Nanoparticle Probes to Objectively Measure Pain Following Back Surgery

Peer Technologies, Pllc, Washington DC

Investigators

Abstract

Abstract Post-operative pain is poorly managed and increases risk for delayed recovery, chronic pain, opioid dependence, and persistent disability. One barrier to effective management of acute pain is the absence of objective measures. We propose to conduct a feasibility study for technology to objectively measure post- operative pain. We have selected back surgery as a model given its frequency, cost, and poor outcomes. Precise tracking of inflammation and pain markers at the surgery site may provide objective measurement of post-operative pain. Local inflammation is necessary for normal wound healing, but the degree of inflammatory response to injury is highly variable across patients. Inflammation from wound healing begins within hours and abates completely within a few days after surgery, when the proliferative phase of wound healing begins. Patient-specific immune states before surgery correlate with protracted recovery, including post-operative pain, fatigue, and functional impairment. Immune cell intracellular signaling in response to biomarkers, such as the cytokine Interleukin-6 (IL-6), has been shown to predict slower recovery and persistent pain following primary hip replacement surgery for osteoarthritis. Patients who have persistent local inflammation may be distinguishable from normal wound healing by monitoring the character and time course of local inflammation at the surgical site. Persistent pain may be associated with higher levels and longer duration of inflammation. We hypothesize that longitudinal objective measurements of epidural temperature and concentrations of interleukin-6 (IL-6) and substance P (SP) will correlate with post-operative pain following back surgery. We have developed novel microscopic magnetic nanoparticle probes that can be safely implanted in the surgical field to allow noninvasive postoperative measurements of precise local temperature and concentrations of these biomarkers. In Aim 1 of this project, we will adapt and optimize the magnetic spectroscopy instrumentation for use in a rat lumbar radiculopathy model. We have already validated for in vivo measurements of infection in a mouse peritoneal cavity. In Aim 2, we will create three grades of surgical injury: minimal (lumbar skin incision only), moderate (L5 laminectomy), and severe (L5 laminectomy and unilateral nerve root ligation) and compare noninvasive nanoparticle-based measurements of epidural temperature, IL-6 concentration, and SP concentration to validated, video-based automated measures of pain behavior in animals (Aim 2a), temperature measured by a thermocouple (Aim 2b), and ELISA-based epidural concentration of IL-6 (Aim 2c) and SP (Aim 2d), at three time points following surgery (1 day, 3 days, and 10 days post-op). Phase I proof of principle demonstration of nanoparticle-based measurements will be considered successful for associations that show a Spearman rank correlation >0.70 and Bland-Altman agreement +/- 20% between methods, allowing us to proceed to a preliminary human safety demonstration in a small clinical series of lumbar laminectomy and fusion patients in Phase II, and potentially expand measurements to include a panel of other important biomarkers. This novel technology may lead to an inexpensive, simple, point of care measurement system for noninvasively tracking post-operative pain.