A Highly Successful and Novel Model for Treatment of Chronic Painful Diabetic Peripheral Neuropathy

OBJECTIVE To investigate why, in spite of a vast variety of treatment agents, the alleviation of pain in patients with diabetic neuropathy is difficult. Previous studies have not used a treatment algorithm based on anatomic site and neuropathophysiological source of the neuropathic pain. RESEARCH DESIGN AND METHODS A model that categorizes the types of pain into three groups (superficial, deep, and muscular) was applied in 75 diabetic patients with chronic (> 12 mo) painful distal symmetrical polyneuropathy in a controlled case series. Twenty-two patients were untreated and 53 patients were treated with imipramine ± mexiletine for deep pain, capsaicin for superficial pain, and stretching exercises and metaxalone ± piroxican for muscular pain. Each type of pain was scored separately on a scale of 0 (none) to 19 (worst), and the total of all three types was used as an index of overall pain. Ability to sleep through the night was scored by a scale of 1 (never) to 5 (always). RESULTS No significant differences were observed in initial pain scores, sleep scores, demographics, biochemistries, or physical findings between the two groups. After 3 mo a significant improvement in scores was noted in the treated but not the untreated patients. In addition, a significant difference was found in the change of scores between the treated and untreated patients: total pain (−18 ± 2 vs. 0 ± 2), deep pain (−7 ± 1 vs. 0 ± 1), superficial pain (−5 ± 1 vs. 0 ± 1), muscular pain (−6 ± 1 vs. 0 ± 1), and sleep (1.2 ± 0.2 vs. 0.2 ± 0.2), all P < 0.0001. In treated patients 21% became pain-free (total pain < 2), 66% had improvement (decrease in total pain > 5, but not total elimination of painful symptoms), and 13% were considered treatment failures (a decrease in total pain of < or = 5). This compares with 0 (P < 0.02), 10 (P < 0.0001), and 90% (P < 0.0001), respectively, in the untreated patients. CONCLUSIONS This study presents a new rationale and hypothesis for the successful treatment of chronic painful diabetic peripheral neuropathy. It uniquely bases the treatment algorithm on the types and sources of the pain.

[1]  Scheffler Nm,et al.  Treatment of painful diabetic neuropathy with capsaicin 0.075%. , 1991, Journal of the American Podiatric Medical Association.

[2]  C. Grunfeld,et al.  A trial of amitriptyline and fluphenazine in the treatment of painful diabetic neuropathy. , 1986, JAMA.

[3]  M. Pfeifer,et al.  RR-variation: the autonomic test of choice in diabetes. , 1988, Diabetes/metabolism reviews.

[4]  F. Lembeck,et al.  Capsaicin applied to peripheral nerve inhibits axoplasmic transport of substance P and somatostatin , 1982, Brain Research.

[5]  A. Boulton,et al.  Continuous Subcutaneous Insulin Infusion in the Management of Painful Diabetic Neuropathy , 1982, Diabetes Care.

[6]  D. Ewing,et al.  A Controlled Trial of Sorbinil, an Aldose Reductase Inhibitor, in Chronic Painful Diabetic Neuropathy , 1983, Diabetes.

[7]  S. Werns,et al.  Phenytoin in the treatment of diabetic symmetrical polyneuropathy , 1977, Clinical pharmacology and therapeutics.

[8]  J. D. Stauffer.  Antidepressants and chronic pain. , 1987, The Journal of family practice.

[9]  J. Kastrup,et al.  MEXILETINE FOR TREATMENT OF CHRONIC PAINFUL DIABETIC NEUROPATHY , 1988, The Lancet.

[10]  E. C. Huskisson,et al.  Graphic representation of pain , 1976, Pain.

[11]  K. Herold,et al.  TREATMENT OF SEVERELY PAINFUL DIABETIC NEUROPATHY WITH AN ALDOSE REDUCTASE INHIBITOR: RELIEF OF PAIN AND IMPROVED SOMATIC AND AUTONOMIC NERVE FUNCTION , 1983, The Lancet.

[12]  K. Brøsen,et al.  The selective serotonin reuptake inhibitor paroxetine is effective in the treatment of diabetic neuropathy symptoms , 1990, Pain.

[13]  G. Slama,et al.  Severe early-onset polyneuropathy in insulin-dependent diabetes mellitus. A clinical and pathological study. , 1992, The New England journal of medicine.

[14]  M. Ellenberg.  Treatment of diabetic neuropathy with diphenylhydantoin. , 1968, New York state journal of medicine.

[15]  Ross Dr,et al.  Treatment of painful diabetic neuropathy with topical capsaicin. , 1989, The New England journal of medicine.

[16]  G. Fromm,et al.  Baclofen as an analgesic in chronic peripheral nerve disease. , 1985, European neurology.

[17]  C. W. Silverblatt,et al.  Clinical Trial of Amitriptyline and Fluphenazine in Diabetic Peripheral Neuropathy , 1981, Southern medical journal.

[18]  T. Onaya,et al.  Clinical efficacy of a stable prostacyclin analog, iloprost, in diabetic neuropathy. , 1991, Prostaglandins.

[19]  P. Wall,et al.  Pain mechanisms: a new theory. , 1965, Science.

[20]  Trial of ganglioside therapy for diabetic neuropathy , 1987, Muscle & nerve.

[21]  P. Watkins.  Natural history of the diabetic neuropathies. , 1990, The Quarterly journal of medicine.

[22]  J. Bell-Krotoski,et al.  The repeatability of testing with Semmes-Weinstein monofilaments. , 1987, The Journal of hand surgery.

[23]  J. Kastrup,et al.  The effect of intravenous lidocaine on nociceptive processing in diabetic neuropathy , 1990, Pain.

[24]  R Dubner,et al.  Effects of desipramine, amitriptyline, and fluoxetine on pain in diabetic neuropathy. , 1992, The New England journal of medicine.

[25]  B. Lynn,et al.  The effects of locally applied capsaicin on conduction in cutaneous nerves in four mammalian species , 1986, British journal of pharmacology.

[26]  R. Lamping.  Pain due to peripheral nerve damage: An hypothesis , 1985 .

[27]  G. Pasternak,et al.  Analgesic activity of tricyclic antidepressants , 1983, Annals of neurology.

[28]  J. Wang.  Antinociceptive Effect of Intrathecally Administered Serotonin , 1977, Anesthesiology.

[29]  J. Arezzo,et al.  Thermal Sensitivity Tester: Device for Quantitative Assessment of Thermal Sense in Diabetic Neuropathy , 1986, Diabetes.

[30]  B. Clarke,et al.  Pain Relief in Diabetic Neuropathy: The Effectiveness of Imipramine and Related Drugs , 1985, Diabetic medicine : a journal of the British Diabetic Association.

[31]  F. Gómez-Pérez,et al.  Nortriptyline and fluphenazine in the symptomatic treatment of diabetic neuropathy. A double-blind cross-over study , 1985, Pain.

[32]  B. Lynn,et al.  VASCULAR AND SENSORY RESPONSES OF HUMAN SKIN TO MILD INJURY AFTER TOPICAL TREATMENT WITH CAPSAICIN , 1981, British journal of pharmacology.

[33]  R. W. Turkington.  Depression Masquerading as Diabetic Neuropathy , 1980, JAMA.

[34]  M. Bleecker.  A field study with the Optacon , 1984, Neurology.

[35]  H. Sakai,et al.  Clinical usefulness of intrathecal injection of methylcobalamin in patients with diabetic neuropathy. , 1987, Clinical therapeutics.

[36]  F. Joó,et al.  Neurotoxic effect of capsaicin in mammals. , 1987, Acta physiologica Hungarica.

[37]  T F Burks,et al.  The neuropharmacology of capsaicin: review of some recent observations. , 1986, Pharmacological reviews.

[38]  D. Ewing,et al.  Chronic and Remitting Painful Diabetic Polyneuropathy: Correlations With Clinical Features and Subsequent Changes in Neurophysiology , 1988, Diabetes Care.

[39]  A. Boulton.  What causes neuropathic pain? , 1992, Journal of diabetes and its complications.

[40]  R. Griffey,et al.  Diabetic neuropathy. Structural analysis of nerve hydration by magnetic resonance spectroscopy. , 1988, Journal of the American Medical Association (JAMA).

[41]  A. Biegon,et al.  Interaction of tricyclic antidepressants with opiate receptors. , 1980, Biochemical pharmacology.

[42]  A. Boulton,et al.  The Prevalence of Symptomatic, Diabetic Neuropathy in an Insulin-treated Population , 1985, Diabetes Care.

[43]  H. Fields,et al.  Potentiation of morphine antinociception by monoamine reuptake inhibitors in the rat spinal cord , 1985, Pain.

[44]  R. Dubner,et al.  Amitriptyline relieves diabetic neuropathy pain in patients with normal or depressed mood , 1987, Neurology.

[45]  R. Tandan,et al.  Topical capsaicin in painful diabetic neuropathy. Controlled study with long-term follow-up. , 1992, Diabetes care.

[46]  H. Fields,et al.  Amitriptyline potentiates morphine analgesia by a direct action on the central nervous system , 1983, Annals of Neurology.

[47]  A. Jancsó-Gábor,et al.  Pharmacologically induced selective degeneration of chemosensitive primary sensory neurones , 1977, Nature.

[48]  J. Kastrup,et al.  Treatment of chronic painful diabetic neuropathy with intravenous lidocaine infusion. , 1986, British medical journal.

[49]  R. Tandan,et al.  Topical Capsaicin in Painful Diabetic Neuropathy: Effect on Sensory Function , 1992, Diabetes Care.

[50]  B. Bromm,et al.  Imipramine reduces experimental pain , 1986, Pain.

[51]  M. Max.  Towards physiologically based treatment of patients with neuropathic pain , 1990, Pain.

[52]  D. Dvornik.  Aldose reductase inhibitors as pathobiochemical probes. , 1992, Journal of diabetes and its complications.

[53]  K. Cohen,et al.  Efficacy and safety of nonsteroidal anti-inflammatory drugs in the therapy of diabetic neuropathy. , 1987, Archives of internal medicine.

[54]  D. Tarsy,et al.  Does capsaicin relieve the pain of diabetic neuropathy? , 1990, Pain.

[55]  A. Fro̸land,et al.  Imipramine treatment of painful diabetic neuropathy. , 1984, JAMA.

[56]  J. Kastrup,et al.  Intravenous lidocaine infusion — a new treatment of chronic painful diabetic neuropathy? , 1987, Pain.

[57]  H. Beck-Nielsen,et al.  Concentration‐response relationship in imipramine treatment of diabetic neuropathy symptoms , 1990, Clinical pharmacology and therapeutics.

[58]  J. Mitas,et al.  Diabetic Neuropathic Pain: Control by Amitriptyline and Fluphenazine in Renal Insufficiency , 1983, Southern medical journal.

[59]  A. Boulton,et al.  The natural history of painful diabetic neuropathy--a 4-year study. , 1983, Postgraduate medical journal.

[60]  R. T. Malseed,et al.  Enhancement of morphine analgesia by tricyclic antidepressants , 1979, Neuropharmacology.