Fifteen patients with diabetes mellitus who had painful diabetic neuropalhy (PDN) were enrolled in a double-blind study to test the safety and efficacy of capsaicin 0.075% (Axsain, Genderm, Northbrook, IL). Twelve of the 15 patients completed the eight-week sludy. Nine of the 12 patients reported symptomatic relief; of these nine, five used the drug and four used the vehicle. The three patients who reported no relief of symptoms applied the vehicle. Capsaicin is potentially effective when burning pain is a major symptom of PDN. The side effects of capsaicin were limited and minimal. This agent should be considered by clinicians for treatment of PDN

Basha, Karen M.

Whitehouse, Fred W.

English

Henry Ford Health System Scholarly Commons

Henry Ford Hospital Medical Journal Volume 39 Number 2 Article 16 6-1991 Capsaicin: A Therapeutic Option for Painful Diabetic Neuropathy Karen M. Basha Fred W. Whitehouse Follow this and additional works at: https://scholarlycommons.henryford.com/hfhmedjournal  Part of the Life Sciences Commons, Medical Specialties Commons, and the Public Health Commons Recommended Citation Basha, Karen M. and Whitehouse, Fred W. (1991) "Capsaicin: A Therapeutic Option for Painful Diabetic Neuropathy," Henry Ford Hospital Medical Journal : Vol. 39 : No. 2 , 138-140. Available at: https://scholarlycommons.henryford.com/hfhmedjournal/vol39/iss2/16 This Article is brought to you for free and open access by Henry Ford Health System Scholarly Commons. It has been accepted for inclusion in Henry Ford Hospital Medical Journal by an authorized editor of Henry Ford Health System Scholarly Commons. Endocrine Disorders: Principles of Management Capsaicin: A Therapeutic Option for Painful Diabetic Neuropathy Karen M. Basha, BSN, RN, CDE,* and Fred W. Whitehouse, MD' Fifteen patients with diabetes mellitus who had painful diabetic neuropalhy (PDN) were enrolled in a double-blind .study to test the .safety and efficacy of capsaicin 0,075% (Ax.sain. Genderm. Northbrook, IL). Twelve of the 15 patients completed the eight-week slutly. Nine trf the 12 patients reported symptomatic relief: trf these nine, five used the drug and four used Ihe vehicle. The three patients who reported no relief trf symptoms appUed the vehicle. Capsaicin is potentially effective when burning pain is a major sympttmi of PDN. The side effects trf capsaicin were limited and minimal. This agent should he considered hy clinicians for ireatmeni trf PDN. (Henry Ford Hosp Med J 1991:39:138-40) D iabetes mellitus (DM) affects more tiian 12 million people in the United States and its complications are the third leading cause of death today. All individuals with DM are sus-ceptible lo the numerous complications of this disease. The macrovascular and microvascular complications of DM may lead to progressive end-organ involvement, the most pain-ful of which is neuropathy. Clinical manifestations of painful diabetic neuropathy (PDN) include .severe burning ofthe low-er limbs and feet with nocturnal intensification (oflen occur-ring in a stocking-glove distribution), paresthesia, intermittent sharp or stabbing pains, anorexia, weight loss, and depression (1) . Of those with either long-.standing insulin-dependent diabe-tes mellitus (IDDM) or noninsulin-dependent diabetes mellitus (NIDDM), 50%. will be affected by some form of neuropalhy (2) . Treatment of PDN includes biochemical control of the dia-betic slale and appropriate pharmacologic therapy for symptom-atic reliefi A variety of pharmacologic strategies are available including oral medications, such as nonopiate anodynes, tricy-clic antidepressants, phenytoin, and vitamin B (use of some of these may be limited by systemic side effects), and local physio-therapeutics, such as transepidural neural stimulation ("TENS"). Aldose reductase inhibitors are currently being studied, but no consensus yet exists on their efficacy and safety. Capsaicin (Axsain, Genderm, Northbrook, IL), a recently mar-keted topical agent, has been used with some success in post-herpefic neuralgia, post-mastectomy pain syndrome, and PDN. We participated in a mulficenter Capsaicin Study Group and re-port our experience with this new agent in the treatment of PDN. shade family (Solanaceae). It is the chemical substance that makes hot peppers "hot." These plants were introduced in the 15th century in Europe where they were used as a food or condi-ment; they were also thought lo have several medicinal proper-ties. Cap.saicin has also played a role in folk medicine, with its medicinal uses dating back to the 19th century. In recent years, this substance has been available in low concentrations and used in .several over-the-counter preparations for arthritis (3). As a topical cream, capsaicin is marketed in two strengths. 0.025% and 0.075%. The lower strength of capsaicin was ini-tially advised for patients with post-herpetic neuralgia. Use of capsaicin, 0.075%, has recently been studied in clinical trials for the treatment of post-mastectomy pain syndrome and PDN. Its side effects include burning, slinging, and erythema at the site of application (which usually diminishes with repeated use), dry skin, and nasal inhalation irritant reactions. Capsaicin is thought to deplete substance P, a pain-modulating neurotransmitter, at the nerve terminals. Initial applications sensitize the nerve fiber membrane to release substance P, and continued use desensi-tizes the membrane which subsequently reduces local concen-trations of substance P. Hence, the area of capsaicin application becomes less sensitive to pain. This decrease in pain is tempo-rary but is sustained with repeated use of capsaicin (4). Studies suggest that when capsaicin is di.scontinued the deplefion of substance P slops and symptoms retum (5). Pharmacology of Capsaicin Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is an active ingredient found in many botanical species of the night-Submitted for publication: February 2,5, 1991, Accepled for publication: May 20, 1991, •Division of Endocrinology and Metabolism, Henry Ford Hospilal, Address con-espondence lo Ms, Basha, Division of Endocrinology and Melabolisni, Henry Ford Hospilal, 2799 W Grand Blvd, Detroit, Ml 48202, 138 Henry Ford Hosp Med J—Vol 39, No 2, 199 i Capsaicin for PDN—Basha & Whitehou,se Body Area A f f e c t e d : ( f o r Fteripheral Polynemx^sathy) uxxncm OF NEDRALGIA Dermatome Affected: (for Radiculcpathy) PAIN SEVERITY None(O) 1 1 S l i g h t ( l ) t 1 Moderate (2) [ ) Severe(3) [ 1 Very Severie(4) 1 ] Fig 1—Dermatome chart used to record location of pain. Multicenter Capsaicin Study Group A total of 277 diabetic patients (136 IDDM and 141 NIDDM) with PDN were randomized to an eight-week, double-blind, placebo-controlled, multicenter clinical trial using eilher capsa-icin or vehicle (placebo) to evaluate the clinical safety and effi-cacy of topically applied capsaicin cream (0,075%). Patients in-cluded 139 men and 138 women with a mean age of 60 years (range 27 to 81 years). The 12 medical centers across the United States participating in the study each randomized a mean of 20 patients (range 9 to 54) inlo one ofthe two groups. The Henry Ford Hospital group enrolled 15 patients (9 fe-male, 6 male) whose ages ranged from 48 to 79 years (mean 64 years). Eight patients had IDDM; seven patients had NIDDM. The duration of DM ranged from 6 months to 24 years (mean 12 years). Twelve of the patients had peripheral polyneuropathy and three had radiculopathy. The duration of the symptomatic neuralgia ranged from 2 months lo 15 years (mean 4 years). Inclusion criteria included: I) individuals wilh IDDM or NIDDM belween ages 18 to 85 years; 2) a fasting blood glucose < 180 mg/dL or a glycosylated hemoglobin < 11%; 3) presence of either clinical peripheral polyneuropathy or radiculopathy, characterized by local pain and paresthesia confirmed by find-ings on electromyogram (EMG); 4) pain interfering with daily activities and/or sleep at least some of the time; 5) other topical medications applied to the affected areas discontinued at least seven days prior to study entry; 6) all oral medications for pain associated with neuropathy continued but without change in dosage or frequency of administration; 7) medication prescribed for indications other than pain could be initiated provided their use did not interfere with the evaluation of the study drug. In-formed conseni was obtained from all participanls in the study. Exclusion criteria included; I) females who were pregnant or lactating; 2) patients who had open lesions on the affected skin area; 3) individuals with a serious medical or psychiatric dis-ease. Before randomization at a pretreatment visit, the history was obtained and directed neurological examination performed. PATIENT INSTRUCTIONS 1, Apply the medication cream to painful areas of your skin FOUR TIMES A DAY lor the duration o l the sludy. Even if pain slops, continue medication until your iast visit to the clinic, ALWAYS WASH YOUR HANDS AFTER APPLICATION OF THE CREAIVl. AVOID CONTACT WiTH YOUR EYES AND WiTH ANY OPEN WOUNDS OR iRRITATED SKiN WHEN APPLYING THE CREAIVl, KEEP OUT OF REACH OF CHILDREN. 2, When the drug is applied to normal skin, there may be mild to moderale d iscomfor l and burning or sl inging sensations, especiaiiy during the f irsl v^eek of Irealmenl. Repealed appl ical ion usually resulls in el imination or marked decrease of this discom-fort. If you so choose, you may take two |2) tablets of aspirin or acetaminophen (e,g., Tylenoi, Anacin-3, Datril), every four hours, for relief of the discomfort. However, if such discomfort is too disUessing, you should call your doctor, and bolh of you will decide whether you should continue using lhe study medication. 3, Bring all used lubes of medication with you lo your next scheduled visit. 4, Your doctor may consider making changes in your pain medications. If 31 any l ime, you make a change in lhe amounl or lype ot medical ion you are taking, notify your doctor, 5, Your doctor will schedule the clinic visits for you as tol iows: — 2 weeks after your ini l ial visit of the open label study — 8 weeks afler your ini l lai visit — then every 8 weeks, up to a total of one year on the sludy Please contaci your doctor at any time during the sludy if your pain worsens. NOTE: Your doctor will also make a telephone fo l low-up call at 4 and 6 weeks after your initial visit. 6 Once you finish the sludy, your doctor will call you periodically lo assess wheiher your pain has changed after discontinuation of the study medication. Fig 2—Patient instructiems frn- the application erf study medica-tion to the affected areas. Nerve conduction was studied in patients who had not had the test in the previous six months. EMG, used at the onset of the study to confirm the diagnosis of PDN, was not repeated. The anatomical distribution of the pain was recorded on a derma-tome chart (Fig 1). Patients were randomly assigned into one of two study groups ulilizing eilher capsaicin or a vehicle and were instructed lo ap-ply the cream to the affected area four times daily. Each patient was informed ofthe possible side effects of capsaicin and given an instruction sheet to follow (Fig 2). Instructions were reviewed and questions and concerns regarding the protocol were dis-cussed with the patient prior to leaving the clinic. The side effects of capsaicin included mild to moderate bum-ing or stinging when applied to the affected area. If side effects occurred, patients were instructed to lake two tablets of aspirin or acetaminophen every four hours. If symptoms were severe, patients were instructed to contact the clinic promptly lo deter-mine ifthe study drug should be discontinued. Each patient was also instructed to avoid contact with their eyes and mucous membranes when applying the cream and to wash their hands after each use. Al baseline and at weeks 2, 4, 6, and 8, pain was assessed by the patient and nurse coordinator using three stan-dard pain scales; physician global evaluation (PGE), visual ana-logue scale for pain intensity (VAS-P), and visual analogue scale for pain relief (VAS-R). The PGE was completed by the nurse coordinator and physician with input from the patient to assess changes in pain severity compared to baseline. The other two scales were completed by the patient. Patients were instructed to complete these questionnaires based on the time or times of the day the pain was most intense. Henry Ford Hosp Med J—Vol 39, No 2, 1991 Capsaicin for PDN—Basha & Whitehouse 139 Patients Randomized (15) drop out (3) Capsaicin (2) vehicle (1) completed study (12) relief (9) No relief (3) Capsaicin (5) vehicle (4) vehicle (3) Fig 3—Schema frn- double-blind capsaicin studv. Results Ofthe 15 patients enrolled in the Henry Ford Hospital group, seven used capsaicin and eight u.sed the vehicle cream during the study period. Twelve patients completed the trial; of the three patients who dropped out, two did so because of severe burning (1 capsaicin, I vehicle) and one because of treatment failure (capsaicin). Nine patients reported moderate lo complete relief of pain during the trial (5 capsaicin. 4 vehicle), and three patients reported no relief (all vehicle) (Fig 3). Discussion The results of the multicenter Capsaicin Study Group dem-onstrate that capsaicin offers symptomatic relief in the treatment of PDN and radiculopathy (6). These findings were based on the analyses of the efficacy parameters (i.e., PGE, VAS-P, VAS-R). Of the 277 patients randomized nationally, 138 received capsa-icin and 139 received vehicle. Based on the final visit analyses of standard pain scales, 69.5% of the patients in the capsaicin group and 53.4% of the patients in the vehicle group reporied improvement in pain (PGE) (P < 0.012). A total of 38.1 % of the patients in the capsaicin group and 27.1% in the vehicle group reported a decrease in pain intensity (VAS-P) (P < 0.037). Fi-nally. 58.4% of the cap.saicin group and 45.3% of the vehicle group reported they had a relief of pain (VAS-R) (P < 0.004). All of these are significanl at the 5% level (6). In lighl of the overall findings of the multicenter group, we feel that capsaicin is worthy of consideration in the treatment of PDN. The placebo respon.se, not uncommon in pain studies, can be attributed lo the following factors; scheduled visits to talk with the patient regarding pain, patient response to the placebo effeci, and rubbing the area .skin with lanolin ointment which in-creases the local blood supply and is soothing to the skin. Capsaicin is indicated in patients whose primary complaint from neuropalhy is pain. Most patients whose symptoms im-proved with capsaicin reported buming pain as a primary com-plaint. The drug has not yet been studied in patients whose pri-mary complaint is numbness or dysesthesia. A few patients with localized sensory mononeuropathy (intercostal and truncal neu-ropathy or meralgia paresthetica) may also benefit from its use. The goal of therapy, symptomatic relief, should occur two to six weeks after beginning therapy. Therapy is instituted with 0.025% capsaicin applied to the affected area four times daily. Ifno response is achieved, we advise the more concentrated form of 0.075% four times daily. Once relief is obtained, fre-quency of use can be adjusted to maintain symptom control ac-cording to individual need. The advantages of capsaicin are; 1) application directly to the affected area, 2) no systemic effects, and 3) diminished local side effects with repeated use of the cream. Disadvantages in-clude: 1) local side effects at the site ofapplication, which, if .severe, may require discontinuation of the medication; 2) high costof treatment ($53 to $55 for a 45-gram tube of capsaicin at the 0.075% strength and an average of $35 for a 45-gram tube at the 0.025% strength, with each tube permitting two to three weeks of therapy when used as advised); and 3) possible use without medical advice as patients may obtain it over-the-coun-ter without a prescription. If local burning pain is a primary complaint of patients with diabetic neuropathy, the use of capsa-icin merits a trial. Of course, this medication is not used in the presence of skin ulcers or infection. Although the results in our small sample of patients are not decisive, the multicenter report persuades us that the agent has therapeutic benefit. The fre-quency of relief by vehicle cream (in our experience as well as in the multicenter study) emphasizes the need for double-blind studies when assessing clinical effectiveness. References 1, Sperling MA, ed, Phy,sician's guide to insulin-dependent (type I) diabetes: Diagno,si.s and treatment, Alexandria. VA: American Diabetes Association. 1988:123-4, 2, Greene DA. Sima AAF, Alberts JW. Pfeifer MA, Diabetic neuropathy. In: Rifkin H, Porte D Jr. eds, Ellenberg and Rifkin's diabetes mellitus: Theory and practice, 4th ed. New York: Elsevier. 1990:710, 3, Topical capsaicin treatment of diabetic neuropathy (Investigators Bro-chure), Northbrook, IL: Genderm Corporation. 1987, 4, Simone DA. Ochoa J, Early and late effects of prolonged capsaicin on cuta-neous sensibility and neurogenic vasodilation in humans. Pain (in press), ,S, McMahon SB, LewinG, Bloom SR, The consequences of long-term topical capsaicin applicalion in the rat. Pain 1991:44:301-10, 6, The Capsaicin Study Group, Treatment of painful diabetic neuropathy with topical cap,saicin: A multi-center, double-blind, vehicle controlled study. Arch Intern Med (in press). 140 Henry Ford Hosp Med J—Vol 39, No 2, 1991 Capsaicin for PDN—Basha & Whilehouse 

Capsaicin: A Therapeutic Option for Painful Diabetic Neuropathy

https://scholarlycommons.henryford.com/cgi/viewcontent.cgi?article=2767&amp;context=hfhmedjournal

Capsaicin: A Therapeutic Option for Painful Diabetic Neuropathy

Abstract

Similar works

Full text

Available Versions

Henry Ford Health System Scholarly Commons