xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT06022848</url>
    </required_header>
    <id_info>
      <org_study_id>210723</org_study_id>
      <nct_id>NCT06022848</nct_id>
    </id_info>
    <brief_title>Quantitative Sensory Testing and Occipital Nerve Stimulator</brief_title>
    <official_title>Does Occipital Nerve Stimulation Alter Pain Response as Measured by Quantitative Sensory Testing in Patients With Chronic Migraine or Cluster Headache</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Dr Theresa Wodehouse</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Barts &amp; The London NHS Trust</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The primary aim of this study is to assess the reversibility of a range of psychophysical&#xD;
        markers of pain processing in patients with chronic migraine or cluster headache before and&#xD;
        after ONS insertion and comparing to patients having a general anaesthetic (GA) for a&#xD;
        non-painful aetiology at Barts Health NHS Trust. We will also compare with healthy volunteers&#xD;
        not undergoing surgery.&#xD;
  &#xD;
        To establish whether pain perception alters in patients with chronic migraine/cluster&#xD;
        headache having ONS using questionnaires and compare to patients having a general anaesthetic&#xD;
        for a non- painful procedure D &amp; C at Barts Health NHS Trust.&#xD;
  &#xD;
        Are pain markers (Glutamate, TGF-B1) altered with ONS?&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Headache is one of the most common neurological problems accounting for 4% of primary care&#xD;
        consultations and up to 30% of neurology appointments. Even though considerable advances in&#xD;
        the understanding of the pathogenesis of migraine, new pharmacologic treatments and the&#xD;
        emergence of new innovative interventions for difficult cases, in many patients with migraine&#xD;
        remain intractable to medical therapy.&#xD;
  &#xD;
        The trigeminocervical complex (TCC) has a crucial role in the pathophysiology of migraines.&#xD;
        The TCC is a common convergent pathway by which both trigeminal (dural) and cervical (mainly&#xD;
        via the greater occipital nerve) afferent inputs project into higher centres in the thalamus&#xD;
        and cortex. This afferent pathway is further influenced by the conditioned pain modulation&#xD;
        (CPM) pathway originating from the brainstem structures including periaqueductal grey matter,&#xD;
        nucleus raphe magnus, and the rostroventral medulla. There is some evidence to suggest that&#xD;
        increased peripheral sensitization of the afferent inputs of the TCC, generalized central&#xD;
        sensitization of the trigemino-spinal or the second order trigeminal neurons and impaired&#xD;
        descending pain inhibitory pathway, may all contribute to the development of the chronic&#xD;
        intractable or treatment resistant primary headache disorder Neurostimulation techniques for&#xD;
        treating intractable headache range from invasive deep brain stimulation to less invasive&#xD;
        peripheral implantation and stimulation. In 1999 Weiner and Reed described the beneficial&#xD;
        effects of subcutaneous Occipital nerve stimulation (ONS) in patients with medically&#xD;
        intractable, highly disabling chronic headache disorders Open-label studies have suggested&#xD;
        that this treatment modality is effective and safe (Lambru and Matharu 2012). Although the&#xD;
        exact mechanism of action is poorly understood, ONS is thought to act by stimulating the&#xD;
        distal branches of C1, C2 and C3 in turn influencing the TCC favourably by inhibiting the&#xD;
        nociceptive process, resulting in an improvement of symptoms. Previous work has demonstrated&#xD;
        a consistent and sustained improvement in conditioned pain modulation (CPM) following ONS as&#xD;
        confirmed with quantitative sensory testing (QST) (Wodehouse et al, 2014). QST has the&#xD;
        particular advantage of being a functional test that provides a quantitative pain stimulus&#xD;
        and assesses the subject's individual response to the stimulus. QST also provides a reliable&#xD;
        assessment of changes in pain thresholds and the benefit of ONS. However general anaesthetic&#xD;
        has also been demonstrated to cause changes/improvements in pain thresholds, peripheral and&#xD;
        central sensitisation and this effect can be long lasting and may account for&#xD;
        changes/improvements as measured by QST in subjects having ONS that the anaesthetic provides&#xD;
        relief as opposed to the ONS intervention.&#xD;
  &#xD;
        Quantitative sensory testing (QST) QST is a term used to describe different forms of&#xD;
        psychophysical testing of skin, mucosa, or muscle tissue that assess sensory and pain&#xD;
        perception pathways. Nociception inputs can trigger a prolonged but reversible increase in&#xD;
        the excitability and synaptic efficacy of neurons in central nociceptive pathways, the&#xD;
        phenomenon of central sensitisation in turn manifesting as pain hypersensitivity,&#xD;
        particularly dynamic tactile allodynia, and secondary punctate or pressure hyperalgesia and&#xD;
        enhanced temporal summation.&#xD;
  &#xD;
        QST has been used for measuring thresholds for different sensations in neuropathic pain&#xD;
        reflecting the possible nerve fibres that may be implicated in the pathogenesis. Heat&#xD;
        sensation threshold reflects the unmyelinated C-fiber function, cold sensation threshold&#xD;
        reflects the thinly myelinated A-fiber function and vibration threshold reflects the thickly&#xD;
        myelinated AB- fiber function.&#xD;
  &#xD;
        QST tests can be classified into the following:&#xD;
  &#xD;
        Measurement of pressure pain thresholds (PPT) (Static measure): This test measures&#xD;
        sensitivity of peripheral pain pathways to increasing mechanical pressure. A&#xD;
        computer-controlled pressure algometer (available as a bed side instrument) is used to&#xD;
        measure PPTs at a standardized point and compared with the affected area. A standardized&#xD;
        speed of pressure increase of 0.3kg/s is kept constant during pressure application to the&#xD;
        point when perception changes from pressure to pain (pressure pain threshold). This is useful&#xD;
        for confirming small fibres neuropathic lesion.&#xD;
  &#xD;
        Temperature thresholds: Thermal QST evaluates small nerve fibres, using thresholds for warm,&#xD;
        cold, heat-induced pain and cold-induced pain. It involves altering a thermal stimulus until&#xD;
        a sensation is perceived. Four sensory sub-modalities will be measured; C fibre mediated warm&#xD;
        sensation (WS), A-delta fibre mediated cold sensation (CS), heat induced pain (HP) (mostly C&#xD;
        fibre mediated sensation with some involvement of A-delta fibres) and C- and A-delta fibre&#xD;
        mediated cold induced pain (CP).&#xD;
  &#xD;
        Measurement of central sensitisation (Dynamic measure):&#xD;
  &#xD;
        This will be done using 2 different techniques as outlined below.&#xD;
  &#xD;
          1. Conditional Pain Modulation: Activity within the spinal dorsal horn arising from&#xD;
             peripheral nociceptive inputs can be modulated by powerful descending inhibitory and&#xD;
             facilitatory mechanisms. An example is provided by the phenomenon of conditioned pain&#xD;
             modulation (CPM), also known as diffuse noxious inhibitory control (DNIC) or&#xD;
             heterotrophic noxious conditioning stimulation. This refers to an altered response to a&#xD;
             painful stimulus following the administration of a second conditioning stimulus.&#xD;
  &#xD;
             CPM provides one of the main supraspinal pain inhibitory pathways and are impaired in&#xD;
             neuropathic pain. Diffuse noxious inhibitory controls refers to the observation that the&#xD;
             activity of multi-receptive neurons of the spinal cord can be strongly suppressed by an&#xD;
             intensive pain stimulus outside their peripheral receptive field. Induction of CPM can&#xD;
             be done by immersion in ice water (so-called cold-pressor test), or hot water on a&#xD;
             different/distant body part than the one on which the pain perception testing is being&#xD;
             performed. This effect represents a well-established model of endogenous pain&#xD;
             modulation.&#xD;
  &#xD;
          2. Measurement of Temporal summation- Repetitive delivery of a painful stimulus leads to an&#xD;
             increased perception of pain which can be used as a marker for central sensitization.&#xD;
             Seventeen, progressively rigid, monofilament, von Frey fibers (filaments represent&#xD;
             stimuli from 0.039 - 4386mN) will be used on a standardised position on the back decided&#xD;
             by the physician. A baseline NRS score will be obtained from the patient. The von Frey&#xD;
             Fibre will first ascertain the least force that measures a sensation of touch or pain&#xD;
             (pressure pain threshold). The exact threshold is found by repetitive testing using the&#xD;
             ascending fibre sizes. The repetitive stimulation consists of 10 repetitions of a&#xD;
             pressure stimulus applied for 1 second duration for 60 seconds. The magnitude of the&#xD;
             stimulus is set at the level of the subjects' pressure pain threshold. Patients rate the&#xD;
             pain intensity on a NRS for each pressure stimulus, and then for 15 sec after cessation&#xD;
             of 10 stimulations.&#xD;
  &#xD;
        Clinical Data for QST QST measurements have been used world-wide in the assessment of altered&#xD;
        pain experience and have been demonstrated to be safe and well tolerated. There exists&#xD;
        published evidence of QST measurements in chronic pain conditions like osteoarthritis,&#xD;
        fibromyalgia, migraine and other neuropathic pain conditions.&#xD;
  &#xD;
        QST measurements have been used worldwide in the assessment of altered pain experience and&#xD;
        have been demonstrated to be safe and well tolerated. We do not expect any risks associated&#xD;
        with the QST. Any discomfort experienced is transient and patients at all times are in&#xD;
        control with the experience and can stop at any-time.&#xD;
  &#xD;
        In addition, there is evidence to suggest that cytokines induce headache and headache pain.&#xD;
        Furthermore a higher level of cytokines can stimulate the activation of trigeminal nerves,&#xD;
        trigeminal nerve fibre sensitisation, the release vasoactive peptides or other biochemical&#xD;
        mediators like nitric oxide, which results in inflammation. Many studies have investigated&#xD;
        the role of different cytokines in the pathogenesis of migraine but the results remain&#xD;
        controversial. One reason for this may be the differing times of measured cytokines in some&#xD;
        cases ictally in others interictally. For this study we propose to takes samples at baseline&#xD;
        and at the follow up visits and investigate whether there is any alteration in levels of&#xD;
        cytokines with the ONS. We will be focusing on transforming growth factor-beta 1 (TGF-1),&#xD;
        which is a multifunctional proinflammatory cytokine involved in the modulation of cell&#xD;
        growth, differentiation and repairs following injury and immune modulation. Ishizaki et al.,&#xD;
        2005 demonstrated that serum levels of TGF-1 were higher in migraine than in controls. TGF-1&#xD;
        has been described as a platelet-derived cytokine as human platelets contain quantities of&#xD;
        dormant TGF-1 and reports have suggested that platelets play an important role in migraine&#xD;
        and therefore maybe in involved in headache pathogenesis and development of migraines.&#xD;
  &#xD;
        Glutamate is a prominent neurotransmitter and has been implicated in migraine pathogenesis.&#xD;
        Migraine pain-relay centers, including the trigeminal ganglion, trigeminal nucleus caudalis,&#xD;
        and thalamus, contain glutamate-positive neurons, and glutamate activates the trigeminal&#xD;
        nucleus caudalis. Glutamate is implicated in cortical spreading depression, trigeminovascular&#xD;
        activation, and central sensitization. Glutamate in blood (plasma) and urine will be measured&#xD;
        prior to and after ONS.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">September 1, 2019</start_date>
    <completion_date type="Anticipated">November 2024</completion_date>
    <primary_completion_date type="Anticipated">November 2023</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Sequential Assignment</intervention_model>
      <primary_purpose>Screening</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Number of participants with reversibility of a range of psychological markers of pain processing in patients with chronic migraine/cluster headache before and after ONS.</measure>
      <time_frame>4 WEEKS</time_frame>
      <description>Change QST</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Percentage of participants with pain markers (glutamate, TGF-B1) altered with ONS</measure>
      <time_frame>12 months</time_frame>
      <description>PAIN MARKERS ALTERED</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of participants whose functionality and quality of life following ONS - HIT6,</measure>
      <time_frame>4 weeks and 12 months</time_frame>
      <description>Q of L change with ONS</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The effect on functionality and quality of life following ONS - SF-12v2.</measure>
      <time_frame>4 weeks and 12 months</time_frame>
      <description>Q of L change with ONS</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The effect on functionality and quality of life following ONS - HAD</measure>
      <time_frame>4 weeks and 12 months</time_frame>
      <description>Q of L change with ONS</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">40</enrollment>
    <condition>Migraines</condition>
    <arm_group>
      <arm_group_label>Quantitative sensory testing</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>occipital nerve stimulator</intervention_name>
      <description>Quantitative sensory testing</description>
      <arm_group_label>Quantitative sensory testing</arm_group_label>
      <other_name>Quantitative sensory testing</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion criteria&#xD;
  &#xD;
          Subject satisfies standard criteria in the study centre for ONS implantation and the NICE&#xD;
          452 criteria for intractable chronic migraine or cluster headache.&#xD;
  &#xD;
          Patients who have given their written informed consent.&#xD;
  &#xD;
          Patient is able and willing to comply with study procedures and follow up schedule.&#xD;
  &#xD;
          Participants will need a good understanding of the English Language and hence. This is a&#xD;
          requirement not just for this research but also for the success of the interventions and&#xD;
          the full understanding of QST.&#xD;
  &#xD;
          Patients undergoing surgery (non-painful complaint) 'dilatation and curettage' (D&amp;C).&#xD;
  &#xD;
          Exclusion criteria&#xD;
  &#xD;
            -  Any inclusion criteria not met&#xD;
  &#xD;
            -  Female patients of childbearing age who is or plans on becoming pregnant during the&#xD;
               course of the study&#xD;
  &#xD;
            -  Patients with diabetes&#xD;
  &#xD;
            -  Patients known to have a condition that in the investigator's judgment precludes&#xD;
               participation in the study.&#xD;
  &#xD;
            -  Patients who have received an investigational drug or have used an investigational&#xD;
               device in the 30 days preceding to study entry&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Vivek mehta, FRCA MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Barts &amp; The London NHS Trust</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Theresa Wodehoise</last_name>
      <phone>07866813990</phone>
      <email>theresa.wodehouse@nhs.net</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Vivek mehta, FRCA MD FFP MRC</last_name>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Barts health NHS Trust</name>
        <address>
          <city>London</city>
          <zip>EC1A7BE</zip>
          <country>United Kingdom</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Theresa Wodehouse, PhD</last_name>
        <phone>07866813990</phone>
        <email>THERESA.WODEHOUSE@NHS.NET</email>
      </contact>
      <contact_backup>
        <phone>07866813990</phone>
        <email>theresa.wodehouse@nhs.net</email>
      </contact_backup>
    </location>
    <location_countries>
      <country>United Kingdom</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>June 28, 2019</study_first_submitted>
    <study_first_submitted_qc>September 1, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 5, 2023</study_first_posted>
    <last_update_submitted>September 1, 2023</last_update_submitted>
    <last_update_submitted_qc>September 1, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 5, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor-Investigator</responsible_party_type>
      <investigator_affiliation>Barts &amp; The London NHS Trust</investigator_affiliation>
      <investigator_full_name>Dr Theresa Wodehouse</investigator_full_name>
      <investigator_title>Scientist</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Migraine Disorders</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT06022848
  org study id: 210723
  nct id: NCT06022848
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The primary aim of this study is to assess the reversibility of a range of psychophysical
        markers of pain processing in patients with chronic migraine or cluster headache before and
        after ONS insertion and comparing to patients having a general anaesthetic (GA) for a
        non-painful aetiology at Barts Health NHS Trust. We will also compare with healthy volunteers
        not undergoing surgery.
  
        To establish whether pain perception alters in patients with chronic migraine/cluster
        headache having ONS using questionnaires and compare to patients having a general anaesthetic
        for a non- painful procedure D & C at Barts Health NHS Trust.
  
        Are pain markers (Glutamate, TGF-B1) altered with ONS?
  Headache is one of the most common neurological problems accounting for 4% of primary care
        consultations and up to 30% of neurology appointments. Even though considerable advances in
        the understanding of the pathogenesis of migraine, new pharmacologic treatments and the
        emergence of new innovative interventions for difficult cases, in many patients with migraine
        remain intractable to medical therapy.
  
        The trigeminocervical complex (TCC) has a crucial role in the pathophysiology of migraines.
        The TCC is a common convergent pathway by which both trigeminal (dural) and cervical (mainly
        via the greater occipital nerve) afferent inputs project into higher centres in the thalamus
        and cortex. This afferent pathway is further influenced by the conditioned pain modulation
        (CPM) pathway originating from the brainstem structures including periaqueductal grey matter,
        nucleus raphe magnus, and the rostroventral medulla. There is some evidence to suggest that
        increased peripheral sensitization of the afferent inputs of the TCC, generalized central
        sensitization of the trigemino-spinal or the second order trigeminal neurons and impaired
        descending pain inhibitory pathway, may all contribute to the development of the chronic
        intractable or treatment resistant primary headache disorder Neurostimulation techniques for
        treating intractable headache range from invasive deep brain stimulation to less invasive
        peripheral implantation and stimulation. In 1999 Weiner and Reed described the beneficial
        effects of subcutaneous Occipital nerve stimulation (ONS) in patients with medically
        intractable, highly disabling chronic headache disorders Open-label studies have suggested
        that this treatment modality is effective and safe (Lambru and Matharu 2012). Although the
        exact mechanism of action is poorly understood, ONS is thought to act by stimulating the
        distal branches of C1, C2 and C3 in turn influencing the TCC favourably by inhibiting the
        nociceptive process, resulting in an improvement of symptoms. Previous work has demonstrated
        a consistent and sustained improvement in conditioned pain modulation (CPM) following ONS as
        confirmed with quantitative sensory testing (QST) (Wodehouse et al, 2014). QST has the
        particular advantage of being a functional test that provides a quantitative pain stimulus
        and assesses the subject's individual response to the stimulus. QST also provides a reliable
        assessment of changes in pain thresholds and the benefit of ONS. However general anaesthetic
        has also been demonstrated to cause changes/improvements in pain thresholds, peripheral and
        central sensitisation and this effect can be long lasting and may account for
        changes/improvements as measured by QST in subjects having ONS that the anaesthetic provides
        relief as opposed to the ONS intervention.
  
        Quantitative sensory testing (QST) QST is a term used to describe different forms of
        psychophysical testing of skin, mucosa, or muscle tissue that assess sensory and pain
        perception pathways. Nociception inputs can trigger a prolonged but reversible increase in
        the excitability and synaptic efficacy of neurons in central nociceptive pathways, the
        phenomenon of central sensitisation in turn manifesting as pain hypersensitivity,
        particularly dynamic tactile allodynia, and secondary punctate or pressure hyperalgesia and
        enhanced temporal summation.
  
        QST has been used for measuring thresholds for different sensations in neuropathic pain
        reflecting the possible nerve fibres that may be implicated in the pathogenesis. Heat
        sensation threshold reflects the unmyelinated C-fiber function, cold sensation threshold
        reflects the thinly myelinated A-fiber function and vibration threshold reflects the thickly
        myelinated AB- fiber function.
  
        QST tests can be classified into the following:
  
        Measurement of pressure pain thresholds (PPT) (Static measure): This test measures
        sensitivity of peripheral pain pathways to increasing mechanical pressure. A
        computer-controlled pressure algometer (available as a bed side instrument) is used to
        measure PPTs at a standardized point and compared with the affected area. A standardized
        speed of pressure increase of 0.3kg/s is kept constant during pressure application to the
        point when perception changes from pressure to pain (pressure pain threshold). This is useful
        for confirming small fibres neuropathic lesion.
  
        Temperature thresholds: Thermal QST evaluates small nerve fibres, using thresholds for warm,
        cold, heat-induced pain and cold-induced pain. It involves altering a thermal stimulus until
        a sensation is perceived. Four sensory sub-modalities will be measured; C fibre mediated warm
        sensation (WS), A-delta fibre mediated cold sensation (CS), heat induced pain (HP) (mostly C
        fibre mediated sensation with some involvement of A-delta fibres) and C- and A-delta fibre
        mediated cold induced pain (CP).
  
        Measurement of central sensitisation (Dynamic measure):
  
        This will be done using 2 different techniques as outlined below.
  
          1. Conditional Pain Modulation: Activity within the spinal dorsal horn arising from
             peripheral nociceptive inputs can be modulated by powerful descending inhibitory and
             facilitatory mechanisms. An example is provided by the phenomenon of conditioned pain
             modulation (CPM), also known as diffuse noxious inhibitory control (DNIC) or
             heterotrophic noxious conditioning stimulation. This refers to an altered response to a
             painful stimulus following the administration of a second conditioning stimulus.
  
             CPM provides one of the main supraspinal pain inhibitory pathways and are impaired in
             neuropathic pain. Diffuse noxious inhibitory controls refers to the observation that the
             activity of multi-receptive neurons of the spinal cord can be strongly suppressed by an
             intensive pain stimulus outside their peripheral receptive field. Induction of CPM can
             be done by immersion in ice water (so-called cold-pressor test), or hot water on a
             different/distant body part than the one on which the pain perception testing is being
             performed. This effect represents a well-established model of endogenous pain
             modulation.
  
          2. Measurement of Temporal summation- Repetitive delivery of a painful stimulus leads to an
             increased perception of pain which can be used as a marker for central sensitization.
             Seventeen, progressively rigid, monofilament, von Frey fibers (filaments represent
             stimuli from 0.039 - 4386mN) will be used on a standardised position on the back decided
             by the physician. A baseline NRS score will be obtained from the patient. The von Frey
             Fibre will first ascertain the least force that measures a sensation of touch or pain
             (pressure pain threshold). The exact threshold is found by repetitive testing using the
             ascending fibre sizes. The repetitive stimulation consists of 10 repetitions of a
             pressure stimulus applied for 1 second duration for 60 seconds. The magnitude of the
             stimulus is set at the level of the subjects' pressure pain threshold. Patients rate the
             pain intensity on a NRS for each pressure stimulus, and then for 15 sec after cessation
             of 10 stimulations.
  
        Clinical Data for QST QST measurements have been used world-wide in the assessment of altered
        pain experience and have been demonstrated to be safe and well tolerated. There exists
        published evidence of QST measurements in chronic pain conditions like osteoarthritis,
        fibromyalgia, migraine and other neuropathic pain conditions.
  
        QST measurements have been used worldwide in the assessment of altered pain experience and
        have been demonstrated to be safe and well tolerated. We do not expect any risks associated
        with the QST. Any discomfort experienced is transient and patients at all times are in
        control with the experience and can stop at any-time.
  
        In addition, there is evidence to suggest that cytokines induce headache and headache pain.
        Furthermore a higher level of cytokines can stimulate the activation of trigeminal nerves,
        trigeminal nerve fibre sensitisation, the release vasoactive peptides or other biochemical
        mediators like nitric oxide, which results in inflammation. Many studies have investigated
        the role of different cytokines in the pathogenesis of migraine but the results remain
        controversial. One reason for this may be the differing times of measured cytokines in some
        cases ictally in others interictally. For this study we propose to takes samples at baseline
        and at the follow up visits and investigate whether there is any alteration in levels of
        cytokines with the ONS. We will be focusing on transforming growth factor-beta 1 (TGF-1),
        which is a multifunctional proinflammatory cytokine involved in the modulation of cell
        growth, differentiation and repairs following injury and immune modulation. Ishizaki et al.,
        2005 demonstrated that serum levels of TGF-1 were higher in migraine than in controls. TGF-1
        has been described as a platelet-derived cytokine as human platelets contain quantities of
        dormant TGF-1 and reports have suggested that platelets play an important role in migraine
        and therefore maybe in involved in headache pathogenesis and development of migraines.
  
        Glutamate is a prominent neurotransmitter and has been implicated in migraine pathogenesis.
        Migraine pain-relay centers, including the trigeminal ganglion, trigeminal nucleus caudalis,
        and thalamus, contain glutamate-positive neurons, and glutamate activates the trigeminal
        nucleus caudalis. Glutamate is implicated in cortical spreading depression, trigeminovascular
        activation, and central sensitization. Glutamate in blood (plasma) and urine will be measured
        prior to and after ONS.
  allocation: N/A
  intervention model: Sequential Assignment
  primary purpose: Screening
  masking: None (Open Label)
  measure: Number of participants with reversibility of a range of psychological markers of pain processing in patients with chronic migraine/cluster headache before and after ONS.
  time frame: 4 WEEKS
  description: Change QST
  measure: Percentage of participants with pain markers (glutamate, TGF-B1) altered with ONS
  time frame: 12 months
  description: PAIN MARKERS ALTERED
  measure: Number of participants whose functionality and quality of life following ONS - HIT6,
  time frame: 4 weeks and 12 months
  description: Q of L change with ONS
  measure: The effect on functionality and quality of life following ONS - SF-12v2.
  time frame: 4 weeks and 12 months
  description: Q of L change with ONS
  measure: The effect on functionality and quality of life following ONS - HAD
  time frame: 4 weeks and 12 months
  description: Q of L change with ONS
  arm group label: Quantitative sensory testing
  arm group type: Experimental
  intervention type: Procedure
  intervention name: occipital nerve stimulator
  description: Quantitative sensory testing
  arm group label: Quantitative sensory testing
  other name: Quantitative sensory testing
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: Accepts Healthy Volunteers
  last name: Vivek mehta, FRCA MD
  role: Principal Investigator
  affiliation: Barts & The London NHS Trust
  last name: Theresa Wodehoise
  phone: 07866813990
  email: theresa.wodehouse@nhs.net
  last name: Vivek mehta, FRCA MD FFP MRC
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  country: United Kingdom
  responsible party type: Sponsor-Investigator
  investigator affiliation: Barts & The London NHS Trust
  investigator full name: Dr Theresa Wodehouse
  investigator title: Scientist
  mesh term: Migraine Disorders
  sharing ipd: No