Pregabalin Rectifies Aberrant Brain Chemistry, Connectivity, and Functional Response in Chronic Pain Patients

Harris, Richard E.; Napadow, Vitaly; Huggins, John P.; Pauer, L.; Kim, Jieun; Hampson, Johnson P.; Sundgren, Pia C.; Foerster, Bradley R.; Petrou, M.D. Ilya; Schmidt‐Wilcke, Tobias; Clauw, Daniel J.

doi:10.1097/aln.0000000000000017

Cited by 226 publications

(238 citation statements)

References 44 publications

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“…We have shown that gabapentin blocks ICS-induced fibromyalgia-like pain via supraspinal mechanisms, whereas it inhibits nerve injury-induced neuropathic pain via spinal mechanisms (Nishiyori and Ueda, 2008). Consistently, a recent clinical neuroimaging study has shown that pregabalin inhibits neuronal connectivity in the brain regions of fibromyalgia patients (Harris et al, 2013). Therefore, neuropathic pain and fibromyalgia-like pain may show the difference in the site of donepezil actions, possibly owing to their distinct molecular basis.…”

Section: Discussionsupporting

confidence: 48%

Donepezil Reverses Intermittent Stress-Induced Generalized Chronic Pain Syndrome in Mice

Mukae

Uchida

Ueda

2015

J Pharmacol Exp Ther

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Treatment of fibromyalgia is an unmet medical need. To develop novel therapies for the treatment of fibromyalgia, we explored pain therapeutic actions of existing pharmaceuticals, which inhibit the somatic symptoms frequently observed in fibromyalgia patients. This study first examined the therapeutic actions of pilocarpine, which inhibits dry-eye and dry-mouth symptoms, using an experimental fibromyalgia-like chronic pain model produced by intermittent cold stress (ICS) in mice. A single intraperitoneal and intracerebroventricular, but not intrathecal, pilocarpine administration attenuated ICS-induced thermal hyperalgesia and mechanical allodynia, and this action was abolished by muscarinic antagonist pirenzepine (i.c.v.). Treatment with 1-10 mg/kg donepezil (i.p.), which can easily penetrate into the brain, also showed similar therapeutic effects. Importantly, we found that both pilocarpine and donepezil produced antihyperalgesic effects via supraspinal action. Furthermore, repeated donepezil treatments completely cured the ICS-induced hyperalgesia and allodynia even after the cessation of drug treatments. Acute and chronic treatments of these cholinomimetics had no effects on the nociceptive threshold in control animals. By contrast, the lack of morphine (i.c.v.) analgesia initially observed in the ICS model remained in ICS model mice treated with long-term donepezil. Collectively, these findings suggest that stimulation of the muscarinic cholinergic system effectively inhibits some mechanisms underlying chronic pain in the ICS model, but does not inhibit the lack of descending pain-inhibitory mechanisms, which are driven by central morphine.

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Section: Discussionsupporting

confidence: 48%

Donepezil Reverses Intermittent Stress-Induced Generalized Chronic Pain Syndrome in Mice

Mukae

Uchida

Ueda

2015

J Pharmacol Exp Ther

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“…PGB is believed to reduce the magnitude of the enhanced pronociception process in FMS (Crofford et al, 2005;Arnold et al, 2008;Mease et al, 2008). Imaging studies using fMRI confirmed that PGB connects neuronal connectivity and biochemical aspects of pain in FMS (Harris et al, 2013;Kim et al, 2013).…”

Section: Treatmentmentioning

confidence: 94%

Fibromyalgia Syndrome in Need of Effective Treatments

Theoharides

Tsilioni

Arbetman

et al. 2015

J Pharmacol Exp Ther

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Fibromyalgia syndrome (FMS) is a chronic, idiopathic condition of widespread musculoskeletal pain, affecting primarily women. It is clinically characterized by chronic, nonarticular pain and a heightened response to pressure along with sleep disturbances, fatigue, bowel and bladder abnormalities, and cognitive dysfunction. The diagnostic criteria have changed repeatedly, and there is neither a definitive pathogenesis nor reliable diagnostic or prognostic biomarkers. Clinical and laboratory studies have provided evidence of altered central pain pathways. Recent evidence suggests the involvement of neuroinflammation with stress peptides triggering the release of neurosenzitizing mediators. The management of FMS requires a multidimensional approach including patient education, behavioral therapy, exercise, and pain management. Here we review recent data on the pathogenesis and propose new directions for research and treatment.

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“…For instance, it has been shown that pain reduction induced by pregabalin intake was related to a decrease in connectivity between the default mode network (DMN) and the insular cortex [59], which is hyperactivated in patients with chronic pain [60,61]. In another neuroimaging study (i.e., functional MRI) evaluating the effects of M1 tDCS in patients with fibromyalgia, the authors demonstrated that tDCS induced a significant reduction in functional connectivity between the thalamus and the supplementary motor area, the medial prefrontal cortex and the cerebellum [62].…”

Section: How To Improve the Effects Of Tdcs?mentioning

confidence: 99%

Delayed pain decrease following M1 tDCS in spinal cord injury: A randomized controlled clinical trial

Thibaut

Carvalho

Morse

et al. 2017

Neuroscience Letters

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Pregabalin Rectifies Aberrant Brain Chemistry, Connectivity, and Functional Response in Chronic Pain Patients

Cited by 226 publications

References 44 publications

Donepezil Reverses Intermittent Stress-Induced Generalized Chronic Pain Syndrome in Mice

Donepezil Reverses Intermittent Stress-Induced Generalized Chronic Pain Syndrome in Mice

Fibromyalgia Syndrome in Need of Effective Treatments

Delayed pain decrease following M1 tDCS in spinal cord injury: A randomized controlled clinical trial

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