TY - JOUR
T1 - Central noradrenergic blockade prevents autotomy in rat
T2 - Implication for pharmacological prevention of postdenervation pain syndrome
AU - Al-Adawi, Samir
AU - Dawe, Gavin S.
AU - Bonner, Adrian
AU - Stephenson, John D.
AU - Zarei, Mojtaba
N1 - Funding Information:
M.Z. was supported by the Ministry of Health and Medical Education of the Islamic Republic of Iran and G.S.D. by the Medical Research Council. This work formed the MSc project of S.A. We would like to thank Peter Scott for his assistant in the tyrosine hydroxylase assay procedure and Dr. Zeinab Al-Attar for her useful comments on the manuscript.
PY - 2002/3/15
Y1 - 2002/3/15
N2 - Following transection of peripheral nerve, rats exhibit autotomy, which is considered to be the animal model of postdenervation pain syndrome. It has been suggested that phantom limb pain is a result of peripheral denervation leading to reorganization of somatosensory pathways, particularly in the cerebral cortex, which is shown to depend upon central noradrenergic activity. In this study, sciatic and saphenous nerves were sectioned in the left hindpaw of 30 adult rats resulting in complete loss of pain sensation in the hindpaw. A group of rats received normal saline, compared to another group which received N-(2-) Chloroethyl-N-ethyl-2-bromobenzylamine (DSP4) injection 24 h prior to transection. The latter group was also compared to a third group whose central noradrenergic system were also blocked by bilateral injection of 6-OHDA into the ascending noradrenergic bundle 1 week prior to transection. A fourth group received contralateral cortical ablation in addition to peripheral nerve transection and was compared to the first group whose cortex remained intact. The animals were observed daily for 60 days and autotomy was scored in accordance to the system of Wall et al. [42]. After 1 week, control animals began to exhibit autotomy. In contrast, autotomy was absent in rats treated with DSP4, similar to rats which received 6-OHDA. Rats which had contralateral cortical ablation showed a considerably delayed onset of autotomy and a reduction in final autotomy scores. We conclude that autotomy, as a model of postdenervation pain syndrome, can be prevented by blockade of noradrenergically mediated cortical reorganization. The clinical implications of this finding are discussed.
AB - Following transection of peripheral nerve, rats exhibit autotomy, which is considered to be the animal model of postdenervation pain syndrome. It has been suggested that phantom limb pain is a result of peripheral denervation leading to reorganization of somatosensory pathways, particularly in the cerebral cortex, which is shown to depend upon central noradrenergic activity. In this study, sciatic and saphenous nerves were sectioned in the left hindpaw of 30 adult rats resulting in complete loss of pain sensation in the hindpaw. A group of rats received normal saline, compared to another group which received N-(2-) Chloroethyl-N-ethyl-2-bromobenzylamine (DSP4) injection 24 h prior to transection. The latter group was also compared to a third group whose central noradrenergic system were also blocked by bilateral injection of 6-OHDA into the ascending noradrenergic bundle 1 week prior to transection. A fourth group received contralateral cortical ablation in addition to peripheral nerve transection and was compared to the first group whose cortex remained intact. The animals were observed daily for 60 days and autotomy was scored in accordance to the system of Wall et al. [42]. After 1 week, control animals began to exhibit autotomy. In contrast, autotomy was absent in rats treated with DSP4, similar to rats which received 6-OHDA. Rats which had contralateral cortical ablation showed a considerably delayed onset of autotomy and a reduction in final autotomy scores. We conclude that autotomy, as a model of postdenervation pain syndrome, can be prevented by blockade of noradrenergically mediated cortical reorganization. The clinical implications of this finding are discussed.
KW - Autotomy
KW - Chronic pain
KW - Cortical reorganization
KW - Noradrenaline
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U2 - 10.1016/S0361-9230(01)00747-X
DO - 10.1016/S0361-9230(01)00747-X
M3 - Article
C2 - 11927359
AN - SCOPUS:0037086523
SN - 0361-9230
VL - 57
SP - 581
EP - 586
JO - Brain Research Bulletin
JF - Brain Research Bulletin
IS - 5
ER -