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Background Complex regional pain syndrome (CRPS) is related to microcirculation impairment caused by tissue hypoxia and peripheral cytokine overproduction in the affected human limb and chronic post-ischemic pain (CPIP) is considered as an animal model for this intractable disease. Previous studies suggest that the pathogenesis of CPIP involves the hypoxia inducible factor-1α (HIF-1α) and an exaggerated regional inflammatory and free radical response. The inhibition of HIF-1α is known to relieve CPIP. So, propofol, as a free radical scavenger, is very likely to be beneficial in terms of relieving CPIP. Methods We set up a CPIP model using the hindpaw of mice. We administered propofol (10 mg/kg) just after the reperfusion period (early stage) and also on the second day (late stage), as treatment. The analysis evaluated the expression of HIF-1α, free radicals, and inflammasome. Results Propofol administration produced obvious analgesia in both mechanical and thermal evaluation in the early stage of CPIP (2 h after reperfusion). Only a mild analgesic effect was found in the late stage (48 h later after reperfusion). In the early stage, the expression of HIF-1α and the inflammasome marker (NALP1) along with caspase-1 were suppressed by propofol. The free radical level also decreased in the propofol group. But those molecular changes were not founded in the late stage of CPIP. Conclusion Our data demonstrated that propofol produces mice analgesia in the early stage of CPIP and this effect is associated with inhibition of free radical, hypoxia inducible factor and inflammasome.

Nalbuphine (NAL) is recognized as a mixer with the κ‐opioid receptor agonist and the μ‐opioid receptor antagonist. However, whether this drug causes any modifications in neuronal ionic currents is unclear. The effects of NAL on ionic currents in mHippoE‐14 hippocampal neurons were investigated. In the whole‐cell current recordings, NAL suppressed the peak amplitude of voltage‐gated Na+ current (INa) with an IC50 value of 1.9 μM. It shifted the steady‐state inactivation curve of peak INa to the hyperpolarized potential, suggesting that there is the voltage dependence of NAL‐mediated inhibition of peak INa. In continued presence of NAL, subsequent application of either dynorphin A1‐13 (1 μM) or naloxone (30 μM) failed to modify its suppression of peak INa. Tefluthrin (Tef; 10 μM), a pyrethroid known to activate INa, increased peak INa with slowed current inactivation; however, further application of NAL suppressed Tef‐mediated suppression of peak INa followed by an additional slowing of current inactivation. In addition, NAL suppressed the amplitude of M‐type K+ current [IK(M)] with an IC50 value of 5.7 μM, while it slightly suppressed erg‐mediated and delayed‐rectifier K+ currents. In the inside‐out current recordings, NAL failed to modify the activity of large‐conductance Ca2+‐activated K+ channels. In differentiated NG108‐15 neuronal cells, NAL also suppressed the peak INa, and subsequent addition of Tef reversed NAL‐induced suppression of INa. Our study highlights the evidence that in addition to modulate opioid receptors, NAL has the propensity to interfere with ionic currents including INa and IK(M), thereby influencing the functional activities of central neurons.

Background: Huntington’s disease (HD) is an inherited disease characterized by both mental and motor dysfunctions. Our previous studies showed that HD mice demonstrate a diminished pain response. However, few studies have focused on the relationship between HD and morphine analgesia. The purpose of this study is to investigate and compare the analgesic effects of morphine in HD and wild-type (WT) mice. Methods: We used clinically similar transgenic HD mice (7-10 weeks of age with motor dysfunction at 8-9 mo of age) carrying a mutant Huntington CAG trinucleotide repeats to evaluate morphine analgesia. The morphine (10 mg/kg subcutaneously) analgesia was evaluated with a tail-flick in hot water (52°C). Mice spinal cords were harvested at the end of the analgesia studies. An immunofluorescence assay and western blotting were used to identify changes in the cells and cytokines. Results: Our data demonstrate that preonset young HD mice exhibited a better analgesic response to morphine than the WT mice. Western blotting and an immunohistological examination of the lumbar spinal cord tissue indicated less activation of glial cells and astrocytes in the HD mice compared with the WT mice. The production levels of tumor necrosis factor α and interleukine-1β were also lower in the young HD mice. Conclusion: Our data demonstrate better morphine analgesic and less pain-related cytokine responses at the spinal cord level for HD mice. Further studies are needed to determine the morphine analgesia mechanism in HD.

Traumatic rib fracture can cause severe pain and is usually associated with the depression of respiratory drive followed by severe respiratory complications. It is critical for patients with rib fracture to receive adequate analgesia. However, strong opioids and other analgesics often produces side effects and may even cause respiratory suppression. Meanwhile, rib fixation now has become a popular method for treating rib fracture patients. However, the actual molecular mechanism leading to its effectiveness as an analgesia has not been fully investigated, and the best analgesic method for its use in rib fracture patients has not yet been determined. We developed a new animal model for rib fracture and evaluated changes in pain severity after rib fixation. Our data indicated significantly better analgesic behavior if a soft string rib fixation is performed, which is associated with cytokine (interleukine-6 and interleukine-10) decreases in the spinal cord and co-localization with glia cells. Our results provided a treatment suggestion for rib fracture patients and the possible molecular mechanism for the analgesic effects. Further molecular mechanisms and the best therapeutic methods are still needed for this severe painful condition.