Structure and function of trigeminal primary sensory neurons after peripheral nerve injury

Iatrogenic injuries to branches of the trigeminal nerve are common during surgical procedures in the jaws and teeth, and as the repercussion of facial fractures or certain pathologies. A portion of these patients are left with disturbed sensory functions, and some with unpleasant abnormal sensations, including pain. The trigeminal nerve branches have unique characteristics, both in terms of their fibre compositions and their anatomical relationships. It is therefore important to study the specific responses upon injury to this nerve. This thesis has mainly focused on one of the most frequently injured trigeminal nerve branches, the inferior alveolar nerve, and on peripheral mechanisms that may contribute to injury-induced sensory abnormalities.

Electrophysiological recording central to various types of peripheral IAN injuries revealed, that diverse types of IAN injuries are capable of initiating similar raised levels of ectopic afferent activity in myelinated inferior alveolar nerve fibres. Additonal electrophysiological experiments showed that sympathetic nerve fibres at the site of injury do not appear to be essential for the development of ectopic neural activity in myelinated afferent fibres after inferior alveolar nerve injury.

Electron microscopical investigations of IAN injury sites revealed that only a few axonal endbulbs developed following inferior alveolar nerve injury. Thus, endbulbs do not appear to be essential for ectopic neural activity from myelinated afferents in this nerve. Instead, other axonal structures with less conspicuous ultrastructural characteristics must contribute to the abnormal discharge. Further, immunocytochemical ultrastructural investigations showed that sympathetic fibres of the inferior alveolar nerve appear to make relatively few abnormal membrane contacts with sensory axons at the site of injury after inferior alveolar nerve damage.

Immunocytochemical light microscopical investigations of trigeminal and dorsal root ganglia revealed, that sympathetic sprouting fails to develop in the trigeminal ganglion after peripheral nerve injury. Thus, such sprouting within sensory ganglia is not a general phenomenon after PNS injury, but appears to be restricted to specific locations.

In situ hybridisation investigations on the expression of the sodium channel subunit SNS/PN3 rnRNA within the trigeminal ganglion, revealed characteristic changes after inferior alveolar nerve injury which indicate that this a-subunit may be involved in the injury-induced hyperexcitability in orofacial regions. Further, in situ hybridisation and immunofluorescence studies indicated alterations in the synthesis of the sodium channel binding protein ankyrinG. This may also influence the development of sensory abnormalities after nerve damage.

List of scientific papers

I. Bongenhielm U, Robinson PP (1996). Spontaneous and mechanically evoked afferent activity originating from myelinated fibres in ferret inferior alveolar nerve neuromas. Pain. 67(2-3):399-406.
https://pubmed.ncbi.nlm.nih.gov/8951935

II. Bongenhielm U, Robinson PP (1998). Afferent activity from myelinated inferior alveolar nerve fibers in ferrets after constriction or section and regeneration. Pain. 74(2-3):123-132.
https://pubmed.ncbi.nlm.nih.gov/9520226

III. Bongenhielm U, Yates JM, Fried K, Robinson PP (1998). Sympathectomy does not affect the early ectopic discharge from myelinated fibres in ferret inferior alveolar nerve neuromas. Neurosci Lett. 245(2):89-92.
https://pubmed.ncbi.nlm.nih.gov/9605492

IV. Bongenhielm U, Robinson PP, Fried K. Ultrastructural changes in damaged axons after ligation or constriction of the inferior alveolar nerve in the ferret. [Manuscript]

V. Bongenhielm U, Boissonade FM, Westermark A, Robinson PP, Fried K Bongenhielm U, Boissonade FM, Westermark A, Robinson PP, Fried K (1999). Sympathetic nerve sprouting fails to occur in the trigeminal ganglion after peripheral nerve injury in the rat. Pain. 82(3):283-288.
https://pubmed.ncbi.nlm.nih.gov/10488679

VI. Bongenhielm U, Nosrat CA, Nosrat I, Eriksson J, Fjell J, Fried K. Expression of sodium channel SNS/NP3 and ankyrin(G) mRNAs in the trigeminal ganglion after inferior alveolar nerve injury in the rat. [Submitted]