Central Mechanisms

A number of mechanisms may contribute significantly to the central facilitation of pain transmission:

• 'Wind-up'—responses of dorsal horn cells to nociceptive inputs display this phenomenon. When these neurones are repetitively stimulated at physiological frequencies, the synaptic potentials may steadily increase in amplitude with each stimulus. Since this facilitation can be blocked by






Blood and damaged tissue

Direct stimulation of nociceptors

Degranulation of mast cells to release histamine

Activation of kinin receptors on sympathetic nerves


Arachidonic acid

Stimulation of PGE2 and PGI2 receptors in sensory nerves

Release of Substance P from neurones

Increase Na+ conductance and lower threshold potential in neurones


Platelet and mast cells

Direct 5-HT3 receptor activation leading to increase Na+ permeability in sensory neurones

Activation of G-protein leading to decrease in K+ permeability

Decrease firing threshold of nociceptors


Mast cells

Direct action on H1 receptors in sensory neurones cells

Increase Ca2+ permeability

Release of other mediators from endothelial cells

Figure NE.16.

Figure NE.16.

Figure NE. 17 Transmission of pain signals in the spinal cord

both the N-methyl-D-aspartate (NMDA)-receptor antagonists and/or the antagonists of substance P, it is thought that substance P and NMDA receptors are involved in the central facilitation

• Nerve growth factor (NGF)—cytokine-like mediator produced by peripheral tissues during inflammation. It may act specifically on nociceptive afferent neurones, increasing their electrical excitability and facilitating the formation of synaptic contacts. Increased NGF production may be an important mechanism in the pathogenesis of hyperalgesia

• Increased gene expression—accompanies peripheral inflammation and activity in the nociceptive pathway. This may also play a part in long-term modulation

"Gate Control' Theory

'Gate control' theory was first proposed by Wall and Melzack in 1965. It describes how synaptic transmission between primary nociceptive neurones and secondary nociceptive neurones can be modulated or 'gated' by internuncial neurones. In particular inhibitory interneurones in the substantia gelatinosa can exert pre-synaptic inhibition on primary afferent neurones and post synaptic inhibition on secondary neurones, thus closing the 'gate' and decreasing the pain response to a nociceptive stimulus (Figure NE.18). These inhibitory internuncials may be activated by alternative primary afferents (e.g Ap mechanoreceptor afferents) to those responding to the nociceptive stimulus (Ay and C afferents). This enables activated pain fibres to be 'gated' out by other sensations such as rubbing, applied to the affected area. Examples of 'gating' at spinal level include:

• Transcutaneous nerve stimulation

• Dorsal column electrodes

Descending pathways from the brainstem may also activate inhibitory interneurones. It is probable that similar gating also operates at the thalamic level.

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