scholarly journals ERK activation in noradrenergic and serotonergic brainstem nuclei in chronic pain upon noxious stimulation and antidepressants treatment

2009 ◽  
Vol 15 (S3) ◽  
pp. 7-8
Author(s):  
G. Borges ◽  
E. Berrocoso ◽  
A. Ortega-Alvaro ◽  
J. A. Micó ◽  
F. L. Neto
Keyword(s):  
Chronic Pain ◽  
Neuropathic Pain ◽  
Chronic Constriction Injury ◽  
Noxious Stimulation ◽  
Analgesic Action ◽  
Chronic Neuropathic Pain ◽  
Erk Activation ◽  
Pain Transmission ◽  
Extracellular Signal ◽  
Brainstem Nuclei

AbstractChronic neuropathic pain is a pathology that affects thousands of people worldwide. Antidepressants have been prescribed for the treatment of this sort of pain but the mechanisms underlying their analgesic action remain unknown. Extracellular-signal regulated kinases (ERKs) are being implicated in pain transmission and modulation as well as in the pathophysiology of depression. In order to clarify some of the mechanisms which might be related to the analgesic effect of antidepressants, we started by evaluating possible changes in the pattern of activation of ERKs in rats with chronic constriction injury (CCI), an experimental model of chronic

scholarly journals Alpha lipoic acid attenuated neuropathic pain induced by chronic constriction Injury of sciatic nerve in rats

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Prasad Neerati ◽  
Harika Prathapagiri
Keyword(s):  
Neuropathic Pain ◽  
Peripheral Neuropathy ◽  
Sciatic Nerve ◽  
Lipoic Acid ◽  
Normal Saline ◽  
Chronic Constriction Injury ◽  
Thermal Hyperalgesia ◽  
Alpha Lipoic Acid ◽  
Chronic Neuropathic Pain ◽  
Neuropathic Pain Syndrome

Abstract Background Chronic neuropathic pain syndrome is associated with impaired quality of life and is poorly manageable. Alpha lipoic acid (ALA) is a powerful antioxidant and showed its effectiveness on diabetic neuropathy and other acute peripheral nerve injuries but it was not evaluated in the chronic neuropathic pain, chronic constriction injury (CCI) in rat model by using duloxetine (DLX) as standard. Methodology The main objective of the study was to expedite ALA effect on chronic peripheral neuropathy induced by CCI of sciatic nerve in rats. In this study, male Wister rats were randomly divided into six groups (n = 8) including, normal saline, sham operated, surgery control, DLX 30mg/kg treated, ALA treated 25mg/kg, and ALA+DLX. The CCI of sciatic nerve was conducted on all animals except normal saline group and studied for 21 days (i.e. 14 days treatment period & 7 days treatment free period) by using different behavioral, biochemical and, histopathology studies. Results ALA showed minor but significant decrease of thermal hyperalgesia, cold allodynia, malondialdehyde (MDA), total protein, lipid peroxidation, and nitric oxide levels and significant increase of motor coordination, glutathione level and decreased axonal degeneration significantly. These effects sustained even during treatment free period. ALA enhanced the effect of DLX when given in combination by showing sustained effect. In conclusion, ALA acted as potent antioxidant may be this activity is responsible for the potent neuroprotective effect. Conclusion Hence, ALA attenuated the nueroinflammation mediated by chronic peripheral neuropathy. Further studies are warranted with ALA to develop as a clinically relevant therapeutic agent for the treatment of neuropathic pain.

Senkyunolide I Relieves Neuropathic Pain Induced by Chronic Constriction Injury by Inhibiting Activation of Microglia

2021 ◽  
Vol 20 (2) ◽  
pp. 253-258
Author(s):  
Xiaomin Huang ◽  
Miao Huo
Keyword(s):  
Neuropathic Pain ◽  
Chronic Constriction Injury ◽  
Biological Activities ◽  
Bioactive Components ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Induced Apoptosis ◽  
Kinase Pathway ◽  
Senkyunolide I

As an alternative to the use of narcotics, generally refractory to long-term effectiveness, for the management of neuropathic pain, we have explored the utility of senkyunolide I. Senkyunolide I is one of the bioactive components isolated from Ligusticum chuanxiong Hort known to exhibit multiple biological activities. In this study, we report senkyunolide I inhibition of chronic constriction injury induced neuropathic pain. Mechanistically, senkyunolide I inhibited chronic constriction injury induced apoptosis and the activity of microglia via extracellular signal regulated kinase pathway. We therefore suggest that senkyunolide I could serve as a promising drug for the treatment of neuropathic pain.

Chronic neuropathic pain after traumatic peripheral nerve injuries in the upper extremity: prevalence, demographic and surgical determinants, impact on health and on pain medication

2019 ◽  
Vol 20 (1) ◽  
pp. 95-108
Author(s):  
Adriana Miclescu ◽  
Antje Straatmann ◽  
Panagiota Gkatziani ◽  
Stephen Butler ◽  
Rolf Karlsten ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Neuropathic Pain ◽  
Peripheral Nerve ◽  
Upper Extremity ◽  
Nerve Injury ◽  
Persistent Pain ◽  
Peripheral Nerve Injuries ◽  
Nerve Injuries ◽  
Chronic Neuropathic Pain ◽  
Younger Age

AbstractBackground and aimsAside from the long term side effects of a nerve injury in the upper extremity with devastating consequences there is often the problem of chronic neuropathic pain. The studies concerning the prevalence of persistent pain of neuropathic origin after peripheral nerve injuries are sparse. The prevalence and risk factors associated with chronic neuropathic pain after nerve injuries in the upper extremity were assessed.MethodsA standardized data collection template was employed prospectively and retrospectively for all patients with traumatic nerve injuries accepted at the Hand Surgery Department, Uppsala, Sweden between 2010 and 2018. The template included demographic data, pain diagnosis, type of injured nerve, level of injury, date of the lesion and repair, type of procedure, reoperation, time since the procedure, S-LANSS questionnaire (Self report-Leeds Assessment of Neuropathic Symptoms and Signs), RAND-36 (Item short form health survey), QuickDASH (Disability of Shoulder, Arm and Hand) and additional questionnaires concerned medication, pain intensity were sent to 1,051 patients with nerve injuries. Partial proportional odds models were used to investigate the association between persistent pain and potential predictors.ResultsMore than half of the patients undergoing a surgical procedure developed persistent pain. Prevalence of neuropathic pain was 73% of the patients with pain (S-LANSS ≥ 12 or more). Multivariate analysis indicated that injury of a major nerve OR 1.6 (p = 0.013), years from surgery OR 0.91 (p = 0.01), younger age OR 0.7 (p < 0.001), were the main factors for predicting pain after surgery. The type of the nerve injured was the strongest predictor for chronic pain with major nerves associated with more pain (p = 0.019).ConclusionsA high prevalence of chronic pain and neuropathic pain with a negative impact on quality of life and disability were found in patients after traumatic nerve injury. Major nerve injury, younger age and less time from surgery were predictors for chronic pain.

Silencing of IRF3 alleviates chronic neuropathic pain following chronic constriction injury

2017 ◽  
Vol 88 ◽  
pp. 403-408 ◽  
Author(s):  
Rui Li ◽  
Li-guo Wang ◽  
Qi Wang ◽  
Zhi-hua Li ◽  
Ya-li Ma ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Chronic Constriction Injury ◽  
Chronic Neuropathic Pain

Neurosteroid Allopregnanolone Suppresses Median Nerve Injury–induced Mechanical Hypersensitivity and Glial Extracellular Signal–regulated Kinase Activation through γ-Aminobutyric Acid Type A Receptor Modulation in the Rat Cuneate Nucleus

2016 ◽  
Vol 125 (6) ◽  
pp. 1202-1218 ◽  
Author(s):  
Chun-Ta Huang ◽  
Seu-Hwa Chen ◽  
June-Horng Lue ◽  
Chi-Fen Chang ◽  
Wen-Hsin Wen ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Median Nerve ◽  
Nerve Injury ◽  
Type A ◽  
Aminobutyric Acid ◽  
Erk Activation ◽  
Extracellular Signal Regulated Kinase ◽  
Acid Type ◽  
Extracellular Signal ◽  
Median Nerve Injury

Abstract Background Mechanisms underlying neuropathic pain relief by the neurosteroid allopregnanolone remain uncertain. We investigated if allopregnanolone attenuates glial extracellular signal-regulated kinase (ERK) activation in the cuneate nucleus (CN) concomitant with neuropathic pain relief in median nerve chronic constriction injury (CCI) model rats. Methods We examined the time course and cellular localization of phosphorylated ERK (p-ERK) in CN after CCI. We subsequently employed microinjection of a mitogen-activated protein kinase kinase (ERK kinase) inhibitor, PD98059, to clarify the role of ERK phosphorylation in neuropathic pain development. Furthermore, we explored the effects of allopregnanolone (by mouth), intra-CN microinjection of γ-aminobutyric acid type A receptor antagonist (bicuculline) or γ-aminobutyric acid type B receptor antagonist (phaclofen) plus allopregnanolone, and allopregnanolone synthesis inhibitor (medroxyprogesterone; subcutaneous) on ERK activation and CCI-induced behavioral hypersensitivity. Results At 7 days post-CCI, p-ERK levels in ipsilateral CN were significantly increased and reached a peak. PD98059 microinjection into the CN 1 day after CCI dose-dependently attenuated injury-induced behavioral hypersensitivity (withdrawal threshold [mean ± SD], 7.4 ± 1.1, 8.7 ± 1.0, and 10.3 ± 0.8 g for 2.0, 2.5, and 3.0 mM PD98059, respectively, at 7 days post-CCI; n = 6 for each dose). Double immunofluorescence showed that p-ERK was localized to both astrocytes and microglia. Allopregnanolone significantly diminished CN p-ERK levels, glial activation, proinflammatory cytokines, and behavioral hypersensitivity after CCI. Bicuculline, but not phaclofen, blocked all effects of allopregnanolone. Medroxyprogesterone treatment reduced endogenous CN allopregnanolone and exacerbated nerve injury-induced neuropathic pain. Conclusions Median nerve injury-induced CN glial ERK activation modulated the development of behavioral hypersensitivity. Allopregnanolone attenuated glial ERK activation and neuropathic pain via γ-aminobutyric acid type A receptors. Reduced endogenous CN allopregnanolone after medroxyprogesterone administration rendered rats more susceptible to CCI-induced neuropathy.

scholarly journals Dorsal Root Ganglion (DRG) and Chronic Pain

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Amnon A. Berger ◽  
Yao Liu ◽  
HarLee Possoit ◽  
Anna C. Rogers ◽  
Warner Moore ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Chronic Pain ◽  
Neuropathic Pain ◽  
Dorsal Root ◽  
Randomized Trials ◽  
Pain Treatment ◽  
Common Condition ◽  
Significant Morbidity ◽  
Chronic Neuropathic Pain

Context: Chronic neuropathic pain is a common condition, and up to 11.9% of the population have been reported to suffer from uncontrolled neuropathic pain. Chronic pain leads to significant morbidity, lowered quality of life, and loss of workdays, and thus carries a significant price tag in healthcare costs and lost productivity. dorsal root ganglia (DRG) stimulation has been recently increasingly reported and shows promising results in the alleviation of chronic pain. This paper reviews the background of DRG stimulation, anatomical, and clinical consideration and reviews the clinical evidence to support its use. Evidence Acquisition: The DRG span the length of the spinal cord and house the neurons responsible for sensation from the periphery. They may become irritated by direct compression or local inflammation. Glial cells in the DRG respond to nerve injury, producing inflammatory markers and contribute to the development of chronic pain, even after the resolution of the original insult. While the underlying mechanism is still being explored, recent studies explored the efficacy of DRG stimulation and neuromodulation for chronic pain treatment. Results: Several reported cases and a small number of randomized trials were published in recent years, describing different methods of DRG stimulation and neuromodulation with promising results. Though evidence quality is mostly low, these results provide evidence to support the utilization of this technique. Conclusions: Chronic neuropathic pain is a common condition and carries significant morbidity and impact on the quality of life. Recent evidence supports the use of DRG neuromodulation as an effective technique to control chronic pain. Though studies are still emerging, the evidence appears to support this technique. Further studies, including large randomized trials evaluating DRG modulation versus other interventional and non-interventional techniques, are needed to further elucidate the efficacy of this method. These studies are also likely to inform the patient selection and the course of treatment.

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