194 Opiate-Free Pain Therapy Using Carbamazepine-Loaded Microparticles Provides up to 2 Weeks of Pain Relief in a Neuropathic Pain Model

• Published in: Neurosurgery Vol. 65; no. CN_suppl_1; p. 113
• Main Authors: Dai, Haining, Tilley, Dana, Mercedes, Greici, Doherty, Chris, Gulati, Amitabh, Mehta, Neel, Khalil, Amer, Reynolds, Francis M
• Format: Journal Article
• Language: English
• Published: Philadelphia Oxford University Press 01-09-2018; Copyright by the Congress of Neurological Surgeons; Wolters Kluwer Health, Inc
• Subjects: Anticonvulsants; Neurosurgery; Pain
• ISSN: 0148-396X; 1524-4040
• DOI: 10.1093/neuros/nyy303.194

Abstract
INTRODUCTION
As evidenced by the ongoing opioid crisis, there is a great unmet medical need for alternative treatments for patients suffering from pain that do not result in addiction or adverse side effects. Anticonvulsants are effective in managing pain, though high systemic dosing creates unwanted side effects limiting its usage. We hypothesized a biodegradable poly(lactide-co-glycolide) microparticle formulation incorporating the anticonvulsant carbamazepine would provide prolonged pain relief while limiting unwanted systemic side effects.
METHODS
All animals underwent induction of the chronic constriction injury model to induce neuropathic pain states. Animals were randomly divided into a control group receiving injections of saline, bupivacaine, carbamazepine, or unloaded microparticles or into a treatment group receiving either 10 or 20 mg of carbamazepine-loaded microparticles suspended in sterile saline. Mechanical and thermal behavioral testing was conducted using von Frey and plantar-based measurements, respectively. Behavioral measurements were taken before surgery for normal baseline, 3 d after induction of the CCI model for ligation baseline, and at multiple time points following injections for up to 21 d.
RESULTS
Only the carbamazepine control group demonstrated a significant difference from other control groups though only for up to 4 h post-injection. Both treatment groups demonstrated a rapid analgesic response that persisted for 14 d before returning to similar sensitivity levels as the control animals.
CONCLUSION
This 2-component drug-delivery system has been specifically engineering to release a controlled amount of carbamazepine over a 14-d period demonstrating significant anti-nociceptive behavior with no toxicological or observable adverse events via behavioral or histochemical analysis.