The Upregulation of Translocator Protein (18 kDa) Promotes Recovery from Neuropathic Pain in Rats

Wei, Xu-Hong; Xiao, Wei; Chen, Fengying; Zang, Ying; Xin, Wenjun; Pang, Rui‐Ping; Chen, Yuan; Wang, Jun; Li, Yongyong; Shen, Kai-Feng; Zhou, Lijun; Liu, Xianguo

doi:10.1523/jneurosci.0324-12.2013

Cited by 80 publications

(104 citation statements)

References 69 publications

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“…These findings supported the possibility that the up-regulation of neurosteroids might result from increased expression of TSPO. The increase of TSPO is consistent with previous reports in the spinal cord [43,44].…”

Section: Increased Tspo Expression Mediated the Up-regulation Of Neursupporting

confidence: 93%

“…These results are consistent with previous reports that systemic (intraperitoneal) or intrathecal administration of neurosteroids (PROG or AP) relieve or abolish established pain behaviors [17,48,49]. Intrathecal administration of Ro5-4864, another widely-used TSPO activator, also retards or prevents the development of inflammatory and neuropathic pain [43,44].…”

Section: Up-regulation Of Neurosteroids In the Lateral Thalamus Reliesupporting

confidence: 92%

“…Its expression significantly increases in the dorsal horn after neuropathic or inflammatory pain [43,44]. Here, we found that after SNI, TSPO expression increased in the lateral thalamus at a time point similar to the change of neurosteroids.…”

Section: Increased Tspo Expression Mediated the Up-regulation Of Neursupporting

confidence: 58%

“…This divergence might be due to the differences in regions, animal models, and stages of neuropathic pain. For example, we found elevated TSPO in the lateral thalamus in the chronic stage of the SNI model, while that in the dorsal horn occurs much earlier after spinal nerve ligation or CFA-induced inflammatory pain [43,44]. The molecular mechanisms underlying the upregulation of TSPO require further investigation.…”

Section: Increased Tspo Expression Mediated the Up-regulation Of Neurmentioning

confidence: 86%

“…This differs from the spinal cord where TSPO is expressed most extensively in astrocytes and microglia [43,44]. This divergence might be due to the differences in regions, animal models, and stages of neuropathic pain.…”

Section: Increased Tspo Expression Mediated the Up-regulation Of Neurmentioning

confidence: 99%

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Elevated Neurosteroids in the Lateral Thalamus Relieve Neuropathic Pain in Rats with Spared Nerve Injury

et al. 2016

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Neurosteroids are synthesized in the nervous system from cholesterol or steroidal precursors imported from peripheral sources. These compounds are important allosteric modulators of c-aminobutyric acid A receptors (GABA A Rs), which play a vital role in pain modulation in the lateral thalamus, a main gate where somatosensory information enters the cerebral cortex. Using high-performance liquid chromatography/tandem mass spectrometry, we found increased levels of neurosteroids (pregnenolone, progesterone, deoxycorticosterone, allopregnanolone, and tetrahydrodeoxycorticosterone) in the chronic stage of neuropathic pain (28 days after spared nerve injury) in rats.The expression of the translocator protein TSPO, the upstream steroidogenesis rate-limiting enzyme, increased at the same time. In vivo stereotaxic microinjection of neurosteroids or the TSPO activator AC-5216 into the lateral thalamus (AP -3.0 mm, ML ±3.0 mm, DV 6.0 mm) alleviated the mechanical allodynia in neuropathic pain, while the TSPO inhibitor PK 11195 exacerbated it. The analgesic effects of AC-5216 and neurosteroids were significantly attenuated by the GABA A R antagonist bicuculline. These results suggested that elevated neurosteroids in the lateral thalamus play a protective role in the chronic stage of neuropathic pain.

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Section: Increased Tspo Expression Mediated the Up-regulation Of Neursupporting

confidence: 93%

Section: Up-regulation Of Neurosteroids In the Lateral Thalamus Reliesupporting

confidence: 92%

Section: Increased Tspo Expression Mediated the Up-regulation Of Neursupporting

confidence: 58%

Section: Increased Tspo Expression Mediated the Up-regulation Of Neurmentioning

confidence: 86%

Section: Increased Tspo Expression Mediated the Up-regulation Of Neurmentioning

confidence: 99%

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Elevated Neurosteroids in the Lateral Thalamus Relieve Neuropathic Pain in Rats with Spared Nerve Injury

et al. 2016

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Translocator protein expression and localization in human endometrium and endometriosis: A potential target for a noninvasive diagnosis?

Casalechi,

Dela Cruz,

Assis

et al. 2024

Cell Biology International

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The limitations of current imaging methods to detect small or superficial endometriotic lesions prompt the search for new molecular targets. TSPO is an 18 KDa protein located in the outer mitochondrial membrane, which can be traced by positron emission tomography (PET) using specific ligands. TSPO is located mostly in neurons and inflammatory sites outside the brain. We hypothesized that it might also be expressed in the human endometrium and endometrial‐like tissue, being a target for molecular imaging of endometriosis. This prospective cross‐sectional study included 28 women with endometriosis and 11 endometriosis‐free controls. Endometriotic lesions (n = 49) and normal peritoneum (n = 13) from endometriosis patients were obtained during laparoscopy, while samples of eutopic endometrium from patients with endometriosis (n = 28) and from control women (n = 11) were collected in the operating room using a flexible device. TSPO mRNA expression was evaluated by quantitative reverse‐transcription real‐time PCR while protein expression was evaluated by immunohistochemistry with a monoclonal antibody antihuman TSPO. TSPO mRNA expression was detected in an invariable fashion in all tissue types evaluated; however, TSPO protein was found to be more abundant in the glandular epithelium than in the stroma, both in the endometrium and in the endometriotic lesions. Interestingly, hormone therapies did not alter the expression of TSPO, and its presence was mostly negative in tissues adjacent to endometriotic implants. As a proof of concept, the protein expression pattern of TSPO in endometriotic tissue and along the adjacent areas suggests that TSPO‐based molecular imaging might be used for noninvasive endometriosis detection.

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Activation of translocator protein alleviates mechanical allodynia and bladder dysfunction in cyclophosphamide‐induced cystitis through repression of BDNF‐mediated neuroinflammation

Huang

Zhang

et al. 2022

European Journal of Pain

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Background: Bladder pain syndrome/interstitial cystitis (BPS/IC) is a refractory disease accompanied by bladder-related pain and hyperactivity. Studies have shown that the translocator protein (TSPO) modulates neuroinflammation and central sensitisation associated with pain. Moreover, we previously demonstrated that brain-derived neurotrophic factor (BDNF) regulates neuroinflammation and mechanical allodynia in cyclophosphamide (CYP)-induced cystitis through activation of glial cells. Here, we aimed to explore whether activation of TSPO attenuates mechanical allodynia and bladder dysfunction by regulating BDNF induced neuroinflammation in a CYP-induced cystitis model. Methods: Injection of CYP was performed to form a rat model of BPS/IC. The expression of TSPO was regulated by intrathecal injection of the TSPO agonist Ro5-4864. The von Frey filament test was applied to evaluate suprapubic allodynia. Bladder function was assessed using filling cystometry. Western blotting was used to detect the expression of TSPO, BDNF, GFAP, Iba-1, p-p38, p-JNK, TNF-α, and IL-1β, and double immunofluorescence was performed to localise TSPO in the L6-S1 spinal dorsal horn (SDH). Results: TSPO was activated in the SDH after CYP injection and was primarily colocalised with astrocytes. Ro5-4864 reversed mechanical allodynia and bladder dysfunction induced by CYP. Moreover, the upregulation of BDNF and activation of astrocytes and microglia was suppressed by Ro5-4864, resulting in downregulation of p-p38, p-JNK, TNF-α, and IL-1β. Conclusions: Ro5-4864 alleviated mechanical allodynia and bladder dysfunction in the CYP model, possibly by inhibiting the elevation of BDNF and consequent activation of astrocytes and microglia induced neuroinflammation. TSPO may be a potential target for the treatment of BPS/IC.Significance: This study examined the mechanism underlying the ability of the translocator protein to modulate bladder pain syndrome/interstitial cystitis.

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The Upregulation of Translocator Protein (18 kDa) Promotes Recovery from Neuropathic Pain in Rats

Cited by 80 publications

References 69 publications

Elevated Neurosteroids in the Lateral Thalamus Relieve Neuropathic Pain in Rats with Spared Nerve Injury

Elevated Neurosteroids in the Lateral Thalamus Relieve Neuropathic Pain in Rats with Spared Nerve Injury

Translocator protein expression and localization in human endometrium and endometriosis: A potential target for a noninvasive diagnosis?

Activation of translocator protein alleviates mechanical allodynia and bladder dysfunction in cyclophosphamide‐induced cystitis through repression of BDNF‐mediated neuroinflammation

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