Effects of external low intensity focused ultrasound on inflammatory markers in neuropathic pain

Author: Abigail Hellman1, Alicia Clum1, Teresa Maietta1, Adithya Srikanthan1, Vraj Patel1, Drishti Panse1, Olivia Zimmerman1, Paul Neubauer2, Julia Nalwalk1, Emery Williams2, Goutam Ghoshal2, Clif Burdette2, Julie G Pilitsis3
Affiliation: <sup>1</sup> Department of Neuroscience and Experimental Therapeutics, Albany Medical College, Albany, NY, United States. <sup>2</sup> Acoustic Medical Systems, Savoy, IL, United States. <sup>3</sup> Department of Neurosurgery, Albany Medical Center, Albany, NY, United States; Department of Neuroscience and Experimental Therapeutics, Albany Medical College, Albany, NY, United States. Electronic address: jpilitsis@yahoo.com.
Conference/Journal: Neurosci Lett
Date published: 2021 Jul 13
Other: Volume ID: 757 , Pages: 135977 , Special Notes: doi: 10.1016/j.neulet.2021.135977. , Word Count: 274

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.

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.

VFF thresholds were significantly reduced following CPNI in both groups that received the injury (p < 0.001). After liFUS, only the CPNI/liFUS cohort showed a significant increase in mechanical thresholds (p < 0.001). CPNI significantly increased TNFa, IL6, CNTF, IL1b (p < 0.05 for all) levels in the DRG and DH, compared to baseline, consistent with previous work in sciatic nerve injury. LiFUS in CPNI rats resulted in a decrease in these cytokines in DRG 72 h post-therapy (TNFa, IL6, CNTF and IL1b, p < 0.001). In the DH, IL1b, CNTF, and TNFa (p < 0.05 for all) decreased 72 h after liFUS.

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.

Keywords: In vivo; Inflammatory cytokines; Low intensity focused ultrasound (liFUS); Neuropathic pain.

PMID: 34023413 DOI: 10.1016/j.neulet.2021.135977