Neurons dorsal horn

Afferent input from cutaneous and visceral nociceptors is known to converge on spinal neurons, which accounts for the referral of pain between visceral and cutaneous structures (e.g. cardiac pain gets referred to the chest and left upper arm in patients suffering from angina pectoris). Projection neurons in the spinal dorsal horn project to cell nuclei in supraspinal areas such as the thalamus, brainstem and midbrain. Of these, the synaptic junctions in the thalamus play a very important role in the integration and modulation of spinal nociceptive and non-nociceptive inputs. Nociceptive inputs are finally conducted to the cortex where the sensation of pain is perceived (Fig. 1). The mechanisms via which the cortex processes nociceptive inputs are only poorly understood. 

P2X X CM CL Smooth muscle, platelets, cerebellum, dorsal horn spinal neurons a, 3-meATP = ATP = 2-MeSATP, L-p.y-meATP (rapid desensitization) TNP-ATP, lp5l, NF023, NF449 Intrinsic cation channel (Ca2+ and Na+)... 

Fig. 4.1 Hypothetical model of pathogenesis of pain in DSP. (1) Injury of peripheral nerve fibers due to multifocal inflammation and secreted macrophage activation products results in abnormal spontaneous activity of neighboring uninjured nociceptive fibers ( peripheral sensitization ). (2) Furthermore, the aberrant inflammatory response in DRG leads to alterations in neuronal sodium and calcium channel expression and ectopic impulse generation. (3) This results in central remodeling within the dorsal horn due to A-fiber sprouting and synaptic formation with pain fibers in lamina 11, and maintenance of neuropathic pain ( central sensitization ). Reproduced with permission from (Keswani et al. 2002)...

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...

Figure 13.3 Whole-cell patch-clamp recordings of excitatory postsynaptic currents (EPSCs) from dorsal horn neurons of rat (prenatal P2-13) spinal cord slices. The normal evoked EPSC of about 160pA obtained by focal stimulation of nearby tissue was dramatically reduced by addition of a cocktail (CABS) of CNQX 10 pM, D-APV 50 pM, bicuculline 10 pM and strychnine 5 pM to block glutamate, GABAa and glycine receptors. The small residual EPSC shown was blocked by the ATP P2 receptor antagonist suramin and is therefore probably mediated by released ATP. (Prom Bardoni et al. 1997 and reproduced by permission of the Journal of Neuroscience)...

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... 

Figure 21.3 Wind-up in a dorsal horn neuron. Note the increased response to a constant peripheral stimulus as the NMDA receptor is activated. (Unpublished data)...

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. 

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... 

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. 

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. 

Fleetwood-Walker S., Hope P., Mitchell R. (1988). Antinociceptive actions of descending dopaminergic tracts on cat and rat dorsal horn somatosensory neurones. J. Physiol, bond. 399, 335-48. 

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. 

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)... 

Inflammatory pain results from changes both in primary sensory and dorsal horn neurons 933 Peripheral sensitization lowers nociceptor activation threshold 933... 

Central sensitization results in hyper-responsive dorsal horn neurons 933... 

FIGURE 57-3 Transmission between primary sensory and dorsal horn neurons is subject to pre- and postsynaptic excitatory and inhibitory... 

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