Effects of external low intensity focused ultrasound on inflammatory markers in neuropathic pain
Abigail Hellman, Alicia Clum, Teresa Maietta, Adithya Srikanthan, Vraj Patel, Drishti Panse, Olivia Zimmerman, Paul Neubauer, Julia Nalwalk, Emery Williams, Goutam Ghoshal, Clif Burdette, Julie G. Pilitsis
Neuroscience Letters 2021, 757, 135977 · 10.1016/j.neulet.2021.135977
Abstract
Background Changes in inflammatory cytokine levels contribute to the induction and maintenance of neuropathic pain. We have shown that external low intensity focused ultrasound (liFUS) reduces allodynia in a common peroneal nerve injury (CPNI). Here, we investigate an underlying mechanism of action for this treatment and measure the effect of liFUS on inflammatory markers. Methods Male rats were divided into four groups: CPNI/liFUS, CPNI/shamliFUS, shamCPNI/liFUS, and shamCPNI/shamliFUS. Mechanical nociceptive thresholds were measured using Von Frey filaments (VFF) to confirm the absence/presence of allodynia at baseline, after CPNI, and after liFUS. Commercial microarray and ELISA assays were used to assess cytokine expression in the treated L5 dorsal root ganglion (DRG) and dorsal horn (DH) tissue 24 and 72 h after liFUS. Results VFF thresholds were significantly reduced following CPNI in both groups that received the injury (p Conclusion We have demonstrated that liFUS modifies inflammatory cytokines in both DRG and DH in CPNI rats. These data provide evidence that liFUS, reverses the allodynic phenotype, in part, by altering inflammatory cytokine pathways.
Abstract via europepmc.
Exposures
Exposure 1: External liFUS to L5 dorsal root ganglion (DRG)
Target: dorsal root ganglion — “left L5 dorsal root ganglion (DRG)”
Device: other named manufacturer · Acoustic MedSystems Inc ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | not reported | ⚑ |
| Pulse duration (ms) | 13 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 38 | ✓✓✓⚑ |
| Duty cycle (%) | not reportedpulse duration × PRF gives 49.4% | |
| Sonication duration (s) | 180 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
A single external liFUS treatment (3 min at 8 W) was applied through the skin over the L5 DRG using an external landmark (posterior superior iliac spine), positioned so the beam travelled through soft tissue to the DRG without bony reflection; dose determined from a previously conducted dose-response curve. liFUS reverses allodynic responses in CPNI rats for approximately 3 days.
Flags from extraction
exposures[0].fundamental_frequency_khz— Paper states 'a frequency of 38 Hz, pulse width of 13 ms, and period of 90 ns' - these values are internally inconsistent (a 90 ns period implies an ~11 MHz carrier, incompatible with a 13 ms pulse width), and 38 Hz is implausible as an ultrasound carrier frequency. 38 Hz and 13 ms were recorded as PRF and pulse duration respectively per the burst rule reasoning, but the fundamental (carrier) frequency is not clearly stated anywhere in the paper and is left not_reported.exposures[0].timing.pulse_repetition_frequency_hz— The text labels 38 Hz as 'a frequency' rather than explicitly as PRF; interpreted as PRF because 38 Hz is not a plausible ultrasound carrier frequency, but this is an inference, not a direct statement.sham_type— The mechanism of sham liFUS delivery is not described in this paper (only named as 'shamliFUS' groups), so sham_type is set to 'other' per the rule for undescribed sham mechanisms.n_subjects— VFF behavioral n=16/group is reported for each of the two liFUS-exposed groups (CPNI/liFUS, shamCPNI/liFUS) in each of the two separate cohorts (24h, 72h); no single total across cohorts is stated, so the four group sizes are listed.exposures[0]— No pressure, ISPPA, or ISPTA value is reported anywhere in the paper for the liFUS device; only total acoustic power (8 W) is given.