Low intensity trans-spinal focused ultrasound reduces mechanical sensitivity and suppresses spinal microglia activation in rats with chronic constriction injury

Abstract

Low intensity, trans-spinal focused ultrasound (tsFUS) is a noninvasive neuromodulation approach that has been shown to modulate spinal circuit excitability in healthy rats. Here, we evaluated the potential of tsFUS for alleviating neuropathic pain by testing it in a chronic constriction injury (CCI) model. Male rats underwent CCI of the left sciatic nerve and then received tsFUS (2 kHz pulse repetition frequency; 40% duty cycle) or sham stimulation, targeted at spinal segment level L5 for 3 min daily over three days. As expected, CCI causes significant reduction of von Frey Threshold (vFT), a measure of mechanical sensitivity. We found that tsFUS treatment is associated with increased vFT compared to sham; this increase persists beyond the duration of treatment, through days 4 to 23 post-CCI. In spinal cords of tsFUS-treated animals, counts of spinal microglia (Iba1 + cells) and of activated, pro-inflammatory microglia (Iba1 + /CD86 + cells), are reduced compared to sham-treated animals. This reduction in microglia counts is limited to the insonified side of the spinal cord, ipsilateral to CCI. These findings suggest that tsFUS may be a promising approach for treatment of neuropathic pain at early stages, possibly by attenuating the development of microglial-driven inflammation.