Effects of palmatine on BDNF/TrkB-mediated trigeminal neuralgia

Abstract

Trigeminal neuralgia (TN), a sudden, needle-like pain in the distribution area of the trigeminal nerve, can seriously affect the physical and mental health of patients. In chronic pain conditions including TN, increased levels of brain-derived neurotrophic factor (BDNF) may enhance pain transmission. This study compares the effect of palmatine administration on the expression of BDNF and its receptor TrkB (tropomyosin receptor kinase B) in trigeminal ganglion cells of Sprague-Dawley rats in a shamversus TN model group. Within 14 days of surgery, the mechanical allodynia threshold of the TN group was significantly lower than that of the sham group, while the TN + palmatine group had a higher mechanical pain sensitivity threshold than the TN group (p < 0.05). Real-time quantitative PCR, immunohistochemistry, and immunofluorescence showed that BDNF and TrkB expression in the TN group was higher than that in the sham group, while palmatine treatment could reverse these changes. Western blotting showed that palmatine treatment could reduce the elevated phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) in TN rats. Thus, the BDNF/TrkB pathway may be involved in the pain transmission process of TN, and palmatine treatment may reduce pain transmission by inhibiting the BDNF/TrkB pathway and suppressing ERK1/2 phosphorylation.

Inhibitory Effects of Palmatine on P2X7 Receptor Expression in Trigeminal Ganglion and Facial Pain in Trigeminal Neuralgia Rats

“…Our work revealed that 2 weeks after the treatment of TN rats with palmatine, the reduced mechanical pain threshold was significantly increased, indicating that palmatine could alleviate the neuropathic pain caused by TN. Previous work in our laboratory has shown that palmatine treatment can inhibit trigeminal neuralgia, which may be related to the downregulation of the expression of BDNF and CGRP in trigeminal ganglion neurons (He et al, 2020;Liu et al, 2020a). Moreover, after treatment with palmatine or P2X7 shRNA, the upregulated P2X7 expression at both mRNA and protein levels in TN rats was significantly counteracted.…”

Pain Relief in a Trigeminal Neuralgia Model via Optogenetic Inhibition on Trigeminal Ganglion Itself With Flexible Optic Fiber Cannula

“…The main sensory neurons of the head and face transmit pain through the TG. As a result, TG-linked components have been a widely held concern in TN research ( Liu et al, 2020 ). All such observations point to the importance of the TG in the circuitry of trigeminal neuropathic pain.…”

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

“…An investigation of glial cell activity in the trigeminal nucleus following ION ligature in rats showed that microglia and astrocytes are activated under the influence of the chemokine CCL2 at different time points, suggesting that glial cell activation is associated with the development and maintenance of PTNP [62]. Furthermore, neuroplastic changes and hyperexcitability of the central nervous system were suggested to result from substantial alterations in the expression of certain growth factors (e.g., NGF [40] and BDNF [45]) and markers of neuronal activity (e.g., p-p38 [46,51] and p-ERK [34,46,51,52]) in the brain stem and the higher central nervous system such as the mPFC. A study has shown that ERK, p38, and JNK MAPKs are accelerated in the TG of the CCI-ION rat model and that their inhibitors significantly reversed the effect of facial mechanical allodynia, suggesting that MAPKs are therapeutic targets for the treatment of chronic pain in PTNP [46].…”

“…The activation of glial cells (e.g., microglia and astrocytes) and enhancement of the interaction between neurons and glial cells occur in the trigeminal pathway [33,56]; thus, treatment with glial cell inhibitors produces antiallodynic effects [70]. Upregulation of the expression of growth factors such as NGF [40] and BDNF [45] could cause neuroplastic changes and enhance pain transmission in the trigeminal pathway [40,45]; hence, suppression of the expression of BDNF and its receptor TrkB in the TG inhibits the development of orofacial pain phenotypes [45]. Furthermore, activation of MAP kinase in the TG suggests accelerated pain signal transmission in the trigeminal pathway, thus, administration of MAP kinase inhibitors into the TG reverses facial mechanical allodynia [46].…”

“…Neurotrophin-3/local (lip)/heat[104], Olcegepant (CGRP receptor antagonist)/iv/mech [92],. Palmatine (alkaloid derived from dried rhizomes)/ip/mech [45],. PD98059 (MEK inhibitor)/intracisternal/mech [105],.…”