Intracerebroventricular injection of propranolol blocked analgesic and neuroprotective effects of resveratrol following L5 spinal nerve ligation in rat

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Mohammad Ali Zabihian ◽  
Mehdi Hosseini ◽  
Farideh Bahrami ◽  
Maryam Iman ◽  
Maedeh Ghasemi ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Analgesic Activity ◽  
Antioxidant Activities ◽  
Electrophysiological Study ◽  
Spinal Nerve ◽  
Spinal Nerve Ligation ◽  
Neuroprotective Effects ◽  
Analgesic Effects ◽  
Pain Symptoms ◽  
The Brain

Abstract Objectives Resveratrol as a natural polyphenolic agent can alleviate neuropathic pain symptoms. The mechanism of analgesic activity of resveratrol is far from clear. The current study examine whether analgesic activity of resveratrol is mediated by its neuroprotective and anti-oxidant activity in the neuropathic pain. We further examine whether analgesic activity of resveratrol is mediated by β-adrenoceptors in the brain. Methods Neuropathic pain induced by L5 spinal nerve ligation (SNL). Male Wistar rats assigned into sham, SNL, SNL + resveratrol (40 μg/5 μL), and SNL + resveratrol + propranolol (a non-selective β-adrenoceptor antagonist, 30 μg/5 μL) groups. Drugs injected intracerebroventricular (ICV) at day SNL surgery and daily for 6 days following SNL. Thermal allodynia and anxiety examined on days of −1, 2, 4, and 6 following SNL. Electrophysiological study performed on day 6 following SNL for evaluation of resveratrol effects on sciatic nerve conduction velocity (NCV). The activity of catalase (Cat) and superoxide dismutase (SOD) enzymes in the brain assessed on days 6 following SNL. Results Resveratrol significantly decreased thermal allodynia (and not anxiety) in all experimental days. Additionally, resveratrol significantly increased NCV, and also normalized the disrupted Cat and SOD activities following neuropathic pain. Furthermore, propranolol significantly blocked the analgesic and neuroprotective effects of resveratrol. Conclusions It is suggested that the analgesic effects of resveratrol is mediated by its neuroprotective and antioxidant activities in the neuropathic rats. Furthermore, propranolol blocked the analgesic and neuroprotective effects of resveratrol.

Overexpression of GDNF in the Uninjured DRG Exerts Analgesic Effects on Neuropathic Pain Following Segmental Spinal Nerve Ligation in Mice

2011 ◽  
Vol 12 (11) ◽  
pp. 1130-1139 ◽  
Author(s):  
Kumiko Takasu ◽  
Atsushi Sakai ◽  
Hideki Hanawa ◽  
Takashi Shimada ◽  
Hidenori Suzuki
Keyword(s):  
Neuropathic Pain ◽  
Spinal Nerve ◽  
Spinal Nerve Ligation ◽  
Analgesic Effects

Peripheral Nerve Injury Reduces Analgesic Effectsof Systemic Morphine via Spinal 5-Hydroxytryptamine 3 Receptors

2014 ◽  
Vol 121 (2) ◽  
pp. 362-371 ◽  
Author(s):  
Masafumi Kimura ◽  
Hideaki Obata ◽  
Shigeru Saito
Keyword(s):  
Neuropathic Pain ◽  
Peripheral Nerve ◽  
Noradrenaline Release ◽  
Peripheral Nerve Injury ◽  
Analgesic Effect ◽  
Spinal Dorsal Horn ◽  
Spinal Nerve ◽  
Spinal Nerve Ligation ◽  
Analgesic Effects ◽  
Spinal Dorsal

Abstract Background: Morphine produces powerful analgesic effects against acute pain, but it is not effective against neuropathic pain, and the mechanisms underlying this reduced efficacy remain unclear. Here, the authors compared the efficacy of systemic morphine between normal rats and rats with peripheral nerve injury, with a specific focus on descending serotonergic mechanisms. Methods: After L5 spinal nerve ligation injury, male Sprague–Dawley rats were subjected to behavioral testing, in vivo microdialysis of the spinal dorsal horn to determine serotonin (5-hydroxytryptamine [5-HT]) and noradrenaline release, and immunohistochemistry (n = 6 in each group). Results: Intraperitoneal administration of morphine (1, 3, or 10 mg/kg) produced analgesic effects in normal and spinal nerve ligation rats, but the effects were greater in normal rats (P < 0.001). Morphine increased 5-HT release (450 to 500% of the baseline), but not noradrenaline release, in the spinal dorsal horn via activation of serotonergic neurons in the rostral ventromedial medulla. Intrathecal pretreatment with ondansetron (3 μg), a 5-HT3 receptor antagonist, or 5,7-dihydroxytryptamine creatinine sulfate (100 μg), a selective neurotoxin for serotonergic terminals, attenuated the analgesic effect of morphine (10 mg/kg) in normal rats but increased the analgesic effect of morphine in spinal nerve ligation rats (both P < 0.05). Conclusions: Systemic administration of morphine increases 5-HT levels in the spinal cord, and the increase in 5-HT contributes to morphine-induced analgesia in the normal state but attenuates that in neuropathic pain through spinal 5-HT3 receptors. The plasticity of the descending serotonergic system may contribute to the reduced efficacy of systemic morphine in neuropathic pain.

scholarly journals miRNA 146a-5p-loaded poly(d,l-lactic-co-glycolic acid) nanoparticles impair pain behaviors by inhibiting multiple inflammatory pathways in microglia

Nanomedicine ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. 1113-1126
Author(s):  
Thuỳ Linh Phạm ◽  
Yuhua Yin ◽  
Hyeok Hee Kwon ◽  
Nara Shin ◽  
Song I Kim ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Inflammatory Response ◽  
P38 Mapk ◽  
Glycolic Acid ◽  
Spinal Nerve ◽  
Spinal Nerve Ligation ◽  
Pain Model ◽  
Pain Behaviors ◽  
Analgesic Effects ◽  
Neuropathic Pain Model

Aims: We investigated whether miRNA (miR) 146a-5p-loaded nanoparticles (NPs) can attenuate neuropathic pain behaviors in the rat spinal nerve ligation-induced neuropathic pain model by inhibiting activation of the NF-κB and p38 MAPK pathways in spinal microglia. Materials & methods: After NP preparation, miR NPs were assessed for their physical characteristics and then injected intrathecally into the spinal cords of rat spinal nerve ligation rats to test their analgesic effects. Results: miR NPs reduced pain behaviors for 11 days by negatively regulating the inflammatory response in spinal microglia. Conclusion: The anti-inflammatory effects of miR 146a-5p along with nanoparticle-based materials make miR NPs promising tools for treating neuropathic pain.

scholarly journals Three-dimensional analysis of the characteristics of joint motion and gait pattern in a rodent model following spinal nerve ligation

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Takayuki Seto ◽  
Hidenori Suzuki ◽  
Tomoya Okazaki ◽  
Yasuaki Imajo ◽  
Norihiro Nishida ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Pain Intensity ◽  
Rat Model ◽  
Gait Pattern ◽  
Spinal Nerve ◽  
Spinal Nerve Ligation ◽  
Joint Motion ◽  
Behavioral Reactions ◽  
Post Operation ◽  
The Right

Abstract Background The spinal nerve ligation (SNL) rat is well known as the most common rodent model of neuropathic pain without motor deficit. Researchers have performed analyses using only the von Frey and thermal withdrawal tests to evaluate pain intensity in the rat experimental model. However, these test are completely different from the neurological examinations performed clinically. We think that several behavioral reactions must be observed following SNL because the patients with neuropathic pain usually have impaired coordination of the motions of the right–left limbs and right–left joint motion differences. In this study, we attempted to clarify the pain behavioral reactions in SNL rat model as in patients. We used the Kinema-Tracer system for 3D kinematics gait analysis to identify new characteristic parameters of each joint movement and gait pattern. Results The effect of SNL on mechanical allodynia was a 47 ± 6.1% decrease in the withdrawal threshold during 1–8 weeks post-operation. Sagittal trajectories of the hip, knee and ankle markers in SNL rats showed a large sagittal fluctuation of each joint while walking. Top minus bottom height of the left hip and knee that represents instability during walking was significantly larger in the SNL than sham rats. Both-foot contact time, which is one of the gait characteristics, was significantly longer in the SNL versus sham rats: 1.9 ± 0.15 s vs. 1.03 ± 0.15 s at 4 weeks post-operation (p = 0.003). We also examined the circular phase time to evaluate coordination of the right and left hind-limbs. The ratio of the right/left circular time was 1.0 ± 0.08 in the sham rats and 0.62 ± 0.15 in the SNL rats at 4 weeks post-operation. Conclusions We revealed new quantitative parameters in an SNL rat model that are directly relevant to the neurological symptoms in patients with neuropathic pain, in whom the von Frey and thermal withdrawal tests are not used at all clinically. This new 3D analysis system can contribute to the analysis of pain intensity of SNL rats in detail similar to human patients’ reactions following neuropathic pain.

scholarly journals Oral Gabapentin Activates Spinal Cholinergic Circuits to Reduce Hypersensitivity after Peripheral Nerve Injury and Interacts Synergistically with Oral Donepezil

2007 ◽  
Vol 106 (6) ◽  
pp. 1213-1219 ◽  
Author(s):  
Ken-ichiro Hayashida ◽  
Renée Parker ◽  
James C. Eisenach
Keyword(s):  
Neuropathic Pain ◽  
Nerve Injury ◽  
Intrathecal Injection ◽  
Spinal Nerve ◽  
Male Rats ◽  
Additive Interaction ◽  
Alzheimer Dementia ◽  
Routes Of Administration ◽  
Withdrawal Threshold ◽  
The Brain

Background Gabapentin administration into the brain of mice reduces nerve injury-induced hypersensitivity and is blocked by intrathecal atropine and enhanced by intrathecal neostigmine. The authors tested the relevance of these findings to oral therapy by examining the efficacy of oral gabapentin to reduce hypersensitivity after nerve injury in rats and its interaction with the clinically used cholinesterase inhibitor, donepezil. Methods Male rats with hypersensitivity after spinal nerve ligation received gabapentin orally, intrathecally, and intracerebroventricularly with or without intrathecal atropine, and withdrawal threshold to paw pressure was determined. The effects of oral gabapentin and donepezil alone and in combination on withdrawal threshold were determined in an isobolographic design. Results Gabapentin reduced hypersensitivity to paw pressure by all routes of administration, and was more potent and with a quicker onset after intracerebroventricular than intrathecal injection. Intrathecal atropine reversed the effect of intracerebroventricular and oral gabapentin. Oral gabapentin and donepezil interacted in a strongly synergistic manner, with an observed efficacy at one tenth the predicted dose of an additive interaction. The gabapentin-donepezil combination was reversed by intrathecal atropine. Conclusions Although gabapentin may relieve neuropathic pain by actions at many sites, these results suggest that its actions in the brain to cause spinal cholinergic activation predominate after oral administration. Side effects, particularly nausea, cannot be accurately determined on rats. Nevertheless, oral donepezil is well tolerated by patients in the treatment of Alzheimer dementia, and the current study provides the rationale for clinical study of combination of gabapentin and donepezil to treat neuropathic pain.

scholarly journals Nefopam downregulates autophagy and c-Jun N-terminal kinase activity in the regulation of neuropathic pain development following spinal nerve ligation

2018 ◽  
Vol 18 (1) ◽  
Author(s):  
Seon-Hee Oh ◽  
Myung Ha Yoon ◽  
Kyung Joon Lim ◽  
Byung Sik Yu ◽  
In Gook Jee ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Kinase Activity ◽  
Spinal Nerve ◽  
Spinal Nerve Ligation
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