Modulation of Trigeminal Spinal Subnucleus Caudalis Neuronal Activity Following Regeneration of Transected Inferior Alveolar Nerve in Rats (original) (raw)
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Journal of Neuroscience, 2012
The transection of the inferior alveolar nerve (IANx) produces allodynia in the whisker pad (V2 division) of rats. Ectopic discharges from injured trigeminal ganglion (TG) neurons and thalamocortical reorganization are possible contributors to the sensitization of uninjured V2 primary and CNS neurons. To test which factor is more important, TG and ventroposterior medial nucleus (VPM) neurons were longitudinally followed before, during, and after IANx for up to 80 d. Spontaneous discharges and mechanical stimulation-evoked responses were recorded in conscious and in anesthetized states. Results show (1) a sequential increase in spontaneous activities, first in the injured TG neurons of the IAN (2-30 d), followed by uninjured V2 ganglion neurons (6-30 d), and then VPM V2 neurons (7-30 d) after IANx; (2) ectopic discharges included burst and regular firing patterns in the IAN and V2 branches of the TG neurons; and (3) the receptive field expanded, the modality shifted, and long-lasting after-discharges occurred only in VPM V2 neurons. All of these changes appeared in the late or maintenance phase (7-30 d) and disappeared during the recovery phase (40-60 d). These observations suggest that ectopic barrages in the injured IAN contribute more to the development of sensitization, whereas the modality shift and evoked after-discharges in the VPM thalamic neurons contribute more to the maintenance phase of allodynia by redirecting tactile information to the cortex as nociceptive.
Preliminary results and evidence of early regeneration in inferior alveolar nerve fibers
Surgical and Radiologic Anatomy, 2002
Inferior alveolar nerve (IAN) damage can occur in trauma, cyst enucleation, sagittal split osteotomy or third molar removal, and the consequences are a loss of sensation to the mandibular teeth, gingiva and lower lip. Because of its anatomical position in a bony canal, IAN suture is rarely evoked. The aim of this study was to demonstrate the reality of IAN regeneration by using electrophysiological and histological methods after experimental section and suture of this nerve in rabbits. Nine adult female animals were used for the experiments. Six months after section and suturing using 10.0 nylon with a conventional technique, electrical stimulation of the nerve was performed to record electrophysiological activity. Each rabbit was its own reference. In each case, an action potential was recorded after microsurgical repair and definitively suppressed by section of the nerve. Morphometric analysis showed a decrease in the number of nerve fibers in the operated nerve versus the control nerve. The histological study showed an increase in nerve fibers with a cross-sectional area of 19–36 and 37–73 µm2 and a decrease in the smaller fibers (2–4 and 5–7 µm2). This preliminary study confirms the possibility of nerve regeneration in rabbits 6 months after section and conventional suturing. The French version of this article is available in the form of electronic supplementary material and can be obtained by using the Springer Link server located at http://dx.doi.org/10.1007/s00276-002-0068-8\. Les lésions du nerf alvéolaire inférieur (NAI) peuvent survenir en cas de traumatisme, d'énucléation de kyste, d'ostéotomie sagittale ou d'avulsion de troisième molaire et entraînent une perte de sensibilité des dents mandibulaires, de la gencive et de la lèvre inférieure. En raison de sa situation anatomique au sein d'un canal osseux, la suture du NAI est rarement envisagée. Le but de cette étude était de démontrer la réalité de la régénération du NAI à l'aide de méthodes électrophysiologique et histologique après section expérimentale et suture chez le lapin. Neuf animaux adultes femelles ont été utilisés pour l'expérimentation. Six mois après section et suture conventionnelle à l'aide de fils de suture en nylon 10.0, une stimulation électrique du nerf a été réalisée afin d'enregistrer l'activité électrophysiologique. Chaque lapin était sa propre référence. Dans chaque cas, un potentiel d'action a été enregistré après réparation microchirurgicale et définitivement supprimé par la section du nerf. Une analyse morphométrique a souligné la diminution du nombre des fibres nerveuses chez le lapin opéré versus le lapin témoin. Une étude histologique a montré une augmentation du nombre des fibres nerveuses ayant une surface, en section transversale, comprise entre 19–36 µm2 et 37–73 µm2, et une diminution de celles ayant une surface comprise entre 2–4 et 5–7 µm2. Cette étude préliminaire confirme la possibilité d'une régénération nerveuse chez le lapin, six mois après section et suture conventionnelle.
Neuronal plasticity of trigeminal ganglia in mice following nerve injury
Journal of Pain Research, 2017
Background: Nerve injury may induce neuropathic pain. In studying the mechanisms of orofacial neuropathic pain, attention has been paid to the plastic changes that occur in the trigeminal ganglia (TGs) and nucleus in response to an injury of the trigeminal nerve branches. Previous studies have explored the impact of sciatic nerve injury on dorsal root ganglia (DRGs) and it has shown dramatic changes in the expression of multiple biomarkers. In large, the changes in biomarker expression in TGs after trigeminal nerve injury are similar to that in DRGs after sciatic nerve injury. However, important differences exist. Therefore, there is a need to study the plasticity of biomarkers in TGs after nerve injury in the context of the development of neuropathic pain-like behaviors. Aim: The aim of this study was to investigate the plasticity of biomarkers associated with chronic persistent pain in TGs after trigeminal nerve injury. Materials and methods: To mimic the chronic nature of the disorder, we used an intraoral procedure to access the infraorbital nerve (ION) and induced a nerve injury in mice. Immunohistochemistry and quantification were used for revealing the expression level of each biomarker in TGs after nerve injury. Results: Two weeks after partial ION injury, immunohistochemistry results showed strongly upregulated expressions of activating transcription factor 3 and neuropeptide Y (NPY) in the ipsilateral TGs. Microglial cells were also activated after nerve injury. In regard to positive neuronal profile counting, however, no significant difference in expression was observed in galanin, substance P, calcitonin gene-related peptide, neuronal nitric oxide synthase, phosphorylated AKT, or P2X3 in ipsilateral TGs when compared to contralateral TGs. Conclusion: In this study, the expression and regulation of biomarkers in TGs have been observed in response to trigeminal nerve injury. Our results suggest that NPY and Iba1 might play crucial roles in the pathogenesis of orofacial neuropathic pain following this type of injury. Further investigations on the relevance of these changes may help to target suitable treatment possibilities for trigeminal neuralgia.
Pain, 2002
Induction of Fos protein-like immunoreactivity in the trigeminal spinal nucleus caudalis and upper cervical cord following noxious and nonnoxious mechanical stimulation of the whisker pad of the rat with an inferior alveolar nerve transection Abstract After transection of the inferior alveolar nerve (IAN: the third branch of the trigeminal nerve), the whisker pad area, which is innervated by the second branch of the trigeminal nerve, showed hypersensitivity to mechanical stimulation. Two days after IAN transection, the threshold intensity for escape behavior to mechanical stimulation of the ipsilateral whisker pad area was less than 1.0 g, a sign of allodynia, and returned to the preoperative level (preoperative threshold: 52.0 g) at 32 days after surgery. This decrement of escape threshold lasted for more than 3 weeks. The whisker pad area contralateral to the IAN transection also showed a decrease in escape threshold to non-noxious mechanical stimulation as compared with sham-operated rats. However, the change in threshold intensity for the side contralateral to transection was not as pronounced as that on the ipsilateral side. Fos protein-like immunoreactive (LI) cells were observed in the superficial laminae but not dominant in deeper laminae of the trigeminal spinal nucleus caudalis (Vc) and the first segment of the spinal cord (C1) after non-noxious mechanical stimulation of the whisker pad area in the rats with IAN transection. Fos protein-LI cells were expressed bilaterally in the Vc and C1, but were more numerous on the ipsilateral side to transection than on the contralateral side. The largest number of Fos protein-LI cells was observed at 2400 mm caudal from the trigeminal subnucleus interporalis (Vi)-Vc border both in ipsilateral and contralateral sides. The number of Fos protein-LI cells increased after application of 1, 4, and 16 g stimuli as compared to rats without mechanical stimulation. Furthermore, an extensively greater number of Fos protein-LI cells were expressed both in superficial and deep laminae of the bilateral Vc and C1 of the spinal cord after subcutaneous injection of mustard oil into the whisker pad. Fos protein expression after mustard oil injection was much stronger than that observed after any mechanical stimulation in the rats with IAN transection. These data suggest that the change in the numbers and spatial arrangement of nociceptive neurons in the Vc and C1 after IAN transection reflect the development of mechanical hyperalgesia in the area adjacent to the IAN innervated region. Pain 95 (2002) 225-238
Journal of Neurotrauma, 2013
Nerve-related complications have been frequently reported in dental procedures, and a very frequent type of occurrence involves the inferior alveolar nerve (IAN). The nerve injury in humans often results in persistent pain accompanied by allodynia and hyperalgesia. In this investigation, we used an experimental IAN injury in rats, which was induced by a Crile hemostatic clamp, to evaluate the effects of laser therapy on nerve repair. We also studied the nociceptive behavior (von Frey hair test) before and after the injury and the behavioral effects of treatment with laser therapy (emitting a wavelength of 904 nm, output power of 70 Wpk, a spot area of *0.1 cm 2 , frequency of 9500 Hz, pulse time 60 ns and an energy density of 6 J/cm 2). As neurotrophins are essential for the process of nerve regeneration, we used immunoblotting techniques to preliminarily examine the effects of laser therapy on the expression of nerve growth factor (NGF) and brainderived neurotrophic factor (BDNF). The injured animals treated with laser exhibited an improved nociceptive behavior. In irradiated animals, there was an enhanced expression of NGF (53%) and a decreased BDNF expression (40%) after laser therapy. These results indicate that BDNF plays a locally crucial role in pain-related behavior development after IAN injury, increasing after lesions (in parallel to the installation of pain behavior) and decreasing with laser therapy (in parallel to the improvement of pain behavior). On the other hand, NGF probably contributes to the repair of nerve tissue, in addition to improving the pain-related behavior.
Trigeminal ganglion cell response to mental nerve transection and repair in the rat
Journal of Oral and Maxillofacial Surgery, 1999
Animal studies have suggested that peripheral nerve transection results in substantial loss of ganglion cells and the selective survival of cells based on size. The implications are that subsequent repair of peripheral nerve injuries will be determined by the numerical density and character of the surviving cells. The purpose of this study was twofold: First, to determine the effect of mental nerve transection without repair on trigeminal ganglion cell density and morphology in adult rats, and second, to determine the variation of trigeminal ganglion cell density and morphology after immediate and delayed repair. Materials and Methods: *Professor, Department of Oral and Maxillofacial Surgery, Univer-delayed repair of the transected nerve altered sity of North Carolina at Chapel Hill, School of Dentistry, Chapel the spectrum of surviving cells based on size or Hill, NC.
Properties of nociceptive and non-nociceptive neurons in trigeminal subnucleus oralis of the rat
Brain Research, 1990
Recent studies have provided evidence suggesting the involvement of rostral components of the V brainstem complex such as trigeminal (V) subnucleus oralis in orofacial pain mechanisms. Since there has been no detailed investigation of the possible existence of nociceptive oralis neurons in the rat to substantiate this recent evidence, the present study was initiated to determine if neurons responsive to noxious orofacial stimuli were present in subnucleus oralis and to characterize their functional properties. In anesthetized rats, recordings were made of the extracellular activity of single neurons functionally characterized as low-threshold mechanoreceptive (LTM), wide dynamic range (WDR) or nociceptive-specific (NS) neurons. The 342 LTM neurons responded only to light mechanical stimulation of orofacial tissues. The mechanoreceptive field of the LTM neurons included the intraoral region in 28% and was localized to the adjacent perioral area in 65%. For 95% the field was localized within one V division. Responses evoked in LTM neurons by electrical stimulation of the orofacial mechanoreceptive field revealed A fiber afferent inputs but no activity that could be attributed to C fiber afferent inputs. The 72 nociceptive neurons included 52 WDR neurons which responded to light (e.g. tactile) as well as noxious (e.g. heavy pressure; pinch) mechanical stimulation of perioral cutaneous and intraoral structures, and 20 NS neurons which responded exclusively to noxious mechanical stimuli. They also differed from the LTM neurons in that 36% of the WDR and 20% of the NS neurons had a mechanoreceptive field involving more than one V division. However, in accordance with our findings for the LTM neurons, the majority of WDR and NS neurons had a mechanoreceptive field involving the intraoral and perioral representations of the mandibular and/or maxillary divisions; those neurons having a mandibular field which especially included intraoral structures predominated in the dorsomedial zone of subnucleus oralis whereas those with a perioral mechanoreceptive field which particularly involved the maxillary division were concentrated in the ventrolateral zone of oralis. In contrast to the LTM neurons, 57% of the WDR and 67% of the NS neurons showed evidence of electrically evoked C fiber as well as A fiber afferent inputs from their mechanoreceptive field. We also noted suppression of the electrically evoked responses by heating of the tail or pinching of the paw. This effect was considered to be a reflection of diffuse noxious inhibitory controls, and was seen in NS as well as WDR neurons; most, but not all, of these neurons received A fiber as well as C fiber orofacial afferent inputs. These findings provide support for recent evidence suggesting that V subnucleus oralis is an important element in orofacial pain processing, and further indicate that oralis may be involved particularly in intraoral and perioral nociceptive mechanisms.
Neuroscience, 2001
Changes in neuropeptide expression in afferent nerve fibres may play a role in the persistent sensory abnormalities that can be experienced following trigeminal nerve injuries. We have therefore studied changes in the expression of the neuropeptides substance P, calcitonin gene-related peptide, enkephalin, galanin, neuropeptide Y and vasoactive intestinal polypeptide in the trigeminal ganglion following peripheral nerve injury. In anaesthetised adult female ferrets, the left inferior alveolar nerve was sectioned and recovery allowed for three days, three weeks or 12 weeks prior to perfusion-fixation. During a second procedure, one week prior to perfusion, the inferior alveolar nerve was exposed and an injection made central to the injury site using a mixture of 4 % Fluorogold and 4 % isolectin B4 conjugated to horseradish peroxidase to identify cell bodies with axons in the inferior alveolar nerve and cells with unmyelinated axons within this population, respectively. Control animal...