Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

ACC 2024 Congress

Catch up on all the top stories and latest evidence in cardiology research with our ACC 2024 Congress hub page.
ADVANCED SEARCH
Log in
Top
Current Diabetes Reports
Published in: Current Diabetes Reports 4/2011

01-08-2011

Painful Diabetic Neuropathy is More than Pain Alone: Examining the Role of Anxiety and Depression as Mediators and Complicators

Authors: Rakesh Jain, Shailesh Jain, Charles L. Raison, Vladimir Maletic

Published in: Current Diabetes Reports | Issue 4/2011

Login to get access

Abstract

A wealth of information exists regarding the plight of patients suffering with diabetic peripheral neuropathic pain (DPNP). Although physical pain is certainly a primary challenge in the management of this condition, disorders associated with emotional pain—especially depression and anxiety—also greatly complicate the clinician’s efforts to attain optimal outcomes for DPNP patients. This article reviews the high rate of comorbidity between DPNP and depression/anxiety with a focus on why this pattern of comorbidity exists and what can be done about it. To accomplish this, the many physiologic similarities between neuropathic pain and depression/anxiety are reviewed as a basis for better understanding how, and why, optimal treatment strategies use behavioral and pharmacologic modalities known to improve both physical pain and symptoms of depression and anxiety. We conclude by highlighting that screening, diagnosing, and optimally treating comorbid depression/anxiety not only improves quality of life, these but also positively impacts DPNP pain.
Literature
1.
Daly M. Diabetes and depression–a risky combination. Nurs N Z. 2010;16(2):14–5.PubMed
2.
• Bair MJ et al. Prevalence of pain and association with quality of life, depression and glycaemic control in patients with diabetes. Diabet Med. 2010; 27(5):578–84. This article demonstrates the significant association between diabetes and pain.PubMedCrossRef
3.
Kessler RC, McGonagle KA, Zhao S, Nelson CB. Lifetime and 12 month prevalence of DSM-III-R psychiatric disorders in the United States. Arch Gen Psychiatry. 1994;51:8–19.PubMed
4.
Michaud CM, Murray CJ, Bloom BR. Burden of disease - implications for future research. JAMA. 2001;285(5):535–9.PubMedCrossRef
5.
Vehik K, Dabelea D. The changing epidemiology of type 1 diabetes: why is it going through the roof? Diabetes Metab Res Rev. 2010.
6.
Farag YM, Gaballa MR. Diabesity: an overview of a rising epidemic. Nephrol Dial Transplant. 2011;26(1):28–35.PubMedCrossRef
7.
• Li C et al. Diabetes and anxiety in US adults: findings from the 2006 behavioral risk factor surveillance system. Diabet Med. 2008; 25(7):878–81. This article articulates the issue of anxiety disorders in adults with diabetes.PubMedCrossRef
8.
Collins MM, Corcoran P, Perry IJ. Anxiety and depression symptoms in patients with diabetes. Diabet Med. 2009;26(2):153–61.PubMedCrossRef
9.
Gore M, Brandenburg N, Dukes E, Hoffman DL, Tai KS, Stacey B. Pain severity in diabetic peripheral neuropathy is associated with patient functioning, symptom levels of anxiety and depression, and sleep. J Pain Symptom Manage. 2005;30(4):374–85.PubMedCrossRef
10.
de Groot M, Anderson R, Freedland KE, Clouse RE, Lustman PJ. Association of depressive and diabetic complications: a meta-analysis. Psychosom Med. 2001;63(4):619–30.PubMed
11.
Waitzfelder B et al. Correlates of depression among people with diabetes: The Translating Research Into Action for Diabetes (TRIAD) study. Prim Care Diabetes. 2010;4(4):215–22.PubMedCrossRef
12.
Pouwer F et al. Prevalence of comorbid depression is high in out-patients with Type 1 or Type 2 diabetes mellitus. Results from three out-patient clinics in the Netherlands. Diabet Med. 2010;27(2):217–24.PubMedCrossRef
13.
Yoshida S et al. Neuropathy is associated with depression independently of health-related quality of life in Japanese patients with diabetes. Psychiatry Clin Neurosci. 2009;63(1):65–72.PubMedCrossRef
14.
Sulaiman N, Handam A, Tamim H, Mahmood DA, Young D, The prevalence and coorelates of depression and anxiety in a sampe of diabetic patients in Sharjah, United Arab Emirates. BMC Fam Pract. 2010; 11.
15.
Raval A, Dhanaraj E, Bhansali A, Grover S, Tiwari P. Prevalence and determinants of depression in type 2 diabetes patients in a tertiary care centre. Indian J Med Res. 2010;132:195–200.PubMed
16.
Wagner JA, Tennen H, Osborn CY. Lifetime depression and diabetes self-management in women with Type 2 diabetes: a case-control study. Diabet Med. 2010;27(6):713–7.PubMedCrossRef
17.
Katon WJ et al. The relationship between changes in depression symptoms and changes in health risk behaviors in patients with diabetes. Int J Geriatr Psychiatry. 2010;25(5):466–75.PubMedCrossRef
18.
Rubin RR et al. Cardiovascular disease risk factors, depression symptoms and antidepressant medicine use in the Look AHEAD (Action for Health in Diabetes) clinical trial of weight loss in diabetes. Diabetologia. 2010;53(8):1581–9.PubMedCrossRef
19.
Ahola AJ et al. Depression is associated with the metabolic syndrome among patients with type 1 diabetes. Ann Med. 2010;42(7):495–501.PubMedCrossRef
20.
Raval A et al. Prevalence & determinants of depression in type 2 diabetes patients in a tertiary care centre. Indian J Med Res. 2010;132:195–200.PubMed
21.
Herzer M, Hood KK. Anxiety symptoms in adolescents with type 1 diabetes: association with blood glucose monitoring and glycemic control. J Pediatr Psychol. 2010;35(4):415–25.PubMedCrossRef
22.
Le TK, Able SL, Lage MJ. Resource use among patients with diabetes, diabetic neuropathy, or diabetes with depression. Cost Eff Resour Alloc. 2006;4:18.PubMedCrossRef
23.
Boulanger L, Zhao Y, Bao Y, Russell MW. A retrospective study on the impact of comorbid depression or anxiety on healthcare resource use and costs among diabetic neuropathy patients. BMC Health serv Res. 2009; 9(111).
24.
Lin EH et al. Depression and advanced complications of diabetes: a prospective cohort study. Diabetes Care. 2010;33(2):264–9.PubMedCrossRef
25.
Ali S et al. The association between depression and health-related quality of life in people with type 2 diabetes: a systematic literature review. Diabetes Metab Res Rev. 2010;26(2):75–89.PubMedCrossRef
26.
•• Pouwer F, Kupper N, Adriaanse MC. Does emotional stress cause type 2 diabetes mellitus? A review from the European Depression in Diabetes (EDID) Research Consortium. Discov Med. 2010; 9(45):112–8. This thought-provoking article asks an important question: does stress act as a catalyst for the development of type 2 diabetes (and presumably its complications) in a prospective fashion? PubMed
27.
• Pan A et al. Bidirectional association between depression and type 2 diabetes mellitus in women. Arch Intern Med. 2010; 170(21):1884–91. This article offers a well-reasoned look at the data on the bi-irectional nature of diabetes and depression.PubMedCrossRef
28.
Atlantis E et al. Diabetes incidence associated with depression and antidepressants in the Melbourne Longitudinal Studies on Healthy Ageing (MELSHA). Int J Geriatr Psychiatry. 2010;25(7):688–96.PubMedCrossRef
29.
Nouwen A et al. Type 2 diabetes mellitus as a risk factor for the onset of depression: a systematic review and meta-analysis. Diabetologia. 2010;53(12):2480–6.PubMedCrossRef
30.
31.
Costigan M, Scholz J, Woolf CJ. Neuropathic pain: a maladaptive response of the nervous system to damage. Annual Review of Neuroscience. 2009;32(1):1–32.PubMedCrossRef
32.
• Doupis J et al. Microvascular reactivity and inflammatory cytokines in painful and painless peripheral diabetic neuropathy. J Clin Endocrinol Metab. 2009; 94(6):2157–63. This is an excellent review of the issue of inflammatory cytokines in DPNP.PubMedCrossRef
33.
34.
Scholz J, Woolf CJ. The neuropathic pain triad: neurons, immune cells and glia. Nat Neurosci. 2007;10(11):1361–8.PubMedCrossRef
35.
• Maletic V, Raison CL. Neurobiology of depression, fibromyalgia and neuropathic pain. Front Biosci. 2009; 14:5291–338. This article offers a comprehensive review of the shared neurobiology of pain and depression.PubMedCrossRef
36.
Baron R. Mechanisms of disease: neuropathic pain–a clinical perspective. Nat Clin Pract Neurol. 2006;2(2):95–106.PubMedCrossRef
37.
38.
Moalem G, Tracey DJ. Immune and inflammatory mechanisms in neuropathic pain. Brain Res Rev. 2006;51(2):240–64.PubMedCrossRef
39.
Ji RR et al. Central sensitization and LTP: do pain and memory share similar mechanisms? Trends Neurosci. 2003;26(12):696–705.PubMedCrossRef
40.
Ren K, Dubner R. Neuron-glia crosstalk gets serious: role in pain hypersensitivity. Curr Opin Anaesthesiol. 2008;21(5):570–9.PubMedCrossRef
41.
Yunus MB. Role of central sensitization in symptoms beyond muscle pain, and the evaluation of a patient with widespread pain. Best Pract Res Clin Rheumatol. 2007;21(3):481–97.PubMedCrossRef
42.
Woolf CJ, Mannion RJ. Neuropathic pain: aetiology, symptoms, mechanisms, and management. Lancet. 1999;353(9168):1959–64.PubMedCrossRef
43.
Kendler KS, Thornton LM, Gardner CO. Stressful life events and previous episodes in the etiology of major depression in women: an evaluation of the “kindling” hypothesis. Am J Psychiatry. 2000;157(8):1243–51.PubMedCrossRef
44.
Post RM. Kindling and sensitization as models for affective episode recurrence, cyclicity, and tolerance phenomena. Neurosci Biobehav Rev. 2007;31(6):858–73.PubMedCrossRef
45.
Miller L. Neurosensitization: A model for persistent disability in chronic pain, depression, and posttraumatic stress disorder following injury. NeuroRehabilitation. 2000;14(1):25–32.PubMed
46.
Dadabhoy D et al. Biology and therapy of fibromyalgia. Evidence-based biomarkers for fibromyalgia syndrome. Arthritis Res Ther. 2008;10(4):211.PubMedCrossRef
47.
Tracey I, Mantyh PW. The cerebral signature for pain perception and its modulation. Neuron. 2007;55(3):377–91.PubMedCrossRef
48.
Blackburn-Munro G, Blackburn-Munro RE. Chronic pain, chronic stress and depression: coincidence or consequence? J Neuroendocrinol. 2001;13(12):1009–23.PubMedCrossRef
49.
Schweinhardt P et al. Investigation into the neural correlates of emotional augmentation of clinical pain. Neuroimage. 2008;40(2):759–66.PubMedCrossRef
50.
Borsook D et al. Neuroimaging revolutionizes therapeutic approaches to chronic pain. Mol Pain. 2007;3:25.PubMedCrossRef
51.
52.
Apkarian AV et al. Human brain mechanisms of pain perception and regulation in health and disease. Eur J Pain. 2005;9(4):463–84.PubMedCrossRef
53.
Raison CL, Capuron L, Miller AH. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol. 2006;27(1):24–31.PubMedCrossRef
54.
55.
Apkarian AV et al. Chronic back pain is associated with decreased prefrontal and thalamic gray matter density. J Neurosci. 2004;24(46):10410–5.PubMedCrossRef
56.
Sorensen L et al. Differences in metabolites in pain-processing brain regions in patients with diabetes and painful neuropathy. Diabetes Care. 2008;31(5):980–1.PubMedCrossRef
57.
58.
Cauda F et al. Low-frequency BOLD fluctuations demonstrate altered thalamocortical connectivity in diabetic neuropathic pain. BMC Neurosci. 2009;10:138.PubMedCrossRef
59.
Frodl T et al. Effect of hippocampal and amygdala volumes on clinical outcomes in major depression: a 3-year prospective magnetic resonance imaging study. J Psychiatry Neurosci. 2008;33(5):423–30.PubMed
60.
Matthews SC et al. Decreased functional coupling of the amygdala and supragenual cingulate is related to increased depression in unmedicated individuals with current major depressive disorder. J Affect Disord. 2008;111(1):13–20.PubMedCrossRef
61.
Baliki MN et al. Chronic pain and the emotional brain: specific brain activity associated with spontaneous fluctuations of intensity of chronic back pain. J Neurosci. 2006;26(47):12165–73.PubMedCrossRef
62.
Goncalves L et al. Neuropathic pain is associated with depressive behaviour and induces neuroplasticity in the amygdala of the rat. Exp Neurol. 2008;213(1):48–56.PubMedCrossRef
63.
Tsigos C, Chrousos GP. Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress. J Psychosom Res. 2002;53(4):865–71.PubMedCrossRef
64.
Strouse TB. The relationship between cytokines and pain/depression: a review and current status. Curr Pain Headache Rep. 2007;11(2):98–103.PubMedCrossRef
65.
Rajkowska G, Miguel-Hidalgo JJ. Gliogenesis and glial pathology in depression. CNS Neurol Disord Drug Targets. 2007;6(3):219–33.PubMedCrossRef
66.
Pav M et al. Neurobiological aspects of depressive disorder and antidepressant treatment: role of glia. Physiol Res. 2008;57(2):151–64.PubMed
67.
McNally L, Bhagwagar Z, Hannestad J. Inflammation, glutamate, and glia in depression: a literature review. CNS Spectr. 2008;13(6):501–10.PubMed
68.
Tsuda M, Inoue K, Salter MW. Neuropathic pain and spinal microglia: a big problem from molecules in “small” glia. Trends Neurosci. 2005;28(2):101–7.PubMedCrossRef
69.
Zieglgansberger W, Berthele A, Tolle TR. Understanding neuropathic pain. CNS Spectr. 2005;10(4):298–308.PubMed
70.
Chapman CR, Tuckett RP, Song CW. Pain and stress in a systems perspective: reciprocal neural, endocrine, and immune interactions. J Pain. 2008;9(2):122–45.PubMedCrossRef
71.
Wieseler-Frank J, Maier SF, Watkins LR. Immune-to-brain communication dynamically modulates pain: physiological and pathological consequences. Brain Behav Immun. 2005;19(2):104–11.PubMedCrossRef
72.
Acee AM. Detecting and managing depression in type II diabetes: PHQ-9 is the answer! Medsurg Nurs. 2010;19(1):32–8.PubMed
73.
van Steenbergen-Weijenburg KM et al. Validation of the PHQ-9 as a screening instrument for depression in diabetes patients in specialized outpatient clinics. BMC Health Serv Res. 2010;10:235.PubMedCrossRef
74.
Brennan C et al. The hospital anxiety and depression scale: a diagnostic meta-analysis of case-finding ability. J Psychosom Res. 2010;69(4):371–8.PubMedCrossRef
75.
Lloyd CE, Dyer PH, Barnett AH. Prevalence of symptoms of depression and anxiety in a diabetes clinic population. Diabet Med. 2000;17(3):198–202.PubMedCrossRef
76.
Spitzer RL et al. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006;166(10):1092–7.PubMedCrossRef
77.
Lowe B et al. Validation and standardization of the Generalized Anxiety Disorder Screener (GAD-7) in the general population. Med Care. 2008;46(3):266–74.PubMedCrossRef
78.
• Reddy P et al. Identification of depression in diabetes: the efficacy of PHQ-9 and HADS-D. Br J Gen Pract. 2010; 60(575):239–45. This article offers a fair balanced review of the benefits and potential pitfalls of using PHQ-9 and HADS-D in DPNP patients.CrossRef
79.
Gonzalez JS, Esbitt SA. Depression and treatment nonadherence in type 2 diabetes: assessment issues and an integrative treatment approach. Epidemiol Psichiatr Soc. 2010;19(2):110–5.PubMed
80.
Fortmann AL et al. Support for disease management, depression, self-care, and clinical indicators among Hispanics with type 2 diabetes in San Diego County, United States of America. Rev Panam Salud Publica. 2010;28(3):230–4.PubMedCrossRef
81.
Echeverry D et al. Effect of pharmacological treatment of depression on A1C and quality of life in low-income Hispanics and African Americans with diabetes: a randomized, double-blind, placebo-controlled trial. Diabetes Care. 2009;32(12):2156–60.PubMedCrossRef
82.
Bogner HR, de Vries HF. Integrating type 2 diabetes mellitus and depression treatment among African Americans: a randomized controlled pilot trial. Diabetes Educ. 2010;36(2):284–92.PubMedCrossRef
83.
Ell K et al. Collaborative care management of major depression among low-income, predominantly Hispanic subjects with diabetes: a randomized controlled trial. Diabetes Care. 2010;33(4):706–13.PubMedCrossRef
84.
• Ismail K et al. A randomised controlled trial of cognitive behaviour therapy and motivational interviewing for people with Type 1 diabetes mellitus with persistent sub-optimal glycaemic control: a Diabetes and Psychological Therapies (ADaPT) study. Health Technol Assess. 2010; 14(22):1–101, iii-iv. This article demosntates the importnace of nonpharmacologic interventions in diabetes. PubMed
85.
van Bastelaar K et al. Development and reach of a web-based cognitive behavioural therapy programme to reduce symptoms of depression and diabetes-specific distress. Patient Educ Couns. 2010.
86.
Kuritzky L. Managing diabetic peripheral neuropathic pain in primary care. J Fam Pract. 2010;59(5 Suppl):S15–22.PubMed
87.
Tesfaye S. Advances in the management of diabetic peripheral neuropathy. Curr Opin Support Palliat Care. 2009;3(2):136–43.PubMedCrossRef
88.
89.
Smink BE, Egberts ACG, Lusthof KJ. The relationship between benzodiazepine use and traffic accident: a systematic litreature review. CNS Drugs. 2010;24(8):639–53.PubMedCrossRef
90.
Uzun S et al. Side effects of treatment with benzodiazepines. Psychiatr Danub. 2010;22(1):90–3.PubMed
91.
Skljarevski V et al. Evaluating the maintenance of effect of duloxetine in patients with diabetic peripheral neuropathic pain. Diabetes Metab Res Rev. 2009;25(7):623–31.PubMedCrossRef
92.
Rynn M et al. Efficacy and safety of duloxetine in the treatment of generalized anxiety disorder: a flexible-dose, progressive-titration, placebo-controlled trial. Depress Anxiety. 2008;25(3):182–9.PubMedCrossRef
93.
Kornstein SG et al. A randomized, double-blind study of increasing or maintaining duloxetine dose in patients without remission of major depressive disorder after initial duloxetine therapy. J Clin Psychiatry. 2008;69(9):1383–92.PubMedCrossRef
94.
Abrahamian H et al. Diabetes mellitus and co-morbid depression: treatment with milnacipran results in significant improvement of both diseases (results from the Austrian MDDM study group). Neuropsychiatr Dis Treat. 2009;5:261–6.PubMedCrossRef
95.
Lieberman DZ, Massey SH. Desvenlafaxine in major depressive disorder: an evidence-based review of its place in therapy. Core Evid. 2010;4:67–82.PubMed
96.
Pae CU et al. Milnacipran: beyond a role of antidepressant. Clin Neuropharmacol. 2009;32(6):355–63.PubMedCrossRef
97.
Golden RN, Nicholas L. Antidepressant efficacy of venlafaxine. Depress Anxiety. 2000;12 Suppl 1:45–9.PubMedCrossRef
98.
Di Guilmi MN et al. Pregabalin modulation of neurotransmitter release is mediated by change in intrinsic activation/inactivation properties of CaV2.1 calcium channels. J Pharmacol Exp Ther. 2010.
99.
Satosh J, Yagihashi S, Baba M, Suzuki M. Efficacy and safety of pregabalin for treating neuropathic pain associated with diabetic peripheral neuropathy: a 14 week, randomized, double blind, placebo-controlled trial. Diabet Med. 2011;28(1):109–16.CrossRef
100.
Montgomery SA, Herman BK, Schweizer E. The efficacy of pregabalin and benzodiazepines in generalized anxiety disorder presenting with high levels of insomnia. Int Clin Psychopharmacology. 2009;24(4):214–22.CrossRef
101.
Bryan C et al. The impact of diabetes on depression treatment outcomes. Gen Hosp Psychiatry. 2010;32(1):33–41.PubMedCrossRef
102.
Osborn CY, Kozak C, Wagner J. Theory in practice: helping providers address depression in diabetes care. J Contin Educ Health Prof. 2010;30(3):172–9.PubMedCrossRef
103.
Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Arlington, VA: APA Press; 2000.
Metadata
Title
Painful Diabetic Neuropathy is More than Pain Alone: Examining the Role of Anxiety and Depression as Mediators and Complicators
Authors
Rakesh Jain
Shailesh Jain
Charles L. Raison
Vladimir Maletic
Publication date
01-08-2011
Publisher
Current Science Inc.
Published in
Current Diabetes Reports / Issue 4/2011
Print ISSN: 1534-4827
Electronic ISSN: 1539-0829
DOI
https://doi.org/10.1007/s11892-011-0202-2

Other articles of this Issue 4/2011

Current Diabetes Reports 4/2011 Go to the issue

Clinical Trial Report

Does Therapy Targeting Normal SBP of Less than 120 mm Hg Reduce Major CV Events in T2DM Patients?

ReviewPaper

AGEs, RAGE, and Diabetic Retinopathy

ReviewPaper

What is the Role of Hyperbaric Oxygen in the Management of Diabetic Foot Disease?

ReviewPaper

Microvascular Modifications in Diabetic Retinopathy

ReviewPaper

Cell-Based Therapies for Diabetic Retinopathy

ReviewPaper

Imaging of Diabetic Retinopathy and Diabetic Macular Edema

ACC 2024 Congress Coverage

Cardiology Video

Highlights from the ACC 2024 Congress

Watch now

Watch official videos from the ACC congress summarizing key highlights from the last year in heart failure, cardiomyopathies, valvular disease, pulmonary vascular disease, and pediatric cardiology.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits