Multiply repeatable and adjustable on-demand phototriggered local anesthesia

Abstract

A phototriggerable system whereby patients could repeatedly and non-invasively control the timing and dosage of local anesthesia according to their needs would be beneficial for perioperative pain and perhaps obviate the need for oral narcotics. However, clinical application of phototriggerable systems have been limited by concerns over phototoxicity of lasers and limited tissue penetration of light. To address these limitations, we increased the devices’ effective sensitivity to light by co-delivering a second compound, dexmedetomidine, that potentiates the effect of delivered local anesthetics. The concurrent release of dexmedetomidine enhanced the efficacy of released local anesthetics, greatly increasing the number of triggerable nerve blocks (up to nine triggerable events upon a single injection) and reducing the irradiance needed to induce nerve block by 94%. The intensity and duration of on-demand analgesia could be adjusted by varying the intensity and duration of irradiance, which could not only be delivered by lasers, but also by light-emitting diodes, which are less expensive, safer, and more portable.

Prolonged Duration Local Anesthesia Using Liposomal Bupivacaine Combined With Liposomal Dexamethasone and Dexmedetomidine

“…Lipo-DMED or Lipo-DexP with Lipo-PBS did not result in nerve block. These results also implied that free DMED and DexP did not have intrinsic peripheral nerve blocking activity, as has been reported elsewhere 13,27 .…”

“…The adjuvant molecules used here work by distinct but partially overlapping mechanisms. One possibility is that the activation of C-fiber glucocorticoid receptors 12 by DexP may block nerve signal transduction and be combined with the vasoconstriction effect of DMED 6,28 mediated by the α 2 -adrenergic receptor 27,29 , or DMED’s direct action on the peripheral nerve, where the inhibition of the hyperpolarization-activated cation current (I h current) blocks pain signal transduction 8 , to produce such prolongation effects. The exact mechanism remains to be studied.…”

“…26 Fieller’s theorem was used to construct a 95% confidence interval (CI) around the fold-difference of prolonged nerve block between co-injection of Lipo-Bup with Lipo-DMED and Lipo-DexP as compared to Lipo-Bup. 27 Effect sizes regarding mean differences in block duration relative to Lipo-Bup+Lipo-DMED+Lipo_DexP were determined by ANOVA and shown graphically with 95% CIs. In this work, detection of large mean differences or effects (4–5 hours) in nerve block duration would be considered scientifically meaningful.…”

Ultrasound-triggered local anaesthesia

“…Pharmacokinetic studies were performed by injection SRho-loaded liposomes at a dosage of 1.5 mg/kg and constant volume of 200 µL. The blood was processed using a previously reported method 77 . In brief, at predetermined time points, blood was collected from the tail.…”

Strategies for Targeted Delivery to the Peripheral Nerve

“…The same investigators have also explored local anesthetic delivery systems that are triggered by near-infrared light ( Rwei et al, 2015 , 2017b ). In this case, the liposomal formulation contains a NIR-absorbing photosensitizer that triggers release of TTX in the presence of 730 nm light.…”