Evaluation of Propranolol's Effect on Pain and Inflammation.

Degrees Centigrade Heat pain was induced with a thermal sensory analyzer (TSA-II, Medoc Advanced Medical Systems, Durham, North Carolina). A thermode was placed in contact with skin on the upper thigh. Starting at a comfortable temperature, the thermode temperature was increased at a measured rate. Study participants pushed a button of a hand-held device at the onset of pain at which point the thermode immediately reduced the temperature. Measurements for analgesia were taken at the sites of non-injured skin. Change form baseline was calculated by subtracting baseline values from the average values obtained 1 and 2 hours after starting the drug infusion.

Degrees Centigrade Heat pain was induced with a thermal sensory analyzer (TSA-II, Medoc Advanced Medical Systems, Durham, North Carolina). A thermode was placed in contact with skin on the upper thigh. Starting at a comfortable temperature, the thermode temperature was increased at a measured rate. Study participants pushed a button of a hand-held device at the onset of pain at which point the thermode immediately reduced the temperature. Measurements for anti-hyperalgesia were taken at the sites of tissue injury. Change form baseline was calculated by subtracting baseline values from the average values obtained 1 and 2 hours after starting the drug infusion.

A metal rod of 0.24 mm diameter mounted onto 10 different weights (1.0, 2.0, 4.1, 8.2,16.3, 20, 32.7,49.0, 65.3, and 81.3g) will be placed perpendicularly onto the skin. Starting with the lightest probe, consecutively heavier probes will be used until a subject reports pain. Subsequently, the same or the next lighter probe will be used if pain is reported for the preceding stimulus, or the same or the next heavier probe will be used if no pain is reported for the preceding stimulus.The procedure will be repeated until seven perceptional changes (painful/non-painful) are registered. Measurements for analgesia were taken at the sites of non-injured skin. Change form baseline was calculated by subtracting baseline values from the average values obtained 1 and 2 hours after starting the drug infusion.

A metal rod of 0.24 mm diameter mounted onto 10 different weights (1.0, 2.0, 4.1, 8.2,16.3, 20, 32.7,49.0, 65.3, and 81.3g) will be placed perpendicularly onto the skin. Starting with the lightest probe, consecutively heavier probes will be used until a subject reports pain. Subsequently, the same or the next lighter probe will be used if pain is reported for the preceding stimulus, or the same or the next heavier probe will be used if no pain is reported for the preceding stimulus.The procedure will be repeated until seven perceptional changes (painful/non-painful) are registered. Measurements for anti-hyperalgesia were taken at the sites of tissue injury. Change form baseline was calculated by subtracting baseline values from the average values obtained 1 and 2 hours after starting the drug infusion.

TNFα (ng/mL) was measured in interstitial fluid after collecting samples as follows: Microdialysis catheters (very small, custom-made, sterile, semi-permeable, micro-dialysis catheters) were placed after the 1st laser Doppler measurement. Two catheters were placed at an experimentally inflamed skin site on the left leg. A continuous infusion of sterile 1% albumin solution was started using a programmable pump set at a rate of 2.5µl/min. Samples were collected hourly throughout the remainder of the study day. Samples for analysis were collected before, and 2 and 3 hours after starting the drug infusion. Difference form baseline was calculated by subtracting the baseline concentration form the average concentration determined in samples collected during drug infusion.

IL-1β (ng/mL) was measured in interstitial fluid after collecting samples as follows: Microdialysis catheters (very small, custom-made, sterile, semi-permeable, micro-dialysis catheters) were placed after the 1st laser Doppler measurement. Two catheters were placed at an experimentally inflamed skin site on the left leg. A continuous infusion of sterile 1% albumin solution was started using a programmable pump set at a rate of 2.5µl/min. Samples were collected hourly throughout the remainder of the study day. Samples for analysis were collected before, and 2 and 3 hours after starting the drug infusion. Difference form baseline was calculated by subtracting the baseline concentration form the average concentration determined in samples collected during drug infusion.

IL-2 (ng/mL) was measured in interstitial fluid after collecting samples as follows: Microdialysis catheters (very small, custom-made, sterile, semi-permeable, micro-dialysis catheters) were placed after the 1st laser Doppler measurement. Two catheters were placed at an experimentally inflamed skin site on the left leg. A continuous infusion of sterile 1% albumin solution was started using a programmable pump set at a rate of 2.5µl/min. Samples were collected hourly throughout the remainder of the study day. Samples for analysis were collected before, and 2 and 3 hours after starting the drug infusion. Difference form baseline was calculated by subtracting the baseline concentration form the average concentration determined in samples collected during drug infusion.

IL-6 (ng/mL) was measured in interstitial fluid after collecting samples as follows: Microdialysis catheters (very small, custom-made, sterile, semi-permeable, micro-dialysis catheters) were placed after the 1st laser Doppler measurement. Two catheters were placed at an experimentally inflamed skin site on the left leg. A continuous infusion of sterile 1% albumin solution was started using a programmable pump set at a rate of 2.5µl/min. Samples were collected hourly throughout the remainder of the study day. Samples for analysis were collected before, and 2 and 3 hours after starting the drug infusion. Difference form baseline was calculated by subtracting the baseline concentration form the average concentration determined in samples collected during drug infusion.

GMCSF (ng/mL) was measured in interstitial fluid after collecting samples as follows: Microdialysis catheters (very small, custom-made, sterile, semi-permeable, micro-dialysis catheters) were placed after the 1st laser Doppler measurement. Two catheters were placed at an experimentally inflamed skin site on the left leg. A continuous infusion of sterile 1% albumin solution was started using a programmable pump set at a rate of 2.5µl/min. Samples were collected hourly throughout the remainder of the study day. Samples for analysis were collected before, and 2 and 3 hours after starting the drug infusion. Difference form baseline was calculated by subtracting the baseline concentration form the average concentration determined in samples collected during drug infusion.

IL-8 (ng/mL) was measured in interstitial fluid after collecting samples as follows: Microdialysis catheters (very small, custom-made, sterile, semi-permeable, micro-dialysis catheters) were placed after the 1st laser Doppler measurement. Two catheters were placed at an experimentally inflamed skin site on the left leg. A continuous infusion of sterile 1% albumin solution was started using a programmable pump set at a rate of 2.5µl/min. Samples were collected hourly throughout the remainder of the study day. Samples for analysis were collected before, and 2 and 3 hours after starting the drug infusion. Difference form baseline was calculated by subtracting the baseline concentration form the average concentration determined in samples collected during drug infusion.

IL-10 (ng/mL) was measured in interstitial fluid after collecting samples as follows: Microdialysis catheters (very small, custom-made, sterile, semi-permeable, micro-dialysis catheters) were placed after the 1st laser Doppler measurement. Two catheters were placed at an experimentally inflamed skin site on the left leg. A continuous infusion of sterile 1% albumin solution was started using a programmable pump set at a rate of 2.5µl/min. Samples were collected hourly throughout the remainder of the study day. Samples for analysis were collected before, and 2 and 3 hours after starting the drug infusion. Difference form baseline was calculated by subtracting the baseline concentration form the average concentration determined in samples collected during drug infusion.

IL-12 (ng/mL) was measured in interstitial fluid after collecting samples as follows: Microdialysis catheters (very small, custom-made, sterile, semi-permeable, micro-dialysis catheters) were placed after the 1st laser Doppler measurement. Two catheters were placed at an experimentally inflamed skin site on the left leg. A continuous infusion of sterile 1% albumin solution was started using a programmable pump set at a rate of 2.5µl/min. Samples were collected hourly throughout the remainder of the study day. Samples for analysis were collected before, and 2 and 3 hours after starting the drug infusion. Difference form baseline was calculated by subtracting the baseline concentration form the average concentration determined in samples collected during drug infusion.

Laser Doppler images were recorded at baseline and at 2 and 3 hours after starting the drug infusion to provide measurements of peripheral blood flow as an objective measure of inflammation. Blood flow was quantified by arbitrary perfusion units. Baseline measurements were subtracted from the average measurements obtained 2 and 3 hours after starting the drug infusion.