Facial Neuropathy
Conditions
Keywords
pain, neuropathic, face, trigeminal
Brief summary
The aim of this project is to evaluate the effects of the anticonvulsant drug lamotrigine (trade name Lamictal) on neuropathic facial pain or neuralgia using functional magnetic resonance imaging (fMRI).
Detailed description
Currently there are no pharmacological agents that can control neuropathic pain akin to the efficacy of antibiotics for bacterial infection. All current neuropathic pain drugs have approximately the same efficacy of less than 30% in controlled trials, and many of these drugs do not have known mechanisms of action. fMRI studies may provide insight into how brain circuitry is altered by chronic pain, and how these drugs act on altered circuitry. The trigeminal system in particular offers unique advantages for studying such alterations, including a large central representation and high degree of somatotopy. The administration of lamotrigine to neuropathic pain patients in conjunction with fMRI will allow us to compare subjective ratings of pain with objective measures of neural activity during increased conditions of allodynia/hyperalgesia.
Interventions
DRUGLamotrigine
: 25mg and 50mg tablets
DRUGPlacebo (for Lamotrigine)
Sugar pill manufactured to mimic Lamotrigine tablets
Sponsors
GlaxoSmithKline
Pain and Analgesia Imaging and Neuroscience Group
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* 18-60 years of age * Right-handed non-smokers * Diagnosed with facial pain * Continuous pain for more than 3 months * Spontaneous pain greater than 3 of 10 * Allodynia to brush greater than 5 of 10
Exclusion criteria
* Medications * Depression * Significant medical problems * Claustrophobia * Abnormal EKG * Significant drug or alcohol history * Positive drug screen * Weight greater than 285 lbs * History of allergy to anticonvulsants * Tattoos with metallic ink on upper body * Any neurostimulator devices, or metal cochlear, ocular, or cardiac implants or other metal near vital areas * Exposure to shrapnel or metal filings * Other metallic surgical hardware
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Blood Oxygenation Level-dependent (BOLD) Changes in Neural Pain Circuitry Following Treatment With Lamotrigine During Experimentally Induced Pain States | Week 10 during scanning session | fMRI scans acquired Stimuli Type: Brush Stimulation Regions: Face (V2) Right and Left Sides Rating: Pain/ unpleasantness fMRI scans acquired Stimuli Type: Cold, threshold -1°C Stimulation Regions: Face (V2) Right and Left Sides Rating: Pain/ unpleasantness \*\*Extra time allotted for probe repositioning\*\* fMRI scans acquired Stimuli Type: Heat, threshold +1°C Stimulation Regions: Face (V2) Right and Left Sides Rating: Pain/ unpleasantness \*\*Extra time allotted for probe repositioning\*\* Cortical, subcortical, and brain stem sensory regions Z-scores Increase or decrease in activation as affected by the drug |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Subjective Ratings of Pain During Magnetic Resonance Scanning | week 10 (during the scan) | Quantitative Sensory Testing (QST) Stimuli Type: Heat, Cold, Brush Stimulation Regions: Face Affected and contralateral Unaffected mirror area Rating: Pain/ unpleasantness Stimuli Type: Cold, threshold -1°C Stimulation Regions: Face Affected and contralateral Unaffected mirror area Rating: Pain/ unpleasantness Stimuli Type: Heat, threshold +1°C Stimulation Regions: Face Affected and contralateral Unaffected mirror area Rating: Pain/ unpleasantness Ratings on a likert scale of 0-10 with 0 being defined as no pain and 10 being defined as worst possible pain |
Countries
United States
Participant flow
Recruitment details
This study recruited adult males and females ages 18 to 60 with diagnosed facial neuropathic pain.
Participants by arm
| Arm | Count |
|---|---|
| Lamotrigine The drug lamotrigine or placebo will be given for 9 weeks prior to imaging session 1. A rescue drug, Gabapentin, will be provided during both arms of the study for pain control. Patients will taper off the Gabapentin 2 weeks before each scan date. After a taper and washout period lamotrigine or placebo (cross over) will be administered. At the end of the trial (after imaging session 2), a taper for drug/placebo will be given. Patients will be required to maintain a pain diary during the study, documenting the perceived effects of the drug on the severity of their pain and keeping track of their subjective pain ratings day to day. Patients will also complete the McGill Pain Questionnaire at each visit.
Lamotrigine: : 25mg and 50mg tablets | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | Lamotrigine |
|---|---|
| Age, Customized Ages 18 to 60 Years | 6 participants |
| Allodynia brush greater than 5 of 10 | 6 participants |
| Continuous pain for more than 3 months | 6 participants |
| Diagnosed with facial pain | 6 participants |
| Non-smokers | 6 participants |
| Region of Enrollment United States | 6 participants |
| Right-handed | 6 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 2 Participants |
| Spontaneous pain greater than 3 of 10 | 6 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 6 | 0 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 |
Outcome results
Primary
Blood Oxygenation Level-dependent (BOLD) Changes in Neural Pain Circuitry Following Treatment With Lamotrigine During Experimentally Induced Pain States
fMRI scans acquired Stimuli Type: Brush Stimulation Regions: Face (V2) Right and Left Sides Rating: Pain/ unpleasantness fMRI scans acquired Stimuli Type: Cold, threshold -1°C Stimulation Regions: Face (V2) Right and Left Sides Rating: Pain/ unpleasantness \*\*Extra time allotted for probe repositioning\*\* fMRI scans acquired Stimuli Type: Heat, threshold +1°C Stimulation Regions: Face (V2) Right and Left Sides Rating: Pain/ unpleasantness \*\*Extra time allotted for probe repositioning\*\* Cortical, subcortical, and brain stem sensory regions Z-scores Increase or decrease in activation as affected by the drug
Time frame: Week 10 during scanning session
Population: The data's primary comparisons no longer exists per intervention.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lamotrigine vs Placebo | Blood Oxygenation Level-dependent (BOLD) Changes in Neural Pain Circuitry Following Treatment With Lamotrigine During Experimentally Induced Pain States | Heat Affected Thalamus (10,-14,8) | -2.9294 Z-statistic |
| Lamotrigine vs Placebo | Blood Oxygenation Level-dependent (BOLD) Changes in Neural Pain Circuitry Following Treatment With Lamotrigine During Experimentally Induced Pain States | Heat Affected Post-Central (-56,-12,28) | -2.7323 Z-statistic |
| Lamotrigine vs Placebo | Blood Oxygenation Level-dependent (BOLD) Changes in Neural Pain Circuitry Following Treatment With Lamotrigine During Experimentally Induced Pain States | Cold Affected Post-Central (68, -8, 32) | -2.5114 Z-statistic |
| Lamotrigine vs Placebo | Blood Oxygenation Level-dependent (BOLD) Changes in Neural Pain Circuitry Following Treatment With Lamotrigine During Experimentally Induced Pain States | Cold Affected Thalamus (-4, -8, 0) | -3.033 Z-statistic |
| Lamotrigine vs Placebo | Blood Oxygenation Level-dependent (BOLD) Changes in Neural Pain Circuitry Following Treatment With Lamotrigine During Experimentally Induced Pain States | Brush Affected Post-Central (66,-16,14) | 3.905 Z-statistic |
| Lamotrigine vs Placebo | Blood Oxygenation Level-dependent (BOLD) Changes in Neural Pain Circuitry Following Treatment With Lamotrigine During Experimentally Induced Pain States | Brush Affected Thalamus (-14,-22, 4) | -3.791 Z-statistic |
| Lamotrigine vs Placebo | Blood Oxygenation Level-dependent (BOLD) Changes in Neural Pain Circuitry Following Treatment With Lamotrigine During Experimentally Induced Pain States | Brush Affected Spinal Trigeminal Nucles(2,-48,-68) | 2.9058 Z-statistic |
Secondary
Subjective Ratings of Pain During Magnetic Resonance Scanning
Quantitative Sensory Testing (QST) Stimuli Type: Heat, Cold, Brush Stimulation Regions: Face Affected and contralateral Unaffected mirror area Rating: Pain/ unpleasantness Stimuli Type: Cold, threshold -1°C Stimulation Regions: Face Affected and contralateral Unaffected mirror area Rating: Pain/ unpleasantness Stimuli Type: Heat, threshold +1°C Stimulation Regions: Face Affected and contralateral Unaffected mirror area Rating: Pain/ unpleasantness Ratings on a likert scale of 0-10 with 0 being defined as no pain and 10 being defined as worst possible pain
Time frame: week 10 (during the scan)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lamotrigine vs Placebo | Subjective Ratings of Pain During Magnetic Resonance Scanning | Heat Affected | 5.5 scores on a pain scale | Standard Deviation 2 |
| Lamotrigine vs Placebo | Subjective Ratings of Pain During Magnetic Resonance Scanning | Heat Unaffected | 4 scores on a pain scale | Standard Deviation 3 |
| Lamotrigine vs Placebo | Subjective Ratings of Pain During Magnetic Resonance Scanning | Cold Affected | 2.5 scores on a pain scale | Standard Deviation 1.2 |
| Lamotrigine vs Placebo | Subjective Ratings of Pain During Magnetic Resonance Scanning | Cold Unaffected | 1.1 scores on a pain scale | Standard Deviation 1 |
| Lamotrigine vs Placebo | Subjective Ratings of Pain During Magnetic Resonance Scanning | Brush Affected | 3.9 scores on a pain scale | Standard Deviation 2.1 |
| Lamotrigine vs Placebo | Subjective Ratings of Pain During Magnetic Resonance Scanning | Brush Unaffected | .4 scores on a pain scale | Standard Deviation 0.3 |
| Lamotrigine | Subjective Ratings of Pain During Magnetic Resonance Scanning | Brush Affected | 2.8 scores on a pain scale | Standard Deviation 2.8 |
| Lamotrigine | Subjective Ratings of Pain During Magnetic Resonance Scanning | Heat Affected | 3.2 scores on a pain scale | Standard Deviation 1.5 |
| Lamotrigine | Subjective Ratings of Pain During Magnetic Resonance Scanning | Cold Unaffected | 2.2 scores on a pain scale | Standard Deviation 1.75 |
| Lamotrigine | Subjective Ratings of Pain During Magnetic Resonance Scanning | Heat Unaffected | 3 scores on a pain scale | Standard Deviation 2 |
| Lamotrigine | Subjective Ratings of Pain During Magnetic Resonance Scanning | Brush Unaffected | 1.2 scores on a pain scale | Standard Deviation 2.2 |
| Lamotrigine | Subjective Ratings of Pain During Magnetic Resonance Scanning | Cold Affected | 2.1 scores on a pain scale | Standard Deviation 1.5 |
Comparison: Visual analog scale (VAS) ratings in the scanner. Measures of pain ratings to evoked stimuli during scanning for heat applied to the affected side.p-value: <0.05t-test, 2 sided
Comparison: VAS rating in the scanner. Measures of pain rating to evoke stimuli during scanning for heat applied to the unaffected side.p-value: >0.05t-test, 2 sided
Comparison: VAS rating in the scanner. Measures of pain rating to evoke stimuli during scanning for cold applied to the affected side.p-value: >0.05t-test, 2 sided
Comparison: VAS rating in the scanner. Measures of pain rating to evoke stimuli during scanning for cold applied to the unaffected side.p-value: >0.05t-test, 2 sided
Comparison: VAS rating in the scanner. Measures of pain rating to evoke stimuli during scanning for brush applied to the affected side.p-value: >0.05t-test, 2 sided
Comparison: VAS rating in the scanner. Measures of pain rating to evoke stimuli during scanning for brush applied to the unaffected side.p-value: >0.05t-test, 2 sided