Attenuation Effect of Spinal Manipulation on Neuropathic and Postoperative Pain Through Activating Endogenous Anti-Inflammatory Cytokine Interleukin 10 in Rat Spinal Cord

Song, Xue-Jun; Huang, Zhi-Jiang; Wc, Song; Song, Xuesong; Fuhr, Arlan F.; Rosner, Anthony L.; Ndtan, Harrison; Rupert, Ronald L.

doi:10.1016/j.jmpt.2015.12.004

Cited by 23 publications

(58 citation statements)

References 30 publications

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“…The expression of c-Fos is inducted after DRG inflammation, DRG neuron hyperexcitability, and neuropathic pain hypersensitivity [75,76], including PAR2 involved nociception [77]. c-Fos increases the expression of proinflammatory cytokines and causes neurochemical alterations in the DRG neurons [18,78]. In the present study, the pain induced by SL-NH2 injection indicated that PAR2 is activated.…”

Section: Discussionsupporting

confidence: 51%

“…PKC is one of the downstream pathways of PAR2 which contributes to neuropathic pain and blocking PKC can significantly diminish the hyperalgesia [17]. Moreover, PKC pathway can trigger the expression of the proinflammatory cytokines in DRG and spinal cord [18]. Since PAR2 is present in DRG neuronal populations, the role of PAR2 activation in the neuronal inflammation and the mediation of PKC activation via PAR2 remains unknown.…”

Section: Introductionmentioning

confidence: 99%

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The mechanisms of protease-activated receptor 2 in mediating pain behaviors through nonselective cation channel signaling

Yue

Wang

Lau

et al. 2020

Preprint

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Background: Activation of purinergic receptor P2X ligand-gated ion channel 3 (P2X3), transient receptor potential vanilloid type 1 (TRPV1), and transient receptor potential ankyrin 1 (TRPA1) by their specific ligands is a major mechanism contributing to magnified pain responses. The relationship between these nonselective cation channels and proteinase-activated receptor 2 (PAR2) activation mediated pain is still to be clarified.Methods: In this study, both in vitro model of dorsal root ganglion (DRG) neurons with PAR2 agonist SL-NH2 challenge and SL-NH2-induced pain rat model were used to approach these questions. The expression of P2X3, TRPV1, and TRPA1 in DRG neurons was investigated by quantitative real-time RT-PCR, Western blot, and immunofluorescence. The involvement of the PLCβ3/PKCε signaling pathway was also determined. The behavior test for mechanical allodynia and thermal hyperalgesia was performed. Results: SL-NH2 induced upregulation of P2X3, TRPV1, and TRPA1 through phosphorylation of phospholipase Cβ3 (PLCβ3) and protein kinase Cε (PKCε) signaling pathway in DRG neurons in vitro and in vivo. SL-NH2 also elevated the proportion of P2X3-, TRPV1-, and TRPA1-expressing neurons. The upregulation of P2X3, TRPV1, and TRPA1 and phosphorylation of PLCβ3 and PKCε in DRG neurons was paralleled with mechanical allodynia and thermal hyperalgesia behaviors in rats. Conclusions: The data of the present study imply that SL-NH2 as a noxious stimulus activates PAR2 which induces TRPV1, TRPA1, and P2X3 upregulation through PLCβ3/PKCε signaling pathway, thereby decreasing activation thresholds and increasing excitability, resulting in sustained nociceptive activity in DRG neurons, and then causing mechanical allodynia and thermal hyperalgesia behaviors. These data expanded our knowledge about PAR2-mediated pain sensitivity and its relationship with TRPV1, TRPA1, and P2X3 and provided new opportunities on management of pain behaviors.

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Section: Discussionsupporting

confidence: 51%

Section: Introductionmentioning

confidence: 99%

The mechanisms of protease-activated receptor 2 in mediating pain behaviors through nonselective cation channel signaling

Yue

Wang

Lau

et al. 2020

Preprint

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“…Basic science (Vaillant et al 2012; Reed et al 2013; Reed et al 2014b; Onifer et al 2015; Reed et al 2015a; Reed et al 2015b; Song et al 2016) and clinical (Bishop et al 2011; Nougarou et al 2013; Sparks et al 2013; Bialosky et al 2014; Nougarou et al 2014; Page et al 2014) studies have begun to focus much greater attention on potential physiological mechanisms associated with non-pharmacological manual therapy interventions. A functional magnetic resonance imaging study investigating supraspinal activation related to noxious mechanical stimulation pre-and post-thrust spinal manipulation reported that while bilateral activation of the thalami, cerebellum, amygdala, periaqueductal gray, insular cortex, anterior cingulated cortex, somatosensory cortices, supplementary motor area, and premotor areas occurred with peripheral noxious stimulation; only the insular cortex demonstrated a significant relationship between pain-reduction and post-spinal manipulation (Sparks et al 2013).…”

Section: Discussionmentioning

confidence: 99%

Decreased spontaneous activity and altered evoked nociceptive response of rat thalamic submedius neurons to lumbar vertebra thrust

et al. 2017

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Objectives The thalamus is a central structure important to modulating and processing all mechanoreceptor input destined for the cortex. A large number of diverse mechanoreceptor endings are stimulated when a high velocity low amplitude thrust is delivered to the lumbar spine during spinal manipulation. The objective of this study was to determine if a lumbar thrust alters spontaneous and/or evoked nociceptive activity in medial thalamic submedius (Sm) neurons. Methods Extracellular recordings were obtained from 94 thalamic Sm neurons in 54 urethane-anesthetized adult Wistar rats. Spontaneous activity was recorded 5min before and after an L5 control (no thrust) and thrust (85% rat body weight; 100ms) procedure. In a subset of responsive nociceptive specific neurons, mean changes in noxious evoked response (10s pinch with clip; 795g) at 3 sites (tail, contra- and ipsilateral hindpaw) were determined following an L5 thrust. Mean changes in Sm spontaneous activity (60s bins) and evoked noxious response were compared using a mixed model repeated measures ANOVA with Bonferonni post hoc t-tests and paired t-tests, respectively. Results Compared to control, spontaneous Sm activity decreased 180–240s following the lumbar thrust (p<0.005). Inhibitory evoked responses were attenuated in the contralateral hindpaw following an L5 thrust compared to control (p<0.05). No other changes in spontaneous or noxious evoked Sm activity were found. Conclusions A delayed, but prolonged suppression of spontaneous Sm activity along with changes in noxious evoked inhibitory responses in the contralateral hindpaw following lumbar vertebra thrust suggest that thalamic submedius neurons may play a role in central pain modulation related to manual therapy intervention.

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“…67 The use of osteopathic manipulation, whether provided by US-trained osteopathic physicians or foreign-trained osteopaths, has shown measurable improvements with muscle function, pain reduction, and emotional distress. [68][69][70][71][72][73][74][75][76] In a pilot study by Perrin et al, 68 Although osteopathic ME/CFS research is limited, enough is known about OMM to support its application for patients with ME/CFS. Treatments have been shown to decrease muscle pain, cortical potentials, and muscle spasms.…”

Section: Osteopathic Medicinementioning

confidence: 99%

Understanding Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and the Emerging Osteopathic Approach: A Narrative Review

Larrimore¹,

Ramnot²,

Jaghab³

et al. 2019

The Journal of the American Osteopathic Association

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Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating syndrome of unknown origin, characterized by profound postexertional malaise and fatigue, unrefreshing sleep, cognitive impairments, immune dysfunction, pain, autonomic dysfunction, and neuroendocrine symptoms. Although ME/CFS is well documented within the medical literature, it remains difficult to diagnosis and manage. Some of the current challenges include an absence of diagnostic markers, differing diagnostic criteria, and an overall lack of awareness within the medical community. As a result, patients are often frustrated by the difficulties in acquiring a diagnosis and from the overall lack of available treatments. In an effort to increase awareness, this review discusses disease pathophysiology, clinical presentation, and treatment options, while also highlighting the benefits of an osteopathic approach.

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Attenuation Effect of Spinal Manipulation on Neuropathic and Postoperative Pain Through Activating Endogenous Anti-Inflammatory Cytokine Interleukin 10 in Rat Spinal Cord

Cited by 23 publications

References 30 publications

The mechanisms of protease-activated receptor 2 in mediating pain behaviors through nonselective cation channel signaling

The mechanisms of protease-activated receptor 2 in mediating pain behaviors through nonselective cation channel signaling

Decreased spontaneous activity and altered evoked nociceptive response of rat thalamic submedius neurons to lumbar vertebra thrust

Understanding Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and the Emerging Osteopathic Approach: A Narrative Review

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