Version July 2025
INTRODUCTION —
Postmastectomy pain syndrome (PMPS) is a chronic neuropathic pain disorder that can occur following breast cancer-related operative procedures [1-3]. The optimal approaches to reducing the risk of and managing PMPS used in our center are presented here. The clinical manifestations and diagnosis of PMPS are reviewed separately. (See "Clinical manifestations and diagnosis of postmastectomy pain syndrome".)
RISK REDUCTION —
Because the development of postmastectomy pain syndrome (PMPS) is complex and the treatment options are limited, the focus of current research is on perioperative measures that can mitigate the modifiable risk factors for PMPS and thereby prevent patients from developing PMPS in the first place. The specific risk factors targeted include acute postoperative pain, operative axillary nerve injury, and preexisting psychosocial impairments.
Preventive analgesia — Severe acute postoperative pain results in increased incidence of persistent chronic postoperative pain. Management of postoperative pain has evolved from the sole administration of opioid medication in response to pain to the administration of a variety of medications and use of techniques to prevent acute and chronic pain.
Preventive analgesia involves using local or regional techniques (eg, wound infiltration, pectoral nerve, or paravertebral blocks) and systemic analgesics (eg, ibuprofen, ketorolac, gabapentin) before, during, and after surgery to manage pain from surgical incisions. (See "Approach to the management of acute pain in adults", section on 'Preventive analgesia for postoperative pain'.)
Although management of acute postoperative pain as it arises may also reduce the risk of chronic neuropathic pain, there are no supporting data from randomized trials designed for patients undergoing breast cancer operations.
Our approach — Our approach to preventive analgesia is consistent with evidence-based enhanced recovery after surgery (ERAS) protocols [4], and the specifics vary between mastectomy and breast-conserving surgery (lumpectomy):
●For patients undergoing mastectomy without reconstruction, we administer 1000 mg of acetaminophen and 600 mg of gabapentin orally in the preoperative period (300 mg the night before surgery, 300 mg the morning of surgery). Intraoperative interventions include an ultrasound-guided pectoral I and II nerve block administered by the anesthesiologist after induction of general anesthesia, intraoperative administration of a five-level pectoral intercostal fascial nerve block and a serratus nerve block administered by the surgeon after removal of the breast from the chest wall. Intravenous ketorolac may be administered if there is no contraindication. Oral gabapentin is continued around the clock for seven days after surgery.
●For patients undergoing mastectomy with immediate implant-based reconstruction, a similar protocol is used, with continuation of oral gabapentin around the clock for 14 days after surgery. Additionally, for patients under age 40 and/or those with an underlying history of anxiety/depression, intravenous ketamine may be administered at 0.25 mg/kg every 60 minutes. The last dose of ketamine should be at least one hour prior to end of surgery time to avoid dissociative side effects.
●For patients suffering from pre-existing vasomotor symptoms, venlafaxine XR 75 mg/day can be prescribed starting up to two weeks prior to surgery.
●Nerve blocks administered consist of a mixture of liposomal bupivacaine and 0.25% bupivacaine without epinephrine, total dose determined based on the patient's weight to maximum safe dose.
This ERAS protocol has resulted in the ability to discharge patients home the same day of mastectomy (with or without immediate implant-based reconstruction) in the vast majority of our patients.
●For patients undergoing lumpectomy, we infiltrate the surgical field with a mixture of lidocaine and 0.25% bupivacaine prior to any surgical incision, but generally omit the premedications and nerve blocks.
Supporting evidence — Most prospective studies identified a perioperative benefit (eg, fewer postoperative analgesic requirements) for administration of preventive analgesia for patients undergoing breast cancer procedures [5,6]. However, long-term pain control and reduced risk of PMPS with preventive analgesia have not been clearly established. This apparent dissociation between short- and long-term benefits is disconcerting given that acute pain is a known risk factor for chronic pain [7]. Variations in study design, including application and duration of administration of preventive analgesics and duration of observation, limit direct comparison between treatments.
Short-term benefit — The following medications or techniques have been associated with short-term pain relief in women undergoing breast cancer operations:
●Local anesthetic infiltration
•Wound infiltration with a local anesthetic can provide immediate postoperative pain control lasting for several hours [8]. A randomized trial of 46 patients undergoing a mastectomy or breast conservation surgery with an axillary dissection found that patients receiving ropivacaine wound infiltration (20 mL, 7.5 mg/mL) had less pain at rest at six hours compared with patients receiving placebo saline (12 versus 32 approximate Visual Analogue Scale [VAS] score, respectively) [5]. In addition, patients with wound infiltration also had less pain on mobilization of the ipsilateral arm at six hours postoperatively (25 versus 38 approximate VAS score, respectively). However, there was no difference in pain and comfort scores two months after the procedure.
•In a randomized trial that included 106 women undergoing a mastectomy for breast cancer, women treated with a local infiltration of bupivacaine 100 mg in 40 mL immediately prior to incision required less morphine 4 to 12 hours postoperatively compared with women receiving a placebo infiltration of 40 mL of saline (1.24 versus 2.35 mg, p = 0.02) [9]. In addition, women treated with bupivacaine had a lower postoperative pain intensity score at the 4th postoperative hour (mean VAS score 0.85 versus 1.69, p = 0.004) and 12th postoperative hour (mean VAS score 0.48 versus 0.96, p = 0.02). Women receiving bupivacaine also required less intraoperative fentanyl administration (0.38 versus 0.43 mg, p = 0.011).
●Regional blocks
•Local anesthetic agents – For regional nerve blocks, longer-acting local anesthetic agents, such as bupivacaine or ropivacaine, are commonly used. Liposomal bupivacaine has been shown to be a safe and effective pain reliever in the immediate postoperative period. In a retrospective study of 90 patients undergoing implant-based breast reconstruction, the use of a single dose of liposomal bupivacaine was found to be more effective than intravenous/oral narcotic pain medication as well as an indwelling bupivacaine pump in reducing postoperative pain and length of stay [10]. Adding liposomal bupivacaine to standard bupivacaine can help prolong the analgesic benefits of regional nerve blocks.
•Paravertebral nerve block – In a trial of 218 women undergoing breast cancer surgery, patients who received ultrasound-guided T2 to T5 multilevel paravertebral nerve blocks before surgery reported less pain at 48 hours after surgery and were less likely to develop neuropathic pain at 6 (12 versus 24 percent) and 12 months [11].
•Pectoral nerve block – First described in 2011, the pectoral nerve block is an easy and reliable superficial block that aims to block the pectoral nerves; the intercostobrachial nerves; intercostal nerves III, IV, V, and VI; and the long thoracic nerves [12]. Together, blockade of these nerves can provide complete analgesia during breast surgery. The pectoral nerve block has been shown to result in lower pain scores and lower perioperative opioid consumption in women with breast cancer undergoing modified radical mastectomy without reconstruction [13-16]. Pectoral nerve blocks can be administered by the anesthesiologist under ultrasound guidance (preincision) or by the surgeon (postmastectomy before reconstruction) in the operative field. A randomized single-blinded study in 2023 showed no significant difference in postoperative pain scores or duration of analgesia [17] in these two approaches.
•Serratus plane block – Used to treat pain from rib fractures, chest tubes, and even thoracotomies, serratus plane blocks have been shown to decrease postoperative pain scores and opioid consumption in patients undergoing mastectomy [18,19]. Local anesthesia is administered into the fascial plane, either superficial or deep to the serratus anterior muscle. In a randomized controlled trial comparing serratus plane block versus paravertebral block, the serratus block resulted in lower postoperative pain scores and appeared to be more effective than the paravertebral block for postoperative analgesia [20]. Given that it is technically an easier block to administer and can be done after induction of anesthesia with the patient asleep, this may be more readily utilized compared with paravertebral blocks.
•Erector spinae plane block – One of the newest techniques that has been described is the erector spinae plane block, which was first described in 2016 for the treatment of chronic thoracic neuropathic pain and postoperative pain in thoracic surgery [21]. This fascial plane block is performed by depositing local anesthetic in the fascial plane deep to the erector spinae muscle at the tip of the transverse process of the vertebra. Hence, the local anesthetic is distributed in the craniocaudal fascial plane to cover several dermatomes. Additionally, it diffuses anteriorly to the paravertebral and epidural spaces and laterally to the intercostal space at several levels. A meta-analysis of 11 randomized trials evaluating the efficacy of erector spinae plane blocks in breast cancer surgery found that patients under general anesthesia who received erector spinae plane blocks consistently had lower pain scores and decreased narcotic consumption than those who had general anesthesia alone [22]. Two additional trials comparing erector spinae plane block to paravertebral nerve block showed equal efficacy [22]. Compared with pectoral nerve block, however, erector spinae plane block appears to be less effective at decreasing postoperative pain scores and narcotic consumption [8,23,24].
●Systemic medications
•Gabapentin – Preoperative administration of oral gabapentin provides effective postoperative analgesia [25]. In a randomized trial of 50 patients undergoing a total mastectomy and axillary dissection, the mean postoperative morphine consumption was significantly lower for women receiving oral gabapentin 600 mg one hour before the procedure compared with women receiving an oral placebo (5.8±4.2 versus 11.0±3.4 mg, respectively) [6]. In addition, the median time to first administration of morphine was significantly longer for women receiving gabapentin (90 minutes [37.5 to 120, range] versus 0 minutes [0 to 90, range]), respectively. This trial did not assess longer-term pain control.
•Ketamine – Ketamine is well known to improve pain and reduce opioid use in the acute postoperative period. A 2021 meta-analysis of 13 randomized trials studied perioperative intravenous administration of ketamine either alone or in conjunction with regional nerve blocks (eg, paravertebral or pectoral nerve blocks) [26]. Compared with placebo, intravenous ketamine alone was effective in reducing wound pain intensity during the first six hours after surgery and in decreasing opioid consumption during the first 24 hours after surgery, without increasing adverse gastrointestinal or central nervous system events. Similarly, adding intravenous ketamine to regional nerve blocks also decreased wound pain and opioid consumption in the first six and 24 hours after surgery, respectively.
A 2024 randomized double-blind study in women undergoing mastectomy found that administration of ketamine (1 mg/kg) with local infiltration of 0.25% bupivacaine resulted in lower pain scores and opioid use compared with local infiltration of 0.25% bupivacaine alone [27].
KALPAS (Ketamine Analgesia for Long-lasting Pain After Surgery) is a phase III, multicenter, randomized, placebo-controlled, double-blinded trial funded by the National Institutes of Health to study the effectiveness of ketamine in reducing PMPS [28]. The study aims to compare continuous perioperative ketamine infusion versus single-dose ketamine in the recovery room versus placebo for reducing PMPS. Participants will be followed for one year after surgery. The primary outcome is pain at the surgical site three months after the index surgery [28].
•NSAIDs – According to a Cochrane review, there is low-certainty evidence that nonsteroidal anti-inflammatory drug (NSAIDs) may reduce postoperative pain, nausea and vomiting, and postoperative opioid use after breast surgery [29].
Surgeons are often hesitant to use or prescribe NSAIDs after breast surgery due to concerns over bleeding. In a subset analysis of a prospective cohort study of patients undergoing breast surgery published in 2019, 115 patients who received ketorolac and 99 patients who did not were analyzed for bleeding complications [30]. No difference was found (2 percent ketorolac versus 2.6 percent no ketorolac). In a 2021 meta-analysis, the authors found that the perioperative use of NSAIDs did not increase the risk of hematoma, return to the operating room for bleeding, and blood transfusions compared with the non-NSAID groups [31]. These studies included 12 types of NSAIDs (the most common being ketorolac, diclofenac, and ibuprofen) and spanned over a wide range of procedures (including breast, abdomen, and plastics). Thus, NSAIDs are unlikely to be the cause of postoperative bleeding complications, and surgeons should be comfortable using NSAIDs perioperatively to decrease postoperative pain and opioid consumption.
Long-term benefit — The following medications or techniques have been studied for their effect on long-term postoperative pain relief in women undergoing breast cancer operations:
●Local anesthetic administration – While local wound infiltration has been shown to reduce immediate postoperative pain, two double-blinded randomized trials showed that wound infiltration with local anesthesia, whether through repeat injections or continuous infusion with a catheter, was ineffective in reducing the intensity of chronic pain [32,33].
●Regional nerve blocks – In a meta-analysis of 16 studies involving 102 patients, there was moderate- to high-level evidence that pectoral nerve block reduces PMPS compared with no regional anesthesia [34]. A randomized trial found that ultrasound-guided T2 to T5 multilevel paravertebral nerve blocks before breast cancer surgery reduced the incidence of neuropathic pain at 6 (12 versus 24 percent) and 12 months [11]. A systematic review of 10 randomized controlled trials on the efficacy of perioperative blocks in the prevention of PMPS found that PECS II blocks and thoracic paravertebral blocks were both effective at reducing pain at six months postoperation [35].
●Systemic medications
•Venlafaxine – In a prospective study of 100 patients undergoing a partial or total mastectomy with an axillary dissection, significantly fewer patients treated with venlafaxine 75 mg for two weeks beginning the evening before the procedure had chest wall pain at six months compared with patients treated with a placebo (19 versus 55 percent) [36]. Fewer patients treated with venlafaxine also had arm pain (17 versus 45 percent) and axillary pain (19 versus 51 percent) at six months. However, there was no difference in the use of opioids for immediate postoperative pain control.
In a double-blinded randomized trial comparing extended-release venlafaxine 37.5 mg/day, gabapentin 300 mg/day, and placebo for 10 days, starting the night before surgery, both gabapentin and venlafaxine decreased postoperative pain and analgesic requirements immediately after surgery, but only venlafaxine significantly reduced the incidence and intensity of chronic pain at six months postoperatively [37].
•Gabapentin/pregabalin – In a systemic review of PMPS prevention modalities [25], eight randomized trials testing the efficacy of gabapentin and four randomized trials testing the efficacy of pregabalin in reducing PMPS showed that administered perioperatively, these medications can decrease acute postoperative pain and reduce opioid consumption in the initial postoperative period, but neither drug appears to reduce the development of chronic postoperative pain [37-42].
•Ketamine – A 2021 meta-analysis of 13 randomized trials reported that perioperative use of ketamine was associated with improved postoperative depression symptoms and decreased incidence of PMPS [26].
Preservation of axillary nerves — The axilla contains sensory (eg, intercostal brachial trunk, peripheral intercostal branches) and motor (eg, long thoracic, thoracodorsal, pectoral) nerves (figure 1). The anatomy of the axilla and the technique for performing an axillary lymph node dissection (ALND) and preserving the motor and sensory nerves are described separately. (See "Technique of axillary lymph node dissection".)
ALND is a well-recognized intraoperative risk factor for PMPS [43,44]. Many patients who undergo an ALND experience some degree of postoperative pain, hypersensitivity, and/or hyposensitivity in the axilla and medial aspect of the upper arm. This alteration in sensitivity is the result of transecting or traumatizing the sensory intercostal brachial nerves (ICBN) [45]. Findings from randomized trials, prospective studies, and retrospective reviews reveal inconsistent results for preservation of the intercostal brachial nerves. While some studies identified that preservation of the nerve is associated with decreased sensory deficits and/or less discomfort in the upper arm and axilla [46], other studies have found minimal effect on chronic sensory deficits and/or pain [16,47].
A meta-analysis published in 2023 pooled data from 11 studies that evaluated the efficacy of preservation of the ICBN versus dissection of the ICBN [48]. These studies favored the preservation of ICBN in terms of anesthesia and hypoesthesia (odds ratio [OR] 0.50, 95% CI 0.31-0.82 and OR 0.33, 95% CI 0.16-0.68, respectively). Conversely, these studies favored dissection of the ICBN in terms of hyperesthesia (OR 4.34, 95% CI 1.43-13.15). Importantly, no significant difference was detected between ICBN preservation and dissection in terms of pain (OR 0.68, 95% CI 0.28-1.61) or analgesia (OR 1.46, 95% CI 0.05-45.69).
Sentinel lymph node biopsy (SLNB) is associated with a lower incidence of PMPS compared with ALND [49,50]. The adoption of SLNB as the current standard care for assessing axillary metastatic disease is a major contributor to reducing the incidence of PMPS.
Psychosocial intervention — Multiple studies have found that active preoperative psychological counseling and social support can reduce the severity of PMPS [51]. Acute and chronic pain may be caused or exacerbated by psychosocial risk factors such as anxiety, depression, and interpersonal conflicts [52,53]. Psychosocial factors associated with postoperative persistent pain include psychological strength and resilience, social factors, emotional factors, anxiety, and sleep-related factors [51]. Approximately one-half of patients diagnosed with cancer exhibit some, if not all, of these emotional difficulties [54]. (See "Patients with cancer: Overview of the clinical features and diagnosis of psychiatric disorders".)
The term "somatization" refers to a psychosocial impairment syndrome consisting of physical symptoms that cannot be explained by a known medical disease. Preoccupation with symptoms, such as chronic pain following breast cancer procedures, may indicate somatization. It is plausible that patients with somatization syndrome may experience PMPS in the absence of detectable clinical abnormalities. (See "Somatic symptom disorder: Epidemiology, clinical features, and course of illness" and "Somatic symptom disorder: Assessment and diagnosis".)
Psychosocial and pharmacologic interventions can reduce pain and psychosocial distress, and the best preventive intervention may be one that combines pharmacologic and psychosocial treatments [52]. Psychosocial interventions should start once the diagnosis of psychosocial impairment is made and be continued at least until the time of surgery, when pharmacologic interventions should be initiated to reduce acute postoperative pain to the greatest extent possible. (See "Management of psychiatric disorders in patients with cancer".)
Reducing preoperative psychosocial distress, relieving acute postoperative pain, and enhancing postoperative recovery provide the greatest potential to prevent chronic pain after breast cancer surgery.
MANAGEMENT —
Since neuropathic pain, such as postmastectomy pain syndrome (PMPS), manifests months after the axillary operation, an assessment for chronic pain should be considered as a component of long-term follow-up of breast cancer patients. Management of PMPS should be initiated upon diagnosis, as with other chronic neuropathic pain disorders.
Our approach
●For patients amenable to taking medications, we prescribe gabapentin if the symptom is predominantly neuropathic pain or venlafaxine if the pain is accompanied by other vasomotor symptoms such as hot flashes. We start gabapentin at 900 mg/day and titrate up to 1800 mg/day in 6 to 12 weeks if necessary. (See 'Pharmacotherapy' below.)
●For patients who are reluctant to accept medical therapy at the time PMPS is diagnosed, we offer them both acupuncture and hypnotherapy, or continued observation and assessment for worsening symptoms if they decline. (See 'Integrative approaches' below.)
●For patients with a suspected traumatic neuroma that responds to local anesthetic infiltration, we performed diagnostic tests and consider excision of the neuroma. (See 'Neuroma excision' below.)
●For patients with chronic pain associated with an axillary scar, we refer them for possible scar release with or without autologous fat grafting. (See 'Axillary scar release' below.)
Pharmacotherapy — Pharmacologic therapy remains the initial treatment for PMPS, although patients with neuropathic pain may respond poorly to commonly used analgesics, such as acetaminophen, nonsteroidal anti-inflammatory drugs, and opioid analgesics. (See "Patients with cancer: Overview of the clinical features and diagnosis of psychiatric disorders" and "Overview of pharmacologic management of chronic pain in adults".)
Antiepileptic medications, such as gabapentin, which inhibit neurotransmitter release, have proven efficacy in several neuropathic pain conditions and are our preferred initial approach [42,51,55]. Multiple studies have shown the utility of gabapentin in PMPS, with >50 percent pain relief at four weeks, and sustained pain relief up to a three-month follow-up period [56]. Other antiepileptic medications, such as carbamazepine, have been used with moderate efficacy. (See "Overview of pharmacologic management of chronic pain in adults".)
Serotonin-noradrenaline reuptake inhibitors, such as venlafaxine and duloxetine, can enhance pain signal inhibition and provide effective pain relief for patients with neuropathic pain (table 1) [42,56]. In addition, tricyclic antidepressants such as amitriptyline [57], imipramine, nortriptyline, and doxepin are a pharmacologic mainstay for chronic pain conditions with or without depression [51]. These drugs primarily work by inhibiting monoamine receptors at the presynaptic terminal. Inhibition of noradrenaline has been implicated as a major driver of pain relief in these patient populations [56]. However, adverse side effects often limit the tolerability of these medications (table 2). Common side effects include anticholinergic symptoms, sex drive changes, and fluctuations in weight, all of which may prove a barrier to patients wishing to manage their PMPS symptoms [56]. (See "Overview of pharmacologic management of chronic pain in adults".)
Surgical interventions — The following surgical interventions have been shown to be effective in treating PMPS in appropriately selected patients:
Neuroma excision — Somatic pain from entrapment or irritation of intercostal nerves may be a cause of chronic pain in some PMPS patients [58]. Patients with a painful neuroma that develops at the end of a transected nerve and causes painful nerve impulses along the distribution of the involved nerve may benefit from surgical excision of the neuroma [59]. (See "Peripheral nerve tumors", section on 'Neuroma'.)
Neuromas are typically diagnosed clinically. Palpation of the chest wall may trigger painful radiating impulses and help identify the location of the neuroma. Once localized, a diagnostic test is performed by infiltrating the site with 1% lidocaine. If pain relief is achieved with local infiltration, excision of the neuroma may provide permanent relief.
Neurectomy aims to interrupt the abnormal discharge from the distal pain receptor to the central nervous system by proximally transecting the affected nerve [42].
During the operative procedure, the neuromas are most commonly identified at the site of transection of the intercostal brachial nerves along the lateral chest wall. Under tension, the nerves are dissected from the scar, the neuromas resected, and the cut proximal ends allowed to retract deep into the intercostal muscles where the risk of recurrence is lower.
Two case series that included a total of 14 patients, followed for an average of 24 months after intervention, demonstrated 80 percent partial or complete relief of their pain [60,61]. A study in 2022 described the result of neuroma resection in seven patients (each with one to six neuromas resected) [59]. The authors found 86 percent were "pain-free or considerably improved" after six months. In all studies, the intercostal nerve(s) causing pain was identified and confirmed using a diagnostic nerve block, and then neuroma excision was performed.
Although positive results have been described with this type of procedure, it is important to note that neuropathic pain can recur, in some cases, months after the surgery. Therefore, long-term follow-up of these patients is required to evaluate the true effectiveness of this procedure [42].
Axillary scar release — Anecdotally, if a scar in the axilla is the etiology of pain, an axillary scar release can be performed with or without fat grafting. (See "Z-plasty", section on 'Indications'.)
Autologous fat grafting — Autologous fat grafting has been found to be beneficial in select cases of PMPS [58].The mechanism is not well elucidated, but several potential benefits of fat grafting are hypothesized, including (1) improved vascularization; (2) creation of a cushion around a transected nerve stump, reducing nerve compression and stimulation; (3) secretion of anti-inflammatory molecules that improve tissue differentiation and scar softness; and (4) nerve entrapment liberation. The effectiveness of fat grafting in PMPS is based on the principles of regenerative medicine. Specifically, stromal and vascular component of fat tissue contains crucial mesenchymal stem cells which play a significant role in sustaining the viability of grafted fat cells by secreting various cytokines and growth factors, leading to neoangiogenesis, immunomodulation, and anti-inflammatory effects [35].
In several comparative studies [2,62,63] and small trials [64,65], fat grafting was associated with reduced postoperative pain and/or analgesic medication use after both mastectomy or lumpectomy. In a meta-analysis published in 2023, the authors pooled data from both randomized controlled trials and observations studies [66]. Overall, a total of 266 patients received autologous fat grafting and 164 were in the control group. The mean percentage reduction in Visual Analogue Scale score was 19.8 (95% CI 10.82-28.82). Additionally, fat transfer was associated with improved breast softness, cosmesis, and psychosocial well-being. These results suggest that autologous fat grafting is a promising treatment for reducing pain caused by PMPS. More large high-quality trials are needed to evaluate the potential efficacy of this procedure.
Interventional procedures — Interventional procedures such as regional nerve or fascial plane blocks can be used to treat PMPS as well, but usually as a last resort in patients who have failed medical therapy and are not candidates for surgical intervention. Ideally, the problematic nerves are identified by a thorough history and physical examination, and after real-time visualization under ultrasound, they are directly targeted for perineural injections with local anesthetics, steroids, or neurolytic substances such as alcohol. If the pain is not consistent with a specific nerve or others appear to involve multiple nerves, various regional or interfascial plane blocks can be used as an option for pain relief [51]. (See "Thoracic nerve block techniques".)
Injury to the intercostobrachial nerve, either through direct injury, traction, or postsurgical inflammation, is thought to be a possible contributing factor to postmastectomy pain. In a small case series, an intercostobrachial nerve block was shown to relieve PMPS [67].
Another emerging potential target for an interventional procedure for PMPS is the serratus plane block. The serratus plane block is an ultrasound-guided nerve block that is able to anesthetize the hemithorax. Both a superficial serratus plane block [68] and the deep serratus anterior plane block [69] have been shown to alleviate chest wall pain related to PMPS with short-term follow-up, and more longitudinal studies are needed.
Additionally, given the increasing popularity of the erector spinae plane block (ESPB) to help with acute postoperative analgesia and chronic pain conditions, there is now some evidence that ESPB may be an effective tool to help treat women with severe PMPS [70].
Pulsed radiofrequency (PRF) on the thoracic dorsal root ganglion of the intercostobrachial nerves has also been studied. In a randomized trial, 64 patients randomly received either PRF on the thoracic dorsal root ganglion of the intercostobrachial nerves or PRF on the thoracic paravertebral nerves [71]. At three and six months, the group that received PRF on the thoracic dorsal root ganglion had lower rates of postmastectomy pain. In a randomized, double-blinded clinical trial published in 2024, the authors evaluated the efficacy of ultrasound-guided stellate ganglion destruction with alcohol versus thermal ablation in women suffering from PMPS and found that alcohol ablation was more effective at decreasing pain scores [72]. Given the inherent risks and technical difficulty of targeting thoracic dorsal root ganglions or stellate ganglions, these options should only be considered as second- or third-line therapy in those patients who have failed to respond to lesser invasive treatments.
Physical therapy — Rehabilitation protocols for PMPS are highly variable and should be individualized [73]. Four core techniques are hypothesized to be beneficial in the functional rehabilitation of PMPS: restoring joint mobility and preventing tendon shortening with passive mobilization techniques, reducing pain with myofascial release and sustained trigger point compression, addressing tight muscles with manual stretching and transverse strain, and strengthening shoulder girdle muscles with active and/or active-assisted mobilization [74]. An earlier systematic review of these core modalities demonstrated that a multimodal approach, involving stretching and active exercises, was useful for the treatment of breast cancer pain [75]. A systematic review of six randomized controlled trials assessing the impact of physical therapy on PMPS demonstrated inconsistent results, with some studies showing little benefit while others showed significant reduction in PMPS symptoms [35].
A trial of 392 women who were at high risk of developing arm morbidity after breast cancer surgery found that, compared with usual care, a physiotherapist-led exercise program improved upper limb function, reduced pain, and reduced upper arm disability symptoms at 12 months without increasing complications, lymphedema, or adverse events [76].
A 2022 meta-analysis that included 18 trials confirmed that exercise is beneficial for improving the quality of life and pain severity in women with PMPS [77]. Physical activity not only reduces the intensity of pain, depression, and anxiety symptoms in women affected by PMPS, but also results in reductions in biomarkers of inflammation including cortisol and ACTH [78]. Given that it is a relatively low cost and safe intervention, physical exercise should be regarded as a vital part of quality of life and pain management for women with PMPS [8].
Integrative approaches — Approximately 25 to 60 percent of breast cancer patients have used at least one form of complementary and alternative medicine (CAM) to treat cancer pain and the side effects of chemotherapy and radiation and to improve quality of life [79].
There is growing evidence that integrative approaches during and after breast cancer treatment can help improve quality of life for breast cancer patients [79]. Integrative oncology aims to combine the delivery of evidence-based complementary therapies with conventional treatments for breast cancer. Complementary therapies encompass a broad range of mind and body practices along with lifestyle interventions, including guided imagery, acupuncture, hypnosis (guided meditation), and biofeedback. They have also been used in managing chronic neuropathic pain. (See "Overview of the clinical uses of acupuncture" and "Overview of complementary, alternative, and integrative medicine practices in oncology care, and potential risks and harm" and "Approach to the management of chronic non-cancer pain in adults", section on 'Complementary and integrative health therapies'.)
●Hypnosis – A systematic review of 13 randomized trials involving breast cancer patients found that hypnosis may improve pain from a variety of sources, including surgery and radiotherapy [80]. In a randomized clinical trial published in 2022, 40 patients randomized to hypnosis versus control were assessed at five points before and after surgery [81]. The results showed that after surgery, the hypnosis group had a statistically significant reduction in pain intensity, improved sleep, and life enjoyment compared with the control group. Another study evaluated the impact of perioperative hypnosedation on PMPS [82]. With a mean follow-up of four years, the authors found a statistically lower incidence of PMPS in the patients who underwent perioperative hypnosis. It is unclear how patient selection may play a role in studies involving hypnosis as highly suggestible patients report greater benefits from hypnosis. Nonetheless, hypnosis may be considered as a complementary therapy for PMPS and improving the quality of life in these patients.
●Acupuncture – Acupuncture, which is a modality derived from traditional Chinese medicine, is believed to increase the production of endogenous analgesic neurotransmitters and modulate the perception of pain [83]. Acupuncture is an effective treatment strategy to manage some of the symptoms associated with breast cancer surgery, including pain, numbness, limited range of motion, and lymphedema [8,84]. Studies have demonstrated that acupuncture is a safe alternative with minimal complications or side effects .
•In a large multicenter randomized clinical trial conducted in China from 2016 to 2018, 576 patients scheduled to undergo mastectomy were randomized to sham control versus single acupoint versus combined acupoints [85]. Transcutaneous electrical acupoint stimulation (TEAS) was applied for 30 minutes before induction of anesthesia. The sham-operated control group received electrode attachment but without stimulation. Anesthesiologists and surgeons were blinded to the interventions. At six months, PMPS was reported in 34.6 percent sham-control group versus 22.1 percent in the combined acupoints group (odds ratio 0.68, 95% CI 0.52-0.89). This study supports the potential role of TEAS in reducing PMPS.
●Music therapy – Music therapy is the use of music as a therapeutic intervention and has been evaluated in a number of controlled studies for pain in cancer patients. While more research is needed, music therapy has been shown to reduce pain specifically among women experiencing pain from breast surgery [8,86].
SUMMARY AND RECOMMENDATIONS
●Definition – Postmastectomy pain syndrome (PMPS) is a chronic neuropathic pain disorder that can occur following breast cancer-related operative procedures.
●Risk reduction – The focus of current research is on perioperative measures that can mitigate the modifiable risk factors for PMPS and thereby prevent patients from developing PMPS in the first place.
•Preventive analgesia – Preventive analgesia may minimize immediate postoperative pain but may not eliminate the development of PMPS.
-We premedicate mastectomy patients with oral acetaminophen (1000 mg) and gabapentin (600 mg) and perform a pectoral I and II nerve block, five-level intercostal fascial nerve block, and serratus plane block after removal of the breast. Intraoperative ketorolac may be administered in the absence of any contraindications. For patients under age 40 and/or those with underlying anxiety/depression, intraoperative ketamine may also be administered.
-For lumpectomy patients, we simply infiltrate the skin with a mixture of lidocaine and bupivacaine before surgical incision and generously within the subcutaneous tissues, breast parenchyma, and pectoral fascia to maximum safe dose. (See 'Preventive analgesia' above.)
•Preserving axillary nerves – Transecting or traumatizing the intercostal brachial nerve during an axillary lymph node dissection can result in altered sensations in the medial upper arm. To minimize the risk of sensory deficits, we suggest preserving the intercostal brachial nerve during the axillary dissection (Grade 2C), unless gross metastatic disease is present. (See 'Preservation of axillary nerves' above.)
•Psychosocial intervention – Acute and chronic pain may be caused or exacerbated by psychosocial risk factors, such as anxiety, depression, and interpersonal conflicts. In such patients, psychosocial interventions (including pharmacologic and psychosocial treatments) should start once the diagnosis of psychosocial impairment is made and be continued at least until the time of surgery, when pharmacologic interventions should be initiated to reduce acute postoperative pain to the greatest extent possible. (See 'Psychosocial intervention' above and "Management of psychiatric disorders in patients with cancer".)
●Management – Once PMPS is established, treatment options include the following.
•Pharmacotherapy – For patients with predominantly neuropathic pain who desire medical therapy, we suggest gabapentin as the first-line therapy (Grade 2C). We start at 900 mg/day and titrate up to 1800 mg/day as necessary in 6 to 12 weeks. For patients with both neuropathic pain and vasomotor symptoms such as hot flashes, we suggest venlafaxine XR 75 mg/day as the first-line therapy (Grade 2C). (See 'Pharmacotherapy' above and "Overview of pharmacologic management of chronic pain in adults", section on 'Pharmacologic therapy for neuropathic or nociplastic pain'.)
•Surgical interventions – For patients with pain from a traumatic neuroma, we initially infiltrate the site with a local anesthetic (eg, 1% lidocaine). For patients who experience pain relief following this procedure, we then perform an excision of the neuroma. Patients with a painful axillary scar may benefit from scar release and/or autologous fat grafting. (See 'Surgical interventions' above.)
•Integrative care – For patients who prefer complementary and alternative medicine therapies, we prescribe acupuncture, hypnosis, or music therapy (see 'Integrative approaches' above). We emphasize these may be used in conjunction with pharmacotherapy, not just as an alternative.
