Carbamazepine (CBZ) and oxcarbazepine (OXC) are first-choice medical treatments. Although other drugs may be effective, these are indicated when the patient cannot reach the therapeutic dosage of CBZ/OXC because of adverse events. Patients unresponsive to CBZ/OXC should be made aware of the available surgical interventions. Surgical procedures (including percutaneous lesions to the ganglion/root, microvascular decompression (MVD) in the posterior fossa, and gamma knife radiosurgery) are extremely efficacious with relatively few complications: each procedure has some advantage and disadvantage with respect to the other. Only MVD is a non-destructive procedure 1)
Carbamazepine-associated withdrawal reaction (CAWR) is dependent on the pre-operative dosage and the changing rate of pre- and post-operative CBZ blood concentrations 2).
The goal of a study was to determine if the incorporation of carbamazepine, into a biodegradable microparticle for local sustained perineural release would be an efficacious analgesic following a peripheral injury.
Following induction of the chronic constriction injury model in Sprague-Dawley rats, mechanical allodynia testing was performed using von Frey filaments and thermal allodynia was evaluated using the Hargreaves method. Histology and blood work were performed to evaluate toxicity as well to monitor drug and metabolite presence over time.
A 2-fold increase in hindpaw withdrawal thresholds in animals receiving carbamazepine loaded microparticles relative to controls was observed for up to 14 days after treatment. Drug and metabolite had a peak blood concentration of 54.7ng/mL and dropped off exponentially to less than 5ng/mL over a few days.
This formulation reduced systemic exposure to carbamazepine over 1,000-fold relative to traditional analgesic dosing regimens. This two-component drug-delivery system has been specifically engineered to release a controlled amount of carbamazepine over a 14 day period providing significant pain relief with no toxicological or observable adverse events via behavioral or histochemical analysis 4).