Development of Neuropathic Pain by Thermal Injury using Radiofrequency Thermocoagulation in a Rat Infraorbital Nerve

Study Design: Retrospective study. Objective: Zygomaticomaxillary complex (ZMC) fractures are common facial injuries with heterogeneity regarding aetiologies, fracture types, infraorbital nerve (ION) involvement, and treatment methods. The aim of this study was to identify associations between aetiologies, fracture types, and neurological complications. Additionally, treatment methods and recovery time were investigated. Methods: Medical files of 272 patients with unilateral and bilateral ZMC fractures were reviewed, whose cases were managed from January 2014 to January 2019 at the Department of Oral and Maxillofacial Surgery, University hospitals Leuven, Belgium. History of ION sensory dysfunction and facial nerve motoric dysfunction were noted during follow-up. Results: ION hypoaesthesia incidence was 37.3%, with the main causes being fall accidents, road traffic accidents, and interpersonal violence. Significant predictors of ION hypoaesthesia were Zingg type B fractures ( P = 0.003), fracture line course through the infraorbital canal ( P < .001), orbital floor fracture ( P < 0.001), and ZMC dislocation or mobility ( P = 0.001). Conclusion: Of all ZMC fractures, 37.3% exhibited ION hypoaesthesia. Only ZMC Zingg type B fractures (74.0%) were significantly more associated with ION hypoaesthesia. ION hypoesthesia was more likely (OR = 2.707) when the fracture line course ran through the infraorbital canal, and was less dependent on the degree of displacement. Neuropathic pain symptoms developed after ZMC fractures in 2.2% patients, posing a treatment challenge. Neuropathic pain symptoms were slightly more common among women, and were associated only with type B or C fractures. No other parameters were found to predict the outcome of this post-traumatic neuropathic pain condition.

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(−)-α-Bisabolol reduces nociception and trigeminal central sensitisation in acute orofacial neuropathic pain induced by infraorbital nerve injury

Life Sciences ◽

10.1016/j.lfs.2019.04.032 ◽

2019 ◽

Vol 227 ◽

pp. 122-128 ◽

Cited By ~ 3

Author(s):

L.T. Melo ◽

V. Panchalingam ◽

P. Cherkas ◽

A.R. Campos ◽

L. Avivi-Arber ◽

...

Keyword(s):

Neuropathic Pain ◽

Nerve Injury ◽

Infraorbital Nerve ◽

Central Sensitisation

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Microglia–Astrocyte Communication via C1q Contributes to Orofacial Neuropathic Pain Associated with Infraorbital Nerve Injury

International Journal of Molecular Sciences ◽

10.3390/ijms21186834 ◽

2020 ◽

Vol 21 (18) ◽

pp. 6834

Author(s):

Sayaka Asano ◽

Yoshinori Hayashi ◽

Koichi Iwata ◽

Akiko Okada-Ogawa ◽

Suzuro Hitomi ◽

...

Keyword(s):

Neuropathic Pain ◽

Glial Fibrillary Acidic Protein ◽

Nerve Injury ◽

Fluorescence Intensity ◽

Time Window ◽

Infraorbital Nerve ◽

Nociceptive Neurons ◽

Mechanical Hypersensitivity ◽

Injury Causes ◽

Immunohistochemical Analyses

Trigeminal nerve injury causes a distinct time window of glial activation in the trigeminal spinal subnucleus caudalis (Vc), which are involved in the initiation and maintenance phases of orofacial neuropathic pain. Microglia-derived factors enable the activation of astrocytes. The complement component C1q, which promotes the activation of astrocytes, is known to be synthesized in microglia. However, it is unclear whether microglia–astrocyte communication via C1q is involved in orofacial neuropathic pain. Here, we analyzed microglia-astrocyte communication in a rat model with infraorbital nerve injury (IONI). The orofacial mechanical hypersensitivity induced by IONI was significantly attenuated by preemptive treatment with minocycline. Immunohistochemical analyses revealed that minocycline inhibited the increase in c-Fos immune-reactive (IR) cells and the fluorescence intensity of both Iba1 and glial fibrillary acidic protein (GFAP) in the Vc following IONI. Intracisternal administration of C1q caused orofacial mechanical hypersensitivity and an increase in the number of c-Fos-IR cells and fluorescence intensity of GFAP. C1q-induced orofacial mechanical hypersensitivity was completely abrogated by intracisternal administration of fluorocitrate. The present findings suggest that the enhancement in the excitability of Vc nociceptive neurons is produced by astrocytic activation via the signaling of C1q released from activated microglia in the Vc following IONI, resulting in persistent orofacial neuropathic pain.

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Differential anti-neuropathic pain effects of tetrodotoxin in sciatic nerve- versus infraorbital nerve-ligated rats – Behavioral, pharmacological and immunohistochemical investigations

Neuropharmacology ◽

10.1016/j.neuropharm.2009.09.003 ◽

2010 ◽

Vol 58 (2) ◽

pp. 474-487 ◽

Cited By ~ 22

Author(s):

Valérie Kayser ◽

Florent Viguier ◽

Myrto Ioannidi ◽

Jean-François Bernard ◽

Alban Latrémolière ◽

...

Keyword(s):

Neuropathic Pain ◽

Sciatic Nerve ◽

Infraorbital Nerve

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Preventative pregabalin treatment in a partial infraorbital nerve ligation model (PIONL) decreases neuropathic pain

Journal of Pain ◽

10.1016/j.jpain.2012.01.229 ◽

2012 ◽

Vol 13 (4) ◽

pp. S55

Author(s):

C. Rivat ◽

M. Xu ◽

R. Koopmans ◽

A. Cahana ◽

P. Richebe

Keyword(s):

Neuropathic Pain ◽

Infraorbital Nerve

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TLR8 in the trigeminal ganglion contributes to the maintenance of trigeminal neuropathic pain

10.21203/rs.2.24451/v1 ◽

2020 ◽

Author(s):

Lin-Xia Zhao ◽

Xue-Qiang Bai ◽

De-Li Cao ◽

Xiao-Bo Wu ◽

Ming Jiang ◽

...

Keyword(s):

Neuropathic Pain ◽

Trigeminal Ganglion ◽

Proinflammatory Cytokines ◽

Facial Pain ◽

Calcium Concentration ◽

Infraorbital Nerve ◽

Rt Pcr ◽

Pain Hypersensitivity ◽

Trigeminal Neuropathic Pain ◽

Significant Health

Abstract Background: Trigeminal neuropathic pain (TNP) is a significant health problem whereas the involved mechanism has not been completely elucidated. Toll-like receptors (TLRs) are recently demonstrated to be expressed in the dorsal root ganglion and involved in chronic pain. How TLR8 is expressed in the trigeminal ganglion (TG) after infraorbital nerve injury and whether TLR8 is involved in TNP have not been investigated.Methods: TNP model was established by the partial infraorbital nerve ligation (pIONL) in mice. The effect of TLR8 and its agonist VTX-2337 on pain hypersensitivity was checked by facial pain behavioral test. The immunostaining, real-time RT-PCR, and western blot were used to evaluate the expression of TLR8, pERK, pp38, and proinflammatory cytokines in the TG. The intracellular concentration of Ca 2+ was detected by the calcium imaging.Results: TLR8 was persistently increased in TG neurons in pIONL-induced TNP model. In addition, deletion of Tlr8 or knockdown of Tlr8 in the TG attenuated pIONL-induced mechanical allodynia, reduced the activation of ERK and p38, and decreased the expression of proinflammatory cytokines in the TG. Furthermore, intra-TG injection of TLR8 agonist VTX-2337 induced facial pain hypersensitivity. VTX-2337 also increased intracellular calcium concentration, induced activation of ERK and p38, and increased the proinflammatory cytokines expression in the TG.Conclusions: TLR8 contributes to the maintenance of TNP through increasing MAPK-mediated neuroinflammation. Targeting TLR8 signaling may be effective for the treatment of TNP.

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Microglia and Inhibitory Circuitry in the Medullary Dorsal Horn: Laminar and Time-Dependent Changes in a Trigeminal Model of Neuropathic Pain

10.20944/preprints202103.0186.v1 ◽

2021 ◽

Author(s):

Nuria García-Magro ◽

Yasmina B. Martin ◽

Pilar Negredo ◽

Francisco Zafra ◽

Carlos Avendaño

Keyword(s):

Neuropathic Pain ◽

Dorsal Horn ◽

Substantial Reduction ◽

Negative Control ◽

Infraorbital Nerve ◽

Survival Times ◽

Medullary Dorsal Horn ◽

Inhibitory Circuitry ◽

Basic Features ◽

Heterogeneous Reduction

Craniofacial neuropathic pain affects millions of people worldwide and is often difficult to treat. Two key mechanisms underlying this condition are a loss of the negative control exerted by inhibitory interneurons and an early microglial reaction. Basic features of these mechanisms, however, are still poorly understood. Using the chronic constriction injury of the infraorbital nerve (CCI-IoN) model of neuropathic pain in mice, we have examined the changes in the expression of GAD, the synthetic enzyme of GABA, and GlyT2, the membrane transporter of glycine, as well as the microgliosis that occur at early (5 days) and late (21 days) stages post-CCI in the medullary and upper spinal dorsal horn. Our results show that CCI-IoN induces a down-regulation of GAD at both postinjury survival times, uniformly across the superficial laminae. The expression of GlyT2 showed a more discrete and heterogeneous reduction due to the basal presence in lamina III of ‘patches’ of higher expression, interspersed within a less immunoreactive ‘matrix’, which showed a more substantial reduction in the expression of GlyT2. These patches coincided with foci lacking any perceptible microglial reaction, which stood out against a more diffuse areas of strong microgliosis. These findings may provide clues to better understand the neural mechanisms underlying allodynia in neuropathic pain syndromes.

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Dopaminergic Modulation of Orofacial Mechanical Hypersensitivity Induced by Infraorbital Nerve Injury

International Journal of Molecular Sciences ◽

10.3390/ijms21061945 ◽

2020 ◽

Vol 21 (6) ◽

pp. 1945

Author(s):

Hiroharu Maegawa ◽

Nayuka Usami ◽

Chiho Kudo ◽

Hiroshi Hanamoto ◽

Hitoshi Niwa

Keyword(s):

Neuropathic Pain ◽

Control System ◽

Receptor Agonist ◽

Dopamine D2 Receptor ◽

Intraperitoneal Administration ◽

D2 Receptor ◽

Infraorbital Nerve ◽

Gamma Aminobutyric Acid ◽

The Impact ◽

Dopaminergic Control

While the descending dopaminergic control system is not fully understood, it is reported that the hypothalamic A11 nucleus is its principle source. To better understand the impact of this system, particularly the A11 nucleus, on neuropathic pain, we created a chronic constriction injury model of the infraorbital nerve (ION-CCI) in rats. ION-CCI rats received intraperitoneal administrations of quinpirole (a dopamine D2 receptor agonist). ION-CCI rats received microinjections of quinpirole, muscimol [a gamma-aminobutyric acid type A (GABAA) receptor agonist], or neurotoxin 6-hydroxydopamine (6-OHDA) into the A11 nucleus. A von Frey filament was used as a mechanical stimulus on the maxillary whisker pad skin; behavioral and immunohistochemical responses to the stimulation were assessed. After intraperitoneal administration of quinpirole and microinjection of quinpirole or muscimol, ION-CCI rats showed an increase in head-withdrawal thresholds and a decrease in the number of phosphorylated extracellular signal-regulated kinase (pERK) immunoreactive (pERK-IR) cells in the superficial layers of the trigeminal spinal subnucleus caudalis (Vc). Following 6-OHDA microinjection, ION-CCI rats showed a decrease in head-withdrawal thresholds and an increase in the number of pERK-IR cells in the Vc. Our findings suggest the descending dopaminergic control system is involved in the modulation of trigeminal neuropathic pain.

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Alleviation of trigeminal neuropathic pain by electroacupuncture: the role of hyperpolarization-activated cyclic nucleotide-gated channel protein expression in the Gasserian ganglion

Acupuncture in Medicine ◽

10.1177/0964528419841614 ◽

2019 ◽

Vol 37 (3) ◽

pp. 192-198

Author(s):

Liuyue Yang ◽

Weihua Ding ◽

Zerong You ◽

Jinsheng Yang ◽

Shiqian Shen ◽

...

Keyword(s):

Neuropathic Pain ◽

Protein Expression ◽

Cyclic Nucleotide ◽

Mechanical Allodynia ◽

Infraorbital Nerve ◽

Gasserian Ganglion ◽

Sprague Dawley ◽

Trigeminal Neuropathic Pain ◽

Sprague Dawley Rats ◽

Gated Channel

Introduction: The aim of this study was to examine the effect of electroacupuncture (EA) on trigeminal neuropathic pain in rats and explore the potential mechanism underlying the putative therapeutic effect of EA. Methods: Trigeminal neuropathic pain behavior was induced in rats by unilateral chronic constriction injury of the distal infraorbital nerve (dIoN-CCI). EA was administered at ST2 ( Sibai) and Jiachengjiang. A total of 60 Sprague Dawley rats were divided into the following four groups ( n = 15 per group) to examine the behavioral outcomes after surgery and/or EA treatment: sham (no ligation); dIoN-CCI (received isoflurane only, without EA treatment); dIoN-CCI+EA-7d (received EA treatment for 7 days); and dIoN-CCI+EA-14d (received EA treatment for 14 days). Both evoked and spontaneous nociceptive behaviors were measured. Of these, 12 rats ( n = 4 from sham, dIoN-CCI, and dIoN-CCI+EA-14d groups, respectively) were used to analyze protein expression of hyperpolarization-activated cyclic nucleotide-gated (HCN) channel in the Gasserian ganglion (GG) by immunohistochemistry. Results: dIoN-CCI rats exhibited mechanical allodynia and increased face-grooming activity that lasted at least 35 days. EA treatment reduced mechanical allodynia and face-grooming in dIoN-CCI rats. Overall, 14 days of EA treatment produced a prolonged anti-nociceptive effect as compared to 7-day EA treatment. The counts of HCN1 and HCN2 immunopositive puncta were increased in the ipsilateral GG in dIoN-CCI rats and were reduced by 14 days of EA treatment. Discussion: EA treatment relieved trigeminal neuropathic pain in dIoN-CCI rats, and this effect was dependent on the duration of EA treatment. The downregulation of HCN expression may contribute to the anti-nociceptive effect of EA in this rat model of trigeminal neuropathic pain.

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