Yuzo Yamaguchi

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

&NA; 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’.

Properties of hyperactive cells in rat spinal cord after peripheral nerve section

cord under ketamine anesthesia. Electrical stimulations (ES) were given to the sectioned nerve, contralateral intact sciatic nerve or the thalamus and reversible cold blocking was introduced at segment T3 of the spinal cord or at proximal axon of the cut nerve. RESULTS: The HN appeared as early as 18 hours after the section and could be recorded even after 200 days in autotomized rats. The firing rates were greater in the autotomized rats than in the nonautotomized rats. Recording sites of HN spread widely in the gray matter of the ipsiand contralateral spinal cord. About one third of HN were suppressed by ES to the cut nerve or to the contralateral intact nerve and about 10% of HN were facilitated by weak ES to the cut nerve. About 70% of HN showed either decrease or increase of activity during cold blocking of the spinal cord and about half of HN showed similar effects during blocking of the cut nerve. Units with activity smaller than 40 Hz were rarely influenced by the spinal blocking. About half of HN showed decrease of firing by ES to the ventrobasal thalamic nuclei. These HN often showed rhythmic bursting pattern. Interspike interval histograms of rhythmic bursting activities peaked between 2 and 20 msec. In some cases, ES to the cut nerve influenced on the spontaneous rhythm and triggered bursting activities. CONCLUSION: Autotomy is correlated with spinal hyperactivity after peripheral nerve section. The spinal hyperactivity is partly due to peripheral influences of the sectioned nerve and partly exerted by descending influences of supraspinal centers including inhibition from the thalamus.

Relation of abnormal burst activity of spinal neurons to the recurrence of autotomy in rats.

Two groups of rats received different amounts of peripheral deafferentations; one group received sections of sciatic nerve (S-rats) and the other received sections of sciatic and saphenous nerves (SS-rats). In Experiment 1 the occurrence of autotomy was compared between S- and SS-rats for up to 70 days after the surgery. Autotomy in SS-rats frequently recurred until 40 days after denervation whereas in S-rats it scarcely recurred. In Experiment 2 spontaneous activity was recorded from the spinal cords in S- and SS-rats, and the proportion of burst firing cells (B-cells), characterized by periodic and high frequency bursts, was compared. In both S- and SS-rats with fresh wounds the occurrence of B-cells was high until 40 days after denervation. However, B-cells were still frequently observed in SS-rats with old wounds until 40 days after denervation, whereas B-cells were scarcely found in S-rats with similar old wounds. This finding corresponded well with the behavioral observation in Experiment 1. The data strongly suggests that the continuance of a high proportion of B-cells in the spinal cord plays an essential role for the induction of recurrent autotomy.

Inhibitory and facilitatory effects of peripheral electrical stimulation on autotomy induced by deafferentation in the rat

Aim of Investigation: Spontaneous antidromic action potentials (AI?.) have been reported in primary afferent axons following axotomy of their peripheral processes. We wished to verify this, quantitate the fiber conduction velocity (CV) spectrum, and determine if such activity was affected by a potassium channel-blocking agent (Gallamine). Methods : Under pentobarbital anesthesia, 28 rats underwent unilateral sa

Effects of peripheral nerve stimulation on neuronal hyperactivity in the spinal cord following sciatic nerve section of the rat

iZZii? neurotomy. One to eight weeks later, the rats were again anesthetized, and microfilament recordings were carried out in the proximal stump of the nerve after removal of the neuroma. Spike-triggered averaging was used to determine the direction of propagation and velocity of recorded APs. Gallamine (20 mg initial dose, 10 mg every 30 minutes) was given (IV) and the nerve was reexamined for spontaneous activity. Control recordings were performed in six rats. Results : Compared to controls, significantly more antidromic activity in bominated and unmyelinated fibers occurred in chronically axotomized nerves. This was further increased by gallamine in A fibers, but not in C fibers . Receptive fields could be demonstrated in 4% of axons with spontaneous activity. The average CV of these active fibers (16.85 + 20.73 m/s) was significantly slower than similarly active fibers in neuroiiias (p< .OOl). Conclusions: Axotomy produces spontaneous activity in A and C fibers _ central to a nerve section. Such activitv in mvelinated fibers is increased by potassium channel blockade. Rarely, this activity may be accounted for by the presence of peripherally dichotomizing axons. This activity occurs in a relatively slower conducting population of axons than does similar activity in neuromas.