Activation of microglial GPR109A alleviates thermal hyperalgesia in female lupus mice by suppressing IL ‐18 and glutamatergic synaptic activity

Background: Neuropathic pain is one of the contributors to the global burdens of illness. At present many patients do not achieve satisfactory pain relief even with synthetic pain-killers. Taking this into consideration, it is necessary to search for natural product-derived alternative treatment with confirmed safety and efficacy. Ageratum conyzoides L is a plant often used as analgesic in Indonesia, however, anti-neuropathic pain activity of this plant is still unknown. Objective: To determine the anti-neuropathic pain activity of the essential oil and non-essential oil component (distillation residue) of A. conyzoides L. Methods: We conducted separation of the essential oil component from other secondary metabolites through steam distillation. Both components were tested for anti-neuropathic pain activity using chronic constriction injury animal models with thermal hyperalgesia and allodynia tests. The animals were divided into 7 test groups namely normal, sham, negative, positive (pregabalin at 0.195 mg/20 g BW of mice), essential oil component (100 mg/kg BW), and non-essential oil component (100 mg/kg BW). Naloxone was tested against the most potent anti-neuropathic pain component (essential oil or nonessential oil) to investigate the involvement of opioid receptor. Results: The GC-MS of the essential oil component indicated the presence of 60 compounds. Meanwhile, non-essential oil components contained alkaloid, flavonoid, polyphenol, quinone, steroid, and triterpenoid. This non-essential oil component contained a total flavonoid equivalent to 248.89 ppm quercetin. The anti-neuropathic pain activity test showed significantly higher activity of the essential oil component compared to the non-essential oil component and negative groups (p<0.05). Furthermore, the essential oil component showed equal activity to pregabalin (p>0.05). However, this activity was abolished by naloxone, indicating the involvement of opioid receptor in the action of the essential oil component. Conclusion: The essential oil component of A. conyzoides L is a potential novel substance for use as anti-neuropathic pain.

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NERVE INJURY-INDUCED MECHANICAL BUT NOT THERMAL HYPERALGESIA IS ATTENUATED IN NEUROKININ-1 RECEPTOR KNOCKOUT MICE

Journal of the Peripheral Nervous System ◽

10.1046/j.1529-8027.2000.00022-24.x ◽

2000 ◽

Vol 5 (4) ◽

pp. 242-242

Author(s):

H Mansikka ◽

Rn Sheth ◽

C DeVries ◽

H Lee ◽

R Winchurch ◽

...

Keyword(s):

Nerve Injury ◽

Knockout Mice ◽

Thermal Hyperalgesia ◽

Neurokinin 1 Receptor ◽

Neurokinin 1

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NIR Laser Photobiomodulation Induces Neuroprotection in an In Vitro Model of Cerebral Hypoxia/Ischemia

Molecular Neurobiology ◽

10.1007/s12035-021-02496-6 ◽

2021 ◽

Author(s):

Elisabetta Gerace ◽

Francesca Cialdai ◽

Elettra Sereni ◽

Daniele Lana ◽

Daniele Nosi ◽

...

Keyword(s):

Laser Radiation ◽

Cerebral Ischemia ◽

Molecular Mechanisms ◽

Hippocampal Slices ◽

Treatment Protocol ◽

Synaptic Activity ◽

Laser Source ◽

Therapeutic Window ◽

Hypoxia Ischemia ◽

Nir Laser

AbstractBrain photobiomodulation (PBM) is an innovative treatment for a variety of neurological conditions, including cerebral ischemia. However, the capability of PBM for ischemic stroke needs to be further explored and its mechanisms of action remain currently unclear. The aim of the present research was to identify a treatment protocol capable of inducing neuroprotection and to investigate the molecular mechanisms activated by a dual-wavelength near infrared (NIR) laser source in an organotypic hippocampal slice model of hypoxia/ischemia. Hippocampal slices were exposed to oxygen and glucose deprivation (OGD) for 30 min followed by NIR laser light (fluence 3.71, 7.42, or 14.84 J/cm2; wavelengths 808 nm and 905 nm) delivered immediately or 30 min or 60 min after OGD, in order to establish a therapeutic window. Neuronal injury was assessed by propidium iodide fluorescence 24 h later. Our results show that NIR laser irradiation attenuates OGD neurotoxicity once applied immediately or 30 min after OGD. Western blot analysis of proteins involved in neuroinflammation (iNOS, COX-2, NFkB subunit p65, and Bcl-2) and in glutamatergic-mediated synaptic activity (vGluT1, EAAT2, GluN1, and PSD95) showed that the protein modifications induced by OGD were reverted by NIR laser application. Moreover, CA1 confocal microscopy revealed that the profound morphological changes induced by OGD were reverted by NIR laser radiation. In conclusion, NIR laser radiation attenuates OGD neurotoxicity in organotypic hippocampal slices through attenuation of inflammatory mechanisms. These findings shed light on molecular definition of NIR neuroprotective mechanisms, thus underlining the potential benefit of this technique for the treatment of cerebral ischemia.

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