RESUMO
BACKGROUND: Potential peripheral sources of deep pain can require invasive evocative tests for their assessment. Here we perform research whose ultimate goal is development of a non-invasive evocative test for deep painful tissue. METHODS: We used a rat model of inflammation to show that intense focused ultrasound (iFU) differentially stimulates inflamed versus control tissue and can identify allodynia. To do so we applied iFU to inflamed and normal tissue below the skin of rats' hind paws and measured the amount of ultrasound necessary to induce paw withdrawal. RESULTS: iFU of sufficient strength (spatial and temporal average intensities ranged from 100-350 W/cm(2)) caused the rat to withdraw its inflamed paw, while the same iFU applied to the contralateral paw failed to induce withdrawal, with sensitivity and specificity generally greater than 90%. iFU stimulation of normal tissue required twice the amount of ultrasound to generate a withdrawal than did inflamed tissue, thereby assessing allodynia. Finally, we verified in a preliminary way the safety of iFU stimulation with acute histological studies coupled with mathematical simulations. CONCLUSIONS: Given that there exist systems to guide iFU deep to the skin, image-guided iFU may one day allow assessment of patient's deep, peripheral pain generators.
RESUMO
We tested the hypothesis that neuropathic tissue is more sensitive to stimulation by intense focused ultrasound (iFU) than control tissue. We created a diffusely neuropathic paw in rats via partial ligation of the sciatic nerve, whose sensitivity to iFU stimulation we compared with sham-surgery and normal control paws. We then applied increasing amounts of iFU (individual 0.2 s pulses at 1.15 MHz) to the rats' paws, assaying for their reliable withdrawal from that stimulation. Neuropathic rats preferentially withdrew their injured paw from iFU at smaller values of iFU intensity (84.2 W/cm(2) ± 25.5) than did sham surgery (97.7 W/cm(2) ± 11.9) and normal control (> 223 W/cm(2)) animals, with greater sensitivity and specificity (85% for neuropathic rats and 50% each of sham surgery and normal control rats). These results directly support our hypothesis as well as Gavrilov's idea that doctors may some day use iFU stimulation to diagnose patients with neuropathies.
