125I-Labelled botulinum a neurotoxin: Pharmacokinetics in cats after intramuscular injection

Abstract

1. On unilateral injection of sublethal doses of 125I-botulinum A neurotoxin (BTA) into one gastrocnemius muscle of the cat we found after 48 h: a) A disto-proximal gradient of radioactivity (RA) had developed in the sciatic nerve of the injected side. b) The ventral roots of the spinal cord half segments supplying the injected muscle showed a higher RA than the ventral roots of the contralateral control side. c) The spinal cord half segments innervating the injected muscle had a RA much higher than the corresponding segments of the contralateral side. However, a small rise of RA was also observed in the contralateral half segments. 2. In histoautoradiographs of the (ligatured) ventral roots the RA was strictly confined to the intraaxonal space of a few nerve fibres. 3. On injection of equal doses of 125I-BTA into either gastrocnemius muscle we found after 38 h: a) Direct stimulation of only one of the injected muscle caused the RA to reach a higher level in the spinal cord half segments ipsilateral to the stimulated muscle than in the spinal cord half segments of the non-stimulated side. b) Unilateral stimulation of one gastrocnemius nerve under the influence of gallamine or unilateral antidromic stimulation of the dorsal roots L7, S1 failed to cause a difference in RA between stimulated and non-stimulated side.

Botulinum toxin type A for neuropathic pain in patients with spinal cord injury

“…Some evidence of the central mechanisms of the antinociceptive activity of BTX‐A has been shown. Although the evidence is limited, axonal transport of BTX‐A from the periphery to the central nervous system has been demonstrated 15, 31, 32, 33, 34, 35. In a recent study by Marinelli et al, BTX‐A was subcutaneously injected into the plantar surface of the hind paw of a sciatic nerve injury mouse model.…”

Botulinum toxin type-A therapy in cluster headache: an open study

“…Alternatively, it is discussed that BTX-A may reduce or even prevent sensitisation of peripheral trigeminal afferents, which through attenuation of the nociceptive input may also result in inhibition of central sensitisation [24]. In the context of neurogenic inflammation, there is evidence that BTX-A is retrogradely transported into the CNS [25] and modulates the release of neurotransmitters such as substance P [26] or CGRP [27] in the trigeminal terminals.…”

Botulinum toxin A, brain and pain

“…As suggested by some earlier studies, the toxin might penetrate into the central nervous system by axonal transport (Habermann et al, 1974;Wiegand et al, 1976;Wiegand and Wellhöner 1977). To trace the possible spread of BoNT/A into the CNS, the authors employed 125 I-radiolabelled BoNT/A injections into the cat gastrocnemius muscles.…”