Abstract
The aim of this study was to investigate the efficiency of intrathecal glial cell line-derived neurotrophic factor (GDNF) on nitric oxide (NO) and nitric oxide synthase (NOS) activity following a spinal nerve ligation (SNL) of male Sprague Dawley rats. The rats were randomly divided into four groups: normal (control), sham-operated, SNL (SNL followed by a physiological saline injection into the subarachnoid space), and GDNF (SNL followed by a GDNF injection into the subarachnoid space). Each group was divided into three subgroups (n = 10). The rats in each subgroup were euthanised 3, 7, and 14 days after the operation. Rat behaviour was evaluated before euthanising, and the ipsilateral spinal cords were harvested after euthanising to determine the NO content and NOS activity. Compared with the control and sham-operated groups, the NO content and NOS activity in the SNL group increased significantly 3 days after the operation; this increase was maintained until 14 days after the operation (P < 0.01 or 0.05). A significant decrease was observed in the NO content and NOS activity in the GDNF group compared with the SNL group. The decrease continued until 14 days after the operation (P < 0.01 or 0.05). The results indicated that the NO and NOS activity in the rat spinal cord are associated with SNL-induced neuropathic pain. The decreased neuropathic pain from the intrathecal GDNF is correlated with the decrease in NO content and NOS activity in the spinal cord. Key words: Glial cell line-derived neurotrophic factor, neuralgia, nitric oxide, nitric oxide synthase.
Highlights
Glial cell line-derived neurotrophic factor (GDNF) is a small protein that was isolated and purified from the mouse glial cell line B49 in 1993 (Lin et al, 1993)
The results indicated that the nitric oxide (NO) and nitric oxide synthase (NOS) activity in the rat spinal cord are associated with SNLinduced neuropathic pain
Compared with the control and sham-operated groups, total NOS (TNOS) activity in the spinal nerve ligation (SNL) group was significantly increased on day 3 and was maintained until 14 days after the operation (P < 0.01)
Summary
Glial cell line-derived neurotrophic factor (GDNF) is a small protein that was isolated and purified from the mouse glial cell line B49 in 1993 (Lin et al, 1993). A number of studies demonstrate that in the nociceptive information delivery process, nitric oxide (NO), as a messenger, is involved in the pain regulation of the peripheral and central nervous system at different levels, in the pain regulation of the spinal cord. Increasing evidence shows that nitric oxide synthase (NOS) inhibitors have a significant anti-nociceptive effect, and that spinal cord plasticity based on the NO synthesis system plays an important role in the maintenance and occurrence of pain following a nerve injury (Meller et al, 1992, 1994; Yaksh, 1999). The aim of this study was to induce a rat neuropathic pain model through spinal nerve ligation (SNL) and to observe the changes in NO content and NOS activity to investigate the GDNF mechanism on
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