Clinical Trial: Painful Channelopathies Study

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Painful Channelopathies Study

Brief Summary:

To understand the pathophysiological basis of heritable pain syndromes. This will consist of a number of components:

• Determine the genetic basis for heritable pain syndromes.
• Investigate the pain symptoms, psychological co-morbidity and quality of life in patients with heritable pain syndromes.
• Use quantitative sensory testing to investigate abnormalities in sensory processing.
• Use imaging modalities to investigate the neural correlates of pain perception in heritable channelopathies.
• In select patients to perform skin biopsy to determine if there has been any damage to C-fibres.
• To perform skin biopsy in order to culture fibroblasts and neural crest stem cells for future studies into the molecular basis of altered pain perception.
• To use neurophysiological tests, the axon reflex, and conditioning challenges to determine how peripheral nerves, in heritable channelopathies and unusual pain syndromes, have been altered.
• Microneurographic recordings for directly detecting the function of pain fibres in peripheral nerves. Knowledge gained from the study will be used to aid the further development of genetic testing and specific pain questionnaires for the diagnosis of heritable pain syndromes secondary to channelopathies.
• Ultimately better knowledge of underlying pathophysiology in these heritable pain conditions may inform the development of novel treatments.

Detailed Summary:

Very little is currently known about the sensory characteristics and central processing of pain in patients with heritable channelopathies. The investigators will carefully study the phenotype of such patients in terms of pain symptomatology, sensory processing as revealed by quantitative sensory testing and correlate this with genotype. In select patients the investigators will perform skin biopsy to determine whether there is any evidence of damage to small fibres and would also like to generate fibroblast and neural crest stem cell cultures for future studies of the molecular basis for channel dysfunction.

The study will provide new insights into the peripheral and central nervous system mechanisms involved in the processing of pain.

The investigators will restrict themselves to channelopathies causing somatic pain syndromes and will not be investigating migraine. The following conditions will be considered: Erythromelalgia, Paroxysmal extreme pain disorder, Familial episodic pain syndrome, patients with episodic pain symptoms for which a cause cannot be found and patients with reduced pain sensibility.

1.2.1 Quantitative sensory testing (QST)

QST is a method for accurately determining sensory thresholds in human skin and is particularly useful for determining dysfunction in the nociceptive smaller diameter nerve fibres, although the precise utility of QST in routine clinical neuropathic pain management perhaps requires some further evaluation. There is also increasing interest in using QST in combination with assessment of pain descriptors to give insights into the underlying pathophysiological mechanisms of chronic pain. For example, the presence of brush evoked dynamic allodynia indicates sensitisation at the spinal le
Sponsor: King's College London

Current Primary Outcome: Pain score [ Time Frame: Day 7 ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Age [ Time Frame: Day 1 ]
  Number of years
• Gender [ Time Frame: Day 1 ]
  Chromosome gender (male/female)
• Ethnicity [ Time Frame: Day 1 ]
  Ethnic group
• Detailed medical history [ Time Frame: Day 1 ]
  Number and name of medications that were taken previously by the patient
• Pain related anxiety [ Time Frame: Day 1 ]
  Patients will answer the Pain Anxiety Symptoms Scale (PASS-20)
• Measures of quality of life [ Time Frame: Day 1 ]
  Patients will answer the 36-Item Short Form Survey -quality of life questionnaire-
• Measures of sleep interference [ Time Frame: Day 1 ]
  Sleep quality is assessed through the use of questionnaires
• Nerve Conduction Studies [ Time Frame: Day 1 ]
  Neurophysiology will be conducted to assess nerve integrity. Amplitude will be measured in microvolts.
• Nerve Conduction Studies [ Time Frame: Day 1 ]
  Neurophysiology will be conducted to assess nerve integrity. Latency will be measured in milliseconds.
• Microneurography Studies [ Time Frame: Day 1 ]
  This is a minimally invasive technique in which the activity of single nerve fibre is recorded from peripheral nerves and is for directly detecting the function of pain fibres in peripheral nerves in humans.
• Sensory Thermal Thresholds [ Time Frame: Day 1 ]
  Thermal thresholds will be measured in degrees centigrade
• Sensory Mechanical Detection Thresholds [ Time Frame: Day 1 ]
  Mechanical Detection Thresholds will be measured in millinewtons
• Intra-Epidermal Nerve Fibre density [ Time Frame: Day 1 ]
  Measurement of nerve fibres in the skin of patients (taken depending of the pain related area)
• Skin biopsy [ Time Frame: Day 1 ]
  Collection and culture of fibroblasts and neural crest stem cells for assessing differences in the rheobase measured in amperes.
• Axon reflex measurement [ Time Frame: Day 1 ]
  Application of agents such as histamine via iontophoresis which will stimulate the peripheral nerve endings of C fibres inducing a vasodilatation, which is visible as a flare response of the skin (area in square centimeters with flare).
• Functional Magnetic Resonance Imaging [ Time Frame: Day 30 ]
  Brain activity related to the pain condition
• Blood samples - DNA [ Time Frame: Within 6 months of visit ]
  Blood samples coupled with detailed phenotype data will investigate potential gene associations in the development of painful or painless conditions.

Original Secondary Outcome: Same as current

Information By: King's College London

Dates:
Date Received: February 5, 2016
Date Started: February 2012
Date Completion:
Last Updated: February 20, 2017
Last Verified: February 2017