A review of the effects of pregabalin on sleep disturbance across multiple clinical conditions

Sleep Medicine Reviews

Volumn 18, Issue 3, 2014, Pages 261-271

  Roth, Thomas ^a   Arnold, Lesley M ^b   Garcia Borreguero, Diego ^c   Resnick, Malca ^d   Clair, Andrew G ^d  

^a HENRY FORD HEALTH SYSTEM   (United States)

^b UNIVERSITY OF CINCINNATI   (United States)

^c SLEEP RESEARCH INSTITUTE   (Spain)

^d PFIZER INC   (United States)

Author keywords

Patient report; Polysomnography; Pregabalin; Sleep disturbance

Indexed keywords

PLACEBO; PREGABALIN;

DIABETIC PERIPHERAL NEUROPATHY; DRUG EFFECT; FIBROMYALGIA; FOCAL EPILEPSY; GENERALIZED ANXIETY DISORDER; HUMAN; NEUROPATHIC PAIN; OBSERVATIONAL STUDY; PARTIAL ONSET; PERIPHERAL NEUROPATHY; POLYSOMNOGRAPHY; POSTHERPETIC NEURALGIA; RESTLESS LEGS SYNDROME; REVIEW; SEIZURE; SLEEP DISORDER; SPINAL CORD INJURY;

EID: 84897115689     PISSN: 10870792     EISSN: 15322955     Source Type: Journal    
DOI: 10.1016/j.smrv.2013.07.005     Document Type: Review

References (97)

1. Hays R.D., Stewart A.L. Sleep measures. Measuring functioning and well being 1992, 235-259. Duke University Press, Durham, NC. A.L. Stewart, J.E. Ware (Eds.).
2. Hamilton M. The assessment of anxiety states by rating. Br J Med Psychol 1959, 32:50-55.
3. Hamilton M. Development of a rating scale for primary depressive illness. Br J Clin Psychol 1967, 6:278-296.
4. Vranken J.H. Mechanisms and treatment of neuropathic pain. Cent Nerv Syst Agents Med Chem 2009, 9:71-78.
5. Galer B.S., Gianas A., Jensen M.P. Painful diabetic polyneuropathy: epidemiology, pain description, and quality of life. Diabetes Res Clin Pract 2000, 47:123-128.
6. Widerstrom-Noga E.G., Felipe-Cuervo E., Yezierski R.P. Chronic pain after spinal injury: interference with sleep and daily activities. Arch Phys Med Rehabil 2001, 82:1571-1577.
7. Oster G., Harding G., Dukes E., Edelsberg J., Cleary P.D. Pain, medication use, and health-related quality of life in older persons with postherpetic neuralgia: results from a population-based survey. JPain 2005, 6:356-363.
8. Mundel T., Martin S., LaMoreaux L., Hotary L., Roth T. Polysomnographic evaluation of sleep disturbance in neuropathic pain. Sleep 2003, 26(abstract suppl.):A354.
9. Boyle J., Eriksson M.E., Gribble L., Gouni R., Johnsen S., Coppini D.V., et al. Randomized, placebo-controlled comparison of amitriptyline, duloxetine, and pregabalin in patients with chronic diabetic peripheral neuropathic pain: impact on pain, polysomnographic sleep, daytime functioning, and quality of life. Diabetes Care 2012, 35:2451-2458.
10. Richter R.W., Portenoy R., Sharma U., LaMoreaux L., Bockbrader H., Knapp L.E. Relief of painful diabetic peripheral neuropathy with pregabalin: a randomized, placebo-controlled trial. JPain 2005, 6:253-260.
11. Lesser H., Sharma U., LaMoreaux L., Poole R.M. Pregabalin relieves symptoms of painful diabetic neuropathy: a randomized controlled trial. Neurology 2004, 63:2104-2110.
12. Rosenstock J., Tuchman M., LaMoreaux L., Sharma U. Pregabalin for the treatment of painful diabetic peripheral neuropathy: a double-blind, placebo-controlled trial. Pain 2004, 110:628-638.
13. Tölle T., Freynhagen R., Versavel M., Trostmann U., Young J.P. Pregabalin for relief of neuropathic pain associated with diabetic neuropathy: a randomized, double-blind study. Eur J Pain 2008, 12:203-213.
14. Arezzo J.C., Rosenstock J., Lamoreaux L., Pauer L. Efficacy and safety of pregabalin 600mg/d for treating painful diabetic peripheral neuropathy: a double-blind placebo-controlled trial. BMC Neurol 2008, 8:33.
15. Satoh J., Yagihash S., Baba M., Suzuki M., Arakawa A., Yoshiyama T., et al. Efficacy and safety of pregabalin for treating neuropathic pain associated with diabetic peripheral neuropathy: a 14-week randomized, double-blind, placebo-controlled trial. Diabet Med 2011, 28:109-116.
16. Sabatowski R., Gálvez R., Cherry D.A., Jacquot F., Vincent E., Maisonobe P. Pregabalin reduces pain and improves sleep and mood disturbances in patients with post-herpetic neuralgia: results of a randomised, placebo-controlled clinical trial. Pain 2004, 109:26-35.
17. Dworkin R.H., Corbin A.E., Young J.P., Sharma U., LaMoreaux L., Bockbrader H., et al. Pregabalin for the treatment of postherpetic neuralgia: a randomized, placebo-controlled trial. Neurology 2003, 60:1274-1283.
18. van Seventer R., Feister H.A., Young J.P., Stoker M., Versavel M., Rigaudy L. 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, 22:375-384.
19. Stacey B., Barrett J.A., Whalen E., Phillips K.F., Rowbotham M. Pregabalin for postherpetic neuralgia: placebo-controlled trial of fixed and flexible dosing regimens on allodynia and time to onset of pain relief. JPain 2008, 9:1006-1017.
20. Ogawa S., Suzuki M., Arakawa A., Araki S., Yoshiyama T. Evaluation of the efficacy and safety of pregabalin in the treatment of postherpetic neuralgia - a randomized, double-blind, multicenter, placebo-controlled study. JJpn Soc Pain Clin 2010, 17:141-152.
21. Freynhagen R., Strojek K., Griesing T., Whalen E., Balkenohl M. Efficacy of pregabalin in neuropathic pain evaluated in a 12-week, randomised, double-blind, multicentre, placebo-controlled trial of flexible- and fixed-dose regimens. Pain 2005, 115:254-263.
22. Baron R., Brunnmüller U., Brasser M., May M., Binder A. Efficacy and safety of pregabalin in patients with diabetic peripheral neuropathy or postherpetic neuralgia: open-label, non-comparative, flexible-dose study. Eur J Pain 2008, 12:850-858.
23. Guan Y., Ding X., Cheng Y., Fan D., Tan L., Wang Y., et al. Efficacy of pregabalin for peripheral neuropathic pain: results of an 8-week, flexible-dose, double-blind, placebo-controlled study conducted in China. Clin Ther 2011, 33:159-166.
24. Siddall P.J., Cousins M.J., Otte A., Griesing T., Chambers R., Murphy T.K. Pregabalin in central neuropathic pain associated with spinal cord injury: a placebo-controlled trial. Neurology 2006, 67:1792-1800.
25. Cardenas D.D., Neishoff E.C., Suda K., Goto S., Sanin L., Kaneko T., et al. Arandomized trial of pregabalin in patients with neuropathic pain due to spinal cord injury. Neurology 2013, 80:533-539.
26. Saldaña M.T., Navarro A., Pérez C., Masramón X., Rejas J. Patient-reported-outcomes in subjects with painful lumbar or cervical radiculopathy treated with pregabalin: evidence from medical practice in primary care settings. Rheumatol Int 2010, 30:1005-1015.
27. Baron R., Freynhagen R., Tolle T., Cloutier C., Leon T., Murphy T.K., et al. The efficacy and safety of pregabalin in the treatment of neuropathic pain associated with chronic lumbosacral radiculopathy. Pain 2010, 150:420-427.
28. Kim J.S., Bashford G., Murphy T.K., Martin A., Dror V., Cheung R. Safety and efficacy of pregabalin in patients with central post-stroke pain. Pain 2011, 152:1018-1023.
29. van Seventer R., Bach F., Toth C., Serpell M., Temple J., Murphy T.K., et al. Pregabalin in the treatment of posttraumatic peripheral neuropathic pain: a randomized double-blind trial. Eur J Neurol 2010, 17:1082-1089.
30. Mańas A., Ciria J.P., Fernández M.C. Post hoc analysis of pregabalin vs. non-pregabalin treatment in patients with cancer-related neuropathic pain: better pain relief, sleep and physical health. Clin Transl Oncol 2011, 13:656-663.
31. Perez C., Navarro A., Saldana M.T., Martinez S., Rejas J. Patient-reported outcomes in subjects with painful trigeminal neuralgia receiving pregabalin: evidence from medical practice in primary care settings. Cephalalgia 2009, 29:781-790.
32. Simpson D.M., Schifitto G., Clifford D.B., Murphy T.K., Durso-De Cruz E., Glue P., et al. Pregabalin for painful HIV neuropathy: a randomized, double-blind, placebo-controlled trial. Neurology 2010, 74:413-420.
33. Xochilcal-Morales M., Manuel Castro E., Aniceto Guajardo-Rosas J., Nava Obergon T., Acevedo J., Gavidia Chucan M., et al. Aprospective, open-label, multicentre study of pregabalin in the treatment of neuropathic pain in Latin America. Int J Clin Pract 2010, 64:1301-1309.
34. Moon D.E., Lee D.I., Lee S.C., Song S.O., Yoon D.M., Yoon M.H., et al. The efficacy and safety of pregabalin using a flexible, optimized dose schedule in subjects with peripheral neuropathic pain: a 10-week, randomized, double-blind, placebo-controlled, multicenter study. Clin Ther 2010, 32:2370-2385.
35. Anastassiou E., Iatrou C.A., Vlaikidis N., Vafiadou M., Stamatiou G., Plesia E., et al. Impact of pregabalin treatment on pain, pain-related sleep interference and general well-being in patients with neuropathic pain: a non-interventional, multicentre, post-marketing study. Clin Drug Investig 2011, 31:417-426.
36. Pregabalin for peripheral neuropathic pain: results of a multicenter, non-comparative, open-label study in Indian patients. Int J Clin Pract 2006, 60:1060-1067. Lyrica Study Group.
37. Gilron I., Wajsbrot D., Therrien F., Lemay J. Pregabalin for peripheral neuropathic pain: a multicenter, enriched enrollment randomized withdrawal placebo-controlled trial. Clin J Pain 2011, 27:185-193.
38. Toelle T.R., Varvara R., Nimour M., Emir B., Brasser M. Pregabalin in neuropathic pain related to DPN, cancer and back pain: analysis of a 6-week observational study. Open Pain J 2012, 5:1-11.
39. Perez-Lloret S., Rojas G.M., Menoni M.C., Ruiz G., Velasquez C., Rodriguez H., et al. Pregabalin beneficial effects on sleep quality or health-related quality of life are poorly correlated with reduction on pain intensity after an 8-week treatment course. Clin Neuropharmacol 2012, 35:21-24.
40. van Seventer R., Serpell M., Bach F., Morlion B., Zlateva G., Bushmakin A.G., et al. Relationships between changes in pain severity and other patient-reported outcomes: an analysis in patients with posttraumatic peripheral neuropathic pain. Health Qual Life Outcomes 2011, 9.
41. Wolfe F., Clauw D.J., Fitzcharles M.A., Goldenberg D.L., Katz R.S., Mease P., et al. The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res 2010, 62:600-610.
42. Harding S.M. Sleep in fibromyalgia patients: subjective and objective findings. Am J Med Sci 1998, 315:367-376.
43. Branco J., Atalaia A., Paiva T. Sleep cycles and alpha-delta sleep in fibromyalgia syndrome. JRheumatol 1994, 21:1113-1117.
44. Rizzi M., Sarzi-Puttini P., Atzeni F., Capsoni F., Andreoli A., Pecis M., et al. Cyclic alternating pattern: a new marker of sleep alteration in patients with fibromyalgia?. JRheumatol 2004, 31:1193-1199.
45. Roth T., Lankford A., Bhadra P., Whalen E., Resnick E.M. Effect of pregabalin on sleep in patients with fibromyalgia and sleep maintenance disturbance: a randomized, placebo-controlled, 2-way crossover polysomnography study. Arthritis Care Res (Hoboken) 2012, 64:597-606.
46. Crofford L.J., Rowbotham M.C., Mease P.J., Russell I.J., Dworkin R.H., Corbin A.E., et al. Pregabalin for the treatment of fibromyalgia syndrome: results of a randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2005, 52:1264-1273. Pregabalin 1008-105 Study Group.
47. Mease P.J., Russell I.J., Arnold L., Florian H., Young J.P., Martin S.A., et al. Arandomized, double-blind, placebo-controlled, phase III trial of pregabalin in the treatment of patients with fibromyalgia. JRheumatol 2008, 35:502-514.
48. Arnold L.M., Russell I.J., Diri E.W., Duan W.R., Young J.P., Sharma U., et al. A14-week, randomized, double-blinded, placebo-controlled monotherapy trial of pregabalin in patients with fibromyalgia. JPain 2008, 9:792-805.
49. Pauer L., Winkelmann A., Arsenault P., Jespersen A., Whelan L., Atkinson G., et al. An international, randomised, double-blind, placebo-controlled, phase III trial of pregabalin monotherapy in the treatment of patients with fibromyalgia. JRheumatol 2011, 38:2643-2652.
50. Straube S., Derry S., Moore R.A., McQuay H.J. Pregabalin in fibromyalgia - meta-analysis of efficacy and safety from company clinical trial reports. Rheumatology (Oxford) 2010, 49:706-715.
51. Russell I.J., Crofford L.J., Cappelleri J., Bushmakin A., Sadosky A., Leon T., et al. The effect of pregabalin on sleep disturbance symptoms among individuals with fibromyalgia syndrome. Sleep Med 2009, 10:604-610.
52. Emir B., Murphy K., Petersel D., Whalen E. Treatment response to pregabalin in fibromyalgia: effect of patient baseline characteristics. Expert Opin Pharmacother 2010, 11:2275-2280.
53. Moore R.A., Straube S., Paine J., Phillips C., Derry S., McQuay H.J. Fibromyalgia: moderate and substantial pain intensity reduction predicts improvement in other outcomes and substantial quality of life gain. Pain 2010, 149:360-364.
54. Ekbom K.A. Restless legs syndrome. Acta Med Scand 1945, 158(Suppl.):122.
55. Hening W., Walters A.S., Allen R.P., Montplaisir J., Myers A., Ferini-Strambi L. Impact, diagnosis and treatment of restless legs syndrome (RLS) in a primary care population: the REST (RLS epidemiology, symptoms, and treatment) primary care study. Sleep Med 2004, 5:237-246.
56. Hornyak M., Feige B., Voderholzer U., Philipsen A., Riemann D. Polysomnography findings in patients with restless legs syndrome and in healthy controls: a comparative observational study. Sleep 2007, 30:861-865.
57. Allen R., Becker P.M., Bogan R., Schmidt M., Kushida C.A., Fry J.M., et al. Ropinirole decreases periodic leg movements and improves sleep parameters in patients with restless legs syndrome. Sleep 2004, 27:907-914.
58. Garcia-Borreguero D., Larrosa O., Williams A.M., Albares J., Pascual M., Palacios J.C., et al. Treatment of restless legs syndrome with pregabalin: a double-blind, placebo-controlled study. Neurology 2010, 74:1897-1904.
59. Allen R., Chen C., Soaita A., Wohlberg C., Knapp L., Peterson B.T., et al. Arandomized, double-blind, 6-week, dose-ranging study of pregabalin in patients with restless legs syndrome. Sleep Med 2010, 11:512-519.
60. de Weerd A., de Haas S., Otte A., Trenité D.K., van Erp G., Cohen A., et al. Subjective sleep disturbance in patients with partial epilepsy: a questionnaire-based study on prevalence and impact on quality of life. Epilepsia 2004, 45:1397-1404.
61. Touchon J., Baldy-Moulinier M., Billiard M., Besset A., Cadhillac J. Sleep organization and epilepsy. Epilepsy Res 1991, 2:73-81.
62. Bazil C.W. Epilepsy and sleep disturbance. Epilepsy Behav 2003, 4(Suppl.2):S39-S45.
63. Legros B., Bazil C.W. Effects of antiepileptic drugs on sleep architecture: a pilot study. Sleep Med 2003, 4:51-55.
64. Romigi A., Izzi F., Marciani M.G., Torelli F., Zannino S., Pisani L.R., et al. Pregabalin as add-on therapy induces REM sleep enhancement in partial epilepsy: a polysomnographic study. Eur J Neurol 2009, 16:70-75.
65. de Haas S., Otte A., de Weerd A., van Erp G., Cohen A., van Gerven J. Exploratory polysomnographic evaluation of pregabalin on sleep disturbance in patients with epilepsy. JClin Sleep Med 2007, 3:473-478.
66. Bazil C.W., Dave J., Cole J., Stalvey J., Drake E. Pregabalin increases slow-wave sleep and may improve attention in patients with partial epilepsy and insomnia. Epilepsy Behav 2012, 23:422-425.
67. Lee B.I., Yi S., Hong S.B., Kim M.-K., Lee S.A., Lee S.K., et al. Pregabalin add-on therapy using a flexible, optimized dose schedule in refractory partial epilepsies: a double-blind, randomized, placebo-controlled, multicenter trial. Epilepsia 2009, 50:464-474.
68. Rivera-Castaño L., Leal-Cantu R., Abreu P., Guerrero M., Davila G. A21-week open-label clinical trial of pregabalin as an add-on therapy in partial seizures at multiple centers in Mexico (PREPS Mexico). Epilepsy Res 2012, 100:74-79.
69. Sancho J., Ivanez V., Molins A., Lopez Gomez V., Masramon X., Perez M. Changes in seizures severity and quality of life in patients with refractory partial epilepsy. Epilepsy Behav 2010, 19:409-413.
70. Tsounis S., Kimiskidis V., Kazis D., Gkiatas K., Garganis K., Karageorgiou K., et al. An open-label, add-on study of pregabalin in patients with partial seizures: a multicenter trial in Greece. Seizure 2011, 20:701-705.
71. Ryvlin P., Kalviainen R., Von Raison F., Giordano S., Emir B. Pregabalin in partial seizures: a pragmatic 21-week, open-label study (PREPS). Eur J Neurol 2010, 17:726-732.
72. Papadimitriou G.N., Linkowski P. Sleep disturbance in anxiety disorders. Int Rev Psychiatry 2005, 17:229-236.
73. Johnson E.O., Roth T., Breslau N. The association of insomnia with anxiety disorders and depression: exploration of the direction of risk. JPsychiatr Res 2006, 40:700-708.
74. Monti J.M., Monti D. Sleep disturbance in generalized anxiety disorder and its treatment. Sleep Med Rev 2000, 4:263-276.
75. Fuller K.H., Waters W.F., Binks P.G., Anderson T. Generalized anxiety and sleep architecture: a polysomnographic investigation. Sleep 1997, 20:370-376.
76. Kasper S., Herman B., Nivoli G., Van Ameringen M., Petralia A., Mandel F., et al. Efficacy of pregabalin and venlafaxine-XR in generalized anxiety disorder: results of a double-blind, placebo-controlled 8-week trial. Int Clin Psychopharmacol 2009, 24:87-96.
77. Feltner D.E., Crockatt J.G., Dubovsky S.J., Cohn C.K., Shrivastava R.K., Targum S.D., et al. Arandomized, double-blind, placebo-controlled, fixed-dose, multicenter study of pregabalin in patients with generalized anxiety disorder. JClin Psychopharmacol 2003, 23:240-249.
78. Pande A.C., Crockatt J.G., Feltner D.E., Janney C.A., Smith W.T., Weisler R., et al. Pregabalin in generalized anxiety disorder: a placebo-controlled trial. Am J Psychiatry 2003, 160:533-540.
79. Pohl R.B., Feltner D.E., Fieve R.R., Pande A.C. Efficacy of pregabalin in the treatment of generalized anxiety disorder: double-blind, placebo-controlled comparison of BID versus TID dosing. JClin Psychopharmacol 2005, 25:151-158.
80. Rickels K., Pollack M.H., Feltner D.E., Lydiard R.B., Zimbroff D.L., Bielski R.J., et al. Pregabalin for treatment of generalized anxiety disorder: a 4-week, multicenter, double-blind, placebo-controlled trial of pregabalin and alprazolam. Arch Gen Psychiatry 2005, 62:1022-1030.
81. Montgomery S.A., Tobias K., Zornberg G.L., Kasper S., Pande A.C. Efficacy and safety of pregabalin in the treatment of generalized anxiety disorder: a 6-week, multicenter, randomized, double-blind, placebo-controlled comparison of pregabalin and venlafaxine. JClin Psychiatry 2006, 67:771-782.
82. Montgomery S., Chatamra K., Pauer L., Whalen E., Baldinetti F. Efficacy and safety of pregabalin in elderly people with generalised anxiety disorder. Br J Psychiatry 2008, 193:389-394.
83. Feltner D., Wittchen H.U., Kavoussi R., Brock J., Baldinetti F., Pande A.C. Long-term efficacy of pregabalin in generalized anxiety disorder. Int Clin Psychopharmacol 2008, 23:18-28.
84. Lydiard R.B., Rickels K., Herman B., Feltner D.E. Comparative efficacy of pregabalin and benzodiazepines in treating the psychic and somatic symptoms of generalized anxiety disorder. Int J Neuropsychopharmacol 2010, 13:229-241.
85. Montgomery S.A., Herman B.K., Schweizer E., Mandel F.S. Efficacy of pregabalin and benzodiazepines in generalized anxiety disorder presenting with high levels of insomnia. Int Clin Psychopharmacol 2009, 24:214-222.
86. Bollu V., Bushmakin A., Cappelleri J., Chen C., Feltner D., Wittchen H. Pregabalin reduces sleep disturbance in patients with generalized anxiety disorder via both direct and indirect mechanisms. Eur J Psychiatry 2010, 24:18-27.
87. Rubio G., Bobes J., Cervera G., Teran A., Perez M., Lopez-Gomez V., et al. Effects of pregabalin on subjective sleep disturbance symptoms during withdrawal from long-term benzodiazepine use. Eur Addict Res 2011, 17:262-270.
88. Hindmarch I., Dawson J., Stanley N. Adouble-blind study in healthy volunteers to assess the effects on sleep of pregabalin compared with alprazolam and placebo. Sleep 2005, 28:187-193.
89. Garcia-Borreguero D., Larrosa O., de la Llave Y., Verger K., Masramon X., Hernandez G. Treatment of restless legs syndrome with gabapentin: a double-blind, cross-over study. Neurology 2002, 59:1573-1579.
90. Kushida C.A., Walters A.S., Becker P., Thein S.G., Perkins A.T., Roth T., et al. Arandomized, double-blind, placebo-controlled, crossover study of XP13512/GSK1838262 in the treatment of patients with primary restless legs syndrome. Sleep 2009, 32:159-168.
91. Winkelman J.W., Bogan R.K., Schmidt M.H., Hudson J.D., DeRossett S.E., Hill-Zabala C.E. Randomized polysomnography study of gabapentin enacarbil in subjects with restless legs syndrome. Mov Disord 2011, 26:2065-2072.
92. Foldvary-Schaefer N., De Leon Sanchez I., Karafa M., Mascha E., Dinner D., Morris H.H. Gabapentin increases slow-wave sleep in normal adults. Epilepsia 2002, 43:1493-1497.
93. Lo H., Yang C., Lo H.G., Lee C., Ting H., Tzang B. Treatment effects of gabapentin for primary insomnia. Clin Neuropharmacol 2010, 33:84-90.
94. Walsh J.K., Roth T. Pharmacologic treatment of insomnia: benzodiazepine receptor agonists. Principles and practice of sleep medicine 2011, 905-915. Elsevier Saunders, St. Louis, MO. 5th ed. M.H. Kryger, T. Roth, W.C. Dement (Eds.).
95. Dooley D.J., Taylor C.P., Donevan S., Feltner D. Ca2+ channel alpha2delta ligands: novel modulators of neurotransmission. Trends Pharmacol Sci 2007, 28:75-82.
96. Lyrica US prescribing information [online]. Available at: [accessed 01.07.13]. http://labeling.pfizer.com/ShowLabeling.aspx?id=561.
97. Pauer L., Atkinson G., Murphy T.K., Petersel D., Zeiher B. Long-term maintenance of response across multiple fibromyalgia symptom domains in a randomized withdrawal study of pregabalin. Clin J Pain 2012, 7:609-614.