Functional Cerebral Neurovascular Mapping During Focused Ultrasound Peripheral Neuromodulation of Neuropathic Pain

Abstract

Background Nociceptive pain is required for healthy function, yet, neuropathic pain (disease or injury) can be severely debilitating. Though a wide-array of treatment options are available, they are often systemic and/or invasive. As a promising neuromodulation treatment, Focused ultrasound (FUS) is a noninvasive and highly spatially-targeted technique shown to stimulate neural activity, yet, effects on pain signaling are currently unknown. Objective Develop and validate a method for studying FUS nerve stimulation modulation of pain-evoked neural responses in vivo. Methods We developed a high-resolution functional ultrasound (fUS) method capable of mapping cortical responses in healthy and neuropathic pain mice in response to FUS neuromodulation treatment. Results FUS-evoked hemodynamic responses are correlated with the intensity of peripheral neuromodulation. We confirm functional connectivity is altered in neuropathic mice and demonstrate that FUS can modulate neuropathic pain-evoked hemodynamics. Conclusions The findings presented herein provides evidence for an FUS-based nerve pain method and validates the fUS technique developed for monitoring pain-evoked hemodynamics. Significance We anticipate that the findings presented herein describe a noninvasive and flexible nerve modulation technique for pain mitigation, furthering evidence for clinical translation.

Abstract via europepmc.

Flags from extraction

• n_subjects — Wild-type (10) and SNI (9) group totals given separately; some wild-type mice received only whisker or electrical stimulation, and not all SNI mice were sonicated, so the list is not the number exposed to FUS.
• exposures[0].in_situ.pressure_kpa — Described as a derated rarefactional pressure; derating method and medium not stated, so recorded as in_situ derating.
• exposures[0].unspecified_domain.isppa_w_cm2 — Subscripts lost in the text extraction (I , I); order assumed ISPTA 3.2 mW/cm2 then ISPPA 3.2 W/cm2; values look inconsistent with 9.57 MPa, so treat with caution.
• exposures[0].unspecified_domain.ispta_w_cm2 — Stated as 3.2 mW/cm2; converted to 0.0032 W/cm2. Subscripts lost in the text.
• exposures[0].timing.duty_cycle_pct — Paper gives 0.1% DC (wild-type, and also '0.1% DC effective' for the 10 Hz protocol in Methods) and 1% DC for the 10 Hz, 10 s protocol in Results; 10 Hz x 1 ms would be 1%. Recorded as the two stated values.
• exposures[0].timing.sonication_duration_s — 10 s applies to the neuropathic pain protocol; the wild-type protocol is a train of 5 pulses at 1 Hz with no duration stated.
• exposures[0].timing.protocol_description — Single 1 ms pulses; wild-type train of 5 pulses at 1 Hz, neuropathic pain mice 10 Hz for 10 s.
• sham_type — FUS-sham groups are described only as groups without FUS; mechanism not given.
• exposures[0].device.family — No transducer maker named; only a 3.1 MHz focused transducer, with an Agilent function generator and E&I amplifier.
• conditions — Healthy wild-type mice plus spared nerve injury (neuropathic pain) mice.