Journal of Neurology

, Volume 252, Issue 6, pp 677–686

Postherpetic neuralgia: Topical lidocaine is effective in nociceptor–deprived skin

  • G. Wasner
  • A. Kleinert
  • A. Binder
  • J. Schattschneider
  • R. Baron
ORIGINAL CONTRIBUTION

Abstract

Objectives

Topical lidocaine is effective in postherpetic neuralgia (PHN). The aim of the present investigation was to classify patients according to their predominant peripheral nociceptor function and to compare these data with the results of a controlled study using dermal lidocaine patch.

Methods

Within the skin area of maximal pain QST (thermotest) and QCART (histamine iontophoresis and laser Doppler flowmetry) were performed prospectively in 18 PHN patients. A controlled study using cutaneous lidocaine (lidocaine 5% patch, IBSA) followed.

Results

Six patients (group I, sensitised nociceptors) had no sensory loss. Heat pain thresholds were equal or lower than on the contralateral side. Histamine–induced flare and axon reflex vasodilatation were not different on both sides. Histamine evoked pain increased. In 12 patients (group II, nociceptor impairment) heat pain thresholds were higher than contralateral. Histamine–induced flare was impaired or abolished. Histamine did not induce any sensation. Lidocaine was efficacious in the entire group of patients. Subgroup analysis revealed that patients with impairment of nociceptor function had significantly greater pain reduction under lidocaine vs placebo. Patients with preserved and sensitised nociceptors demonstrated no significant pain relief.

Conclusions

PHN patients differ concerning their cutaneous nociceptor function: In the group I pain is caused by pathologically sensitised nociceptors. In subset II there is a loss of function of cutaneous C–nociceptors within the allodynic skin. Patients responded well to topical lidocaine even if the skin was completely deprived of nociceptors. Different underlying mechanims of lidocaine action in nociceptor–deprived skin are discussed.

Key words

zoster allodynia neuropathic pain pathophysiological mechanisms 

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References

  1. 1.
    Argoff CE (2000) New analgesics for neuropathic pain: the lidocaine patch. Clin J Pain 16:S62–S66PubMedGoogle Scholar
  2. 2.
    Bao L, Wang HF, Cai HJ, Tong YG, Jin SX, Lu YJ, et al. (2002) Peripheral axotomy induces only very limited sprouting of coarse myelinated afferents into inner lamina II of rat spinal cord. Eur J Neurosci 16:175–185PubMedGoogle Scholar
  3. 3.
    Baron R, Saguer M (1993) Postherpetic neuralgia. Are C-nociceptors involved in signalling and maintenance of tactile allodynia? Brain 116:1477–1496PubMedGoogle Scholar
  4. 4.
    Baron R, Schwarz K, Kleinert A, Schattschneider J, Wasner G (2001) Histamine-induced itch converts into pain in neuropathic hyperalgesia. Neuroreport 12:3475–3478CrossRefPubMedGoogle Scholar
  5. 5.
    Bernstein JE, Korman NJ, Bickers DR, Dahl MV, Millikan LE (1989) Topical capsaicin treatment of chronic postherpetic neuralgia. J Am Acad Dermatol 21:265–270PubMedGoogle Scholar
  6. 6.
    Caterina MJ, Leffler A, Malmberg AB, Martin WJ, Trafton J, Petersen-Zeitz KR, et al. (2000) Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science 288:306–313CrossRefPubMedGoogle Scholar
  7. 7.
    Chacur M, Milligan ED, Gazda LS, Armstrong C, Wang H, Tracey KJ, et al. (2001) A new model of sciatic inflammatory neuritis (SIN): induction of unilateral and bilateral mechanical allodynia following acute unilateral peri-sciatic immune activation in rats. Pain 94:231–244CrossRefPubMedGoogle Scholar
  8. 8.
    Decosterd I, Ji RR, Abdi S, Tate S, Woolf CJ (2002) The pattern of expression of the voltage-gated sodium channels Na(v)1.8 and Na(v)1.9 does not change in uninjured primary sensory neurons in experimental neuropathic pain models. Pain 96:269–277CrossRefPubMedGoogle Scholar
  9. 9.
    Eide PK, Jorum E, Stubhaug A, Bremnes J, Breivik H (1994) Relief of post-herpetic neuralgia with the Nmethyl-D-aspartic acid receptor antagonist ketamine: a double-blind, crossover comparison with morphine and placebo. Pain 58:347–354CrossRefPubMedGoogle Scholar
  10. 10.
    Fields HL, Rowbotham M, Baron R (1998) Postherpetic neuralgia: irritable nociceptors and deafferentation. Neurobiol Dis 5:209–227PubMedGoogle Scholar
  11. 11.
    Fruhstorfer H, Lindblom U, Schmidt WC (1976) Method for quantitative estimation of thermal thresholds in patients. J Neurol Neurosurg Psychiatry 39:1071–1075PubMedGoogle Scholar
  12. 12.
    Galer BS, Rowbotham MC, Perander J, Friedman E (1999) Topical lidocaine patch relieves postherpetic neuralgia more effectively than a vehicle topical patch: results of an enriched enrollment study. Pain 80:533–538CrossRefPubMedGoogle Scholar
  13. 13.
    Gammaitoni AR, Alvarez NA, Galer BS (2003) Safety and tolerability of the lidocaine patch 5%, a targeted peripheral analgesic: a review of the literature. J Clin Pharmacol 43:111–117CrossRefPubMedGoogle Scholar
  14. 14.
    Gilden DH, Dueland AN, Cohrs R, Martin JR, Kleinschmidt-DeMasters BK, Mahalingam R (1991) Preherpetic neuralgia. Neurology 41:1215–1218PubMedGoogle Scholar
  15. 15.
    Head H, Campbell AW (1900) The pathology of herpes zoster and its bearing on sensory location. Brain 23:353–523Google Scholar
  16. 16.
    Heyer G, Hornstein OP, Handwerker HO (1989) Skin reactions and itch sensation induced by epicutaneous histamine application in atopic dermatitis and controls. J Invest Dermatol 93: 492–496CrossRefPubMedGoogle Scholar
  17. 17.
    Khodorova A, Meissner K, Leeson S, Strichartz GR (2001) Lidocaine selectively blocks abnormal impulses arising from noninactivating Na channels. Muscle Nerve 24:634–647CrossRefPubMedGoogle Scholar
  18. 18.
    Koski CL (1992) Peripheral neuropathy: new concepts and treatments.Humoral mechanisms in immune neuropathies. Neurol Clin 10:629–649PubMedGoogle Scholar
  19. 19.
    Lynn B (1990) Capsaicin: actions on nociceptive C-fibres and therapeutic potential. Pain 41:61–69CrossRefPubMedGoogle Scholar
  20. 20.
    Meier T, Wasner G, Faust M, Kuntzer T, Ochsner F, Hueppe M, et al. (2003) Efficacy of lidocaine patch 5% in the treatment of focal peripheral neuropathic pain syndromes: a randomized, double-blind, placebo-controlled study. Pain 106:151–158CrossRefPubMedGoogle Scholar
  21. 21.
    Michaelis M, Vogel C, Blenk KH, Jänig W (1997) Algesics excite axotomised afferent nerve fibres within the first hours following nerve transection in rats. Pain 72:347–354CrossRefPubMedGoogle Scholar
  22. 22.
    Noordenbos W (1959) Pain. Elsevier. AmsterdamGoogle Scholar
  23. 23.
    Nurmikko T, Bowsher D (1990) Somatosensory findings in postherpetic neuralgia. J Neurol Neurosurg Psychiatry 53:135–141PubMedGoogle Scholar
  24. 24.
    Oaklander AL (2001) The density of remaining nerve endings in human skin with and without postherpetic neuralgia after shingles. Pain 92:139–145CrossRefPubMedGoogle Scholar
  25. 25.
    Oaklander AL, Romans K, Horasek S, Stocks A, Hauer P, Meyer RA (1998) Unilateral postherpetic neuralgia is associated with bilateral sensory neuron damage. Ann Neurol 44:789–795CrossRefPubMedGoogle Scholar
  26. 26.
    Orstavik K, Weidner C, Schmidt R, Schmelz M, Hilliges M, Jorum E, et al. (2003) Pathological C-fibres in patients with a chronic painful condition. Brain 126:567–578CrossRefPubMedGoogle Scholar
  27. 27.
    Pappagallo M, Oaklander AL, Quatrano-Piacentini AL, Clark MR, Raja SN (2000) Heterogenous patterns of sensory dysfunction in postherpetic neuralgia suggest multiple pathophysiologic mechanisms. Anesthesiology 92:691–698CrossRefPubMedGoogle Scholar
  28. 28.
    Petersen KL, Fields HL, Brennum J, Sandroni P, Rowbotham MC (2000) Capsaicin evoked pain and allodynia in post-herpetic neuralgia. Pain 88:125–133CrossRefPubMedGoogle Scholar
  29. 29.
    Rowbotham MC, Davies PS,Verkempinck C, Galer BS (1996) Lidocaine patch: double-blind controlled study of a new treatment method for post-herpetic neuralgia. Pain 65:39–44CrossRefPubMedGoogle Scholar
  30. 30.
    Rowbotham MC, Fields HL (1989) Post-herpetic neuralgia: the relation of pain complaint, sensory disturbance, and skin temperature. Pain 39:129–144CrossRefPubMedGoogle Scholar
  31. 31.
    Rowbotham MC, Fields HL (1996) The relationship of pain, allodynia and thermal sensation in post-herpetic neuralgia. Brain 119:347–354PubMedGoogle Scholar
  32. 32.
    Rowbotham MC, Yosipovitch G, Connolly MK, Finlay D, Forde G, Fields HL (1996) Cutaneous innervation density in the allodynic form of postherpetic neuralgia. Neurobiol Dis 3:205–214CrossRefPubMedGoogle Scholar
  33. 33.
    Ruppenthal M (1980) Changes of the central nervous system in herpes zoster. Acta Neuropathol (Berl) 52:59–68CrossRefPubMedGoogle Scholar
  34. 34.
    Santha P, Jancso G (2003) Transganglionic transport of choleragenoid by capsaicin-sensitive C-fibre afferents to the substantia gelatinosa of the spinal dorsal horn after peripheral nerve section. Neuroscience 116:621–627CrossRefPubMedGoogle Scholar
  35. 35.
    Schmelz M, Schmidt R, Bickel A, Handwerker HO, Torebjörk HE (1997) Specific C-receptors for itch in human skin. J Neurosci 17:8003–8008PubMedGoogle Scholar
  36. 36.
    Schmidt R, Schmelz M, Forster C, Ringkamp M, Torebjörk E, Handwerker H (1995) Novel classes of responsive and unresponsive C nociceptors in human skin. J Neurosci 15:333–341PubMedGoogle Scholar
  37. 37.
    Schüller TB, Hermann K, Baron R (2000) Quantitative assessment and correlation of sympathetic, parasympathetic, and afferent small fiber function in peripheral neuropathy. J Neurol 247:267–272CrossRefPubMedGoogle Scholar
  38. 38.
    Torebjörk HE, Lundberg LE, LaMotte RH (1992) Central changes in processing of mechanoreceptive input in capsaicin-induced secondary hyperalgesia in humans. J Physiol (Lond) 448: 765–780PubMedGoogle Scholar
  39. 39.
    Watson CP, Deck JH, Morshead C, Van der Kooy D, Evans RJ (1991) Post-herpetic neuralgia: further post-mortem studies of cases with and without pain. Pain 44:105–117CrossRefPubMedGoogle Scholar
  40. 40.
    Watson CP, Morshead C, Van der Kooy D, Deck J, Evans RJ (1988) Post-herpetic neuralgia: post-mortem analysis of a case. Pain 34:129–138CrossRefPubMedGoogle Scholar
  41. 41.
    Woolf CJ, Shortland P, Coggeshall RE (1992) Peripheral nerve injury triggers central sprouting of myelinated afferents. Nature 355:75–78CrossRefPubMedGoogle Scholar
  42. 42.
    Yarnitsky D, Ochoa JL (1990) Studies of heat pain sensation in man: perception thresholds, rate of stimulus rise and reaction time. Pain 40:85–91CrossRefPubMedGoogle Scholar
  43. 43.
    Zacks SI, Langfitt RW, Elliott FA (1964) Herpetic neuritis: a light and electron microscopic study. Neurology 14:744–750PubMedGoogle Scholar

Copyright information

© Steinkopff-Verlag 2005

Authors and Affiliations

  • G. Wasner
    • 1
  • A. Kleinert
    • 1
  • A. Binder
    • 1
  • J. Schattschneider
    • 1
  • R. Baron
    • 1
  1. 1.Dept. of Neurological Pain Research and TherapyNeurological Clinic, Universitätsklinikum Schleswig-Holstein, Campus KielKielGermany

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