scholarly journals Loss of cortical control over the descending pain modulatory system determines the development of the neuropathic pain state in rats

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Robert AR Drake ◽  
Kenneth A Steel ◽  
Richard Apps ◽  
Bridget M Lumb ◽  
Anthony E Pickering
Keyword(s):  
Neuropathic Pain ◽  
Nerve Injury ◽  
Inhibitory Control ◽  
Affective State ◽  
Cortical Control ◽  
Post Injury ◽  
Ongoing Activity ◽  
Sensory Hypersensitivity ◽  
Pain State ◽  
Neuropathic Pain State

The loss of descending inhibitory control is thought critical to the development of chronic pain but what causes this loss in function is not well understood. We have investigated the dynamic contribution of prelimbic cortical neuronal projections to the periaqueductal grey (PrL-P) to the development of neuropathic pain in rats using combined opto- and chemogenetic approaches. We found PrL-P neurons to exert a tonic inhibitory control on thermal withdrawal thresholds in uninjured animals. Following nerve injury, ongoing activity in PrL-P neurons masked latent hypersensitivity and improved affective state. However, this function is lost as the development of sensory hypersensitivity emerges. Despite this loss of tonic control, opto-activation of PrL-P neurons at late post-injury timepoints could restore the anti-allodynic effects by inhibition of spinal nociceptive processing. We suggest that the loss of cortical drive to the descending pain modulatory system underpins the expression of neuropathic sensitisation after nerve injury.

scholarly journals Loss of cortical control over the descending pain modulatory system determines the development of the neuropathic pain state in rats

2020 ◽  
Author(s):  
RAR Drake ◽  
KAJ Steel ◽  
R Apps ◽  
BM Lumb ◽  
AE Pickering
Keyword(s):  
Neuropathic Pain ◽  
Nerve Injury ◽  
Inhibitory Control ◽  
Affective State ◽  
Cortical Control ◽  
Post Injury ◽  
Ongoing Activity ◽  
Sensory Hypersensitivity ◽  
Pain State ◽  
Neuropathic Pain State

AbstractThe loss of descending inhibitory control is thought critical to the development of chronic pain but what causes this loss in function is not well understood. We have investigated the dynamic contribution of prelimbic cortical neuronal projections to the periaqueductal grey (PrL-P) to the development of neuropathic pain in rats using combined opto- and chemo-genetic approaches. We found PrL-P neurons to exert a tonic inhibitory control on thermal withdrawal thresholds in uninjured animals. Following nerve injury, ongoing activity in PrL-P neurons masked latent hypersensitivity and improved affective state. However, this function is lost as the development of sensory hypersensitivity emerges. Despite this loss of tonic control, opto-activation of PrL-P neurons at late post-injury timepoints could restore the anti-allodynic effects by inhibition of spinal nociceptive processing. We suggest that the loss of cortical drive to the descending pain modulatory system underpins the expression of neuropathic sensitisation after nerve injury.

scholarly journals Effects of Exogenous Galanin on Neuropathic Pain State and Change of Galanin and Its Receptors in DRG and SDH after Sciatic Nerve-Pinch Injury in Rat

PLoS ONE ◽  
2012 ◽  
Vol 7 (5) ◽  
pp. e37621 ◽  
Author(s):  
Xiaofeng Xu ◽  
Xiangdong Yang ◽  
Ping Zhang ◽  
Xiuying Chen ◽  
Huaxiang Liu ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Pain State ◽  
Neuropathic Pain State

Effect of Methylprednisolone on Neuropathic Pain and Spinal Glial Activation in Rats

2004 ◽  
Vol 100 (5) ◽  
pp. 1249-1257 ◽  
Author(s):  
Kenji Takeda ◽  
Shigehito Sawamura ◽  
Hiroshi Sekiyama ◽  
Hisayoshi Tamai ◽  
Kazuo Hanaoka
Keyword(s):  
Neuropathic Pain ◽  
Mechanical Allodynia ◽  
Day Treatment ◽  
Thermal Hyperalgesia ◽  
Spinal Nerve ◽  
Spinal Nerve Ligation ◽  
Glial Activation ◽  
Pain State ◽  
Protein Immunoreactivity ◽  
Neuropathic Pain State

Background Basic data are lacking regarding the efficacy and mechanisms of action of corticosteroids in neuropathic pain. Because recent studies indicate that spinal glial activation mediates the pathologic pain states, the authors sought to determine the effects of systemic and intrathecal methylprednisolone on the development and maintenance of neuropathic pain and spinal glial activation in a rat model. Methods Rats were anesthetized, and L5 and L6 spinal nerves were tightly ligated. Then, continuous infusion of systemic (4 mg x kg(-1) x day(-1)) or intrathecal (80 microg x kg(-1) x day(-1)) methylprednisolone or saline was started. Mechanical allodynia and thermal hyperalgesia were evaluated on days 4 and 7 postoperatively with von Frey and Hargreaves tests, respectively. Spinal astrocytic activation was evaluated with glial fibrillary acidic protein immunoreactivity on day 7. In other groups of rats, continuous 3-day treatment with intrathecal methylprednisolone or saline was started 7 days after spinal nerve ligation, when neuropathic pain had already developed. Behavioral tests and immunostaining were performed up to 3 weeks after the treatment. Results Spinal nerve ligation induced mechanical allodynia and thermal hyperalgesia on days 4 and 7 postoperatively. Glial fibrillary acidic protein immunoreactivity was remarkably enhanced on day 7. Both systemic and intrathecal methylprednisolone inhibited the development of neuropathic pain states and glial activation. Three-day treatment with intrathecal methylprednisolone reversed existing neuropathic pain state and glial activation up to 3 weeks after the treatment. Conclusion : Systemic and intrathecal methylprednisolone inhibited spinal glial activation and the development and maintenance of a neuropathic pain state in a rat model of spinal nerve ligation.

Post-injury administration of minocycline: An effective treatment for nerve-injury induced neuropathic pain

2011 ◽  
Vol 70 (3) ◽  
pp. 305-312 ◽  
Author(s):  
Xiao-Peng Mei ◽  
Hao Xu ◽  
Cheng Xie ◽  
Jun Ren ◽  
Yang Zhou ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Effective Treatment ◽  
Nerve Injury ◽  
Post Injury

scholarly journals Albiflorin Attenuates Mood Disorders Under Neuropathic Pain State by Suppressing the Hippocampal NLRP3 Inflammasome Activation During Chronic Constriction Injury

2020 ◽  
Author(s):  
Pei Liu ◽  
Jianjun Chen ◽  
Shuai Ma ◽  
Jianjun Zhang ◽  
Jianyu Zhou
Keyword(s):  
Neuropathic Pain ◽  
Mood Disorders ◽  
Nlrp3 Inflammasome ◽  
Chronic Constriction Injury ◽  
Anxiety And Depression ◽  
Inflammasome Activation ◽  
Nuclear Factor ◽  
Nlrp3 Inflammasome Activation ◽  
Pain State ◽  
Neuropathic Pain State

Abstract Background Neuropathic pain is a multifaceted and ubiquitous disease across the globe. Mood disorders, such as anxiety and depression, are frequently observed in patients suffering from neuropathic pain. Both neuropathic pain and comorbid mood disorders seriously impact quality of life. Accumulated evidence shows that activation of the NOD-like receptor protein 3 (NLRP3) inflammasome is involved in the neuroinflammatory pathogenesis of neuropathic pain, anxiety, and depression. However, the role of the NLRP3 inflammasome in the pathological process of anxiety and depression under the neuropathic pain state has not been fully described. Albiflorin, a monoterpene glycoside, may be a potential regulator of the NLRP3 inflammasome, but it is not clear whether albiflorin relates to NLRP3 inflammasome activation. Methods We used a systematic pharmacological method to confirm whether the activation of the NLRP3 inflammasome in the hippocampus was involved in the development of neuropathic pain associated with mood disorders and whether albiflorin could be an effective treatment for these symptoms. Results The NLRP3 inflammasome contributed to the neuropathic pain and comorbid anxiety and depression-like behaviors induced by chronic constriction injury of the sciatic nerve, and albiflorin may relieve these symptoms via inhibition of the NLRP3 inflammasome activity. Moreover, albiflorin enhanced the translocation of the nuclear factor erythroid 2-related factor 2 into the nucleus and suppressed nuclear factor-kappa B activity in the hippocampus. Conclusions Albiflorin, as a potential therapeutic agent, might greatly improve the overall symptoms of neuropathic pain.

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