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Post Herpetic Neuralgia Stephen May. Introduction "O’er ladies’ lips, who straight on kisses dream;Which oft the angry Mab with blisters plagues." Romeo.

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Presentation on theme: "Post Herpetic Neuralgia Stephen May. Introduction "O’er ladies’ lips, who straight on kisses dream;Which oft the angry Mab with blisters plagues." Romeo."— Presentation transcript:

1 Post Herpetic Neuralgia Stephen May

2 Introduction "O’er ladies’ lips, who straight on kisses dream;Which oft the angry Mab with blisters plagues." Romeo and Juliet (W. Shakespeare). "Whether or not the unknown infectious material of chickenpox could under certain circumstances manifest itself instead as a zoster eruption." James von Bokay 1892.

3 Introduction Smallpox and chickenpox different 1904 Ernest Tyzzer Zoster fluid could infect with varicella 1925 Kundratitz Weller et al in 1958 : same virus responsible for both Hope-Simpson : zoster is due to varicella virus reactivation

4 Introduction PHN is one of the most painful neuropathic conditions Usually VZV reactivation PHN : 1-6 mth post acute HZ Risk increases with age Usually a single unilateral dermatome Thoracic and V1 most common

5 Pathophysiology Acute infection : necrotising reaction in dorsal horn Large myelinated fibres are most extensively damaged Increased transfer at dorsal horn from smaller fibres (nociceptive info) Reduced innervation noted at affected skin Changes evident in CNS

6 Pathophysiology PHN – 2 types of pain Steady, aching, boring pain Paroxysmal lancing pain Allodynia, hyperalgesia, hyperaesthesia often occur Explained by 2 different mechanisms

7 Pathophysiology Sensitisation Acute injury -> ongoing discharge and hyperexcitability of nociceptor (peripheral sensitisation) Prolonged nociceptor discharge -> enhanced dorsal horn response to afferent neurones with expansion of receptive field (central sensitisation) Explains allodynia without marked sensory loss

8 Pathophysiology Deafferentation VZV reactivation in DRG - >inflammation -> neural damage and oedema Reduced endoneurial blood flow (↑P) Neural destruction Loss of afferent neurones -> spontaneous activity in deafferenated central neurones Constant pain in area of sensory loss and minimal allodynia

9 Pathophysiology Reactive sprouting of spinal terminals of A B mechanoreceptors to receptors formerly occupied by C-fibres results in hyperalgesia and allodynia

10 Pathophysiology 3 subtypes 1) Irritable nociceptor subtype Damaged primary afferent nociceptors responsible for allodynia Little deficit in sensory thresholds as sensory signalling still occurs

11 Pathophysiology 2) Deafferenated allodynic subtype Primary afferents more extensively damaged C fibres develop neuromata (spont discharge ) -> dorsal horn sensitisation Selective loss of C fibres (touch preserved) Surviving A B fibres discharge normally -> light touch signalling pain

12 Pathophysiology 2) Deafferenated non-allodynic subtype V. Extensive nerve damage Skin insensitive to all modalities Pain as a consequence of central sensitisation and neuronal reorganisation

13 Management : Prevention Increasing evidence for vaccination Acts to increase cell mediated immunity 2006 : UFDA have approved use Amitriptyline has been suggested as prophylactic drug

14 Management : Acute HZ Antivirals Corticosteroids Standard analgesia ? Epidural LA + steroid beneficial for pain Possibly only short term effect and no clear evidence in reducing PHN incidence

15 Management : PHN Mainstay of treatment is Anticonvulsants Antidepressants Opiates Increasing evidence for lidocaine patches as first line therapy

16 Management : PHN TCA’s : NNT 2.3 for 50% pain relief 30% minor SE’s, 4% more severe SE NNH 22 (major), 3.7 (minor) SSRI better tolerated but less effective GONIP trial (nortriptyline v gabapentin) : similar effects on pain and sleep, gabapentin better tolerated

17 Management : PHN Only 2/3 taking carbamazepine or gabapentin for neuropathic pain get benefit ? Best for lancinating or burning pain NNT 3.9, RR 2.5 Pregabalin may be tried where gabapentin not tolerated ? Lamotrigine – not licensed for PHN in Europe

18 Management : PHN Lidocaine patch 5% Reasonable first line choice and cost effective NO SIGNIFICANT SYSTEMIC SE’S Can get mild skin reaction Shown to have central effects

19 Management : PHN Opiates – partially effective, not 1 st line Capsaicin –NNT 5.3 for 0.075% Will increase pain in irritable nociceptor subgroup – contraindicated TENS – to be effective : need sufficient innervation from normally conducting fast fibres

20 Management : PHN Epidural LA + Steroid Evidence of effects on reducing pain General consensus is of little effect on PHN development ? Intrathecal methyprednisolone Occasional small scale evidence for peripheral or sympathetic blocks – no RCT

21 Management : Miscellaneous Prostaglandin E2 UVB in acute HZ ? Myofascial component in resistant cases LA + steroid local infiltration Botulinum toxin A Local skin excision (irritable nociceptor subgroup) Intrathecal baclofen Iv ATP

22 References 1) Bandolier. 2) Gabapentin for acute and chronic pain, Cochrane review 2005 3) Anticonvulsant drugs for acute and chronic pain, Cochrane review 2007 4) Kanari et al. Effectiveness of Prostaglandin E1 for the treatment of patients with neuropathic pain following herpes zoster. Pain Med. 2007 Jan-Feb; 8(1): 36-40 5) Smith and Roberts. Sequential Medication Strategies for Post Herpetic Neuralgia : A Cost-Effectiveness Analysis. Pain 2007 Jan 19 6) Opstelten et al. Treatment of patients with herpes zoster by epidural injection of steroids and local anaesthetics : less pain after one month but no effect on long-term post herpetic neuralgia – a randomized trial. Ned Tijdschr Geneeskd 2006. Dec 2; 150(48) : 2649-55 7) Sederholm and Patterson. Zoster vaccine to prevent post herpetic neuralgia. J. Pain Palliat Care Pharmacother 2006; 20(4) : 41-2 8) Rotty et al. Interleukin 2 – A potential treatment option for post herpetic neuralgia. Clin Infect Dis 2006 Dec15; 43(12) : e109- 10 9) Chen et al. Treatment of postherpetic neuralgia with intravenous administration of vitaminC. Anesth Analg.2006; 103: 1616- 1617 10)Key Topics in Chronic Pain. Bios. Grady,Severn, Eldridge 11)Geha et al. Brain activity for spontaneous pain of post herpetic neuralgia and its modulation by lidocaine patch therapy. Pain 2006 Oct 24 Article in press (corrected proof viewed online) 12)Vister and Kwai. Salmon Calcitonin in the treatment of post herpetic neuralgia. Anaesth Intensive Care. 2006 Oct; 34(5) : 668- 71 13) Holcomb and Weinberg. A novel vaccine (zostavax) to prevent herpes zoster and postherpetic neuralgia. J Drugs Dermatol. 2006 Oct; 5(9): 863-6

23 References 14)Holodnig. Prevention of shingles by varicella zoster virus vaccination. Expert Rev Vaccines. 2006 Aug: 5(4) : 431-43 15)Chandra et al. Gabapentin versus nortriptyline in post herpetic neuralgia patients : a randomized, double-blind clinical trial – The GONIP Trial. Int J Clin Pharmacol Ther. 2006 Aug: 44(8): 358-63 16)Jalali et al. Broad band ultraviolet B phototherapy in zoster patients may reduce the incidence and severity of post herpetic neuralgia. Photodermatol Photoimmunal Photomed. 2006 Oct;22(5) 232-7 17)Niv and Maltsman-Tseikhin. Post Herpetic Neuralgia : the never- ending challenge. Pain Pract 2005 Dec; 5(4): 327-40 18)Humpenstall et al. Analgesic Therapy in Postherpetic Neuralgia : A Quantitative Systematic Review. PLOS Med 2005 Jul; 2(7)e164 19)Weiner and Schmader. Post Herpetic Pain: More Then Sensory Neuralgia? Pain Med 2006 May-Jun: 7(3) 243-9 20)Stolker et al. The PINE study of epidural steroids and local anaesthetics to prevent postherpetic neuralgia : a randomized controlled trial. Lancet 2006 Jan 21; 367(9506): 219-24 21)Amjad and Mashhood. The efficacy of local infiltration of triamcinolone acetonide with lignocaine compared with lignocaine alone in the treatment of postherpetic neuralgia. J Coll Physician Surg Pak. 2005 Nov; 15(11): 683-5 22)Oxman et al. A vaccine to prevent herpes zoster and post herpetic neuralgia in older adults. N Engl J Med 2005 Jun 2; 352(22): 2271- 84 23)Hardy. Relief of pain in acute herpes zoster by nerve blocks and possible prevention of post herpetic neuralgia. Canadian Journal of Anesthesia 52:186-190 (2005)

24 References 24)Hagashida et al. Analgesic effect of intravenous ATP on postherpetic neuralgia in comparison with responses to intravenous ketamine and lidocaine. J Anaesth 2005 ; 19(1): 31-5 25)Kumar et al. Neuraxial and sympathetic blocks in herpes zoster and post herpetic neuralgia : an appraisal of current evisence. Reg Anaesth Pain Med 2004 Sep-Oct; 29(5): 454-61 26)Davies and Galer. Review of lidocaine patch 5% studies in the treatment of postherpetic neuralgia. Drugs 2004; 64(9): 937-47 27)Hsu-Tang et al. Botulinum toxin. A relieved neuropathic pain in a case of post herpetic neuralgia. Pain Medicine Vol 6. No 1, 89-91 28)Peterson et al. Relief of Post Herpetic Neuralgia by Surgical Removal of Painful Skin. Pain 98(1-2):119-26, 2002 Jul 29)Hosny et al. Response of intractable post herpetic neuralgia to intrathecal baclofen. Pain Physician : 2004;7:345-347 30)Johnson and Dwarkin. Clinical Review. Treatment of Herpes Zoster and Postherpetic Neuralgia. BMJ: 2003;32(6):748-50 31)Hayashida et al. Analgesic effect of intravenous ATP on post herpetic neuralgia in comparison to responses to intravenous ketamine and lidocaine. J. Anaesth 2005; 19(1): 31-5

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