Nociceptive synapse

GABAb receptors mediate the slow and prolonged physiological effects of the inhibitory neurotransmitter GABA. Functional GABAb receptors are comprised of two subunits, GABAbR1 and GABAbR2. Both subunits are G-protein-coupled receptors, which couple to the Gi/o family and are densely expressed at spinal nociceptive synapses. 

Larsson M, Broman J (2006) Pathway-specific bidirectional regulation of Ca +/calmodulin-dependent protein kinase n at spinal nociceptive synapses after acute noxious stimulation. J Neurosci 26 4198 205... 

N-type Ca2+ channels for instance are located at presynaptic termini of neurons where they are directly involved in the regulation of neurotransmitter release. Staining of the dorsal laminae of the rat spinal cord revealed a complementary distribution of class A and class B Ca2+ channels in nerve terminals in the deeper versus the superficial laminae. Many of the nerve terminals immunoreactive for class B N-type Ca2+ channels also contain substance P, an important neuropeptide in pain pathways, suggesting the N-type Ca2+ channels are predominant at synapses that carry nociceptive information to the spinal cord (Westernbroek etal., 1998). 

Opioids basically exert their analgesic effects by inhibiting synaptic transmission in key pain pathways in the spinal cord and brain. This inhibitory effect is mediated by opioid receptors that are located on both presynaptic and postsynaptic membranes of pain-mediating synapses (Fig. 14—2). In the spinal cord, for example, receptors are located on the presynaptic terminals of primary (first-order) nociceptive afferents, and when bound by opioids, they directly decrease the release of pain-mediating transmitters such as substance P.35,38 Opioid drug-receptor interactions also take place on the postsynaptic membrane of the secondary afferent neuron—that is, the second-order nociceptive afferent neuron in the spinal cord.19,33 When stimulated, these receptors also inhibit pain transmission by hyperpolarizing the postsynaptic neuron.19... 

The 5-HT3 receptors are found in both the peripheral nervous system and central nervous system (CNS), where they mediate last synaptic transmission at synapses (3). In the CNS, they are located predominantly at intemeurones, where they modulate the release of a range of neurotransmitters (4-9). There is some evidence that 5-HT3 receptors play roles in brain reward mechanisms and in neurological phenomena such as anxiety, psychosis, nociception, and cognitive function (10,11), and in the first few years following the discovery of these receptors, there was also much interest in the therapeutic potential of 5-HT3 receptor antagonists for antipsychotic, antinociceptive, and other psychiatric disorders (12-15). This potential has not yet been realized, but there is still active research in this area (16), and their current major therapeutic target is against emesis in cancer chemotherapy and irritable bowel syndrome (17,18). 

Neuronal projections from the hypothalamus to other regions of the brain relay important output information that influence blood pressure, appetite, thirst, circadian rhythm, behavior, nociception (pain perception), and others factors. Although many of these neurons release neurotransmitter amines at synapses, some of them are known to release neurotransmitter peptides. These include, among others, peptides that closely resemble hormones formed in the gastrointestinal system as well as the endogenous opiates (Table 31-3). 

Nociceptive transmission takes place in A5 and C-afferent nerve fibers. Stimulation of large-diameter, sparsely myelinated A5 fibers evokes sharp, well-localized pain, whereas stimulation of unmyelinated, small-diameter C fibers produces dull, aching, and poorly localized pain. These afferent, nociceptive pain fibers synapse in various layers (laminae) of the spinal cord s dorsal hom, releasing a... 

Li P, Zhou M (1998) Silent glutamatergic synapses and nociception in mammalian spinal cord. Nature 393 695-698. 

The dorsal funiculus (DF-)SOCP synapses in the dorsal column nuclei and converges with the VF-SOCP at the level of the inferior olive. The DF-SOCP is activated from high threshold muscle afferents and from both tactile and nociceptive cutaneous afferents... 

Larsson M, Broman J (2005) Different basal levels of CaMKn phosphorylated at Thr286/ 287 at nociceptive and low-threshold primary afferent synapses. Eur J Neurosci 21 2445-2458... 

The ascending pain pathway commences at the afferent nociceptive fibres which send information to the brain via the spinal cord where they form synapses with its dorsal horn where pain is comprehended. 

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