Magnesium sulphate injected subcutaneously suppresses autotomy in peripherally deafferented rats.
In rats, recent evidence suggests that injury discharge caused by peripheral nerve section releases excitatory amino acids into the spinal cord which in turn influences decisively the development of autotomy, a self-mutilation behaviour directed towards the denervated areas. Autotomy has been proposed as a behavioural correlate of the neuropathic pain which occurs in humans after complete nerve lesions. Mg2+ ions have been shown to offer protection from neurological and degenerative disorders in which excitatory amino acids are putatively involved. To ascertain the preventive value of Mg2+ administration on autotomy, male rats underwent unilateral ligation and transection of the sciatic and saphenous nerves 30 min after being injected subcutaneously (s.c.) with 300 or 600 mg/kg MgSO4 or saline. Thereafter, autotomy was monitored for 8 weeks. Serum, lumbosacral (L1-S1) and brain magnesium levels were analyzed 0, 30, 60, 120, 180, 240, 360 min and 24 h after the s.c. injection of 600 mg/kg MgSO4. Serum magnesium levels increased quickly from 1.02 mM (0 time) to 4.52 mM (at 60 min) and dropped afterwards to reach physiological levels at 6 h. Peak increments in L1-S1 and brain Mg2+ levels were smaller (32% and 30%, respectively) although maintained for at least 6 h. Magnesium pretreatment in a significant and dose-dependent manner (1) largely suppressed autotomy, (2) decreased final autotomy scores, (3) delayed autotomy onset, and (4) decreased the percentage of animals engaged in high autotomy behaviors. The data support a role for excitatory amino acids in determining susceptibility to autotomy and suggest a hopeful way to prevent neuropathic pain in humans after peripheral deafferentation.
Feria
Manuel
M
Departments of Pharmacology, Faculty of Medicine, University of La Laguna, TenerifeSpain Departments of Physiology, Faculty of Medicine, University of La Laguna, TenerifeSpain.
Abad
Faustino
F
Sánchez
Alberto
A
Abreu
Pedro
P
D000818:Animals; D001921:Brain / Q000378:metabolism; D003714:Denervation; D007279:Injections, Subcutaneous; D008278:Magnesium Sulfate / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D009475:Neurons, Afferent / Q000502:physiology*; D010146:Pain / Q000523:psychology*; D010525:Peripheral Nerves / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000502:physiology; D012652:Self Mutilation / Q000523:psychology*; D013116:Spinal Cord / Q000378:metabolism
D008278:Magnesium Sulfate