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

2020 ◽  
Author(s):  
Lin-Xia Zhao ◽  
Xue-Qiang Bai ◽  
De-Li Cao ◽  
Xiao-Bo Wu ◽  
Ming Jiang ◽  
...  

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.

Author(s):  
Lin-Xia Zhao ◽  
Ming Jiang ◽  
Xue-Qiang Bai ◽  
De-Li Cao ◽  
Xiao-Bo Wu ◽  
...  

AbstractTrigeminal neuropathic pain (TNP) is a significant health problem but the involved mechanism has not been completely elucidated. Toll-like receptors (TLRs) have recently been demonstrated to be expressed in the dorsal root ganglion and involved in chronic pain. Here, we show that TLR8 was persistently increased in the trigeminal ganglion (TG) neurons in model of TNP induced by partial infraorbital nerve ligation (pIONL). In addition, deletion or knockdown of Tlr8 in the TG attenuated pIONL-induced mechanical allodynia, reduced the activation of ERK and p38-MAPK, and decreased the expression of pro-inflammatory cytokines in the TG. Furthermore, intra-TG injection of the TLR8 agonist VTX-2337 induced pain hypersensitivity. VTX-2337 also increased the intracellular Ca2+ concentration, induced the activation of ERK and p38, and increased the expression of pro-inflammatory cytokines in the TG. These data indicate that TLR8 contributes to the maintenance of TNP through increasing MAPK-mediated neuroinflammation. Targeting TLR8 signaling may be effective for the treatment of TNP.


2020 ◽  
Author(s):  
Jaisan Islam ◽  
Elina KC ◽  
Byeong Ho Oh ◽  
Soochong Kim ◽  
Sang-hwan Hyun ◽  
...  

Abstract Background Previous studies have reported that electrical stimulation of the motor cortex is effective in reducing trigeminal neuropathic pain; however, the effects of optical motor cortex stimulation remain unclear. Objective The present study aimed to investigate whether optical stimulation of the primary motor cortex can modulate chronic neuropathic pain in rats with infraorbital nerve constriction injury. Methods Animals were randomly divided into a trigeminal neuralgia group, a sham group, and a control group. Trigeminal neuropathic pain was generated via constriction of the infraorbital nerve and animals were treated via selective inhibition of calcitonin gene-related peptide in the trigeminal ganglion. We assessed alterations in behavioral responses in the pre-stimulation, stimulation, and post-stimulation conditions. In vivo extracellular recordings were obtained from the ventral posteromedial nucleus of the thalamus, and viral and α-CGRP expression were investigated in the primary motor cortex and trigeminal ganglion, respectively. Results We found that optogenetic stimulation significantly improved pain behaviors in the trigeminal neuralgia animals and it provided more significant improvement with inhibited α-CGRP state than active α-CGRP state. Electrophysiological recordings revealed decreases in abnormal thalamic firing during the stimulation-on condition. Conclusion Our findings suggest that optical motor cortex stimulation can alleviate pain behaviors in a rat model of trigeminal neuropathic pain. Transmission of trigeminal pain signals can be modulated via knock-down of α-CGRP and optical motor cortex stimulation.


2020 ◽  
Author(s):  
Jaisan Islam ◽  
Elina KC ◽  
Byeong Ho Oh ◽  
Soochong Kim ◽  
Sang-hwan Hyun ◽  
...  

Abstract Background: Previous studies have reported that electrical stimulation of the motor cortex is effective in reducing trigeminal neuropathic pain; however, the effects of optical motor cortex stimulation remain unclear. Objective: The present study aimed to investigate whether optical stimulation of the primary motor cortex can modulate chronic neuropathic pain in rats with infraorbital nerve constriction injury.Methods: Animals were randomly divided into a trigeminal neuralgia group, a sham group, and a control group. Trigeminal neuropathic pain was generated via constriction of the infraorbital nerve and animals were treated via selective inhibition of calcitonin gene-related peptide in the trigeminal ganglion. We assessed alterations in behavioral responses in the pre-stimulation, stimulation, and post-stimulation conditions. In vivo extracellular recordings were obtained from the ventral posteromedial nucleus of the thalamus, and viral and α-CGRP expression were investigated in the primary motor cortex and trigeminal ganglion, respectively.Results: We found that optogenetic stimulation significantly improved pain behaviors in the trigeminal neuralgia animals and it provided more significant improvement with inhibited α-CGRP state than active α-CGRP state. Electrophysiological recordings revealed decreases in abnormal thalamic firing during the stimulation-on condition.Conclusion: Our findings suggest that optical motor cortex stimulation can alleviate pain behaviors in a rat model of trigeminal neuropathic pain. Transmission of trigeminal pain signals can be modulated via knock-down of α-CGRP and optical motor cortex stimulation.


2000 ◽  
Vol 5 (1) ◽  
pp. 107-113 ◽  
Author(s):  
Allan S Gordon

Practitioners are often presented with patients who complain bitterly of facial pain. The trigeminal nerve is involved in four conditions that are sometimes mixed up. The four conditions - trigeminal neuralgia, trigeminal neuropathic pain, postherpetic neuralgia and atypical facial pain - are discussed under the headings of clinical features, differential diagnosis, cause and treatment. This article should help practitioners to differentiate one from the other and to manage their care.


2013 ◽  
Vol 35 (3) ◽  
pp. E10 ◽  
Author(s):  
Alberto Feletti ◽  
Giannantonio Zanata Santi ◽  
Francesco Sammartino ◽  
Marzio Bevilacqua ◽  
Piero Cisotto ◽  
...  

Object Peripheral nerve field stimulation has been successfully used for many neuropathic syndromes. However, it has been reported as a treatment for trigeminal neuropathic pain or persistent idiopathic facial pain only in the recent years. Methods The authors present a review of the literature and their own series of 6 patients who were treated with peripheral nerve stimulation for facial neuropathic pain, reporting excellent pain relief and subsequent better social relations and quality of life. Results On average, pain scores in these patients decreased from 10 to 2.7 on the visual analog scale during a 17-month follow-up (range 0–32 months). The authors also observed the ability to decrease trigeminal pain with occipital nerve stimulation, clinically confirming the previously reported existence of a close anatomical connection between the trigeminal and occipital nerves (trigeminocervical nucleus). Conclusions Peripheral nerve field stimulation of the trigeminal and occipital nerves is a safe and effective treatment for trigeminal neuropathic pain and persistent idiopathic facial pain, when patients are strictly selected and electrodes are correctly placed under the hyperalgesia strip at the periphery of the allodynia region.


2005 ◽  
Vol 11 (4) ◽  
pp. 608-616 ◽  
Author(s):  
Alice Meunier ◽  
Alban Latrémolière ◽  
Annie Mauborgne ◽  
Sylvie Bourgoin ◽  
Valérie Kayser ◽  
...  

2012 ◽  
Vol 5;15 (5;9) ◽  
pp. E725-E732
Author(s):  
Jackson Cohen

Background: Facial pain occurring after traumatic injury of the facial branches of the trigeminal nerve is a medical condition that is often very difficult to treat. Patients are quite disabled by their symptoms and most therapies are ineffective in relieving this pain. Peripheral nerve stimulation has been used as a treatment to provide pain relief for this type of intractable atypical facial pain. Objective: To describe a minimally invasive peripheral nerve stimulation surgical technique for treating posttraumatic trigeminal neuralgia. Study Design: Case report based on a patient seen in a university setting with posttraumatic trigeminal neuropathic pain who underwent a minimally invasive technique for the placement of a peripheral nerve stimulator. Setting: University-based outpatient clinic. Methods: A patient with a clinical picture suggestive of trigeminal neuropathic pain secondary to trauma involving the V1 and V2 branches of the trigeminal nerve was selected. Conservative management was attempted with no improvement before peripheral nerve stimulation was tried with a minimally invasive surgical technique. We recorded the patient’s subjective assessment of pain and daily function before and after the procedure. Results: Following the procedure, the patient’s pain score decreased approximately 50% and the patient reported a better quality of life with improvement in daily function as well as a more positive outlook on her condition. There were no complications after the procedure and the patient reported no complaints with the device. Limitations: Case report. Conclusions: This surgical technique for placing peripheral nerve stimulators allows for a minimally invasive approach for the treatment of intractable posttraumatic trigeminal neuralgia with potentially less risk of facial nerve damage. This case confirms the need for further studies to be done in the future to prove the safety and effectiveness of this technique. Key Words: Peripheral nerve stimulation, posttraumatic trigeminal neuralgia, neuropathic pain, minimally invasive technique, facial pain.


2012 ◽  
Vol 1;15 (1;1) ◽  
pp. 27-33 ◽  
Author(s):  
David A. Stidd

Facial pain is a complex disease with a number of possible etiologies. Trigeminal neuropathic pain (TNP) is defined as pain caused by a lesion or disease of the trigeminal branch of the peripheral nervous system resulting in chronic facial pain over the distribution of the injured nerve. First line treatment of TNP includes management with anticonvulsant medication (carbamazepine, phenytoin, gabapentin, etc.), baclofen, and analgesics. TNP, however, can be a condition difficult to adequately treat with medical management alone. Patients with TNP can suffer from significant morbidity as a result of inadequate treatment or the side effects of pharmacologic therapy. TNP refractory to medical management can be considered for treatment with a growing number of invasive procedures. Peripheral nerve stimulation (PNS) is a minimally invasive option that has been shown to effectively treat medically intractable TNP. We present a case series of common causes of TNP successfully treated with PNS with up to a 2 year follow-up. Only one patient required implantation of new electrode leads secondary to electrode migration. The patients in this case series continue to have significant symptomatic relief, demonstrating PNS as an effective treatment option for intractable TNP. Though there are no randomized trials, peripheral neuromodulation has been shown to be an effective means of treating TNP refractory to medical management in a growing number of case series. PNS is a safe procedure that can be performed even on patients that are not optimal surgical candidates and should be considered for patients suffering from TNP that have failed medical management. Key words: Trigeminal neuropathic pain, peripheral nerve stimulation, neuromodulation, intractable pain, facial trauma, postherpetic neuralgia


2019 ◽  
Vol 37 (3) ◽  
pp. 192-198
Author(s):  
Liuyue Yang ◽  
Weihua Ding ◽  
Zerong You ◽  
Jinsheng Yang ◽  
Shiqian Shen ◽  
...  

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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