This article reviews some recent findings on peripheral mechanisms related to the development of oro-facial pain after trigeminal nerve injury. Chronic injury-induced oro-facial pain is not in itself a life-threatening condition, but patients suffering from this disorder undoubtedly have a reduced quality of life. The vast majority of the work on pain mechanisms has been carried out in spinal nerve systems. Those studies have provided great insight into mechanisms of neuropathic spinal pain, and much of the data from them is obviously relevant to studies of trigeminal pain. However, it is now clear that the pathophysiology of the trigeminal nerve (a cranial nerve) is in many ways different to that found in spinal nerves. Whereas some of the changes seen in animal models of trigeminal nerve injury mimic those occurring after spinal nerve injury (e.g., the development of spontaneous activity from the damaged axons), others are different, such as the time-course of the spontaneous activity, some of the neuropeptide changes in the trigeminal ganglion, and the lack of sprouting of sympathetic terminals in the ganglion. Recent findings provide new insights that help our understanding of the etiology of chronic injury-induced oro-facial pain. Future investigations will hopefully explain how data gained from these studies relate to clinical pain experience in man and should enable the rapid development of new therapeutic regimes.

The vanilloid receptor VR1 and the vanilloid receptor-like protein VRL-1 are associated with polymodal nociceptors, and may be important for pain processing in normal and injured teeth. Using immunohistochemistry, we have studied the distribution of these receptors in rat pulpal or gingival trigeminal ganglion neurons that were identified through retrograde labeling with fluoro-gold. Twenty-one percent to 34% of tooth pulp-innervating neurons were VRl-positive, while 32%-51% were VRL-1-immunoreactive. However, double-labeling experiments revealed that VR1 and VRL-1 rarely co-existed in the same cells, but rather seemed to be confined to separate subpopulations. Among the gingival neurons, about 25% were VR1-positive and about 41% were VRL-1-immunoreactive. A lesion of the inferior alveolar nerve, which supplies mandibular teeth and gingiva, resulted in a marked down-regulation of VR1 in the affected trigeminal ganglion cells. A down-regulation of VRL-l was also indicated. The results suggest that both VR1 and VRL-1 could have significant roles in pulpal and gingival nociceptive transduction.

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Peripheral nerve injury induces sprouting of sympathetic nerve fibers in dorsal root ganglia after spinal nerve injury. In the present study, we sought to determine the extent of intraganglionic noradrenergic sprouting in the trigeminal system. The inferior alveolar nerve, a major branch of the mandibular division, or the infraorbital nerve of the maxillary division was either ligated or chronically constricted in Sprague-Dawley rats and recovery permitted for either 2-3 or 6-9 weeks. In some animals both nerves were injured. Using immunohistochemistry with tyrosine hydroxylase antibodies, we found no signs of sympathetic nerve fiber sprouting in the trigeminal ganglion after injury. In contrast, sciatic nerve injury in rat littermates induced a widespread autonomic nerve outgrowth in affected DRGs. Thus, sensory ganglion sympathetic nerve sprouting does not seem to be a general outcome of PNS injury, but is restricted to certain specific locations. Sympathetic nerve fiber networks that surround primary sensory neurons have been suggested to form a structural basis for interactions between the sympathetic and sensory nervous systems after PNS injury. Such interactions, sometimes resulting in paraesthesia or dysaesthesia in patients, appear to be less common in territories innervated by the trigeminal nerve than in spinal nerve regions. The lack of injury-induced intraganglionic sympathetic sprouting in the trigeminal ganglion may help to explain this observation.