Pain management strategies following thoracic surgery: best practices and innovations

Abstract

Pain after thoracic surgery can be among the most severe, complex, and difficult to manage of any procedure. Acute pain has somatic, visceral, and neuropathic components, and its severity is the strongest modifiable predictor of chronic post-surgical pain. Inadequate analgesia drives complications, delays recovery, and may progress to chronic post-surgical pain. This review synthesizes the pathophysiology of acute and chronic pain after thoracic surgery, examines the updated guideline recommendations for regional anesthesia, describes methods that can be used as part of a comprehensive pain control protocol after thoracic surgery, and points to promising future developments. Surgical approach is a powerful determinant of pain, and minimally invasive access reduces acute pain relative to open thoracotomy. Multimodal analgesia combining systemic agents with procedure-specific regional anesthesia remains the foundation of perioperative management, but guidelines strongly emphasize the use of regional anesthesia as an adjunct for pain control. Recent studies suggest that moving towards surgeon-administered blocks and implementation of developing technologies may improve the efficacy and decrease the resources needed for analgesia after thoracic surgery. Future priorities include trials with standardized outcomes, cost-effectiveness analyses, validation of newer therapies, and long-term follow-up. Overall, protocols for pain management after thoracic surgery should focus on an evidence-based, patient-centered framework for analgesia selection to optimize recovery and reduce the rate of complications.

Introduction

Background

Pain after thoracic surgery is among the most complex and severe of any surgical procedure and has a significant impact on morbidity and mortality. Poorly controlled pain after surgery can prolong hospital stay, increase admission costs, and worsen patient outcomes (1). Additionally, inadequate analgesia after thoracic surgery increases the risk of pneumonia and cardiac complications, impairs mobility, indirectly increasing the risk of thromboembolic complications, and delays recovery (2,3). Uncontrolled acute postoperative pain is the strongest modifiable risk factor for chronic post-surgical pain (CPSP), which affects up to one-third of patients after thoracic surgery. Therefore, optimizing perioperative analgesia is essential to enhancing patient-centered outcomes.

Multimodal analgesia remains the foundation of modern perioperative pain management, combining non-opioid systemic agents, such as acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase-2 (COX-2) inhibitors, and muscle relaxants, with procedure-specific regional anesthesia to achieve additive or synergistic analgesic effects while minimizing opioid exposure. Adjunct medications, including gabapentinoids, ketamine, and dexmedetomidine, further expand the toolkit (4-6).

Rationale and objective

The 2022 and 2025 PROcedure-SPECific postoperative pain managemenT (PROSPECT) Guidelines, developed by the European Society of Regional Anesthesia and Pain Therapy for open thoracotomy and video-assisted thoracic surgery (VATS), the 2026 American Society of Anesthesiologists (ASA) Practice Guidelines, and several landmark randomized trials have substantially reshaped post-operative pain management, creating a need to synthesize best practices tailored to patient characteristics (7-9). The guidelines emphasize the role of regional anesthesia in conjunction with systemic therapies for managing pain after thoracic surgery. A growing body of evidence from randomized trials and meta-analyses has examined new ways to deliver and personalize this care, including surgeon-delivered single-shot regional techniques (10-12), extended-release local anesthetics such as liposomal bupivacaine (LB) (13), and machine-learning and pharmacogenomic approaches (14). In this review, we aim to coalesce the current understanding of the physiology underlying acute and chronic pain after thoracic surgery, recent guideline changes that have been made based on the latest evidence (particularly regarding regional anesthesia), innovations in the delivery of care, and how these should be applied in a patient-centered approach to postoperative pain management.

Pathophysiology of post-thoracic surgery pain

Mechanisms of acute postoperative pain

Post-operative thoracic surgical pain arises from multiple mechanisms (e.g., the intercostal nerves and multiple nociceptive inputs from the chest wall, thoracic viscera, and diaphragm), which contribute to challenges in pain management. The dominant contributor is injury to the intercostal nerves, which can be injured during retraction, trocar placement, rib fracture or resection, or entrapment during closure. The resulting pain has both nociceptive and neuropathic components (15,16). Superimposed on the pain from intercostal nerve injury are somatic pain (from the chest-wall muscles, periosteum, costovertebral joints, and costal parietal pleura) and visceral pain (from the lung and mediastinal structures). This visceral input is sensed via vagal and sympathetic fibers and is characteristically diffuse and poorly localized, whereas irritation of the diaphragm and mediastinal pleura is referred through the phrenic nerve and perceived as ipsilateral shoulder pain, which is typically refractory to intercostal-directed blockade (17). Thoracostomy tubes and rib plates can also contribute to post-surgical pain after the initial surgical insult subsides. Sustained nociceptive input from these sources drives a peripheral-to-central sensitization cascade. At the periphery, inflammatory mediators lower the activation threshold of intercostal nociceptors, causing hyperalgesia. Repetitive input to the spinal dorsal horn then produces progressively amplified signals that result in central sensitization and neuroinflammatory glial activation outlasting the initiating injury (5,15,18), which causes a progression to chronic pain over time if the cycle is not interrupted. Given this complex pathophysiology, a multimodal and multidisciplinary approach is required for adequate acute pain control.

Transition from acute to CPSP

CPSP after thoracotomy, defined as pain persisting beyond 2 months postoperatively, is common, affecting approximately 25% to 55% of patients depending on surgical approach and follow-up duration; a meta-analysis of 90 studies (19,001 patients) reported a pooled prevalence of 38% (19-21). CPSP is a mixed pain syndrome with a prominent neuropathic component that arises from intercostal nerve injury and manifests as burning, shooting, or allodynic pain, coexisting with nociceptive-somatic pain. Depending on the assessment method, approximately one-third to two-thirds of affected patients have an identifiable neuropathic component (16,19,21,22). Chronic pain is hypothesized to arise from intercostal nerve injury, central sensitization, and neuroinflammatory pathways, supported by studies demonstrating increased sensitivity at operative scars and electromyography confirming nerve-injury patterns (15). The factor most strongly associated with CPSP is uncontrolled acute postoperative pain during the first postoperative days. Other significant risk factors include chest tube maintenance greater than 4 days, age less than 60 years, female gender, pre-existing mental health conditions, and pre-existing chronic pain (19,23). Of these, the primary modifiable factors are early pain control, reduced chest tube duration, and psychological support.

High-risk populations and consequences of inadequate pain control

Adequate analgesia in the immediate postoperative period is necessary to prevent both short- and long-term complications. The most common acute pain-related complications include pulmonary, thromboembolic, cardiac events, and CPSP progression. In one prospective observational study, delay in adequate analgesia doubled the risk of postoperative complications (24). Several patient populations face disproportionate risk. First, patients with chronic obstructive pulmonary disease (COPD) are the most consistently identified high-risk group. A meta-analysis of over 31,000 patients found that patients with COPD had 2.5-fold increased odds of pulmonary complications (25). Patients with COPD have limited pulmonary reserve, making them especially vulnerable to the splinting, atelectasis, and pneumonia that follow inadequate analgesia. Second, elderly patients (≥65 years in most studies) may report lower pain scores and use fewer opioids, but they are more sensitive to opioid adverse effects and are prone to undertreatment from communication barriers such as sensory or cognitive impairment, language differences, and post-anesthetic confusion (26-28). Third, operative approach strongly influences the severity of postoperative pain; open thoracotomy carries a 6.8-fold increased risk of CPSP compared with minimally invasive approaches (16). Finally, patients with psychological vulnerability (e.g., preoperative anxiety, depression, or chronic pain) have higher rates of both severe acute pain and CPSP. A large prospective cohort (n=8,350) found that preoperative anxiety [odds ratio (OR) 1.52; 95% confidence interval (CI) 1.23–1.86] and multiple preoperative psychological symptoms (OR 1.84; 95% CI: 1.48–2.28) were associated with an increased odds for CPSP (23,29). Pre-existing chronic pain is a strong predictor of developing new CPSP (OR 2.9; 95% CI: 1.9–4.2), and opioid-tolerant patients [≥60 morphine milligram equivalents (MME)/day] are classified as high-risk by the American Society for Enhanced Recovery/Perioperative Quality Initiative (ASER/POQI) due to the compounded challenges of tolerance, hyperalgesia, and the inherently painful nature of the procedure (30,31).

Surgical approach is among the strongest determinants of both acute and chronic pain after thoracic surgery. Open thoracotomy, through rib retraction and direct intercostal nerve trauma, produces more severe acute pain and a substantially higher risk of CPSP than minimally invasive surgery, whereas VATS is independently protective against CPSP (16,30). This gradient has driven the shift toward VATS and robotic-assisted thoracic surgery (RATS) and has lessened the necessary intensity of regional analgesia strategies (32). RATS and VATS produce broadly comparable postoperative pain, although some data suggest RATS modestly reduces early symptom burden (33). Because they reduce the risk of intercostal neuralgia, subxiphoid and subcostal approaches are attractive modifications of transthoracic minimally invasive techniques. A randomized trial of 262 patients undergoing lung resection found lower early pain and earlier mobilization with a subxiphoid as compared with an intercostal VATS approach (34). A prospective study of 833 lobectomies found less moderate-to-severe pain and better quality of life at one and three months (35). The subxiphoid approach, however, carries a higher rate of intraoperative arrhythmia from cardiac compression, potentially limiting its use in patients with cardiac comorbidity (34,36).

Systemic therapies for pain control in thoracic surgery

Standard multimodal therapy

The PROSPECT guidelines recommend using systemic non-opioid analgesics and regional anesthesia as first-line therapy with selective use of adjunctive medications (e.g., ketamine and alpha-2 adrenergic agonists) in opioid-sparing patient care pathways (7,37). Depending on patient comorbidities, acetaminophen and an NSAID or COX-2-selective inhibitor should be initiated perioperatively and continued postoperatively to provide sustained analgesic coverage. Pre-operative initiation of systemic analgesia is part of many enhanced recovery protocols. Pre-emptive medications are given as a single scheduled oral or intravenous dose, typically acetaminophen plus an NSAID or COX-2 inhibitor with or without a gabapentinoid, rather than as an infusion, in contrast to the infusion-based adjuncts (ketamine and intravenous lidocaine) discussed below. Administering these agents before (rather than after) incision does not independently confer a clear analgesic advantage. Therefore, the emphasis of timing should focus on establishing effective coverage by emergence (7,37). Pre-emptive medications are effective. A randomized trial of 90 patients undergoing VATS demonstrated that intravenous acetaminophen in addition to a thoracic paravertebral block (PVB) lowered pain scores through 48 hours and reduced intraoperative sufentanil and postoperative oxycodone consumption compared with PVB alone (38). NSAID and COX-2 inhibitor use should be used cautiously in patients with higher renal, cardiovascular, and gastrointestinal risk profiles; selective COX-2 agents are generally preferred when these risks are present (7). Gabapentinoids were historically incorporated into thoracic enhanced-recovery pathways, but mixed evidence and adverse effects have tempered their routine use. A randomized controlled trial (RCT) of 100 patients undergoing VATS randomized to peri-operative pregabalin versus placebo found no reduction in cumulative pain, postoperative morphine consumption, or development of CPSP (39). Systemic opioids are reserved as rescue analgesics for breakthrough pain not controlled by non-opioid multimodal and regional therapy. High-quality head-to-head comparisons of opioid agent, route, or scheduling specific to thoracic surgery are limited and no specific agent is preferred (7).

Adjunct medications

Sub-anesthetic intravenous ketamine (or its enantiomer esketamine), an N-methyl-D-aspartate (NMDA) receptor antagonist, has been investigated as a perioperative analgesic adjunct in thoracic surgery; by blocking the NMDA receptor it attenuates dorsal-horn central sensitization and opioid-induced hyperalgesia, producing opioid-sparing analgesia. A meta-analysis of nine randomized trials enrolling 556 patients undergoing thoracotomy found that adding ketamine to morphine reduced pain and post-operative opioid consumption over the first three days (5). In a randomized trial of 100 patients undergoing VATS lung resection, intravenous esketamine combined with either an erector spinae plane (ESP) block or an intercostal nerve block (ICNB) improved 24-hour Quality of Recovery-15 (QoR-15) scores by 6.1 points (95% CI: 4.0–8.1; P<0.001) compared with placebo (40). The ASRA/AAPM/ASA consensus supports subanesthetic dosing, delivered as an induction bolus followed by a continuous intraoperative (and, where tolerated, postoperative) infusion. A representative regimen is an induction bolus of approximately 0.25 to 0.35 mg/kg followed by an infusion of 0.1 to 0.25 mg/kg/h (41). In centers with adequate resources, these patients can be monitored outside of the intensive care setting by staff trained for moderate sedation, but its adverse effect profile limits its use outside operative and intensive care at many centers (41). As the S(+)-enantiomer, esketamine is roughly twice as potent, so approximately half these doses are used (40). Although not a procedure-specific PROSPECT recommendation, ketamine remains a reasonable opioid-sparing adjunct in selected patients (7,8).

Dexmedetomidine, an alpha-2 adrenergic agonist, improves analgesia and reduces opioid requirements when administered as an intraoperative or postoperative intravenous infusion. A meta-analysis of 12 randomized trials enrolling 905 thoracic surgical patients found that perioperative dexmedetomidine lowered resting pain scores; it additionally reduced postoperative nausea and vomiting compared with placebo. This effect was true for both thoracotomy and VATS cohorts; both intravenous and regional administration improved pain control (42). Bradycardia and hypotension are the most common adverse effects and require titration in patients with limited hemodynamic reserve. Clonidine, a less selective alpha-2 agonist, has less supporting evidence in thoracic surgery. A network meta-analysis of 124 randomized trials (26,257 cardiac surgical patients) found that clonidine modestly reduced resting pain at 24 hours (mean difference −0.38 points; 95% CI: −0.73 to −0.04) and shortened the duration of mechanical ventilation (43). A randomized trial of 60 patients undergoing elective thoracotomy found that adding clonidine to epidural bupivacaine prolonged analgesia and reduced rescue analgesic use, although sedation scores were higher (44). These alpha-2 agonists are not specifically recommended in guidelines but are reasonable adjuncts in select patients.

Intravenous lidocaine reduces pain through local and central nervous modulation and anti-inflammatory effects (45). In an RCT of 154 patients undergoing VATS lung resection, intraoperative intravenous lidocaine reduced major complications compared with remifentanil (3.7% vs. 11.8%; P=0.037) and approximately halved pulmonary complications (OR 0.35; 95% CI: 0.17–0.72) (46). International consensus recommends an initial bolus of no more than 1.5 mg/kg of ideal body weight over 10 minutes, followed by an infusion of no more than 1.5 mg/kg/h for up to 24 hours. Further, guidelines regard lidocaine as a high-risk medicine given the potential for local anesthetic systemic toxicity (47). It should not be combined with continuous regional local-anesthetic infusions, and consensus advises a 4-hour separation between intravenous lidocaine and any nerve block (47). Like ketamine, intravenous lidocaine is not a procedure-specific PROSPECT recommendation, but it is a reasonable adjunct, most useful when regional catheter techniques are not implemented (7).

Regional anesthesia techniques for thoracic surgery

Regardless of approach, regional anesthesia remains a cornerstone of perioperative pain management in thoracic surgery, recommended in current guidelines not only for patient comfort but to reduce complications and expedite recovery (32). The PROSPECT guidelines recommend thoracic epidural analgesia (TEA) or PVB as first-line interventions for open thoracotomy, and PVB or ESP block as first-line options for VATS/RATS. TEA is explicitly not recommended for routine VATS/RATS, marking a change from prior recommendations (8,9). When first-line options are contraindicated, second-line alternatives include ESP block (for thoracotomy), rhomboid intercostal block (RIB), and ICNB. These techniques also differ in technical demand and operator dependence: TEA has the steepest learning curve, PVB is intermediate, and the fascial-plane blocks (ESP, RIB, and SAP) are comparatively straightforward to learn. Cryoanalgesia or acupuncture are reserved for patients in whom all regional techniques are contraindicated (8,9). Comparative features of each technique are summarized in Table 1, and key recent clinical trials evaluating these techniques are summarized in Table 2.

Table 1. Comparison of regional anesthesia techniques recommended by the PROSPECT guidelines.

Technique	Open thoracotomy (PROSPECT)	VATS (PROSPECT)	Coverage/mechanism	Key adverse effects or drawbacks	Key contraindications
TEA	First-line (co-equal with PVB)	Not recommended	Bilateral spinal nerve root blockade; multi-level thoracic coverage	Hypotension; urinary retention; LE motor weakness; epidural hematoma/abscess	Anticoagulation; prior spinal surgery; vertebral fracture; altered mental status
PVB	First-line (co-equal with TEA)	First-line (co-equal with ESP)	Ipsilateral multi-dermatomal somatic + sympathetic blockade	Fewer systemic effects vs. TEA; rare pneumothorax	Relative: coagulopathy (fewer restrictions than TEA)
ESP block	Second-line	First-line (co-equal with PVB)	Fascial plane; superficial target; variable spread	Low pneumothorax/vascular risk; possible inconsistent coverage	None established
RIB block	Second-line	Not addressed	Lateral cutaneous branches + dorsal rami at medial scapular border	Limited comparative data	None established
ICNB	Second-line	Not recommended†	Direct intercostal nerve block at multiple levels	Shorter duration (single-shot)	None established; caution in coagulopathy
SAP block	Not recommended	Second-line	Lateral cutaneous branches T2-T9; anterolateral chest wall	Efficacy versus other blocks not well established in head-to-head trials	No absolute contraindications

^†, clinical trials (Spaans et al. 2025, Coppens et al. 2025) have since been published showing ICNB benefit in minimally invasive thoracic surgery. ESP, erector spinae plane; ICNB, intercostal nerve block; LE, lower extremity; PROSPECT, PROcedure-SPECific postoperative pain managemenT; PVB, paravertebral block; RIB, rhomboid intercostal block; SAP, serratus anterior plane; TEA, thoracic epidural analgesia; VATS, video-assisted thoracic surgery.

Table 2. Key contemporary clinical trials evaluating regional anesthesia techniques in thoracic surgery.

Author [year] (ref)	Regional anesthesia investigated (approach, patients enrolled)	Key outcome or comparison
Chaudhary et al. [2020] (48)	ESP block vs. ICNB (VATS, n=78)	Faster anesthesia recovery, shorter PACU stay, better pulmonary function preservation
Fiorelli et al. [2020] (49)	ESP block vs. ICNB (mini-thoracotomy, n=60)	ESP superior in static/dynamic pain, opioid use, satisfaction, respiratory muscle strength
Chenesseau et al. [2023] (11)	Surgeon vs. anesthesiologist US-guided PVB (VATS, n=196)	Surgeon-performed PVB noninferior; comparable opioid consumption and pain scores
Moorthy et al. [2023] (50)	Anesthesiologist US-guided ESP catheter vs. surgeon-placed PVB catheter (VATS, n=80)	Higher QoR-15 at 24 and 48 h with ESP; no difference in pain or opioid consumption
Andrade Filho et al. [2024] (51)	Continuous ESP vs. PVB (thoracotomy or VATS, n=120)	Continuous ESP inferior to PVB at 24 h (non-inferiority not met)
Jackson et al. [2024] (52)	SAP block vs. placebo (VATS, n=92)	No significant reduction in 24-h opioid consumption
Leviel et al. [2024] (53)	SAP + PVB combination vs. single block (VATS, n=156)	Combined SAP + PVB lower pain scores at rest and on cough vs. either alone
Spaans et al. [2025] (10)	Single-shot ICNB vs. TEA vs. continuous PVB (VATS, n=450)	ICNB noninferior to TEA for pain control
Coppens et al. [2025] (12)	Surgeon ICNB vs. ESP (VATS, n=100)	ICNB reduced opioid consumption; no difference in satisfaction or LOS
Koliakos et al. [2025] (54)	Cryoanalgesia (VATS, n=80)	No benefit on pain or opioid requirements
Weksler et al. [2025] (55)	Cryoablation of intercostal nerves (VATS, n=103)	Higher neuropathy scores at 2 weeks; no analgesic benefit
Tang et al. [2025] (56)	Dexmedetomidine vs. ropivacaine adjuvant for single-shot PVB (VATS, n=120)	Dexmedetomidine extended analgesia, reduced opioid demand, shortened LOS
Shelley et al. [2026] (57)	PVB vs. TEA (thoracotomy, n=770)	No significant difference in 6-mo CPSP, QALYs, or costs
Li et al. [2026] (58)	Liposomal bupivacaine vs. bupivacaine + dexamethasone for PVB (VATS, n=78)	56% extension of analgesia (1,160 vs. 743 min); lower day-1 pain scores

CPSP, chronic post-surgical pain; ESP, erector spinae plane; ICNB, intercostal nerve block; LOS, length of stay; PACU, post-anesthesia care unit; PVB, paravertebral block; QALY, quality-adjusted life-year; QoR-15, Quality of Recovery-15; SAP, serratus anterior plane; TEA, thoracic epidural analgesia; US, ultrasound; VATS, video-assisted thoracic surgery.

TEA

TEA involves placement of a catheter into the thoracic epidural space, enabling continuous or intermittent administration of local anesthetics (most commonly bupivacaine or ropivacaine) which may be combined with a lipophilic opioid such as fentanyl or hydromorphone (59). Local anesthetics attenuate nociceptive input by inhibiting sodium channels in spinal nerve roots and dorsal horn neurons, while co-administered opioids bind spinal cord opioid receptors for a synergistic analgesic effect (60). Current guidelines recommend epidural local anesthetics as the foundation of TEA, but evidence supports the addition of lipophilic opioids to control pain or when local anesthetic alone provides inadequate pain relief or dermatomal coverage (8,9). The bilateral sympathetic blockade produced by TEA contributes to its analgesic profile but is simultaneously responsible for many of its adverse effects (15), including hypotension, urinary retention, and lower extremity motor weakness. Rare but serious complications include epidural hematoma or abscess (15,59). According to the American Society of Regional Anesthesia and Pain Medicine (ASRA) Guidelines, TEA is contraindicated in patients with active anticoagulation that cannot be safely interrupted, and relatively contraindicated in patients with local infection, prior spinal surgery, or vertebral fracture (2,61).

TEA has long been regarded as the gold standard for post-thoracotomy pain management (15,62). A landmark meta-analysis demonstrated superior postoperative analgesia versus parenteral opioids up to four days after surgery, with the greatest benefit when local anesthetic was included (60). A systematic review of 125 RCTs (9,044 patients) found that epidural analgesia reduced postoperative mortality (3.1% vs. 4.9%; OR 0.60; 95% CI: 0.39–0.93) and was associated with decreased incidence of atrial fibrillation, deep vein thrombosis, respiratory depression, atelectasis, pneumonia, and ileus compared with systemic opioid analgesia (63). Despite its efficacy, TEA's adverse effect profile limits its use in many settings.

Compared with ESP, serratus anterior plane (SAP), PVB, or ICNB, meta-analyses demonstrate that TEA for VATS/RATS perioperative pain management does not significantly reduce opioid consumption, nausea and vomiting, pulmonary complications, or length of stay (64). PVB may be preferable given the risk of bleeding or epidural puncture complications (65). The PROSPECT Guidelines explicitly advise against its routine use in VATS/RATS, a decisive departure from prior paradigms (8). The 2026 ASA Guidelines reinforce this position, recommending neuraxial or fascial plane blocks within a multimodal regimen for minimally invasive cardiothoracic surgery (9).

PVB

PVB involves injection of local anesthetic into the paravertebral space adjacent to the vertebral body, producing ipsilateral somatic and sympathetic nerve blockades across multiple dermatomes. PVB may be placed percutaneously under ultrasound guidance or by the surgeon under thoracoscopic visualization and can be delivered in one of several ways (2,3). A single-site catheter delivering continuous pump infusion relies on longitudinal spread of local anesthetic within the paravertebral space to reach adjacent dermatomes and delivers continuous analgesia, with the requirement of tying the patient to a pump. Single-shot injections at multiple levels instead achieve segmental breadth directly, depositing anesthetic at each targeted dermatome without indwelling hardware that may limit mobility, but cannot be easily re-dosed. Intermittent boluses through a single-site catheter are an intermediate approach that prolongs a single-site block and allows re-dosing, either by manual injection without a continuous pump or through a patient-controlled analgesia device. Current anesthesia society guidelines, including the PROSPECT and ASA guidelines, recommend PVB as a first-line technique without specifying delivery method, leaving the choice to institutional expertise, expected pain duration, and patient preference (8,9).

Multiple systematic reviews and meta-analyses have established that PVB provides comparable analgesic efficacy to TEA for post-thoracotomy pain management. A Cochrane review found continuous PVB offered comparable pain control as TEA (15,66). Though a recent meta-analysis of 35 randomized trials found that TEA provides modestly lower pain scores at 24 hours as compared with PVB, these differences were no longer significant by 48 hours (67). TEA has not been found to independently reduce the risk of CPSP. The TOPIC2trial, a multicenter RCT of 770 thoracotomy patients across 15 UK centers, found no significant difference in CPSP at six months [PVB 22% vs. TEA 16%; adjusted risk ratio (RR) 1.32; 95% CI: 0.93–1.86; P=0.12] and no significant differences in quality-adjusted life-years or costs (57). However, compared with TEA, PVB carries substantially lower rates of hypotension (OR 0.13; 95% CI: 0.06–0.31), urinary retention (OR 0.23), and nausea and vomiting (OR 0.38), without the bilateral sympathectomy or lower extremity motor weakness associated with TEA (50,67).

For VATS, PVB is recommended as a first-choice regional analgesic technique alongside ESP block (8,9). A meta-analysis of 21 RCTs (1,391 patients) found that PVB had the greatest effect on 24-hour opioid consumption and demonstrated superior analgesia in the middle and late postoperative periods, with advantages in reducing nausea, emesis, and pruritus compared with other techniques (65,68). The optimal delivery method and choice of adjuvant agents remain under active investigation (56). A randomized clinical trial demonstrated that surgeon-performed PVB under thoracoscopic visualization was noninferior to anesthesiologist-performed ultrasound-guided PVB, with comparable opioid consumption and pain scores, a practical advantage in settings with limited anesthesiology staffing (11).

ESP block

The ESP block is performed by injecting local anesthetic deep to the erector spinae muscle at the tip of the transverse process. Its superficial target is technically simpler to identify than the paravertebral space, broadening accessibility across practitioners with varying levels of regional anesthesia experience (69). Because the injection site is distant from the pleura and major vascular structures, ESP block carries a lower risk of pneumothorax and vascular injury compared with PVB, contributing to its rapid adoption in many thoracic surgical practices. ESP block has also been associated with rapid recovery from anesthesia, shorter post-anesthesia care unit stays, and improved preservation of pulmonary function parameters compared with ICNB (48).

In open thoracotomy, a meta-analysis found that ESP block produced the greatest reduction in pain scores at 24 hours among regional techniques evaluated (70). A randomized trial comparing ESP block with ICNB for mini-thoracotomy found ESP superior for pain scores, analgesic requirements, patient satisfaction, and preservation of respiratory muscle strength, highlighting its efficacy (49).

The PROSPECT guidelines recommend ESP block as a co-first-choice technique alongside PVB for VATS, and the 2026 ASA guideline includes ESP block among the fascial plane blocks recommended for minimally invasive cardiothoracic surgery (8,9). The available evidence behind these recommendations is mixed. A meta-analysis of 25 studies (1,847 patients) found PVB superior to ESP block for early analgesia (0–6 hours) but comparable at 24 and 48 hours (71). A non-inferiority RCT of 120 patients undergoing lung surgery found continuous ESP inferior to continuous PVB over 24 hours (51). Conversely, a randomized trial of 80 VATS patients found that continuous ESP catheter produced higher QoR-15 scores at 24 and 48 hours compared with surgeon-placed PVB catheter, without differences in pain scores or opioid consumption (50). A propensity-matched study of 107 VATS patients found ESP associated with lower pain scores at rest and with cough at 24 hours compared with PVB (72). Taken together, ESP block is a practical and safe first-line alternative to PVB for VATS, with the caveat that PVB may offer modestly superior early analgesia and that variable fascial plane spread may result in inconsistent coverage in some patients (3).

RIB

A RIB deposits local anesthetic between the rhomboid major muscle and the intercostal muscles at the medial scapular border under ultrasound guidance, targeting the lateral cutaneous branches of the intercostal nerves and dorsal rami. In a randomized trial by Manici et al., 84 patients undergoing VATS for lung cancer received either RIB or PVB, and the two groups showed no difference in 24-hour opioid consumption, pain scores, or rescue analgesic requirements (73). Its inclusion in the 2025 PROSPECT Guidelines as a second-line option reflects an emerging evidence base, though further studies in open thoracotomy populations are needed (8).

ICNBs

ICNB involves injection of local anesthetic around intercostal nerves at multiple levels spanning the surgical field, and can be performed percutaneously, under ultrasound guidance, or directly by the surgeon under thoracoscopic visualization. A systematic review found that ICNB provides a modest opioid-sparing effect versus systemic analgesia alone, peaking at 48 hours, but is generally inferior to TEA and PVB in thoracotomy (74). However, ICNB has emerged as a compelling analgesic option for VATS and RATS, bolstered by the landmark 2025 multicenter noninferiority trial (n=450 patients, 11 centers). Single-shot ICNB at levels T2-T10 under direct thoracoscopic visualization was noninferior to TEA for pain control (mean proportion of pain scores ≥4: 29.5% vs. 20.7%; upper limit of 1-sided 98.65% CI =16.1%, within the prespecified 17.5% margin) (10). Another RCT of 100 patients undergoing single-port VATS found that surgeon-performed ICNB significantly reduced opioid consumption compared with ESP block, with no differences in patient satisfaction, complications, or length of stay (12). In meta-analyses, ICNB demonstrated superior analgesic effects in the middle and late postoperative periods and the lowest probability of postoperative nausea and vomiting among regional techniques evaluated (68,75). The single-shot approach is technically straightforward, can be performed by the surgeon during VATS, and eliminates the need for catheter management or anesthesiology co-management.

SAP block

The SAP block targets the lateral cutaneous branches of the intercostal nerves (T2-T9) by injection superficial or deep to the serratus anterior muscle at the midaxillary line, providing analgesia primarily to the anterolateral chest wall (76). Multiple meta-analyses have established that SAP block significantly reduces postoperative pain compared with placebo (77,78). However, a randomized placebo-controlled trial of 92 patients undergoing thoracoscopic lung resection found no significant reduction in 24-hour opioid consumption (52). The THORACOSOPIC trial (n=156) found that combining SAP block with PVB produced significantly lower pain scores at rest and on cough compared with either technique alone (53). The PROSPECT guidelines position SAP block as a second-choice option for VATS, recommended when first-line techniques are not feasible or are contraindicated (7,32).

Alternative techniques when regional analgesia is contraindicated

When all forms of regional analgesia are contraindicated (e.g., severe coagulopathy, local infection at potential block sites, or patient refusal) guidelines recommend consideration of cryoanalgesia or acupuncture as analgesic adjuncts, though supporting evidence remains limited (8). Cryoanalgesia applies extreme cold (−60 to −80 ℃) to intercostal nerves via cryoprobe, inducing reversible axonal degeneration while preserving the endoneurium, allowing subsequent nerve regeneration. Evidence is conflicting: a prospective randomized trial of 200 thoracotomy patients found significantly improved pain scores and reduced opioid consumption, with cutaneous sensory changes resolving within six months (79). Conversely, RCTs of VATS patients found no benefit on pain or opioid requirements; one trial reported higher neuropathy scores at 2 weeks in the cryoanalgesia group (54,55). Further investigation is needed to define optimal parameters, patient selection, and the technique’s potential contribution to CPSP.

Electroacupuncture has been investigated as an adjunctive modality. A meta-analysis of 11 RCTs found significant reductions in 24-hour pain scores and total opioid consumption versus sham or conventional analgesia (80). Overall evidence quality remains low due to high heterogeneity, small samples, and variable protocols, but its favorable safety profile supports consideration as an adjunct when conventional regional techniques cannot be employed (8,81,82).

Patient-centered and personalized pain management

The expanding repertoire of analgesic techniques underscores a central theme of contemporary thoracic surgical care: no single strategy fits all scenarios. The 2025 PROSPECT Guidelines explicitly frame the choice between first-line techniques as one guided by patient and clinician preference, reflecting a broader shift toward individualized pain management and allowing for adjustments based on center expertise and resources (8,32).

Individualized risk stratification

Effective personalization begins with preoperative risk stratification. A meta-analysis by Clephas et al. of 56 thoracic surgery studies identified preoperative pain (OR 2.86; 95% CI: 1.94–4.21), higher acute postoperative pain intensity on day one, longer surgical duration, and open thoracotomy as significant prognostic factors for CPSP (30). Additional risk factors include younger age, female sex, anxiety, depression, and preoperative opioid use (83,84). The Society of Cardiovascular Anesthesiologists (SCA) recommends that preoperative evaluation should incorporate screening for modifiable and non-modifiable risk factors to guide analgesic planning, for example prioritizing aggressive regional analgesia and multimodal opioid-sparing strategies in high-CPSP-risk patients (2).

Shared decision-making and patient education

Shared decision-making and preoperative education are complementary components of individualized pain management. The PROSPECT Guidelines position clinician-patient dialogue as central to analgesic selection: the choice should incorporate patient values regarding trade-offs between potency and adverse effects, supported by multidisciplinary collaboration among surgical, anesthetic, and acute pain teams (3,8,85). The ASER/POQI and SCA advisories similarly recommend individualized preoperative education on multimodal analgesia, opioid risks, and realistic pain expectations, noting that expectation management improves satisfaction and decreases opioid demand (2,31). Education should also address functional recovery goals and physiotherapy participation.

Special populations

Elderly patients have age-related pharmacokinetic and pharmacodynamic changes that heighten sensitivity to opioids, increasing the risk of delirium, respiratory depression, falls, and constipation; regional techniques are particularly valuable as opioid-sparing strategies in this group (27,28). The American Geriatrics Society (AGS) Beers Criteria should guide avoidance of potentially inappropriate medications. Cautious use of NSAIDs is recommended, preferring COX-2 selective agents with gastroprotection (8), and gabapentinoids should be initiated with slow titration to minimize sedation, dizziness, and the increased risk of delirium and pneumonia observed with perioperative gabapentin use in older surgical patients (86). For elderly patients, documented pain management goals are recommended per the ACS Geriatric Surgery Verification Program (8,27).

Opioid-tolerant patients (≥60 MME/day) require continuation of baseline opioid therapy to prevent withdrawal, with the primary objective of managing acute surgical pain while avoiding persistent escalation beyond the preoperative dose. Multimodal strategies should maximize non-opioid adjuncts including ketamine, intravenous lidocaine infusions, gabapentinoids, and regional techniques (31,87). Given their higher likelihood of developing CPSP, setting expectations pre-operatively and early involvement of acute and chronic pain teams is especially important in this population.

Prevention and management of CPSP

Preventive strategies

Prevention of CPSP begins before incision: preoperative expectation-setting in the clinic is itself a modifiable factor, as patients‘ expectations of postoperative pain significantly influence its measured severity after thoracic surgery (88). The most consistently identified modifiable risk factor for CPSP is the severity of acute postoperative pain, with higher day-one pain scores significantly increasing risk (30). In another, moderate-to-severe acute postoperative pain carried an OR of 32.61 (95% CI: 13.37–79.54) for CPSP development, making optimal acute pain control the single most impactful preventive intervention (16). The PROSPECT Guidelines recommend first-line regional analgesia combined with acetaminophen and NSAIDs or COX-2 inhibitors as the foundation for both acute pain management and CPSP prevention (8). Among regional techniques, ICNB is the only intervention with meta-analytic evidence demonstrating a direct reduction in CPSP risk (OR 0.76; 95% CI: 0.61–0.95; moderate-certainty evidence), confirmed by trial sequential analysis (30). VATS itself is a protective factor against CPSP (OR 0.54; 95% CI: 0.43–0.66), reinforcing the role of minimally invasive surgery as a primary preventive strategy (16,30). Despite earlier interest in gabapentinoids as a strategy for CPSP prevention, thoracic-specific evidence does not support routine use, and the PROSPECT guidelines do not include a specific recommendation for perioperative gabapentinoids given limited thoracic-specific evidence and undefined optimal dosing (8).

Treatment of established CPSP

When CPSP develops, management follows principles for chronic neuropathic pain, as a neuropathic component is present in a substantial proportion of patients. The 2025 Neuropathic Pain Special Interest Group of the International Association for the Study of Pain (NeuPSIG) updated guidelines recommend gabapentinoids (gabapentin or pregabalin) and serotonin-norepinephrine reuptake inhibitors (SNRIs: duloxetine or venlafaxine) as first-line pharmacotherapy, with tricyclic antidepressants [number needed to treat (NNT) 4.6; 95% CI: 3.2–7.7] as an alternative first-line option in non-elderly patients (89,90). Topical agents, such as lidocaine 5% plasters and high-concentration capsaicin 8% patches, are recommended as second-line treatments and may be particularly appropriate as first-line options in elderly or frail patients to avoid systemic adverse effects (89,91). Opioids are reserved as third-line agents, with strong opioids recommended only after failure of other treatments and for the shortest possible duration (89,92).

For refractory CPSP, interventional approaches (e.g. radiofrequency ablation, pulsed radiofrequency, botulinum toxin injections, transcutaneous electrical nerve stimulation, and spinal cord stimulation) have been described, but limited data preclude conclusive recommendations (92,93). Multidisciplinary pain management programs incorporating cognitive-behavioral therapy or acceptance and commitment therapy are recommended (93). A substantial proportion of patients with chronic post-thoracotomy pain self-manage without medical supervision, 65% in one study, making structured follow-up with early CPSP identification and timely pain specialist referral essential (20,94).

Future directions and innovation priorities

Trial design, standardized outcomes, and cost-effectiveness

Heterogeneous outcome measures, anesthetic regimens, and comparator groups hamper cross-study comparisons; the ASA acknowledged its 2026 guidelines were constrained by low evidence strength from risk of bias and inconsistent reporting (3,9,70). Future trials should adopt standardized endpoints, validated patient-reported outcomes, and follow-up extending beyond 24–72 hours, because CPSP affects a substantial proportion of patients and acute pain severity is its strongest modifiable predictor (10,30,83). Health-economic data are similarly sparse: TOPIC2 found no difference in quality-adjusted life-years or costs between PVB and TEA, but comparable analyses are lacking for the single-shot, surgeon-performed techniques increasingly favored in minimally invasive surgery, whose reduced staffing and catheter requirements carry a plausible but untested cost advantage (57).

Developing innovations in pain control

One of the most practice-changing developments is data suggesting that a surgeon-delivered, single-shot block can now match TEA, long the gold standard for thoracotomy. A 2025 multicenter noninferiority trial found single-shot intercostal block noninferior to TEA (10). Separate randomized trials found surgeon-performed thoracoscopic PVB noninferior to anesthesiologist-delivered ultrasound-guided PVB and surgeon-performed ICNB superior to ESP block for opioid consumption (11,12). Collectively, these reduce the resources required to deliver adequate pain control, specifically reliance on regional pain specialists and limited hospital unit resources.

LB, an extended-release local anesthetic, shows promise in addressing the finite duration of single-shot blocks. A meta-analysis of nine RCTs (915 patients) found LB reduced opioid consumption and pain scores through 72 hours versus conventional local anesthetics (13). A trial using paravertebral LB administration found a 56% improved duration of analgesia, as compared with bupivacaine-dexamethasone (1,160 vs. 743 minutes; P<0.001), and resulted in earlier ambulation (58). A double-blind randomized trial of 146 VATS patients found LB PVB reduced three-month CPSP compared with bupivacaine (28.6% vs. 48.6%; P<0.001) (95), consistent with a propensity-matched cohort in which LB intercostal block was associated with lower three-month CPSP than ropivacaine (33.5% vs. 42.3%; aOR 0.68) (96). An RCT (NCT07134660) is currently underway to confirm these findings (97). Optimal delivery route and cost-effectiveness remain unresolved questions, and further studies are needed.

Pharmacogenomic-guided prescribing and machine learning-based pain prediction are converging as the next frontier in personalization of postoperative analgesia. CYP2D6 and OPRM1 polymorphisms affect opioid efficacy and adverse-effect risk profiles (98). Genotype-guided opioid selection shows promise for improving pain control with lower opioid requirements (14,99). For instance, a machine-learning model trained on 647 thoracic oncology patients predicted postoperative neuropathic pain with an area under the curve of 0.86, indicating good model discrimination, with surgical approach, surgeon expertise, chest-tube duration, acute pain, and C-reactive protein as leading predictors (100). Although these studies are intriguing, their validation remains in its infancy (14).

Strengths and limitations

This review synthesizes a broad evidence base encompassing multiple systematic reviews, major meta-analyses, landmark randomized trials, and current practice guidelines to provide a timely and clinically practical summary of pain management after thoracic surgery. As a review, it is subject to inherent limitations. The underlying literature is heterogeneous in design, patient populations, and outcome measures, limiting direct cross-trial comparisons. Evidence supporting several individual regional techniques derives from small or single-center trials with variable blinding and follow-up. This review did not conduct a formal systematic search and may not capture all relevant literature.

Conclusions

As minimally invasive techniques and opioid-sparing multimodal analgesia have become more common, the management of pain after thoracic surgery has undergone a fundamental transformation. In particular, the shift toward less invasive regional analgesia alternatives to TEA for minimally invasive thoracic surgery represents the most significant change in pain management strategies. Nonetheless, patient-centered approaches, incorporating preoperative risk stratification, shared decision-making, expectation management, and attention to special populations, are essential for optimizing outcomes, and the prevention of CPSP demands aggressive acute pain control, consideration of minimally invasive surgical approaches, and structured postoperative follow-up. As thoracic surgery continues to evolve toward less invasive approaches and accelerated recovery pathways, pain management strategies must continue to adapt. Pain management is not merely a component of complication prevention after thoracic surgery; it is a cornerstone upon which successful surgical outcomes are built.

Supplementary

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Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.