Oxytocin Relieves Neuropathic Pain Through GABA Release and Presynaptic TRPV1 Inhibition in Spinal Cord

Sun, Wuping; Zhou, Qian; Ba, Xiyuan; Feng, Xiao-Jin; Hu, X X; Cheng, Xiao-E; Liu, Tao; Guo, Jing; Xiao, Lizu; Jin, Jonghwa; Xiong, Dehua; Hao, Yue; Chen, Zixian; Jiang, Changyu

doi:10.3389/fnmol.2018.00248

Cited by 66 publications

(50 citation statements)

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“…Ramirez and others studied the effect of surgical hypophysectomy and the effect on the hypothalamic region, but such findings do not seem to explain how radiosurgery works. The quick-acting effect on pain relief after radiosurgical hypophysectomy goes beyond the eventual tumor response to hormonal alterations and pose even more complex questions as to the likely radiobiological effect of radiosurgery; it also possibly supports the idea of 'radiomodulation,' as the clinical effects are much faster than what is expected of tissue response or ablation to a high dose of radiation [16]. Our center directs the highest isodose towards the neurohypophysis.…”

Section: Discussionmentioning

confidence: 70%

Automated Stereotactic Gamma Ray Radiosurgery to the Pituitary Gland in Terminally Ill Cancer Patients with Opioid Refractory Pain

Lovo¹,

Campos²,

Caceros³

et al. 2019

Cureus

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Introduction We report our initial series of terminally ill cancer patients treated with radiosurgery to the pituitary gland to alleviate pain. Methods A fully automated rotating gamma ray unit was used to deliver a high dose of radiation (150Gy) using an 8 mm collimator to the neurohypophysis in 11 patients suffering from opioid-refractory pain deriving from cancer. Results From November 2016 to November 2018, 11 patients were treated, and 10 were eligible for follow-up evaluation. Pain from bone metastases was present in 70%; others suffered from neuropathic and visceral pain. The median survival was 119.7 days (range: 32 to 370). The visual analogue scale (VAS) was nine (7-10) and standardized to 10; eight patients (80%) responded. The average VAS at the time of response was three (range: 1-6), and the average time to response was 2.8 days (range: 2-5). In the first week, 40% of the patients categorized the result as 'excellent', 30% deemed the result 'good', and 20% reported the result as 'poor'. One patient (10%) referred to the result as 'regular'. Those who responded were able to reduce their medications by at least 25%. The one-month average VAS score was five (range: 1-6), 60% reported a 'good' effect, 20% reported 'excellent' results, and 20% had no response. Of the study participants, 60% maintained their level of medicine consumption at lower than baseline. At the end of life, five patients (50%) presented substantial pain, two (20%) never had a therapeutic effect, and three (30%) died without substantial pain. There were no clinical complications that could be attributed directly to the treatment. Conclusion Radiosurgery to the pituitary gland is effective and safe and warrants further investigation to understand its potential role in palliative care in cancer patients.

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Section: Discussionmentioning

confidence: 70%

Automated Stereotactic Gamma Ray Radiosurgery to the Pituitary Gland in Terminally Ill Cancer Patients with Opioid Refractory Pain

Lovo¹,

Campos²,

Caceros³

et al. 2019

Cureus

View full text Add to dashboard Cite

show abstract

“…In this context, two recent studies (Nersesyan et al, 2017 ; Sun et al, 2018 ) add a new layer to the analgesic mechanisms of the OT, suggesting that apart from the role of OTR and its downstream mechanism, this peptide also interacts (directly or indirectly) with the transient receptor potential vanilloid type1 (TRPV1) at peripheral and spinal levels. Certainly, since this channel physiologically functions as a detector of noxious stimuli (Caterina et al, 2000 ) and appears to be crucial for the transition from acute to chronic pain (Choi et al, 2016 ), there is a strong motivation to develop molecules modulating TRPV1 to treat neuropathic pain.…”

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confidence: 99%

Oxytocin, GABA, and TRPV1, the Analgesic Triad?

González‐Hernández

Charlet

2018

Front. Mol. Neurosci.

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“…Since OT plays its effects mainly by activating OTRs in the spinal cord (Jiang et al, 2014;Sun et al, 2018), we then confirmed whether spinal OTRs mediate intrathecal OT induced scratching behavior. Selective activating OTRs by its agonist, TGOT or TC OT39 (also an antagonist of V1aR) produced scratching behaviors equivalent to that induced by the same dose of OT, whereas antagonizing OTR by its antagonist, Atosiban attenuated OT-induced scratching behaviors, indicating that OTRs mediates intrathecal OT induced scratching behavior.…”

Section: Discussionmentioning

confidence: 53%

“…This intense and acute scratching behavior is usually masked by the analgesic effect of OT. However, the starting and peak time of these two actions are different: intrathecal OT-induced hindpaw scratching behavior is most obvious within 5 min, whereas the analgesic effect of intrathecal OT is most significant during 20-30 min after injection (Sun et al, 2018). These findings caught our attention.…”

Section: Discussionmentioning

confidence: 92%

Oxytocin Elicits Itch Scratching Behavior via Spinal GRP/GRPR System

Guo

Matsuda

et al. 2020

Front. Neurosci.

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Oxytocin (OT), a neuropeptide involved in the regulation of complex social and sexual behavior in mammals, has been proposed as a treatment for a number of psychiatric disorders including pain. It has been well documented that central administration of OT elicits strong scratching and grooming behaviors in rodents. However, these behaviors were only described as symptoms, few studies have investigated their underlying neural mechanisms. Thus, we readdressed this question and undertook an analysis of spinal circuits underlying OT-induced scratching behavior in the present study. We demonstrated that intrathecal OT induced robust but transient hindpaw scratching behaviors by activating spinal OT receptors (OTRs). Combining the pre-clinical and clinical evidence, we speculated that OT-induced scratching may be an itch symptom. Further RNAscope studies revealed that near 80% spinal GRP neurons expressed OTRs. OT activated the expression of c-fos mRNA in spinal GRP neurons. Chemical ablation of GRPR neurons significantly reduced intrathecal OT-induced scratching behaviors. Given GRP/GRPR pathway plays an important role in spinal itch transmission, we proposed that OT binds to the OTRs expressed on the GRP neurons, and activates GRP/GRPR pathway to trigger itch-scratching behaviors in mice. These findings provide novel evidence relevant for advancing understanding of OT-induced behavioral changes, which will be important for the development of OT-based drugs to treat a variety of psychiatric disorders.

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Oxytocin Relieves Neuropathic Pain Through GABA Release and Presynaptic TRPV1 Inhibition in Spinal Cord

Cited by 66 publications

References 50 publications

Automated Stereotactic Gamma Ray Radiosurgery to the Pituitary Gland in Terminally Ill Cancer Patients with Opioid Refractory Pain

Automated Stereotactic Gamma Ray Radiosurgery to the Pituitary Gland in Terminally Ill Cancer Patients with Opioid Refractory Pain

Oxytocin, GABA, and TRPV1, the Analgesic Triad?

Oxytocin Elicits Itch Scratching Behavior via Spinal GRP/GRPR System

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