Increased uptake and transport of cholera toxin B‐subunit in dorsal root ganglion neurons after peripheral axotomy: Possible implications for sensory sprouting

Abstract

In the present study we show that, in contrast to the rat, injection of cholera toxin B-subunit (CTB) into the intact sciatic nerve of Macaca mulatta monkey gives rise to labelling of a sparse network of fibers in laminae I-II of spinal cord and of some mainly small dorsal root ganglion (DRG) neurons. Twenty days after sciatic nerve cut, the percentage of CTB-positive lumbar 5 (L5) DRG neuron profiles increased from 11% to 73% of all profiles. In the spinal cord, a marked increase in CTB labelling was seen in laminae I, II, and the dorsal part of lamina III. In the rat L5 DRGs, 18 days after sciatic nerve cut, the percentage of CTB- and CTB conjugated to horseradish peroxidase (HRP)-labelled neuron profiles increased from 45% to 81%, and from 54% to 87% of all neuron profiles, respectively. Cell size measurements in the rat showed that most of the CTB-positive neuron profiles were small in size after axotomy, whereas most were large in intact DRGs. In the rat spinal dorsal horn, a dense network of CTB-positive fibers covered the whole dorsal horn on the axotomized side, whereas CTB-labelled fibers were mainly seen in laminae III and deeper laminae on the contralateral side. A marked increase in CTB-positive fibers was also seen in the gracile nucleus. The present study shows that in both monkey and rat DRGs, a subpopulation of mainly small neurons acquires the capacity to take up CTB/CTB-HRP after axotomy, a capacity normally not associated with these DRG neurons. These neurons may transganglionically transport CTB and CTB-HRP. Thus, after peripheral axotomy, CTB and CTB-HRP are markers not only for large but also for small DRG neurons and, thus, possibly also for both myelinated and unmyelinated primary afferents in the spinal dorsal horn. These findings may lead to a reevaluation of the concept of sprouting, considered to take place in the dorsal horn after peripheral nerve injury.

Analysis of the distribution of binding sites for the plant lectin Bandeiraea simplicifolia I‐isolectin B4 on primary sensory neurones in seven mammalian species

“…The results of this study confirm previous reports of BSI-B 4 binding in the rat, mouse, and rabbit (Streit et al, 1985;Kruger, 1988, 1990;Plenderleith et al, 1992;Plenderleith and Snow, 1993;Kitchener et al, 1994;Wang et al, 1994), and are entirely consistent with studies reporting BSI-B 4 binding in dorsal root ganglia and spinal cord of the chicken (Scott et al, 1990), echidna (Ashwell and Zhang, 1997), opossum (Knott et al, 1999), and rhesus monkey (Tong et al, 1999). Furthermore, recent studies have reported BSI-B 4 binding sites on human primary sensory neurones collected either post-mortem or from patients undergoing surgery (Yiangou et al, 2000;Alavi et al, 2001).…”

Two-Tiered Inhibition of Axon Regeneration at the Dorsal Root Entry Zone

“…It should be noted that not all labeled axons that reached the entry zone were able to cross with NT-3 treatment (the axonal density in the PNS side of the DREZ is clearly greater than that on the CNS side). However, CTB labels myelinated GM-1 ganglioside-expressing neurons (small and large), which accounts for ϳ45% of all somatic afferents (Tong et al, 1999). TrkC-expressing neurons are nearly exclusively large in diameter and account for ϳ25% of all DRG neurons (McMahon et al, 1994).…”

Neuropathy-Induced Spinal GAP-43 Expression Is Not a Main Player in the Onset of Mechanical Pain Hypersensitivity

“…As such, it was thought that low-threshold A fibers directly innervate nociceptionspecific neurons in lamina I, resulting in the gating of nonnoxious stimuli to pain pathways. Although the evidence for A fiber sprouting has been shown to be subject to methodological bias by tracing procedures (Bao et al, 2002;Tong et al, 1999), neuropathy-induced increases in spinal GAP-43 expression still suggest that fiber sprouting occurs within the superficial dorsal horn. Spinal GAP-43 expression was previously reported to be regulated in unmyelinated fibers following nerve injury (Coggeshall et al, 1991).…”