Morphine reverses the effects of 1-methyl-4-phenylpyridinium in PC12 cells through activating PI3K/Akt

Aim of the study: Parkinson’s disease (PD) is a neurodegenerative disorder. It is caused by the degeneration of dopaminergic neurons and the dopamine (DA) deletion in the substantia nigra pars compacta (SNpc). Morphine elevates the level of dopamine in the mesolimbic dopamine system and plays a role in alleviating PD symptoms. However, the molecular mechanism is still unclear. The aim of the study is to investigate the mechanism on morphine alleviating PD symptoms.

Materials and methods: The viability of PC12 cells was measured by using MTT assay. The expressions of tyrosine hydroxylase (TH), thioredoxin-1 (Trx-1), CyclinD1 and Cyclin-dependent kinase5 (Cdk5) were detected by Western Blot.

Results: In present study, we found that morphine increased the cell viability in PC12 cells. 1-methyl-4-phenylpyridi-nium (MPP+) reduced the cell viability and TH expression, which were reversed by morphine. MPP+ decreased the expressions of Trx-1, CyclinD1, Cdk5, which were restored by morphine. Moreover, the role of morphine in restoring the expressions of Trx-1, CyclinD1 and Cdk5 decreased by MPP+ was abolished by LY294002, phosphatidylinositol-3-kinase (PI3K)/Akt inhibitor.

Conclusions: These results suggest that morphine reverses effects induced by MPP þ through activating PI3K/Akt pathway.     

Significant reduction of postoperative pain and opioid analgesics requirement with an Enhanced Recovery After Thoracic Surgery protocol

ObjectiveTo evaluate differences in postoperative pain control and opioids requirement in thoracic surgical patients following implementation of an Enhanced Recovery after Thoracic Surgery protocol with a comprehensive postoperative pain management strategy.Material and MethodsA retrospective analysis of a prospectively maintained database of patients undergoing pulmonary resections by robotic thoracoscopy or thoracotomy from January 1, 2017, to January 31, 2019, was conducted. Multimodal pain management strategy (opioid-sparing analgesics, infiltration of liposomal bupivacaine to intercostal spaces and surgical sites, and elimination of thoracic epidural analgesia use in thoracotomy patients) was implemented as part of Enhanced Recovery after Thoracic Surgery on February 1, 2018. Outcome metrics including patient-reported pain levels, in-hospital and postdischarge opioids use, postoperative complications, and length of stay were compared before and after protocol implementation.ResultsIn total, 310 robotic thoracoscopy and 62 thoracotomy patients met the inclusion criteria. This pain management strategy was associated with significant reduction of postoperative pain in both groups with an overall reduction of postoperative opioids requirement. Median in-hospital opioids use (morphine milligram equivalent per day) was reduced from 30 to 18.36 (P = .009) for the robotic thoracoscopy group and slightly increased from 15.48 to 21.0 (P = .27) in the thoracotomy group. More importantly, median postdischarge opioids prescribed (total morphine milligram equivalent) was significantly reduced from 480.0 to 150.0 (P < .001) and 887.5 to 150.0 (P < .001) for the thoracoscopy and thoracotomy groups, respectively. Similar short-term perioperative outcomes were observed in both groups before and following protocol implementation.ConclusionsImplementation of Enhanced Recovery after Thoracic Surgery allows safe elimination of epidural use, better pain control, and less postoperative opioids use, especially a drastic reduction of postdischarge opioid need, without adversely affecting outcomes.     

Additional Peripheral Nerve Block to Periarticular Injection Has No Benefit for Patients Undergoing TKA: A Factorial Propensity Score–Matched Analysis Comparing Four Multimodal Analgesic Techniques

BackgroundControversy remains over what and how many analgesic techniques are required as the most effective multimodal pain regimen in total knee arthroplasty (TKA). This study aimed to evaluate the effect of additional analgesic methods combined with periarticular injection (PAI) analgesia for TKA.MethodsUsing retrospective cohort data, patients undergoing TKA with spinal anesthesia and PAI were divided into 4 groups. Group A (control) comprised 66 patients; group B (73 patients) had additional adductor canal block; group C (70 patients) obtained additional femoral nerve block, and group D (73 patients) received additional adductor canal block and intrathecal morphine. Propensity score matching was applied to compare visual analog scale (VAS) for pain intensity, cumulative morphine use (CMU), knee flexion angle, straight leg raise, length of hospital stay, and postoperative nausea and vomiting.ResultsThere was no significant difference regarding VAS and morphine use, when either group B or C was compared with group A. Group D had significantly lower VAS than groups A, B, and C during the first 24 hours after surgery and required significantly less CMU than groups A and B. However, the pain score of group D increased afterward, with significantly longer length of hospital stay than groups A and B. There was no difference in straight leg raise among the groups.ConclusionAdditional peripheral nerve block to PAI provides no benefit for patients undergoing TKA. Adjuvant intrathecal morphine could significantly reduce the VAS and CMU in the acute postoperative period; however, rebound pain with prolonged hospital stays was observed.     

Adrenomedullin: an important participant in neurological diseases

Adrenomedullin,a peptide with multiple physiological functions in nervous system injury and disease,has aroused the interest of researchers.This review summarizes the role of adrenomedullin in neuropathological disorders,including pathological pain,brain injury and nerve regeneration,and their treatment.As a newly characterized pronociceptive mediator,adrenomedullin has been shown to act as an upstream factor in the transmission of noxious information for various types of pathological pain including acute and chronic inflammatory pain,cancer pain,neuropathic pain induced by spinal nerve injury and diabetic neuropathy.Initiation of glia-neuron signaling networks in the peripheral and central nervous system by adrenomedullin is involved in the formation and maintenance of morphine tolerance.Adrenomedullin has been shown to exert a facilitated or neuroprotective effect against brain injury including hemorrhagic or ischemic stroke and traumatic brain injury.Additionally,adrenomedullin can serve as a regulator to promote nerve regeneration in pathological conditions.Therefore,adrenomedullin is an important participant in nervous system diseases.     

Randomized trial of bupivacaine with epinephrine versus bupivacaine liposome suspension in patients undergoing minimally invasive lung resection

ObjectivesThoracic surgery can cause significant pain, and multiple strategies have been developed to control pain after surgery. We compared 2 bupivacaine formulations given intraoperatively: bupivacaine with epinephrine (1,200,000) or liposomal bupivacaine.MethodsThis was a randomized, open-label study (NCT03560362). Eligible patients were adults scheduled for a minimally invasive lung procedure. Incision sites were injected with bupivacaine with epinephrine or liposomal bupivacaine before incision, and each intercostal space was injected with 1 mL of bupivacaine with epinephrine or liposomal bupivacaine entering the thoracic cavity. Patient-controlled analgesia was initiated in the recovery room. Pain was recorded using a visual analog scale. The primary outcome was the amount of narcotics taken during the postoperative hospital stay.ResultsWe recruited 50 patients; 25 received bupivacaine with epinephrine, and 25 received liposomal bupivacaine. The treatment groups were similar in age, histology, and procedure performed. There were no statistical differences between the treatment groups in the amount of narcotics required during the hospital stay (36.3 mg for bupivacaine and 38 mg for liposomal bupivacaine) or in pain assessed the day of surgery (5 and 5), the first day (3.5 and 2.3), second day (3 and 2.6), 2 weeks (0 and 1), or 3 months (0 and 0) postoperatively. Hospital length of stay and complications were also similar.ConclusionsIn a small, randomized study, we did not find significant differences between bupivacaine with epinephrine or liposomal bupivacaine in mitigating pain after minimally invasive lung resection. We currently favor using the less expensive nonliposomal bupivacaine preparations until additional data are available.     

主动应用吗啡治疗特发性肺间质纤维化的对照研究

目的 观察主动应用吗啡治疗特发性肺间质纤维化 （IPF） 患者呼吸困难的有效性及安全性。方法 33例因明显的呼吸困难加重而住院治疗的IPF患者依入院先后顺序被分为观察组 （16例） 和对照组 （17例）。对照组给予呼吸支持、 糖皮质激素等常规治疗; 观察组在对照组基础上主动予以低剂量吗啡1 mg皮下注射, 每日3次, 住院期间全程给予。观察记录2组患者间入院后不同时间点视觉模拟量表 （VAS） 评分、 住院时间、 住院期间呼吸困难急性发作次数和累计糖皮质激素用量以及不良反应发生情况。结果 2组入院时VAS 评分差异无统计学意义, 观察组入院后第4天、 出院前2 d及出院时VAS评分均较对照组降低 （P＜0.05）; 2组平均住院时间差异无统计学意义 （P＞0.05）;观察组住院期间出现呼吸困难加重次数、 糖皮质激素累计处方剂量均较对照组减少 （P＜0.05）; 2组患者均未出现呼吸抑制相关不良反应, 观察组便秘比例大于对照组, 恶心比例小于对照组 （P＜0.05）。结论 主动应用吗啡治疗有助于缓解IPF相关呼吸困难, 且安全有效。