Primary afferent terminals

In conclusion, data from biochemical, physiological/pharmacological and immunocyto-chemical studies concur in supporting Glu as a primary afferent neurotransmitter. Although it cannot be excluded that a subpopulation of primary afferent terminals that have escaped investigation transmit their signals by other means, the available evidence speaks strongly in favor of Glu as a transmitter in most, if not all, primary afferent terminals (Fig. 4). This of course does not exclude that other compounds, e.g. peptides, are co-released with Glu from selected populations of primary afferent terminals. 

Biochemical studies and retrograde labeling with D-[ H]aspartate provide strong evidence for an excitatory amino acid as transmitter in the corticofugal input to the spinal cord (Storm-Mathisen and Ottersen, 1988 Rustioni and Weinberg, 1989 Fig. 4). That Glu serves as a corticospinal neurotransmitter is further supported by the presence of high levels of Glu in corticospinal terminals in the dorsal horn (Valtschanoff et al., 1993). 

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They act as analgesics by inhibiting release of nociceptive neurotransmitters from primary afferent terminals as well as by depressing post-synaptic potentials on second order neurons. Opioid receptors are also present on some nociceptors and their expression and peripheral transport is increased upon peripheral inflammation. Peripheral opioid analgesia has been established in animal models. Although clinical studies have yielded mixed results so far, this field holds great promise. Despite side effects, such as euphoria, dysphoria, sedation, respiratory depression and obstipation and tolerance and dependence phenomena which arise upon... 

Dendrobine at a dose of 3 X 10-5 M reduced the dorsal root potential and reflex. It provoked a mild hyperpolarization in both dorsal and ventral roots of frog isolated spinal cord. It affected the (3-alanine- and taurine-induced depolarization of primary afferent terminals and reversibly blocked the presynaptic inhibition caused by antidromic conditioning stimulation of the ventral root potential induced by repetitive antidromic stimulation of ventral root and lowered maximum. It would be interesting to learn whether further research of the Dendrobium species discloses any alkaloid interfering with the glycinergic system, an aspect discussed under the following heading. 

In contrast to the cellular localization of Y1 receptors, spinal Y2 receptors are located on primary afferent terminals (Brumovsky et al., 2005). Y1 receptor deletion increased acute heat, inflammatory, and neuropathic pain sensitivities (Kuphal et al.,... 

Broman J, Adahl F (1994) Evidence for vesicular storage of glutamate in primary afferent terminals. Neuroreport 5 1801-1804. 

Broman J, Anderson S, Ottersen OP (1993) Enrichment of glutamate-like immunoreactivity in primary afferent terminals throughout the spinal cord dorsal horn. Eur J Neurosci 5 1050-1061. 

De Biasi S, Rustioni A (1988) Glutamate and substance P coexist in primary afferent terminals in the superficial laminae of spinal cord. Proc Natl Acad Sci USA 85 7820-7824. 

De Biasi S, Vitellaro-Zuccarello I, Bernardi P, Valtschanoff JG, Weinberg RJ (1994a) Ultrastructural and immunocytochemical characterization of primary afferent terminals in the rat cuneate nucleus. J Comp Neurol 547 275-287. 

Valtschanoff JG, Phend KD, Bemardi PS, Weinberg RJ, Rustioni A (1994) Amino acid immunocytochemistry of primary afferent terminals in the rat dorsal horn. J Comp Neurol 346 237-252. 

Kainate receptor subunit mRNAs are not abundant in the adult spinal cord, and GluR6 is not expressed at all (Tdlle et al., 1993). In the dorsal horn, occasional cells express the GluR5 and GluR7 subunit genes, and more cells contain KA2 mRNA (Tolle et al., 1993). Kainate receptors are probably in subsets of AMPA receptor-positive cells. Most of the GluRS protein in the dorsal horn is on the primary afferent terminals of DRG cells (Woolf and Costigan, 1999). 

Immunoreactivity for CBIR and p-opioid receptors (MOR) is also colocalized on lamina II interneurons at the ultrastructural level (Salio et al. 2001). In this work, CBIR was predominantly localized postsynaptically in dendrites and cell bodies, but immunoreactive axons and axon terminals were also observed (Salio et al. 2001). Both species showed rare labeling of the plasma membrane. Since MORI is not colocalized with GABA (Gong et al. 1997 Kemp et al. 1996), these data support the presence of CBIR in distinct populations of intrinsic spinal neurons (Salio et al. 2001). By contrast, colocalization of CBIR with MORI in thin primary afferent terminals could not be convincingly demonstrated in this work (Salio et al. 2001). 

At the same time, several other mechanisms may be activated to compensate for some of the excitatory effect, perhaps to keep the system from being hyperreactive. These mechanisms include (1) presynaptic inhibition of glutamate release from the primary afferent terminals, (2) activation of the NKl receptors on the soma/dendrite of GABAergic intemeurons to enhance GABA release, and (3) an enhanced glycine synaptic transmission via an enhanced glycine receptor function through a protein kinase C or a Ca/calmodulin dependent protein kinase 11 pathway (Fig. 2). 

The mechanism whereby capsaicin treatment of adult animals brings about a loss of peptides from sensory nerves is not clear. The possibilities include degeneration of those neurons, interference with terminal storage capacity, inhibition of peptide synthesis, or blockade of axonal transport. As described earlier, there is no evidence for capsaicin-induced degeneration after subcutaneous treatment of adult animals. This is supported by the observation that peptide levels partially recover in affected areas some time after treatment (Gamse et al., 19806). The results obtained after intrathecal treatment suggest a direct effect on primary afferent terminals... 

Barber, R. P., Vaughn, J. E., Saiton, K., McLaughlin, B. J., and Roberts, E., 1978, GABAergic terminals are presynaptic to primary afferent terminals in the substantia gelatinosa of the rat spinal cord, Brain Res. 141 35-55. 

Levy, R. A, 1974, GABA a direct depolarizing action at the mammalian primary afferent terminal. Brain Res. 76 155-160. 

Opioid-induced analgesia is produced through the action of opioid receptors on presynaptic terminals of the C-fibers and A-delta fibers. These fibers, which transmit nociceptive messages, are inhibited by the indirect effects of opioids, which in turn reduce the release of neurotransmitters such as substance P, CGRP, and glutamate. This effect occurs in the peripheral nervous system as well as at the primary afferent terminals in the spinal cord. 

Merighi A, Bardoni R, Salio C et al (2008) Presynaptic functional trkB receptors mediate the release of excitatory neurotransmitters from primary afferent terminals in lamina II (substantia gelatinosa) of posmatal rat spinal cord. Dev Neurobiol 68 457-475... 

Larsson M, Persson S, Ottersen OP et al (2001) Quantitative analysis of immunogold labeling indicates low levels and non-vesicular localization of L-aspartate in rat primary afferent terminals. J Comp Neurol 430 147-159... 

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