Translational Study of the Effects of Neural Mobilization in Patients With Lomboisquiatalgia
Condition: Low Back Pain, Mechanical; Pain; Neuropathic Pain
MeSH terms: Neuralgia; Low Back Pain
Study type: Interventional

Summary: 
      The spinal nerve injury in humans often results in neuropathic pain characterized by
      spontaneous burning pain accompanied by allodynia and hyperalgesia. In this sense,
      lomboisquiatalgia is a neuropathy that is characterized by narrowing the intervertebral
      foramen of the lumbar vertebrae, leading a lumbar chronic pain which irradiate to a lower
      limb, being a clinical condition of difficult treatment. Neural Mobilization is a noninvasive
      technique used by physiotherapists. The technique aims to restore mobility and elasticity of
      the peripheral nervous system by tenses which are imposed on the roots, nerves, spinal cord
      and their respective meninges. This technique has been standardized in basic research and has
      shown promising results. However, clinically, this technique lacks randomized, controlled and
      double blind studies. Therefore, the investigators have to evaluate the effects of Neural
      Mobilization technique in patients with lomboisquiatalgia. In this study the investigators
      will treat patients three times a week, with ten minute treatment time per session, with 25
      oscillations per minute for ten sessions. Many tools will be used to assess the effects of
      the protocol applied, for example: evaluation sheet, visual analogue scale (VAS), quality of
      life assessment - WHOQOL-bref questionnaire of Roland Morris disability, oswestry index on
      disability (version 2.0), enzyme-linked immunosorbent assays for the measurement of cytokines
      in the blood tissue. In this way, the investigators can contribute and understand the
      mechanisms involved in the rehabilitation process.
    

Detailed description: 
      Translational study of the effects of Neural Mobilization in patients with lomboisquiatalgia

      The spinal nerve injury in humans often results in neuropathic pain characterized by
      spontaneous burning pain accompanied by allodynia and hyperalgesia [1]. These signs and
      symptoms occur in the continuous presence of ectopic focus of the afferent peripheral nervous
      system (peripheral sensitization) to the central nervous system (CNS) (central
      sensitization). After the traumatic experience both peripheral sensitization and central
      sensitization contributes to the appearance of poorly adaptive responses in the spinal cord
      as well as in the brain, contributing to chronicity and maintenance of neuropathic pain [2,
      3]. The pain-induced neuropathy is currently being associated with the involvement of glial
      cells located in the spinal cord [4, 5]. Glial cells synthesize several substances, many of
      which are also released by nociceptive neurons that modulate the pain response, among which
      we can mention prostaglandins, glutamate, arachidonic acid, nitric oxide and cytokines pro
      inflammatory [6-9]. Pro-inflammatory cytokines appear to be involved in hyperalgesia and
      mechanical allodynia arising from nerve injury due to compression. Many studies have
      demonstrated that in models of peripheral nerve trunks ischemia, in rats, occurs an increase
      in pro-inflammatory cytokines that may be related to myelin damage and edema [10, 11].
      Furthermore, studies using nerve compression model, increased identified interleukins (IL-6
      or TNF) in rats with allodynia [12]. In this sense, the interleukins (IL) are proteins
      produced by T groups and many of these cells are involved in IL activation of lymphocytes,
      each of which has its effect on IL specific groups of cells expressing specific receptors
      which are identified by numbers: IL-1, IL4, IL-6, IL-10 [13]. Kraychete et. al. (2009),
      analyzed by means of blood samples the levels of pro-inflammatory cytokines in the plasma of
      patients with and without neuropathic pain, and found that patients with neuropathies had
      higher levels of these cytokines [14]. Kukkar et. al. (2012), a model of neuropathic pain
      (CCI) observed an increase of TNF-α level in the sciatic nerve after treatment with aliskiren
      (an anti-hipertensive drug) and a decrease in TNF-α with consequent improvement in
      nociception [15].

      In clinical practice, has been extensively reported that neuropathic pain is difficult to
      treat due to inadequate understanding of the cellular and molecular mechanisms involved in
      the development and maintenance of this kind of pain [16, 17]. The therapeutic options for
      the control of neuropathic pain have increased in recent years [18]. However, responses to
      treatments is still not satisfactory. The neurosurgical treatments include pharmacological
      treatments, such as antidepressants, anticonvulsants, gabapentin, carbamazepine, systemic
      administration of local anesthetics, topical agents, narcotic analgesics and non-narcotic
      antiarrhythmics [17, 18]. Still, as a complementary non-invasive and non-pharmacological
      treatment, we find in the literature, the use of therapeutic resources for rehabilitation,
      depending on the kinf of injury. In this context, Neural Mobilization techniques have shown
      excellent prognosis in patients with differents kind of pain, besides other advantages, such
      as low operating cost, easy to use and no adverse effects [19]. Neural Mobilization is a
      noninvasive technique used by physiotherapists, this technique aims is, to restore mobility
      and elasticity of the peripheral nervous system by strains imposed on nerve trunks, roots,
      nerves, spinal cord and their wraps, the meninges due to the imposition of movements and
      joint angles [20].

      Currently, the technique has been used as a method of evaluation and treatment of several
      diseases that affect the central nervous system (such as Stroke) or peripheral (herniated
      discs or nerve impingement) and structures such as, the muscles due to the existing
      integration between the musculoskeletal system and the nervous system [19, 21-23]. The
      healthy relationship, away from injuries, between peripheral nerves and locomotor system with
      respect to their tissue interfaces allows individuals to move from free and without pain
      [24]. Research by Dworkin et al., (2007) points out that the Neural mobilization is effective
      in conditions of musculoskeletal injuries to functional and pathological diagnosis [21].
      However, the authors mention that for each musculoskeletal condition a kind of neural
      mobilization should be performed. Also depending on the clinical condition of the patient
      other therapies may be included in treatment plan. Our group has been studying last six
      years, and standardizing the technique Neural Mobilization (MOB) in rats. Encouraging results
      were found using our treatment protocol. We demonstrated that the MOB reduced nociceptive
      frame, through the involvement of opioid receptors in the central nervous system (PAG) and
      peripheral (DRG), involvement of substance P, TRPV 1, NGF, PO (protein zero), intense
      regeneration process in sciatic nerve and, exponential increase in muscle strength
      [25-28,34]. Thus, we believe that Neural Mobilization technique, through basic research,
      appears to be effective in the antinociceptive process.

      EXPECTED RESULTS:

      Is consensus that therapeutic alternatives for the treatment of neuropathic pain are needed.
      Physical therapy has been shown by Neural Mobilization technique is efetive in pain control.
      This project becomes important because of the lack of consistent controlled, randomized and
      double blind, demonstrating the benefits effect of Neural Mobilization technique in patients
      with neuropathic pain. The lomboisquiatalgia is characterized by narrowing of the
      intervertebral foramen of the lumbar vertebrae and spinal nerve projection site. It is a
      clinical complication difficult to diagnose and very easy to be confused with herniated disc,
      piriformis syndrome or even osteoarthritis disc. The isquiatalgia is induced by nerve root
      compression (local projection roots which form the sciatic nerve between L3 and L4 and L5 and
      S1), most often caused by a protrusion of nucleus pulposus by virtue of disruption of the
      fibrous rings symphysis intervertebral [30]. Neural mobilization technique is able to induces
      an antinociceptive effect in model of cronic pain, reason it is an important clinical tool in
      the treatment of patients with neuropathic pain [28, 20, 31]. Thus, we believe that we need
      to perform, randomize, control the frequently sessions and time of treatment to bring from
      basic research to now to the clinic in order to better understand the mechanism involved in
      this kind of pain. In this way, we can contribute effectively and understand the mechanisms
      involved in the rehabilitation process of these patients, correlating with improvement in
      pain and consequent improvement of life of patients.

      AINS

      Evaluate the effects of Neural Mobilization technique on the quality of life, biochemical
      changes in patients with lomboisquiatalgia using:

        -  Check the immediate effect of neural mobilization technique on pain of patients with
           lomboisquiatalgia through pain scale;

        -  Check and analysis if Neural mobilization technique increase the functional of patients
           with lomboisquiatalgia;

        -  Examine the impact of treatment with Neural Mobilization in pro- and anti inflammatory
           citokynes (IL-1β, IL-6, IL-10, TNFa and fractalquina) through the analysis of patients
           blood tissue;

        -  Check possible adverse effects of Neural Mobilization technique in patients with
           lomboisquiatalgia.

      SCIENTIFIC AND TECHNOLOGICAL CHALLENGES AND THE MEANS AND METHODS TO OVERCOME THEM

        -  Study and ethics of design: will be a randomized, controlled, double-blind, in
           accordance with the ethical standards of the Declaration of Helsinki, as approved by the
           Ethics Committee in Research with Human Subjects at the University Nove , São Paulo, SP,
           Brazil (2 44079115.1.1001.5511).

        -  Participants: Subjects will be recruited from the Integrated Health Clinic at the
           University Nove in Sao Paulo / SP, even through phone contact, e-mail and letters to
           orthopedic doctors, clinicians and neurologists. Potentially eligible subjects will be
           invited for an interview and a screening procedure performed by a physiotherapist. After
           eligibility, subjects will sign the Term of Free and Clear (TCLE), according to
           Resolution 196/96 of the National Health Council, confirming the participation in the
           survey.

        -  Calculation of the sample: The sample size was calculated based on the Analog Scale
           pain, which was considered the primary end point. To this end, the variance reported in
           a study by Murphy et al., 2006, whose objective was to evaluate the Neural mobilization
           as a technique for the treatment of lumbar spinal stenosis. Considering the mean and
           standard deviation of the pre- intervention and post-intervention this study, with an
           alpha value ( α ) of 0.05 and 90% power test, it was determined that 40 subjects were
           required , It is 20 for each experimental group and 20 for each control group [32].

      Evaluation of outcomes

        -  Visual Analogue Scale: The primary outcome of interest will be assessed by Visual
           Analogue Scale (VAS). The VAS is to assist in the assessment of pain intensity in the
           participant.

        -  Questionnaire WHOQOL-BREF: The WHOQOL-bref questionnaire is a specific questionnaire,
           short and quick application, developed by the World Health Organization (WHO) in order
           to standardize the assessment of quality of life.

        -  Disability Questionnaire Roland Morris - RMDQ: Roland and Morris developed in 1983 a
           questionnaire to assess functional disability of patients with low back pain.

        -  Oswestry Disability Index (ODQ - version 2.0): The Oswestry disability Index (Oswestry
           Low Back Pain Disability Questionnaire (ODQ) aims to assess dysfunction in individuals
           with low back pain by analyzing the activities of daily living.

        -  Enzyme-linked immunosorbent assays for the measurement of cytokines: To assess the
           impact of Neural Mobilization technical front of interleukin pro- and anti-inflammatory
           collecting blood tissue will be necessary (for blood collection will follow the manual
           techniques for collection ministry of Health of the blood [33] of each patient to the
           enzyme immunoassays for each specific cytokine). Will be made two blood collections, the
           original measure (the first session) and after the last session (tenth session)
           treatment. The blood tissue will initially be stored after collection and centrifuged
           for 20 minutes at 3000 rpm. For dosage fractalkine, cytokines (IL-1β, IL-6 and IL-10 and
           TNF-α) specific reagents will be used in Milliplex®TM Map Kit (Millipore Corporation,
           Darmstadt- Germany) according to the protocol specified by the manufacturer.

      REFERENCES - I excuse references because have limit of characters
    

Intervention name(s): Neural Mobilization (exercise)
Intervention type(s): Other
Intervention description(s): Initially patients will be informed about the procedures. After the guidelines, the hip and knee are palpated to start the joint angles. Then, the knee joint is positioned in extension and remained so throughout the treatment. In addition, the hip joint is bent until the moment that will be perceived a minimum strength of the muscles of the posterior region of thigh and leg (discarding muscle stretching). Neural mobilization is started at the time when the ankle joint will be manipulated in dorsiflexion at a frequency of approximately 20 oscillations per minute, with a pause of 25 seconds of rest. In the last two minutes of therapy, we will include cervical flexion, in order to intend the neuraxis, keeping artuculares amplitudes.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment