Spinal Microglia Initiate and Maintain Hyperalgesia in a Rat Model of Chronic Pancreatitis

Liu, Pei–Yi; Lu, Ching–Liang; Wang, Chia–Chuan; Lee, I‐Hui; Hsieh, Jen-Chuen; Chen, Chun–Chia; Lee, Hsing–Feng; Lin, Han‐Chieh; Chang, Full‐Young; Lee, Shou–Dong

doi:10.1053/j.gastro.2011.09.041

Cited by 46 publications

(40 citation statements)

References 33 publications

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“…For example, CP patients are more sensitive to painful abdominal and rectal stimuli (37). This increased sensitivity may reflect changes in central neuronal pathways of the spinal cord and brain (47, 48). Brain MRI studies show alteration in brain thickness and microstructure in cingulate and prefrontal cortices correlating to CP patients' clinical pain scores (49, 50), reminiscent of changes seen in patients that suffer from other chronic pain states (e.g.…”

Section: Resultsmentioning

confidence: 99%

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Mechanism, assessment and management of pain in chronic pancreatitis: Recommendations of a multidisciplinary study group

et al. 2016

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Description Pain in patients with chronic pancreatitis (CP) remains the primary clinical complaint and source of poor quality of life. However, clear guidance on evaluation and treatment is lacking. Methods Pancreatic Pain working groups reviewed information on pain mechanisms, clinical pain assessment and pain treatment in CP. Levels of evidence were assigned using the Oxford system, and consensus was based on GRADE. A consensus meeting was held during PancreasFest 2012 with substantial post-meeting discussion, debate, and manuscript refinement. Results Twelve discussion questions and proposed guidance statements were presented. Conference participates concluded: Disease Mechanism: Pain etiology is multifactorial, but data are lacking to effectively link symptoms with pathologic feature and molecular subtypes. Assessment of Pain: Pain should be assessed at each clinical visit, but evidence to support an optimal approach to assessing pain character, frequency and severity is lacking. Management: There was general agreement on the roles for endoscopic and surgical therapies, but less agreement on optimal patient selection for medical, psychological, endoscopic, surgical and other therapies. Conclusions Progress is occurring in pain biology and treatment options, but pain in patients with CP remains a major problem that is inadequately understood, measured and managed. The growing body of information needs to be translated into more effective clinical care.

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Section: Resultsmentioning

confidence: 99%

“…In animal models, changes in the CNS have been reported at the spinal cord level where non-neuronal cells, including microglia and astrocytes, are activated (47, 48). These cells play a pivotal role in central sensitization in a number of models of persistent neuropathic pain.…”

Section: Resultsmentioning

confidence: 99%

Mechanism, assessment and management of pain in chronic pancreatitis: Recommendations of a multidisciplinary study group

et al. 2016

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“…Phosphorylated p38 in microglia is known to be involved in inflammatory, neuropathic, and visceral pain. 108,184 As discussed in 1.2.4, endogenous electroacupuncture-induced opioids reduce the release of neurotransmitters such as SP and subsequently inhibit glial cell activation, which might decrease p38 phosphorylation and inhibit visceral pain.…”

Section: Visceral Pain Modelsmentioning

confidence: 99%

Mechanisms of Acupuncture–Electroacupuncture on Persistent Pain

Zhang

Lao

Ren³

et al. 2014

Anesthesiology

619

465

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In the last decade, preclinical investigations of electroacupuncture mechanisms on persistent tissue-injury (inflammatory), nerve-injury (neuropathic), cancer, and visceral pain have increased. These studies show that electroacupuncture activates the nervous system differently in health than in pain conditions, alleviates both sensory and affective inflammatory pain, and inhibits inflammatory and neuropathic pain more effectively at 2–10 Hz than at 100 Hz. Electroacupuncture blocks pain by activating a variety of bioactive chemicals through peripheral, spinal, and supraspinal mechanisms. These include opioids, which desensitize peripheral nociceptors and reduce pro-inflammatory cytokines peripherally and in the spinal cord, and serotonin and norepinephrine, which decrease spinal n-methyl-d-aspartate receptor subunit GluN1 phosphorylation. Additional studies suggest that electroacupuncture, when combined with low dosages of conventional analgesics, provides effective pain management that can forestall the side effects of often-debilitating pharmaceuticals.

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“…For chronic pancreatitis, Qian et al 68 measured increased mechanical allodynia (pain resulting from a stimulus that would not normally provoke pain) in the TNBS model of chronic pancreatitis, which was associated with increased astrocytic Toll-like receptor (TLR)3 expression and reversible upon administration of TLR3 antisense oligodeoxynucleotide. Liu et al 69 showed increased nocifensive behaviour and spinal microglial activity in rats with TNBS-induced chronic pancreatitis, which were reversible upon intrathecal administration of the microglial inhibitor minocycline.…”

Section: Th9mentioning

confidence: 99%

“…87 On the basis of these functions, Schwann cells might, at least in theory, assume several other functions that go beyond our current scarce knowledge. Even less clear is the reaction of central glial cells (astrocytes and microglia), to pancreatic disease, yet these cells seem to assume an activated state during experimental chronic pancreatitis 69 and as a result of invasion into somatic nerves such as the sciatic nerve. 46 Nonetheless, based on the most up-to-date data, glial cells, although long perceived as orphan cells of the nervous system with insufficiently understood functions, might be major actors within nerve-cancer interactions in pancreatic cancer.…”

Section: A Role For Glial Cells: Still Orphan?mentioning

confidence: 99%

Neural plasticity in pancreatitis and pancreatic cancer

Demir

Frieß

Ceyhan

2015

Nat Rev Gastroenterol Hepatol

169

146

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Pancreatic nerves undergo prominent alterations during the evolution and progression of human chronic pancreatitis and pancreatic cancer. Intrapancreatic nerves increase in size (neural hypertrophy) and number (increased neural density). The proportion of autonomic and sensory fibres (neural remodelling) is switched, and are infiltrated by perineural inflammatory cells (pancreatic neuritis) or invaded by pancreatic cancer cells (neural invasion). These neuropathic alterations also correlate with neuropathic pain. Instead of being mere histopathological manifestations of disease progression, pancreatic neural plasticity synergizes with the enhanced excitability of sensory neurons, with Schwann cell recruitment toward cancer and with central nervous system alterations. These alterations maintain a bidirectional interaction between nerves and non-neural pancreatic cells, as demonstrated by tissue and neural damage inducing neuropathic pain, and activated neurons releasing mediators that modulate inflammation and cancer growth. Owing to the prognostic effects of pain and neural invasion in pancreatic cancer, dissecting the mechanism of pancreatic neuroplasticity holds major translational relevance. However, current in vivo models of pancreatic cancer and chronic pancreatitis contain many discrepancies from human disease that overshadow their translational value. The present Review discusses novel possibilities for mechanistically uncovering the role of the nervous system in pancreatic disease progression.

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Spinal Microglia Initiate and Maintain Hyperalgesia in a Rat Model of Chronic Pancreatitis

Cited by 46 publications

References 33 publications

Mechanism, assessment and management of pain in chronic pancreatitis: Recommendations of a multidisciplinary study group

Mechanism, assessment and management of pain in chronic pancreatitis: Recommendations of a multidisciplinary study group

Mechanisms of Acupuncture–Electroacupuncture on Persistent Pain

Neural plasticity in pancreatitis and pancreatic cancer

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