Whether preemptive analgesic interventions are more effective than conventional regimens in managing acute postoperative pain remains controversial. We systematically searched for randomized controlled trials that specifically compared preoperative analgesic interventions with similar postoperative analgesic interventions via the same route. The retrieved reports were stratified according to five types of analgesic interventions: epidural analgesia, local anesthetic wound infiltration, systemic N-methyl-d-aspartic acid (NMDA) receptor antagonists, systemic nonsteroidal antiinflammatory drugs (NSAIDs), and systemic opioids. The primary outcome measures analyzed were the pain intensity scores, supplemental analgesic consumption, and time to first analgesic consumption. Sixty-six studies with data from 3261 patients were analyzed. Data were combined by using a fixed-effect model, and the effect size index (ES) used was the standardized mean difference. When the data from all three outcome measures were combined, the ES was most pronounced for preemptive administration of epidural analgesia (ES, 0.38; 95% confidence interval [CI], 0.28-0.47), local anesthetic wound infiltration (ES, 0.29; 95% CI, 0.17-0.40), and NSAID administration (ES, 0.39; 95% CI, 0.27-0.48). Whereas preemptive epidural analgesia resulted in consistent improvements in all three outcome variables, preemptive local anesthetic wound infiltration and NSAID administration improved analgesic consumption and time to first rescue analgesic request, but not postoperative pain scores. The least proof of efficacy was found in the case of systemic NMDA antagonist (ES, 0.09; 95% CI, -0.03 to 0.22) and opioid (ES, -0.10; 95% CI, -0.26 to 0.07) administration, and the results remain equivocal.

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European Society of Anaesthesiology.

Failed epidural anaesthesia or analgesia is more frequent than generally recognized. We review the factors known to influence the success rate of epidural anaesthesia. Reasons for an inadequate epidural block include incorrect primary placement, secondary migration of a catheter after correct placement, and suboptimal dosing of local anaesthetic drugs. For catheter placement, the loss of resistance using saline has become the most widely used method. Patient positioning, the use of a midline or paramedian approach, and the method used for catheter fixation can all influence the success rate. When using equipotent doses, the difference in clinical effect between bupivacaine and the newer isoforms levobupivacaine and ropivacaine appears minimal. With continuous infusion, dose is the primary determinant of epidural anaesthesia quality, with volume and concentration playing a lesser role. Addition of adjuvants, especially opioids and epinephrine, may substantially increase the success rate of epidural analgesia. Adjuvant opioids may have a spinal or supraspinal action. The use of patient-controlled epidural analgesia with background infusion appears to be the best method for postoperative analgesia.

Summary Effective peri‐operative pain management is a prerequisite for optimal recovery after surgery. Despite published evidence‐based guidelines from several professional groups, postoperative pain management remains inadequate. The procedure‐specific pain management (PROSPECT) collaboration consists of anaesthetists and surgeons with broad international representation that provide healthcare professionals with practical and evidence‐based recommendations formulated in a way that facilitates clinical decision‐making across all stages of the peri‐operative period on a procedure‐specific basis. The aim of this manuscript is to provide a detailed description of the current PROSPECT methodology with the intention of providing the rigour and transparency in which procedure‐specific pain management recommendations are developed. The high methodological standards of the recommendations should improve the quality of clinical practice.

Caesarean section is associated with moderate-to-severe postoperative pain, which can influence postoperative recovery and patient satisfaction as well as breastfeeding success and mother-child bonding. The aim of this systematic review was to update the available literature and develop recommendations for optimal pain management after elective caesarean section under neuraxial anaesthesia. A systematic review utilising procedure-specific postoperative pain management (PROSPECT) methodology was undertaken. Randomised controlled trials published in the English language between 1 May 2014 and 22 October 2020 evaluating the effects of analgesic, anaesthetic and surgical interventions were retrieved from MEDLINE, Embase and Cochrane databases. Studies evaluating pain management for emergency or unplanned operative deliveries or caesarean section performed under general anaesthesia were excluded. A total of 145 studies met the inclusion criteria. For patients undergoing elective caesarean section performed under neuraxial anaesthesia, recommendations include intrathecal morphine 50-100 µg or diamorphine 300 µg administered pre-operatively; paracetamol; non-steroidal anti-inflammatory drugs; and intravenous dexamethasone administered after delivery. If intrathecal opioid was not administered, single-injection local anaesthetic wound infiltration; continuous wound local anaesthetic infusion; and/or fascial plane blocks such as transversus abdominis plane or quadratus lumborum blocks are recommended. The postoperative regimen should include regular paracetamol and non-steroidal anti-inflammatory drugs with opioids used for rescue. The surgical technique should include a Joel-Cohen incision; non-closure of the peritoneum; and abdominal binders. Transcutaneous electrical nerve stimulation could be used as analgesic adjunct. Some of the interventions, although effective, carry risks, and consequentially were omitted from the recommendations. Some interventions were not recommended due to insufficient, inconsistent or lack of evidence. Of note, these recommendations may not be applicable to unplanned deliveries or caesarean section performed under general anaesthesia.

Systemic administration of the local anaesthetic lidocaine is antinociceptive in both acute and chronic pain states, especially in acute postoperative and chronic neuropathic pain. These effects cannot be explained by its voltage-gated sodium channel blocking properties alone, but the responsible mechanisms are still elusive. This narrative review focuses on available experimental evidence of the molecular mechanisms by which systemic lidocaine exerts its clinically documented analgesic effects. These include effects on the peripheral nervous system and CNS, where lidocaine acts via silencing ectopic discharges, suppression of inflammatory processes, and modulation of inhibitory and excitatory neurotransmission. We highlight promising objectives for future research to further unravel these antinociceptive mechanisms, which subsequently may facilitate the development of new analgesic strategies and therapies for acute and chronic pain.

Key points• The peripheral terminals of sensory neurons encode physical and chemical signals into trains of action potentials (APs) and transmit these trains to the CNS.• Although modulation of this process is thought to predominantly reside at synapses, there are also indications that AP trains are incompletely propagated past points at which axons branch. One such site is the T-junction, where the single sensory neuron axon branches into peripheral and central processes.• In recordings from sensory neurons of dorsal root ganglia excised from adult rats, we identified use-dependent failure of AP propagation between the peripheral and central processes that results in filtering of rapid AP trains, especially in C-type neurons.• Propagation failure was regulated by membrane input resistance and Ca 2+ -sensitive K + and Cl − currents. Following peripheral nerve injury, T-junction filtering is reduced in C-type neurons, which may possibly contribute to pain generation.Abstract The T-junction of sensory neurons in the dorsal root ganglion (DRG) is a potential impediment to action potential (AP) propagation towards the CNS. Using intracellular recordings from rat DRG neuronal somata during stimulation of the dorsal root, we determined that the maximal rate at which all of 20 APs in a train could successfully transit the T-junction (following frequency) was lowest in C-type units, followed by A-type units with inflected descending limbs of the AP, and highest in A-type units without inflections. In C-type units, following frequency was slower than the rate at which AP trains could be produced in either dorsal root axonal segments or in the soma alone, indicating that the T-junction is a site that acts as a low-pass filter for AP propagation. Following frequency was slower for a train of 20 APs than for two, indicating that a cumulative process leads to propagation failure. Propagation failure was accompanied by diminished somatic membrane input resistance, and was enhanced when Ca 2+ -sensitive K + currents were augmented or when Ca 2+ -sensitive Cl − currents were blocked. After peripheral nerve injury, following frequencies were increased in axotomized C-type neurons and decreased in axotomized non-inflected A-type neurons. These findings reveal that the T-junction in sensory neurons is a regulator of afferent impulse traffic. Diminished filtering of AP trains at the T-junction of C-type neurons with axotomized peripheral processes could enhance the transmission of activity that is ectopically triggered in a neuroma or the neuronal soma, possibly contributing to pain generation.