Nanoparticle Probes to Objectively Measure Pain Following Back Surgery

AbstractPost operative pain is poorly managed and increases risk for delayed recoverychronic painopioid dependenceand persistent disabilityOne barrier to effective management of acute pain is the absence of objective measuresWe propose to conduct a feasibility study for technology to objectively measure postoperative painWe have selected back surgery as a model given its frequencycostand poor outcomesPrecise tracking of inflammation and pain markers at the surgery site may provide objective measurement of post operative painLocal inflammation is necessary for normal wound healingbut the degree of inflammatory response to injury is highly variable across patientsInflammation from wound healing begins within hours and abates completely within a few days after surgerywhen the proliferative phase of wound healing beginsPatient specific immune states before surgery correlate with protracted recoveryincluding post operative painfatigueand functional impairmentImmune cell intracellular signaling in response to biomarkerssuch as the cytokine InterleukinILhas been shown to predict slower recovery and persistent pain following primary hip replacement surgery for osteoarthritisPatients 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 sitePersistent pain may be associated with higher levels and longer duration of inflammationWe hypothesize that longitudinal objective measurements of epidural temperature and concentrations of interleukinILand substance PSPwill correlate with post operative pain following back surgeryWe 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 biomarkersIn Aimof this projectwe will adapt and optimize the magnetic spectroscopy instrumentation for use in a rat lumbar radiculopathy modelWe have already validated for in vivo measurements of infection in a mouse peritoneal cavityIn Aimwe will create three grades of surgical injuryminimallumbar skin incision onlymoderateLlaminectomyand severeLlaminectomy and unilateral nerve root ligationand compare noninvasive nanoparticle based measurements of epidural temperatureILconcentrationand SP concentration to validatedvideo based automated measures of pain behavior in animalsAimatemperature measured by a thermocoupleAimband ELISA based epidural concentration of ILAimcand SPAimdat three time points following surgerydaydaysanddays post opPhase I proof of principle demonstration of nanoparticle based measurements will be considered successful for associations that show a Spearman rank correlation andgtand Bland Altman agreementbetween methodsallowing us to proceed to a preliminary human safety demonstration in a small clinical series of lumbar laminectomy and fusion patients in Phase IIand potentially expand measurements to include a panel of other important biomarkersThis novel technology may lead to an inexpensivesimplepoint of care measurement system for noninvasively tracking post operative pain Narrative Pain is common following all surgeryand it frequently persists following back surgeryleading to prolonged opioid userepeat surgeriessevere disability and failed back surgery syndromeInflammation is a physiologic marker of painLocal inflammation is necessary for normal wound healingbut inflammatory response is variable across individualsPrecise measurements of inflammation at the surgical site may correlate with postoperative painWe are developing novel technology for noninvasively monitoring local inflammation over time that could provide objective pain measurement at the surgical site