Dorsal horn of spinal

X3 NM 002559 Dorsal root ganglion, superficial dorsal horn of spinal cord, a subset of small-diameter sensory neurons, nucleus of the solitary tract, spinal trigeminal nucleus (important for peripheral pain)... 

On intrathecal injection, it acts on substantia gelatinosa of dorsal horn of spinal cord and inhibit the release of excitatory transmitters. At supraspinal sites, it acts on medulla, mid brain, limbic and cortical areas. 

Dorsal horn of spinal cord, cuneate and gracile nuclei and analogous portions of trigeminal nuclei... 

As a neurotransmitter in the sensory nervous system, high levels of substance P are found in the dorsal horn of the spinal cord as well as in peripheral sensory nerve terminals. However, substance P also plays a significant role as a neuromodulator in the central, sympathetic, and enteric nervous system. NKA and NKB are also localized selectively in the CNS. 

The substantia gelatinosa is part of the dorsal horn of the spinal cord, also called lamina II . The substantia gelatinosa is made up almost exclusively of interneurons (both excitatory and inhibitory), some of which respond only to nociceptive inputs, while others respond also to non-noxious stimuli. 

Figure 1.6 Presynaptic inhibition of the form seen in the dorsal horn of the spinal cord, (a) The axon terminal (i) of a local neuron is shown making an axo-axonal contact with a primary afferent excitatory input (ii). (b) A schematic enlargement of the synapse, (c) Depolarisation of the afferent terminal (ii) at its normal resting potential by an arriving action potential leads to the optimal release of neurotransmitter, (d) When the afferent terminal (ii) is already partially depolarised by the neurotransmitter released onto it by (i) the arriving acting potential releases less transmitter and so the input is less effective...

Bardoni, R, Goldstein, PA, Justin Lee, C, Gee, JG and MacDermott, AB (1997) ATP P2x receptors mediate fast synaptic transmission in the dorsal horn of the rat spinal cord. J. Neurosci. 17 5297-5304. 

The large diameter A/l-afferent fibre enters the dorsal horn of the spinal cord through the medial division of the dorsal root. It then descends through the medial region of lamina I or II, or alternatively, curves around the medial (central) edge of the dorsal horn down to the ventral horn. On reaching deeper laminae, laminae IV and V, the AjS-fibres ascend back up into laminae III and IV where they repeatedly subdivide and form a characteristic termination pattern. The densest arborisation appears to occur in lamina III. Axons originating from specialised muscle stretch receptors have collaterals that pass ventrally to make monosynaptic connections with neurons of laminae V, VI and VII. Some also extend to laminae VIII and IX of the ventral horn where they synapse directly onto motor neurons and form the basis of monosynaptic reflexes. 

The arrival of action potentials in the dorsal horn of the spinal cord, carrying the sensory information either from nociceptors in inflammation or generated both from nociceptors and intrinsically after nerve damage, produces a complex response to pain. Densely packed neurons, containing most of the channels, transmitters and receptors found anywhere in the CNS, are present in the zones where the C-fibres terminate... 

Opioids act in the brain and within the dorsal horn of the spinal cord, where their actions are better understood. The actions of opioids important for analgesia and their side-effects involve pre- and postsynaptic effects (1) reduced transmitter release from nerve terminals so that neurons are less excited by excitatory transmitters, and (2) direct inhibitions of neuronal firing so that the information flow from the neuron is reduced but also inhibitions of inhibitory neurons leading to disinhibition. This dual action of opioids can result in a total block of sensory inputs as they arrive in the spinal cord (Fig. 21.5). Thus any new drug would have to equal this dual action in controlling both transmitter release and neuronal firing. 

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. 

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. 

Endorphins are found primarily in the limbic system, hypothalamus, and brainstem. Enkephalins and dynorphin (in smaller quantities) are found primarily in the periaqueductal gray matter (PAG) of the midbrain, the limbic system, and the hypothalamus. These endogenous substances mimic the effects of morphine and other opiate drugs at many points in the analgesic system, including in the dorsal horns of the spinal cord. 

Pain inhibitory complex in the dorsal horns of the spinal cord... 

Figure 8.2 The endogenous analgesic system. The three major components of the endogenous analgesic system include the periaqueductal gray matter in the midbrain nucleus raphe magnus in the medulla and pain inhibitory complex in the dorsal horns of the spinal cord. This system causes presynaptic inhibition of pain fibers entering the spinal cord. The binding of enkephalin to opioid receptors on the pain fibers prevents release of the neurotransmitter, substance P. As a result, the pain signal is terminated in the spinal cord and does not ascend to higher centers in the CNS.

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. 

FIGURE 1-10 An axonal terminal at the surface of a neuron from the dorsal horn of a rabbit spinal cord contains both dense-core and clear, spherical synaptic vesicles lying above the membrane thickenings. A subsurface cisterna (arrow) is also seen. x68,000. 

Moore, K. A. et al. Partial peripheral nerve injury promotes a selective loss of GABAergic inhibition in the superficial dorsal horn of the spinal cord. /. Neurosci. 22 6724-6731, 2002. 

In addition to the physiological process of autoinhibition, another mechanism of presynaptic inhibition has been identified in the peripheral nervous system, although its precise relevance to the brain is unclear. In the dorsal horn of the spinal cord, for example, the axon terminal of a local neuron makes axo-axonal contact with a primary afferent excitatory input, which leads to a reduction in the neurotransmitter released. This is due to the local neuron partly depolarizing the nerve terminal, so that when the axon potential arrives, the change induced is diminished, thereby leading to a smaller quantity of transmitter being released. In the brain, it is possible that GABA can cause presynaptic inhibition in this way. 

Zhang C, Davies MF, Guo TZ, Maze M (1999) The analgesic action of nitrous oxide is dependent on the release of norepinephrine in the dorsal horn of the spinal cord. Anesthesiology 91,1401-1407... 

Cells in the substantia gelatinosa (lamina II contains highest levels of opioid binding) of the dorsal horn of the spinal cord respond to incoming nociceptive stimuli and regulate, or gate, the transmission of nociceptive impulses to other pathways within the CNS via the... 

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