David A. Chad

Does capsaicin relieve the pain of diabetic neuropathy

Painful peripheral neuropathy is a common complication of diabetes [2]. A variety of approaches to reduce pain are currently used, including simple analgesics, improving diabetic control [l], carbamazepine [8], and tricyclic antidepressants [6,7]. However, side effects are common and cause some patients to stop treatment [7]. The basis for pain in diabetic neuropathy remains elusive so that it has been difficult to target specific therapy for this problem. In animal studies, capsaicin administration results in a loss of sensitivity to several types of nociceptive stimuli [3,5]. Topical application of capsaicin to human skin has a desensitizing effect on chemically and heat-induced pain [4]. We studied whether capsaicin applied to painful areas of the skin produced an analgesic effect in painful diabetic neuropathy. Fifty-eight diabetic patients with painful distal, symmetrical polyneuropathy from 5 centers were entered into the study. Admission criteria included: age 18-85 years; stable and well controlled diabetes; and, moderate to severe pain. Nerve conduction testing confirmed the diagnosis of polyneuropathy in 43 out of 51 patients. The study was double blind and patients were randomized to receive either 0.075% capsaicin or vehicle (both supplied by Galenpharma, Northbrook, IL) for 4 weeks. Of the 46 patients who completed the study, 24 received capsaicin and 22 received vehicle. Patients were instructed to apply study medication liberally to painful areas 4 times a day for the duration of the study. Four capsaicinand 4 vehicle-treated patients noted side effects which included pruritus and burning over the treated areas. We assessed pain severity by standard scales. We used two verbal scales which described pain severity at 2 and 4 weeks compared to baseline (physicians global evaluation and categorical pain scale). In addition, we used two visual analog scales (VAS) indicating pain severity and pain relief. The study protocol was approved by the Human Studies Review Board of each participating institution, and informed consent was obtained from all patients. Five capsaicinand 7 vehicle-treated patients were excluded from data analysis for infractions of the study protocol. The following minimal criteria were used to assess clinical improvement in pain: (1) on the verbal scales, either slight lessening of pain severity or slight improvement in pain; (2) a 10% reduction in pain severity; and (3) on the visual analog scale of relief a 20% easing of the pain. We found that capsaicin treatment did not consistently improve the pain of diabetic neuropathy across the 4 criteria of pain measurement (Table I). After 2 weeks of treatment there was a trend toward improvement in the capsaicin-treated group. By 4 weeks of treatment 67-718 of patients improved in each measurement in the capsaicin group versus 41-508 of patients in the

Case 16-1999

Presentation of Case A 71-year-old, right-handed man was admitted to the hospital because of progressive muscle weakness and difficulty swallowing. The patient had been well until one year earlier, when he had several bouts of pulmonary and paranasal-sinus infections that were treated with amoxicillin. Nine months before admission, his voice was becoming progressively softer and hyponasal. Two months later, muscle weakness developed in the arms and legs, especially on the right side, and subsequently worsened, with loss of muscle bulk. Five months before admission, the patient began to have falls because of a right footdrop, and he had occasional leg .xa0.xa0.

A standardized clinical evaluation of phenotypic diversity in diabetic polyneuropathy.

Abstract Diabetic polyneuropathy (DPN) is a major cause of neuropathic pain and a frequent target condition in analgesic treatment trials. Differences in the clinical symptoms and signs associated with DPN suggest distinct pathophysiological mechanisms underlying nerve damage and dysfunction that are likely to have therapeutic relevance. The aim of this study was to develop a tool for the bedside assessment of painful neuropathies such as DPN that captures the diversity of phenotypes. Sixty-one patients with type 2 diabetes and painful neuropathy, 19 patients with painless DPN, 25 patients with type 2 diabetes but no clinical evidence of neuropathy, and 20 healthy control subjects completed a structured interview (47 items) and a standardized physical examination (39 items). After analyzing critical features of pain and painless symptoms and examining the outcome of physical tests of sensory function, we determined principal components of the phenotypic variance among patients. Increased sensitivity to mechanical or thermal stimuli and, to a lesser extent, the sensory quality of pain or paresthesia were the most discriminating elements of DPN phenotypes. Correlation patterns of symptoms and signs indicated the involvement of functionally distinct nerve fiber populations. We combined interview questions and physical tests identifying these differences in a shortened assessment protocol that we named Standardized Evaluation of Pain and Somatosensory Function (StEPS). The protocol StEPS generates a phenotypic profile of patients with neuropathy. Separate intensity ratings for spontaneous painful symptoms and pain evoked by standard stimuli support a detailed documentation of neuropathic pain and its response to analgesic treatment.

Case records of the Massachusetts General Hospital. Case 14-2011. A woman with asymmetric sensory loss and paresthesias.

From the Departments of Neurology (D.A.C.), Rheumatology (J.H.S.), and Radiology (R.G.), Massachusetts General Hospital; and the Departments of Neurology (D.A.C.), Medicine (J.H.S.), and Radiology (R.G.), Harvard Medical School — both in Boston.

Case records of the Massachusetts General Hospital. Case 7-2012. A 79-year-old man with pain and weakness in the legs.

Dr. Aida E. Kuri (Medicine): A 79-year-old man was admitted to this hospital because of pain and weakness in the legs. The patient had multiple medical problems but had been in his usual state of health until 6 days before admission, when progressive, generalized pain and tingling developed in both legs. Three days before admission, weakness in both legs developed and gradually worsened and he had difficulty walking. On the morning of admission, he was unable to get out of bed. His wife called emergency medical services, and he was brought to the emergency department at this hospital. The patient had no fevers, chills, headache, chest pain, respiratory symptoms, nausea, vomiting, changes in bladder habits, rectal bleeding, or saddle anesthesia (loss of sensation in the area of the buttocks and perineum) and had no history of trauma, falls, contact with sick persons, or recent travel. Eight days before admission, esophagogastroduodenoscopy was performed because of iron-deficiency anemia, with the administration of meperidine and midazolam; multiple nonbleeding duodenal erosions were seen; testing for Helicobacter pylori was negative. The patient had a long history of leg pain that was associated with activity and was relieved with rest, attributed to claudication, which was different from his current symptoms. He had had diabetes mellitus, hypertension, and hyperlipidemia for more than 10 years, as well as peripheral vascular disease, glaucoma, hypothyroidism, vitamin D deficiency, chronic constipation, urinary retention due to prostatic hypertrophy (for which transurethral prostatic resection had been performed 3 years earlier), and for 6 years, worsening chronic kidney disease (stage 3 of 5) (Table 1). He had had a benign colonic adenoma on routine colonoscopy 3 years earlier and a positive tuberculin skin test in the distant past, with negative chest radiographs. He had a history of noncompliance with medications but had recently become more adherent, owing to a visiting nurse and pharmacy-provided prepackaged medications. Daily medications on admission included lisinopril (20 mg), amlodipine (10 mg), metoprolol (200 mg), hydralazine (100 mg in divided doses), furosemide (40 mg), doxazosin (8 mg), simvastatin (40 mg daily for 9 months; previously 20 mg daily for 1.5 years), finasteride (5 mg), levothyroxine (88 μg), ferrous sulfate (325 mg), sodium polystyrene sulfonate (30 g), aspirin (81 mg), and insulin glargine (70 U); other medications were gemfibrozil (600 mg twice daily for 2.5 years), ergocalciferol (50,000 U twice monthly), Case 7-2012: A 79-Year-Old Man with Pain and Weakness in the Legs

Case 7-2012

Dr. Aida E. Kuri (Medicine): A 79-year-old man was admitted to this hospital because of pain and weakness in the legs. The patient had multiple medical problems but had been in his usual state of health until 6 days before admission, when progressive, generalized pain and tingling developed in both legs. Three days before admission, weakness in both legs developed and gradually worsened and he had difficulty walking. On the morning of admission, he was unable to get out of bed. His wife called emergency medical services, and he was brought to the emergency department at this hospital. The patient had no fevers, chills, headache, chest pain, respiratory symptoms, nausea, vomiting, changes in bladder habits, rectal bleeding, or saddle anesthesia (loss of sensation in the area of the buttocks and perineum) and had no history of trauma, falls, contact with sick persons, or recent travel. Eight days before admission, esophagogastroduodenoscopy was performed because of iron-deficiency anemia, with the administration of meperidine and midazolam; multiple nonbleeding duodenal erosions were seen; testing for Helicobacter pylori was negative. The patient had a long history of leg pain that was associated with activity and was relieved with rest, attributed to claudication, which was different from his current symptoms. He had had diabetes mellitus, hypertension, and hyperlipidemia for more than 10 years, as well as peripheral vascular disease, glaucoma, hypothyroidism, vitamin D deficiency, chronic constipation, urinary retention due to prostatic hypertrophy (for which transurethral prostatic resection had been performed 3 years earlier), and for 6 years, worsening chronic kidney disease (stage 3 of 5) (Table 1). He had had a benign colonic adenoma on routine colonoscopy 3 years earlier and a positive tuberculin skin test in the distant past, with negative chest radiographs. He had a history of noncompliance with medications but had recently become more adherent, owing to a visiting nurse and pharmacy-provided prepackaged medications. Daily medications on admission included lisinopril (20 mg), amlodipine (10 mg), metoprolol (200 mg), hydralazine (100 mg in divided doses), furosemide (40 mg), doxazosin (8 mg), simvastatin (40 mg daily for 9 months; previously 20 mg daily for 1.5 years), finasteride (5 mg), levothyroxine (88 μg), ferrous sulfate (325 mg), sodium polystyrene sulfonate (30 g), aspirin (81 mg), and insulin glargine (70 U); other medications were gemfibrozil (600 mg twice daily for 2.5 years), ergocalciferol (50,000 U twice monthly), Case 7-2012: A 79-Year-Old Man with Pain and Weakness in the Legs

Case 14-2011: A Woman with Asymmetric Sensory Loss and Paresthesias

From the Departments of Neurology (D.A.C.), Rheumatology (J.H.S.), and Radiology (R.G.), Massachusetts General Hospital; and the Departments of Neurology (D.A.C.), Medicine (J.H.S.), and Radiology (R.G.), Harvard Medical School — both in Boston.

Case 1-2004: A 49-Year-Old Woman with Asymmetric Painful Neuropathy

Presentation of Case A 49-year-old left-handed woman was evaluated in the neurology clinic because of painful asymmetric neuropathy. The patient had been well until several years earlier, when numbness developed in the right hand. A right carpal-tunnel–release operation had been performed eight months before the current evaluation, but without benefit. During the four months before the evaluation, she experienced increasing burning pain in the same hand, and similar symptoms developed in the left hand. She frequently observed blisters on the first, second, and third digits of the right hand, without any recollection of injury. She had decreased sensation in the .xa0.xa0.

Case 14-2011

From the Departments of Neurology (D.A.C.), Rheumatology (J.H.S.), and Radiology (R.G.), Massachusetts General Hospital; and the Departments of Neurology (D.A.C.), Medicine (J.H.S.), and Radiology (R.G.), Harvard Medical School — both in Boston.

Case 1-2004

Presentation of Case A 49-year-old left-handed woman was evaluated in the neurology clinic because of painful asymmetric neuropathy. The patient had been well until several years earlier, when numbness developed in the right hand. A right carpal-tunnel–release operation had been performed eight months before the current evaluation, but without benefit. During the four months before the evaluation, she experienced increasing burning pain in the same hand, and similar symptoms developed in the left hand. She frequently observed blisters on the first, second, and third digits of the right hand, without any recollection of injury. She had decreased sensation in the .xa0.xa0.