The role of spinal cord activation before neurectomy in the development of autotomy

A model of deafferentation pain is provided by sectioning the sciatic and saphenous nerves in the rat and mouse. This procedure leads to self-mutilation of the denervated hindpaw (autotomy). A noxious stimulus to the denervated area before neurectomy is known to enhance the autotomy. To understand the mechanism underlying this enhancement by prior noxious stimuli, we examined the effects of intrathecal (i.t.) injection of substance P (SP) and somatostatin (SOM) on autotomy behavior. These peptides are known to be released from primary afferent terminals in the dorsal horn by noxious stimuli. A single i.t. injection of SP or SOM just before neurectomy dramatically enhanced autotomy behavior in mice. Autotomy was enhanced in a dose-dependent manner with i.t. injection of SP (0.1-20 nmol) 5 min before neurectomy or SOM (0.1-1.0 nmol) 20 min before neurectomy. Autotomy significantly decreased by extending the interval between i.t. injection of SP or SOM and neurectomy. Intact mice injected with the same doses of SP or SOM showed dose-dependent acute nociceptive responses directed to the hindpaw. The severity of autotomy in neurectomized mice and the duration of acute nociceptive responses induced by the same doses of SP or SOM in intact mice were related. These results suggest that neuropeptides applied to the spinal dorsal horn just before deafferentation induce a state of central neural activation with long-lasting effects on the function of CNS cells. Augmentation of autotomy is a result of this activation which is kept as a 'memory'.