The analgesic effect of propofol associated with the inhibition of hypoxia inducible factor and inflammasome in complex regional pain syndrome

Abstract

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.

Total intravenous anesthesia versus inhalation anesthesia: how do outcomes compare?

“…Preclinical data suggest that propofol-based TIVA could have an analgesic effect. Possible antinociceptive mechanisms include; suppression of proinflammatory cytokines, inhibition of free radicals and hypoxia inducible factor, inhibition of Nmethyl-D-aspartic acid (NMDA) receptors, inhibition of the dorsal horn neurons of the spinal cord, and inhibition of the cannabinoid receptors CB1 and CB2 [20][21][22][23][24]. Since experimental data have shown that propofol effects pain modulation and processing, a group of investigators exposed healthy volunteers to continue propofol infusion and assessed their pain score.…”

Future Directions in Optimizing Anesthesia to Reduce Perioperative Acute Kidney Injury

“…Propofol, an ultra-fast-acting intravenous anesthetic with anti-inflammatory and antioxidant properties [59, 60] and few adverse effects [75], has been widely used in clinical applications. Among the widely used anesthetics, accumulated data suggest that it has a protective effect against renal ischemia/reperfusion injury (IRI) [76].…”

“…In another clinical study, Yoo et al demonstrated a significant reduction in the incidence and severity of AKI in CPB patients undergoing valvular heart surgery using propofol anesthesia compared to sevoflurane. It was also reported that postoperative cystatin C, serum IL-6, C-reactive protein, and fractional neutrophil count were significantly decreased [10], which may be related to the anti-inflammatory property of propofol [60]. However, due to the limitations of the experiment such as the small sample size, the effect of propofol on AKI has always been controversial.…”

Sub-anaesthetic dose of propofol attenuates mechanical allodynia in chronic post-ischaemic pain via regulation of PTEN/PI3K/IL-6 signalling

“…[11][12][13] More recently, propofol administered after CPIP induction was shown to attenuate pain by inhibiting free radical, hypoxia inducible factor and inflammasome. 14 However, the pain signalling mechanism was mediated via peripheral tissues and not at the spinal cord level. Propofol may be a potential therapeutic option for reducing CRPS-induced pain, but centrally mediated pain mechanisms have not been elucidated.…”