Pathway 13-7-6 DETECTION First Step - TISSUE INJURY AND DEAFFERENTATION

Study Notes

Deafferentation is the interruption of afferent input to the CNS due to nerve injury.
While anesthesia is expected, deafferentation can surprisingly lead to pain.
Following nerve damage, neurons undergo significant transcriptional changes, impacting neuropeptides, receptors and sodium channels.
These changes occur as the connection between the nerve cell and peripheral target tissue is lost.
Neurons then transition to either regeneration or cell death.
The trigeminal ganglion, responsible for sensory innervation of the teeth, is particularly vulnerable to deafferentation.

Tooth injury, especially pulp exposure, elicits neural changes both in the trigeminal ganglion and the brainstem.
Pulp extirpation (removal), with its 2000 nerve fibers, triggers neurochemical and degenerative changes in the trigeminal ganglion.
The central projection of these nerves to the spinal nucleus of the trigeminal nerve is also affected, leading to transsynaptic changes.
Tooth extraction, involving both periodontal ligament and pulpal innervation destruction, results in even more pronounced neuronal changes.
These changes, particularly in the trigeminal ganglion and brainstem, significantly impact the central nervous system.

Deafferentation can lead to central sensitization, a condition characterized by an altered sensory perception.
Central sensitization is triggered by the deprivation of normal sensory input to the dorsal horn neurons.
This deprivation makes the neurons hypersensitive to other afferents, leading to a widening of the sensory receptive field.
Phantom tooth pain, often associated with deafferentation, arises from central sensitization.

Following tissue injury or inflammation, sensory ganglion neurons exhibit significant gene expression changes.
These changes extend to their central projections through transsynaptic pathways.
The upregulation of genes like c-fos and sodium channels contributes to altered threshold properties and receptive field size.
C-fos, not normally expressed in brainstem neurons, exhibits prolonged expression in specific brain stem neurons due to chronic pulpitis.

Nerve sprouting, a response to injury, may play a role in central sensitization and persistent pain.
Sprouting of peripheral nerves following pulpitis can transport signaling molecules retrogradely to the cell body, potentially inducing central sensitization.
Reports have confirmed nerve sprouting in inflamed human pulps, suggesting its role in both dentin sensitivity and receptive field expansion.
While the functional implications and their relation to pain mechanisms remain unclear, these reactions are likely involved in healing and nociception after pulpal inflammation.

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