Heat hypersensitivity is attenuated with altered expression level of spinal astrocytes after sciatic nerve injury in TRPV1 knockout mice

Baba, Kazuhiko; Kawasaki, Makoto; Nishimura, Haruki; Suzuki, Hitoshi; Matsuura, Takanori; Fujitani, Teruaki; Tsukamoto, Manabu; Tokuda, Kotaro; Yamanaka, Yoshiaki; Ohnishi, Hideo; Yoshimura, Mitsuhiro; Maruyama, Takashi; Sanada, Kenya; Ueno, Hiroki; Sonoda, Shozo; Nishimura, Kazuaki; Tanaka, Kentaro; Ueta, Yoichi; Sakai, Akinori

doi:10.1016/j.neures.2020.12.007

Cited by 4 publications

(11 citation statements)

References 38 publications

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“…Increased TRPV1 expression in the superficial laminae I-II of the spinal dorsal horn has been reported in various types of pain, such as complete Freund's adjuvant (CFA)-induced inflammatory pain, sciatic nerve injury, diabetes, and paclitaxel-induced neuropathic pain [15][16][17]53]. In our study, too, the expression of spinal TRPV1 increased on D4 after oxaliplatin administration, when the pain behavior was the most developed (Figures 1-3).…”

Section: Discussionsupporting

confidence: 64%

“…Moreover, intraperitoneally injected AMG9810, a TRPV1 antagonist, lowered thermal sensitivity in the partial sciatic nerve ligation (pSNL) model [16]. Moreover, lowered thermal sensitivity was observed in TRPV1 knockout (KO) mice that had pSNL [16,17]. It is known that TRPV1 is expressed mostly in C fibers, which are known to be cold-sensitive fibers [18,19].…”

Section: Discussionmentioning

confidence: 99%

“…In several types of experimental models of neuropathies, such as sciatic nerve injury (SNL), diabetes, and paclitaxel models, TRPV1 expression in the spinal dorsal horn is upregulated [14][15][16]. Treatment with a TRPV1 antagonist attenuates pain behavior in the SNL model [17]. In an animal model of painful diabetic neuropathy, the upregulated spinal TRPV1 mRNA was downregulated with pain amelioration following oral administration of ginger extract and 6-shogaol [18].…”

Section: Introductionmentioning

confidence: 99%

“…In an animal model of painful diabetic neuropathy, the upregulated spinal TRPV1 mRNA was downregulated with pain amelioration following oral administration of ginger extract and 6-shogaol [18]. Moreover, blockade of spinal TRPV1 expression in Trpv1 knockout (KO) mice affects pain behavior, as well the activation of spinal astrocytes [14,17]. In pain conditions, the effect of spinal TRPV1 on spinal astrocytic activation needs to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

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

Lee

et al. 2021

IJMS

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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.

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Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Lee

et al. 2021

IJMS

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“…The hypersensitivity induced by lumbar 4 spinal nerve ligation in mice was completely reversed by the TRPV1 antagonist A-425619 [ 59 ]. The threshold against heat sensitivity in the L5 ipsilateral dorsal horn of the spinal cord was markedly prolonged in Trpv1-/- mice than in WT mice [ 60 ]. Capsazepine, a TRPV1 blocker, could greatly inhibit thermal hypersensitivity in a spinally sensitized state [ 61 ].…”

Section: Discussionmentioning

confidence: 99%

TRPV1 Channel Activated by the PGE2/EP4 Pathway Mediates Spinal Hypersensitivity in a Mouse Model of Vertebral Endplate Degeneration

Liu

Wang

et al. 2021

Oxidative Medicine and Cellular Longevity

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Low back pain (LBP) is the primary cause of disability globally. There is a close relationship between Modic changes or endplate defects and LBP. Endplates undergo ossification and become highly porous during intervertebral disc (IVD) degeneration. In our study, we used a mouse model of vertebral endplate degeneration by lumbar spine instability (LSI) surgery. Safranin O and fast green staining and μCT scan showed that LSI surgery led to endplate ossification and porosity, but the endplates in the sham group were cartilaginous and homogenous. Immunofluorescent staining demonstrated the innervation of calcitonin gene-related peptide- (CGRP-) positive nerve fibers in the porous endplate of LSI mice. Behavior test experiments showed an increased spinal hypersensitivity in LSI mice. Moreover, we found an increased cyclooxygenase 2 (COX2) expression and an elevated prostaglandin E2 (PGE2) concentration in the porous endplate of LSI mice. Immunofluorescent staining showed the colocalization of E-prostanoid 4 (EP4)/transient receptor potential vanilloid 1 (TRPV1) and CGRP in the nerve endings in the endplate and in the dorsal root ganglion (DRG) neurons, and western blotting analysis demonstrated that EP4 and TRPV1 expression significantly increased in the LSI group. Our patch clamp study further showed that LSI surgery significantly enhanced the current density of the TRPV1 channel in small-size DRG neurons. A selective EP4 receptor antagonist, L161982, reduced the spinal hypersensitivity of LSI mice by blocking the PGE2/EP4 pathway. In addition, TRPV1 current and neuronal excitability in DRG neurons were also significantly decreased by L161982 treatment. In summary, the PGE2/EP4 pathway in the porous endplate could activate the TRPV1 channel in DRG neurons to cause spinal hypersensitivity in LSI mice. L161982, a selective EP4 receptor antagonist, could turn down the TRPV1 current and decrease the neuronal excitability of DRG neurons to reduce spinal pain.

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The therapeutic effects of transferring remote ischemic preconditioning serum in rats with neuropathic pain symptoms

Gunduz,

Yurtgezen,

Topuz

et al. 2023

Heliyon

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Heat hypersensitivity is attenuated with altered expression level of spinal astrocytes after sciatic nerve injury in TRPV1 knockout mice

Cited by 4 publications

References 38 publications

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

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

TRPV1 Channel Activated by the PGE2/EP4 Pathway Mediates Spinal Hypersensitivity in a Mouse Model of Vertebral Endplate Degeneration

The therapeutic effects of transferring remote ischemic preconditioning serum in rats with neuropathic pain symptoms

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