FT17 Rebound pain -a misnomer?

Several studies on rebound pain after peripheral nerve blocks are published in the last few years. Rebound pain is a commonly used term to describe strong pain at resolution of peripheral nerve blocks. There is however no formal definition or firm consensus of rebound pain. It is therefore unclear whether authors of different papers are describing the exact same phenomenon. The mechanisms behind rebound pain are also unclear. An important question is whether it simply represents unmasking of the expected nociceptive response after surgery in the absence of adequate analgesia, or if it represents an exaggerated nociceptive response due to a still poorly understood response to the peripheral nerve block itself. In other words: Is rebound pain an actual phenomenon or is it more likely a misnomer, leading to misunderstanding and confusion? For patients, strong pain at block resolution can cause considerable discomfort and fear and may diminish the overall benefits of the block. This is especially important after ambulatory surgery, when patients find themselves discharged and without professional care givers at block resolution. For these patients rebound pain may increase the need for unplanned healthcare resource utilisation after discharge 1 2 Rebound pain is usually referred to as acute postoperative pain after resolution of the sensory nerve block caused by regional anaesthesia. It is also described as an abrupt sensation of clinically significant pain after a long pain free period. Rebound pain is more often reported after dense sensory nerve blocks in contrast to fascial plane blocks like transverse abdominal plane block, erector spinae plane block and quadratus lumborum block, and is often accompanied by an increase in analgesic consumption.3 Some studies use a cut off value of NRS score 7 for what they refer to as rebound pain, others use NRS 8–10.4 5 Another suggested and more precise definition is a mild pain of NRS score less than 4 while the nerve block is working that transition to severe pain represented as a NRS pain score equal or above 7 after block resolution.6 Regardless of whether rebound pain represents a specific phenomenon or not, we do know that a large percentage of patients experience strong pain upon nerve block resolution.7 The incidence is however unknown and varies according to type of surgery and the presence of risk factors for rebound pain. In a retrospective cohort study by Barry and colleagues published in 2020, almost 50% of the patients experienced rebound pain at block resolution after peripheral nerve blocks for a mix of ambulatory surgical procedures.6 In other studies, the reported incidence varies greatly between 9% and 80%.2 7–11 Even though rebound pain is poorly understood, several mechanisms are suggested in the literature. One predominant hypothesis is that rebound pain occurs due to the sudden return of nociceptive sensation as the nerve block wears off. The pain aligns with the expected nociceptive pain response after surgery when adequate pre-emptive and multimodal analgesia is not provided.12 The transition from complete absence of pain when the nerve block is working to a sudden and intense pain from previously suppressed nociceptive signals at block resolution may reduce pain tolerance. Psychological factors like anxiety, fear and fatigue may additionally increase the sensed pain. The inflammatory response to surgery seems to be important for the strong pain at block resolution. Peripheral nerve blocks stop the transmission of nociceptive input to the spinal cord and higher brain areas and therefore may inhibit central sensitisation when the block is working.13 Peripheral nerve blocks like for example brachial plexus blocks may have a small anti-inflammatory effect due to its ability to increase peripheral circulation and thus potentially increase the ‘washing out’ of inflammatory mediators.14 However, the potential anti-inflammatory effect on a remote surgical site seems to be minor and the inflammatory process will continue in the absence of systemic anti-inflammatory prophylaxis.15 An ongoing inflammation at the surgical site may result in sensitisation of peripheral nociceptors. When the nerve block wears off, the patients may be in a state of strong peripheral and central sensitisation from systemic inflammatory mediators. Anti-inflammatory prophylaxis with etoricoxib seems to reduce opioid consumption after surgery, the addition of dexamethasone increases nerve block duration and reduces pain scores.14 The significant effect of dexamethasone to reduce rebound pain strengthens the importance of the inflammatory reaction.8 10 Hyperalgesia, possibly induced by local anaesthetics, has been suggested to contribute to rebound pain after peripheral nerve blocks as rebound pain is often described as a burning sensation. Some studies indicate that a few patients experience hyperalgesia in the aftermath of a nerve block. Transient heat hyperalgesia without hyperalgesia to mechanical stimuli has been demonstrated after sciatic nerve blocks in rats,16 17 but it is important to remember that hyperalgesia to heat stimuli is a normal response to tissue trauma also in the absence of regional anaesthesia.3 The use of regional anaesthesia contribute to reduced perioperative opioid consumption, and as such theoretically prevents opioid-induced hyperalgesia.18 Another theory of rebound pain considers it a reversible nerve injury due to neurotoxicity from potent solutions of local anaesthetics or secondary to nerve injury caused by intrafascicular injection of local anaesthetics or possibly by needle trauma. Another possible cause of transient nerve injury suggested is ischemia caused by compression by local anaesthetics or local vasoconstriction due to local anaesthetics or adjuvants.19 The counterargument to this is that rebound pain only lasts a few hours, significantly shorter than one would expect after nerve injuries. Several factors that increase the risk of rebound pain after peripheral nerve blocks have been identified. Among them are the presence of preoperative pain, young age, female gender, surgery involving bone and the absence of perioperative multimodal analgesia.3 6 9 The absence of perioperative intravenous dexamethasone is highlighted as one of the most important risk factors of rebound pain.6 There are several strategies to reduce rebound pain at block resolution. First, it is important with thorough and repeated patient information, both regarding block offset and expected post-surgical pain. Second, the use of multimodal and prophylactic analgesia is important. Analgesic medication should consist of anti-inflammatory prophylaxis combined with paracetamol and opioids and be initiated in a timely manner. It is important to instruct the patients to take analgesics earlier rather than later when the nerve block is expected to resolve. Third, as nociceptive input and pain generally declines consistently during the hours after surgery, measures to prolong the duration of the nerve block are thought to reduce rebound pain10 20–22 This can be achieved by intravenous, oral or perineural adjuvants or by continuous nerve block catheters. It is important to remember that many potential adjuvants are not licenced for perineural use. Oral and intravenous dexamethasone are shown to prolong nerve block duration and significantly reduce rebound pain.8 10 23 Perineural clonidine and dexmedetomidine prolong nerve block duration, but are not shown to reduce rebound pain, and are associated with side-effects like sedation, bradycardia and dizziness.19 Intravenous ketamine has shown conflicting results while intravenous magnesium has recently been suggested to prolong nerve block duration and reduce rebound pain.8 11 24 25 To conclude, it is not clear if rebound pain is simply a fancy word for poor management of postoperative pain, or if it represents increased pain due to some aspect of the nerve block itself. There are several ongoing studies that hopefully will help us better understand the mechanisms of rebound pain in the future. Regardless of whether rebound pain represents a specific physiological phenomenon or simply the expected nociceptive pain as the nerve block wears off, it is important to explore strategies to reduce the strong pain at block resolution. Literature on this topic published in the last few years singles out intravenous dexamethasone as probably the most important action to reduce this pain and should be combined with a well-timed multimodal analgesic strategy and thorough patient information.References Sunderland S, Yarnold CH, Head SJ, Osborn JA, Purssell A, Peel JK, et al. Regional versus general anesthesia and the incidence of unplanned health care resource utilization for postoperative pain after wrist fracture surgery: results from a retrospective quality improvement project. Reg Anesth Pain Med. 2016;41(1):22–7.Lavand’homme P. Rebound pain after regional anesthesia in the ambulatory patient. Curr Opin Anaesthesiol. 2018;31(6):679–84.Munoz-Leyva F, Cubillos J, Chin KJ. 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