Pain
Conditions
Keywords
lidocaine, allodynia, chronic regional pain syndrome, pain
Brief summary
The purpose of this study is to study if lidocaine, given intravenously, reduces pain.
Detailed description
Clinicians use lidocaine intravenously in a fashion that suggests that it might have analgesic effects. Therefore, we test the hypothesis that lidocaine reduces pain intensity in response to experimental pain.
Interventions
DRUGLidocaine
Lidocaine 2% (2mg/ml) was administered via a computer assisted infusion to achieve a target plasma concentration of 2 mcg/ml; infused within 20 minutes.
Sponsors
American Society of Regional Anesthesia
University of Alabama at Birmingham
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Healthy Adult Volunteers, age \>19 years
Exclusion criteria
* History of Substance Abuse * Coronary Artery Disease (CAD): unstable * Congestive Heart Failure (CHF): unstable * Heart Arrhythmia: symptomatic * Chronic Obstructive Pulmonary Disease (COPD) * Lidocaine Allergy * Diagnostic and Statistical Manual of Mental Disorders (Rev IV): Axis I: Common Axis I disorders include depression, anxiety disorders,bipolar disorder, ADHD, and schizophrenia. Axis II: borderline personality disorder, schizotypal personality disorder, antisocial personality disorder, and mild mental retardation. * Presence of Contraindications for MRI * Presence of electronically, magnetically, and mechanically activated implants * Electronically, magnetically, and mechanically activated implants * Ferromagnetic or electronically operated active devices like automatic cardioverter defibrillators * Cardiac pacemakers * Metallic splinters in the eye * Ferromagnetic haemostatic clips in the central nervous system (CNS) * Claustrophobia * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ischemic Pain | baseline, during 20 minute lidocaine infusion, and 30 minutes after discontinuation of lidocaine infusion | The right arm was exsanguinated by elevating it above heart level for 30 seconds, after which the arm was occluded with a standard blood pressure cuff positioned proximal to the elbow inflated to twice the participant's mean arterial pressure. Participants then performed 20 handgrip exercises of 2-second duration at 4-second intervals at 50% of their maximum grip strength. Pain was rated on a scale from 0 - 10 with 0 being no pain to 10 being the worst pain imaginable. |
| Electrical Pain | Baseline, during 20 minutes lidocaine infusion, and 30 minutes after completion of lidocaine infusion | Peripheral nerve stimulation electrodes were attached to the base and the tip of the third digit and connected to a constant current stimulator (DS7A, Digitimer Ltd, Hertfordshire, England). Ascending electrical stimuli of 2000 mu duration, ranging from 0.5 to 35 mA (ampere) was administered one per second in 0.5 mA increments. Participants were instructed to indicate when they first felt the slightest sense of pain (electrical pain threshold, EPTh) and when they were unable to tolerate a further increase (electrical pain tolerance, EPTo). For each measure, the average of three trials was computed for use in subsequent analyses. Each of the three electrical pain stimuli were presented three times and balanced in order using a Graeco-Latin square design. The pain scale is between 0 and 10, with 0 being no pain and 10 being the worst pain imaginable |
| Heat Pain | baseline, during 20 minute lidocaine infusion, and 30 minutes after completion of lidocaine infusion | The thermal procedure involved a baseline assessment of heat pain threshold and tolerance. Contact heat stimuli were delivered using a computer-controlled Medoc Thermal Sensory Analyzer (TSA-II; Ramat Yishai, Israel), which is a peltier elementbased stimulator. Temperature levels were monitored by a thermistor and returned to a preset baseline of 32°C by active cooling at a rate of 10°C/s. The 3 × 3 cm contact probe was applied to the right forearm. The pain scale is between 0 and 10 with 1 being no pain and 10 being the worst pain imaginable |
| Cold Pain | baseline, during 20 minute infusion, and 30 minutes after lidocaine infusion | The participant's foot was immersed up to the ankle into a container filled with ice water of 3°C. Participants were instructed to maintain their foot in the container until the cold pain became intolerable (cold pain tolerance). The length of time was recorded in seconds. This procedure was repeated once with a gap of at least fifteen minutes in-between repeated tests. The range was 0 seconds to 120 seconds |
| Tactile Sensation | baseline, during 20 minute infusion, and 30 minutes after completion of infusion | Pin prick sensory thresholds (PPT) were obtained by touching the skin in-between the first and second metacarpal bone with a 23-gauge needles which moved freely out of a 10 mL plastic syringe barrel. The pin prick sensation was modified by adding small weights to the 23-gauge needles (from 0.2 to 5.2 mg). A syringe barrel of tuberculin (TB) needles that were cut to different lengths to add the desired weight to the 23-gauge needle. The PPT was determined using the weighted 23-gauge needle in ascending order, according to the method of limits. This assessment was to evaluate whether participants were able to feel the touch of the needle. The participant's arm was placed on a tray table. A linen sheet was suspended in-between two IV poles in such a fashion that the subject's view of his/her hand was blocked. Normal values are between 0.21mg and 5mg. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lidocaine Healthy Volunteers receiving Lidocaine | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lack of Efficacy | 6 |
Baseline characteristics
| Characteristic | Lidocaine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants |
| Age, Continuous | 25 years STANDARD_DEVIATION 4 |
| Region of Enrollment United States | 16 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 16 |
| serious Total, serious adverse events | 0 / 16 |
Outcome results
Primary
Cold Pain
The participant's foot was immersed up to the ankle into a container filled with ice water of 3°C. Participants were instructed to maintain their foot in the container until the cold pain became intolerable (cold pain tolerance). The length of time was recorded in seconds. This procedure was repeated once with a gap of at least fifteen minutes in-between repeated tests. The range was 0 seconds to 120 seconds
Time frame: baseline, during 20 minute infusion, and 30 minutes after lidocaine infusion
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lidocaine Administration | Cold Pain | Baseline - at start of infusion | 42 time in seconds to withdrawal | Standard Error 10.9 |
| Lidocaine Administration | Cold Pain | During 20 minute lidocaine infusion | 50.6 time in seconds to withdrawal | Standard Error 10.9 |
| Lidocaine Administration | Cold Pain | 30 minutes after completion of lidocaine infusion | 51.2 time in seconds to withdrawal | Standard Error 11 |
Primary
Electrical Pain
Peripheral nerve stimulation electrodes were attached to the base and the tip of the third digit and connected to a constant current stimulator (DS7A, Digitimer Ltd, Hertfordshire, England). Ascending electrical stimuli of 2000 mu duration, ranging from 0.5 to 35 mA (ampere) was administered one per second in 0.5 mA increments. Participants were instructed to indicate when they first felt the slightest sense of pain (electrical pain threshold, EPTh) and when they were unable to tolerate a further increase (electrical pain tolerance, EPTo). For each measure, the average of three trials was computed for use in subsequent analyses. Each of the three electrical pain stimuli were presented three times and balanced in order using a Graeco-Latin square design. The pain scale is between 0 and 10, with 0 being no pain and 10 being the worst pain imaginable
Time frame: Baseline, during 20 minutes lidocaine infusion, and 30 minutes after completion of lidocaine infusion
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lidocaine Administration | Electrical Pain | Baseline - at time of lidocaine administration | 2.40 units on a scale | Standard Error 0.34 |
| Lidocaine Administration | Electrical Pain | During 20 minute lidocaine Infusion | 2.04 units on a scale | Standard Error 0.34 |
| Lidocaine Administration | Electrical Pain | 30 minutes after compleition of lidocaine infusion | 2.52 units on a scale | Standard Error 0.34 |
Primary
Heat Pain
The thermal procedure involved a baseline assessment of heat pain threshold and tolerance. Contact heat stimuli were delivered using a computer-controlled Medoc Thermal Sensory Analyzer (TSA-II; Ramat Yishai, Israel), which is a peltier elementbased stimulator. Temperature levels were monitored by a thermistor and returned to a preset baseline of 32°C by active cooling at a rate of 10°C/s. The 3 × 3 cm contact probe was applied to the right forearm. The pain scale is between 0 and 10 with 1 being no pain and 10 being the worst pain imaginable
Time frame: baseline, during 20 minute lidocaine infusion, and 30 minutes after completion of lidocaine infusion
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lidocaine Administration | Heat Pain | Baseline - at start of lidocaine infusion | 3.01 units on a scale | Standard Error 0.42 |
| Lidocaine Administration | Heat Pain | During 20 minute lidocaine infusion | 2.83 units on a scale | Standard Error 0.42 |
| Lidocaine Administration | Heat Pain | 30 minutes after completion of lidocaine infusion | 2.82 units on a scale | Standard Error 0.42 |
Primary
Ischemic Pain
The right arm was exsanguinated by elevating it above heart level for 30 seconds, after which the arm was occluded with a standard blood pressure cuff positioned proximal to the elbow inflated to twice the participant's mean arterial pressure. Participants then performed 20 handgrip exercises of 2-second duration at 4-second intervals at 50% of their maximum grip strength. Pain was rated on a scale from 0 - 10 with 0 being no pain to 10 being the worst pain imaginable.
Time frame: baseline, during 20 minute lidocaine infusion, and 30 minutes after discontinuation of lidocaine infusion
Population: health volunteers
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lidocaine Administration | Ischemic Pain | Baseline (prior to administration) | 4.31 units on a scale | Standard Error 0.48 |
| Lidocaine Administration | Ischemic Pain | During 20 Infusion | 3.49 units on a scale | Standard Error 0.48 |
| Lidocaine Administration | Ischemic Pain | 30 After Infusion completed | 3.44 units on a scale | Standard Error 0.48 |
p-value: <0.001Regression, Linear
Primary
Tactile Sensation
Pin prick sensory thresholds (PPT) were obtained by touching the skin in-between the first and second metacarpal bone with a 23-gauge needles which moved freely out of a 10 mL plastic syringe barrel. The pin prick sensation was modified by adding small weights to the 23-gauge needles (from 0.2 to 5.2 mg). A syringe barrel of tuberculin (TB) needles that were cut to different lengths to add the desired weight to the 23-gauge needle. The PPT was determined using the weighted 23-gauge needle in ascending order, according to the method of limits. This assessment was to evaluate whether participants were able to feel the touch of the needle. The participant's arm was placed on a tray table. A linen sheet was suspended in-between two IV poles in such a fashion that the subject's view of his/her hand was blocked. Normal values are between 0.21mg and 5mg.
Time frame: baseline, during 20 minute infusion, and 30 minutes after completion of infusion
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lidocaine Administration | Tactile Sensation | Baseline - at start of lidocaine administration | .28 weight in mg | Standard Error 0.02 |
| Lidocaine Administration | Tactile Sensation | During 20 minute Infusion | .27 weight in mg | Standard Error 0.02 |
| Lidocaine Administration | Tactile Sensation | 30 Minutes after completion of infusion | .27 weight in mg | Standard Error 0.02 |