The effect of rTMS in the management of pain associated with CRPS

Min Cheol Chang, Sang Gyu Kwak, Donghwi Park, Min Cheol Chang, Sang Gyu Kwak, Donghwi Park

Abstract

Background: Therapeutic management of pain in patients with complex regional pain syndrome (CRPS) is challenging. Repetitive transcranial magnetic stimulation (rTMS) has analgesic effects on several types of pain. However, its effect on CRPS has not been elucidated clearly. Therefore, we conducted a meta-analysis of the available clinical studies on rTMS treatment in patients with CRPS.

Materials and methods: A comprehensive literature search was conducted using the PubMed, EMBASE, Cochrane Library, and SCOPUS databases. We included studies published up to February 09, 2020, that fulfilled our inclusion and exclusion criteria. Data regarding measurement of pain using the visual analog scale before and after rTMS treatment were collected to perform the meta-analysis. The meta-analysis was performed using Comprehensive Meta-analysis Version 2.

Results: A total of three studies (one randomized controlled trial and two prospective observational studies) involving 41 patients were included in this meta-analysis. No significant reduction in pain was observed immediately after one rTMS treatment session or immediately after the entire schedule of rTMS treatment sessions (5 or 10 sessions; P > 0.05). However, pain significantly reduced 1 week after the entire schedule of rTMS sessions (P < 0.001).

Conclusion: rTMS appears to have a functional analgesic effect in patients with CRPS.

Keywords: complex regional pain syndrome; meta-analysis; pain; repetitive regional pain syndrome.

Conflict of interest statement

Conflict of interest: The authors state no conflict of interest.

© 2020 Min Cheol Chang et al., published by De Gruyter.

Figures

Figure 1
Figure 1
Flowchart showing the search results of the meta-analysis.
Figure 2
Figure 2
Changes in the visual analog scale scores immediately after one rTMS treatment session (a), immediately after the completion of the entire schedule of rTMS treatment sessions (5 or 10 sessions) (b), and 1 week after the completion of the entire schedule of rTMS sessions (5 or 10 sessions) (c).
Figure 3
Figure 3
Graphic funnel plot of the included studies, depicting the change in visual analog scale scores immediately after 1 rTMS session.

References

    1. Harden RN, Bruehl S, Perez RS, Birklein F, Marinus J, Maihofner C, et al. Validation of proposed diagnostic criteria (the “Budapest Criteria”) for complex regional pain syndrome. Pain. 2010;150(2):268–74. Epub 2010/05/25. 10.1016/j.pain.2010.04.030. PubMed PMID: 20493633; PubMed Central PMCID: PMCPMC2914601.
    2. Harden RN, Bruehl S, Perez RS, Birklein F, Marinus J, Maihofner C. et al. Validation of proposed diagnostic criteria (the “Budapest Criteria”) for complex regional pain syndrome. Pain. 2010;150(2):268–74. doi: 10.1016/j.pain.2010.04.030. . Epub 2010/05/25. . PubMed PMID: 20493633; PubMed Central PMCID: PMCPMC2914601.
    1. Harden RN, Bruehl S, Stanton-Hicks M, Wilson PR. Proposed new diagnostic criteria for complex regional pain syndrome. Pain Med. 2007;8(4):326–31. Epub 2007/07/06. 10.1111/j.1526-4637.2006.00169.x. PubMed PMID: 17610454
    2. Harden RN, Bruehl S, Stanton-Hicks M, Wilson PR. Proposed new diagnostic criteria for complex regional pain syndrome. Pain Med. 2007;8(4):326–31. doi: 10.1111/j.1526-4637.2006.00169.x. . Epub 2007/07/06. . PubMed PMID: 17610454.
    1. Park D. Recurrent complex regional pain syndrome type I in a patient with amyotrophic lateral sclerosis: a case report. Neurol Sci. 2018;39(8):1487–8. Epub 2018/03/11. 10.1007/s10072-018-3305-6. PubMed PMID: 29524044.
    2. Park D. Recurrent complex regional pain syndrome type I in a patient with amyotrophic lateral sclerosis: a case report. Neurol Sci. 2018;39(8):1487–8. doi: 10.1007/s10072-018-3305-6. Epub 2018/03/11. . PubMed PMID: 29524044.
    1. Lee BJ, Kim JY, Cho HJ, Park D. Sphingosine 1-phosphate receptor modulation attenuate mechanical allodynia in mouse model of chronic complex regional pain syndrome by suppressing pathogenic astrocyte activation. Reg Anesth Pain Med. 2020;45(3):230–8. Epub 2020/01/24. 10.1136/rapm-2019-100801. PubMed PMID: 31969447.
    2. Lee BJ, Kim JY, Cho HJ, Park D. Sphingosine 1-phosphate receptor modulation attenuate mechanical allodynia in mouse model of chronic complex regional pain syndrome by suppressing pathogenic astrocyte activation. Reg Anesth Pain Med. 2020;45(3):230–8. doi: 10.1136/rapm-2019-100801. . Epub 2020/01/24. . PubMed PMID: 31969447.
    1. Lee SH, Lee JM, Kim YH, Choi JH, Jeon SH, Kim DK, et al. Antiallodynic Effects of Bee Venom in an Animal Model of Complex Regional Pain Syndrome Type 1 (CRPS-I). Toxins. 2017;9(9). Epub 2017/09/16. 10.3390/toxins9090285. PubMed PMID: 28914784; PubMed Central PMCID: PMCPMC5618218.
    2. Lee SH, Lee JM, Kim YH, Choi JH, Jeon SH, Kim DK. et al. Antiallodynic Effects of Bee Venom in an Animal Model of Complex Regional Pain Syndrome Type 1 (CRPS-I) Toxins. 2017;9(9) doi: 10.3390/toxins9090285. . Epub 2017/09/16. . PubMed PMID: 28914784; PubMed Central PMCID: PMCPMC5618218.
    1. Kim JH, Park JS, Park D. Anti-allodynic effect of interleukin 10 in a mouse model of complex regional pain syndrome through reduction of NK1 receptor expression of microglia in the spinal cord. J Pain Res 2018;11:1729–41. Epub 2018/09/21. 10.2147/JPR.S166624. PubMed PMID: 30233230; PubMed Central PMCID: PMCPMC6129024.
    2. Kim JH, Park JS, Park D. Anti-allodynic effect of interleukin 10 in a mouse model of complex regional pain syndrome through reduction of NK1 receptor expression of microglia in the spinal cord. J Pain Res. 2018;11:1729–41. doi: 10.2147/JPR.S166624. . Epub 2018/09/21. . PubMed PMID: 30233230; PubMed Central PMCID: PMCPMC6129024.
    1. Mouraux D, Lenoir C, Tuna T, Brassinne E, Sobczak S. The long-term effect of complex regional pain syndrome type 1 on disability and quality of life after foot injury. Disabil Rehabil. 2019;1–9. Epub 2019/08/15. 10.1080/09638288.2019.1650295. PubMed PMID: 31411910.
    2. Mouraux D, Lenoir C, Tuna T, Brassinne E, Sobczak S. The long-term effect of complex regional pain syndrome type 1 on disability and quality of life after foot injury. Disabil Rehabil. 2019:1–9. doi: 10.1080/09638288.2019.1650295. . Epub 2019/08/15. . PubMed PMID: 31411910.
    1. Schwarm FP, Stein M, Uhl E, Maxeiner H, Kolodziej MA. Spinal cord stimulation for the treatment of complex regional pain syndrome leads to improvement of quality of life, reduction of pain and psychological distress: a retrospective case series with 24 months follow up. Scand J Pain. 2020;20(2):253–9. Epub 2019/11/20. 10.1515/sjpain-2019-0081. PubMed PMID: 31743107.
    2. Schwarm FP, Stein M, Uhl E, Maxeiner H, Kolodziej MA. Spinal cord stimulation for the treatment of complex regional pain syndrome leads to improvement of quality of life, reduction of pain and psychological distress: a retrospective case series with 24 months follow up. Scand J Pain. 2020;20(2):253–9. doi: 10.1515/sjpain-2019-0081. . Epub 2019/11/20. . PubMed PMID: 31743107.
    1. Brinkers M, Rumpelt P, Lux A, Kretzschmar M, Pfau G. Psychiatric disorders in complex regional pain syndrome (CRPS): the role of the consultation-Liaison psychiatrist. Pain Res Manag. 2018;2018:2894360. Epub 2018/11/13. 10.1155/2018/2894360. PubMed PMID: 30416634; PubMed Central PMCID: PMCPMC6207853.
    2. Brinkers M, Rumpelt P, Lux A, Kretzschmar M, Pfau G. Psychiatric disorders in complex regional pain syndrome (CRPS): the role of the consultation-Liaison psychiatrist. Pain Res Manag. 2018;2018:2894360. doi: 10.1155/2018/2894360. . Epub 2018/11/13. . PubMed PMID: 30416634; PubMed Central PMCID: PMCPMC6207853.
    1. Choi GS, Chang MC. Effects of high-frequency repetitive transcranial magnetic stimulation on reducing hemiplegic shoulder pain in patients with chronic stoke: a randomized controlled trial. Int J Neurosci. 2018;128(2):110–6. Epub 2017/08/15. 10.1080/00207454.2017.1367682. PubMed PMID: 28805107.
    2. Choi GS, Chang MC. Effects of high-frequency repetitive transcranial magnetic stimulation on reducing hemiplegic shoulder pain in patients with chronic stoke: a randomized controlled trial. Int J Neurosci. 2018;128(2):110–6. doi: 10.1080/00207454.2017.1367682. . Epub 2017/08/15. . PubMed PMID: 28805107.
    1. Choi GS, Kwak SG, Lee HD, Chang MC. Effect of high-frequency repetitive transcranial magnetic stimulation on chronic central pain after mild traumatic brain injury: a pilot study. J Rehabil Med. 2018;50(3):246–52. Epub 2018/02/03. 10.2340/16501977-2321. PubMed PMID: 29392332.
    2. Choi GS, Kwak SG, Lee HD, Chang MC. Effect of high-frequency repetitive transcranial magnetic stimulation on chronic central pain after mild traumatic brain injury: a pilot study. J Rehabil Med. 2018;50(3):246–52. doi: 10.2340/16501977-2321. . Epub 2018/02/03. . PubMed PMID: 29392332.
    1. Gu SY, Chang MC. The effects of 10 Hz repetitive transcranial magnetic stimulation on depression in chronic stroke patients. Brain Stimul. 2017;10(2):270–4. Epub 2016/11/15. 10.1016/j.brs.2016.10.010. PubMed PMID: 27839722.
    2. Gu SY, Chang MC. The effects of 10 Hz repetitive transcranial magnetic stimulation on depression in chronic stroke patients. Brain Stimul. 2017;10(2):270–4. doi: 10.1016/j.brs.2016.10.010. . Epub 2016/11/15. . PubMed PMID: 27839722.
    1. Chang MC, Choo YJ, Park D. The effect of repetitive transcranial magnetic stimulation on motor recovery can be different according to post-stroke periods. Am J Phys Med Rehabil. 2020. Epub 2020/08/01. 10.1097/PHM.0000000000001538. PubMed PMID: 32732741.
    2. Chang MC, Choo YJ, Park D. The effect of repetitive transcranial magnetic stimulation on motor recovery can be different according to post-stroke periods. Am J Phys Med Rehabil. 2020 doi: 10.1097/PHM.0000000000001538. . Epub 2020/08/01. . PubMed PMID: 32732741.
    1. Saltychev M, Laimi K. Effectiveness of repetitive transcranial magnetic stimulation in patients with fibromyalgia: a meta-analysis. Int J Rehabil Res. 2017;40(1):11–8. Epub 2016/12/16. 10.1097/MRR.0000000000000207. PubMed PMID: 27977465.
    2. Saltychev M, Laimi K. Effectiveness of repetitive transcranial magnetic stimulation in patients with fibromyalgia: a meta-analysis. Int J Rehabil Res. 2017;40(1):11–8. doi: 10.1097/MRR.0000000000000207. . Epub 2016/12/16. . PubMed PMID: 27977465.
    1. Lefaucheur JP, Nguyen JP. A practical algorithm for using rTMS to treat patients with chronic pain. Neurophysiol Clin. 2019;49(4):301–7. Epub 2019/08/04. 10.1016/j.neucli.2019.07.014. PubMed PMID: 31375381.
    2. Lefaucheur JP, Nguyen JP. A practical algorithm for using rTMS to treat patients with chronic pain. Neurophysiol Clin. 2019;49(4):301–7. doi: 10.1016/j.neucli.2019.07.014. . Epub 2019/08/04. . PubMed PMID: 31375381.
    1. Gaertner M, Kong JT, Scherrer KH, Foote A, Mackey S, Johnson KA. Advancing transcranial magnetic stimulation methods for complex regional pain syndrome: an open-label study of paired theta burst and high-frequency stimulation. Neuromodulation. 2018;21(4):409–16. Epub 2018/03/06. 10.1111/ner.12760. PubMed PMID: 29504190; PubMed Central PMCID: PMCPMC6033652.
    2. Gaertner M, Kong JT, Scherrer KH, Foote A, Mackey S, Johnson KA. Advancing transcranial magnetic stimulation methods for complex regional pain syndrome: an open-label study of paired theta burst and high-frequency stimulation. Neuromodulation. 2018;21(4):409–16. doi: 10.1111/ner.12760. . Epub 2018/03/06. . PubMed PMID: 29504190; PubMed Central PMCID: PMCPMC6033652.
    1. Picarelli H, Teixeira MJ, de Andrade DC, Myczkowski ML, Luvisotto TB, Yeng LT, et al. Repetitive transcranial magnetic stimulation is efficacious as an add-on to pharmacological therapy in complex regional pain syndrome (CRPS) type I. J Pain. 2010;11(11):1203–10. Epub 2010/05/01. 10.1016/j.jpain.2010.02.006. PubMed PMID: 20430702.
    2. Picarelli H, Teixeira MJ, de Andrade DC, Myczkowski ML, Luvisotto TB, Yeng LT. et al. Repetitive transcranial magnetic stimulation is efficacious as an add-on to pharmacological therapy in complex regional pain syndrome (CRPS) type I. J Pain. 2010;11(11):1203–10. doi: 10.1016/j.jpain.2010.02.006. . Epub 2010/05/01. . PubMed PMID: 20430702.
    1. Pleger B, Janssen F, Schwenkreis P, Volker B, Maier C, Tegenthoff M. Repetitive transcranial magnetic stimulation of the motor cortex attenuates pain perception in complex regional pain syndrome type I. Neurosci Lett. 2004;356(2):87–90. Epub 2004/01/30. 10.1016/j.neulet.2003.11.037. PubMed PMID: 14746870.
    2. Pleger B, Janssen F, Schwenkreis P, Volker B, Maier C, Tegenthoff M. Repetitive transcranial magnetic stimulation of the motor cortex attenuates pain perception in complex regional pain syndrome type I. Neurosci Lett. 2004;356(2):87–90. doi: 10.1016/j.neulet.2003.11.037. . Epub 2004/01/30. . PubMed PMID: 14746870.
    1. Nardone R, Brigo F, Holler Y, Sebastianelli L, Versace V, Saltuari L, et al. Transcranial magnetic stimulation studies in complex regional pain syndrome type I: a review. Acta Neurol Scand. 2018;137(2):158–64. Epub 2017/10/04. 10.1111/ane.12852. PubMed PMID: 28971481.
    2. Nardone R, Brigo F, Holler Y, Sebastianelli L, Versace V, Saltuari L. et al. Transcranial magnetic stimulation studies in complex regional pain syndrome type I: a review. Acta Neurol Scand. 2018;137(2):158–64. doi: 10.1111/ane.12852. . Epub 2017/10/04. . PubMed PMID: 28971481.
    1. Galhardoni R, Correia GS, Araujo H, Yeng LT, Fernandes DT, Kaziyama HH, et al. Repetitive transcranial magnetic stimulation in chronic pain: a review of the literature. Arch Phys Med rehabilitation. 2015;96(4 Suppl):S156–72. Epub 2014/12/02. 10.1016/j.apmr.2014.11.010. PubMed PMID: 25437106.
    2. Galhardoni R, Correia GS, Araujo H, Yeng LT, Fernandes DT, Kaziyama HH. et al. Repetitive transcranial magnetic stimulation in chronic pain: a review of the literature. Arch Phys Med rehabilitation. 2015;96(4 Suppl):S156–72. doi: 10.1016/j.apmr.2014.11.010. . Epub 2014/12/02. . PubMed PMID: 25437106.
    1. Yang S, Chang MC. Effect of repetitive transcranial magnetic stimulation on pain management: a systematic narrative review. Front Neurol. 2020;11:114. Epub 2020/03/07. 10.3389/fneur.2020.00114. PubMed PMID: 32132973; PubMed Central PMCID: PMCPMC7040236.
    2. Yang S, Chang MC. Effect of repetitive transcranial magnetic stimulation on pain management: a systematic narrative review. Front Neurol. 2020;11:114. doi: 10.3389/fneur.2020.00114. . Epub 2020/03/07. . PubMed PMID: 32132973; PubMed Central PMCID: PMCPMC7040236.
    1. Higgins JPGS. Cochrane Handbook for Systematic Reviews of Interventions 5.1.0. The Cochrane Collaboration. 2011.
    2. Higgins JPGS. Cochrane Handbook for Systematic Reviews of Interventions 5.1.0. The Cochrane Collaboration. 2011.
    1. Institute, OHR. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses. 2011.
    2. Institute, OHR. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses. 2011.
    1. J. C. Statistical Power Analysis for the Behavioral Sciences. 1988.
    2. J. C. Statistical Power Analysis for the Behavioral Sciences. 1988.
    1. Hirayama A, Saitoh Y, Kishima H, Shimokawa T, Oshino S, Hirata M, et al. Reduction of intractable deafferentation pain by navigation-guided repetitive transcranial magnetic stimulation of the primary motor cortex. Pain. 2006;122(1–2):22–7. Epub 2006/02/24. 10.1016/j.pain.2005.12.001. PubMed PMID: 16495011.
    2. Hirayama A, Saitoh Y, Kishima H, Shimokawa T, Oshino S, Hirata M. et al. Reduction of intractable deafferentation pain by navigation-guided repetitive transcranial magnetic stimulation of the primary motor cortex. Pain. 2006;122(1–2):22–7. doi: 10.1016/j.pain.2005.12.001. . Epub 2006/02/24. . PubMed PMID: 16495011.
    1. Almeida TF, Roizenblatt S, Tufik S. Afferent pain pathways: a neuroanatomical review. Brain Res. 2004;1000(1–2):40–56. Epub 2004/04/01. 10.1016/j.brainres.2003.10.073. PubMed PMID: 15053950.
    2. Almeida TF, Roizenblatt S, Tufik S. Afferent pain pathways: a neuroanatomical review. Brain Res. 2004;1000(1–2):40–56. doi: 10.1016/j.brainres.2003.10.073. . Epub 2004/04/01. . PubMed PMID: 15053950.
    1. Uglem M, Omland PM, Engstrom M, Gravdahl GB, Linde M, Hagen K, et al. Non-invasive cortical modulation of experimental pain in migraine. Clin Neurophysiol. 2016;127(6):2362–9. Epub 2016/05/15. 10.1016/j.clinph.2016.03.016. PubMed PMID: 27178854.
    2. Uglem M, Omland PM, Engstrom M, Gravdahl GB, Linde M, Hagen K. et al. Non-invasive cortical modulation of experimental pain in migraine. Clin Neurophysiol. 2016;127(6):2362–9. doi: 10.1016/j.clinph.2016.03.016. . Epub 2016/05/15. . PubMed PMID: 27178854.
    1. Leung A, Donohue M, Xu R, Lee R, Lefaucheur JP, Khedr EM, et al. rTMS for suppressing neuropathic pain: a meta-analysis. J Pain. 2009;10(12):1205–16. Epub 2009/05/26. 10.1016/j.jpain.2009.03.010. PubMed PMID: 19464959.
    2. Leung A, Donohue M, Xu R, Lee R, Lefaucheur JP, Khedr EM. et al. rTMS for suppressing neuropathic pain: a meta-analysis. J Pain. 2009;10(12):1205–16. doi: 10.1016/j.jpain.2009.03.010. . Epub 2009/05/26. . PubMed PMID: 19464959.
    1. Garcia-Larrea L, Peyron R, Mertens P, Gregoire MC, Lavenne F, Le Bars D, et al. Electrical stimulation of motor cortex for pain control: a combined PET-scan and electrophysiological study. Pain. 1999;83(2):259–73. Epub 1999/10/27. 10.1016/s0304-3959(99)00114-1. PubMed PMID: 10534598.
    2. Garcia-Larrea L, Peyron R, Mertens P, Gregoire MC, Lavenne F, Le Bars D. et al. Electrical stimulation of motor cortex for pain control: a combined PET-scan and electrophysiological study. Pain. 1999;83(2):259–73. doi: 10.1016/s0304-3959(99)00114-1. . Epub 1999/10/27. . PubMed PMID: 10534598.
    1. Saitoh Y, Osaki Y, Nishimura H, Hirano S, Kato A, Hashikawa K, et al. Increased regional cerebral blood flow in the contralateral thalamus after successful motor cortex stimulation in a patient with poststroke pain. J Neurosurg. 2004;100(5):935–9. Epub 2004/05/13. 10.3171/jns.2004.100.5.0935. PubMed PMID: 15137612.
    2. Saitoh Y, Osaki Y, Nishimura H, Hirano S, Kato A, Hashikawa K. et al. Increased regional cerebral blood flow in the contralateral thalamus after successful motor cortex stimulation in a patient with poststroke pain. J Neurosurg. 2004;100(5):935–9. doi: 10.3171/jns.2004.100.5.0935. . Epub 2004/05/13. . PubMed PMID: 15137612.
    1. de Andrade DC, Mhalla A, Adam F, Texeira MJ, Bouhassira D. Neuropharmacological basis of rTMS-induced analgesia: the role of endogenous opioids. Pain. 2011;152(2):320–6. Epub 2010/12/15. 10.1016/j.pain.2010.10.032. PubMed PMID: 21146300.
    2. de Andrade DC, Mhalla A, Adam F, Texeira MJ, Bouhassira D. Neuropharmacological basis of rTMS-induced analgesia: the role of endogenous opioids. Pain. 2011;152(2):320–6. doi: 10.1016/j.pain.2010.10.032. . Epub 2010/12/15. . PubMed PMID: 21146300.
    1. Pagano RL, Fonoff ET, Dale CS, Ballester G, Teixeira MJ, Britto LR. Motor cortex stimulation inhibits thalamic sensory neurons and enhances activity of PAG neurons: possible pathways for antinociception. Pain. 2012;153(12):2359–69. Epub 2012/09/29. 10.1016/j.pain.2012.08.002. PubMed PMID: 23017297.
    2. Pagano RL, Fonoff ET, Dale CS, Ballester G, Teixeira MJ, Britto LR. Motor cortex stimulation inhibits thalamic sensory neurons and enhances activity of PAG neurons: possible pathways for antinociception. Pain. 2012;153(12):2359–69. doi: 10.1016/j.pain.2012.08.002. . Epub 2012/09/29. . PubMed PMID: 23017297.
    1. Lerner AJ, Wassermann EM, Tamir DI. Seizures from transcranial magnetic stimulation 2012–2016: results of a survey of active laboratories and clinics. Clin Neurophysiol. 2019;130(8):1409–16. Epub 2019/05/21. 10.1016/j.clinph.2019.03.016. PubMed PMID: 31104898; PubMed Central PMCID: PMCPMC7274462.
    2. Lerner AJ, Wassermann EM, Tamir DI. Seizures from transcranial magnetic stimulation 2012–2016: results of a survey of active laboratories and clinics. Clin Neurophysiol. 2019;130(8):1409–16. doi: 10.1016/j.clinph.2019.03.016. Epub 2019/05/21. . PubMed PMID: 31104898; PubMed Central PMCID: PMCPMC7274462.
    1. Dobek CE, Blumberger DM, Downar J, Daskalakis ZJ, Vila-Rodriguez F. Risk of seizures in transcranial magnetic stimulation: a clinical review to inform consent process focused on bupropion. Neuropsychiatr Dis Treat. 2015;11:2975–87. Epub 2015/12/15. 10.2147/NDT.S91126. PubMed PMID: 26664122; PubMed Central PMCID: PMCPMC4670017.
    2. Dobek CE, Blumberger DM, Downar J, Daskalakis ZJ, Vila-Rodriguez F. Risk of seizures in transcranial magnetic stimulation: a clinical review to inform consent process focused on bupropion. Neuropsychiatr Dis Treat. 2015;11:2975–87. doi: 10.2147/NDT.S91126. . Epub 2015/12/15. . PubMed PMID: 26664122; PubMed Central PMCID: PMCPMC4670017.

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir