mov manipulacion al completo

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Fisioterapia Manual Avanzada Movilización / Manipulación MITOS Y REALIDADES PARADIGMA BIOMECÁNICO Gustavo Plaza Manzano Fisioterapeuta Facultad de Medicina Universidad Complutense de Madrid La forma manual de aplicar un movimiento lento, rítmico y/o sostenido, con la finalidad de reproducir movimientos accesorios y/o fisiológicos a lo largo del rango de movilidad pasiva disponible de una articulación. La forma manual de aplicar un impulso, repentino y preciso, de gran velocidad y corta amplitud, cerca del final del rango de movilidad disponible mediante la ejecución de un movimiento fisiológico, un movimiento accesorio o una combinación de ambos. Alcanza un espacio libre, “parafisiológico”, que se encuentra más allá del ROM pasivo disponible. Se distingue por la reproducción de un sonido, a modo de chasquido, característico de articulaciones sinoviales con fuerte cohesión entre sus superficies. Vernon 2005 MOVILIZACIÓN - MANIPULACIÓN TENSIÓN AMPLITUD ARTICULAR PN MP LA MA 80% 90% 2% 100% ZONA NEUTRA ZONA ELÁSTICA IV III II I V MOVILIZACIÓN - MANIPULACIÓN

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Page 1: Mov manipulacion al completo

Fisioterapia Manual Avanzada Movilización / Manipulación

MITOS Y REALIDADES

PARADIGMA BIOMECÁNICO

Gustavo  Plaza  Manzano    Fisioterapeuta  Facultad  de  Medicina  Universidad  Complutense  de  Madrid

La forma manual de aplicar un movimiento lento, rítmico y/o sostenido, con la finalidad de reproducir movimientos accesorios y/o fisiológicos a lo largo del rango de movilidad pasiva disponible de una articulación.

La forma manual de aplicar un impulso, repentino y preciso, de gran velocidad y corta amplitud, cerca del final del rango de movilidad disponible mediante la ejecución de un movimiento fisiológico, un movimiento accesorio o una combinación de ambos.

Alcanza un espacio libre, “parafisiológico”, que se encuentra más allá del ROM pasivo disponible.

Se distingue por la reproducción de un sonido, a modo de chasquido, característico de articulaciones sinoviales con fuerte cohesión entre sus superficies.

Vernon 2005

MOVILIZACIÓN - MANIPULACIÓN

TEN

SIÓ

N

AMPLITUD ARTICULARPN MP LAMA

80% 90%

2%

100%

ZONA NEUTRA ZONA ELÁSTICA

IV

IIIII

I

V

MOVILIZACIÓN - MANIPULACIÓN

Page 2: Mov manipulacion al completo

Los mecanismos de acción de las técnicas de terapia manual no se conocen por completo, pero se cree que los efectos mecánicos y neurofisiológicos desempeñan un papel importante en los mismos.

POSIBLES EFECTOS MOVILIZACIÓN - MANIPULACIÓN

Sistemas del Dolor

Sistema Nervioso Simpático

Sistema Motor

Estructurales-Posturales-Biomecánicos

Mecanismo Placebo

Estimulación de los procesos de reparación tisular.

Modificación del entorno químico de los nociceptores periféricos.

Activación de los mecanismos inhibitorios segmentarios.

Activación de los mecanismos inhibitorios descendentes.

Mecanismo Placebo.

Disminución de la Percepción de Dolor

Wright 2002

¿Qué ocurre en el tejido con el movimiento?

Normalización de la homeostasis del tejido conectivo.

El movimiento favorece el depósito de colágeno en la dirección adecuada, mantiene el equilibrio entre los constituyentes del tejido conectivo, refuerza la regeneración vascular normal, y reduce la formación excesiva de puentes y adherencias.

Existe fuerte evidencia de que la tensión periódica y moderada es esencial para la nutrición y viabilidad del tejido durante la curación.

Page 3: Mov manipulacion al completo

Sistema Modulador Descendente

Representado a nivel del tronco cerebral (SGP, RVM, DLTP), y se encuentran bajo la influencia del cerebro anterior (corteza y límbico).

Puede atenuar o aumentar la transmisión nociceptiva, produciendo analgesia o hiperalgesia, respectivamente.

Efectos sobre el dolor

Numerosos trabajos estudian su efecto sobre el umbral de sensibilidad mecánica y térmica al dolor y sobre las respuestas del sistema nervioso simpático.

Se puede concluir que;

Parecen existir respuestas hipoalgésicas inmediatas, medidas por el aumento de sensibilidad mecánica al dolor y por la disminución de los campos de referencia cutánea del mismo.

Estas respuestas no parecen haber influido sobre el umbral de sensibilidad térmica.

Vicenzino 1998, Vernon 2000, Sterling 2001

No presenta características opioides:

- No afecta a niveles de β-endorfinas.

- No revierte con Naloxona.

- No muestra tolerancia tras aplicaciones repetidas.

- Se atenúa con antagonistas de receptores noradrenérgicos y se bloquea con antagonistas de receptores serotonérgicos (Skyba 2003).

Considerable evidencia respalda que la movilización articular es un estímulo suficiente para inducir respuestas excitatorias simpáticas. Parece existir una correlación entre la rapidez y magnitud de la respuesta excitatoria simpática con el aumento del umbral de sensibilidad mecánica al dolor.

Efectos sobre el Dolor y el SNS

Christian 1998, Vicenzino 2000, Souvlis 1999, Paungmali 2003

Page 4: Mov manipulacion al completo

Se ha investigado el efecto de la movilización cervical en la percepción de dolor, en la función motora y en la función autonómica.

Este estudio mostró un aumento del 22% en el UDP medido a nivel de las articulaciones interapofisarias C5-C6 sintomáticas, una mejora en la función de los músculos cervicales en el test de FCC y un aumento significativo en la conductancia cutánea y una disminución de la temperatura de la piel.

Sterling 2001

Efectos sobre el Dolor, Función Motora y SNS

La movilización articular produce analgesia no opioide, mediada por

serotonina y noradrenalina liberadas desde las regiones rostral

ventromedial del bulbo y dorsolateral ponto-mesencefálica de las vías

descendentes de modulación del dolor.

Skyba DA 2003

Efectos sobre el dolor

journal of orthopaedic & sports physical therapy | volume 44 | number 4 | april 2014 | 231

[ RESEARCH REPORT ]

Spinal manipulation (SM) is a common treatment approach for pain reduction in low back and neck disorders.37,38,41 The effectiveness of SM to treat musculoskeletal pain, such as spinal pain, has been summarized in recent Cochrane reviews.32,56

Overall, the evidence suggests that SM provides improvements in pain re-lief, though similar results have been de-scribed in other competing treatments, such as general practitioner manage-ment, medication, and exercise, in pa-tients with musculoskeletal pain.6,7 It has been shown that the presence of pain in-

duces changes in the anatomy and func-tion of the central and peripheral nervous systems.20,46,53 Therefore, research on an asymptomatic population may be impor-tant to accurately determine the antinoci-ceptive mechanism of SM. Several studies in asymptomatic subjects have shown that SM techniques induce changes in

physiological reflexes,28 increase neu-romuscular excitability,22 and modify sensitivity.30

The mechanisms through which SM alters musculoskeletal pain are still unknown. However, current evidence suggests an interaction between the mechanical stimulus and the associated neurophysiological responses,6,51 includ-ing rapid hypoalgesia with concurrent sympathetic nervous system and mo-tor system excitation, similar to those generated by direct stimulation of the periaqueductal gray matter.61,68 Recent animal studies show that the analgesia produced by joint mobilization involves serotonin and noradrenaline receptors in the spinal cord, thereby performing a supporting role for central mechanisms of pain modulation.60 Several neuropep-tides, such as neurotensin,23 oxytocin,29 or orexin A,3 have been associated with hypoalgesia and pain modulation, and it is well known that cortisol plays an anal-gesic role related to stress responses.4,44 Recent theories have also suggested that chronic pain could be partly maintained by maladaptive physiological responses of the organism facing a recurrent stressor, a situation related to high cortisol lev-els.45,66 To our knowledge, there is a lack of studies analyzing changes in these no-ciception-related biochemical markers in response to manual therapy.

! STUDY DESIGN: Controlled, repeated-mea-sures, single-blind randomized study.

! OBJECTIVES: To determine the effect of cervical or thoracic manipulation on neurotensin, oxytocin, orexin A, and cortisol levels.

! BACKGROUND: Previous studies have re-searched the effect of spinal manipulation on pain modulation and/or range of movement. However, there is little knowledge of the biochemical process that supports the antinociceptive effect of spinal manipulation.

! METHODS: Thirty asymptomatic subjects were randomly divided into 3 groups: cervical manipulation (n = 10), thoracic manipulation (n = 10), and nonmanipulation (control) (n = 10). Blood samples were extracted before, immediately after, and 2 hours after each intervention. Neurotensin, oxytocin, and orexin A were determined in plasma using enzyme-linked immuno assay. Cortisol was measured by microparticulate enzyme immuno assay in serum samples.

! RESULTS: Immediately after the intervention, significantly higher values of neurotensin (P<.05) and oxytocin (P<.001) levels were observed with both cervical and thoracic manipulation, whereas cortisol concentration was increased only in the cervical manipulation group (P<.05). No changes were detected for orexin A levels. Two hours after the intervention, no significant differences were observed in between-group analysis.

! CONCLUSION: The mechanical stimulus pro-vided by spinal manipulation triggers an increase in neurotensin, oxytocin, and cortisol blood levels. Data suggest that the initial capability of the tissues to tolerate mechanical deformation affects the capacity of these tissues to produce an induc-tion of neuropeptide expression. J Orthop Sports Phys Ther 2014;44(4):231-239. Epub 22 January 2014. doi:10.2519/jospt.2014.4996

! KEY WORDS: cortisol, neurotensin, orexin A, oxytocin, spinal manipulation

1Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Universidad Complutense de Madrid, Madrid, Spain. 2Department of Health Sciences, Universidad de Jaén, Jaén, Spain. The protocol for this study was approved by the Ethical Committee in Clinical Research of the Universidad de Jaén, Jaén, Spain. The authors certify that they have no affiliations with or financial involvement in any organization or entity with a direct financial interest in the subject matter or materials discussed in the article. Address correspondence to Dr Fidel Hita-Contreras, Department of Health Sciences (B-3/272). Universidad de Jaén. Campus Las Lagunillas s/n, 23071 Jaén, Spain. E-mail: [email protected] ! Copyright ©2014 Journal of Orthopaedic & Sports Physical Therapy®

GUSTAVO PLAZA-MANZANO, PT1 • FRANCISCO MOLINA, PT, PhD2 • RAFAEL LOMAS-VEGA, PT, PhD2

ANTONIO MARTÍNEZ-AMAT, PhD2 • ALEXANDER ACHALANDABASO, PT1 • FIDEL HITA-CONTRERAS, MD, PhD2

Changes in Biochemical Markers of Pain Perception and Stress Response

After Spinal Manipulation

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journal of orthopaedic & sports physical therapy | volume 44 | number 4 | april 2014 | 231

[ RESEARCH REPORT ]

Spinal manipulation (SM) is a common treatment approach for pain reduction in low back and neck disorders.37,38,41 The effectiveness of SM to treat musculoskeletal pain, such as spinal pain, has been summarized in recent Cochrane reviews.32,56

Overall, the evidence suggests that SM provides improvements in pain re-lief, though similar results have been de-scribed in other competing treatments, such as general practitioner manage-ment, medication, and exercise, in pa-tients with musculoskeletal pain.6,7 It has been shown that the presence of pain in-

duces changes in the anatomy and func-tion of the central and peripheral nervous systems.20,46,53 Therefore, research on an asymptomatic population may be impor-tant to accurately determine the antinoci-ceptive mechanism of SM. Several studies in asymptomatic subjects have shown that SM techniques induce changes in

physiological reflexes,28 increase neu-romuscular excitability,22 and modify sensitivity.30

The mechanisms through which SM alters musculoskeletal pain are still unknown. However, current evidence suggests an interaction between the mechanical stimulus and the associated neurophysiological responses,6,51 includ-ing rapid hypoalgesia with concurrent sympathetic nervous system and mo-tor system excitation, similar to those generated by direct stimulation of the periaqueductal gray matter.61,68 Recent animal studies show that the analgesia produced by joint mobilization involves serotonin and noradrenaline receptors in the spinal cord, thereby performing a supporting role for central mechanisms of pain modulation.60 Several neuropep-tides, such as neurotensin,23 oxytocin,29 or orexin A,3 have been associated with hypoalgesia and pain modulation, and it is well known that cortisol plays an anal-gesic role related to stress responses.4,44 Recent theories have also suggested that chronic pain could be partly maintained by maladaptive physiological responses of the organism facing a recurrent stressor, a situation related to high cortisol lev-els.45,66 To our knowledge, there is a lack of studies analyzing changes in these no-ciception-related biochemical markers in response to manual therapy.

! STUDY DESIGN: Controlled, repeated-mea-sures, single-blind randomized study.

! OBJECTIVES: To determine the effect of cervical or thoracic manipulation on neurotensin, oxytocin, orexin A, and cortisol levels.

! BACKGROUND: Previous studies have re-searched the effect of spinal manipulation on pain modulation and/or range of movement. However, there is little knowledge of the biochemical process that supports the antinociceptive effect of spinal manipulation.

! METHODS: Thirty asymptomatic subjects were randomly divided into 3 groups: cervical manipulation (n = 10), thoracic manipulation (n = 10), and nonmanipulation (control) (n = 10). Blood samples were extracted before, immediately after, and 2 hours after each intervention. Neurotensin, oxytocin, and orexin A were determined in plasma using enzyme-linked immuno assay. Cortisol was measured by microparticulate enzyme immuno assay in serum samples.

! RESULTS: Immediately after the intervention, significantly higher values of neurotensin (P<.05) and oxytocin (P<.001) levels were observed with both cervical and thoracic manipulation, whereas cortisol concentration was increased only in the cervical manipulation group (P<.05). No changes were detected for orexin A levels. Two hours after the intervention, no significant differences were observed in between-group analysis.

! CONCLUSION: The mechanical stimulus pro-vided by spinal manipulation triggers an increase in neurotensin, oxytocin, and cortisol blood levels. Data suggest that the initial capability of the tissues to tolerate mechanical deformation affects the capacity of these tissues to produce an induc-tion of neuropeptide expression. J Orthop Sports Phys Ther 2014;44(4):231-239. Epub 22 January 2014. doi:10.2519/jospt.2014.4996

! KEY WORDS: cortisol, neurotensin, orexin A, oxytocin, spinal manipulation

1Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Universidad Complutense de Madrid, Madrid, Spain. 2Department of Health Sciences, Universidad de Jaén, Jaén, Spain. The protocol for this study was approved by the Ethical Committee in Clinical Research of the Universidad de Jaén, Jaén, Spain. The authors certify that they have no affiliations with or financial involvement in any organization or entity with a direct financial interest in the subject matter or materials discussed in the article. Address correspondence to Dr Fidel Hita-Contreras, Department of Health Sciences (B-3/272). Universidad de Jaén. Campus Las Lagunillas s/n, 23071 Jaén, Spain. E-mail: [email protected] ! Copyright ©2014 Journal of Orthopaedic & Sports Physical Therapy®

GUSTAVO PLAZA-MANZANO, PT1 • FRANCISCO MOLINA, PT, PhD2 • RAFAEL LOMAS-VEGA, PT, PhD2

ANTONIO MARTÍNEZ-AMAT, PhD2 • ALEXANDER ACHALANDABASO, PT1 • FIDEL HITA-CONTRERAS, MD, PhD2

Changes in Biochemical Markers of Pain Perception and Stress Response

After Spinal Manipulation

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journal of orthopaedic & sports physical therapy | volume 44 | number 4 | april 2014 | 235

the same way, the cervical SM group showed increased oxytocin values when compared with the thoracic SM group immediately postintervention (mean difference, –104.16; 95% CI: –174.62, –33.71; P<.002) (FIGURE 4C).

Likewise, in the within-group analy-sis, an increase in oxytocin plasma con-centration levels was detected in both the cervical manipulation and thoracic manipulation groups immediately post-intervention (P<.001) compared to pre-intervention levels (TABLE 3). At 2 hours after the intervention, an increase was found only in the cervical SM group (P<.05) when compared with preinter-vention levels (TABLE 4).

Cortisol Concentration in Blood SamplesUsing a mixed-model ANOVA, the group-by-time interaction for cortisol as a dependent variable was significant (P<.001). Eta-square analysis yielded a 32% effect size (TABLE 2).

Blood samples extracted from the cervical SM group showed a significant increase in cortisol plasma concentration immediately postintervention compared with baseline values (P<.001) (TABLE 3). On the other hand, a significant decrease was detected at 2 hours postintervention in the thoracic SM group when compared with the preintervention values (P<.05) (TABLE 4).

A significant increase in the between-group analysis was found immediately posttreatment in the cervical manipula-tion group compared with the control group (mean difference, 4.60; 95% CI: 0.65, 8.55; P = .018) and the thoracic ma-nipulation group (mean difference, 4.10; 95% CI: 0.15, 8.05; P<.040) (FIGURE 4D).

DISCUSSION

Several studies currently sup-port the idea that the analgesic effect of manual therapy is mediated by

central mechanisms of pain modulation through the modulation of neuropeptide production.5,27,60 To our knowledge, this is the first work to analyze neurotensin,

oxytocin, orexin A, and cortisol levels af-ter a cervical or a thoracic manipulation in asymptomatic subjects.

Neurotensin is a 13-amino acid pro-duced in several regions of the central nervous system, such as the substan-tia nigra, amygdala, hypothalamus, prefrontal cortex, periaqueductal gray matter, and the spinal cord,62 and it has several actions, including analgesia.14,23 Our data indicate an increase in neu-rotensin plasmatic concentration after an SM, suggesting that the mechanical stimulus provided by SM is enough to modulate the liberation of this neuro-peptide. In this sense, neurotensin has long been known to include analgesia among its actions.9,16,23 The analgesic ac-tions of neurotensin are readily distinct from those of the opioids, based on their insensitivity to the highly opioid-selective antagonist naloxone, thus ruling out an opioid mechanism.55 Neurotensin acts as

part of the peripheral and central mecha-nisms of pain modulation,23 because the antinociceptive effect of neurotensin has been reported after the injection of the peptide in many brain areas.62 There are anatomical data suggesting an in-teraction between neurotensin and se-rotonergic neurons. As a matter of fact, neurons of the rostral part of the raphe synthesize neurotensin, whereas neuro-tensin receptors are widely expressed in most of the raphe.18,40,57 The functional role of neurotensin in the raphe remains to be determined, but it may participate in the modulation of some of the known functions of the serotonergic system, in-cluding nociception13 and stress-related responses.19 It may also play a role in mediating stress-induced analgesia, as neurotensin knockout mice and rats pretreated with neurotensin antagonists show no increase in pain tolerance after stress.34 Recent studies with neurotensin

2

0Preintervention O h

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FIGURE 4. Mean and 95% confidence interval for neuropeptide concentration in blood samples. (A) neurotensin, (B) orexin A, (C) oxytocin, (D) cortisol. *P<.05.

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journal of orthopaedic & sports physical therapy | volume 44 | number 4 | april 2014 | 231

[ RESEARCH REPORT ]

Spinal manipulation (SM) is a common treatment approach for pain reduction in low back and neck disorders.37,38,41 The effectiveness of SM to treat musculoskeletal pain, such as spinal pain, has been summarized in recent Cochrane reviews.32,56

Overall, the evidence suggests that SM provides improvements in pain re-lief, though similar results have been de-scribed in other competing treatments, such as general practitioner manage-ment, medication, and exercise, in pa-tients with musculoskeletal pain.6,7 It has been shown that the presence of pain in-

duces changes in the anatomy and func-tion of the central and peripheral nervous systems.20,46,53 Therefore, research on an asymptomatic population may be impor-tant to accurately determine the antinoci-ceptive mechanism of SM. Several studies in asymptomatic subjects have shown that SM techniques induce changes in

physiological reflexes,28 increase neu-romuscular excitability,22 and modify sensitivity.30

The mechanisms through which SM alters musculoskeletal pain are still unknown. However, current evidence suggests an interaction between the mechanical stimulus and the associated neurophysiological responses,6,51 includ-ing rapid hypoalgesia with concurrent sympathetic nervous system and mo-tor system excitation, similar to those generated by direct stimulation of the periaqueductal gray matter.61,68 Recent animal studies show that the analgesia produced by joint mobilization involves serotonin and noradrenaline receptors in the spinal cord, thereby performing a supporting role for central mechanisms of pain modulation.60 Several neuropep-tides, such as neurotensin,23 oxytocin,29 or orexin A,3 have been associated with hypoalgesia and pain modulation, and it is well known that cortisol plays an anal-gesic role related to stress responses.4,44 Recent theories have also suggested that chronic pain could be partly maintained by maladaptive physiological responses of the organism facing a recurrent stressor, a situation related to high cortisol lev-els.45,66 To our knowledge, there is a lack of studies analyzing changes in these no-ciception-related biochemical markers in response to manual therapy.

! STUDY DESIGN: Controlled, repeated-mea-sures, single-blind randomized study.

! OBJECTIVES: To determine the effect of cervical or thoracic manipulation on neurotensin, oxytocin, orexin A, and cortisol levels.

! BACKGROUND: Previous studies have re-searched the effect of spinal manipulation on pain modulation and/or range of movement. However, there is little knowledge of the biochemical process that supports the antinociceptive effect of spinal manipulation.

! METHODS: Thirty asymptomatic subjects were randomly divided into 3 groups: cervical manipulation (n = 10), thoracic manipulation (n = 10), and nonmanipulation (control) (n = 10). Blood samples were extracted before, immediately after, and 2 hours after each intervention. Neurotensin, oxytocin, and orexin A were determined in plasma using enzyme-linked immuno assay. Cortisol was measured by microparticulate enzyme immuno assay in serum samples.

! RESULTS: Immediately after the intervention, significantly higher values of neurotensin (P<.05) and oxytocin (P<.001) levels were observed with both cervical and thoracic manipulation, whereas cortisol concentration was increased only in the cervical manipulation group (P<.05). No changes were detected for orexin A levels. Two hours after the intervention, no significant differences were observed in between-group analysis.

! CONCLUSION: The mechanical stimulus pro-vided by spinal manipulation triggers an increase in neurotensin, oxytocin, and cortisol blood levels. Data suggest that the initial capability of the tissues to tolerate mechanical deformation affects the capacity of these tissues to produce an induc-tion of neuropeptide expression. J Orthop Sports Phys Ther 2014;44(4):231-239. Epub 22 January 2014. doi:10.2519/jospt.2014.4996

! KEY WORDS: cortisol, neurotensin, orexin A, oxytocin, spinal manipulation

1Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Universidad Complutense de Madrid, Madrid, Spain. 2Department of Health Sciences, Universidad de Jaén, Jaén, Spain. The protocol for this study was approved by the Ethical Committee in Clinical Research of the Universidad de Jaén, Jaén, Spain. The authors certify that they have no affiliations with or financial involvement in any organization or entity with a direct financial interest in the subject matter or materials discussed in the article. Address correspondence to Dr Fidel Hita-Contreras, Department of Health Sciences (B-3/272). Universidad de Jaén. Campus Las Lagunillas s/n, 23071 Jaén, Spain. E-mail: [email protected] ! Copyright ©2014 Journal of Orthopaedic & Sports Physical Therapy®

GUSTAVO PLAZA-MANZANO, PT1 • FRANCISCO MOLINA, PT, PhD2 • RAFAEL LOMAS-VEGA, PT, PhD2

ANTONIO MARTÍNEZ-AMAT, PhD2 • ALEXANDER ACHALANDABASO, PT1 • FIDEL HITA-CONTRERAS, MD, PhD2

Changes in Biochemical Markers of Pain Perception and Stress Response

After Spinal Manipulation

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journal of orthopaedic & sports physical therapy | volume 44 | number 4 | april 2014 | 235

the same way, the cervical SM group showed increased oxytocin values when compared with the thoracic SM group immediately postintervention (mean difference, –104.16; 95% CI: –174.62, –33.71; P<.002) (FIGURE 4C).

Likewise, in the within-group analy-sis, an increase in oxytocin plasma con-centration levels was detected in both the cervical manipulation and thoracic manipulation groups immediately post-intervention (P<.001) compared to pre-intervention levels (TABLE 3). At 2 hours after the intervention, an increase was found only in the cervical SM group (P<.05) when compared with preinter-vention levels (TABLE 4).

Cortisol Concentration in Blood SamplesUsing a mixed-model ANOVA, the group-by-time interaction for cortisol as a dependent variable was significant (P<.001). Eta-square analysis yielded a 32% effect size (TABLE 2).

Blood samples extracted from the cervical SM group showed a significant increase in cortisol plasma concentration immediately postintervention compared with baseline values (P<.001) (TABLE 3). On the other hand, a significant decrease was detected at 2 hours postintervention in the thoracic SM group when compared with the preintervention values (P<.05) (TABLE 4).

A significant increase in the between-group analysis was found immediately posttreatment in the cervical manipula-tion group compared with the control group (mean difference, 4.60; 95% CI: 0.65, 8.55; P = .018) and the thoracic ma-nipulation group (mean difference, 4.10; 95% CI: 0.15, 8.05; P<.040) (FIGURE 4D).

DISCUSSION

Several studies currently sup-port the idea that the analgesic effect of manual therapy is mediated by

central mechanisms of pain modulation through the modulation of neuropeptide production.5,27,60 To our knowledge, this is the first work to analyze neurotensin,

oxytocin, orexin A, and cortisol levels af-ter a cervical or a thoracic manipulation in asymptomatic subjects.

Neurotensin is a 13-amino acid pro-duced in several regions of the central nervous system, such as the substan-tia nigra, amygdala, hypothalamus, prefrontal cortex, periaqueductal gray matter, and the spinal cord,62 and it has several actions, including analgesia.14,23 Our data indicate an increase in neu-rotensin plasmatic concentration after an SM, suggesting that the mechanical stimulus provided by SM is enough to modulate the liberation of this neuro-peptide. In this sense, neurotensin has long been known to include analgesia among its actions.9,16,23 The analgesic ac-tions of neurotensin are readily distinct from those of the opioids, based on their insensitivity to the highly opioid-selective antagonist naloxone, thus ruling out an opioid mechanism.55 Neurotensin acts as

part of the peripheral and central mecha-nisms of pain modulation,23 because the antinociceptive effect of neurotensin has been reported after the injection of the peptide in many brain areas.62 There are anatomical data suggesting an in-teraction between neurotensin and se-rotonergic neurons. As a matter of fact, neurons of the rostral part of the raphe synthesize neurotensin, whereas neuro-tensin receptors are widely expressed in most of the raphe.18,40,57 The functional role of neurotensin in the raphe remains to be determined, but it may participate in the modulation of some of the known functions of the serotonergic system, in-cluding nociception13 and stress-related responses.19 It may also play a role in mediating stress-induced analgesia, as neurotensin knockout mice and rats pretreated with neurotensin antagonists show no increase in pain tolerance after stress.34 Recent studies with neurotensin

2

0Preintervention O h

postintervention2 h

postintervention

4

6

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14

A

Neurotensin

0

100

50

150

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Conc

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/mg

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FIGURE 4. Mean and 95% confidence interval for neuropeptide concentration in blood samples. (A) neurotensin, (B) orexin A, (C) oxytocin, (D) cortisol. *P<.05.

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journal of orthopaedic & sports physical therapy | volume 44 | number 4 | april 2014 | 235

the same way, the cervical SM group showed increased oxytocin values when compared with the thoracic SM group immediately postintervention (mean difference, –104.16; 95% CI: –174.62, –33.71; P<.002) (FIGURE 4C).

Likewise, in the within-group analy-sis, an increase in oxytocin plasma con-centration levels was detected in both the cervical manipulation and thoracic manipulation groups immediately post-intervention (P<.001) compared to pre-intervention levels (TABLE 3). At 2 hours after the intervention, an increase was found only in the cervical SM group (P<.05) when compared with preinter-vention levels (TABLE 4).

Cortisol Concentration in Blood SamplesUsing a mixed-model ANOVA, the group-by-time interaction for cortisol as a dependent variable was significant (P<.001). Eta-square analysis yielded a 32% effect size (TABLE 2).

Blood samples extracted from the cervical SM group showed a significant increase in cortisol plasma concentration immediately postintervention compared with baseline values (P<.001) (TABLE 3). On the other hand, a significant decrease was detected at 2 hours postintervention in the thoracic SM group when compared with the preintervention values (P<.05) (TABLE 4).

A significant increase in the between-group analysis was found immediately posttreatment in the cervical manipula-tion group compared with the control group (mean difference, 4.60; 95% CI: 0.65, 8.55; P = .018) and the thoracic ma-nipulation group (mean difference, 4.10; 95% CI: 0.15, 8.05; P<.040) (FIGURE 4D).

DISCUSSION

Several studies currently sup-port the idea that the analgesic effect of manual therapy is mediated by

central mechanisms of pain modulation through the modulation of neuropeptide production.5,27,60 To our knowledge, this is the first work to analyze neurotensin,

oxytocin, orexin A, and cortisol levels af-ter a cervical or a thoracic manipulation in asymptomatic subjects.

Neurotensin is a 13-amino acid pro-duced in several regions of the central nervous system, such as the substan-tia nigra, amygdala, hypothalamus, prefrontal cortex, periaqueductal gray matter, and the spinal cord,62 and it has several actions, including analgesia.14,23 Our data indicate an increase in neu-rotensin plasmatic concentration after an SM, suggesting that the mechanical stimulus provided by SM is enough to modulate the liberation of this neuro-peptide. In this sense, neurotensin has long been known to include analgesia among its actions.9,16,23 The analgesic ac-tions of neurotensin are readily distinct from those of the opioids, based on their insensitivity to the highly opioid-selective antagonist naloxone, thus ruling out an opioid mechanism.55 Neurotensin acts as

part of the peripheral and central mecha-nisms of pain modulation,23 because the antinociceptive effect of neurotensin has been reported after the injection of the peptide in many brain areas.62 There are anatomical data suggesting an in-teraction between neurotensin and se-rotonergic neurons. As a matter of fact, neurons of the rostral part of the raphe synthesize neurotensin, whereas neuro-tensin receptors are widely expressed in most of the raphe.18,40,57 The functional role of neurotensin in the raphe remains to be determined, but it may participate in the modulation of some of the known functions of the serotonergic system, in-cluding nociception13 and stress-related responses.19 It may also play a role in mediating stress-induced analgesia, as neurotensin knockout mice and rats pretreated with neurotensin antagonists show no increase in pain tolerance after stress.34 Recent studies with neurotensin

2

0Preintervention O h

postintervention2 h

postintervention

4

6

8

10

12

14

A

Neurotensin

0

100

50

150

200

250

300

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100

150

200

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300

350

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Preintervention O h postintervention

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Cortisol

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FIGURE 4. Mean and 95% confidence interval for neuropeptide concentration in blood samples. (A) neurotensin, (B) orexin A, (C) oxytocin, (D) cortisol. *P<.05.

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journal of orthopaedic & sports physical therapy | volume 44 | number 4 | april 2014 | 235

the same way, the cervical SM group showed increased oxytocin values when compared with the thoracic SM group immediately postintervention (mean difference, –104.16; 95% CI: –174.62, –33.71; P<.002) (FIGURE 4C).

Likewise, in the within-group analy-sis, an increase in oxytocin plasma con-centration levels was detected in both the cervical manipulation and thoracic manipulation groups immediately post-intervention (P<.001) compared to pre-intervention levels (TABLE 3). At 2 hours after the intervention, an increase was found only in the cervical SM group (P<.05) when compared with preinter-vention levels (TABLE 4).

Cortisol Concentration in Blood SamplesUsing a mixed-model ANOVA, the group-by-time interaction for cortisol as a dependent variable was significant (P<.001). Eta-square analysis yielded a 32% effect size (TABLE 2).

Blood samples extracted from the cervical SM group showed a significant increase in cortisol plasma concentration immediately postintervention compared with baseline values (P<.001) (TABLE 3). On the other hand, a significant decrease was detected at 2 hours postintervention in the thoracic SM group when compared with the preintervention values (P<.05) (TABLE 4).

A significant increase in the between-group analysis was found immediately posttreatment in the cervical manipula-tion group compared with the control group (mean difference, 4.60; 95% CI: 0.65, 8.55; P = .018) and the thoracic ma-nipulation group (mean difference, 4.10; 95% CI: 0.15, 8.05; P<.040) (FIGURE 4D).

DISCUSSION

Several studies currently sup-port the idea that the analgesic effect of manual therapy is mediated by

central mechanisms of pain modulation through the modulation of neuropeptide production.5,27,60 To our knowledge, this is the first work to analyze neurotensin,

oxytocin, orexin A, and cortisol levels af-ter a cervical or a thoracic manipulation in asymptomatic subjects.

Neurotensin is a 13-amino acid pro-duced in several regions of the central nervous system, such as the substan-tia nigra, amygdala, hypothalamus, prefrontal cortex, periaqueductal gray matter, and the spinal cord,62 and it has several actions, including analgesia.14,23 Our data indicate an increase in neu-rotensin plasmatic concentration after an SM, suggesting that the mechanical stimulus provided by SM is enough to modulate the liberation of this neuro-peptide. In this sense, neurotensin has long been known to include analgesia among its actions.9,16,23 The analgesic ac-tions of neurotensin are readily distinct from those of the opioids, based on their insensitivity to the highly opioid-selective antagonist naloxone, thus ruling out an opioid mechanism.55 Neurotensin acts as

part of the peripheral and central mecha-nisms of pain modulation,23 because the antinociceptive effect of neurotensin has been reported after the injection of the peptide in many brain areas.62 There are anatomical data suggesting an in-teraction between neurotensin and se-rotonergic neurons. As a matter of fact, neurons of the rostral part of the raphe synthesize neurotensin, whereas neuro-tensin receptors are widely expressed in most of the raphe.18,40,57 The functional role of neurotensin in the raphe remains to be determined, but it may participate in the modulation of some of the known functions of the serotonergic system, in-cluding nociception13 and stress-related responses.19 It may also play a role in mediating stress-induced analgesia, as neurotensin knockout mice and rats pretreated with neurotensin antagonists show no increase in pain tolerance after stress.34 Recent studies with neurotensin

2

0Preintervention O h

postintervention2 h

postintervention

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6

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10

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14

A

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0

100

50

150

200

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300

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FIGURE 4. Mean and 95% confidence interval for neuropeptide concentration in blood samples. (A) neurotensin, (B) orexin A, (C) oxytocin, (D) cortisol. *P<.05.

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journal of orthopaedic & sports physical therapy | volume 44 | number 4 | april 2014 | 235

the same way, the cervical SM group showed increased oxytocin values when compared with the thoracic SM group immediately postintervention (mean difference, –104.16; 95% CI: –174.62, –33.71; P<.002) (FIGURE 4C).

Likewise, in the within-group analy-sis, an increase in oxytocin plasma con-centration levels was detected in both the cervical manipulation and thoracic manipulation groups immediately post-intervention (P<.001) compared to pre-intervention levels (TABLE 3). At 2 hours after the intervention, an increase was found only in the cervical SM group (P<.05) when compared with preinter-vention levels (TABLE 4).

Cortisol Concentration in Blood SamplesUsing a mixed-model ANOVA, the group-by-time interaction for cortisol as a dependent variable was significant (P<.001). Eta-square analysis yielded a 32% effect size (TABLE 2).

Blood samples extracted from the cervical SM group showed a significant increase in cortisol plasma concentration immediately postintervention compared with baseline values (P<.001) (TABLE 3). On the other hand, a significant decrease was detected at 2 hours postintervention in the thoracic SM group when compared with the preintervention values (P<.05) (TABLE 4).

A significant increase in the between-group analysis was found immediately posttreatment in the cervical manipula-tion group compared with the control group (mean difference, 4.60; 95% CI: 0.65, 8.55; P = .018) and the thoracic ma-nipulation group (mean difference, 4.10; 95% CI: 0.15, 8.05; P<.040) (FIGURE 4D).

DISCUSSION

Several studies currently sup-port the idea that the analgesic effect of manual therapy is mediated by

central mechanisms of pain modulation through the modulation of neuropeptide production.5,27,60 To our knowledge, this is the first work to analyze neurotensin,

oxytocin, orexin A, and cortisol levels af-ter a cervical or a thoracic manipulation in asymptomatic subjects.

Neurotensin is a 13-amino acid pro-duced in several regions of the central nervous system, such as the substan-tia nigra, amygdala, hypothalamus, prefrontal cortex, periaqueductal gray matter, and the spinal cord,62 and it has several actions, including analgesia.14,23 Our data indicate an increase in neu-rotensin plasmatic concentration after an SM, suggesting that the mechanical stimulus provided by SM is enough to modulate the liberation of this neuro-peptide. In this sense, neurotensin has long been known to include analgesia among its actions.9,16,23 The analgesic ac-tions of neurotensin are readily distinct from those of the opioids, based on their insensitivity to the highly opioid-selective antagonist naloxone, thus ruling out an opioid mechanism.55 Neurotensin acts as

part of the peripheral and central mecha-nisms of pain modulation,23 because the antinociceptive effect of neurotensin has been reported after the injection of the peptide in many brain areas.62 There are anatomical data suggesting an in-teraction between neurotensin and se-rotonergic neurons. As a matter of fact, neurons of the rostral part of the raphe synthesize neurotensin, whereas neuro-tensin receptors are widely expressed in most of the raphe.18,40,57 The functional role of neurotensin in the raphe remains to be determined, but it may participate in the modulation of some of the known functions of the serotonergic system, in-cluding nociception13 and stress-related responses.19 It may also play a role in mediating stress-induced analgesia, as neurotensin knockout mice and rats pretreated with neurotensin antagonists show no increase in pain tolerance after stress.34 Recent studies with neurotensin

2

0Preintervention O h

postintervention2 h

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14

A

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0

100

50

150

200

250

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FIGURE 4. Mean and 95% confidence interval for neuropeptide concentration in blood samples. (A) neurotensin, (B) orexin A, (C) oxytocin, (D) cortisol. *P<.05.

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Page 5: Mov manipulacion al completo

Original article

Immediate effects of spinal manipulation on nitric oxide, substance Pand pain perception

Francisco Molina-Ortega a, Rafael Lomas-Vega a, Fidel Hita-Contreras a,*,Gustavo Plaza Manzano b, Alexander Achalandabaso a, Antonio J. Ramos-Morcillo a,Antonio Martínez-Amat aaDepartment of Health Sciences, University of Jaén, Campus Las Lagunillas s/n, 23071 Jaén, SpainbDepartment of Physical Medicine and Rehabilitation, Complutense University School of Medicine, Avda. de Séneca, 2. Ciudad Universitaria, 28040 Madrid,Spain

a r t i c l e i n f o

Article history:Received 6 September 2013Received in revised form15 February 2014Accepted 23 February 2014

Keywords:Spinal manipulationSubstance PNitric oxidePressure pain threshold

a b s t r a c t

Previous studies have analyzed the effects of spinal manipulation on pain sensitivity by using severalsensory modalities, but to our knowledge, no studies have focused on serum biomarkers involved in thenociceptive pathway after spinal manipulation. Our objectives were to determine the immediate effect ofcervical and dorsal manipulation over the production of nitric oxide and substance P, and establishingtheir relationship with changes in pressure pain thresholds in asymptomatic subjects. In this single-blindrandomized controlled trial, 30 asymptomatic subjects (16 men) were randomly distributed into 3groups (n ¼ 10 per group): control, cervical and dorsal manipulation groups. Blood samples wereextracted to obtain serum. ELISA assay for substance P and chemiluminescence analysis for nitric oxidedetermination were performed. Pressure pain thresholds were measured with a pressure algometer atthe C5eC6 joint, the lateral epicondyle and the tibialis anterior muscle. Outcome measures were ob-tained before intervention, just after intervention and 2 h after intervention. Our results indicated anincrease in substance P plasma level in the cervical manipulation group (70.55%) when compared withother groups (p < 0.05). This group also showed an elevation in the pressure pain threshold at C5eC6(26.75%) and lateral epicondyle level (21.63%) immediately after the intervention (p < 0.05). No changesin nitric oxide production were observed. In conclusion, mechanical stimulus provided by cervicalmanipulation increases substance P levels and pressure pain threshold but does not change nitric oxideconcentrations. Part of the hypoalgesic effect of spinal manipulation may be due to the action of sub-stance P.

! 2014 Elsevier Ltd. All rights reserved.

1. Introduction

Manipulation of the spine is a manual therapy technique per-formed to increase range of motion in a joint with decreased jointplay, with the intention of relieving the pain of patients. Spinalmanipulation (SM) involves a high velocity “impulse” or “thrust” ofshort amplitude which is applied to interapophyseal joints. Theeffectiveness of SM to treat musculoskeletal pain has been sum-marized in recent systematic reviews. Overall, evidence suggeststhat SM provides greater relief for pain and function than a placebo

or no treatment (Gross et al., 2010; van Middelkoop et al., 2011).Although SM is widely used in the management of pain, thephysiological basis of its effectiveness remains unknown. It hasbeen proposed that the mechanical stimuli generated by SM couldactivate the liberation of many biochemical mediators from neuraltissue (Skyba et al., 2003).

The perception of pain is clearly a complex process due to thehigh number of biochemical mediators involved. Nitric oxide (NeO), considered as themajor local vasodilator (Takuwa et al., 2010), isa small molecule with a dual role in cell survival (Cauwels et al.,2005) and nociception (Millan, 2002). Nitric oxide is a diffusiblegas that rapidly reacts with oxygen to form nitric oxide derivatessuch as nitrite and nitrate (Lundberg et al., 2008). Although evi-dence exists regarding the beneficial effects of the release of smallamounts of NeO during the inhibition of nociceptive pathways

* Corresponding author. Department of Health Sciences (B-3/272), University ofJaén, Campus Las Lagunillas s/n, 23071 Jaén, Spain. Tel.: þ34 953 212921; fax: þ34953 211875.

E-mail address: [email protected] (F. Hita-Contreras).

Contents lists available at ScienceDirect

Manual Therapy

journal homepage: www.elsevier .com/math

http://dx.doi.org/10.1016/j.math.2014.02.0071356-689X/! 2014 Elsevier Ltd. All rights reserved.

Manual Therapy xxx (2014) 1e7

Please cite this article in press as: Molina-Ortega F, et al., Immediate effects of spinal manipulation on nitric oxide, substance P and painperception, Manual Therapy (2014), http://dx.doi.org/10.1016/j.math.2014.02.007

high -velocity-low -amplitude thrust was applied following thesame anterior to posterior direction.

All the evaluators were blinded to the intervention of thetherapist.

2.3. Outcome measures

Pressure pain threshold measures and blood samples were ob-tained before intervention (pre-intervention), immediately justafter intervention (0 h post-intervention) and 2 h after intervention(2 h post-intervention).

2.3.1. Blood sample preparationTotal blood samples were extracted by venipuncture of the ce-

phalic vein using a Vacutainer system (BectoneDickinson, UnitedKingdom). Blood was collected in tubes for serum separation (BDVacutainer SST II Advance, ref. 367953). After blood extraction,tubes were let stand at room temperature for 1 h until the bloodclotted. Afterward, tubes were centrifuged for 10 min at 2000 g(Avanti J-30I, Beckman Coulter, USA). Supernatant was collected,aliquoted and kept at !80 "C until used.

2.3.2. Nitric oxide determinationTo carry out the analysis, the thawed serum aliquots were mixed

in 1/2/2 (w/v/v) deproteinization buffer (0.5 N NaOH, 10% ZnSO4),briefly shaken and let stand at room temperature for 15 min. Afterthat, samples were centrifuged for 5 min at 13,500 rpm and su-pernatants were collected and maintained at 4 "C until analyzed.

The total amount of nitric oxide and NeO derivates was deter-mined by a modification of the procedure described by Braman andHendrix (1989) using NOA 280i the purge system of Sievers In-struments, model NOA 280i (GE Analytical Instruments, USA). Ni-tric oxide and NeO derivates concentrations were calculated bycomparison with standard solutions of sodium nitrate. Nitric oxideand NeO derivates data were normalized with total protein con-centration of each sample determined using the Bradford assay(Bradford, 1976).

2.3.3. Substance P determinationPlasma determination of SP was determined by using Luminex!

technology with a specific ELISA kit (Milliplex Ref: HNP-35K, Mil-lipore, USA). Substance P data were normalized with total protein

concentration of each sample calculated by the Bradford method(Bradford, 1976).

2.3.4. Pressure pain thresholdA pressure algometer (Pain Test" FPN 100,Wagner Instruments,

USA) was used to measure PPT. In this study several PPT pointswere used to determine the local or regional (C5eC6 zygapophysealjoint, lateral epicondyle) and global effects (tibialis anterior) of thespinal manipulation to verify the presence of segmental and/orcentral modulation of pain (Urban and Gebhart, 1999; Schaible,2007). All measurements were carried out by a well-trained expert.

2.4. Statistical analysis

Demographic and experimental data were treated with theSPSS! 19.0 (IBM, USA) and MedCalc 12.3 (MedCalc, Belgium)

Table 1Baseline characteristics of participants.

Characteristics Control (n ¼ 10) Thoracic (n ¼ 10) Cervical (n ¼ 10)

Mean $ SD Mean $ SD Mean $ SD p-value

Age 25.80 $ 3.22 29.80 $ 4.52 27.80 $ 3.99 0.095Weight 63.60 $ 8.47 73.70 $ 14.33 71.20 $ 14.19 0.196Height 1.71 $ 0.07 1.75 $ 0.06 1.75 $ 0.12 0.528Substance Pa 35.84 $ 9.36 36.23 $ 15.83 38.23 $ 18.34 0.930Nitric oxideb 0.19 $ 0.02 0.12 $ 0.03 0.25 $ 0.17 0.021*PPT C5eC6c 3.76 $ 0.51 3.44 $ 1.54 3.29 $ 0.98 0.622PPT Epic 5.60 $ 3.44 4.63 $ 1.61 4.30 $ 1.65 0.462PPT Tibc 8.54 $ 1.85 7.89 $ 2.23 7.85 $ 2.25 0.721Protein

contentd129.68 $ 35.84 128.79 $ 29.44 123.53 $ 27.07 0.892

*p < 0.05.Abbreviations: PPT C5-C6 (pressure pain threshold at C5eC6 zygapophyseal joint);PPT Epi (pressure pain threshold at right lateral epicondyle); PPT Tib (pressure painthreshold at tibialis anterior muscle).

a Substance P is expressed as pg/mg total protein.b Nitric oxide is expressed as mmol/mg total protein.c PPTs are expressed as kg/cm2.d Protein content is expressed as mg/ml.

Table 2Test-retest reliability for outcomes variables.

Variable CCI SEM MDC

Substance P 0.679 5.303 10.39Nitric oxide 0.620 0.012 0.02PPT C5eC6 0.781 0.239 0.47PPT Epi 0.736 1.768 3.46PPT Tib 0.913 0.546 1.07

Abbreviations: CCI (Intraclass Correlation Coefficient); SEM (Standard Error ofMeasurement); MDC (Minimal Detectable Change); PPT C5eC6 (pressure painthreshold at C5eC6 zygapophyseal joint); PPT Epi (pressure pain threshold at rightlateral epicondyle); PPT Tib (pressure pain threshold at tibialis anterior muscle).

Fig. 2. Mean plots for primary measures in each group and each time point.

F. Molina-Ortega et al. / Manual Therapy xxx (2014) 1e7 3

Please cite this article in press as: Molina-Ortega F, et al., Immediate effects of spinal manipulation on nitric oxide, substance P and painperception, Manual Therapy (2014), http://dx.doi.org/10.1016/j.math.2014.02.007

high -velocity-low -amplitude thrust was applied following thesame anterior to posterior direction.

All the evaluators were blinded to the intervention of thetherapist.

2.3. Outcome measures

Pressure pain threshold measures and blood samples were ob-tained before intervention (pre-intervention), immediately justafter intervention (0 h post-intervention) and 2 h after intervention(2 h post-intervention).

2.3.1. Blood sample preparationTotal blood samples were extracted by venipuncture of the ce-

phalic vein using a Vacutainer system (BectoneDickinson, UnitedKingdom). Blood was collected in tubes for serum separation (BDVacutainer SST II Advance, ref. 367953). After blood extraction,tubes were let stand at room temperature for 1 h until the bloodclotted. Afterward, tubes were centrifuged for 10 min at 2000 g(Avanti J-30I, Beckman Coulter, USA). Supernatant was collected,aliquoted and kept at !80 "C until used.

2.3.2. Nitric oxide determinationTo carry out the analysis, the thawed serum aliquots were mixed

in 1/2/2 (w/v/v) deproteinization buffer (0.5 N NaOH, 10% ZnSO4),briefly shaken and let stand at room temperature for 15 min. Afterthat, samples were centrifuged for 5 min at 13,500 rpm and su-pernatants were collected and maintained at 4 "C until analyzed.

The total amount of nitric oxide and NeO derivates was deter-mined by a modification of the procedure described by Braman andHendrix (1989) using NOA 280i the purge system of Sievers In-struments, model NOA 280i (GE Analytical Instruments, USA). Ni-tric oxide and NeO derivates concentrations were calculated bycomparison with standard solutions of sodium nitrate. Nitric oxideand NeO derivates data were normalized with total protein con-centration of each sample determined using the Bradford assay(Bradford, 1976).

2.3.3. Substance P determinationPlasma determination of SP was determined by using Luminex!

technology with a specific ELISA kit (Milliplex Ref: HNP-35K, Mil-lipore, USA). Substance P data were normalized with total protein

concentration of each sample calculated by the Bradford method(Bradford, 1976).

2.3.4. Pressure pain thresholdA pressure algometer (Pain Test" FPN 100,Wagner Instruments,

USA) was used to measure PPT. In this study several PPT pointswere used to determine the local or regional (C5eC6 zygapophysealjoint, lateral epicondyle) and global effects (tibialis anterior) of thespinal manipulation to verify the presence of segmental and/orcentral modulation of pain (Urban and Gebhart, 1999; Schaible,2007). All measurements were carried out by a well-trained expert.

2.4. Statistical analysis

Demographic and experimental data were treated with theSPSS! 19.0 (IBM, USA) and MedCalc 12.3 (MedCalc, Belgium)

Table 1Baseline characteristics of participants.

Characteristics Control (n ¼ 10) Thoracic (n ¼ 10) Cervical (n ¼ 10)

Mean $ SD Mean $ SD Mean $ SD p-value

Age 25.80 $ 3.22 29.80 $ 4.52 27.80 $ 3.99 0.095Weight 63.60 $ 8.47 73.70 $ 14.33 71.20 $ 14.19 0.196Height 1.71 $ 0.07 1.75 $ 0.06 1.75 $ 0.12 0.528Substance Pa 35.84 $ 9.36 36.23 $ 15.83 38.23 $ 18.34 0.930Nitric oxideb 0.19 $ 0.02 0.12 $ 0.03 0.25 $ 0.17 0.021*PPT C5eC6c 3.76 $ 0.51 3.44 $ 1.54 3.29 $ 0.98 0.622PPT Epic 5.60 $ 3.44 4.63 $ 1.61 4.30 $ 1.65 0.462PPT Tibc 8.54 $ 1.85 7.89 $ 2.23 7.85 $ 2.25 0.721Protein

contentd129.68 $ 35.84 128.79 $ 29.44 123.53 $ 27.07 0.892

*p < 0.05.Abbreviations: PPT C5-C6 (pressure pain threshold at C5eC6 zygapophyseal joint);PPT Epi (pressure pain threshold at right lateral epicondyle); PPT Tib (pressure painthreshold at tibialis anterior muscle).

a Substance P is expressed as pg/mg total protein.b Nitric oxide is expressed as mmol/mg total protein.c PPTs are expressed as kg/cm2.d Protein content is expressed as mg/ml.

Table 2Test-retest reliability for outcomes variables.

Variable CCI SEM MDC

Substance P 0.679 5.303 10.39Nitric oxide 0.620 0.012 0.02PPT C5eC6 0.781 0.239 0.47PPT Epi 0.736 1.768 3.46PPT Tib 0.913 0.546 1.07

Abbreviations: CCI (Intraclass Correlation Coefficient); SEM (Standard Error ofMeasurement); MDC (Minimal Detectable Change); PPT C5eC6 (pressure painthreshold at C5eC6 zygapophyseal joint); PPT Epi (pressure pain threshold at rightlateral epicondyle); PPT Tib (pressure pain threshold at tibialis anterior muscle).

Fig. 2. Mean plots for primary measures in each group and each time point.

F. Molina-Ortega et al. / Manual Therapy xxx (2014) 1e7 3

Please cite this article in press as: Molina-Ortega F, et al., Immediate effects of spinal manipulation on nitric oxide, substance P and painperception, Manual Therapy (2014), http://dx.doi.org/10.1016/j.math.2014.02.007

Considerable evidencia muestra que

la Movilización / Manipulación es un

estímulo suficiente para inducir

respuestas analgésicas inmediatas.

Movilización / Manipulación

Es muy probable que áreas específicas del cerebro y del SNC coordinen estas respuestas.

Schmid 2008, Bialosky 2009, Wright 1995

Efectos sobre la actividad motora

Existe suficiente apoyo documental para afirmar que la movilización/manipulación genera respuestas neuromusculares reflejas asociadas, con efectos inhibidores y facilitadores.

Existe cierta evidencia para pensar que dichas respuestas están mediadas por la estimulación mecánica de receptores musculares y articulares, tanto de bajo como alto umbral. Sin embargo, los mecanismos neurofisiológicos exactos aún son desconocidos.

Se desconoce la relevancia clínica de dichas respuestas.

Gila 2007, Herzog 1999, Lehman 2001, Murphy 1995

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El concepto de que la manipulación reposiciona, coloca o mejora la alineación de las articulaciones es una de las teorías más antiguas acerca de la misma. Y constituye el principal mito de la Terapia Manual.

Estudios biomecánicos recientes que examinan el movimiento vertebral tras una manipulación muestran que esta teoría “posicional” es falsa.

Simplemente demuestran un movimiento vertebral transitorio y asociado a la separación de las superficies articulares.

La radiografía, el TAC o la RMN han mostrado ser métodos poco fiables para el diagnóstico de dolor de espalda. En relación a fuentes de dolor de espalda, la mal-posición vertebral parece ser un epifenómeno.

Evans 2002

Paradigma Biomecánico Movilización / Manipulación

Una de la razones para la concepción de esta teoría se relaciona con la reproducción del ruido articular asociado a la manipulación y causado por la cavitación, el cuál a menudo convenientemente coincide con la mejoría inmediata del dolor.

Antes de que el fenómeno de la cavitación fuera aceptado como el responsable del sonido, los practicantes de la manipulación asociaban el sonido a la sensación de haber “reposicionado el hueso en su lugar”.

Muchos pacientes sostienen todavía este concepto de reposición, y la educación de los mismos para disipar estas creencias es necesaria.

Evans 2002

Paradigma Biomecánico Movilización / Manipulación

Cramer 2002

Paradigma Biomecánico Movilización / Manipulación

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Cramer 2002

Paradigma Biomecánico Movilización / Manipulación

Se ha investigado en sujetos con dolor si la manipulación puede modificar la posición entre el sacro y el ilíaco y si los test posicionales son válidos para determinar las relaciones espaciales entre el sacro y el ilíaco.

Los test posicionales se interpretaron como positivos antes de la manipulación y como negativos tras la misma.

Sin embargo, en los sujetos a estudio la manipulación no modificó la posición del sacro en relación al ilíaco.

Tullberg 1998

Paradigma Biomecánico Movilización / Manipulación

El concepto de Subluxación Quiropráctica es la base esencial de la Quiropraxia.

“No se encuentra evidencia que apoye que la subluxación quiropráctica esté asociada a ningún proceso de enfermedad, o a crear condiciones subóptimas de salud que requieran intervención”.

Al demostrarse por imagen que no existían mal-posiciones vertebrales, se redefinió el término de subluxación quiropráctica:

Mirtz 2009

“Conjunto de cambios patológicos y/o estructurales y/o

funcionales articulares que comprometen la integridad

neural, y que pueden influir en la función de los sistemas,

órganos y en la salud general”.

Paradigma Biomecánico Movilización / Manipulación

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En los 114 años desde el comienzo de la Quiropraxia nunca se ha podido demostrar objetivamente la existencia de las subluxaciones quiroprácticas.

Nunca se ha mostrado que causen interferencia con el sistema nervioso.

Nunca se ha demostrado que provoquen enfermedades.

Los críticos de la quiropraxia llevan señalando esto desde hace décadas, pero ahora los mismos quiropractores llegan a ésta misma conclusión.

Mirtz 2009

Paradigma Biomecánico Movilización / Manipulación

Datos de 367 encuestas a fisioterapeutas especializados en terapia manual

En relación al examen del movimiento pasivo intervertebral:

El hallazgo clínico más importante a la hora de tomar una decisión diagnóstica es el cambio en la resistencia percibida al final del ROM “end feel”.

En menos medida, la provocación o alivio del dolor del paciente o la resistencia percibida a lo largo del ROM.

Trijffel 2009

Paradigma Biomecánico Movilización / Manipulación

Además,

Consideran que este examen es importante a la hora de tomar decisiones terapéuticas.

Confían en que las conclusiones del mismo son válidas.

(la investigación de la validez y precisión no permite conclusiones definitivas)

La mayoría confía en poder llegar a la misma conclusión clínica que otro compañero.

(la evidencia es clara, la fiabilidad inter-examinador es inaceptablemente baja)

Trijffel 2009

Paradigma Biomecánico Movilización / Manipulación

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Datos de 466 encuestas a fisioterapeutas especializados en terapia manual Estados Unidos y Nueva Zelanda.

En relación al examen del movimiento pasivo intervertebral:

La mayoría consideraron que es un procedimiento preciso para estimar la cantidad de movimiento presente en la columna lumbar.

(restricción de movimiento, movimiento normal o exceso de movimiento)

Abbott 2009

Paradigma Biomecánico Movilización / Manipulación

Además, la mayoría admite:

Seleccionar diferentes opciones de tratamiento en base, al menos en parte, a los hallazgos del examen del movimiento pasivo intervertebral.

Que para determinar la expectativa de movimiento que se espera en cada segmento compara la respuesta con los segmentos situados inmediatamente por encima y por debajo.

Abbott 2009

Paradigma Biomecánico Movilización / Manipulación

¿Qué consideras que estás intentando evaluar cuando realizas un movimiento intervertebral pasivo fisiológico en la columna lumbar?

Abbott 2009

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Datos de 118 encuestas a fisioterapeutas especializados en terapia manual Canadá.

En relación a la indicación o no de la manipulación vertebral:

La mayoría consideró que los hallazgos relacionados con hipomovilidad eran los más importantes para indicar o no una manipulación.

- Fijación o bloqueo articular segmentario. 90%.

- Rigidez o limitación de movimiento. 81%

Hurley 2002

Paradigma Biomecánico Movilización / Manipulación

Diferentes disciplinas o líneas de pensamiento en Terapia Manual hacen uso de sistemas de clasificación del movimiento intervertebral basados en percepciones subjetivas relacionadas con la amplitud, calidad o sensación final del movimiento para la toma de decisiones clínicas.

Una parte de estas disciplinas atribuyen el hallazgo de rigidez o hipomovilidad segmentaria como el principal criterio a la hora de seleccionar la manipulación como una opción de tratamiento.

Paradigma Biomecánico Movilización / Manipulación

Mediante RMN se compara la movilidad pasiva intervertebral lumbar entre 45 pacientes con dolor lumbar y 20 sujetos asintomáticos.

Como procedimiento de evaluación se utiliza la movilización PA lumbar.

El número de sujetos que presentó hipomovilidad fue muy bajo:

4.4% de los pacientes.

10% de los sujetos asintomáticos.

Es más, el 40% de los pacientes presentó hipermovilidad en uno o más segmentos de la columna.

Kulig 2007

Paradigma Biomecánico Movilización / Manipulación

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Un experimentado osteópata es capaz de identificar, con buena fiabilidad, la articulación lumbar con signos de disfunción segmentaria que se pueda beneficiar de una manipulación vertebral. Lesión Manipulable.

Sin embargo, en la columna dorsal y sin estar entrenado, el mismo osteópata tiene moderada a baja fiabilidad en identificar signos de disfunción segmentaria.

Esto en una muestra de SUJETOS ASINTOMÁTICOS.

Potter 2006

Paradigma Biomecánico Movilización / Manipulación

En relación al examen del movimiento pasivo intervertebral.

Clasificar los hallazgos en base a percepciones subjetivas relacionadas con la amplitud, calidad, resistencia o sensación final del movimiento ha demostrado tener poca o ninguna fiabilidad cuando se compara la concordancia de los resultados entre diferentes examinadores.

La evidencia es clara en este sentido.

Paradigma Biomecánico Movilización / Manipulación

La evidencia recopilada de los estudios incluidos en esta revisión sistemática indica que la fiabilidad inter-examinador, por parte de los terapeutas manuales, del examen del movimiento pasivo intervertebral de la columna cervical y lumbar es baja.

Trijffel 2005

Fiabilidad y Validez en la Evaluación del Movimiento Pasivo Intervertebral

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Más importante que medir el acuerdo de los hallazgos subjetivos del movimiento entre diferentes evaluadores es:

Medir hasta que punto concuerdan las percepciones subjetivas del movimiento intervertebral con la evaluación objetiva del mismo.

Fiabilidad y Validez en la Evaluación del Movimiento Pasivo Intervertebral

A través de una movilización PA lumbar, 2 examinadores muestran concordancia buena para el nivel vertebral menos móvil y concordancia mala para el nivel más móvil.

En ningún momento hubo concordancia de estos hallazgos con la medición del desplazamiento vertebral en RMN dinámica.

Estos resultados ponen en seria duda la validez de estos procedimientos como método de evaluación del movimiento intervertebral.

Landel 2008

Fiabilidad y Validez en la Evaluación del Movimiento Pasivo Intervertebral

Los resultados de la investigación ponen en seria duda la validez de estos procedimientos como método de evaluación del movimiento intervertebral.

Ninguna de las pruebas de posición y movilidad articular son útiles si carecen de fiabilidad interexaminador. El mismo paciente puede ser diagnosticado por un fisioterapeuta en tener problemas de hipermovilidad y por otro en tener problemas de hipomovilidad, lo que puede resultar en diferentes estrategias de tratamiento.

Para que una prueba pueda ser considerada útil como apoyo a un conjunto o agrupación de pruebas, primero debe mostrar su validez y fiabilidad.

Fiabilidad y Validez en la Evaluación del Movimiento Pasivo Intervertebral

Johanson 2006

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La investigación acerca de la aplicación de movilización y manipulación ha mostrado lo poco específicos que son estos procedimientos.

La cavitación producida durante la manipulación de la columna lumbar no se da en el segmento deseado en +50% de los casos y sólo es específica (cavitación única del nivel deseado) en el 36% de los casos.

No existe correlación entre la manipulación vertebral específica y la localización de la cavitación en la columna lumbar y ASI.

Parece que ni siquiera es necesario la reproducción del sonido para que la misma sea efectiva.

Paradigma Biomecánico Movilización / Manipulación

Ross 2004, Beffa 2004, Flynn 2003

La investigación acerca de la aplicación de movilización y manipulación ha mostrado lo poco específicos que son estos procedimientos.

Mediante RMN se ha demostrado que aplicar movilizaciones PA en la región cervical o lumbar produce movimientos en todos los segmentos vertebrales de cada región.

Por tanto, no pueden ser consideradas como simples deslizamientos de una vértebra sobre otra.

Paradigma Biomecánico Movilización / Manipulación

Lee 2005, Powers 2003

En relación al tratamiento por movilización y manipulación

Diferentes formas de movilización y manipulación parecen tener efectos similares en cuanto a dolor y función percibida.

Estos efectos no parecen depender de la selección de la técnica más “apropiada”.

Paradigma Biomecánico Movilización / Manipulación

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En sujetos con dolor lumbar, se compara el efecto de un tratamiento específico basado en el examen del paciente (nivel vertebral, tipo de técnica y forma de aplicarla) con el efecto de un tratamiento elegido al azar.

Ambos grupos mostraron reducción significativa del dolor y una mejor función.

Elegir la técnica que parece ser la más apropiada no superó ningún resultado medido en este estudio.

Chiradejnant 2003

Paradigma Biomecánico Movilización / Manipulación

En pacientes con dolor lumbar crónico se compara el efecto inmediato, en la intensidad del dolor y en el umbral de dolor a la presión, de una manipulación lumbar específica (basada en el examen físico) con el efecto de una manipulación torácica superior.

Ambos grupos mostraron una mejora clara en el dolor y en el UDP.

En pacientes con dolor lumbar crónico, elegir una manipulación lumbar específica no produce un mejor efecto inmediato sobre el dolor y el

Fernando de Oliveira 2013

Paradigma Biomecánico Movilización / Manipulación

En pacientes con radiculopatía cervical se compara el efecto en dolor, ROM y función de un set de movilizaciones y ejercicios de estabilización con el efecto de añadir, al mismo programa, técnicas dirigidos a aumentar el tamaño del foramen intervertebral.

Ambos grupos mostraron una mejoría clínica y estadísticamente significativa en el seguimiento a 4 y 8 semanas.

Añadir técnicas dirigidas a aumentar el FIV no produce un mejor efecto

Langevin P 2015

Paradigma Biomecánico Movilización / Manipulación

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En sujetos con dolor de cuello se compara el efecto de una manipulación cervical en rotación con el efecto de una manipulación cervical lateral que fueron asignadas al azar.

No se encontraron diferencias mostrando ambos grupos mejoras significativas en cuanto a dolor y rango de movimiento después de 10 sesiones de tratamiento y en el seguimiento a un mes.

En sujetos con dolor cuello, se ha comparado el efecto de una manipulación específica dirigida al segmento “hipomóvil” con el efecto de la misma manipulación en un segmento elegido al azar.

Los resultados no encuentran diferencias entre los grupos mostrando ambos reducción en el dolor cervical.

Paradigma Biomecánico Movilización / Manipulación

Schalkwyk 2000, Haas 2003

Un metaanálisis compara los resultados de diferentes ensayos clínicos en los que se elige o no un procedimiento de movilización y/o manipulación específico para sujetos con dolor lumbar.

En aproximadamente 2/3 de los ensayos, se había elegido un procedimiento específico.

Sin embargo, no existían diferencias a favor de estos ensayos.

La elección o no de una técnica específica de movilización / manipulación no parece influir en un mayor efecto de la Terapia Manual en el dolor lumbar.

Kent 2005

Paradigma Biomecánico Movilización / Manipulación

No se han identificado cambios biomecánicos duraderos.

Los clínicos son incapaces de identificar de forma fiable qué alteraciones biomecánicas requieren TM.

Las fuerzas asociadas con la TM no son específicas para una localización determinada y son variables entre los clínicos.

La elección de la técnica que parece ser la más apropiada, en un análisis biomecánico, no parece que influya en los resultados.

Las respuestas de signos y síntomas se producen en áreas alejadas de la región de aplicación.

A pesar de estas inconsistencias con el modelo biomecánico, otros mecanismos adicionales pueden ser pertinentes para entender los efectos de la TM.

Se sugiere que la fuerza mecánica es necesaria para iniciar una cadena de respuestas neurofisiológicas que producen los resultados asociados con la TM.

Bialosky 2009

Mecanismos de la Terapia Manual

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En relación a las manipulaciones vertebrales en los modelos biomecánicos tradicionales.

Las manipulaciones vertebrales NO colocan los huesos en su lugar.

Las manipulaciones vertebrales NO producen cambios duraderos en la posición de las articulaciones.

La investigación ha demostrado que un diagnóstico de mal-posición NO debe ser un criterio para seleccionar una técnica de manipulación.

En más de la mitad de las veces, la manipulación NO se produce en la articulación seleccionada y, rara vez, es específica de esa articulación.

Con un análisis de posición o de movilidad vertebral, la elección de un nivel vertebral hipomóvil o en “bloqueo” NO influye en un mayor efecto clínico de la manipulación. Además, esta elección, NO supera el efecto de técnicas elegidas al azar.

Paradigma Biomecánico Movilización / Manipulación

En relación a las pruebas pasivas de posición y movilidad intervertebral:

Carecen de un estándar de comparación válido.

NO permiten medir de forma precisa el movimiento pasivo intervertebral.

Otro compañero entrenado NO obtiene los mismos resultados, lo que conduce a categorías diagnósticas y tratamientos diferentes. Incluso el mismo terapeuta NO concuerda con sus propios resultados en momentos diferentes.

Las alteraciones de posición y movilidad son tan comunes en la gente con dolor que sin dolor de espalda. Por tanto, NO se correlacionan con el dolor y no pueden ser consideradas causas del mismo.

La elección de la técnica que parece ser más apropiada, con este examen biomecánico, NO produce mayor efecto clínico que las

Paradigma Biomecánico Movilización / Manipulación

Paradigma Biomecánico Movilización / Manipulación

Parece evidente que evaluar el movimiento mediante percepciones subjetivas no es válido para tomar decisiones terapéuticas. Existe una alta probabilidad de elegir y aplicar un tratamiento erróneo.

En relación al examen del movimiento intervertebral, ¿existe alguna utilidad que sea respaldada por la investigación?

Las movilizaciones PA en columna cervical y lumbar han mostrado alto grado de sensibilidad y especificidad al ser comparadas con bloqueos anestésicos.

Tienen concordancia alta, inter e intra examinador, para detectar niveles vertebrales sintomáticos.

Dependen en cierto grado de la comunicación verbal con el paciente para lograr la concordancia perfecta.

Jull 1988, 1997, Phillips 1996

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¿Qué consideras que estás intentando evaluar cuando realizas un movimiento pasivo accesorio PA central en la columna lumbar?

Abbott 2009

Existe evidencia parcial acerca del efecto de una intervención por movilización / manipulación seleccionada en base a la localización de niveles vertebrales sintomáticos.

(Niveles vertebrales en donde el procedimiento manual reproduce parcial o totalmente el dolor del paciente).

Se ha demostrado que la movilización produce mayor reducción de dolor cuando ésta se aplica en el nivel vertebral que el fisioterapeuta identifica como más sintomático y con mayor capacidad de reproducir el síntoma del paciente.

Chiradejnant 2002

Paradigma Biomecánico Movilización / Manipulación

“La incapacidad de demostrar la superioridad sobre el placebo no implica falta de eficacia; puede reflejar únicamente similitud de mecanismos. La comparación de un tratamiento con el placebo no es, en consecuencia, una comparación de dos mecanismos, sino tan sólo la comparación de su capacidad de activar el mismo mecanismo….”. Lawes 2002

Mecanismos cerebrales específ icos parecen mediar la respuesta al placebo.

El grado en que una persona responde a un placebo está vinculado íntimamente a la actividad que registre el área del cerebro destinada a obtener un beneficio o una recompensa.

Mecanismo Placebo

Lawes 2002, Scott 2007

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Se ha estudiado el efecto en la percepción de dolor de crear expectativas positivas, negativas o neutras en cuanto al resultado de la manipulación.

Expectativa positiva: “la manipulación es un procedimiento muy efectivo que se utiliza para tratar el dolor lumbar bajo, y esperamos que reduzca su percepción de dolor”.

Expectativa negativa: “la manipulación es un procedimiento ineficaz que se utiliza para tratar el dolor lumbar bajo, y esperamos un empeoramiento temporal de su percepción de dolor”.

Expectativa neutra: “la manipulación es un procedimiento que se utiliza para tratar el dolor lumbar bajo y desconocemos sus efectos en la percepción de dolor”.

Bialosky 2008

Mecanismo Placebo

Los sujetos que reciben la expectativa negativa muestran un aumento importante en la percepción de dolor en el área corporal donde se crea la expectativa del resultado, y que parece condicionar el efecto de hipoalgesia que se atribuye a la manipulación.

La mayor parte de los estudios de investigación en Terapia Manual concluyen que ésta puede ser efectiva en el alivio del dolor y en la mejoría de la función en pacientes con dolor musculoesquelético.

No está claro cómo deben ser aplicadas las diferentes maniobras en relación al orden de las mismas, intensidad, frecuencia, tiempo de duración, etc...

Movilización / Manipulación