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. 2017 Oct 3:10:2355-2364.
doi: 10.2147/JPR.S138626. eCollection 2017.

Optical inactivation of the anterior cingulate cortex modulate descending pain pathway in a rat model of trigeminal neuropathic pain created via chronic constriction injury of the infraorbital nerve

Hyeong Cheol Moon  1 , Won Ik Heo  2 , Yon Ji Kim  3 , Daae Lee  4 , So Yoon Won  5 , Hong Rae Kim  1 , Seung Man Ha  1 , Youn Joo Lee  6 , Young Seok Park  1
Affiliations

Optical inactivation of the anterior cingulate cortex modulate descending pain pathway in a rat model of trigeminal neuropathic pain created via chronic constriction injury of the infraorbital nerve

Hyeong Cheol Moon et al. J Pain Res. .

Abstract

Purpose: The anterior cingulate cortex (ACC) plays a critical role in the initiation, development, and maintenance of neuropathic pain. Recently, the effects of optical stimulation on pain have been investigated, but the therapeutic effects of optical stimulation on trigeminal neuralgia (TN) have not been clearly shown. Here, we investigated the effects of optical inhibition of the ACC on TN lesions to determine whether the alleviation of pain affects behavior performance and thalamic neuron signaling.

Materials and methods: TN lesions were established in animals by generating a chronic constriction injury of the infraorbital nerve, and the animals received injections of AAV-hSyn-eNpHR3.0-EYFP or a vehicle (phosphate-buffered saline [PBS]) in the ACC. The optical fiber was fixed into the ipsilateral ACC after the injection of adeno-associated virus plasmids or vehicle. Behavioral testing, consisting of responses to an air puff and cold allodynia, was performed, and thalamic neuronal activity was monitored following optical stimulation in vivo. Optical stimulation experiments were executed in three steps: during pre-light-off, stimulation-light-on, and post-light-off states. The role of the optical modulation of the ACC in response to pain was shown using a combination of optical stimulation and electrophysiological recordings in vivo.

Results: Mechanical thresholds and facial cold allodynia scores were significantly improved in the TN lesion group during optical stimulation compared to those in the control group. Thalamic neuronal activity, consisting of the firing rate (spikes/s) and burst rate (bursts/s), was also decreased during optical stimulation.

Conclusion: Reciprocal optical inhibition of the ACC can alleviate pain-associated behavior and decrease abnormal thalamic sensory neuron activity in the trigeminal neuropathic rat model. The descending pain pathway can modulate thalamic neurons from the ACC following optical stimulation.

Keywords: anterior cingulate cortex; neuropathic pain; optogenetics; trigeminal neuralgia.

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Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Timeline of this study. Abbreviation: TN, trigeminal neuralgia.
Figure 2
Figure 2
Facial allodynia behavior test. Notes: Changes in the mechanical thresholds of the sham-operated and TN-lesioned rats were assessed for 2 weeks using air puffs. TN-lesioned rats (n = 14) responded at significantly lower ipsilateral mechanical thresholds than sham-operated rats (n = 10) (A). Cold allodynia scores for sham-operated and TN-lesioned rats were obtained over 2 weeks by dropping acetone on the animal’s face. TN-lesioned rats exhibited a significant increase in ipsilateral facial allodynia compared to sham-operated rats (B). All data represent the mean ± SD values. The two-way ANOVA followed by Tukey’s post hoc test was used. **p < 0.01, and ***p < 0.001 for comparisons between each groups. Abbreviations: TN, trigeminal neuralgia; SD, standard deviation; ANOVA, analysis of variance.
Figure 3
Figure 3
Results of the pain allodynia behavior test according to optical stimulation in the pre, laser-on, and post states. Notes: Mechanical thresholds were increased (A), and the cold allodynia scores were decreased (B) during optical stimulation. All data are presented as mean ± SD. The two-way ANOVA followed by Tukey’s post hoc test was used. **p < 0.01, and ***p < 0.001 for comparisons between each groups. Abbreviations: SD, standard deviation; ANOVA, analysis of variance; TN, trigeminal neuralgia; NpHR, Natronomonas pharaonis.
Figure 4
Figure 4
Alterations in thalamic output depending on the optogenetic inhibition of the ACC. Notes: Differences in spontaneous and evoked firing rates in the neurons of the VPM between sham-operated and TN lesions (A) (n = 8). Overall single neuronal activity in the thalamus by optical stimulation (B). Burst firing rates following optical stimulation (C). Real-time firing rates (histogram) in TN-vehicle (D), TN-NpHR (E), and sham-operated (F) rats. Unpaired t-test comparison between sham-operated and TN groups. The two-way ANOVA test was used to compare neuronal activity according to the optical stimulation and different groups. Abbreviations: ACC, anterior cingulate cortex; TN, trigeminal neuralgia; NpHR, Natronomonas pharaonis; ANOVA, analysis of variance; VPM, ventral posteromedial thalamic nucleus.
Figure 5
Figure 5
A confocal image shows AAV-hSyn-eNpHR3.0-EYFP expression in the ACC. Notes: Illustration showing the position of the ACC (A). Fluorescent images show DAPI and EYFP staining, as well as the merge between these markers (×200; B–D) in the ACC. Abbreviations: AAV, adeno-associated virus; ACC, anterior cingulate cortex; DAPI, 4’,6-diamidino-2-phenylindole; EYFP, enhanced yellow fluorescent protein.
See this image and copyright information in PMC

References

    1. Okeson JP. Bell’s Orofacial Pains: The Clinical Management of Orofacial Pain. Chicago, IL, USA: Quintessence Publishing Company; 2005.
    1. Liao C, Zhang W, Yang M, Zhong W, Liu P, Li S. Microvascular decompression for trigeminal neuralgia: the role of mechanical allodynia. World Neurosurg. 2016;91:468–472. - PubMed
    1. Vogt BA, Miller MW. Cortical connections between rat cingulate cortex and visual, motor, and postsubicular cortices. J Comp Neurol. 1983;216(2):192–210. - PubMed
    1. Vogt BA. In: Cingulate cortex. Peters A, Johns EG, editors. New York: Plenum Publishing Corporation; 1985.
    1. Fuchs PN, Peng YB, Boyette-Davis JA, Uhelski ML. The anterior cingulate cortex and pain processing. Front Integr Neurosci. 2014;8:35. - PMC - PubMed