Knock-down of JAK2 and PTEN on pain behavior in rat model of trigeminal neuropathic pain

Li, Linan; Yao, Lingling; Wang, Fengjuan

doi:10.1016/j.gene.2019.144080

Cited by 8 publications

(6 citation statements)

References 24 publications

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“…Active astrogliosis evidenced by remarkable intense fluorescent immunoreactivity of GFAP expression (green) in spinal cord dorsal horn of CPIP mice were observed, whereas administration of propofol resulted in a reduction in GFAP expression in CPIP mice (Figure 4 responses. 17,19,20,39 These results suggest that subanaesthetic dose of propofol could produce analgesic effects for CRPS via modulating PI3K/AKT signalling.…”

Section: Effect Of Propofol On Pten/pi3k/akt Expression In Mice With ...mentioning

confidence: 79%

Sub-anaesthetic dose of propofol attenuates mechanical allodynia in chronic post-ischaemic pain via regulation of PTEN/PI3K/IL-6 signalling

et al. 2023

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Background: Propofol is an intravenous anaesthetic drug that has been shown to reduce inflammatory pain. Complex regional pain syndrome (CRPS) type I is a pain condition characterized by autonomic, motor and sensory disturbance. The chronic post-ischaemic pain (CPIP) model is a well-established model to recapture CRPS-I syndromes pre-clinically by non-invasive ischaemic-reperfusion (IR) injury. In this study, we investigated the analgesic effects of propofol and underlying mechanisms in mitigating CRPS pain using the CPIP model. Methods: Sub-anaesthetic dose of propofol (25mg/kg) was intravenously delivered to the CPIP model and sham control. Nociceptive behavioural changes were assayed by the von Frey test. Molecular assays were used to investigate expression changes of PTEN, PI3K, AKT and IL-6 underlying propofol-mediated analgesic effects. Pharmacological inhibition was applied for PTEN/PI3K/AKT pathway manipulation. Results: Both pre- and post-operative administration of propofol attenuated mechanical allodynia induced by CPIP. Propofol could modulate PTEN/PI3K/AKT signalling pathway by increasing active PTEN and reducing phosphorylated PI3K, phosphorylated AKT and IL-6 expression in the spinal dorsal horn, which promoted pain relief in the CPIP model. Inhibition of PTEN with bpV abolished the analgesic effects produced by propofol in CPIP mice. Conclusion: Sub-anaesthetic dose of propofol administration resulted in the activation of PTEN, inhibition of both PI3K/AKT signalling and IL-6 production in the spinal cord, which dramatically reduced CPIP-induced pain. Our findings lay the foundation in using propofol for the treatment of CRPS with great therapeutic implications.

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Section: Effect Of Propofol On Pten/pi3k/akt Expression In Mice With ...mentioning

confidence: 79%

Sub-anaesthetic dose of propofol attenuates mechanical allodynia in chronic post-ischaemic pain via regulation of PTEN/PI3K/IL-6 signalling

et al. 2023

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“…For the study of TN, a variety of animal models (Table 1) [3,[40][41][42][43][44][45][46][47][48][49][50][51][52][53] have been developed. All of these animal models contributed to the discovery of vital information about the TN pathway or TN therapeutic management.…”

Section: Different Animal Models For Trigeminal Neuralgia Studymentioning

confidence: 99%

Recent update on trigeminal neuralgia

Islam

Park

2022

J Korean Ster Func Neurosurg

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Trigeminal neuralgia (TN), a long-term disorder affecting the trigeminal nerve, is a form of debilitating neuropathic pain. Although the underlying pathogenesis of TN is debatable, loss of myelin along the trigeminal nerve due to direct compression from a blood vessel or secondary to other conditions such as multiple sclerosis or stroke is thought to be the principal cause. Paroxysmal sporadic pain, with unilateral onset, is the main phenomenon of TN. TN is typically diagnosed clinically. Medications, surgery, and complementary techniques are among the current therapy options for altering the neural circuits associated with TN. Nevertheless, anti-epileptic and tricyclic antidepressant medications are recognized as first-line treatments, and surgical treatment may be required for patients who have not obtained a therapeutic effect with at least three medications, have experienced intolerable side effects, or have symptoms that are not resolving. Stimulation of brain regions is an emerging off-label technique that has the potential to offer pain relief from TN, but sufficient data and more extensive studies on both animals and humans are yet to be published. More specifically, convenient diagnostic techniques and affordable treatment modalities for TN have become crucial needs in order to reduce the psychological and socio-economical losses caused by TN.

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“…<1> GDNF [38], Patched-1 (Hedgehog pathway readout) mRNA [36] <6> CGRP [30] Trigeminal ganglion Upregulation: [31], p-IκB kinase [31], p-NF-κB p65 [31], p-p38 [31] <13> EphA4 [69], IL-1β [70], JAK2 [71], p-NF-κB [72], p-p38 [72], PTEN [71], VEGF [73] <11> ATF-3 [33], BrdU (mitotic marker) [33], CD11b [33], GFAP [33], NK1 receptor [33] <12> p-ERK [34] <13> OX-42 (microglial activation) [35,74], PPARG [75] Downregulation: <1> Glutamate transporter 1 [76] <9> GRK2 [70] <10> KCC2 [77] <11> CGRP [33], GAD65 [78], SP [33] Upper central nervous system Upregulation: [95], Gabapentin/ip/mech. [95], Gabapentin/po/mech., spon.…”

Section: Trigeminal Neuron (Axon)mentioning

confidence: 99%

“…<3> (-)-α-Bisabolol (natural terpene)/po/mech [106]. <4> Capsazepine (down of JAK2)/it/mech [71],. l-α-Aminoadipic acid (astrocytic specific inhibitor) /intracisternal/mech [70],.…”

mentioning

confidence: 99%

Potential Molecular Targets for Treating Neuropathic Orofacial Pain Based on Current Findings in Animal Models

Nagakura

Nagaoka

Kurose

2021

IJMS

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This review highlights potential molecular targets for treating neuropathic orofacial pain based on current findings in animal models. Preclinical research is currently elucidating the pathophysiology of the disease and identifying the molecular targets for better therapies using animal models that mimic this category of orofacial pain, especially post-traumatic trigeminal neuropathic pain (PTNP) and primary trigeminal neuralgia (PTN). Animal models of PTNP and PTN simulate their etiologies, that is, trauma to the trigeminal nerve branch and compression of the trigeminal root entry zone, respectively. Investigations in these animal models have suggested that biological processes, including inflammation, enhanced neuropeptide-mediated pain signal transmission, axonal ectopic discharges, and enhancement of interactions between neurons and glial cells in the trigeminal pathway, are underlying orofacial pain phenotypes. The molecules associated with biological processes, whose expressions are substantially altered following trigeminal nerve damage or compression of the trigeminal nerve root, are potentially involved in the generation and/or exacerbation of neuropathic orofacial pain and can be potential molecular targets for the discovery of better therapies. Application of therapeutic candidates, which act on the molecular targets and modulate biological processes, attenuates pain-associated behaviors in animal models. Such therapeutic candidates including calcitonin gene-related peptide receptor antagonists that have a reasonable mechanism for ameliorating neuropathic orofacial pain and meet the requirements for safe administration to humans seem worth to be evaluated in clinical trials. Such prospective translation of the efficacy of therapeutic candidates from animal models to human patients would help develop better therapies for neuropathic orofacial pain.

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Knock-down of JAK2 and PTEN on pain behavior in rat model of trigeminal neuropathic pain

Cited by 8 publications

References 24 publications

Sub-anaesthetic dose of propofol attenuates mechanical allodynia in chronic post-ischaemic pain via regulation of PTEN/PI3K/IL-6 signalling

Sub-anaesthetic dose of propofol attenuates mechanical allodynia in chronic post-ischaemic pain via regulation of PTEN/PI3K/IL-6 signalling

Recent update on trigeminal neuralgia

Potential Molecular Targets for Treating Neuropathic Orofacial Pain Based on Current Findings in Animal Models

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