Accumulating evidence suggests that activation of spinal microglia contributes to the development of inflammatory and neuropathic pain. However, the role of spinal microglia in the maintenance of chronic pain remains controversial. Bone cancer pain shares features of inflammatory and neuropathic pain, but the temporal activation of microglia and astrocytes in this model is not well defined. Here, we report an unconventional role of spinal microglia in the maintenance of advanced-phase bone cancer pain in a female rat model. Bone cancer elicited delayed and persistent microglial activation in the spinal dorsal horn on days 14 and 21, but not on day 7. In contrast, bone cancer induced rapid and persistent astrocytic activation on days 7-21. Spinal inhibition of microglia by minocycline at 14 d effectively reduced bone cancer-induced allodynia and hyperalgesia. However, pretreatment of minocycline in the first week did not affect the development of cancer pain. Bone cancer increased ATP levels in CSF, and upregulated P2X7 receptor, phosphorylated p38, and IL-18 in spinal microglia. Spinal inhibition of P2X7/p-38/IL-18 pathway reduced advanced-phase bone cancer pain and suppressed hyperactivity of spinal wide dynamic range (WDR) neurons. IL-18 induced allodynia and hyperalgesia after intrathecal injection, elicited mechanical hyperactivity of WDR neurons in vivo, and increased the frequency of mEPSCs in spinal lamina IIo nociceptive synapses in spinal cord slices. Together, our findings demonstrate a novel role of microglia in maintaining advanced phase cancer pain in females via producing the proinflammatory cytokine IL-18 to enhance synaptic transmission of spinal cord nociceptive neurons.

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In China, acupuncture has been considered an effective method for treating gastrointestinal (GI) dysfunction diseases for thousands of years. In fact, acupuncture has gained progressive acceptance from both practitioners and patients worldwide. However, the therapeutic effects and underlying mechanisms in treating GI dysfunction have not yet been established due to a lack of systematic and comprehensive review articles. Therefore, the aim of this review is to discuss the efficacy of acupuncture as a treatment for GI dysfunction and the associated underlying mechanisms. A search of PubMed was conducted for articles that were published over the past 10 years using the terms "acupuncture", "gastrointestine", and other relevant keywords. In the following review, we describe the effect and underlying mechanisms of acupuncture on GI function from the perspectives of GI motility, visceral sensitivity, the GI barrier, and the brain-gut axis. The dual regulatory effects of acupuncture may manifest by promoting gastric peristalsis in subjects with low initial gastric motility, and suppressing peristalsis in subjects with active initial motility. In addition, the regulation of acupuncture on gastric motility may be intensity-dependent. Our findings suggest that further studies are needed to investigate the effects and more systematic mechanisms in treating GI dysfunction, and to promote the application of acupuncture for the treatment of GI diseases.

Individuals involved in shift work are more likely to become overweight or obese. Appropriate preventive interventions in the organization of shift schedules according to ergonomic criteria would allow shift workers to avoid potential health impairment.