No abstract

There is evidence that reflex conduction in the spinal cord is disturbed when the axons of the anterior horn cells are regenerating after division (Campbell, 1944; Downman, Eccles & McIntyre, 1953). There is also evidence of altered synaptic function in ganglia after degenerative section of postganglionic fibres (Acheson, 1952). Our attention was first drawn to this problem during an investigation of the pathways through the inferior mesenteric ganglion in the rabbit (Brown & Pascoe, 1952); we found that degenerative section of postganglionic trunks caused complete failure of synaptic transmission between preganglionic nerves and the cells with cut axons. We accordingly undertook a systematic investigation of the phenomenon, using other ganglionic systems in which the fibre connexions are less complex than in the inferior mesenteric. Our experiments have shown that the preganglionic nerve and its endings are unaffected, and that conduction in the proximal portion of the divided axon is substantially normal; the defect responsible for the failure of synaptic transmission lies in the soma of the neurones. Preliminary accounts of some of this work have appeared (Brown, McLennan & Pascoe, 1952a, b). METHODSGanglia and nerve trunks isolated from the body and suspended in Locke's solution were used in many experiments, the technique being identical with that previously described (Brown & Pascoe, 1952). In other experiments we stimulated and recorded from nerves and ganglia in the living animal. Rabbits were anaesthetized with intravenous urethane, 1.8 g/kg, and cats with chloralose, 100 mg/kg, after preliminary ethyl chloride and ether. For recording from the inferior mesenteric ganglion and nerves, the abdomen was opened in the middle line and the anterior wall was sewn to a metal ring to form a bath which was filled with liquid paraffin. In ordinary circumstances the bath so formed was warmed by radiant heat from above, but when different temperatures were needed, the paraffin was circulated with a pump through a coil kept in a bath at the required temperature. Similar arrangements were used for the stellate ganglion, a large piece of the chest wall, including the four upper ribs being removed.The stimuli, which were applied to the nerve through platinum electrodes, were square voltage

SUMMARY1. The effects of intravenous morphine, (-)-naloxone and (+ )-naloxone have been studied on three ipsilateral cutaneo-muscular reflexes in spinal rabbits.2. Morphine, 3 mg/kg caused a slow-onset depression of all three reflexes. This effect was naloxone reversible.3. The ipsilateral extensor reflexes, sural to gastrocnemius medialis and saphenous to vastus lateralis were both enhanced to more than double control size following a 5 sag/kg dose of naloxone given in the absence of morphine. For the suralgastrocnemius reflex, naloxone potentiated the reflex drive from all groups of myelinated afferent fibres.4. The ipsilateral flexion reflex, sural to semitendinosus, was only weakly enhanced by naloxone, the 5 ,ug dose leading to an increase in the size of the reflex to 130 % of control. 5. All observed actions of naloxone were stereospecific as the enantiomer (+ )-naloxone failed to affect any of the reflexes even in a dose of 50 ltg/kg.6. We conclude from these findings that opioid peptides are tonically released in rabbit spinal cord, and that they have differential effects in control of flexion and extension reflexes. It is suggested that the ipsilateral extension reflexes are held under a more powerful opioid-mediated depression than that operating upon the flexion reflexes, and that this difference may be related to the greater inhibitory inflow to extensor motoneurones from ipsilateral skin areas.

The depolarization of the cat's superior cervical ganglion by drugs has been studied by Paton & Perry (1953) and by Lundberg & Thesleff (1953). Their experiments were made in vivo with known quantities of drugs injected into the ganglionic circulation. This technique, whilst preserving the ganglion in a physiological condition, is not ideal for quantitative studies. With the ganglia isolated in vitro the concentration of drug can be more easily controlled and electrical recording is easier. A technique has been developed for measuring the potential changes produced by drugs on the isolated superior cervical ganglia of rats and rabbits. This has been used to study the depolarizing action of acetylcholine and its modification by tubocurarine. Some of the results have been reported in a preliminarv communication (Pascoe, 1955b). METHODSDissection. Rabbits were anaesthetized with a 25 % solution of urethane 1.8 g/kg by ear vein.The ganglia with the pre-and post-ganglionic trunks were dissected and placed in cold Locke's solution. The postganglionic nerve used was the internal carotid nerve. The ganglionic capsule and postganglionic sheath were slit with fine scissors and removed. For survival operations on rabbits anaesthesia was produced by sodium pentobarbitone followed by ether and full aseptic precautions observed. Rats were anaesthetized with either 25% urethane 1-6 g/kg or 6% sodium pentobarbitone 1 ml./kg intraperitoneally; for survival operations open ether was used.Recording. To avoid the effects of amplifier drift when measuring long-lasting potential differences a fluid-moving electrode was used similar to that described by Fatt (1950). This enabled drugs to be added to the fluid surrounding the ganglion without mechanical or electrical disturbance. The apparatus is shown in Fig. 1. The preparation was supported vertically in the inner chamber with the postganglionic trunk uppermost. Platinum electrodes (not shown in the diagram) were used for stimulating the preganglionic trunk at the beginning of most experiments to check ganglionic transmission and the degree of damage by dissection. The recording electrodes were silver/silver chloride/agar saline with balsa wood wicks connecting with the preparation. The uppermost electrode was on the cut end of the postganglionic nerve; in later experiments it actually formed the point of attachment for the nerve. A second non-polarizable electrode (not shown) was placed on the ganglion, and these two electrodes were used when recording the postganglionic response to preganglionic stimulation. A third electrode was placed below the level of

In recent years a considerable volume of information has accumulated about conduction through the ganglia of the sympathetic nervous system. The pathways through the superior cervical ganglion, the stellate and the inferior mesenteric ganglion of the cat have been studied in detail (Eccles, 1935(Eccles, , 1943Lloyd, 1937;Bronk, Tower, Solandt & Larrabee, 1938), and accurate figures are available for conduction velocities in afferent and efferent fibres for refractory periods and for synaptic delays in these ganglia.Our attention was originally directed towards the inferior mesenteric ganglion of the rabbit by our need to secure, for another purpose, a ganglion with a long post-ganglionic trunk and capable of survival for long periods after isolation from the body. Preliminary tests revealed fibre connexions in this ganglion of greater complexity than we had suspected, and transmission phenomena which distinguished it in some respects from those previously studied. A preliminary account of some of the experiments has already appeared (Brown & Pascoe, 1951). METHODSAll our experiments have been made on the inferior mesenteric ganglion of the rabbit, isolated from the body and suspended in Locke's solution. Gross anatomy and nomencaureThe inferior mesenteric ganglion of the rabbit is a single (unpaired) structure lying within the mesocolon in the cranio-ventral angle between the inferior mesenterio artery and the aorta (Fig. 1). It is connected with the sympathetic ganglionated chain through the inferior splanchnic nerves. The only one of these large enough for dissection and convenient manipulation runs from the cranial pole of the ganglion, cranio-dorsally and may be 1-15 cm in length. A smaller splanchnic nerve is sometimes visible running ventrally from the chain to enter the middle of the ganglion. Only on a few occasions have we succeeded in dissecting this in a viable condition. Other minute filaments can also be seen running from the chain towards the ganglion or its connexions and are presumably subsidiary inferior splanchnic nerves.Ruinning from the caudal pole of the ganglion is a complex network of branches, some emanating from the ganglion itself and others from nerve fibres on the colonic vein and inferior PH. CXVIII. 8