Extracellular ATP and cAMP signaling promote Piezo2-dependent mechanical allodynia after trigeminal nerve compression injury.

Trigeminal neuralgia (TN) is a type of severe paroxysmal neuropathic pain commonly triggered by mild mechanical stimulation in the orofacial area. Piezo2, a mechanically gated ion channel that mediates tactile allodynia in neuropathic pain, can be potentiated by a cyclic adenosine monophosphate (cAMP)-dependent signaling pathway that involves the exchange protein directly activated by cAMP 1 (Epac1). To study whether Piezo2-mediated mechanotransduction contributes to peripheral sensitization in a rat model of TN after trigeminal nerve compression injury, the expression of Piezo2 and activation of cAMP signal-related molecules in the trigeminal ganglion (TG) were detected. Changes in purinergic P2 receptors in the TG were also studied by RNA-seq. The expression of Piezo2, cAMP, and Epac1 in the TG of the TN animals increased after chronic compression of the trigeminal nerve root (CCT) for 21 days, but Piezo2 knockdown by shRNA in the TG attenuated orofacial mechanical allodynia. Purinergic P2 receptors P2X4, P2X7, P2Y1, and P2Y2 were significantly up-regulated after CCT injury. In vitro, Piezo2 expression in TG neurons was significantly increased by exogenous adenosine 5'-triphosphate (ATP) and Ca2+ ionophore ionomycin. ATP pre-treated TG neurons displayed elevated [Ca2+ ]i and faster increase in responding to blockage of Na+ /Ca2+ exchanger by KB-R7943. Furthermore, mechanical stimulation of cultured TG neurons led to sustained elevation in [Ca2+ ]i in ATP pre-treated TG neurons, which is much less in naïve TG neurons, or is significantly reduced by Piezo2 inhibitor GsMTx4. These results indicated a pivotal role of Piezo2 in peripheral mechanical allodynia in the rat CCT model. Extracellular ATP, Ca2+ influx, and the cAMP-to-Epac1 signaling pathway synergistically contribute to the pathogenesis and the persistence of mechanical allodynia.

Cranial nerve V2 and Vidian nerve trauma secondary to lateral pterygoid recess encephalocele repair.

BACKGROUND: The incidence of adverse sequelae related to trauma of cranial nerve V2 (V2) and the Vidian nerve (VN) during endoscopic pterygoid recess repair (PRR) of lateral sphenoid encephalocele is insufficiently reported in the medical literature. As part of our quality assessment and improvement program we sought to analyze the incidence and severity of V2 and VN injury during a 9-year experience (2010-2018) with PRR. METHODS: Hypoesthesia, paresthesia, and dry eye and their impact on patient quality of life were sought through chart review and a self-reported 0 to 5 Likert scale for each symptom. RESULTS: Thirty-five patients underwent repair of spontaneous cerebrospinal-fluid (CSF) rhinorrhea, with 11 consecutive patients undergoing endoscopic PRR. Mean follow-up for PRR was 32.5 months (range, 2.4 to 103.3 months). Although definitive management resulted in 100% success, 1 required secondary treatment. Eight patients were available for long-term follow-up (72.7%) and completed a symptom severity questionnaire using a Likert-scale. All patients observed either hypoesthesia, paresthesia, or dry eye of varying gradation (scale, 0 to 5). None described disabling symptoms, and some reported gradual improvement. Numbness, paresthesia, and dry eye were reported by 6 of 8 (75%), 5 of 8 (62.5%), and 4 of 8 (50%) patients, respectively. The mean Likert score among the 8 patients who completed this questionnaire noticing hypoesthesia, paresthesia, and dry eye was 2.6, 1.3, and 1.8, respectively. CONCLUSION: Meticulous surgical technique is paramount for successful PRR and minimizing nerve injury, yet the anatomic variation of the lateral pterygoid recess can be challenging, and neural injury is a real risk. Preoperatively, patients should be counseled that although V2 or VN injury is common, most patients describe resulting symptoms to be rarely bothersome.

Increase in IGF-1 Expression in the Injured Infraorbital Nerve and Possible Implications for Orofacial Neuropathic Pain.

Insulin-like growth factor-1 (IGF-1) is upregulated in the injured peripheral nerve bundle and controls nociceptive neuronal excitability associated with peripheral nerve injury. Here, we examined the involvement of IGF-1 signaling in orofacial neuropathic pain following infraorbital nerve injury (IONI) in rats. IONI promoted macrophage accumulation in the injured ION, as well as in the ipsilateral trigeminal ganglion (TG), and induced mechanical allodynia of the whisker pad skin together with the enhancement of neuronal activities in the subnucleus caudalis of the spinal trigeminal nucleus and in the upper cervical spinal cord. The levels of IGF-1 released by infiltrating macrophages into the injured ION and the TG were significantly increased. The IONI-induced the number of transient receptor potential vanilloid (TRPV) subfamily type 4 (TRPV4) upregulation in TRPV subfamily type 2 (TRPV2)-positive small-sized, and medium-sized TG neurons were inhibited by peripheral TRPV2 antagonism. Furthermore, the IONI-induced mechanical allodynia was suppressed by TRPV4 antagonism in the whisker pad skin. These results suggest that IGF-1 released by macrophages accumulating in the injured ION binds to TRPV2, which increases TRPV4 expression in TG neurons innervating the whisker pad skin, ultimately resulting in mechanical allodynia of the whisker pad skin.

Stereotyped transcriptomic transformation of somatosensory neurons in response to injury.

In mice, spared nerve injury replicates symptoms of human neuropathic pain and induces upregulation of many genes in somatosensory neurons. Here we used single cell transcriptomics to probe the effects of partial infraorbital transection of the trigeminal nerve at the cellular level. Uninjured neurons were unaffected by transection of major nerve branches, segregating into many different classes. In marked contrast, axotomy rapidly transformed damaged neurons into just two new and closely-related classes where almost all original identity was lost. Remarkably, sensory neurons also adopted this transcriptomic state following various minor peripheral injuries. By genetically marking injured neurons, we showed that the injury-induced transformation was reversible, with damaged cells slowly reacquiring normal gene expression profiles. Thus, our data expose transcriptomic plasticity, previously thought of as a driver of chronic pain, as a programed response to many types of injury and a potential mechanism for regulating sensation during wound healing.

Restoration of the Topological Organization of the Trigeminal System Following Trigeminal Nerve Root Injury in the Lamprey.

Two issues were examined regarding the trigeminal system in larval lampreys: (1) for normal animals, double labeling was used to confirm that the trigeminal system has a topological organization; (2) following trigeminal nerve root transections, double labeling was used to test whether the topological organization of the trigeminal system is restored. First, for normal animals, Alexa 488 dextran amine applied to the medial oral hood (anterior head) labeled trigeminal motoneurons (MNs) in the ventromedial part of the trigeminal motor nuclei (nVm) and axons of trigeminal sensory neurons (SNs) in the ventromedial part of the trigeminal descending tracts (dV). Also, Texas red dextran amine (TRDA) applied to the lateral oral hood labeled trigeminal MNs in the dorsolateral nVm and sensory axons in the dorsolateral dV. These results confirm the topological organization of the trigeminal system of normal lampreys. Second, following trigeminal nerve root transections, the physical integrity of the nerves was restored during growth of trigeminal sensory and motor axons. In addition, double labeling indicated a restoration and refinement of the topological organization of the trigeminal system with increasing recovery times, but mainly for nVm. Despite the paucity of growth of trigeminal sensory axons in dV even at long recovery times (12-16 wks), a substantial percentage of experimental animals recovered trigeminal-evoked swimming responses and trigeminal-evoked synaptic responses in reticulospinal (RS) neurons. Following trigeminal nerve root injury, several mechanisms, including axonal guidance cues, probably contribute to the substantial restoration of the topological organization of the lamprey trigeminal system.

Effects of inferior alveolar nerve rupture on bone remodeling of the mandible: A preliminary study.

Although various animal studies have indicated that sensory nerves played an important role in bone metabolism and nerve injury could impair the process of bone remodeling, the actual effect of sensory nerve rupture on human bones remains unclear. The aim of this preliminary study was to investigate the effect of inferior alveolar nerve (IAN) rupture on mandibular bone remodeling of patients underwent bilateral sagittal split ramus osteotomy (BSSRO).Ten patients with unilateral IAN rupture during BSSRO were involved in this study. Neurosensory examinations were employed to assess the sensory function of bilateral IAN. The remodeling process of the post-operational mandible was evaluated by panoramic radiographs and computed tomography (CT) scans.Neurosensory examinations indicated that nerve rupture resulted in significant hypoesthesia at the IAN-rupture side. Assessment of panoramic radiographs showed no evident alterations of bone structure at the IAN-rupture side of mandible. Evaluation of CT images also indicated no statistical difference in bone density and thickness between IAN-rupture side and contralateral side.Accordingly, our study indicated that IAN rupture may not significantly impair the short-term bone remodeling process of human mandible.

Glial Plasticity in the Trigeminal Root Entry Zone of a Rat Trigeminal Neuralgia Animal Model.

The trigeminal root entry zone (TREZ) is the transitional zone of central and peripheral tissue compartments in the trigeminal root. Microvascular compression on the TREZ is the main etiology of most idiopathic trigeminal neuralgia (TN) patients. However, the pathogenesis of TN is still uncertain. To investigate the glial plasticity changes in oligodendrocytes, Schwann cells, astrocytes and microglia/macrophages in the TREZ in TN, immunohistochemical staining and Western blot methods were performed in rats with TN induced by compression injury. The results showed that mechanical compression injury in the trigeminal nerve of the TN rats induced glial plasticity in the TREZ, which dynamically changed the glial interface of the CNS-PNS transitional zone. Additionally, glial fibrillary acidic protein (GFAP)-immunoreactive astrocyte processes significantly proliferated and extended distally from the central region to the peripheral side of the TREZ after nerve compression injury in the TN group. Moreover, the expression of p75 in Schwann cells was upregulated on the peripheral side of the TREZ, and activated Iba-1-immunoreactive microglia/macrophages were observed on both sides of the TREZ. A significantly higher number of Schwann cells, astrocytes and microglia/macrophages were found in the TN group than in the sham operation group (p < 0.05). In conclusion, mechanical compression injury in the TN rats activated various glial cells, including oligodendrocytes, astrocytes, Schwann cells and microglia/macrophages, in the CNS-PNS transitional zone of TREZ. Changes in glial cell plasticity in the TREZ after compression injury might be involved in TN pathogenesis.

Does Piezosurgery Influence the Severity of Neurosensory Disturbance Following Bilateral Sagittal Split Osteotomy?

The present paper aims to evaluate the long-term incidence and severity of the neurosensory disturbance (NSD) of the inferior alveolar nerve following bilateral sagittal split osteotomy (BSSO) of the mandibular ramus performed with piezosurgery. A retrospective study on patients referred to the Maxillofacial Surgery and Dentistry Clinic of the University of Verona for orthognathic surgery between March 2013 and October 2015 was performed. Inclusion criteria were having undergone BSSO with piezosurgery and follow-up lasting at least 24 months. Exclusion criteria were history of surgical infection, osteosynthesis failure or re-do surgery. The extent of mandibular repositioning movements was retrieved and patients underwent 4 clinical neurosensory tests. Descriptive statistical analysis was performed. 52 patients met the inclusion criteria. Average follow-up was 40 months (range 24-75). 83% of the nerves examined have no or slightly altered sensitivity. Seventy-one percent of patients perceive a moderate to none discomfort and none describes the discomfort as serious (Visual Analogue Scale [VAS] >7). The extent of mandibular repositioning did not have significant influence on the development and severity of the NSD. Resulting data led the Authors to infer that using piezosurgery in BSSO, the severity of the NSD of inferior alveolar nerve is reduced, but the incidence of permanent nerve lesions remains unchanged, compared to historical controls.

Distal infraorbital nerve injury: a model for persistent facial pain in mice.

Inflammation or injuries of the trigeminal nerve are often associated with persistent facial pain and its sequelae. A number of models have been described to study trigeminal pain in rodents, but the long-lasting behavioral consequences are unknown. This study characterizes the impact of a distal infraorbital nerve injury, called DIONI, which consists of ligature and transection of distal fibers of the infraorbital nerve. We assessed nociception using a conflict paradigm and optogenetics, and a set of reward, aversion, spatial, temporal, and competition tasks in the IntelliCage to study multiple aspects of cognition, circadian rhythms, and social interactions in groups of mice in home cage environments. Mice with DIONI developed cold and mechanical allodynia, and hypersensitivity towards blue light stimulation. They maintained a long-lasting memory of aversive stimuli (airpuff from above), but had no difficulty in learning appetitive tasks, which consisted in developing a preference for a rewarding corner in the IntelliCage. Indeed, they were more strongly "addicted" to sugar than sham mice but temporarily failed to relearn the location of rewarding sites after corner switching (reversal learning). They were mildly overactive in some tasks but without disruptions of circadian rhythms or impact on social structure. They adopted a strategy to maintain licking with fewer nosepokes, presumably trying to avoid mechanical stimulation of the snout. The results suggest that mice with DIONI develop strong aversive memories and some cognitive inflexibility, but create adaptive strategies to cope with the persistent trigeminal hypersensitivity.

Trigeminal Nerve Transection-Induced Neuroplastic Changes in the Somatosensory and Insular Cortices in a Rat Ectopic Pain Model.

The primary sensory cortex processes competitive sensory inputs. Ablation of these competitive inputs induces neuroplastic changes in local cortical circuits. However, information concerning cortical plasticity induced by a disturbance of competitive nociceptive inputs is limited. Nociceptive information from the maxillary and mandibular molar pulps converges at the border between the ventral secondary somatosensory cortex (S2) and insular oral region (IOR); therefore, S2/IOR is a suitable target for examining the cortical changes induced by a disturbance of noxious inputs, which often causes neuropathic pain and allodynia. We focused on the plastic changes in S2/IOR excitation in a model of rats subjected to inferior alveolar nerve transection (IANX). Our optical imaging using a voltage-sensitive dye (VSD) revealed that the maxillary molar pulp stimulation-induced excitatory propagation was expanded one to two weeks after IANX at the macroscopic level. At the cellular level, based on Ca2+ imaging using two-photon microscopy, the amplitude of the Ca2+ responses and the number of responding neurons in S2/IOR increased in both excitatory and inhibitory neurons. The in vitro laser scanning photostimulation (LSPS) revealed that Layer II/III pyramidal and GABAergic fast-spiking neurons in S2/IOR received larger excitatory inputs from Layer IV in the IANX models, which supports the findings obtained by the macroscopic and microscopic optical imaging. Furthermore, the inhibitory postsynaptic inputs to the pyramidal neurons were decreased in the IANX models, suggesting suppression of inhibitory synaptic transmission onto excitatory neurons. These results suggest that IANX induces plastic changes in S2/IOR by changing the local excitatory and inhibitory circuits.

Pain threshold monitoring during chronic constriction injury of the infraorbital nerve in rats.

Background: The chronic constriction injury (CCI) of the infraorbital nerve (ION) has been used to establish an animal mode of trigeminal neuralgia (TN), but key parameters of the model have not been quantified until now. Objective: The aim of the study was to quantify a standard of pain threshold to evaluate a successful TN model in Sprague-Dawley (SD) rats. Methods: Forty-eight adult SD rats (200-220 g) underwent chronic constriction injury of the infraorbital nerve. The pain threshold was tested one day preoperatively (baseline) and day 1, 3, 7, 14, 28 postoperatively using the up-down method. At day 28, all the animals were killed by dislocation of the cervical spine and the trigeminal nerve specimens were removed for electron microscopy. Results: The baseline pain threshold was 14.40 ± 0.87 g. Postoperatively, all the rats presented an initial reduced sensitivity to mechanical stimulation from day 1 (15.63 ± 1.92 g) through 7 (17.39 ± 1.43 g) after the surgery. At day 14, 32 (66.7%) began to show significant mechanical allodynia (0.71 ± 0.43 g) which did not change significantly till day 28 (0.88 ± 0.54 g). These animals were regarded as successful TN models with a 95% confidence interval of the pain threshold of 0.58-1.27 at Day 14. The electron microscopy demonstrated homogeneously demyelinated changes in those successful TN model animals rather than severe or mild epineurial lesions in those unsuccessful model animals. Conclusion: Our study showed that an animal TN model could be established with a two-week chronic constriction injury of the infraorbital nerve. The mechanical allodynia index <1.27 at Day 14 was suggested as a criterion for a successful model.

Experimental Study on Involvement of the Central Nervous System in Inferior Alveolar Nerve Damage-Associated Hyperalgesia of the Mental Region.

PURPOSE: Involvement of the central nervous system in sensory disturbances of the mental region occurring after inferior alveolar nerve damage was investigated using a rat model of inferior alveolar nerve damage. PATIENTS AND METHODS: The rat inferior alveolar nerve was damaged by ligation with thread, and the course of behavioral changes after surgery was observed for 42 days. In addition, activation of microglia and astroglia in the trigeminal spinal subnucleus caudalis (Vc) was analyzed using immunohistochemistry. c-Fos-positive cells were quantitatively evaluated to analyze the state of neuron excitement. RESULTS: The withdrawal threshold was significantly decreased 5 days after surgery in the inferior alveolar nerve-ligated (IANL) group compared with that in the sham group and subsequently recovered over time. In addition, microglia and astroglia were activated in the Vc region 5 days after surgery in the model group, and c-fos-positive cells were also significantly more frequent in the IANL group. However, no significant difference in the withdrawal threshold was seen between the IANL and sham groups on day 42, nor were any significant differences seen in the amounts of microglia, astroglia, or c-fos-positive cells. CONCLUSIONS: Interactions among microglia, astroglia, and neurons in the central nervous system might be involved in the progression of inferior alveolar nerve damage-associated mental hyperalgesia to a chronic state.

Lipopolysaccharide-mediated inflammatory priming potentiates painful post-traumatic trigeminal neuropathy.

We explored the molecular and behavioral effects of a perineural Lipopolysaccharide (LPS)-mediated inflammatory priming on the development and maintenance of painful post-traumatic trigeminal neuropathy (PPTTN) following infra-orbital nerve chronic constriction injury (CCI-IoN) in rats. Rats were pretreated with repetitive perineural injections in the vicinity of the IoN of either LPS or vehicle (Vhcl) before being submitted to CCI-IoN. Orofacial pain-like behaviors (response to Von Frey Filament testing and spontaneous isolated face grooming) were measured during the period of LPS injections (three weeks) and following CCI-IoN surgery (two weeks). Local LPS administration induced an early pain-like behavior (i.e. an increase in spontaneous pain [SP] or mechanical static allodynia [MSA]) in both conditions, and following CCI-IoN, MSA and SP developed earlier and more severely in LPS-pretreated rats than in the control group. Ipsilateral increases of key neuropathic pain mRNA markers in the IoN parenchyma, trigeminal ganglia (TG) and spinal trigeminal nucleus caudalis (Sp5C) were observed in CCI-IoN injured animals as compared to controls. Although no significant molecular differences could be observed within the IoN parenchyma between LPS and Vhcl-pretreated animals, a significant increase of key inflammatory cytokine Interleukin 1 beta (IL - 1ß) could be found in the TG of LPS-pretreated CCI-injured animals versus controls. Finally, a higher increase of inducible nitric oxide synthase (iNOS) in ipsilateral Sp5C of LPS-pretreated animals was observed as compared to Sp5C of Vhcl-pretreated animals. These results suggest a key role of inflammatory priming in the development and maintenance of PPTTN implicating IL-1ß/iNOS-dependent central sensitization mechanisms.

Identifying criteria for diagnosis of post-traumatic pain and altered sensation of the maxillary and mandibular branches of the trigeminal nerve: a systematic review.

OBJECTIVE: The aim of the study was to systematically identify criteria used to diagnose patients with trigeminal nerve injury. STUDY DESIGN: A systematic review of the literature registered in the PROSPERO database. Inclusion criteria were patients diagnosed with nerve injury of the sensory divisions of the maxillary or mandibular branches of the trigeminal nerve, with reported tests and criteria used for diagnosis and persistent pain or unpleasant sensation associated with nerve injury. RESULTS: In total, 28 articles were included. Diagnostic tests included clinical neurosensory tests (89%), thermal quantitative sensory testing (QST; 25%), electromyography (7%), and patient interview (14%). Neuropathic pain was assessed by using the visual analogue scale (39%); patient use of neuropathic medication (7%); questionnaires, including McGill and PainDETECT (21%). Functional impact was assessed in 14% and psychological impact in 7% of articles. Methodology in performing clinical neurosensory tests, application of diagnostic terms and diagnostic grading of nerve injury was found to be inconsistent among the included articles, making direct comparison of results difficult. CONCLUSIONS: Recommendations for assessment and diagnosis of trigeminal nerve injury have been made based on the best available evidence from the review. There is an urgent requirement for a consensus in diagnostic criteria, criteria for assessment, and outcome reporting among stakeholder organizations to improve knowledge in this field.

Effect of Pregabalin and Diclofenac on tactile allodynia, mechanical hyperalgesia and pro inflammatory cytokine levels (IL-6, IL-1ß) induced by chronic constriction injury of the infraorbital nerve in rats.

The present study evaluated the effects of systemic pregabalin (PG) and diclofenac (Dic) on neuropathic orofacial pain induced by chronic constriction injury (CCI) of the infraorbital nerve (ION) and on the pro-inflammatory cytokines levels in the affected nerve. Fifty-four rats underwent left infra orbital nerve CCI, and 7 days after the procedure as the pain developed, the rats were randomly assigned to one of the treatment groups: PG 300, 30 or 10 mg/kg, Dic 10, 5 or 1 mg/kg or saline group (Sal) (n/group = 8). Addiitonal 8 rats served as naïve control group. Tactile-allodynia and Mechano-hyperalgesia were tested before the surgical procedure and at days 7, 8, and 9 postoperatively. On the 9th day, the rats were euthanized and the affected and contralateral sciatic nerves were harvested to assess IL-6 and IL-1ß nerve levels employing enzyme linked immunosorbent assay (ELISA). Daily injection of PG (all doses) significantly reduced tactile-allodynia and mechano-hyperalgesia (p < .05) while Dic did not. On the 9th day, the ipsilateral nerve IL-6 levels were significantly decreased (p < .05) in the PG and DIC groups compared to the Sal group. IL-1ß levels demonstrated a significant reduction (p < .05) in the PG group when compared to saline. These results suggest that PG but not Dic may be effective in reducing neuropathic orofacial pain. The mechanisms of action may be associated to some extent with reduction in IL-1ß levels in the affected nerve.

Traumatic Neuropathy of the Trigeminal Nerve in a College Trumpet Player: A Case Report.

A 20-year-old college trumpet player presented with a 3-month history of upper lip numbness and worsening playing ability after a marching band performance. Examination demonstrated anesthesia of the upper lip that followed the borders of the trumpet mouthpiece. While playing, the patient had poor range and an airy tone quality. A prescription of complete embouchure rest for 6 weeks and a tailored return to play regimen resulted in resolution of upper lip numbness and improved trumpet playing. Neuropathy of the lip in a brass player is uncommon but highlights the uniqueness of injuries that may be sustained by performing artists. LEVEL OF EVIDENCE: V.

Neurosensory Disturbance of the Inferior Alveolar Nerve After 3025 Implant Placements.

PURPOSE: The aim of this retrospective study was to evaluate the incidence of inferior alveolar nerve (IAN) lesion and duration of sensitivity disturbances after the insertion of dental implants. METHODS: One thousand sixty-five patients (mean age: 58.9 years) enrolled between February 2004 and July 2015 with partial or full mandibular edentulism were selected to receive dental implants for oral rehabilitation. A total of 3025 implants were placed. After surgical procedures, controls were scheduled at suture removal, that is, 10 days after surgery, and repeated at intervals of 1, 3, and 6 months, and comprised patient interview, clinical examination, and sensitivity tests. RESULTS: Only 23 (2.2%) of the 1065 patients presented sensitivity disturbances 1 month after implant insertion, and only 2 (0.19%) after 6 months, though a complete recovery was observed in these patients within 13 months. CONCLUSIONS: Considering the debilitating effects resulting from IAN lesion and the complexity of the therapeutic diagnostic protocols, all patients undergoing oral rehabilitation through dental implants should be evaluated with CBCT imaging.

Piezosurgery for Sagittal Split Osteotomy: Procedure Duration and Postoperative Sensory Perturbation.

PURPOSE: To evaluate piezosurgery for bilateral sagittal split osteotomy (BSSO) for its duration and inferior alveolar nerve (IAN) perturbation. PATIENTS AND METHODS: In this prospective randomized study, the authors evaluated 100 BSSO procedures in 50 patients. Piezoelectric (group I) and conventional (group II) osteotomies were carried out on each side of the mandible of a patient by 2 specialists. The surgeons had at least 1 year of experience using piezosurgery. The period from incision to complete splitting of the mandibular bone was recorded (ie, procedure duration). The intraoperative status (visibility and relocation) of the IAN also was recorded. The neurosensory function of the IAN was measured by the 2-point discrimination threshold and static light touch methods before surgery and postoperatively (1, 3, and 6 weeks and 6 and 12 months). Parameters were compared between the test groups by the paired t, nonparametric Wilcoxon, or χ2 test. RESULTS: Intergroup comparison showed the mean duration of osteotomy was significantly shorter for group I (17 ± 6 vs 25 ± 9 minutes; P < .001). The rate of intraoperative exposures of the IAN was slightly lower for group I (68%) compared with group II (81%). However, the difference was not relevant. Neurosensory disturbance and recovery of the IAN did not differ between groups. CONCLUSION: Piezoelectric osteotomy requires considerably less time than conventional mechanical approaches, but shows no advantage in preventing neurosensory perturbation.

PPARγ Agonists Attenuate Trigeminal Neuropathic Pain.

OBJECTIVES: The aim of this study is to investigate the role of peroxisome proliferator-activated receptor-gamma isoform (PPARγ), in trigeminal neuropathic pain utilizing a novel mouse trigeminal inflammatory compression (TIC) injury model. RESULTS: The study determined that the PPARγ nuclear receptor plays a significant role in trigeminal nociception transmission, evidenced by: 1) Intense PPARγ immunoreactivity is expressed 3 weeks after TIC nerve injury in the spinal trigeminal caudalis, the termination site of trigeminal nociceptive nerve fibers. 2) Systemic administration of a PPARγ agonist, pioglitazone (PIO), attenuates whisker pad mechanical allodynia at doses of 300 mg/kg i.p. and 600 mg/kg p.o. 3) Administration of a PPARγ antagonist, GW9662 (30 mg/kg i.p.), prior to providing the optimal dose of PIO (300 mg/kg i.p.) blocked the analgesic effect of PIO. DISCUSSION: This is the first study localizing PPARγ immunoreactivity throughout the brainstem trigeminal sensory spinal nucleus (spV) and its increase three weeks after TIC nerve injury. This is also the first study to demonstrate that activation of PPARγ attenuates trigeminal hypersensitivity in the mouse TIC nerve injury model. The findings presented here suggest the possibility of utilizing the FDA approved diabetic treatment drug, PIO, as a new therapeutic that targets PPARγ for treatment of patients suffering from orofacial neuropathic pain.