Managing Diabetic Peripheral Neuropathic Pain

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1 Managing Diabetic Peripheral Neuropathic Pain Juzar Hooker Consulting Neurologist, Aga Khan University Hospital, Nairobi

2 Disclosure Eli lilly (have not driven, reviewed or controlled the presentation)

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5 IASP; Tesfaye et al 2010 Definition Pain arising as a direct consequence of abnormalities in the peripheral somatosensory system in people with diabetes No nociceptive stimulus Neuronal hyperexcitability

6 Common problem Up to 50% people with diabetes over time develop neuropathy 3-25% develop painful diabetic peripheral sensory neuropathy 47.5% of diabetic foot ulcers at KNH were neuropathic, and 30% neuroischaemic Tesfaye et al 2011; Nyamu et al 2003

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8 Risk of Peripheral Neuropathy Increases with Longer Duration of Diabetes 100 Prevalence of Distal Polyneuropathy by Duration of Type 2 Diabetes % of Patients Duration of Diabetes (Years) DPNP Adapted from: Eastman. In: NIDDK, 1995.

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17 Key Mechanisms in the Development of Chronic Pain 3. Sensitization of neurons in the brain 1 2. Sensitization and amplification of peripheral input in the dorsal horn 2 1. Sensitization and abnormal peripheral input 2 DPNP 1. Baron. Nat Clin Pract Neurol 2006;2(2): Latremoliere et al. J Pain 2009;10(9): Image courtesy of Apollo Marcom.

18 Diabetic Peripheral Neuropathy Clinical Stages DPN is a progressive disease starting with diminished nerve conduction velocity and ending with amputation Symptoms occur in approximately 25% of patients and may occur any time and/ or intermittently Symptoms (numbness, prickling, pain) Amputation Signs and Symptoms Foot ulcer Pressure sensation, temperature sensation Reflexes Vibratory sensation Nerve conduction velocity Subclinical Time Clinical DPNP Vinik et al. Diabetologia 2000;43(8):

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20 Boulton 2005

21 Boulton 2005

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24 Diabetic Patients Should be Screened DPNP for Neuropathy (Provisional Diagnosis) History/physical exam Inspect for deformities, skin changes Assess symptoms Neurological exam Pressure sensation (monofilament) Muscle stretch reflexes Vibration testing Proprioception Pain sensation (pin prick) Monofilament screening test Boulton et al. Diabet Med 1998;15(6): Boulton et al. Diabetes Care 2004;27(6): Light touch sensation Muscle strength Confirmatory testing Nerve conduction studies Quantitative sensory testing

25 A Boulton 2005

26 Pain Severity Numeric Rating Scale Average Pain, Worst Pain, and Night Pain Pain severity No Pain Measured by an 11- point numeric rating scale Completed by the patient daily to measure the severity of pain Average pain (primary efficacy measure) Worst pain Night pain Scores range from 0 (no pain) to 10 (worst possible pain) Worst Possible Pain

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28 Goals of Neuropathic Pain Treatment Primary goal: reduction in pain 1,2 Secondary goals 1,2 Improvement in physical function Reduction in affective distress Improvement in quality of life Maintenance of positive outcomes Education of patient and providers Achieving these goals depends upon 1 Accurate diagnosis of any underlying etiology Preventive treatment of underlying etiology (eg, diabetes and joint inflammation) DPNP 1. Argoff et al. Mayo Clin Proc 2006;81(4 Suppl):S Turk. Clinical Journal of Pain 2000;16:

29 Nutritional deficiency B12 Boulton 2005

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40 AAN

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43 Global Pharmacological Treatment Guidelines for Neuropathic Pain Including DPNP Medication Class TCAs Including amitriptyline (AMT) Ca Channel α 2 - δ Ligands (gabapentin, pregabalin) SNRIs (duloxetine, venalfaxine) Topical lidocaine Opioid analgesics and tramadol IASP/ NeuPSIG 1 1 st line 1 st line 1 st line 1 st line Canadian Pain Society 2 EFNS 3 NICE 4 JSPC 5 1 st line for PPN, PHN, CP 1 st line for PPN, PHN, CP 1 st line 2 nd line 2 nd line for PPN 1 st line for localized NP 2 nd line except in select circumstances 2 nd line for localized NP 3 rd line 1 st line for PHN if small area of pain/allodynia 2 nd line for PPN, PHN, CP AMT 1 st line, 2 nd line for DPNP and other TCAs if AMT fails Pregabalin 1 st line, 2 nd line for DPNP Duloxetine 1 st line for DPNP 1 st line 1 st line 2 nd line 3 rd line NA 3 rd line 3 rd line DPNP 1. Dworkin et al. Pain 2007;132(3): Moulin et al. Pain Res Manag 2007;12(1): Attal et al. Eur J Neurol 2010;17(9):1113-e88 4. NICE Neuropathic Pain Clinical Guidelines Hosokawa et al. JSPC 2011.

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46 In summary Look for (painful) diabetic neuropathy Exclude other possibilities Optimize glycaemic control and vascular risk Consider Non- pharmacologic therapy Topical therapy Systemic pharmacologic therapy Start low, go slow Choice of drug Monitor therapy Modify treatment Quality of life Foot care