ORIGINAL RESEARCH

DOI: https://doi.org/10.15446/revfacmed.v69n3.80142
Received: 06/06/2019 Accepted: 27/12/2019

Effect of neural therapy on NGF and BDNF serum levels in patients

with chronic pain. A pilot study
Efecto de la terapia neural sobre los niveles séricos del NGF y el BDNF en pacientes con dolor crónico. Estudio piloto

Carolina Garzón1 Jorge Eduardo Caminos2 Juan Pablo Alzate3 Javier Hernando Eslava-Schmalbach4 María
Fernanda Garcés 2
Eduardo Humberto Beltrán-Dussan 5

1
Universidad Nacional de Colombia - Bogotá Campus - Faculty of Medicine - Master’s Degree in Alternative Medicine - Bogotá D.C. - Colombia.
2
Universidad Nacional de Colombia - Bogotá Campus - Faculty of Medicine - Department of Physiological Sciences - Bogotá D.C. - Colombia.
3
Universidad Nacional de Colombia - Bogotá Campus - Faculty of Medicine - Department of Public Health - Bogotá D.C. - Colombia.
4
Universidad Nacional de Colombia - Bogotá Campus - Faculty of Medicine - Department of Surgery - Bogotá D.C. - Colombia.
5
Universidad Nacional de Colombia - Bogotá Campus - Faculty of Medicine - Specialty in Pediatric Oncohematology - Bogotá D.C. -
Colombia. Corresponding author: Eduardo Humberto Beltrán-Dussan. Especialidad en Oncohematología Pediátrica, Facultad de Medicina,
Universidad Nacional de Colombia. Bogotá D.C. Colombia. Email: [email protected].

Abstract
Introduction: Neurotrophins (NT) are a family of proteins consisting of the nerve growth factor (NGF), Garzón C, Caminos JE, Alzate JP, Es-
the brain-derived neurotrophic factor (BDNF) and NT-3 and NT-4/5. These proteins play an essential role lava-Schmalbach JH, Garcés M, Bel-
in neuronal survival, differentiation, and proliferation. trán-Dussan EH. Effect of neural the-
rapy on NGF and BDNF serum levels in
Objectives: To analyze the variations of NGF and BDNF serum levels in patients with chronic pain after
patients with pain. A pilot study. Rev.
undergoing neural therapy and to establish the effects of this type of intervention on their quality of life. Fac. Med. 2021;69(3):e80142. English.
Materials and methods: Prospective pilot study conducted in 10 patients with chronic pain treated with doi: https://doi.org/10.15446/revfac-
neural therapy between July 2017 and April 2018 in Bogotá D.C., Colombia. Three consultations were med.v69n3.80142.
performed (one in which the intervention was initiated, and two follow-up visits every three weeks).
During each consultation, the patients’ quality of life was assessed using the SF-12 scale and their NGF
and BDNF serum levels were measured. Data were analyzed by means of descriptive statistics, using
medians and interquartile ranges for quantitative variables, and absolute frequencies and percentages
for qualitative variables.
Results: The median score on the SF-12 scale tended to improve in the first and second follow-up visits
compared with the baseline score (pre-intervention), particularly during the first follow-up visit (con-
sultation No. 1: 34.5; follow-up No. 1: 39.5, and follow-up No. 2: 38). Median NGF serum levels had a
downward trend after the intervention, particularly in the first follow-up visit (157.6, 42.95, and 237.8,
respectively), and in the case of BNDF, an overall downward trend was also found (29.96, 19.24 and
20.43, respectively). An improvement in quality of life related to the decrease in the serum levels of both
neurotrophins was observed.
Conclusion: Neural therapy intervention reduced NGF and BDNF serum levels and improved the quality
of life of the participants. Therefore, the behavior of these neurotrophins could become a biomarker for
the diagnosis, treatment, and follow-up of patients with chronic pain.
Keywords: Nerve Growth Factors; Pain Management; Local Anesthetics; Quality of Life; Pain (MeSH).

Resumen
Introducción. Las neurotrofinas (NT) son una familia de proteínas conformada por el factor de crecimien- Garzón C, Caminos JE, Alzate JP, Es-
to nervioso (NGF), el factor neurotrófico derivado del cerebro (BDNF) y las neurotrofinas NT-3 y NT-4/5; lava-Schmalbach JH, Garcés M, Bel-
trán-Dussan EH. [Efecto de la terapia
estas proteínas tienen un papel esencial en la supervivencia, diferenciación y proliferación neuronal.
neural sobre los niveles séricos de NGF y
Objetivos. Analizar las variaciones de los niveles séricos del NGF y el BDNF en pacientes con dolor crónico BDNF en pacientes con dolor. Estudio pilo-
luego de recibir terapia neural y establecer los efectos de este tipo de intervención en su calidad de vida. to]. Rev. Fac. Med. 2021;69(3):e80142.
Materiales y métodos. Estudio piloto prospectivo realizado en 10 pacientes con dolor crónico tratados English. doi: https://doi.org/10.15446/
con terapia neural entre julio de 2017 y abril de 2018 en Bogotá D.C., Colombia. Se realizaron 3 consultas revfacmed.v69n3.80142.
(una en la que se inició la intervención y dos de control cada tres semanas) y en cada una se evaluó la ca-
lidad de vida mediante el cuestionario de salud SF-12 y se midieron los niveles séricos del NGF y el BDNF.
Los datos se analizaron mediante estadística descriptiva, utilizando medianas y rangos intercuartiles para
las variables cuantitativas, y frecuencias absolutas y porcentajes para las cualitativas.
Resultados. La mediana de puntaje del cuestionario SF-12 tendió a mejorar en el primer y segundo
control comparada con la puntuación inicial (antes de la intervención), en particular en el primer control
(consulta 1: 34.5; control 1: 39.5, y control 2: 38). La mediana de los niveles séricos del NGF tendió a
disminuir luego de la intervención, en particular en el primer control (157.6, 42.95 y 62.2, respectivamen-
te), y en el caso del BNDF, la tendencia global también fue hacia la disminución (29.96, 19.24 y 20.43,
respectivamente). Se observó una mejora en la calidad de vida relacionada con la disminución de los ni-
veles séricos de ambas neurotrofinas.
Conclusión. La intervención de terapia neural produjo una reducción en los niveles séricos del NGF y el
BDNF y mejoró la calidad de vida de los participantes; por tanto, el comportamiento de estas neurotro-
finas podría convertirse en un biomarcador para el diagnóstico, tratamiento y seguimiento de pacientes
con dolor crónico.
Palabras clave: Factores de crecimiento nervioso; Manejo del dolor; Anestésicos locales; Calidad de
vida; Dolor (DeCS).

1/7
Neural therapy and NGF and BDNF serum levels https://doi.org/10.15446/revfacmed.v69n3.80142

Introduction to specific sites, determined based on each patient’s

medical history, this therapy modifies interferences in
Neurotrophins, also known as neurotrophic factors, were signaling systems and restores the proper functioning
first described in the 1960’s by Rita Levi-Montalcini, of the biological program.20-22
as reported by Bradshaw et al.1 Currently, it is known Considering the above, the objectives of this study
that they are proteins that modulate the processes of were to analyze changes in NGF and BDNF serum lev-
neuronal differentiation, maturation, growth, regen- els in patients with chronic pain after receiving neural
eration, survival and death and that they regulate the therapy and to determine the impact of this type of in-
mechanisms involved in synaptic processes and neu- tervention on their quality of life.
ronal plasticity.2-5 Likewise, they induce differentiation
of progenitor cells for the formation of new neurons. Materials and methods
Neurotrophin production was initially identified in
tissues considered as targets, on which actions of the Design and study population
nervous system are performed; however, it is now com-
monly accepted that its production is both central and A prospective pilot study was conducted in 10 patients
peripheral.6 It has also been demonstrated that these with chronic pain who attended the Neural Therapy
molecules belong to a family of growth factors and that Consultation Service of the master’s degree in Alterna-
they bind to receptors in neuronal cells. tive Medicine offered by the Faculty of Medicine of the
There are two types of receptors to which neurotro- Universidad Nacional de Colombia between July 2017
phins can bind: p75 and the Trk family (tyrosine kinase), and April 2018. Data were collected during 3 consul-
which, once activated, trigger intracellular signaling tations, one at the start of the intervention and two at
cascades that end with the expression of the genes re- follow-up consultations every 3 weeks. At each visit,
sponsible for neuronal response.7-9 the patients’ quality of life was assessed using the SF-
The neurotrophins described in humans to date are 12 health questionnaire and their NGF and BDNF serum
nerve growth factor (NGF), brain-derived neurotrophic levels were measured.
factor (BDNF), neurotrophin 3 (NT-3) and neurotrophin The following inclusion criteria were taken into
4/5 (NT-4/5).10-12 Others such as NT-6 and NT-7 have consideration for patient selection: being treated by
recently been found in some animal species.13 the neural therapy service for chronic pain;23 being
NGF is released by the target cells of the nervous system. between 18 and 60 years of age; attending the 3
It plays a fundamental role in the survival and mainte- consultations; agreeing to participate in the study;
nance processes of sympathetic and sensory neurons, and signing the informed consent form. In contrast,
has a high affinity for TrkA receptors, and is considered patients with hemorrhagic syndromes; immunocom-
an inflammatory mediator and pain modulator.14 promised; with cancer undergoing chemotherapy or
BDNF acts on neurons of the central and peripher- radiotherapy; with convulsive or degenerative dis-
al nervous system and aims to maintain the survival of orders; heavy alcohol users, drug addicts, or those
existing neurons and promote the growth and differen- who were under the influence of sedatives or hypnot-
tiation of new ones, keeping synaptic mechanisms in ics at the time of consultation; patients in treatments
optimal conditions. It has been identified in the hippo- involving the use of needles; patients with chronic kid-
campus, the cerebellum, the cerebral cortex, the ventral ney disease and chronic metabolic disease; and those
tegmental area, and the basal forebrain, which are ar- who did not consent to the administration of the tests
eas involved in the mechanisms of learning, memory, were all excluded.
and motivation. Likewise, BDNF is one of the most active
neurotrophins in neurogenesis, has also been detect- Procedures
ed in several peripheral tissues, and its receptors are
TrkB and p75.15 During the first consultation, each patient was inter-
NGF and BDNF are responsible for the optimal mainte- viewed to obtain their medical history and establish the
nance of the communication mechanisms of the nervous therapy to be implemented according to the parameters
system, both central and peripheral, and therefore alter- of neural therapy. Quality of life was evaluated before
ations in their concentration are observed in pathological the intervention by doing a clinical assessment and ad-
states.16,17 ministering the SF-12 questionnaire; a blood sample
In 2018, Patatel et al.18 confirmed that NGF is an im- was also taken to measure pre-intervention NGF and
portant peripheral pain mediator, especially in relation BDNF serum levels. Before the end of this first consul-
to inflammation, since elevated levels are associated tation, the neural therapy intervention was performed.
with hyperalgesia. Likewise, García-Cosamalón et al.19 Subsequently, two follow-up consultations took place
reported an increase in NGF and BDNF serum levels and every three weeks when, once again, NGF and BDNF
their receptors in cases of pain associated with diseases serum levels were measured, and quality of life was as-
of the intervertebral disc; moreover, this increase was sessed using the SF-12 questionnaire. Based on clinical
related to the activity of pro-inflammatory cytokines. evaluation, instrument scores, and symptomatic man-
On the other hand, neural therapy is a medical treat- ifestations of pain in each patient, neural therapy was
ment that involves the use of local anesthetics such as adjusted during each intervention.
procaine or lidocaine in low doses, taking into account Finally, the serum values of the two neurotrophins
their cell membrane stabilizing action, dielectric ca- tested in the 10 patients and the scores obtained in
pacity and other properties that influence the nervous the SF-12 questionnaire in each of the 3 consultations
system and are the object of research. When applied were analyzed.

2/7
Neural therapy and NGF and BDNF serum levels https://doi.org/10.15446/revfacmed.v69n3.80142

Instruments Serum analysis

SF-12 Health Questionnaire Commercially available enzyme-linked immunosorbent

assay (ELISA) kits were used to measure NGF and BDNF
The SF-12 questionnaire was created in 1996 as a short- serum levels: the ab99978 kit was used for BDNF and
er version of the SF-36 health questionnaire; it assesses the ab99986 kit for NGF; both are produced by Abcam®.
the same items as the original through more concise All measurements were made according to the manu-
questions, yet the scoring and interpretation are same. facturer’s instructions.
The instrument is administered in 5 to 10 minutes and
is composed of 12 questions or items that evaluate pos- Statistical analysis
itive and negative aspects of health status related to
the following considerations: Data were analyzed by means of descriptive statis-
tics, using medians and interquartile ranges (IQR) for
General health perception: to assess patients’ personal quantitative variables, and absolute frequencies and
perception of their health. percentages for qualitative variables. Data for the vari-
Physical functioning: to assess the extent to which ables BDNF, NGF and SF-12 questionnaire score were
health status limits moderate or strenuous physi- presented separately depending on the consultation
cal activity. (consultation 1, follow-up 1 and follow-up 2).
Role - physical: to assess the extent to which phys-
ical health interferes with work and other daily Ethical considerations
activities.
Pain: to assess the severity of pain and its impact on The study took into account the ethical principles for
usual work, both at home and away. medical research in human subjects established by the
Energy/vitality: to compare the sensation of ener- Declaration of Helsinki27 and the scientific, technical and
gy and vitality with the sensation of tiredness and administrative standards for health research of Resolution
exhaustion. 8430 of 1993 of the Ministry of Health of Colombia.28 The
Social functioning: to assess the degree to which phys- research project was approved by the Ethics Committee
ical or emotional health problems interfere with the of the Faculty of Medicine of the Universidad Nacion-
usual social life. al de Colombia according to Minutes No. 017-205-16
Role - emotional: to assess the extent to which emo- of September 22, 2016.
tional problems interfere with work or other daily All patients who took part in the study read, accepted,
activities. and signed the informed consent. The confidentiality of
Mental health: to assess overall mental health, includ- patients’ identities, personal information, and test re-
ing aspects such as depression, anxiety, behavior sults contained in their medical records was maintained.
control, and general well-being.
Results
The response options of this instrument are presented
using Likert scales (with scores from 2 to 6 depending The median age of the participants was 40.5 years (IQR:
on the item). The total score ranges from 0 to 100, and 33-45) and most patients were female (80%). All pa-
the lowest score implies a worse health-related quali- tients consulted for pain in various body areas with a
ty of life. Scores from items of the same dimension are median duration of 9 years (IQR: 5-16) and all reported
averaged to create specific scores, and unanswered having received treatment with conventional or alter-
items are not considered.24-26 native medicine previously (Table 1).

Table 1. Characteristics of the study participants.

Patient Age (years) Sex Type of pain Pain duration
1 53 Female Abdominal and lumbar pain 2 months
2 33 Female Thoracolumbar pain 19 years
3 39 Male Low back pain 16 years
4 26 Female Pelvic pain and dysmenorrhea 10 years
Pain in the left breast due to chronic
5 42 Female 5 months
mastitis
6 45 Female Headache 5 years
7 40 Female Joint pains 11 years
8 41 Female Low back pain 25 years
9 27 Female Joint pains 8 years
10 56 Male Lower limb pain 7 years
Source: Own elaboration.

3/7
Neural therapy and NGF and BDNF serum levels https://doi.org/10.15446/revfacmed.v69n3.80142

The median score obtained by participants in the SF- consultation, it was 34.5 (IQR: 30-37); in the first fol-
12 questionnaire tended to improve in the follow-up low-up, 39.5 (IQR: 34-43), and in the second follow-up,
visits, being more evident in the first one. At the initial 38 (IQR: 36-41) (Figure 1).

45
Total score in the SF-12 questionnaire

40

35

30

25

Consultation 1 Consultation 2 Consultation 3

Figure 1. Box-and-whisker plot of the scores obtained by the participants in the

SF12 health questionnaire.
Source: Own elaboration.

The median NGF serum levels tended to decrease af- 51.9-237.8); in the first follow-up, 42.95 (IQR: 25.9-
ter the intervention, particularly in the first follow-up. 90.4), and in the second follow-up 62.2 (IQR: 0-223.7)
During the initial consultation, it was 157.6 (IQR: (Figure 2).

600

400
NGF (pg/mL)

200

Consultation 1 Consultation 2 Consultation 3

Figure 2. Box-and-whisker plot of variations in nerve growth factor levels in the participants.
Source: Own elaboration.

BDNF serum levels also had an overall downward NGF levels in the first follow-up in 9 patients, which was
trend. In the initial consultation, the value was 29.96 less evident in the second follow-up, and that there
(IQR: 26.76-33.4); in the first follow-up, 19.24 (IQR: was a general correlation between decreased BDNF and
16.43-24.52), and in the second follow-up, 20.43 (IQR: NGF levels before the intervention versus the first and
12.81-35.18) (Figure 3). second follow-ups in 7 patients. Overall, there was an
After analyzing the results, it was found that there improvement in quality of life and a decrease in neuro-
was a correlation between the decrease in BDNF and trophin serum levels.

4/7
Neural therapy and NGF and BDNF serum levels https://doi.org/10.15446/revfacmed.v69n3.80142

60

50

BDNF (pg/mL)
40

30

20

10

Consultation 1 Consultation 2 Consultation 3

Figure 3. Box-and-whisker plot of variations in brain-derived growth factor levels

in the participants.
Source: Own elaboration.

Discussion communication in all human biological systems through

circuits (communication and feedback) organized ver-
Considering that the nervous system is the most elab- tically, creating an information network that runs from
orate communication system in humans and that its the periphery to the central levels.
plasticity allows it to interact with other systems, there The findings of this study lead us to consider that,
is an increasing interest in analyzing variations in neu- after improving biological conditions by removing the
rotrophin serum levels when using neural therapy to interfering fields that keep patients in a constant state of
treat patients with chronic pain. inflammation, neural therapy not only improves symptoms
The present study found that interventions with this and, thus, quality of life, but also lowers neurotrophin
type of therapy resulted in an overall improvement in serum levels because the irritation caused by the in-
pain symptoms, which were assessed using the parame- flammatory process is reduced. This has been reported
ters of the SF-12 questionnaire, as well as in a decrease in studies comparing analgesics and other conventional
in the median NGF and BDNF serum levels, bearing in strategies, which have shown a decrease in neurotro-
mind that, compared with the measurement before the phin levels as a result of treatment.36-38
intervention, they showed a downward trend in the two Therefore, analyzing the behavior of neurotrophin se-
follow-up consultations. These findings coincide with rum levels following neural therapy interventions could
those reported by authors such as McKelvey et al.29 be used as a biomarker for therapeutic success and fol-
and Miller et al.30 in patients who have experienced im- low-up of chronic pain patients.39 This is corroborated by
provements after undergoing pain treatments that inhibit Tu et al.,40 who evaluated the response of neurotrophins
the action of these neurotrophins. with interventions such as acupuncture and obtained
The literature has reported that the clinical course of pa- results similar to those of the present study.
tients undergoing chronic pain treatment varies depending
on factors related to the initial causes of the manifesta- Conclusions
tions, which could explain the variations in the quality of
life and behavior of the serum levels of neurotrophins in The neural therapy intervention resulted in a reduction
these patients.31 Furthermore, many aspects about neu- in NGF and BDNF serum levels, which had increased
rotrophins, which are associated with biological processes in response to each patient’s pathological processes
involving the nervous system, are still unknown.32 and improved their quality of life. Consequently, it is
Similarly, there is evidence of elevated BDNF serum considered that the behavior of serum levels of these
levels in post-traumatic situations related to multiple neurotrophins could be a biomarker for the diagnosis,
traumas involving painful processes, such wars, which treatment, and follow-up of patients with chronic pain.
are known as post-traumatic brain injury and post-trau- However, further studies with larger samples and longer
matic stress disorders.33 follow-up times are necessary to confirm the findings
It should be noted that the effects of neural thera- reported here.
py are not always evident since the beginning; in fact,
pain may worsen at first and subsequently improve.34 Conflicts of interest
As stated by Fisher,35 one of the fundamental pillars
of neural therapy is the autonomic system. It controls None stated by the authors.

5/7
Neural therapy and NGF and BDNF serum levels https://doi.org/10.15446/revfacmed.v69n3.80142

Funding 16. Sohrabji F, Lewis DK. Estrogen-BDNF Interactions: Implica-

tions for Neurodegenerative Diseases. Front Neuroendocrinol.
The present study was funded with resources from the 2006;27(4):404-14. https://doi.org/fjgz5q.
Faculty of Medicine and the Research Directorate of the 17. Phillips C. Brain-Derived Neurotrophic Factor, Depression,
Universidad Nacional de Colombia through the research and Physical Activity: Making the Neuroplastic Connection.
project modality. Neural Plast. 2017;2017:7260130. https://doi.org/gbw579.
18. Patel MK, Kaye AD, Urman RD. Tanezumab: Therapy target-
Acknowledgments ing nerve growth factor in pain pathogenesis. J Anaesthesiol
Clin Pharmacol. 2018;34(1):111-6.
To the patients who, with their help, made this study 19. García-Cosamalón J, Del Valle ME, Calavia MG, García-Suárez O,
possible. López-Muñiz A, Otero J, et al. Intervertebral disc, sensory
nerves and neurotrophins: who is who in discogenic pain. J.
References Anat. 2010;217(1):1-15. https://doi.org/czcwzb.
20. Beltran-Dussan EH, Urrego-Mendoza DZ. Un sistema médico
1. Bradshaw RA, Mobley W, Rush RA. Nerve Growth Factor denominado medicina Neuralterapéutica. In: Beltran-Dussan EH,
and Related Substances: A Brief History and an Introduc- Vega JA, editors. Medicina Neuralterapéutica: un abordaje
tion to the International NGF Meeting Series. Int J Mol Sci. desde los sistemas médicos complejos. Bogotá D.C.: Edi-
2017;18(6):1143. https://doi.org/gbmcxr. torial Universidad Nacional de Colombia; 2013. p. 29-49.
2. Blum R, Konnerth A. Neurotrophin-Mediated Rapid Signaling 21. Dosch JP, Dosch M. Manual Of Neural Therapy Acording To-
in the Central Nervous System: Mechanisms and Functions. Huneke. 2nd ed. New York: Thieme; 2006.
Physiology (Bethesda). 2005;20:70-8. https://doi.org/fkxzmh. 22. Atalay NS, Sahin F, Atalay A, Akkaya N. Comparison of effica-
3. Numakawa T, Odaka H, Adachi N. Actions of Brain-Derived cy of neural therapy and physical therapy in chronic low back
Neurotrophic Factor and Glucocorticoid Stress in Neurogene- pain. Afr J Tradit Complement Altern Med. 2013;10(3):431-5.
sis. Int J Mol Sci. 2017;18(11):2312. https://doi.org/gcq2k2. https://doi.org/gh3v.
4. da Silva-Meirelles L, Simon D, Regner A. Neurotrauma: 23. Katz J, Rosenbloom BN, Fashler S. Chronic Pain, Psycho-
The Crosstalk between Neurotrophins and Inflammation in pathology, and DSM-5 Somatic Symptom Disorder. Can J
the Acutely Injured Brain. Int J Mol Sci. 2017;18(5):1082. Psychiatry. 2015;60(4):160-7. https://doi.org/gfkp3t.
https://doi.org/gddshg. 24. Ware J, Kosinski M, Keller SD. A 12-Item Short-Form Health
5. Shohayeb B, Diab M, Ahmed M, Ng DCH. Factors that influence Survey: Construction of scales and preliminary tests of re-
adult neurogenesis as potential therapy. Transl Neurodege- liability and validity. Medical Care. 1996;34(3):220-33.
ner. 2018;7:4. https://doi.org/gf6chs. https://doi.org/bnqf8d.
6. Brick RM, Sun AX, Tuan RS. Neurotrophically Induced Mes- 25. Huo T, Guo Y, Shenkman E, Muller K. Assessing the reliabili-
enchymal Progenitor Cells Derived from Induced Pluripotent ty of the short form 12 (SF-12) health survey in adults with
Stem Cells Enhance Neuritogenesis via Neurotrophin and Cy- mental health conditions: a report from the wellness incen-
tokine Production. Stem Cells Transl Med. 2018;7(1):45-58. tive and navigation (WIN) study. Health Qual Life Outcomes.
https://doi.org/gg7k. 2018;16(1):34. https://doi.org/gc3pzp.
7. Kernie SG, Parada LF. The Molecular Basis for Understanding 26. White MK, Maher SM, Rizio AA, Bjorner JB. A meta-ana-
Neurotrophins and Their Relevance to Neurologic Disease. lytic review of measurement equivalence study findings of
Arch Neurol. 2000;57(5):654-7. https://doi.org/dgx9bq. the SF-36® and SF-12® Health Surveys across electron-
8. Mitre M, Mariga A, Chao MV. Neurotrophin signalling: nov- ic modes compared to paper administration. Qual Life Res.
el insights into mechanisms and pathophysiology. Clin Sci 2018;27(7):1757-67. https://doi.org/gdrrm3.
(Lond). 2017;131(1):13-23. https://doi.org/gg7m. 27. World Medical Association (WMA). WMA Declaration of Helsin-
9. Sánchez-Sánchez J, Arévalo JC. A Review on Ubiquitination ki – Ethical principles for medical research involving human
of Neurotrophin Receptors: Facts and Perspectives. Int J Mol subjects. Fortaleza: 64th WMA General Assembly; 2013.
Sci. 2017;18(3):630. https://doi.org/f9v89f. 28. Colombia. Ministerio de Salud. Resolución 8430 de 1993 (oc-
10. Aydemir O, Deveci A. [BDNF Measurement in Stress-Related tubre 4): Por la cual se establecen las normas científicas,
Mood Disorders: A Review of Clinical Studies]. Turk Psiki- técnicas y administrativas para la investigación en salud.
yatri Derg. 2009;20(4):385-91. Bogotá D.C.; octubre 4 de 1993.
11. Numakawa T, Suzuki S, Kumamaru E, Adachi N, Richards M, 29. McKelvey L, Shorten GD, O’Keeffe GW. Nerve growth fac-
Kunugi H. BDNF Function and Intracellular Signaling in tor-mediated regulation of pain signalling and proposed new
Neurons. Histol Histopathol. 2010;25(2):237-58. https:// intervention strategies in clinical pain management. J Neu-
doi.org/ghxmst. rochem. 2013;124(3):276-89. https://doi.org/f4hjqz.
12. Al-Qudah MA, Al-Dwairi A. Mechanisms and regulation of neu- 30. Miller RE, Malfait AM, Block JA. Current status of nerve growth
rotrophin synthesis and secretion. Neurosciences (Riyadh). factor antibodies for the treatment of osteoarthritis pain. Clin
2016;21(4):306-13. https://doi.org/gddsh8. Exp Rheumatol. 2017;35(5 Suppl 107):85-7.
13. Lucini C, D’Angelo L, Cacialli P, Palladino A, de Girolamo P. 31. Bernard SA, Chelminski PR, Ives TJ, Ranapurwala SI. Man-
BDNF, Brain, and Regeneration: Insights from Zebrafish. agement of Pain in the United States-A Brief History and
Int J Mol Sci. 2018;19(10):3155. https://doi.org/gfndvf. Implications for the Opioid Epidemic. Health Serv Insights.
14. Indo Y. NGF-dependent neurons and neurobiology of emo- 2018;11:1178632918819440. https://doi.org/gf6gmq.
tions and feelings: Lessons from congenital insensitivity to 32. Koskela M, Bäck S, Võikar V, Richie CT, Domanskyi A, Harvey BK,
pain with anhidrosis. Neurosci Biobehav Rev. 2018;87:1-16. et al. Update of neurotrophic factors in neurobiology of addiction
https://doi.org/gdbmm6. and future directions. Neurobiol Dis. 2017;97(Pt B):189-200.
15. Shen T, You Y, Joseph C, Mirzaei M, Klistorner A, Graham SL, https://doi.org/f9g9m5.
et al. BDNF Polymorphism: A Review of Its Diagnostic and 33. Kaplan GB, Vasterling JJ Vedak PC. Brain-derived neurotrophic
Clinical Relevance in Neurodegenerative Disorders. Aging factor in traumatic brain injury, post-traumatic stress dis-
Dis. 2018;9(3):523-36. https://doi.org/gh3t. order, and their comorbid conditions: role in pathogenesis

6/7
Neural therapy and NGF and BDNF serum levels https://doi.org/10.15446/revfacmed.v69n3.80142

and treatment. Behav Pharmacol. 2010;21(5-6):427-37. Mediates Nociception in Chronic Neuropathic Pain. Biol Psy-
https://doi.org/crxw3n. chiatry. 2017;82(8):608-18. https://doi.org/gh3x.
34. Pinilla-Bonilla LB. Validez y fuerza científica de los fundamentos 38. Liu B, Liu Y, Li N, Zhang J, Zhang X. Oxycodone regulates
de la terapia neural: Un estudio de la obra de Speranzky. In: Bel- incision-induced activation of neurotrophic factors and re-
tran-Dussan EH, Vega JA, editors. Medicina Neuralterapéutica: ceptors in an acute post-surgery pain rat model. J Pain Res.
un abordaje desde los sistemas médicos complejos. Bogotá D.C.: 2018;11:2663-74. https://doi.org/gh3z.
Editorial Universidad Nacional de Colombia; 2013. p. 51-72. 39. Keefe KM, Sheikh IS, Smith GM. Targeting Neurotrophins to
35. Fisher L. Terapia Neural según Huneke. 3rd ed. México D.F.: Specific Populations of Neurons: NGF, BDNF, and NT-3 and
Armin Reimers; 2012 Their Relevance for Treatment of Spinal Cord Injury. Int J
36. Khan N, Smith MT. Neurotrophins and Neuropathic Pain: Mol Sci. 2017;18(3):548. https://doi.org/gdh73v.
Role in Pathobiology. Molecules. 2015;20(6):10657-88. 40. Tu WZ, Li SS, Jiang X, Qian XR, Yang GH, Gu PP, et al. Effect
https://doi.org/f7kcgs. of electro-acupuncture on the BDNF-TrkB pathway in the
37. Zhang H, Qian YL, Li C, Liu D, Wang L, Wang XY, et al. Brain-De- spinal cord of CCI rats. Int J Mol Med. 2018;41(6):3307-15.
rived Neurotrophic Factor in the Mesolimbic Reward Circuitry https://doi.org/gh32.

7/7