Duloxetine, a serotonin and noradrenaline reuptake inhibitor, and celecoxib, a non-steroidal anti-inflammatory drug, are commonly used analgesics for persistent pain, however with moderate gastrointestinal side effects or analgesia tolerance. One promising analgesic strategy is to give a combined prescription, allowing the maximal or equal efficacy with fewer side effects. In the current study, the efficacy and side effects of combined administration of duloxetine and celecoxib were tested in the mouse formalin pain model. The subcutaneous (s.c.) injection of formalin into the left hindpaw induced significant somatic and emotional pain evaluated by the biphasic spontaneous flinching of the injected hindpaw and interphase ultrasonic vocalizations (USVs) during the 1 h after formalin injection, respectively. Pretreatment with intraperitoneal (i.p.) injection of duloxetine or celecoxib at 1 h before formalin injection induced the dose-dependent inhibition on the second but not first phase pain responses. Combined administration of duloxetine and celecoxib showed significant analgesia for the second phase pain responses. Combination analgesia on the first phase was observed only with higher dose combination. A statistical difference between the theoretical and experimental ED50 for the second phase pain responses was observed, which indicated synergistic interaction of the two drugs. Concerning the emotional pain responses revealed with USVs, we assumed that the antinociceptive effects were almost completely derived from duloxetine, since celecoxib was ineffective when administered alone or reduced the dosage of duloxetine when given in combination. Based on the above findings, acute concomitant administration of duloxetine and celecoxib showed synergism on the somatic pain behavior but not emotional pain behaviors.

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Background: The cisterna Intrathecal Drug Delivery system (IDDS) with morphine has proven to be effective in treating refractory cancer pain above the middle thoracic vertebrae level in some countries. However, it has not been fully investigated in others. We designed the current project to investigate the efficacy and safety of cisterna IDDS for pain relief in refractory pain above the middle thoracic vertebrae level in advanced cancer patients. Methods: This study protocol allows for eligible cancer patients to receive the cisterna IDDS operation. Pain intensity (Visual Analogue scale, VAS), quality of life (36-Item Short-Form Health Survey, SF-36), and depression (Self-Rating Depression scale, SDS) are assessed along with side effects in the postoperative follow-up visits. Recent literature suggests a potential role for cisterna IDDS morphine delivery for refractory pain states above the middle thoracic level. Conclusion: The results of this study may provide further evidence that cisterna IDDS of morphine can serve as an effective and safe pain relief strategy for refractory pain above the middle thoracic vertebrae level in advanced cancer patients.

Background: Recent studies have shown that migraine headache is often associated with concomitant gastrointestinal diseases. There is a higher prevalence of headaches in patients with gastrointestinal disorders. These associations between migraine and gastrointestinal disorders suggest a potential link to a bidirectional modulation of gut microbiota and brain function. The underlying working mechanistic links between migraine and gastrointestinal diseases may include increased intestinal epithelial permeability and inflammation. Objective: This review presents an overview of the relationship between gut microbiota and brain function, especially with regard to migraine headache. Study Design: Literature review. Setting: Anesthesia and Operation Center, Department of Anesthesiology, Chinese PLA General Hospital. Methods: The present investigation included a PubMed search using the following terms: migraine headache, gut microbiota, brain function, and probiotics. Results: In this literature review, we mainly discussed the relationship between gut microbiota and brain function, especially with regard to migraine headache. The potential effects of probiotics supplement on migraine headache were also included. Limitations: There is limited evidence from clinical studies of the positive effects of probiotics in patients with migraine headache. Large-scale randomized, placebo-controlled clinical trials are warranted to evaluate the clinical efficacy and safety of probiotics in patients with migraine headache. Conclusions: Similar to migraine headache, disorders of the brain involving depression and anxiety have been demonstrated to be associated with increased gut permeability. An improvement in gut microbiota and reduction of inflammation can have positive effects on strengthening gut and brain function. Moreover, it can be inferred that probiotics may have a beneficial effect on the frequency and severity of migraine headache attacks. Large-scale randomized, placebo-controlled studies are warranted in the future to evaluate the clinical efficacy and safety of probiotics in patients with migraine headache. Key words: Migraine headache, gut microbiota, brain function, probiotics

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