The implication of transient receptor potential canonical 6 in BDNF-induced mechanical allodynia in rat model of diabetic neuropathic pain

Life Sciences ◽  
2021 ◽  
Vol 273 ◽  
pp. 119308
Author(s):  
Bei Miao ◽  
Yue Yin ◽  
Guangtong Mao ◽  
Benhuo Zhao ◽  
Jiaojiao Wu ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Rat Model ◽  
Mechanical Allodynia ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Diabetic Neuropathic Pain ◽  
Transient Receptor Potential Canonical ◽  
Transient Receptor

Transient receptor potential canonical 5 mediates inflammatory mechanical and spontaneous pain in mice

2021 ◽  
Vol 13 (595) ◽  
pp. eabd7702
Author(s):  
Katelyn E. Sadler ◽  
Francie Moehring ◽  
Stephanie I. Shiers ◽  
Lauren J. Laskowski ◽  
Alexander R. Mikesell ◽  
...  
Keyword(s):  
Mechanical Allodynia ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Skin Incision ◽  
Spontaneous Pain ◽  
Cell Disease ◽  
Mechanical Hypersensitivity ◽  
Transient Receptor Potential Canonical ◽  
Pain Models ◽  
Transient Receptor

Tactile and spontaneous pains are poorly managed symptoms of inflammatory and neuropathic injury. Here, we found that transient receptor potential canonical 5 (TRPC5) is a chief contributor to both of these sensations in multiple rodent pain models. Use of TRPC5 knockout mice and inhibitors revealed that TRPC5 selectively contributes to the mechanical hypersensitivity associated with CFA injection, skin incision, chemotherapy induced peripheral neuropathy, sickle cell disease, and migraine, all of which were characterized by elevated concentrations of lysophosphatidylcholine (LPC). Accordingly, exogenous application of LPC induced TRPC5-dependent behavioral mechanical allodynia, neuronal mechanical hypersensitivity, and spontaneous pain in naïve mice. Lastly, we found that 75% of human sensory neurons express TRPC5, the activity of which is directly modulated by LPC. On the basis of these results, TRPC5 inhibitors might effectively treat spontaneous and tactile pain in conditions characterized by elevated LPC.

Antinociceptive Effects of Isosakuranetin in a Rat Model of Peripheral Neuropathy

Pharmacology ◽  
2017 ◽  
Vol 100 (3-4) ◽  
pp. 201-207 ◽  
Author(s):  
Shushan Jia ◽  
Yong Zhang ◽  
Jingui Yu
Keyword(s):  
Neuropathic Pain ◽  
Peripheral Neuropathy ◽  
Rat Model ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Sprague Dawley ◽  
Transient Receptor Potential Melastatin ◽  
Antinociceptive Effects ◽  
Cold Hyperalgesia ◽  
Transient Receptor

Chronic pain remains a challenging clinical reality, yet currently available analgesics are insufficient to meet clinical needs. Increasing attention has been paid to bioactive compounds from natural plants, which may be efficacious against pain. This study examined the antinociceptive effects of isosakuranetin, a plant-derived transient receptor potential melastatin 3 blocker, in a rat model of peripheral neuropathy. Adult male Sprague-Dawley rats were first allowed to go through the chronic constriction injury surgery to develop neuropathic pain. They were then treated with isosakuranetin (1.5, 3, or 6 mg/kg) intraperitoneally and the effects on mechanical, thermal, and cold hyperalgesia were assessed using the von Frey filament test, Hargreaves' plantar test, and cold plate test, respectively. Isosakuranetin dose-dependently alleviated mechanical, thermal, and cold hyperalgesia and the antinociceptive potency was similar across the assays. In the rotarod test, isosakuranetin did not significantly affect motor performance within the doses tested, confirming the antinociceptive specificity. In summary, these findings suggest that isosakuranetin may be useful in treating neuropathic pain and deserves further investigation.

scholarly journals JI017 Attenuates Oxaliplatin-Induced Cold Allodynia via Spinal TRPV1 and Astrocytes Inhibition in Mice

2021 ◽  
Vol 22 (16) ◽  
pp. 8811
Author(s):  
Ji Hwan Lee ◽  
Hyunseung Ji ◽  
Seong-Gyu Ko ◽  
Woojin Kim
Keyword(s):  
Neuropathic Pain ◽  
Dorsal Horn ◽  
Mechanical Allodynia ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Zingiber Officinale ◽  
Pcr Analysis ◽  
Transient Receptor Potential Vanilloid ◽  
Trpv1 Antagonist ◽  
Transient Receptor

Oxaliplatin, a well-known chemotherapeutic agent, can induce severe neuropathic pain, which can seriously decrease the quality of life of patients. JI017 is an herb mixture composed of Aconitum carmichaelii, Angelica gigas, and Zingiber officinale. Its anti-tumor effect has been reported; however, the efficacy of JI017 against oxaliplatin-induced allodynia has never been explored. Single oxaliplatin injection [6 mg/kg, intraperitoneal, (i.p.)] induced both cold and mechanical allodynia, and oral administration of JI017 (500 mg/kg) alleviated cold but not mechanical allodynia in mice. Real-time polymerase chain reaction (PCR) analysis demonstrated that the upregulation of mRNA of spinal transient receptor potential vanilloid 1 (TRPV1) and astrocytes following oxaliplatin injection was downregulated after JI017 treatment. Moreover, TRPV1 expression and the activation of astrocytes were intensely increased in the superficial area of the spinal dorsal horn after oxaliplatin treatment, whereas JI017 suppressed both. The administration of TRPV1 antagonist [capsazepine, intrathecal (i.t.), 10 μg] attenuated the activation of astrocytes in the dorsal horn, demonstrating that the functions of spinal TRPV1 and astrocytes are closely related in oxaliplatin-induced neuropathic pain. Altogether, these results suggest that JI017 may be a potent candidate for the management of oxaliplatin-induced neuropathy as it decreases pain, spinal TRPV1, and astrocyte activation.

scholarly journals The P2X7 Receptor Is Involved in Diabetic Neuropathic Pain Hypersensitivity Mediated by TRPV1 in the Rat Dorsal Root Ganglion

2021 ◽  
Vol 14 ◽  
Author(s):  
Anhui Wang ◽  
Xiangchao Shi ◽  
Ruoyang Yu ◽  
Bao Qiao ◽  
Runan Yang ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Dorsal Root Ganglion ◽  
Rat Model ◽  
Dorsal Root ◽  
Transient Receptor Potential ◽  
Intrathecal Injection ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Diabetic Neuropathic Pain ◽  
Satellite Glial Cells

The purinergic 2X7 (P2X7) receptor expressed in satellite glial cells (SGCs) is involved in the inflammatory response, and transient receptor potential vanilloid 1 (TRPV1) participates in the process of neurogenic inflammation, such as that in diabetic neuropathic pain (DNP) and peripheral neuralgia. The main purpose of this study was to explore the role of the P2X7 receptor in DNP hypersensitivity mediated by TRPV1 in the rat and its possible mechanism. A rat model of type 2 diabetes mellitus-related neuropathic pain (NPP) named the DNP rat model was established in this study. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) of DNP rats were increased after intrathecal injection of the P2X7 receptor antagonist A438079, and the mRNA and protein levels of TRPV1 in the dorsal root ganglion (DRG) were decreased in DNP rats treated with A438079 compared to untreated DNP rats; in addition, A438079 also decreased the phosphorylation of p38 and extracellular signal-regulated kinase 1/2 (ERK1/2) in the DNP group. Based on these results, the P2X7 receptor might be involved in DNP mediated by TRPV1.

scholarly journals Antagonism of Transient Receptor Potential Ankyrin Type-1 Channels as a Potential Target for the Treatment of Trigeminal Neuropathic Pain: Study in an Animal Model

2018 ◽  
Vol 19 (11) ◽  
pp. 3320 ◽  
Author(s):  
Chiara Demartini ◽  
Rosaria Greco ◽  
Anna Zanaboni ◽  
Oscar Francesconi ◽  
Cristina Nativi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Neuropathic Pain ◽  
Mechanical Allodynia ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Infraorbital Nerve ◽  
Trigeminal Neuropathic Pain ◽  
Trpv1 Channels ◽  
Transient Receptor

Transient receptor potential ankyrin type-1 (TRPA1) channels are known to actively participate in different pain conditions, including trigeminal neuropathic pain, whose clinical treatment is still unsatisfactory. The aim of this study was to evaluate the involvement of TRPA1 channels by means of the antagonist ADM_12 in trigeminal neuropathic pain, in order to identify possible therapeutic targets. A single treatment of ADM_12 in rats 4 weeks after the chronic constriction injury of the infraorbital nerve (IoN-CCI) significantly reduced the mechanical allodynia induced in the IoN-CCI rats. Additionally, ADM_12 was able to abolish the increased levels of TRPA1, calcitonin gene-related peptide (CGRP), substance P (SP), and cytokines gene expression in trigeminal ganglia, cervical spinal cord, and medulla induced in the IoN-CCI rats. By contrast, no significant differences between groups were seen as regards CGRP and SP protein expression in the pars caudalis of the spinal nucleus of the trigeminal nerve. ADM_12 also reduced TRP vanilloid type-1 (TRPV1) gene expression in the same areas after IoN-CCI. Our findings show the involvement of both TRPA1 and TRPV1 channels in trigeminal neuropathic pain, and in particular, in trigeminal mechanical allodynia. Furthermore, they provide grounds for the use of ADM_12 in the treatment of trigeminal neuropathic pain.

scholarly journals Satellite glial cells in sensory ganglia express functional transient receptor potential ankyrin 1 that is sensitized in neuropathic and inflammatory pain

2020 ◽  
Vol 16 ◽  
pp. 174480692092542 ◽  
Author(s):  
Seung Min Shin ◽  
Brandon Itson-Zoske ◽  
Yongsong Cai ◽  
Chensheng Qiu ◽  
Bin Pan ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Nerve Injury ◽  
Glial Cells ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Allyl Isothiocyanate ◽  
Sensory Ganglia ◽  
Satellite Glial Cells ◽  
Intracellular Ca ◽  
Transient Receptor

Transient receptor potential ankyrin 1 (TRPA1) is well documented as an important molecule in pain hypersensitivity following inflammation and nerve injury and in many other cellular biological processes. Here, we show that TRPA1 is expressed not only by sensory neurons of the dorsal root ganglia (DRG) but also in their adjacent satellite glial cells (SGCs), as well as nonmyelinating Schwann cells. TRPA1 immunoreactivity is also detected in various cutaneous structures of sensory neuronal terminals, including small and large caliber cutaneous sensory fibers and endings. The SGC-expressed TRPA1 is functional. Like DRG neurons, dissociated SGCs exhibit a robust response to the TRPA1-selective agonist allyl isothiocyanate (AITC) by an increase of intracellular Ca2+ concentration ([Ca2+]i). These responses are abolished by the TRPA1 antagonist HC030031 and are absent in SGCs and neurons from global TRPA1 null mice. SGCs and neurons harvested from DRG proximal to painful tissue inflammation induced by plantar injection of complete Freund’s adjuvant show greater AITC-evoked elevation of [Ca2+]i and slower recovery compared to sham controls. Similar TRPA1 sensitization occurs in both SGCs and neurons during neuropathic pain induced by spared nerve injury. Together, these results show that functional TRPA1 is expressed by sensory ganglia SGCs, and TRPA1 function in SGCs is enhanced after both peripheral inflammation and nerve injury, and suggest that TRPA1 in SGCs may contribute to inflammatory and neuropathic pain.

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