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Norepinephrine can act via alpha(2)-adrenoceptors to reduce the hyper-excitability of spinal dorsal horn neurons following chronic nerve injury
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Jiang, Lu-Yang, Li, Shu-Ren, Zhao, Fei-Yue, Spanswick, David and Lin, Mao-Tsun (2010) Norepinephrine can act via alpha(2)-adrenoceptors to reduce the hyper-excitability of spinal dorsal horn neurons following chronic nerve injury. Journal of the Formosan Medical Association, Vol.109 (No.6). pp. 438-445. doi:10.1016/S0929-6646(10)60075-7 ISSN 0929-6646.
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Official URL: http://dx.doi.org/10.1016/S0929-6646(10)60075-7
Abstract
Background/Purpose: Rats display behavioral signs of neuropathic pain lasting for months in the chronic constriction injury (CCI) model. During intrathecal anesthesia, the administered drugs mainly diffuse directly into the superficial neurons in the spinal dorsal horn. This study aimed to investigate the effect of bath application of norepinephrine on whole cell patch clamp recordings from spinal cord slices of CCI rats with allodynia.
Methods: An assessment of paw withdrawal threshold in response to mechanical stimulation was performed on the operated side on the day before surgery and was repeated after recovery from anesthesia and on the 7(th) and 14(th) days after surgery. Spinal cord slice preparations containing dorsal horn neurons were obtained from both sham-operated rats and CCI rats (after the 14(th) postoperative day behavior test).
Results: Compared with normal controls, CCI rats had significantly lower levels of both hyperpolarization and spike threshold in single action potentials recorded from lamina I and II neurons of the spinal dorsal horn. In contrast, a series of action potential recordings showed that the percentage of spiking neurons of the spinal dorsal horn of CCI rats were significantly higher than those of normal controls. The CCI-induced reduction in hyperpolarization, as well as the increased numbers of spinal dorsal horn spiking neurons could be significantly reduced by norepinephrine application. The norepinephrine-induced increased hyperpolarization and input resistance could be abolished by the application of an alpha(2)-adrenoceptor antagonist (idazoxan; 200 nM).
Conclusion: The results suggest that chronic nerve injury may induce neuropathic pain by increasing the excitability of spinal dorsal horn neurons. This excitability can be reduced by norepinephrine.
Item Type: | Journal Article | ||||
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Subjects: | R Medicine | ||||
Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School | ||||
Journal or Publication Title: | Journal of the Formosan Medical Association | ||||
Publisher: | Journal Elsevier (Singapore) Pte Ltd. | ||||
ISSN: | 0929-6646 | ||||
Official Date: | June 2010 | ||||
Dates: |
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Volume: | Vol.109 | ||||
Number: | No.6 | ||||
Number of Pages: | 8 | ||||
Page Range: | pp. 438-445 | ||||
DOI: | 10.1016/S0929-6646(10)60075-7 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Restricted or Subscription Access |
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