Second-order neurons

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... 

The cell bodies of second-order sensory neurons are found in the dorsal horn. These neurons receive input from afferent neurons (first-order sensory neurons) entering the CNS from the periphery of the body through the dorsal... 

Second-order sensory neuron that transmits impulses to higher levels of the CNS... 

As discussed, the first-order neuron is the afferent neuron that transmits impulses from a peripheral receptor toward the CNS. Its cell body is located in the dorsal root ganglion. This neuron synapses with the second-order neuron whose cell body is located in the dorsal horn of the spinal cord or in the medulla of the brainstem. The second-order neuron travels upward and synapses with the third-order neuron, whose cell body is located in the thalamus. Limited processing of sensory information takes place in the thalamus. Finally, the third-order neuron travels upward and terminates in the somatosensory cortex where more complex, cortical processing begins. 

The mechanism of action of these anesthetics involves the blockade of sodium channels in the membrane of the second-order sensory neuron. The binding site for these anesthetics is on a subunit of the sodium channel located near the internal surface of the cell membrane. Therefore, the agent must enter the neuron in order to block the sodium channel effectively. Without the influx of sodium, neurons cannot depolarize and generate an action potential, so the second-order sensory neuron cannot be stimulated by impulses elicited by pain receptors associated with the first-order sensory neuron. In other words, the pain signal is effectively interrupted at the level of the spinal cord and does not travel any higher in the CNS. In this way, the brain does not perceive pain. 

The second-order sensory neuron transmits impulses ultimately to the left side of the brain. This permits the awareness of pain, identification of its source, and, if necessary, postural adjustment. As discussed, impulses in this pathway do not play a role in the reflex per se. 

Centrally mediated hyperalgesia involves the hyperexcitability of second-order sensory neurons in the dorsal horn of the spinal cord. In the case of severe or persistent tissue injury, C fibers fire action potentials... 

Stimulation of a nociceptor in the periphery of the body elicits action potentials in the first-order neuron, which transmits the signal to the second-order neuron in the dorsal horn of the spinal cord. From the spinal cord, the signal is transmitted to several regions of the brain. The most prominent ascending nociceptive pathway is the spinothalamic tract. Axons of the second-order sensory neurons project to the contralateral (opposite) side of the spinal cord and ascend in the white matter, terminating in the thalamus (see Figure 8.1). The thalamus contributes to the basic sensation or awareness of pain only it cannot determine the source of the painful stimulus. 

Referred pain most likely results from the convergence of visceral and somatic afferent fibers on the same second-order neurons in the dorsal horn of the spinal cord (see Figure 8.3). Therefore, the brain has no way of identifying the original source of the pain. Because superficial inputs normally predominate over visceral inputs, higher centers may incorrectly attribute the pain to the skin instead of the deeper tissue. 

Morphine may be administered orally, intravenously, or epidurally. An advantage of epidural administration is that it provides effective analgesia while minimizing the central depressant effects associated with systemic administration. The mechanism of action with the epidural route of administration involves opioid receptors on the cell bodies of first-order sensory neurons in the dorsal root ganglia as well as their axon terminals in the dorsal hom. Stimulation of these receptors inhibits release of substance P and interrupts transmission of the pain signal to the second-order sensory neuron. 

The Ap fibres are examples of afferents that stimulate inhibitory interneurones (in the substantia gelatinosa (SG)) and, therefore, prevent nociceptive transmission to the CNS. The C fibres are examples of afferents that inhibit inhibitory interneurones and, therefore, enhance nociceptive transmission. Note that both types of fibre stimulate the second-order neurone (2°) directly but it is the intemeurone that modifies the transmission. 

Impulse traffic in the neo- and pa-leospinothalamic pathways is subject to modulation by descending projections that originate from the reticular formation and terminate at second-order neurons, at their synapses with first-order neurons, or at spinal segmental interneurons (descending antinociceptive system). This system can inhibit impulse transmission from first- to second-order neurons via release of opio-peptides (enkephalins) or monoamines (norepinephrine, serotonin). 

Stimulation of 5-HT4 receptors on the presynaptic terminal of submucosal intrinsic primary afferent nerves enhances the release of their neurotransmitters, including calcitoningene-related peptide, which stimulate second-order enteric neurons to promote the peristaltic reflex (Figure 62-4). These enteric neurons stimulate proximal bowel contraction (via acetylcholine and substance P) and distal bowel relaxation (via nitric oxide and vasoactive intestinal peptide). 

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... 

Spinal sites of opioid action. Mu (v), delta (5), and kappa ( ) agonists reduce transmitter release from presynaptic terminals of nociceptive primary afferents. Mu-agonists also hyperpolarize second-order pain transmission neurons by increasing K+ conductance, evoking an inhibitory postsynaptic potential. 

Olfactory perception translates abstract chemical features of odorants into meaningful neural information to elicit appropriate behavioral responses (Shepherd, 1994 Buck, 1996). Specialized bipolar olfactory sensory neurons (OSNs) are responsible for the initial events in odor recognition. These have ciliated dendrites exposed to the environment, and a single axon that extends into the brain and forms synapses with second order projection neurons (PNs) (Shepherd, 1994 Buck, 1996). In arthropods and mammals, the first olfactory synapse is organized into glomeruli, spherical structures in which afferent olfactory neuron axons synapse with projection neuron dendrites (Hildebrand and Shepherd, 1997). 

The identification of DOR genes has permitted analysis of many different aspects of olfactory biology in the fruit fly. We now know the complete repertoire of genes that are likely to recognize odorants. Techniques exist to measure the response properties of a given OR and to examine the function of the neuron in vivo. The first- and second-order olfactory projections have been mapped anatomically. Although the fly is generally deemed to be too small for... 

Hains, B. C., Saab, C. Y., Klein, J. P., Craner, M. J., and Waxman, S. G. (2004). Altered sodium channel expression in second-order spinal sensory neurons contributes to pain after peripheral nerve injury. J. Neurosci. 24, 4832-4839. 

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