Trigeminal Injury Causes kappa Opioid-Dependent Allodynic, Glial and Immune Cell Responses in Mice

Aita, Megumi; Byers, Margaret R.; Chavkin, Charles; Xu, Mei

doi:10.1186/1744-8069-6-8

Cited by 40 publications

(30 citation statements)

References 47 publications

(68 reference statements)

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“…3 A shows examples of confocal microscopy images from WT or R192Q KI ganglion sections that were co-immunostained with antibodies against Iba1 and CD11b, an adhesion molecule marker for active macrophages and microglia [37], [38], [39].…”

Section: Resultsmentioning

confidence: 99%

TNFα Levels and Macrophages Expression Reflect an Inflammatory Potential of Trigeminal Ganglia in a Mouse Model of Familial Hemiplegic Migraine

et al. 2013

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Latent changes in trigeminal ganglion structure and function resembling inflammatory conditions may predispose to acute attacks of migraine pain. Here, we investigated whether, in trigeminal sensory ganglia, cytokines such as TNFα might contribute to a local inflammatory phenotype of a transgenic knock-in (KI) mouse model of familial hemiplegic migraine type-1 (FHM-1). To this end, macrophage occurrence and cytokine expression in trigeminal ganglia were compared between wild type (WT) and R192Q mutant CaV2.1 Ca2+ channel (R192Q KI) mice, a genetic model of FHM-1. Cellular and molecular characterization was performed using a combination of confocal immunohistochemistry and cytokine assays. With respect to WT, R192Q KI trigeminal ganglia were enriched in activated macrophages as suggested by their morphology and immunoreactivity to the markers Iba1, CD11b, and ED1. R192Q KI trigeminal ganglia constitutively expressed higher mRNA levels of IL1β, IL6, IL10 and TNFα cytokines and the MCP-1 chemokine. Consistent with the report that TNFα is a major factor to sensitize trigeminal ganglia, we observed that, following an inflammatory reaction evoked by LPS injection, TNFα expression and macrophage occurrence were significantly higher in R192Q KI ganglia with respect to WT ganglia. Our data suggest that, in KI trigeminal ganglia, the complex cellular and molecular environment could support a new tissue phenotype compatible with a neuroinflammatory profile. We propose that, in FHM patients, this condition might contribute to trigeminal pain pathophysiology through release of soluble mediators, including TNFα, that may modulate the crosstalk between sensory neurons and resident glia, underlying the process of neuronal sensitisation.

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Section: Resultsmentioning

confidence: 99%

TNFα Levels and Macrophages Expression Reflect an Inflammatory Potential of Trigeminal Ganglia in a Mouse Model of Familial Hemiplegic Migraine

et al. 2013

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“…Microglial activation indicated by up-regulation of OX-42 is commonly used as a biomarker for detection of neuropathic injury in either the spinal cord or the spinal trigeminal nucleus [22-24]. Central microglial response can be activated by either neuronal injury or peripheral nerve inflammation [25].…”

Section: Resultsmentioning

confidence: 99%

Orofacial neuropathic pain mouse model induced by Trigeminal Inflammatory Compression (TIC) of the infraorbital nerve

Zhang

Lyons

et al. 2012

Mol Brain

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BackgroundTrigeminal neuropathic pain attacks can be excruciating for patients, even after being lightly touched. Although there are rodent trigeminal nerve research models to study orofacial pain, few models have been applied to studies in mice. A mouse trigeminal inflammatory compression (TIC) model is introduced here which successfully and reliably promotes vibrissal whisker pad hypersensitivity.ResultsThe chronic orofacial neuropathic pain model is induced after surgical placement of chromic gut suture in the infraorbital nerve fissure in the maxillary bone. Slight compression and chemical effects of the chromic gut suture on the portion of the infraorbital nerve contacted cause mild nerve trauma. Nerve edema is observed in the contacting infraorbital nerve bundle as well as macrophage infiltration in the trigeminal ganglia. Centrally in the spinal trigeminal nucleus, increased immunoreactivity for an activated microglial marker is evident (OX42, postoperative day 70). Mechanical thresholds of the affected whisker pad are significantly decreased on day 3 after chromic gut suture placement, persisting at least 10 weeks. The mechanical allodynia is reversed by suppression of microglial activation. Cold allodynia was detected at 4 weeks.ConclusionsA simple, effective, and reproducible chronic mouse model mimicking clinical orofacial neuropathic pain (Type 2) is induced by placing chromic gut suture between the infraorbital nerve and the maxillary bone. The method produces mild inflammatory compression with significant continuous mechanical allodynia persisting at least 10 weeks and cold allodynia measureable at 4 weeks.

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“…This is probably due to the complexity in performing surgical procedure on trigeminal nerve on animals. IoN-CCI 25 , the application of complete Freund’s adjuvant (CFA) to the orbital portion of the IoN 3 , and unilateral partial ligation of the IoN (pIONL) 1, 28 are three commonly used animal models to study trigeminal neuropathic pain. All IoN-CCI procedures described and used by others are also complex and difficult to perform 10, 12, 13, 25 .…”

Section: Discussionmentioning

confidence: 99%

An Improved Rodent Model of Trigeminal Neuropathic Pain by Unilateral Chronic Constriction Injury of Distal Infraorbital Nerve

Ding

You

Shen

et al. 2017

The Journal of Pain

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The number of studies on trigeminal nerve injury using animal models remains limited. A rodent model of trigeminal neuropathic pain was first developed in the 1994, in which chronic constriction injury is induced by ligation of the infraorbital nerve (IoN-CCI). This animal model has served as a major tool to study trigeminal neuropathic pain. Unfortunately, the surgical procedure in this model is complicated and far more difficult than ligation of peripheral nerves (e.g. sciatic nerve). The aim of this study was to improve on the current surgical procedure of IoN ligation to induce trigeminal neuropathic pain in rats. We demonstrate that the IoN can be readily accessed through a small facial incision. Chronic constriction injury can be induced by ligation of a segment at the distal infraorbital nerve (dIoN-CCI). This dIoN-CCI procedure is simple, minimally invasive and time-saving. Our data show that the dIoN-CCI procedure consistently induced both acute and chronic nociceptive behaviors in rats. Daily gabapentin treatment attenuated mechanical allodynia and reduced face-grooming episodes in dIoN-CCI rats. Perspective The orofacial pain caused by trigeminal nerve damage is severe and perhaps more debilitating than other types of neuropathic pain. However, studies on trigeminal neuropathic pain remain limited. This is largely due to the lack of proper animal models given the complexity of the existing surgical procedure required to induce trigeminal nerve injury. Our improved dIoN-CCI model is likely to make it more accessible to study the cellular and molecular mechanisms of neuropathic pain caused by trigeminal nerve damage.

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Trigeminal Injury Causes kappa Opioid-Dependent Allodynic, Glial and Immune Cell Responses in Mice

Cited by 40 publications

References 47 publications

TNFα Levels and Macrophages Expression Reflect an Inflammatory Potential of Trigeminal Ganglia in a Mouse Model of Familial Hemiplegic Migraine

TNFα Levels and Macrophages Expression Reflect an Inflammatory Potential of Trigeminal Ganglia in a Mouse Model of Familial Hemiplegic Migraine

Orofacial neuropathic pain mouse model induced by Trigeminal Inflammatory Compression (TIC) of the infraorbital nerve

An Improved Rodent Model of Trigeminal Neuropathic Pain by Unilateral Chronic Constriction Injury of Distal Infraorbital Nerve

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