There are many definitions of rebound pain (RP). All of them have in common the same characteristics: the pain is a severe pain related to regional anesthesia, which occurs after the resolution of the sensory peripheral nerve block (PNB) in the first 12-24 hours after the performing of the PBN, with a duration around 2 hours and does not respond to intravenous opioid administration (Henningsen et al., 2018). The patients describe RP mainly as an intense burning or aching pain (Williams et al., 2007). Although some authors described RP after regional anesthesia as an adverse effect when the block wore off, which impacts the postoperative analgesic benefit by diminishing the overall benefit (Dada et al., 2019), other researchers acknowledged that RP correlates more evident with regional anesthesia for surgical procedures performed under regional anesthesia and more frequently after a single-injection peripheral nerve block (Abdallah et al., 2015; Munoz-Leyva et al., 2020).

This lecture approaches RP from the perspective of the following questions:

1. What are the risk factors for RP?

2. How intense or severe is the RP?

3. When occurs the RP, and what is the mechanism involved?

4. What do we know about the epidemiology of the RP?

5. How can we manage RP?

Regarding the first question, independent study groups identified risk factors as younger age, female gender (Lautenbacher et al., 2005; Li et al., 2022), bone surgery, and the absence of intraoperative intravenous dexamethasone (Barry et al., 2021). For other researchers, the most important risk factor and predictor of rebound pain was preoperative pain (Gramke et al., 2009).

The type of surgery is also a significant risk factor for RP, mainly upper and lower limb surgery, such as shoulder surgery performed under brachial plexus block (Hadzic et al., 2005; Kim et al., 2018), ankle fracture surgery under popliteal sciatic nerve block (Henningsen et al., 2018). When the sensory block revolves in the case of RP, there is a dramatic increase in pain score and opioid consumption, which is not the case for fascial blocks such as tranversus abdominis plane block, pectoral nerves, erector spinae or quadratus lumborum blocks.

2. The intensity of RP appears to be higher after shoulder surgery than complex knee surgery (Williams et al., 2007).

Both RP intensity and incidence are reduced in patients older than 60 years old after primary ankle fracture surgery (Sort et al., 2017). The site of surgery might influence the intensity of RP. In another study, the intensity of RP was reported as excruciating pain at night, with a duration of around two hours and a burning characteristic (Henningsen et al., 2018).

One important concern regarding orthopaedic surgery is an almost three-fold increased risk of developing moderate to severe chronic pain compared with all other types of surgery at one year. Besides the existence of preoperative pain, type of surgery, and percentage of time in severe pain as risk factors of chronic postsurgical pain, there is another important newly identified risk factor, which is a high percentage of time in severe pain in the first 24 h postoperatively (Fletcher et al., 2015)). Therefore, controlling the pain in the first 24 h postoperatively offers a better outcome for longue term and targets a new management goal in prevention of the chronic pain.

3. PNB and regional anesthesia are preferred techniques for ambulatory surgery because of the advantages offered: decreased postanesthesia care unit need and low incidence of nausea, decreased postoperative pain, and lower opioid consumption(Liu et al., 2005). Therefore, RP could be unpleasant and challenging to treat patients in the ambulatory surgery setting when it occurs at home, mostly at night. If pain occurs during sleep, it is intense and wakes the patient, making it difficult for them to go back to sleep (Stone et al., 2022)).

The mechanism of RP is described as an intense burning pain more a neuropathic mechanism than a nociceptive component after nerve block (Williams et al., 2007). In neuropathic pain, ongoing burning pain is caused by abnormal spontaneous C-fibers activity and hyperexcitability of nociceptors (Truini, 2017)).

As I mentioned before, RP occurs frequently and is more severe in patients younger than 60. Although the mechanism is not understood, there are age-related differences in muscle as deep tissue and skin as superficial tissue, nociception increases in peripheral nerve sensitivity to local anesthetics, and peripheral nerve conduction velocity is lower in the elderly.

(Verdu et al., 2000)).

However, the later outcomes of the patients are not influenced by the intensity of the RP. From the patient side, RP does not outweigh the early postoperative benefits of a pain-free interval(Liu et al., 2005).

4. The incidence of RP could reach around 40% of patients for ambulatory surgery and may be due to abnormal spontaneous C-fiber hyperactivity and nociceptor hyper-excitability without mechanical nerve lesions. The incidence of RP is unknown but could reach 40% of patients at PNB resolution (Lavand’homme, 2018). The incidence differs after discharge following inpatient care, and it is 12-13% for severe-to-extreme pain. Another study for ambulatory surgery finds an incidence of 30% of severe pain after 24 hours (McGrath et al., 2004)).

5. Strategies used to manage RP are multiple and involve different approaches.

One of the most important and easy to perform is preoperative education of the patient. The patient should be informed about the limits of regional anesthesia and warned about the possibility of severe but transient pain at the resolution of PNB. Also, they should be instructed to take the rescue analgesic medication prescribed before discharge rather earlier than later. ‘Acknowledging ‘rebound pain’ after the use of regional anesthesia associated with patient counseling regarding early narcotic administration may allow patients to have more effective postoperative pain control (Galos et al., 2016)).

Also important is the preoperative evaluation of the anxiety score and catastrophizing tendencies because both scores significantly correlate with postoperative pain scores (Granot & Ferber, 2005).

Another strategy is using continuous catheter PNB techniques. Increasing the sensory block allows more time for healing, decreases the inflammatory process, and impacts the incidence of RP. Although this strategy has advantages, it remains not the first option for the patient in ambulatory surgery. The main limitations are that the technique is time-consuming, can be performed by highly skilled personnel, and has a failure rate.

The third strategy is using local anesthetic adjuvants in single-injection PNB to prolong the duration of the sensory block. Many experimental and clinical studies study different combinations of local anesthetics with clonidine, dexamethasone, buprenorphine, and dexmedetomidine. So far, the most challenging adjuvant is dexamethasone because it is cheap and easy to find, but the perineural use is off-label. Although dexamethasone (perineural more so than intravenous) can prolong the analgesic benefit of PNB (Heesen et al., 2018), the authors of a recent review prefer systemic administration intravenously of dexamethasone over a perineural route because of a better understanding of potential side effects during intravenously application mode (Streb et al., 2022)).

The duration of the PNB can be achieved with liposomal bupivacaine as an effective strategy to prolong the duration of analgesia (up to 72 h) with single-injection PNB. Still, current evidence fails to support its routine use.

Multimodal analgesia is another strategy recommended, which combines PNB with systemic multimodal analgesia for improving postoperative pain and related outcomes. Multimodal analgesia addresses peripheral sensitization and other physiological responses mediated by the humoral inflammatory response to surgery. These mechanisms are unaffected by the PNB. Different classes of analgesic could be combined: acetaminophen, non-steroidal anti-infammatory drugs/COX-2 inhibitors, oral opioids. As mentioned previously, the administration of the multimodal analgesia before the sensory block resolution could lower the intensity and severity of RP.

Conclusion RP is a transient acute severe pain that appears when the sensory block of regional anesthesia resolves. Although the intensity of pain, RP does not impact significantly the opioid consumption at 24 h, quality of recovery, or patient satisfaction. There is no evidence of an association between RP and chronic postoperative pain. It is important to inform the patient preoperatively about this phenomenon and the patients in ambulatory surgery to recognize RP and to have a perioperative management plan. Preoperative patient education and counseling, the preemptive starting of the multimodal analgesia, using of continuous catheter techniques, or prolonging the duration of PNB with adjuvants are all effective strategies for better care of postoperative pain with a favorable benefit-risk ratio for the patient.

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