Epidural administration of neostigmine-loaded nanofibers provides extended analgesia in rats.
BACKGROUND
In this study, neostigmine-loaded electrospun nanofibers were prepared and then their efficacy and duration of analgesic action were studied after epidural administration in rats by repeated tail flick and formalin tests.


METHODS
The neostigmine poly vinyl alcohol (PVA) nanofibers were fabricated by electrospinning methods. The nanofibers (1 mg) were injected into the lumbar epidural space (L5-L6) of rats (n = 6). Cerebrospinal fluid samples of rats were collected 1, 5 and 24 hours after injection and then were sampled once weekly for 4 weeks. Free-neostigmine concentration was measured in the samples spectrophotometrically. Rat nociceptive responses were evaluated by repeated tail-flick and formalin tests for 5 weeks after the nanofibers (1 mg) injection. Locomotor activity of rats was measured in the open-field at the same period.


RESULTS
The cerebrospinal fluid concentration of free neostigmine reached 5 μg/ml five hours after injection and remained constant until the end of the experiments. The tail-flick latency of treated rats was significantly (p < 0.01) increased and remained constant up to 4 weeks. Pain scores of the rats in both phases of formalin test were significantly (p < 0.01) reduced during the same periods, Epidural injection of the nanofibers had no effect on locomotor activity of rats in an open-field.


CONCLUSIONS
Our results indicate that the neostigmine nanofibers can provide sustained release of neostigmine for induction of prolonged analgesia after epidural administration. High tissue distribution and penetration of the nanofibers in dorsal horn can increase thermal and chemical analgesia duration without altering locomotor activity in rats for 4 weeks.
Department of Biology, Sciences School, Shahed University, Tehran, IRAN. Yosefifardm@shahed.ac.ir.
Masoomeh
M
Yosefifard
Department of Biology, Sciences School, Shahed University, Tehran, IRAN. hassanpour@Shahed.ac.ir.
Majid
M
Hassanpour-Ezatti
D000700:Analgesics / Q000008:administration & dosage* / Q000134:cerebrospinal fluid / Q000737:chemistry; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage* / Q000134:cerebrospinal fluid / Q000737:chemistry; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D004337:Drug Carriers; D005557:Formaldehyde; D007268:Injections, Epidural; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D057139:Nanofibers; D009388:Neostigmine / Q000008:administration & dosage* / Q000134:cerebrospinal fluid / Q000737:chemistry; D059225:Nociception / Q000187:drug effects*; D010146:Pain / Q000134:cerebrospinal fluid / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control* / Q000523:psychology; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects*; D011142:Polyvinyl Alcohol / Q000737:chemistry*; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D013997:Time Factors
D000700:Analgesics; D002800:Cholinesterase Inhibitors; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005557:Formaldehyde; D009388:Neostigmine; D011142:Polyvinyl Alcohol