The function of small sensory fibers in hind-paw skin was measured by recording latency of hind-paw withdrawal to a heat stimulus using a thermal nociception test device (UARD) as described in technical detail elsewhere (37). The temperature of the device glass surface was stabilized at 30°C and the heating rate was 1°C/sec, with a 20 s cut-off. Measurements were made on both hind paws and repeated four times. The median of the four measurements for each hind paw was calculated and thermal response latency of the mouse calculated by averaging the median measurements of left and right hind paws.

The function of large myelinated sensory fibers in hind-paw skin was measured by recording sensitivity to light touch using manual von Frey filaments (range of 0.16 to 6.0 grams of force, Kom Kare, Inc.) as described in detail elsewhere (37). The testing filament sequence was used to calculate the 50% paw withdrawal threshold (in grams of force) for each hind paw exactly as described elsewhere (38).

Impaired motor function can disrupt behavioral responses upon sensory stimuli. To ensure that behavioral responses were not due to impaired motor function, motor coordination of the animals was measured using a 1.25 inch diameter rotarod (Stoelting Co.) as described previously (37) with the rate of rotation increased from the starting speed of four rotations per minute (RPM) to a maximum of 40 RPM within 120 s. After 120 s, rods consistently rotated at 40 RPM for another 180 s. One acclimation run was performed before the test run.