The Localized Action on the Spinal Cord of Intramuscularly Injected Tetanus Toxin

Abstract

Local tetanus limited to one leg was studied in cats after intramuscular injection of tetanus toxin. 1. The electric and mechanical response of the affected muscle after a single stimulus to the intact sensory-motor nerve is greater in amplitude and duration than the response of the corresponding muscle of the unaffected leg (Fig. 1). 2. This augmented response of the muscle is associated with an augmented response arising from the ipsilateral portion of the spinal cord, while the contralateral part of the cord is unaffected, as demonstrated by electrographic records from the motor nerves (Figs. 2 to 5). 3. The augmented muscular response is abolished when the reflex arc is broken, but the augmented response in the spinal cord is independent of changes in the muscle, the neuromuscular junction, the afferent and efferent peripheral nerves, and the dorsal root ganglia. 4. The augmented spinal response develops in the absence of the peripheral signs of local tetanus. Hence the pathogenesis of the altered state in the spinal cord is independent of the peripheral effects of the toxin. 5. In local tetanus, therefore, the toxin injected intramuscularly acts selectively upon the segments of the spinal cord which supply the innervation of the injected area. 6. The augmented spinal response may be prevented by section of the nerve trunks supplying the area of injection prior to the injection of the toxin. 7. It is concluded that in local tetanus the toxin is carried to the spinal cord by way of peripheral nerves.

The action of tetanus toxin on the inhibition of motoneurones

“…Acheson et al (1942) demonstrated that intramuscular injection of toxin into cats produced local tetanus associated with increased polysynaptic reflexes, whereas the monosynaptic reflexes were almost normal. The loss of inhibition was demonstrated in the rabbit, although not recognized as such, by Davies et al (1954).…”

“…Following such an injection the typical symptoms of local tetanus developed in 18-20 hr (cf. Fildes, 1929;Acheson, Ratnoff & Schoenbach, 1942;Hutter, 1951;Davies, Morgan, Wright & Wright, 1954). Consequently, the preparation of both hind limbs and of both sides of the cord was commenced 8-12 hr after the injection so that a comparison of reflexes on the two sides could be made before the development of local tetanus and at various times thereafter.…”

Tetanus toxin reduces local and descending regulation of the H-reflex

“…A comparison of the effect of tetanus toxin with stimulation at 0.2 Hz and 20 Hz from a representative animal is shown in Figure A. Tetanus toxin appeared to decrease rate‐dependent depression of the H‐wave, an effect visible in previous recordings made with 4–8 Hz simulation . The effect of the toxin on rate‐dependent depression of the H‐wave was examined in greater detail by stimulating the medial plantar nerve with a train of 10 pulses delivered at increasing frequencies.…”

“…As well as increasing reflex activation by a purely peripheral effect on the monosynaptic reflex, tetanus toxin also appeared to decrease inhibition of the H‐wave resulting from activation of the descending pathway. The effect likely took place at a local level, because such a small amount of toxin injected intramuscularly would be expected to remain almost exclusively within the spinal segments that innervate the injected muscle rather than ascend the spinal cord …”

Pathologic physiology, pharmacology, and therapeutics of tetanus

“…Existing local tetanus is abolished by nerve section. 10,166,276,299 3. After the injection of toxin into the hind limb of one parabiotic rat, local tetanus occurs in the other rat only if a crossed regenerated nerve is present.…”