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The fast inhibitory synaptic transmission mediated by the γ-aminobutyric acid type A receptor (GABAA R) within spinal dorsal horn exerts a gating control over the synaptic conveyance of nociceptive information from the periphery to higher brain regions. Although a large body of evidence has demonstrated that the impairment of GABAergic inhibition alone is sufficient to elicit pain hypersensitivity in intact animals, the underlying mechanisms remain to be characterized. The present study shows that Ca(2+) /calmodulin-dependent protein kinase II (CaMKII) is an important signaling protein downstream of reduced GABAergic inhibition. We found that pharmacological removal of inhibition by intrathecal application of the GABAA R antagonist bicuculline significantly enhanced the autophosphorylation of CaMKII at Thr286 in spinal dorsal horn of mice. In addition to increased CaMKII activity, bicuculline also promoted CaMKII interaction with N-methyl-D-aspartate (NMDA)-subtype glutamate receptors and induced the translocation of CaMKII from cytosolic compartments to the synaptosomal membrane fraction. Immunoblotting analysis revealed that the phosphorylation levels of NMDA receptor NR2B subunit at Ser1303 and of AMPA-subtype glutamate receptor GluR1 subunit at Ser831, two important CaMKII phosphorylation sites, were substantially enhanced after bicuculline application. Behavioral tests illustrated that intrathecal administration of the CaMKII inhibitor KN-93, NMDA receptor antagonist D-APV, or AMPA receptor antagonist GYKI 52466 effectively ameliorated the mechanical allodynia evoked by bicuculline. These data thus indicate that CaMKII signaling is critical for the reduced inhibition to evoke spinal sensitization.

To investigate the predictive factors of pain intensity during the first 48 hours after spinal correction and fusion operations for idiopathic scoliosis patients.A total of 290 scoliosis patients who underwent posterior spinal instrumentation and fusion operations were enrolled in this study. A standard surgical and analgesic method was implemented for all participants and pain intensity was evaluated at fixed times within 48 hours after the operation. Variables including demographics (age, sex, body mass index [BMI], patient sources), surgical variables (procedure, duration of operation), intraoperative variables (total transfusion, autologous transfusion, heterogeneous transfusion, fluid intake, use of preventive analgesia) were investigated.On univariate analysis, BMI, transfusion type and not implementing preventive analgesia were associated with more serious pain after a scoliosis correction operation. Multivariate analysis indicated that receiving heterogeneous transfusion and not implementing preventive analgesia were significant predictive factors for moderate and severe pain after the spinal correction operation.Our research indicated that the type of transfusion and preventive analgesia were significantly associated with the severity of pain. Body mass and patient sources should be considered before surgery. For patients under high risk of moderate and severe pain, the type of transfusion must be taken into consideration. This study explored the influencing factors of postoperative pain from a novel perspective, but some limitations existed in this present study, and future studies are needed.

Introduction: Mycophenolate mofetil (MMF), a new type of immunosuppressant, has emerged as a frontline agent for treating autoimmune diseases. Mycophenolic acid (MPA) is an active metabolite of MMF. MPA exposure varies greatly among individuals, which may lead to adverse drug reactions such as gastrointestinal side effects, infection, and leukopenia. Genetic factors play an important role in the variation of MPA levels and its side effects. Although many published studies have focused on MMF use in patients after organ transplant, studies that examine the use of MMF in patients with autoimmune diseases are still lacking. Methods: This study will not only explore the genetic factors affecting MPA levels and adverse reactions but also investigate the relationships between UGT1A9 −118(dT)9/10, UGT1A9 -1818T>C, UGT2B7 802C>T, SLCO1B1 521T>C, SLCO1B3 334T>G, IMPDH1 −106G>A and MPA trough concentration (MPA C 0 ), along with adverse reactions among Chinese patients with autoimmune diseases. A total of 120 patients with autoimmune diseases were recruited. The MPA trough concentration was detected using the enzyme multiplied immunoassay technique (EMIT). Genotyping was performed using a real-time polymerase chain reaction (PCR) system and validated allelic discrimination assays. Clinical data were collected for the determination of side effects. Results: SLCO1B1 521T>C demonstrated a significant association with MPA C 0 /d (p=0.003), in which patients with the CC type showed a higher MPA C 0 /d than patients with the TT type (p=0.001) or the CT type (p=0.000). No significant differences were found in MPA C 0 /d among the other SNPs. IMPDH1 −106G>A was found to be significantly related to infections (p=0.006). Subgroup analysis revealed that UGT2B7 802C>T was significantly related to Pneumocystis carinii pneumonia infection (p=0.036), while SLCO1B1 521T>C was associated with anemia (p=0.029). Conclusion:For Chinese autoimmune disease patients, SLCO1B1 521T>C was correlated with MPA C 0 /d and anemia. IMPDH1 −106G>A was significantly related to infections. UGT2B7 802C>T was significantly related to Pneumocystis carinii pneumonia infection.

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