Abstract
BackgroundIn 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.MethodsThe 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.ResultsThe 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.ConclusionsOur 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.
Highlights
In this study, neostigmine-loaded electrospun nanofibers were prepared and their efficacy and duration of analgesic action were studied after epidural administration in rats by repeated tail flick and formalin tests
In clinical studies intrathecal neostigmine infusion is used for induction of prolonged analgesia in chronic patients [3], the application of a catheter for drug infusion would increase the risk of infection in patients and requires complicated surgery
Morphology of electrospun nanofibers According to the SEM micrograph shown in Figure 2, electrospun free poly vinyl alcohol nanofibers (A) and the neostigmine-loaded nanofibers (B) were circular in cross-section with an average diameter ranging from 500 nm up to 1,000 nm
Summary
Neostigmine-loaded electrospun nanofibers were prepared and their efficacy and duration of analgesic action were studied after epidural administration in rats by repeated tail flick and formalin tests. An alternative procedure for increasing the duration of neostigmine action after epidural injection is its combination with other drugs [4]. This method might induce side effects such as nausea, vomiting, sedation and respiratory depression in patients. Scientists compared the epidural or intrathecal anesthetic efficacy of same doses of an analgesic compound with two kinds of nociceptive stimulus such as tail flick and formalin test. It is certain that the selected dose of the drug is effective for different kinds of pain
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