Central sprouting and functional plasticity of regenerated primary afferents

Abstract

A combination of neuroanatomical and electrophysiological techniques was used to study the effects of peripheral axotomy and regeneration of primary afferents on their central projections in the spinal cord. Individual regenerated afferent fibers were impaled with HRP-filled electrodes in the dorsal columns of alpha-chloralose-anesthetized cats and activated by current pulses delivered via the intracellular electrode. The resulting cord dorsum potentials (CDPs) were recorded at four rostrocaudal locations and HRP was iontophoretically injected into the fiber. Central distributions of boutons and CDPs were compared with peripheral receptor type to determine the accuracy of peripheral regeneration and the effects of central-peripheral mismatches. Reconstruction of the central projections of 13 individual afferents for which the adequate stimulus and CDPs had been recorded revealed many abnormalities. For example, unlike controls, four group I and II afferents with central projections typical of proprioceptors (concentrated in laminae V, VI, and VII) innervating either cutaneous or noncutaneous targets evoked measurable CDPs. Three other group II or A beta afferents innervating low-threshold mechanoreceptors with central terminations confined to the dorsal horn exhibited extensive collateralization in laminae I and II in addition to large numbers of terminals in laminae III-IV. These fibers activated central networks whose adaptation behavior was identical to those evoked by high-threshold mechanoreceptive afferents in controls. These results suggest that primary afferents and their central connections are capable of significant modifications following axotomy and regeneration. In addition, the anatomical studies indicate some reorganization in the laminar distribution of boutons as well as in bouton size.

A feed-forward spinal cord glycinergic neural circuit gates mechanical allodynia

“…In addition, other circuits such as GABAergic circuit may also contribute to the gate control, as we have found some GABAergic inhibitory connections in this region. Sprouting of Aβ afferents dorsally into laminae IIo and I, the area that normally receives nociceptive input, was also implicated in nerve injury-induced mechanical allodynia (43)(44)(45)(46)(47), but several latter studies argue against the hypothesis of Aβ afferent sprouting (12,48,49).…”

Collateral Sprouting of Uninjured Primary Afferent A-Fibers into the Superficial Dorsal Horn of the Adult Rat Spinal Cord after Topical Capsaicin Treatment to the Sciatic Nerve

“…Large myelinated mechanoreceptive A␤ fibers normally terminate in lamina III-VI, small myelinated nociceptive A␦ fibers in laminae I and V, and small unmyelinated nociceptive C-fibers in lamina II (substantia gelatinosa) (Brown, 1981;Molander et al, 1984;Molander and Grant, 1985;Willis and Coggeshall, 1991). After injury, however, using B fragment of cholera toxin conjugated to horseradish peroxidase (B-HRP) to selectively label myelinated fibers (Robertson and Grant, 1985;Rivero-Melian and Grant, 1990;Robertson et al, 1991), peripheral axotomy has been shown to cause longlasting sprouting of A-fibers into lamina II, an area in which they do not normally terminate Koerber et al, 1994;Woolf et al, 1995). Intracellular injections have shown that at least some of these fibers are A␤ afferents from lamina III Shortland and Woolf, 1993;Koerber et al, 1994).…”

“…After injury, however, using B fragment of cholera toxin conjugated to horseradish peroxidase (B-HRP) to selectively label myelinated fibers (Robertson and Grant, 1985;Rivero-Melian and Grant, 1990;Robertson et al, 1991), peripheral axotomy has been shown to cause longlasting sprouting of A-fibers into lamina II, an area in which they do not normally terminate Koerber et al, 1994;Woolf et al, 1995). Intracellular injections have shown that at least some of these fibers are A␤ afferents from lamina III Shortland and Woolf, 1993;Koerber et al, 1994).…”

Distribution and Injury-Induced Plasticity of Cadherins in Relationship to Identified Synaptic Circuitry in Adult Rat Spinal Cord

“…In addition, peripheral nerve crush or axotomy is associated with synaptic structural plasticity within the neuropil of lamina II. Such plasticity includes synaptic and terminal degeneration of certain C-fiber nociceptive afferents (Knyihar and Csillik, 1976;Kapadia and LaMotte, 1987), as well as sprouting and regeneration of synaptic contacts in which remaining C-fibers or mechanoreceptive A␤-fibers have been implicated (Csillik and Knyihar, 1975;Woolf et al, 1992;Koerber et al, 1994;Kohama et al, 2000). The molecular mechanisms that specify dorsal horn synaptic circuitry and contribute to injuryrelated structural synaptic plasticity and retargeting are mostly unexplored.…”