Norepinephrine can Act via α2-Adrenoceptors to Reduce the Hyper-excitability of Spinal Dorsal Horn Neurons Following Chronic Nerve Injury

Jiang, Lu-Yang; Li, Shu-Ren; Zhao, Fei-Yue; Spanswick, David; Lin, Mao-Tsun

doi:10.1016/S0929-6646(10)60075-7

« Previous Next »Journal of the Formosan Medical Association
Volume 109, Issue 6 , Pages 438-445, June 2010

Norepinephrine can Act via α₂-Adrenoceptors to Reduce the Hyper-excitability of Spinal Dorsal Horn Neurons Following Chronic Nerve Injury

Lu-Yang Jiang
- Department of Anaesthesiology, Beijing Friendship Hospital affiliated to Capital Medical University, Beijing, China
Shu-Ren Li
- Department of Anaesthesiology, Beijing Friendship Hospital affiliated to Capital Medical University, Beijing, China
- Correspondence to: Dr Shu-Ren Li, Department of Anaesthesiology, Beijing Friendship Hospital affiliated to Capital Medical University, Beijing 100050, China
Fei-Yue Zhao
- NeuroSolutions Ltd, Warwick Medical School, University of Warwick, Coventry, UK
David Spanswick
- Division of Clinical Sciences, Warwick Medical School, University of Warwick, Coventry, UK
Mao-Tsun Lin
- Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan
- Correspondence to: Dr Mao-Tsun Lin, Department of Medical Research, Chi Mei Medical Center, Taiwan

Received 6 May 2009; received in revised form 8 July 2009; accepted 11 August 2009.

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 α₂-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.

Key Words: α₂-adrenoceptors , allodynia , neuropathic pain , norepinephrine , spinal dorsal horn