Drugs & Aging

, Volume 26, Issue 10, pp 883–892


In the Treatment of Postherpetic Neuralgia
Adis Drug Profile


  • ▲ Pregabalin is the pharmacologically active S-enantiomer of 3-aminomethyl-5-methyl-hexanoic acid. It has a similar pharmacological profile to that of its developmental predecessor gabapentin, but had greater analgesic activity in rodent models of neuropathic pain.

  • ▲ Pregabalin is thought to act by reducing the excessive release of several excitatory neurotransmitters by binding to the α2-δ protein subunit of voltage-gated calcium channels.

  • ▲ Oral pregabalin 150–600 mg/day, administered in two or three divided doses, was significantly more effective than placebo in relieving pain and improving pain-related sleep interference in four randomized, double-blind, multicentre studies of 4–13 weeks’ duration in patients with postherpetic neuralgia (PHN).

  • ▲ Pregabalin achieved a faster onset of pain relief than placebo. The median times to the onset of pain relief with fixed and flexible doses of pregabalin were 1.5 and 3.5 days compared with <4 weeks with placebo.

  • ▲ Pregabalin was generally well tolerated when titrated over 1 week to fixed dosages (maximum 600 mg/day) in clinical trials in mostly elderly PHN patients. Adverse events were usually mild to moderate in severity.


  1. 1.
    Zin CS, Nissen LM, Smith MT, et al. An update on the pharmacological management of post-herpetic neuralgia and painful diabetic neuropathy. CNS Drugs 2008; 22(5): 417–42PubMedCrossRefGoogle Scholar
  2. 2.
    Kanazi GE, Johnson RW, Dworkin RH. Treatment of postherpetic neuralgia: an update. Drugs 2000 May; 59(5): 1113–26PubMedCrossRefGoogle Scholar
  3. 3.
    van Wijck AJM, Opstelten W, van Essen GA, et al. Long term follow-up of herpes zoster patients: a prospective cohort. In: van Wijck AJM. Postherpetic neuralgia [thesis]. Utrecht: Utrecht University, 2006: 60–70Google Scholar
  4. 4.
    Dworkin RH, O’Connor AB, Backonja M, et al. Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain 2007; 132: 237–51PubMedCrossRefGoogle Scholar
  5. 5.
    Gilron I, Bailey JM, Tu D, et al. Morphine, gabapentin, or their combination for neuropathic pain. N Engl J Med 2005 Mar; 352(13): 1324–34PubMedCrossRefGoogle Scholar
  6. 6.
    Huckle R. Pregabalin Pfizer. Curr Opin Investig Drugs 2004; 5(1): 82–9Google Scholar
  7. 7.
    Frampton JE, Foster RH. Pregabalin in the treatment of postherpetic neuralgia. Drugs 2005; 65(1): 111–8PubMedCrossRefGoogle Scholar
  8. 8.
    Bryans JS, Wustrow DJ. 3-Substituted GABA analogs with central nervous system activity: a review. Med Res Rev 1999; 19: 149–77PubMedCrossRefGoogle Scholar
  9. 9.
    Lauria-Horner BA, Pohl RB. Pregabalin: a new anxiolytic. Expert Opin Investig Drugs 2003; 12(4): 663–72PubMedCrossRefGoogle Scholar
  10. 10.
    Taylor CP, Angelotti T, Fauman E, et al. Pharmacology and mechanism of action of pregabalin: the calcium channel α2-δ (alpha2-delta) subunit as a target for antiepileptic drug discovery. Epilepsy Res 2007; 73: 137–50PubMedCrossRefGoogle Scholar
  11. 11.
    Fink K, Dooley DJ, Meder WP, et al. Inhibition of neuronal Ca2+ influx by gabapentin and pregabalin in the human neocortex. Neuropharmacology 2002 Feb; 42(2): 229–36PubMedCrossRefGoogle Scholar
  12. 12.
    Dooley DJ, Donovan CM, Meder WP, et al. Preferential action of gabapentin and pregabalin at P/Q-type voltage-sensitive calcium channels: inhibition of K+-evoked [3H]-norepinephrine release from rat neocortical slices. Synapse 2002 Sep 1;45(3): 171–90PubMedCrossRefGoogle Scholar
  13. 13.
    Dooley DJ, Taylor CP, Donevan S, et al. Ca2+ channel α2δ ligands: novel modulators of neurotransmission. Trends Pharmacol Sci 2007; 28(2): 75–82PubMedCrossRefGoogle Scholar
  14. 14.
    Field MJ, Cox PJ, Stott E, et al. Identification of the α2-δ-1 subunit of voltage-dependent calcium channels as a molecular target for pain mediating the analgesic actions of pregabalin. Proc Natl Acad Sci U S A 2006; 103(46): 17537–42PubMedCrossRefGoogle Scholar
  15. 15.
    Belliotti TR, Capiris T, Ekhato IV, et al. Structure-activity relationships of pregabalin and analogues that target the α2-δ protein. J Med Chem 2005 Apr; 48(7): 2294–307PubMedCrossRefGoogle Scholar
  16. 16.
    Pfizer. Lyrica® (pregabalin): full prescribing information [online]. Available from URL: http://www.pfizer.com/files/products/uspi_lyrica.pdf [Accessed 2009 May 19]
  17. 17.
    Nozaki-Taguchi N, Chaplan SR, Higuera ES, et al. Vincristine-induced allodynia in the rat. Pain 2001 Jul; 93(1): 69–76PubMedCrossRefGoogle Scholar
  18. 18.
    Field MJ, McCleary S, Hughes J, et al. Gabapentin and pre-gabalin, but not morphine and amitriptyline, block both static and dynamic components of mechanical allodynia induced by streptozocin in the rat. Pain 1999 Mar; 80(1–2): 391–8PubMedCrossRefGoogle Scholar
  19. 19.
    Field MJ, Bramwell S, Hughes J, et al. Detection of static and dynamic components of mechanical allodynia in rat models of neuropathic pain: are they signalled by distinct primary sensory neurones? Pain 1999 Nov; 83(2): 303–11PubMedCrossRefGoogle Scholar
  20. 20.
    Wallin J, Cui JG, Yakhnitsa V, et al. Gabapentin and pregabalin suppress tactile allodynia and potentiate spinal cord stimulation in a model of neuropathy. Eur J Pain 2002; 6(4): 261–72PubMedCrossRefGoogle Scholar
  21. 21.
    Chen SR, Xu Z, Pan HL. Stereospecific effect of pregabalin on ectopic afferent discharges and neuropathic pain induced by sciatic nerve ligation in rats. Anesthesiology 2001 Dec; 95(6): 1473–9PubMedCrossRefGoogle Scholar
  22. 22.
    Field MJ, Holloman EF, McCleary S, et al. Evaluation of gabapentin and S-(+)-3-isobutylgaba in a rat model of post-operativepain. J Pharmacol Exp Ther 1997 Sep; 282(3): 1242–6PubMedGoogle Scholar
  23. 23.
    Field MJ, Oles RJ, Lewis AS, et al. Gabapentin (neurontin) and S-(+)-3-isobutylgaba represent a novel class of selective antihyperalgesic agents. Br J Pharmacol 1997 Aug; 121(8): 1513–22PubMedCrossRefGoogle Scholar
  24. 24.
    Hurley RW, Chatterjea D, Rose Feng M, et al. Gabapentin and pregabalin can interact synergistically with naproxen to produce antihyperalgesia. Anesthesiology 2002 Nov; 97(5): 1263–73PubMedCrossRefGoogle Scholar
  25. 25.
    Partridge BJ, Chaplan SR, Sakamoto E, et al. Characterization of the effects of gabapentin and 3-isobutyl-γ-aminobutyric acid on substance P-induced thermal hyperalgesia. Anesthesiology 1998 Jan; 88(1): 196–205PubMedCrossRefGoogle Scholar
  26. 26.
    Jun JH, Yaksh TL. The effect of intrathecal gabapentin and 3-isobutyl-γ-aminobutyric acid on the hyperalgesia observed after thermal injury in the rat. Anesth Analg 1998 Feb; 86(2): 348–54PubMedGoogle Scholar
  27. 27.
    Jones DL, Sorkin LS. Systemic gabapentin and S(+)-3-isobutyl-γ-aminobutyric acid block secondary hyperalgesia. Brain Res 1998 Nov 9; 810(1–2): 93–9PubMedCrossRefGoogle Scholar
  28. 28.
    Fehrenbacher JC, Taylor CP, Vasko MR. Pregabalin and gabapentin reduce release of substance P and CGRP from rat spinal tissues only after inflammation or activation of protein kinase C. Pain 2003; 105: 133–44PubMedCrossRefGoogle Scholar
  29. 29.
    Hindmarch I, Trick L, Ridout F, et al. A double-blind, placebo- and positive-internal-controlled (alprazolam) investigation of the cognitive and psychomotor profile of pregabalin in healthy volunteers. Psychopharmacology (Berl) 2005 Dec; 183(2): 133–43CrossRefGoogle Scholar
  30. 30.
    Bockbrader HN, Hunt T, Strand J, et al. Pregabalin pharmacokinetics and safety in healthy volunteers: results from two phase 1 studies. [abstract no. P06.051]. Neurology 2000 Apr; 54Suppl. 3: 421Google Scholar
  31. 31.
    Dworkin RH, Corbin AE, Young Jr JP, et al. Pregabalin for the treatment of postherpetic neuralgia: a randomized, placebo-controlled trial. Neurology 2003 Apr 22; 60(8): 1274–83PubMedCrossRefGoogle Scholar
  32. 32.
    Randinitis EJ, Posvar EL, Alvey CW, et al. Pharmacokinetics of pregabalin in subjects with various degrees of renal function. J Clin Pharmacol 2003 Mar; 43(3): 277–83PubMedCrossRefGoogle Scholar
  33. 33.
    Busch JA, Strand JC, Posvar EL, et al. Pregabalin (CL-1008) single-dose pharmacokinetics and safety/tolerance in healthy subjects after oral administration of pregabalin solution or capsule doses [abstract no. 2.108]. Epilepsia 1998; 39Suppl. 6: 58Google Scholar
  34. 34.
    Sabatowski R, Galvez R, Cherry DA, et al. Pregabalin reduces pain and improves sleep and mood disturbances in patients with postherpetic neuralgia: results of a randomised, placebo-controlled clinical trial. Pain 2004; 109: 26–35PubMedCrossRefGoogle Scholar
  35. 35.
    van Seventer R, Feister HA, Young JP, et al. Efficacy and tolerability of twice-daily pregabalin for treating pain and related sleep interference in postherpetic neuralgia: a 13-week, randomized trial. Curr Med Res Opin 2006; 22(2): 375–84PubMedCrossRefGoogle Scholar
  36. 36.
    Stacey BR, Barrett JA, Whalen E, et al. Pregabalin for postherpetic neuralgia: placebo-controlled trial of fixed and flexible dosing regimens on allodynia and time to onset of pain relief. J Pain 2008; 9(11): 1006–17PubMedCrossRefGoogle Scholar
  37. 37.
    Stacey BR, Dworkin RH, Murphy K, et al. Pregabalin in the treatment of refractory neuropathic pain: results of a 15-month open-label trial. Pain Med 2008; 9(8): 1202–08PubMedCrossRefGoogle Scholar
  38. 38.
    Farrar JT, Young Jr JP, LaMoreaux L, et al. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain 2001 Nov; 94(2): 149–58PubMedCrossRefGoogle Scholar
  39. 39.
    Rodriguez MJ, Diaz S, Vera-Llonch M, et al. Cost-effectiveness analysis of pregabalin versus gabapentin in the managment of neuropathic pain due to diabetic polyneuropathy or post-herpetic neuralgia. Curr Med Res Opin 2007; 23(10): 2585–96PubMedCrossRefGoogle Scholar
  40. 40.
    Tarride J-E, Gordon A, Vera-Llonch M, et al. Cost-effectiveness of pregabalin for the management of neuropathic pain associated with diabetic peripheral neuropathy and postherpetic neuralgia: a Canadian perspective. Clin Ther 2006; 28(11): 1922–34PubMedCrossRefGoogle Scholar
  41. 41.
    O’Connor AB, Noyes K, Holloway RG. A cost-effectiveness comparison of despiramine, gabapentin, and pregabalin for treating postherpetic neuralgia. J Am Geriatr Soc 2007; 55: 1176–84PubMedCrossRefGoogle Scholar
  42. 42.
    Liedgrens H, Hertel N, Gabriel A, et al. Cost-effectiveness analysis of a lidocaine 5% medicated plaster compared with gabapentin and pregabalin for treating postherpetic neuralgia: a German perspective. Clin Drug Invest 2008; 28(9): 583–601CrossRefGoogle Scholar
  43. 43.
    Smith KJ, Roberts MS. Sequential medication strategies for postherpetic neuralgia: a cost-effectiveness analysis. J Pain 2007; 8(5): 396–404PubMedCrossRefGoogle Scholar
  44. 44.
    European Medicines Agency. Lyrica® (pregabalin): summary of product characteristics [online]. Available from URL: http://www.emea.europa.eu/humandocs/PDFs/EPAR/lyrica [Accessed 2009 May 19]

Copyright information

© Adis Data Information BV 2009

Authors and Affiliations

  1. 1.Adis, a Wolters Kluwer BusinessMairangi Bay, North Shore 0754, AucklandNew Zealand

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