Prabhala et al., from the Department of Neuroscience and Experimental Therapeutics, Department of Pathology and Laboratory Medicine, Department of Neurosurgery, Department of Neuroscience and Experimental Therapeutics, Albany Medical College, Acoustic Med Systems, Savoy United States, was to assess the effects of external focused ultrasound on sensory thresholds utilizing a common peroneal nerve injury (CPNI) rat model. CPNI was induced by ligating the common peroneal nerve (CPN) of the left hind paw. Neuropathic phenotype was confirmed using the Von Frey Fibers (VFF) with a 50% mechanical detection threshold below 4.0. The Place Escape Avoidance Paradigm (PEAP) was employed as a behavioral correlate. External FUS treatment was applied to the left L4,5 DRG at 8 W for 3-minutes. There were two treatment groups; one received a single FUS treatment, while the other received two. Control groups consisted of one sham CPNI group that received FUS treatment and a CPNI group that received sham FUS treatment. Behavioral tests were conducted pre-CPNI surgery, 1-week post-surgery, and for 1-week post-FUS treatment(s). CPNI surgery resulted in lower VFF mechanical thresholds in the left hind paw compared to baseline (p < 0.0001) and increased proportion of time spent on bright side compared to baseline values on PEAP (p = 0.0473), indicating neuropathic state. FUS treatment increased VFF thresholds after 24-hours (p < 0.0001), 48-hours (p = 0.0079), and 72-hours (p = 0.0164). VFF returned to baseline values from day 4-7. Following a second FUS treatment on day 8, increased mechanical thresholds were similarly observed after 24-hours (p = 0.0021), 48-hours (p < 0.0001), and 72-hours (p = 0.0256). Control group analysis showed (1) CPNI rats experienced no change in mechanical thresholds following sham FUS treatment and (2) Sham CPNI rats receiving FUS did not experience significantly different mechanical thresholds compared to baseline and post-CPNI values. Post-FUS histological analysis demonstrated healthy ganglion cells without chromatolysis.
The results demonstrate changes in VFF and PEAP in rats who underwent CPNI. Single and multiple doses of external FUS increase mechanical thresholds without inducing histological damage. Based on this results, they demonstrated the potential of FUS to serve as a non-pharmacological and non-ablative neuromodulatory approach for the treatment of allodynia and neuropathic pain 1).