, 2011 during their regular clinic visits. All met the diagnostic criteria of central pain outlined in Table 1. Table 3 details patient characteristics.

Interestingly, the majority of patients related that anti-inflammatory drugs, over-the-counter medications, and the neuropathic agent, gabapentin, are ineffective at controlling their symptoms (Table 4). I have previously attempted to use topical γ-aminobutyric acid and diazepam in this patient population with little effect. Also, I have had only limited and temporary responses in this patient group with topical homeopathic agents and lidocaine gels and patches. In fact, I have come to view a good response with topical salicylates, lidocaine, and homeopathic agents to indicate that a peripheral pain site is active irrespective of whether central pain is present.

How To Use Topical Opioids and Carisoprodol
Most patients with central pain report using topical agents daily (Tables 5 and 6, page 34). These agents work within minutes and usually provide relief for up to 4 hours. Many patients use an ancillary measure, such as a hot towel or heating pad, to increase the effectiveness of topical agents. Some patients combine infrared or electric current devices (eg, transcutaneous electrical nerve stimulation) with the topical agent. The back, neck, and foot along with the large joints, hips and knees, are the most used anatomical sites of application.



Why patients use topical agents and what therapeutic effect they receive is critical to understanding the desire of central pain patients to use topical opioids and carisoprodol. About 66% of patients report using it when their pain sites begin to ache or flare. Periodic allodynia and hyperalgesia occur in these patients, and a significant percentage use their topical agents when burning or itching begins or when it is painful to touch the site. Approximately 33% use their topical agent to assist in mobilization and in getting out of bed each morning. More than 40% say topical opioids help them sleep, as insomnia is a severe problem encountered by patients with central pain. The excess sympathetic discharge, allodynia, and hyperalgesia that affect the skin are contributory factors to the severe insomnia observed in these patients.

Side Effects
Of the 37 patients in this study, 2 reported a side effect. One stated the topical agent caused some skin irritation that prevented its use as frequently as the desired. The second patient reported hives, which disappeared after she changed brands of the cold cream used to make the topical. We have previously performed serum testing on patients who used topical opioids. Two patients who reported topical morphine use four or more times per day showed trace serum 
levels up to 15 ng/mL.

Patients with chronic pain must be clinically evaluated to determine if they have central pain, peripheral pain, or a combination of both conditions. Patients with central pain have impaired neurologic mechanisms that inhibit descending pain signals emanating from the brain. The excess descending signals result in episodes of allodynia, hyperalgesia, and excess sympathetic discharge with such symptoms as tachycardia, hyperreflexia, diaphoresis, and vasoconstriction (cold extremities). Insomnia is at least partially related to uncontrolled, central output of pain signals.

Topical opioids and carisoprodol help control some of the symptoms and problems inherent to central pain. They are inexpensive, have low abuse potential, are easy to use, and are quite effective in controlling several troublesome symptoms.

Last updated on: November 17, 2011
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