Year 2020 / Volume 27 / Number 4

Special Article

Clinical pathophysiology in patients with sickle cell disease: the transition from acute to chronic pain

Rev. Soc. Esp. Dolor. 2020; 27(4): 257-268 / DOI: 10.20986/resed.2020.3814/2020

Borja Mugabure, Silvia González, Amaia Uría, Antía Osorio


ABSTRACT

Patients with sickle cell disease (SCD) suffer from severe pain that often begins in childhood and increases in severity over the course of a lifetime, leading to hospitalization and poor quality of life over the years. A unique feature of SCD is vase-occlusive crises (VOC) characterized by recurrent and unpredictable episodes of acute pain. Microvascular occlusion during a VOC results in decreased oxygen supply to the periphery and injury from ischemia and subsequent reperfusion, inflammation, oxidative stress and endothelial dysfunction, all of which can perpetuate a harmful pain-causing microenvironment. On the other hand, in addition to episodic acute pain, SCD patients also report chronic pain, defined as almost daily pain over a 6-month period associated to either sicologic or social morbidities. They may be due to chronic lesions such as skin ulcers, avascular bone necrosis or infarctions in various organs. In addition, central sensitization appears to be directly involved in the chronicity of pain and there is a clearly under-diagnosed and under-treated component of neuropathic pain. Current treatment of moderate to severe pain in SCD is based primarily on opioids; either as an oral quick release outpatient or in the form of patient-controlled intravenous analgesia in the hospital. However, long-term opioid use is associated with multiple side effects. This review presents the latest advances in the understanding of the pathology of pain in SCD and describes objectives based on mechanisms that may help to develop new therapeutic and/or preventive strategies to improve pain in SCD.



RESUMEN

Los pacientes con enfermedad de células falciformes (ECF), también denominada drepanocítica, sufren un dolor intenso que suele comenzar durante la infancia y aumenta su gravedad a lo largo de la vida, lo que lleva a la hospitalización y a una mala calidad de vida a lo largo de los años. Una característica única de la ECF son las crisis vaso-oclusivas (CVO), caracterizadas por episodios recurrentes e impredecibles de dolor agudo. La obstrucción microvascular durante una CVO provoca una disminución del suministro de oxígeno a la periferia y una lesión por isquemia y posterior reperfusión, inflamación, estrés oxidativo y disfunción endotelial, todo lo cual puede perpetuar un microambiente nocivo que provoca dolor. Por otro lado, además de los dolores agudos episódicos, los pacientes con ECF también padecen dolor crónico, definido como dolor casi diario durante un periodo de 6 meses, asociado a trastornos psicosociales. Pueden deberse a lesiones crónicas como úlceras cutáneas, necrosis avascular ósea o infartos en diversos órganos. Asimismo, la sensibilización central parece estar directamente involucrada en la cronicidad del dolor y existe un componente de dolor neuropático claramente infradiagnosticado e infratratado. El tratamiento actual del dolor moderado a intenso en la ECF se basa principalmente en la administración de los opioides, vía oral, de liberación rápida ambulatoria o en forma de analgesia controlada por el paciente vía intravenosa intrahospitalaria. Sin embargo, el uso de opioides a largo plazo está asociado con múltiples efectos secundarios. Esta revisión presenta los últimos avances en la comprensión de la fisiopatología del dolor en la ECF y se describen los mecanismos subyacentes que pueden ayudar a desarrollar nuevas estrategias terapéuticas y/o preventivas para mejorar el dolor en la ECF.





Complete Article

Nuevo comentario

Security code:
CAPTCHA code image
Speak the codeChange the code
 

Comentarios

No comments in this article

Bibliografía

1. Steinberg MH. Management of sickle cell disease. N Engl J Med. 1999;340(13):1021-30. DOI: 10.1056/NEJM199904013401307.
2. Hassell KL. Population estimates of sickle cell disease in the US. Am J Prev Med. 2010;38(4 Suppl.):S512-21. DOI: 10.1016/j.amepre.2009.12.022.
3. Modell B, Darlison M. Global epidemiology of haemoglobin disorders and derived service indicators. Bull World Health Organ. 2008;86(6):480-7. DOI: 10.2471/blt.06.036673.
4. Lanzkron S, Carroll CP, Haywood C Jr. The burden of emergency department use for sickle-cell disease: an analysis of the national emergency department sample database. Am J Hematol. 2010;85(10):797-9. DOI: 10.1002/ajh.21807.
5. Han J, Saraf SL, Zhang X, Gowhari M, Molokie RE, Hassan J, et al. Patterns of opioid use in sickle cell disease. Am J Hematol. 2016;91(11):1102-6. DOI: 10.1002/ajh.24498.
6. Brousseau DC, Owens PL, Mosso AL, Panepinto JA, Steiner CA. Acute care utilization and rehospitalizations for sickle cell disease. JAMA. 2010;303(13):1288-94. DOI: 10.1001/jama.2010.378.
7. Smith WR, Penberthy LT, Bovbjerg VE, McClish DK, Roberts JD, Dahman B, et al. Daily assessment of pain in adults with sickle cell disease. Ann Intern Med. 2008;148(2):94-101. DOI: 148/2/94 [pii].
8. Sil S, Cohen LL, Dampier C. Psychosocial and functional outcomes in youth with chronic sickle cell pain. Clin J Pain. 2016;32(6):527-33. DOI: 10.1097/AJP.0000000000000289.
9. Bakshi N, Ross D, Krishnamurti L. Presence of pain on three or more days of the week is associated with worse patient reported outcomes in adults with sickle cell disease. J Pain Res. 2018;11:313-8. DOI: 10.2147/JPR.S150065.
10. Brandow AM, Brousseau DC, Pajewski NM, Panepinto JA. Vaso-occlusive painful events in sickle cell disease: impact on child well-being. Pediatr Blood Cancer. 2010;54(1):92-7. DOI: 10.1002/pbc.22222.
11. Wong TE, Brandow AM, Lim W, Lottenberg R. Update on the use of hydroxyurea therapy in sickle cell disease. Blood. 2014;124(26):3850-7. DOI: 10.1182/blood-2014-08-435768.
12. FDA. Approved L-Glutamine Powder for the Treatment of Sickle Cell Disease. (Cited 1 October 2017). Available from: https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm566097.htm.
13. Tran H, Gupta M, Gupta K. Targeting novel mechanisms of pain in sickle cell disease. Blood. 2017;130(22):2377-85. DOI: 10.1182/blood-2017-05-782003.
14. Brandow AM, Zappia KJ, Stucky CL. Sickle cell disease: a natural model of acute and chronic pain. Pain. 2017;158(Suppl. 1):S79-S84. DOI: 10.1097/j.pain.0000000000000824.
15. Ezenwa MO, Molokie RE, Wang ZJ, Yao Y, Suarez ML, Dyal B, et al. Differences in sensory pain, expectation, and satisfaction reported by outpatients with cancer or sickle cell disease. Pain Manag Nurs. 2018;19(4):322-32. DOI: 10.1016/j.pmn.2017.11.010.
16. Dampier C, Palermo TM, Darbari DS, Hassell K, Smith W, Zempsky W. AAPT diagnostic criteria for chronic sickle cell disease pain. J Pain. 2017;18(5):490-8. DOI: 10.1016/j.jpain.2016.12.016.
17. Baliki MN, Apkarian AV. Nociception, pain, negative moods, and behavior selection. Neuron. 2015;87(3):474-91. DOI: 10.1016/j.neuron.2015.06.005.
18. Basbaum AI, Bautista DM, Scherrer G, Julius D. Cellular and molecular mechanisms of pain. Cell. 2009;139(2):267-84. DOI: 10.4097/kjae.2009.57.3.277.
19. Porreca F, Navratilova E. Reward, motivation, and emotion of pain and its relief. Pain. 2017;158(suppl 1):S43-9. DOI: 10.1097/j.pain.0000000000000798.
20. Apkarian AV, Bushnell MC, Treede RD, Zubieta JK. Human brain mechanisms of pain perception and regulation in health and disease. Eur J Pain. 2005;9(4):463-84. DOI: 10.1016/j.ejpain.2004.11.001.
21. Basbaum AI, Bautista DM, Scherrer G, Julius D. Cellular and molecular mechanisms of pain. Cell. 2009;139(2):267-84. DOI: 10.1016/j.cell.2009.09.028.
22. Shibin Du, Corinna Lin, Yuan-Xiang Tao. Updated mechanisms underlying sickle cell disease-associated pain. Neurosci Lett. 2019;712:134471. DOI: 10.1016/j.neulet.2019.134471.
23. Bhatt RR, Martin SR, Evans S, Lung K, Coates TD, Zeltzer LK, et al. The effect of hypnosis on pain and peripheral blood flow in sickle-cell disease: a pilot study. J Pain Res. 2017;10:1635-44. DOI: 10.2147/jpr.s131859.
24. 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. DOI: 10.1182/blood-2013-04-498105.
25. 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. 2015;101(5):566-77. DOI: 10.3324/haematol.2015.136523.
26. 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):456-5. DOI: 10.1182/blood-2010-01-260372.
27. 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. DOI: 10.1111/j.1365-2141.2011.08977.x.
28. 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. DOI: 10.1371/journal.pone.0160608.
29. 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. DOI: 10.1097/j.pain.0000000000000104.
30. Valverde Y, Benson B, Gupta M, Gupta K. Spinal glial activation and oxidative stress are alleviated by treatment with curcumin or coenzyme Q in sickle mice. Haematologica. 2015;101(2):e44-e47. DOI: 10.3324/haematol.2015.137489.
31. Savage WJ, Everett AD, Casella JF. Plasma glial fibrillary acidic protein levels in a child with sickle cell disease and stroke. Acta Haematol. 2011;125(3):103-6. DOI: 10.1159/000321791.
32. Campbell CM, Moscou-Jackson G, Carroll CP, Kiley K, Haywood C Jr, Lanzkron S, et al. An evaluation of central sensitization in patients with sickle cell disease. J Pain. 2016;17(5):617-7. DOI: 10.1016/j.jpain.2016.01.475.
33. Brandow AM, Farley RA, Panepinto JA. Early insights into the neurobiology of pain in sickle cell disease: aA systematic review of the literature. Pediatr Blood Cancer. 2015;62(9):1501-11. DOI: 10.1002/pbc.25574.
34. Jacob E, Chan VW, Hodge C, Zeltzer L, Zurakowski D, Sethna NF. Sensory and thermal quantitative testing in children with sickle cell disease. J Pediatr Hematol Oncol. 2015;37(3):185-9. DOI: 10.1097/MPH.0000000000000214.
35. Darbari DS, Hampson JP, Ichesco E, Kadom N, Vezina G, Evangelou I, et al. Frequency of hospitalizations for pain and association with altered brain network connectivity in sickle cell disease. J Pain. 2015;16(11):1077-86. DOI: 10.1016/j.jpain.2015.07.005.
36. Case M, Zhang H, Mundahl J, Datta Y, Nelson S, Gupta K, et al. Characterization of functional brain activity and connectivity using EEG and fMRI in patients with sickle cell disease. Neuroimage Clin. 2017;14:1-17. DOI: 10.1016/j.nicl.2016.12.024.
37. Colombatti R, Ermani M, Rampazzo P, Renzo Manara, Maria Montanaro, Giuseppe Basso, et al. Cognitive evoked potentials and neural networks are abnormal in children with sickle cell disease and not related to the degree of anaemia, pain and silent infarcts. Br J Haematol. 2014;169(4):597-600 DOI: 10.1111/bjh.13232.
38. Kato GJ, Steinberg MH, Gladwin MT. Intravascular hemolysis and the pathophysiology of sickle cell disease. J Clin Invest. 2017;127(3):750-60. DOI: 10.1172/JCI89741.
39. Smith WR, Bauserman RL, Ballas SK, McCarthy WF, Steinberg MH, Swerdlow PS, et al. Climatic and geographic temporal patterns of pain in the Multicenter Study of Hydroxyurea. Pain. 2009;146(1-2):91-8. DOI: 10.1016/j.pain.2009.07.008.
40. Glassberg J, Spivey JF, Strunk R, Boslaugh S, DeBaun MR. Painful episodes in children with sickle cell disease and asthma are temporally associated with respiratory symptoms. J Pediatr Hematol Oncol. 2006;28(8):481-5. DOI: 10.1097/01.mph.0000212968.98501.2b.
41. Yoong WC, Tuck SM. Menstrual pattern in women with sickle cell anaemia and its association with sickling crises. J Obstet Gynaecol. 2002;22(4):399-401. DOI: 10.1080/01443610220141362.
42. Resar LM, Oski FA. Cold water exposure and vaso-occlusive crises in sickle cell anemia. J Pediatr. 1991;118(3):407-9. DOI: 10.1016/s0022-3476(05)82156-0.
43. Woolf CJ, Salter MW. Neuronal plasticity: increasing the gain in pain. Science. 2000;288(5472):1765-9. DOI: 10.1126/science.288.5472.1765.
44. Wilkie DJ, Molokie R, Boyd-Seal D, Kim YO, Zong S, Wittert H, 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 DOI: 10.1016/s0027-9684(15)30471-5.
45. Brandow AM, DeBaun MR. Key Components of Pain Management for Children and Adults with Sickle Cell Disease. Hematol Oncol Clin North Am. 2018;32(3):535-50. DOI: 10.1016/j.hoc.2018.01.014.
46. McClish DK, Smith WR, Levenson JL, Aisiku IP, Roberts JD, Roseff SD, et al. Comorbidity, pain, utilization, and psychosocial outcomes in older versus younger sickle cell adults: the PiSCES project. BioMed Res Int 2017;2017:4070547. DOI: 10.1155/2017/4070547.
47. Han J, Zhou J, Saraf SL, Gordeuk VR, Calip GS. Characterization of opioid use in sickle cell disease. Pharmacoepidemiol Drug Saf. 2018;27(5):479-86. DOI: 10.1002/pds.4291.
48. Schatz AA, Oliver TK, Swarm RA, Paice JA. Darbar DE, Dowel Deborah, el al. Bridging the gap among clinical practice guidelines for pain management in cancer and sickle cell disease. J Natl Compr Canc Netw. 2020;18(4):392-9. DOI: 10.6004/jnccn.2019.7379.
49. Jonassaint CR, Jones VL, Leong S, Frierson GM. A systematic review of the association between depression and health care utilization in children and adults with sickle cell disease. Br J Haematol. 2016;174(1):136-47. DOI: 10.1111/bjh.14023.
50. Levenson JL, McClish DK, Dahman BA, Bovbjerg VE, Citero VA, Penberthy LT, et al. Depression and anxiety in adults with sickle cell disease: the PiSCES project. Psychosom Med. 2008;70(2):192-6. DOI: 10.1097/PSY.0b013e31815ff5c5.
51. Brandow AM, Farley RA, Panepinto JA. Neuropathic pain in patients with sickle cell disease. Pediatr Blood Cancer. 2014;61(3):512-7. DOI: 10.1002/pbc.24838.
52. 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. DOI: 10.1097/MPH.0000000000000265.
53. Molokie RE, Wilkie DJ, Wittert, Suarez HM, 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. DOI: 10.1016/j.ejphar.2013.10.062.
54. 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. DOI: 10.1016/j.pmn.2017.07.003.
55. 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. DOI: 10.1111/papr.12674.
56. Lubega FA, DeSilva MS, Munube D, Nkwine R, Tumukunde J, Agaba PK, et al. Low dose ketamine versus morphine for acute severe vaso occlusive pain in children: a randomized controlled trial. Scand. J Pain 2018;18(1):19-27. DOI: 10.1515/sjpain-2017-0140.
57. Palm N, Floroff C, Hassig TB, Boylan A, Kanter J. Low-dose ketamine infusion for adjunct management during vaso-occlusive episodes in adults with sickle cell disease: a case series. J Pain Palliat Care Pharmacother. 2018;32(1):1-7- DOI: 10.1080/15360288.2018.1468383.

Tablas y Figuras

Table I

Figure 1

Table II

Figure 2

Artículos relacionados

A case of neuralgic amyotrophy after vaccination against COVID-19

Rev. Soc. Esp. Dolor. 2023; 30(3): 187-190 / DOI: 10.20986/resed.2023.4021/2022

Have the concepts of obstetric analgesia changed in the last 100 years?

Rev. Soc. Esp. Dolor. 2023; 30(2): 125-130 / DOI: 10.20986/resed.2023.4018/2022

Pharmacogenetics in analgesic response: towards a sex-differences personalized medicine

Rev. Soc. Esp. Dolor. 2023; 30(2): 115-124 / DOI: 10.20986/resed.2023.4042/2022

Attitudes and current knowledge of the spanish pain treatment specialist regarding medical cannabis

Rev. Soc. Esp. Dolor. 2022; 29(13): 52-57 / DOI: 10.20986/resed.2022.4032/2022

OFA in major surgery. Experience at a secondary level hospital

Rev. Soc. Esp. Dolor. 2022; 29(1): 8-14 / DOI: 10.20986/resed.2022.3991/2022

Retrolaminar ultrasound guided block as analgesic treatment for post herpetic neuralgia: case report

Rev. Soc. Esp. Dolor. 2021; 28(6): 350-353 / DOI: 10.20986/resed.2022.3920/2021

Recommendations for the safe prescription of opioids in patients with a history or risk of abuse

Rev. Soc. Esp. Dolor. 2021; 28(6): 343-349 / DOI: 10.20986/resed.2022.3935/2021

New opioids with different intracellular mechanism of action; is a new therapeutic window opening up?

Rev. Soc. Esp. Dolor. 2021; 28(5): 292-297 / DOI: 10.20986/resed.2021.3891/2021

Efficacy and complications of analgesic techniques for the treatment of moderate to severe postoperative acute pain

Rev. Soc. Esp. Dolor. 2021; 28(5): 264-265 / DOI: 10.20986/resed.2021.3942/2021

The unsolved problem of postoperative pain: critical analysis and prospects for improvement

Rev. Soc. Esp. Dolor. 2021; 28(4): 232-238 / DOI: 10.20986/resed.2021.3917/2021

Persistent hiccups after epidural injection of betamethasone: a case report

Rev. Soc. Esp. Dolor. 2021; 28(2): 169-171 / DOI: 10.20986/resed.2021.3914/2021

Postoperative ketamine efficacy in patients receiving chronic opioids undergoing spinal surgery

Rev. Soc. Esp. Dolor. 2021; 28(2): 92-99 / DOI: 10.20986/resed.2021.3825/2020

Parsonage-turner after rabies vaccination due to bat bite: case report

Rev. Soc. Esp. Dolor. 2021; 28(1): 57-61 / DOI: 10.20986/resed.2021.3832/2020

Bilateral spinal erector plane block for pectus excavatum surgery in pediatric patient

Rev. Soc. Esp. Dolor. 2021; 28(1): 53-56 / DOI: 10.20986/resed.2021.3846/2020

Transitional pain clinic

Rev. Soc. Esp. Dolor. 2020; 27(6): 369-374 / DOI: 10.20986/resed.2020.3840/2020

Study of pain in rehabilitation treatments

Rev. Soc. Esp. Dolor. 2020; 27(6): 361-368 / DOI: 10.20986/resed.2020.3809/2020

Back to the future in the treatment of postoperative acute pain

Rev. Soc. Esp. Dolor. 2020; 27(5): 285-286 / DOI: 10.20986/resed.2020.3850/2020

Erector spinalis plane block as a neuropathic pain management in post-burned pediatric patient

Rev. Soc. Esp. Dolor. 2020; 27(2): 127-132 / DOI: 10.20986/resed.2020.3776/2019

Management of breakthrough pain associated with the cure of skin ulcers

Rev. Soc. Esp. Dolor. 2020; 27(2): 113-126 / DOI: 10.20986/resed.2020.3755/2019

Peripheral acting Mu opioid receptor antagonists in the treatment of the opioid-induced constipation: review

Rev. Soc. Esp. Dolor. 2020; 27(1): 37-49 / DOI: 10.20986/resed.2020.3717/2018

Effectiveness of patient-controlled analgesia in acute and chronic pain after cardiac surgery: a prospective study

Rev. Soc. Esp. Dolor. 2020; 27(1): 24-36 / DOI: 10.20986/resed.2020.3747/2019

Key factors governing spinal cord opioid bioavailability in the management of acute pain

Rev. Soc. Esp. Dolor. 2019; 26(6): 359-367 / DOI: 10.20986/resed.2019.3737/2019

Cervical epidural anesthesia and analgesia for upper limb surgery

Rev. Soc. Esp. Dolor. 2019; 26(5): 304-308 / DOI: 10.20986/resed.2019.3686/2018

New strategies for postoperative pain control in tonsillectomy surgery. Is all that glitters gold?

Rev. Soc. Esp. Dolor. 2019; 26(5): 270-275 / DOI: 10.20986/resed.2019.3742/2019

Comparative analysis of vital signs in acutely hospitalized patients according to the pain intensity

Rev. Soc. Esp. Dolor. 2019; 26(4): 215-220 / DOI: 10.20986/resed.2019.3707/2018

Analgesia and anaesthesia in red-haired, any special precaution?

Rev. Soc. Esp. Dolor. 2019; 26(3): 206-206 / DOI: 10.20986/resed.2018.3647/2017

Erector spinae plane block for multiple unilateral ribs fractures.

Rev. Soc. Esp. Dolor. 2019; 26(3): 199-202 / DOI: 10.20986/resed.2019.3687/2018

Optimization of postoperative pain management based on a new technological tool. Pain map

Rev. Soc. Esp. Dolor. 2019; 26(3): 154-165 / DOI: 10.20986/resed.2019.3696/2018

Myofascial pain syndrome as a cause of postoperative acute pain in hip surgery

Rev. Soc. Esp. Dolor. 2019; 26(2): 117-119 / DOI: 10.20986/resed.2019.3655/2018

Dexmedetomidine as peripheral nerve block adjuvant

Rev. Soc. Esp. Dolor. 2019; 26(2): 103-115 / DOI: 10.20986/resed.2018.3695/2018

Effectiveness of hand crossing to produce analgesia in patients with chronic pain of the upper limb

Rev. Soc. Esp. Dolor. 2019; 26(2): 81-88 / DOI: 10.20986/resed.2019.3674/2018

Project adapta: adequacy of treatment in breakthrough cancer pain

Rev. Soc. Esp. Dolor. 2019; 26(1): 31-43 / DOI: 10.20986/resed.2018.3661/2018

Use of major opioids for control of pain in hospitalized patients

Rev. Soc. Esp. Dolor. 2018; 25(6): 318-324 / DOI: 10.20986/resed.2018.3629/2017

Farmacologic adyuvants with saving effect of opioids in the perioperative period

Rev. Soc. Esp. Dolor. 2018; 25(5): 278-290 / DOI: 10.20986/resed.2018.3663/2018

Epidural analgesia vs. surgical wound analgesia to control acute post-operative pain in open colon surgery

Rev Soc Esp Dolor 2017; 24(5): 234-240 / DOI: 10.20986/resed.2017.3559/2016

Instrucciones para citar

Mugabure B, González S, Uría A, Osorio A. Clinical pathophysiology in patients with sickle cell disease: the transition from acute to chronic pain. Rev Soc Esp Dolor 2020; 27(4): 257-268 / DOI: 1020986/resed20203814/2020


Descargar a un gestores de citas

Descargue la cita de este artículo haciendo clic en uno de los siguientes gestores de citas:

Métrica

Este artículo ha sido visitado 47965 veces.
Este artículo ha sido descargado 30 veces.

Estadísticas de Dimensions


Estadísticas de Plum Analytics

Ficha Técnica

Recibido: 17/04/2020

Aceptado: 07/07/2020

Prepublicado: 07/07/2020

Publicado: 04/08/2020

Tiempo de revisión del artículo: 62 días

Tiempo de prepublicación: 81 días

Tiempo de edición del artículo: 109 días


Compartir

Este artículo ha sido valorado por 1 lectores .
Reader rating:
Rate this article:
© 2024 Revista de la Sociedad Española del Dolor
ISSN: 1134-8046   e-ISSN: 2254-6189

      Indexada en: