Long-term neuropathic pain

Transcription

1 Long-term neuropathic pain Per Hansson, Professor, MD, DMSci, DDS, specialist in neurology (and pain management) -Dept of Pain Management and Research, Oslo University Hospital, Oslo, Norway - Norwegian National Advisory Unit on Neuropathic Pain -Clinical Pain Research, Karolinska Institutet, Stockholm, Sweden

2 -Definition (2011) -Conditions -Epidemiology -Identification algorithm (2016) -Clinical phenomenology -Sensory examination -Pharmacological treatment (2015)+ central neurostimulation (2016)

3 Definition of neuropathic pain Old IASP definition: Neuropathic pain: Pain initiated or caused by a primary lesion or dysfunction in the nervous system. (+neurogenic pain) Merskey & Bogduk 1994 Suggested definition by NeuPSIG of IASP: Pain araising as a direct consequence of a lesion or disease affecting the somatosensory system Treede et al Current IASP definition: Pain caused by a lesion or disease of the somatosensory nervous system ( Jensen et al. 2011

4 Conditions in which neuropathic pain may appear Peripheral Polyneuropathy Mononeuropathy/mononeuropathy multiplex Plexopathy Radiculopathy Causes: Trauma, metabolic, pressure, cancer, infection, autoimmune disease, vitamin deficiences, kidney disease, hereditary, radiation, medications, idiopathic etc Neuropathic pain conditions Peripheral Amputation: stump and phantom pain Post herpetic neuralgia CRPS type 2 Trigeminal and glossopharyngeal neuralgia CNS conditions in which neuropathic pain may appear Stroke MS SCI including cordotomy Vascular malformation of brain or spinal cord Inflammatory disease other than MS Syringomyelia/bulbia Traumatic brain injury Tumor Abscess

5 Conditions in which neuropathic pain may appear Peripheral Neuropathic pain conditions Peripheral Polyneuropathy Mononeuropathy/mononeuropathy multiplex Plexopathy Radiculopathy Causes: Trauma, metabolic, pressure, cancer, infection, vitamin deficiences, autoimmune diseases, kidney disease, hereditary, radiation, medications, etc Amputation: stump and phantom pain Post herpetic neuralgia CRPS type 2 Trigeminal and glossopharyngeal neuralgia Nerve injury or disease usually is a painless condition!!! CNS conditions in which neuropathic pain may appear Stroke MS SCI including cordotomy Syringomyelia/bulbia Vascular malformation of brain or spinal cord Inflammatory disease other than MS Traumatic brain injury Tumor Abscess

6 Epidemiology of neuropathic pain Prevalence of 3-18 %!!

7 Point prevalence/incidence of a few specific NeP conditions.. Painful diabetic polyneuropathy (pp 20%) Post herpetic neuralgia (pp 5-30%) Central post stoke pain (1 st year i 8-10%) P.o/P.t nerve injury (pp 5-35%) Central neuropathic pain after SCI (pp 30-50%) Central neuropathic pain in MS (pp 28%)

8 NeP is a clinical description and not (yet) a diagnosis!

9 2013 C -Not an uncommon problem on a population basis -Should be shown how it affects patient and society, suffering + costs (work place and health care) -Underreporting of conditions where neuropathic pain is the dominating symptom

10 The first step has been taken. Treede et al. 2015

11 Identification 2016

12 Leading complaint Pain History History of relevant neurological lesion or disease a and Pain distribution neuroanatomically plausible b No Unlikely to be neuropathic pain Yes Possible neuropathic pain Examination Pain is associated with sensory signs in the same neuroanatomically plausible distribution c Yes Probable neuropathic pain Confirmatory tests Diagnostic test confirming a lesion or disease of the somatosensory nervous system explaining the pain Yes Definite neuropathic pain d Finnerup et al. 2016

13 All neuropathic pains are projected

14 Carefully completed pain drawings as part of the computerized patient chart

15

16 Finnerup et al. 2016

17 Neuroanatomical pain distribution Beware and of variable variations innervation territories innervation! Foerster 1933

18 Eid & Hegazy 2011 Loukas et al. 2008

19 Clinical phenomenology-many disguises Spontaneous Pain (not all patients) Evoked Pain (minority of patients) Continuous Paroxymal/ intermittent Allodynia Hyperalgesia Also hypoesthesia, non-painful spontaneous/evoked phenomena, i.e., paresthesia, dysesthesia. Mechanical, Thermal Dynamic, Static Cold Any combinations=numerous phenotypes..

20 Leading complaint Pain History History of relevant neurological lesion or disease a and Pain distribution neuroanatomically plausible b No Unlikely to be neuropathic pain Yes Possible neuropathic pain Examination Pain is associated with sensory signs in the same neuroanatomically plausible distribution c Yes Probable neuropathic pain Confirmatory tests Diagnostic test confirming a lesion or disease of the somatosensory nervous system explaining the pain Yes Definite neuropathic pain d Finnerup et al. 2016

21 A focus on clinical (and quantitative) sensory examination! Because pain is part of the somtosensory system

22 Bedside examination of skin sensibility Brush/cotton bud/tuning fork-a-beta fibers Cold (A-delta) and warm (C) metallic rollers- the Lindblom rollers Pin (A-delta/C) Based on Ulf Lindblom---Hansson 1994

23 You have to have a plan!!!! Practical tips: Unilateral pathology: Step 1. Compare sides. Altered or no difference? Step 2. Outline spatial extension by titrating borders of area suspected to be altered-inside out or outside in? Repeat border survey reproducible? Hypophenomena? Tactile allodynia? Hansson et al. 2001

24 Look for a proximo-distal gradient in dyingback PNP. Practical tips: Polyneuropathy

25 Sensory abnormalities in neuropathy/neuropathic pain- may be different for different modalities! Touch (dma), pressure (sma) and cold Based on Ulf Lindblom---Hansson 1994

26 QST, e.g., thermal testing Four thermal percepts

27 Thermal testing Motor ability and attention! Method of limits---perception threshold tracking techniques Verdugo & Ochoa 1992

28 Leading complaint Pain History History of relevant neurological lesion or disease a and Pain distribution neuroanatomically plausible b No Unlikely to be neuropathic pain Yes Possible neuropathic pain Examination Pain is associated with sensory signs in the same neuroanatomically plausible distribution c Yes Probable neuropathic pain Confirmatory tests Diagnostic test confirming a lesion or disease of the somatosensory nervous system explaining the pain Yes Clinical neurophys., MRI, surgeon knows, chemotherapy, etc Definite neuropathic pain d Finnerup et al. 2016

29 Small fiber neuropathy-affected fibers and symptoms cold (A-delta) warmth (C) pain (A-delta/C) postganglionic efferents (C) preganglionic? Hoeijmakers et al. 2012

30 Small fiber neuropathy NaV1.7 NaV1.8 NaV1.9 Hoeijmakers et al. 2012; 2015

31 Bedside QST Techniques to survey SFN-not conventional neurophysiology Autonomic IENFD Microneurography CCM LEPs, or CHEPS or PREP GENETICS-if so far idiopathic

32 Leading complaint Pain History History of relevant neurological lesion or disease a and Pain distribution neuroanatomically plausible b No Unlikely to be neuropathic pain Yes Possible neuropathic pain Examination Pain is associated with sensory signs in the same neuroanatomically plausible distribution c Yes Probable neuropathic pain Confirmatory tests Diagnostic test confirming a lesion or disease of the somatosensory nervous system explaining the pain Yes Definite neuropathic pain d Causality Finnerup et al. 2016

33 All prerequisites fullfilled but pain still not to be equated with NeP (P or C) without further consideration! CAUSALITY? In peripheral nerve/root injury, pain in entire or partial innervation territory of injured structure? -Verified S1 radiculopathy with continuous pain in heel only. Aggravated by walking and pressure to heel area. NeP? Nociceptive / inflammatory?

34 All prerequisites fullfilled but pain still not to be equated with NeP (P or C) without further consideration! CAUSALITY? Pain in, e.g., stroke and SCI: When hemi, at level or all-below - CNeP; when patchy - CNeP or m-s pain? m-s = musculoskeletal

35 NeuPSIG/IASP (not acute, not trigeminal neuralgia, not children, drug specific recommendations, not condition specific) "Grading of Recommendations, Assessment, Development, and Evaluation" (GRADE) Finnerup et al. 2015

36 Finnerup et al jan weeks treatment or 3 weeks follow-up of single treatments -RCT, DB, parallel or cross-over, at least n=10 in each group -active comparator ok if 1 st or 2 nd line -study outcome based on POM (pain) -quality rated by OQS -GRADE classification to assess recommendations based on drug or drug class, 5 level recom

37 Drug, not specific condition (peripheral or central) Finnerup et al. 2015

38 Order of precedence? Finnerup et al. 2015

39 Finnerup et al. 2015

40 Finnerup et al. 2015

41 Still, at the end of the day % of patients across diagnostic entities report at least 50 % pain relief. No predictors for choice of therapy. Attal et al Hansson et al. 2009

42 State of the art of pharmacological treatment! Few pharmacological substances primarily developed to target neuropathic pain did ever make it to the market! None of the studied drugs target precisely mechanisms underlying initiation and maintenance of the pain! The majority of evidence based meds used are borrowed from other therapeutic areas and work in a minority of patients only

43 Current treatment concepts Target mechanisms underlying initiation and maintenance of pain----na-channels? Aim at other targets that can modulate activity without addressing mechanisms of initiation or maintenance, e.g., gabapentinoids, antidepressants, capsaicin patch, lidocaine patch Peripheral NeP Dorsal horn of spinal cord NMDA-receptor and spinal hyperexcitability (c.s., wind-up) tricyclic antidepressants Descending net facilitation (5HT3?), a spino-bulbo-spinal loop NA/5HT re-uptake inhibition antidepressants/tra madol Opioid receptor opioids/tramadol Ca-channel alterations (N-type VDCC) gabapentin/pregabalin/antidepressants Na-channel alterations (Nav 1.? VGSC) carbamazepine, lamotrigine, antidepressants, oxcarbazepine Based on Hansson & Dickenson, Pain 2005

44 NeP, CBLP, CRPS 1, FM conventional SCS, EMCS, DBS, rtms, tdcs

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46 "Grading of Recommendations, Assessment, Development, and Evaluation" (GRADE) High hopes for the future: -Large scale multicenter studies -Homogenous NeP populations -QoL assessments -Assess satisfaction with treatment -Define better cortical targets -Assess predictive factors Guidelines to be updated in 5 years