Mol Pain
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Acupuncture at pericardium 6 (PC6) shows a consistently positive efficacy in nausea response suggested by consensus expert guidelines. Nausea encompasses aversive symptom as well as strong emotional components. Disgust is a subjective emotion of uneasy commonly accompanying with a physiological response that is accompanied by strong visceral sensations (e.g., nausea). ⋯ We also found evidence for radical reorganizations of local stronger casual interaction patterns to disgust-induced brain responses targeted by acupuncture at different acupoints. This study provided the brain substrate for acupuncture on aversion modulation. The coupling between the cerebellum (nodulus) and insula supported interoception system and vestibular control which provided the specific neural basis.
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The medial prefrontal cortex is a key area for the regulation of pain and emotion. However, the functional involvement of the medial prefrontal cortex for visceral nociception, at the neuronal or synaptic level, is obscure yet. ⋯ Behaviorally, inhibition of gamma-aminobutyric acid-ergic synaptic transmission alleviated the visceral pain and anxiety. It is thus for the first time showing that the excitation-inhibition ratio is increased in the medial prefrontal cortex after chronic myocardial infarction, which may come from the reduced intrinsic activity of gamma-aminobutyric acid-ergic neurons and is important for regulating the angina pectoris and anxiety induced by chronic myocardial infarction.
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Background Intense nociceptive signaling arising from ongoing injury activates primary afferent nociceptive systems to generate peripheral sensitization. ERK1/2 phosphorylation in dorsal root ganglion can be used to visualize intracellular signal activity immediately after noxious stimulation. The aim of this study was to investigate spatiotemporal characteristics of ERK1/2 phosphorylation against tissue injury in the primary afferent neurons. ⋯ Levobupivacaine treatment inhibited phosphorylated ERK1/2 induction, carbenoxolone treatment inhibited glial phosphorylated ERK1/2 at 2 min after the injury, and carbenoxolone inhibited pain hypersensitivity and neuronal phosphorylated ERK1/2 at 1 h after the injury. Conclusion ERK1/2 phosphorylation in A-fiber neurons and satellite glial cells immediately after injury contributes to the generation of pain hypersensitivity. Signal communication between neurons and satellite glial cells expands the duration of neuronal ERK1/2 phosphorylation and pain hypersensitivity at 1 h after tissue injury.
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Paclitaxel is one of the most commonly used drugs to treat breast cancer. Its major dose-limiting toxicity is paclitaxel-induced peripheral neuropathy (PIPN). PIPN persists into survivorship and has a negative impact on patient's mood, functional status, and quality of life. No interventions are available to treat PIPN. A critical barrier to the development of efficacious interventions is the lack of understanding of the mechanisms that underlie PIPN. Mitochondrial dysfunction has been evaluated in preclinical studies as a hypothesized mechanism for PIPN, but clinical data to support this hypothesis are limited. The purpose of this pilot study was to evaluate for differential gene expression and perturbed pathways between breast cancer survivors with and without PIPN. ⋯ This study is the first to provide molecular evidence that a number of mitochondrial dysfunction mechanisms identified in preclinical models of various types of neuropathic pain including chemotherapy-induced peripheral neuropathy are found in breast cancer survivors with persistent PIPN and suggest genes for validation and as potential therapeutic targets.
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Evidence suggests that there are both nociceptive and neuropathic components of cancer-induced pain. We have observed that changes in intrinsic membrane properties and excitability of normally non-nociceptive Aβ sensory neurons are consistent in rat models of peripheral neuropathic pain and cancer-induced pain. This has prompted a comparative investigation of the intracellular electrophysiological characteristics of sensory neurons and of the ultrastructural morphology of the dorsal horn in rat models of neuropathic pain and cancer-induced pain. ⋯ Furthermore, both cancer-induced pain and neuropathic pain models showed abundant abnormal axonal sprouting in bundles of myelinated axons in the ipsilateral spinal laminae IV and V. The patterns of changes show consistency between rat models of cancer-induced pain and neuropathic pain. These findings add to the body of evidence that animal models of cancer-induced pain and neuropathic pain share features that may contribute to the peripheral and central sensitization and tactile hypersensitivity in both pain states.