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Neuropathic Pain and Sickle Cell Disease: a Review of Pharmacologic Management

  • Other Pain (N Vadivelu and AD Kaye, Section Editors)
  • Published:
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Abstract

Purpose of Review

Sickle cell disease (SCD) remains among the most common and severe monogenic disorders present in the world today. Although sickle cell pain has been traditionally characterized as nociceptive, a significant portion of sickle cell patients has reported neuropathic pain symptoms. Our review article will discuss clinical aspects of SCD-related neuropathic pain, epidemiology of neuropathic pain among individuals with SCD, pain mechanisms, and current and future potential pharmacological interventions.

Recent Findings

Neuropathic pain in SCD is a complicated condition that often has a lifelong and significant negative impact on life; therefore, improved pain management is considered a significant and unmet need. Neuropathic pain mechanisms are heterogeneous, and the difficulty in determining their individual contribution to specific pain types may contribute to poor treatment outcomes in this population.

Summary

Our review article outlines several pharmacological modalities which may be employed to treat neuropathic pain in SCD patients.

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References

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. •• Ashley-Koch A, Yang Q, Olney RS. Sickle hemoglobin (Hb S) allele and sickle cell disease: a HuGE review. Am J Epidemiol. 2000;151(9):839–45. Very strong review manuscript summarizing the pathophysiology of sickle cell pain and its treatment modalities.

  2. Platt OS, Thorington BD, Brambilla DJ, Milner PF, Rosse WF, Vichinsky E, et al. Pain in sickle cell disease–rates and risk factors. N Engl J Med. 1991;325:11–6.

    Article  CAS  PubMed  Google Scholar 

  3. Platt OS, Brambilla DJ, Rosse WF, Milner PF, Castro O, Steinberg MH, et al. Mortality in sickle cell disease–life expectancy and risk factors for early death. N Engl J Med. 1994;330:1639–44.

    Article  CAS  PubMed  Google Scholar 

  4. Hassell KL. Population estimates of sickle cell disease in the U.S. Am J Prev Med. 2010;38(Suppl):S512–21.

    Article  PubMed  Google Scholar 

  5. •• Piel FB, Patil AP, Howes RE, et al. Global epidemiology of sickle haemoglobin in neonates: a contemporary geostatistical model-based map and population estimates. Lancet. 2013;381:142–51. Very strong review manuscript summarizing the pathophysiology of sickle cell pain and its treatment modalities.

  6. Ballas SK. Current issues in sickle cell pain and its management. Hematology. 2007;2007(1):97–105.

    Article  Google Scholar 

  7. Rees DC, Williams TN, Gladwin MT. Sickle-cell disease. Lancet. 2010;376:2018–31.

    Article  CAS  PubMed  Google Scholar 

  8. Manwani D, Frenette PS. Vaso-occlusion in sickle cell disease: pathophysiology and novel targeted therapies. Blood. 2013;122(24):3892–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Uwaezuoke SN, Ayuk AC, Ndu IK, Eneh C, Mbanefo NR, Ezenwosu OU. Vaso-occlusive crisis in sickle cell disease: current paradigm on pain management. J Pain Res. 2018;11:3141–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Brandow AM, Farley RA, Panepinto JA. Neuropathic pain in patients with sickle cell disease. Pediatr Blood Cancer. 2014;61(3):512–7.

    Article  PubMed  Google Scholar 

  11. Antunes FD, Propheta VG, Vasconcelos HA, Cipopolotti R. Neuropathic pain in patients with sickle cell disease: a cross-sectional study assessing teens and young adults. Ann Hematol. 2017;96(7):1121–5.

    Article  CAS  PubMed  Google Scholar 

  12. Charache S, Terrin ML, Moore RD, Dover GJ, Barton FB, Eckert SV, et al. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. N Engl J Med. 1995;332:1317–22.

    Article  CAS  PubMed  Google Scholar 

  13. Okpala I. Leukocyte adhesion and the pathophysiology of sickle cell disease. Curr Opin Hematol. 2006;13(1):40–4.

    Article  CAS  PubMed  Google Scholar 

  14. Nkrumah FK, Neequaye JE, Ankra-Badu G. Bone marrow in sickle cell anaemia at time of anaemic crisis. Arch Dis Child. 1984;59(6):561–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Brandow AM, Panepinto JA. Clinical interpretation of quantitative sensory testing as a measure of pain sensitivity in patients with sickle cell disease. J Pediatr Hematol Oncol. 2016;38(4):288–93.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Pope M, Albo C, Kidwell KM. Evolution of chronic pain in sickle-cell disease. Blood. 2016;128(22):1297.

    Article  Google Scholar 

  17. Ahmadi M, Poormansouri S, Beiranvand S, Sedighie L. Predictors and correlates of fatigue in sickle cell disease patients. Int J Hematol Oncol Stem Cell Res. 2018;12(1):69–76.

    PubMed  PubMed Central  Google Scholar 

  18. Aguilar C, Vichinsky E, Neumayr L. Bone and joint disease in sickle cell disease. Hematol Oncol Clin N Am. 2005;19:929–41.

    Article  Google Scholar 

  19. Adam SS, Flahiff CM, Kamble S, Telen MJ, Reed SD, de Castro LM. Depression, quality of life, and medical resource utilization in sickle cell disease. Blood Adv. 2017;1(23):1983–92.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Mahdi N, Al-Ola K, Khalek NA, Almawi WY. Depression, anxiety, and stress comorbidities in sickle cell anemia patients with vaso-occlusive crisis. J Pediatr Hematol Oncol. 2010;32(5):345–9.

    Article  PubMed  Google Scholar 

  21. Hasan SP, Hashmi S, Alhassen M, Lawson W, Castro O. Depression in sickle cell disease. J Natl Med Assoc. 2003;95(7):533–7 http://www.ncbi.nlm.nih.gov/pubmed/12911250.

    PubMed  PubMed Central  Google Scholar 

  22. Belgrave FZ, Molock SD. The role of depression in hospital admissions and emergency treatment of patients with sickle cell disease. J Natl Med Assoc. 1991;83:777–81.

    PubMed  PubMed Central  CAS  Google Scholar 

  23. Benton TD, Ifeagqu JA, Smith-Whitley K. Anxiety and depression in children and adolescents with sickle cell disease. Curr Psych Rep. 2007;9:114–21.

    Article  Google Scholar 

  24. Levenson JL, McClish DK, Dahman BA, Bovbjerg VE, et al. Depression and anxiety in adults with sickle cell disease: the PiSCES project. Psychosom Med. 2008;70(2):192–6.

    Article  PubMed  Google Scholar 

  25. Treede RD, Jensen TS, Campbell JN, et al. Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology. 2008;70(18):1630–5.

    Article  CAS  PubMed  Google Scholar 

  26. Torrance N, Smith BH, Bennett MI, Lee AJ. The epidemiology of chronic pain of predominantly neuropathic origin: results from a general population survey. J Pain. 2006;7:281–9.

    Article  PubMed  Google Scholar 

  27. •• Gustorff B, Dorner T, Likar R, et al. Prevalence of self-reported neuropathic pain and impact on quality of life: a prospective representative survey. Acta Anaesthesiol Scand. 2008;52:132–6. Very strong review manuscript summarizing the pathophysiology of sickle cell pain and its treatment modalities.

  28. Bouhassira D, Lanteri-Minet M, Attal N, et al. Prevalence of chronic pain with neuropathic characteristics in the general population. Pain. 2008;136:380–7.

    Article  PubMed  Google Scholar 

  29. Haanpaa M, Attal N, Backonja M, et al. NeuPSIG guidelines on neuropathic pain assessment. Pain. 2011;152(1):14–27.

    Article  PubMed  Google Scholar 

  30. Ballas S. Sickle cell disease and sickle cell pain mimic other disorders. J Pain. 2012;13(4):S11. https://doi.org/10.1016/j.jpain.2012.01.050.

    Article  Google Scholar 

  31. Asher SW. Multiple cranial neuropathies, trigeminal neuralgia, and vascular headaches in sickle cell disease, a possible common mechanism. Neurology. 1980;30(2):210. https://doi.org/10.1212/wnl.30.2.210.

    Article  PubMed  CAS  Google Scholar 

  32. Konotey-Ahulc F. Mental-nerve neuropathy: a complication of sickle-cell crisis. Lancet. 1972;300(7773):388. https://doi.org/10.1016/s0140-6736(72)91788-6.

    Article  Google Scholar 

  33. Slavin ML, Barondes MJ. Ischemic optic neuropathy in sickle cell disease. Am J Ophthalmol. 1988;105(2):212–3. https://doi.org/10.1016/0002-9394(88)90191-2.

    Article  PubMed  CAS  Google Scholar 

  34. Rothman SM, Nelson JS. Spinal cord infarction in a patient with sickle cell anemia. Neurology. 1980;30(10):1072. https://doi.org/10.1212/wnl.30.10.1072.

    Article  PubMed  CAS  Google Scholar 

  35. Shields RW, Harris JW, Clark M. Mononeuropathy in sickle cell anemia: anatomical and pathophysiological basis for its rarity. Muscle Nerve. 1991;14(4):370–4. https://doi.org/10.1002/mus.880140412.

    Article  PubMed  Google Scholar 

  36. Wilkie DJ, Molokie R, Boyd-Seal D, Suarez ML, Kim YO, Zong S, et al. Patient-reported outcomes: descriptors of nociceptive and neuropathic pain and barriers to effective pain management in adult outpatients with sickle cell disease. J Natl Med Assoc. 2010;102(1):18–27. https://doi.org/10.1016/s0027-9684(15)30471-5.

    Article  PubMed  Google Scholar 

  37. Brandow AM, Stucky CL, Hillery CA, Hoffmann RG, Panepinto JA. Patients with sickle cell disease have increased sensitivity to cold and heat. Am J Hematol. 2012;88(1):37–43. https://doi.org/10.1002/ajh.23341.

    Article  PubMed  PubMed Central  Google Scholar 

  38. O’Leary JD, Crawford MW, Odame I, Shorten GD, Mcgrath PA. Thermal pain and sensory processing in children with sickle cell disease. Clin J Pain. 2014;30(3):244–50. https://doi.org/10.1097/ajp.0b013e318292a38e.

    Article  PubMed  Google Scholar 

  39. Ezenwa MO, Molokie RE, Wang ZJ, Yao Y, Suarez ML, Pullum C, et al. Safety and utility of quantitative sensory testing among adults with sickle cell disease: indicators of neuropathic pain? Pain Practice. 2015;16(3):282–93. https://doi.org/10.1111/papr.12279.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Campbell CM, Moscou-Jackson G, Carroll CP, Kiley K, Haywood C, Lanzkron S, ... Haythornthwaite JA (2016). An evaluation of central sensitization in patients with sickle cell disease. J Pain, 17(5), 617–627. doi:https://doi.org/10.1016/j.jpain.2016.01.475.

  41. Paszty C. Transgenic knockout mice with exclusively human sickle hemoglobin and sickle cell disease. Science. 1997;278(5339):876–8. https://doi.org/10.1126/science.278.5339.876.

    Article  PubMed  CAS  Google Scholar 

  42. Kohli DR, Li Y, Khasabov SG, Gupta P, Kehl LJ, Ericson ME, et al. Pain-related behaviors and neurochemical alterations in mice expressing sickle hemoglobin: modulation by cannabinoids. Blood. 2010;116(3):456–65. https://doi.org/10.1182/blood-2010-01-260372.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Zappia KJ, Garrison SR, Hillery CA, Stucky CL. Cold hypersensitivity increases with age in mice with sickle cell disease. Pain. 2014;155(12):2476–85. https://doi.org/10.1016/j.pain.2014.05.030.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Cataldo G, Rajput S, Gupta K, Simone DA. Sensitization of nociceptive spinal neurons contributes to pain in a transgenic model of sickle cell disease. Pain. 2015;156(4):722–30. https://doi.org/10.1097/j.pain.0000000000000104.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Uhelski ML, Gupta K, Simone DA. Sensitization of C-fiber nociceptors in mice with sickle cell disease is decreased by local inhibition of anandamide hydrolysis. Pain. 2017;158(9):1711–22. https://doi.org/10.1097/j.pain.0000000000000966.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Vincent L, Vang D, Nguyen J, Gupta M, Luk K, Ericson ME, et al. Mast cell activation contributes to sickle cell pathobiology and pain in mice. Blood. 2013;122(11):1853–62. https://doi.org/10.1182/blood-2013-04-498105.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Zuo Y, Perkins NM, Tracey DJ, Geczy CL. Inflammation and hyperalgesia induced by nerve injury in the rat: a key role of mast cells. Pain. 2003;105(3):467–79. https://doi.org/10.1016/s0304-3959(03)00261-6.

    Article  PubMed  Google Scholar 

  48. Amadesi S. Protease-activated receptor 2 sensitizes the capsaicin receptor transient receptor potential vanilloid receptor 1 to induce hyperalgesia. J Neurosci. 2004;24(18):4300–12. https://doi.org/10.1523/jneurosci.5679-03.2004.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Hillery CA, Kerstein PC, Vilceanu D, Barabas ME, Retherford D, Brandow AM, et al. Transient receptor potential vanilloid 1 mediates pain in mice with severe sickle cell disease. Blood. 2011;118(12):3376–83. https://doi.org/10.1182/blood-2010-12-327429.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Ristoiu V, Shibasaki K, Uchida K, Zhou Y, Ton BT, Flonta M, et al. Hypoxia-induced sensitization of transient receptor potential vanilloid 1 involves activation of hypoxia-inducible factor-1 alpha and PKC. Pain. 2011;152(4):936–45. https://doi.org/10.1016/j.pain.2011.02.024.

    Article  PubMed  CAS  Google Scholar 

  51. Sadler K, Zappia K, Weyer A, Ohara C, Hillery C, Stucky C. Chemokine receptor 2 (CCR2) mediates persistent sickle cell disease pain. J Pain. 2018;19(3):S13. https://doi.org/10.1016/j.jpain.2017.12.062.

    Article  Google Scholar 

  52. Chen Y, Luo F, Yang C, Kirkmire CM, Wang ZJ. Acute inhibition of Ca2/calmodulin-dependent protein kinase II reverses experimental neuropathic pain in mice. J Pharmacol Exp Ther. 2009;330(2):650–9. https://doi.org/10.1124/jpet.109.152165.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Zeitz K, Giese K, Silva A, Basbaum A. The contribution of autophosphorylated alpha-calcium–calmodulin kinase II to injury-induced persistent pain. Neuroscience. 2004;128(4):889–98. https://doi.org/10.1016/j.neuroscience.2004.07.029.

    Article  PubMed  CAS  Google Scholar 

  54. Price TJ, Jeske NA, Flores CM, Hargreaves KM. Pharmacological interactions between calcium/calmodulin-dependent kinase II α and TRPV1 receptors in rat trigeminal sensory neurons. Neurosci Lett. 2005;389(2):94–8. https://doi.org/10.1016/j.neulet.2005.07.029.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Wang ZJ, Wilkie DJ, Molokie R. Neurobiological mechanisms of pain in sickle cell disease. Hematology. 2010;2010(1):403–8. https://doi.org/10.1182/asheducation-2010.1.403.

    Article  PubMed  Google Scholar 

  56. He Y, Wilkie DJ, Nazari J, Wang R, Messing RO, Desimone J, et al. PKCδ-targeted intervention relieves chronic pain in a murine sickle cell disease model. J Clin Investig. 2016;126(8):3053–7. https://doi.org/10.1172/jci86165.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Cain DM, Vang D, Simone DA, Hebbel RP, Gupta K. Mouse models for studying pain in sickle disease: effects of strain, age, and acuteness. Br J Haematol. 2011;156(4):535–44. https://doi.org/10.1111/j.1365-2141.2011.08977.x.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. Lei J, Benson B, Tran H, Ofori-Acquah SF, Gupta K. Comparative analysis of pain behaviours in humanized mouse models of sickle cell anemia. PLoS One. 2016;11(8):e0160608. https://doi.org/10.1371/journal.pone.0160608.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Kenyon N, Wang L, Spornick N, Khaibullina A, Almeida LE, Cheng Y, et al. Sickle cell disease in mice is associated with sensitization of sensory nerve fibers. Exp Biol Med. 2014;240(1):87–98. https://doi.org/10.1177/1535370214544275.

    Article  CAS  Google Scholar 

  60. Wang Y, Wang X, Chen W, Gupta K, Zhu X. Functional MRI BOLD response in sickle mice with hyperalgesia. Blood Cell Mol Dis. 2017;65:81–5. https://doi.org/10.1016/j.bcmd.2017.03.005.

    Article  CAS  Google Scholar 

  61. Vang D, Paul JA, Nguyen J, Tran H, Vincent L, Yasuda D, et al. Small-molecule nociceptin receptor agonist ameliorates mast cell activation and pain in sickle mice. Haematologica. 2015;100(12):1517–25. https://doi.org/10.3324/haematol.2015.128736.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Stojanovic KS, Thiolière B, Garandeau E, Lecomte I, Bachmeyer C, Lionnet F. Chronic myeloid leukaemia and sickle cell disease: could imatinib prevent vaso-occlusive crisis? Br J Haematol. 2011;155(2):271–2. https://doi.org/10.1111/j.1365-2141.2011.08670.x.

    Article  CAS  Google Scholar 

  63. Murphy M, Close J, Lottenberg R, Rajasekhar A. Effectiveness of imatinib therapy for sickle cell anemia and chronic myeloid leukemia. Am J Med Sci. 2014;347(3):254–5. https://doi.org/10.1097/maj.0000000000000228.

    Article  PubMed  Google Scholar 

  64. Luo F, Yang C, Chen Y, Shukla P, Tang L, Wang LX, et al. Reversal of chronic inflammatory pain by acute inhibition of Ca2/calmodulin-dependent protein kinase II. J Pharmacol Exp Ther. 2008;325(1):267–75. https://doi.org/10.1124/jpet.107.132167.

    Article  PubMed  CAS  Google Scholar 

  65. Molokie RE, Wilkie DJ, Wittert H, Suarez ML, Yao Y, Zhao Z, et al. Mechanism-driven phase I translational study of trifluoperazine in adults with sickle cell disease. Eur J Pharmacol. 2014;723:419–24. https://doi.org/10.1016/j.ejphar.2013.10.062.

    Article  PubMed  CAS  Google Scholar 

  66. Attal N, Cruccu G, Baron R, Haanpää M, Hansson P, Jensen TS, et al. EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision. Eur J Neurol. 2010;17(9):1113–e88. https://doi.org/10.1111/j.1468-1331.2010.02999.x.

    Article  PubMed  CAS  Google Scholar 

  67. Finnerup N, Attal N, Haroutounian S. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. J Vasc Surg. 2015;62(4):1091. https://doi.org/10.1016/j.jvs.2015.08.010.

    Article  Google Scholar 

  68. Moulin D, Boulanger A, Clark A, Clarke H, Dao T, Finley G, ... Williamson, O. (2014). Pharmacological management of chronic neuropathic pain: revised consensus statement from the Canadian Pain Society. Pain Res Manag 19(6), 328–335. doi:https://doi.org/10.1155/2014/754693.

  69. Neuropathic pain in adults: pharmacological management in non-specialist settings. (n.d.). Retrieved from https://www.nice.org.uk/Guidance/CG173

  70. Lee Y-C, Chen P-P. A review of SSRIs and SNRIs in neuropathic pain. Expert Opin Pharmacother. 2010;11(17):2813–25. https://doi.org/10.1517/14656566.2010.507192.

    Article  PubMed  CAS  Google Scholar 

  71. Fields HL, Heinricher MM, Mason P. Neurotransmitters in nociceptive modulatory circuits. Annu Rev Neurosci. 1991;14:219–45. https://doi.org/10.1146/annurev.ne.14.030191.001251.

    Article  PubMed  CAS  Google Scholar 

  72. Sindrup SH, Otto M, Finnerup NB, Jensen TS. Antidepressants in the treatment of neuropathic pain. Basic Clin Pharmacol Toxicol. 2005;96(6):399–409. https://doi.org/10.1111/j.1742-7843.2005.pto_96696601.x.

    Article  CAS  PubMed  Google Scholar 

  73. Simpson D. Gabapentin and venlafaxine for the treatment of painful diabetic neuropathy. J Clin Neuromuscul Dis. 2001;3(2):53–62 http://www.ncbi.nlm.nih.gov/pubmed/19078655.

    Article  CAS  PubMed  Google Scholar 

  74. Ballas SK, Gupta K, Adams-Graves P. Sickle cell pain: a critical reappraisal. Blood. 2012;120(18):3647–56. https://doi.org/10.1182/blood-2012-04-383430.

    Article  PubMed  CAS  Google Scholar 

  75. Field MJ, Cox PJ, Stott E, Melrose H, Offord J, Su TZ, et al. Identification of the 2- -1 subunit of voltage-dependent calcium channels as a molecular target for pain mediating the analgesic actions of pregabalin. Proc Natl Acad Sci. 2006;103(46):17537–42. https://doi.org/10.1073/pnas.0409066103.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  76. Luo ZD, Calcutt NA, Higuera ES, Valder CR, Song YH, Svensson CI, et al. Injury type-specific calcium channel alpha 2delta -1 subunit up-regulation in rat neuropathic pain models correlates with antiallodynic effects of gabapentin. J Pharmacol Exp Ther. 2002;303(3):1199–205. https://doi.org/10.1124/jpet.102.041574.

    Article  PubMed  CAS  Google Scholar 

  77. Kukkar A, Bali A, Singh N, Jaggi AS. Implications and mechanism of action of gabapentin in neuropathic pain. Arch Pharm Res. 2013;36(3):237–51. https://doi.org/10.1007/s12272-013-0057-y.

    Article  PubMed  CAS  Google Scholar 

  78. Maneuf Y, Blake R, Andrews N, McKnight A. Reduction by gabapentin of K + -evoked release of [ 3 H]-glutamate from the caudal trigeminal nucleus of the streptozotocin-treated rat. Br J Pharmacol. 2004;141(4):574–9. https://doi.org/10.1038/sj.bjp.0705579.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Yoshizumi M, Parker RA, Eisenach JC, Hayashida K. Gabapentin inhibits γ-amino butyric acid release in the locus coeruleus but not in the spinal dorsal horn after peripheral nerve injury in rats. Anesthesiology. 2012;116(6):1347–53. https://doi.org/10.1097/ALN.0b013e318254e6fd.

    Article  PubMed  CAS  Google Scholar 

  80. Butkovic D, Toljan S, Mihovilovic-Novak B. Experience with gabapentin for neuropathic pain in adolescents: report of five cases. Pediatr Anesth. 2006;16(3):325–9. https://doi.org/10.1111/j.1460-9592.2005.01687.x.

    Article  Google Scholar 

  81. Low AK, Ward K, Wines AP. Pediatric complex regional pain syndrome. J Pediatr Orthop. 2007;27(5):567–72. https://doi.org/10.1097/BPO.0b013e318070cc4d.

    Article  PubMed  Google Scholar 

  82. Rusy L, Troshynski T, Weisman S. Gabapentin in phantom limb pain management in children and young adults: report of seven cases. J Pain Symptom Manag. 2001;21(1):78–82 http://www.ncbi.nlm.nih.gov/pubmed/11223317.

    Article  CAS  Google Scholar 

  83. Lauder GR, White MC. Neuropathic pain following multilevel surgery in children with cerebral palsy: a case series and review. Pediatr Anesth. 2005;15(5):412–20. https://doi.org/10.1111/j.1460-9592.2005.01431.x.

    Article  CAS  Google Scholar 

  84. Friedrichsdorf SJ, Nugent AP. Management of neuropathic pain in children with cancer. Curr Opin Support Palliat Care. 2013;7(2):131–8. https://doi.org/10.1097/SPC.0b013e3283615ebe.

    Article  PubMed  Google Scholar 

  85. Nottage KA, Hankins JS, Faughnan LG, James DM, Richardson J, Christensen R, et al. Addressing challenges of clinical trials in acute pain: the pain management of vaso-occlusive crisis in children and young adults with sickle cell disease study. Clin Trials J Soc Clin Trials. 2016;13(4):409–16. https://doi.org/10.1177/1740774516636573.

    Article  Google Scholar 

  86. •• Gilron I, Bailey JM, Tu D, Holden RR, Weaver DF, Houlden RL. Morphine, gabapentin, or their combination for neuropathic pain. N Engl J Med. 2005;352(13):1324–34. https://doi.org/10.1056/NEJMoa042580. Very strong review manuscript summarizing the pathophysiology of sickle cell pain and its treatment modalities.

  87. •• Backonja M, Glanzman RL. Gabapentin dosing for neuropathic pain: evidence from randomized, placebo-controlled clinical trials. Clin Ther. 2003;25(1):81–104. https://doi.org/10.1016/S0149-2918(03)90011-7. Very strong review manuscript summarizing the pathophysiology of sickle cell pain and its treatment modalities.

  88. Brandow AM, Farley RA, Dasgupta M, Hoffmann RG, Panepinto JA. The use of neuropathic pain drugs in children with sickle cell disease is associated with older age, female sex, and longer length of hospital stay. J Pediatr Hematol Oncol. 2015;37(1):10–5. https://doi.org/10.1097/MPH.0000000000000265.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  89. Schlaeger JM, Molokie RE, Yao Y, Suarez ML, Golembiewski J, Wilkie DJ, et al. Management of sickle cell pain using pregabalin: a pilot study. Pain Manag Nurs. 2017;18(6):391–400. https://doi.org/10.1016/j.pmn.2017.07.003.

    Article  PubMed  Google Scholar 

  90. Correia CR, Soares AT, Azurara L, Palaré MJ. Use of gabapentin in the treatment of chronic pain in an adolescent with sickle cell disease. BMJ Case Rep. 2017;bcr-2016-218614. doi:https://doi.org/10.1136/bcr-2016-218614.

  91. Miroslav B, Beydoun A, Edwards KR, Schwartz SL, Fonseca V, Hes M, et al. Gabapentin for the symptomatic treatment of painful neuropathy in patients with diabetes mellitus: a randomized controlled trial. JAMA. 1998;280(21):1831. https://doi.org/10.1001/jama.280.21.1831.

    Article  Google Scholar 

  92. Bockbrader HN, Wesche D, Miller R, Chapel S, Janiczek N, Burger P. A comparison of the pharmacokinetics and pharmacodynamics of pregabalin and gabapentin. Clin Pharmacokinet. 2010;49(10):661–9. https://doi.org/10.2165/11536200-000000000-00000.

    Article  PubMed  CAS  Google Scholar 

  93. Pérez C, Navarro A, Saldaña MT, Masramón X, Rejas J. Pregabalin and gabapentin in matched patients with peripheral neuropathic pain in routine medical practice in a primary care setting: findings from a cost-consequences analysis in a nested case-control study. Clin Ther. 2010;32(7):1357–70. https://doi.org/10.1016/j.clinthera.2010.07.014.

    Article  PubMed  Google Scholar 

  94. Pathan H, Williams J. Basic opioid pharmacology: an update. Br J Pain. 2012;6(1):11–6. https://doi.org/10.1177/2049463712438493.

    Article  PubMed  PubMed Central  Google Scholar 

  95. Baron R, Binder A, Wasner G. Neuropathic pain: diagnosis, pathophysiological mechanisms, and treatment. Lancet Neurol. 2010;9(8):807–19. https://doi.org/10.1016/S1474-4422(10)70143-5.

    Article  PubMed  Google Scholar 

  96. •• Rowbotham MC, Twilling L, Davies PS, Reisner L, Taylor K, Mohr D. Oral opioid therapy for chronic peripheral and central neuropathic pain. N Engl J Med. 2003;348(13):1223–32. https://doi.org/10.1056/NEJMoa021420. Very strong review manuscript summarizing the pathophysiology of sickle cell pain and its treatment modalities.

  97. McNicol ED, Midbari A, Eisenberg E. Opioids for neuropathic pain. Cochrane Database Syst Rev. 2013. https://doi.org/10.1002/14651858.CD006146.pub2.

  98. •• Smith HS. Opioids and neuropathic pain. Pain Physician. 2012;15(3 Suppl):ES93–110 http://www.ncbi.nlm.nih.gov/pubmed/22786465. Very strong review manuscript summarizing the pathophysiology of sickle cell pain and its treatment modalities.

  99. Brookoff D, Polomano R. Treating sickle cell pain like cancer pain. Ann Intern Med. 1992;116(5):364–8 http://www.ncbi.nlm.nih.gov/pubmed/1736768.

    Article  CAS  PubMed  Google Scholar 

  100. Fein DM, Avner JR, Scharbach K, Manwani D, Khine H. Intranasal fentanyl for initial treatment of vaso-occlusive crisis in sickle cell disease. Pediatr Blood Cancer. 2017;64(6):e26332. https://doi.org/10.1002/pbc.26332.

    Article  CAS  Google Scholar 

  101. Kelly GS, Stewart RW, Strouse JJ, Anders JF. Intranasal fentanyl improves time to analgesic delivery in sickle cell pain crises. Am J Emerg Med. 2018;36(7):1305–7. https://doi.org/10.1016/j.ajem.2017.11.015.

    Article  PubMed  Google Scholar 

  102. LeBlanc Z, Vance C, Payne J, Zhang J, Hilliard L, Lebensburger JD, et al. Management of severe chronic pain with methadone in pediatric patients with sickle cell disease. Pediatr Blood Cancer. 2018;65(8):e27084. https://doi.org/10.1002/pbc.27084.

    Article  PubMed  CAS  Google Scholar 

  103. Cole TB, Sprinkle RH, Smith SJ, Buchanan GR. Intravenous narcotic therapy for children with severe sickle cell pain crisis. Am J Dis Child. 1986;140(12):1255–9 http://www.ncbi.nlm.nih.gov/pubmed/3776942.

    PubMed  CAS  Google Scholar 

  104. Gerber N, Apseloff G. Death from a morphine infusion during a sickle cell crisis. J Pediatr. 1993;123(2):322–5. https://doi.org/10.1016/S0022-3476(05)81713-5.

    Article  PubMed  CAS  Google Scholar 

  105. Jones CM, Paulozzi LJ, Mack KA. Sources of prescription opioid pain relievers by frequency of past-year nonmedical use. JAMA Intern Med. 2014;174(5):802–3. https://doi.org/10.1001/jamainternmed.2013.12809.

    Article  PubMed  PubMed Central  Google Scholar 

  106. Darbari DS, Neely M, van den Anker J, Rana S. Increased clearance of morphine in sickle cell disease: implications for pain management. J Pain. 2011;12(5):531–8. https://doi.org/10.1016/j.jpain.2010.10.012.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  107. Weber M, Vang D, Velho P, et al. Morphine promotes renal pathology in sickle mice. Int J Nephrol Renov Dis. 2012;109. https://doi.org/10.2147/IJNRD.S33813.

  108. Birken CS, Khambalia A, Dupuis A, Pastor A, Lee M, Padavattan K, et al. Morphine is associated with acute chest syndrome in children hospitalized with sickle cell disease. Hosp Pediatr. 2013;3(2):149–55 http://www.ncbi.nlm.nih.gov/pubmed/24340416.

    Article  PubMed  Google Scholar 

  109. Kopecky EA, Jacobson S, Joshi P, Koren G. Systemic exposure to morphine and the risk of acute chest syndrome in sickle cell disease. Clin Pharmacol Ther. 2004;75(3):140–6. https://doi.org/10.1016/j.clpt.2003.10.007.

    Article  PubMed  CAS  Google Scholar 

  110. Finklestein Y, Schechter T, Garcia-Bournissen F, et al. Is morphine exposure associated with acute chest syndrome in children with vaso-occlusive crisis of sickle cell disease? A 6-year case-crossover study. Clin Ther. 2007;29(12):2738–43. https://doi.org/10.1016/j.clinthera.2007.12.016.

    Article  CAS  Google Scholar 

  111. Gupta M, Msambichaka L, Ballas SK, Gupta K. Morphine for the treatment of pain in sickle cell disease. Sci World J. 2015;2015:1–10. https://doi.org/10.1155/2015/540154.

    Article  CAS  Google Scholar 

  112. Cummins TR. Setting up for the block: the mechanism underlying lidocaine’s use-dependent inhibition of sodium channels. J Physiol. 2007;582(1):11. https://doi.org/10.1113/jphysiol.2007.136671.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  113. •• Sommer C, Cruccu G. Topical treatment of peripheral neuropathic pain: applying the evidence. J Pain Symptom Manag. 2017;53(3):614–29. https://doi.org/10.1016/j.jpainsymman.2016.09.015. Very strong review manuscript summarizing the pathophysiology of sickle cell pain and its treatment modalities.

  114. •• Derry S, Wiffen PJ, Moore RA, Quinlan J. Topical lidocaine for neuropathic pain in adults. In: Derry S, editor. Cochrane database of systematic reviews. Chichester: John Wiley & Sons, Ltd; 2014. https://doi.org/10.1002/14651858.CD010958.pub2.

    Chapter  Google Scholar 

  115. Katz NP, Gammaitoni AR, Davis MW, Dworkin RH. Lidocaine patch 5% reduces pain intensity and interference with quality of life in patients with postherpetic neuralgia: an effectiveness trial. Pain Med. 2002;3(4):324–32. https://doi.org/10.1046/j.1526-4637.2002.02050.x.

    Article  PubMed  Google Scholar 

  116. Devers A, Galer BS. Topical lidocaine patch relieves a variety of neuropathic pain conditions: an open-label study. Clin J Pain. 2000;16(3):205–8 http://www.ncbi.nlm.nih.gov/pubmed/11014393.

    Article  CAS  PubMed  Google Scholar 

  117. Galer BS, Rowbotham MC, Perander J, Friedman E. Topical lidocaine patch relieves postherpetic neuralgia more effectively than a vehicle topical patch: results of an enriched enrollment study. Pain. 1999;80(3):533–8. https://doi.org/10.1016/S0304-3959(98)00244-9.

    Article  PubMed  CAS  Google Scholar 

  118. Rowbotham MC, Davies PS, Fields HL. Topical lidocaine gel relieves postherpetic neuralgia. Ann Neurol. 1995;37(2):246–53. https://doi.org/10.1002/ana.410370216.

    Article  PubMed  CAS  Google Scholar 

  119. Rowbotham MC, Fields HL. Topical lidocaine reduces pain in post-herpetic neuralgia. Pain. 1989;38(3):297–301. https://doi.org/10.1016/0304-3959(89)90216-9.

    Article  PubMed  CAS  Google Scholar 

  120. Cheville AL, Sloan JA, Northfelt DW, Jillella AP, Wong GY, Bearden III JD, et al. Use of a lidocaine patch in the management of postsurgical neuropathic pain in patients with cancer: a phase III double-blind crossover study (N01CB). Support Care Cancer. 2009;17(4):451–60. https://doi.org/10.1007/s00520-008-0542-x.

    Article  PubMed  PubMed Central  Google Scholar 

  121. Ho K-Y, Huh BK, White WD, Yeh C-C, Miller EJ. Topical amitriptyline versus lidocaine in the treatment of neuropathic pain. Clin J Pain. 2008;24(1):51–5. https://doi.org/10.1097/AJP.0b013e318156db26.

    Article  PubMed  Google Scholar 

  122. Rousseau V, Morelle M, Arriuberge C, Darnis S, Chabaud S, Launay V, et al. Efficacy and tolerance of lidocaine 5% patches in neuropathic pain and pain related to vaso-occlusive sickle cell crises in children: a prospective multicenter clinical study. Pain Pract. 2018;18(6):788–97. https://doi.org/10.1111/papr.12674.

    Article  PubMed  Google Scholar 

  123. Rasolofo J, Poncelet M, Rousseau V, Marec-Berard P. Efficacité des emplâtres de lidocaïne 5% sur les douleurs des crises vaso-occlusives chez l’enfant drépanocytaire. Arch Pédiatrie. 2013;20(7):762–7. https://doi.org/10.1016/j.arcped.2013.04.013.

    Article  CAS  Google Scholar 

  124. Manzanares J, Julian M, Carrascosa A. Role of the cannabinoid system in pain control and therapeutic implications for the management of acute and chronic pain episodes. Curr Neuropharmacol. 2006;4(3):239–57 http://www.ncbi.nlm.nih.gov/pubmed/18615144.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Richardson JD. Cannabinoids modulate pain by multiple mechanisms of action. J Pain. 2000;1(1):2–14. https://doi.org/10.1016/S1526-5900(00)90082-8.

    Article  Google Scholar 

  126. Small-Howard AL, Shimoda LMN, Adra CN, Turner H. Anti-inflammatory potential of CB1-mediated cAMP elevation in mast cells. Biochem J. 2005;388(2):465–73. https://doi.org/10.1042/BJ20041682.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  127. Valenzano KJ, Tafesse L, Lee G, Harrison JE, Boulet JM, Gottshall SL, et al. Pharmacological and pharmacokinetic characterization of the cannabinoid receptor 2 agonist, GW405833, utilizing rodent models of acute and chronic pain, anxiety, ataxia and catalepsy. Neuropharmacology. 2005;48(5):658–72. https://doi.org/10.1016/j.neuropharm.2004.12.008.

    Article  PubMed  CAS  Google Scholar 

  128. Whiting PF, Wolff RF, Deshpande S, di Nisio M, Duffy S, Hernandez AV, et al. Cannabinoids for medical use. JAMA. 2015;313(24):2456–73. https://doi.org/10.1001/jama.2015.6358.

    Article  PubMed  CAS  Google Scholar 

  129. Herzberg U, Eliav E, Bennett G, Kopin IJ. The analgesic effects of R(+)-WIN 55,212–2 mesylate, a high affinity cannabinoid agonist, in a rat model of neuropathic pain. Neurosci Lett. 1997;221(2–3):157–60. https://doi.org/10.1016/S0304-3940(96)13308-5.

    Article  PubMed  CAS  Google Scholar 

  130. Karst M, Salim K, Burstein S, Conrad I, Hoy L, Schneider U. Analgesic effect of the synthetic cannabinoid CT-3 on chronic neuropathic pain. JAMA. 2003;290(13):1757–62. https://doi.org/10.1001/jama.290.13.1757.

    Article  PubMed  CAS  Google Scholar 

  131. Stockings E, Campbell G, Hall WD, Nielsen S, Zagic D, Rahman R, et al. Cannabis and cannabinoids for the treatment of people with chronic noncancer pain conditions. Pain. 2018;159(10):1932–54. https://doi.org/10.1097/j.pain.0000000000001293.

    Article  PubMed  CAS  Google Scholar 

  132. Mücke M, Phillips T, Radbruch L, Petzke F, Häuser W. Cannabis-based medicines for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2018. https://doi.org/10.1002/14651858.CD012182.pub2.

  133. Vincent L, Vang D, Nguyen J, Benson B, Lei J, Gupta K. Cannabinoid receptor-specific mechanisms to alleviate pain in sickle cell anemia via inhibition of mast cell activation and neurogenic inflammation. Haematologica. 2016;101(5):566–77. https://doi.org/10.3324/haematol.2015.136523.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  134. Howard J, Anie KA, Holdcroft A, Korn S, Davies SC. Cannabis use in sickle cell disease: a questionnaire study. Br J Haematol. 2005;131(1):123–8. https://doi.org/10.1111/j.1365-2141.2005.05723.x.

    Article  PubMed  Google Scholar 

  135. Wambebe CO, Bamgboye EA, Badru BO, Khamofu H, Momoh JA, Ekpeyong M, et al. Efficacy of niprisan in the prophylactic management of patients with sickle cell disease. Curr Ther Res. 2001;62(1):26–34. https://doi.org/10.1016/S0011-393X(01)80039-4.

    Article  CAS  Google Scholar 

  136. Ameh SJ, Tarfa FD, Ebeshi BU. Traditional herbal management of sickle cell anemia: lessons from Nigeria. Anemia. 2012;2012:1–9. https://doi.org/10.1155/2012/607436.

    Article  Google Scholar 

  137. Courts J, Maskill V, Gray A, Glue P. Signs and symptoms associated with synthetic cannabinoid toxicity: systematic review. Australas Psychiatry. 2016;24(6):598–601. https://doi.org/10.1177/1039856216663733.

    Article  PubMed  Google Scholar 

  138. •• Dzierżanowski T. Prospects for the use of cannabinoids in oncology and palliative care practice: a review of the evidence. Cancers (Basel). 2019;11(2):129. https://doi.org/10.3390/cancers11020129. Very strong review manuscript summarizing the pathophysiology of sickle cell pain and its treatment modalities.

  139. Semple DM, McIntosh AM, Lawrie SM. Cannabis as a risk factor for psychosis: systematic review. J Psychopharmacol. 2005;19(2):187–94. https://doi.org/10.1177/0269881105049040.

    Article  PubMed  Google Scholar 

  140. Ibrahim MM, Deng H, Zvonok A, Cockayne DA, Kwan J, Mata HP, et al. Activation of CB2 cannabinoid receptors by AM1241 inhibits experimental neuropathic pain: pain inhibition by receptors not present in the CNS. Proc Natl Acad Sci. 2003;100(18):10529–33. https://doi.org/10.1073/pnas.1834309100.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  141. Dhopeshwarkar A, Mackie K. CB2 cannabinoid receptors as a therapeutic target--what does the future hold? Mol Pharmacol. 2014;86(4):430–7. https://doi.org/10.1124/mol.114.094649.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Mariam Salisu Orhurhu & Vwaire Orhurhu

  2. Johns Hopkins School of Medicine, Baltimore, MD, USA

    Robert Chu, Lauren Claus & Jacob Roberts

  3. Meharry Medical College, Nashville, TN, USA

    Bisi Salisu

  4. Department of Anesthesia, Critical Care, and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Boston, MA, 02215, USA

    Ivan Urits

  5. Massachusetts College of Pharmacy and Health Sciences, Boston, MA, USA

    Ejovwoke Orhurhu

  6. Valley Anesthesiology and Pain Consultants, Phoenix, AZ, USA

    Omar Viswanath & Alan D. Kaye

  7. Department of Anesthesiology, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, USA

    Omar Viswanath & Alan D. Kaye

  8. Department of Anesthesiology, Creighton University School of Medicine, Omaha, NE, USA

    Omar Viswanath & Alan D. Kaye

  9. Department of Anesthesiology, Louisiana State University Health Sciences Center, New Orleans, LA, USA

    Omar Viswanath & Alan D. Kaye

  10. Department of Anesthesiology, Medical University South Carolina, Charleston, SC, USA

    Aaron J. Kaye

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Mariam Salisu Orhurhu, Robert Chu, Lauren Claus, Jacob Roberts, Bisi Salisu, Ivan Urits, Ejovwoke Orhurhu, Omar Viswanath, Alan D Kaye, Aaron J. Kaye, and Vwaire Orhurhu declare no conflict of interest. Dr. Kaye is a Section Editor for the journal. He has not been involved in the review of this manuscript. He is also a speaker for Merck.

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Orhurhu, M.S., Chu, R., Claus, L. et al. Neuropathic Pain and Sickle Cell Disease: a Review of Pharmacologic Management. Curr Pain Headache Rep 24, 52 (2020). https://doi.org/10.1007/s11916-020-00885-5

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