Post-mastectomy pain syndrome: A timely review of its predisposing factors and current approaches to treatment

Background: Post mastectomy pain syndrome (PMPS) is a type of neurogenic pain that persists for a long period after surgery for breast cancer. The present study aims to find out the prevalence of this syndrome and investigate its contributing risk factors. Methods: A descriptive cross-sectional study was carried out among 167womenoperated for breast cancer. Patients with either modified radical mastectomy(MRM) or breast conserving therapy (BTC) were enrolled in the study. Detailed medical history with special emphasis on the presence of pain and its characteristics, duration and location were performed to all patients. Full clinical examination was also performed to exclude other possible causes of pain. All expected risk factors were traced and correlated to the patient condition. Reviewing of medical records of all patients was performed to find out operation details, tumor stage and way of management of axillary lymph nodes. Results: Eighty seven (52%) out of the 167 studied women reported PMPS. The mean age was 54 ± 18.3 years. The incidence of PMPS was more evident in younger age group and in women with advanced tumor stage. There is significant decrease in the incidence of PMPS in patients underwent sentinel lymph node biopsy (SLNB) (Chi-2=4.10 & P-value=0.043).Moderate and severe pain were most commonly reported among patients underwent MRM while mild pain was most commonly reported among patients underwent BCT (Chi-2=17.51 & P-value=0.001). Intercostobrachial neuralgia was the most commonly reported type of pain among patients underwent MRM and patients underwent BCT (Chi-2=10.47 & P-value=0.015). Pain occurred more frequently at the shoulder, axilla and arm complex (48.3%). Conclusion: PMPS is an evident problem. Cancer surgeons should clearly identify patients who are at risk aiming to minimize or even eliminate the chance of developing this syndrome.

Post Mastectomy Pain Syndrome (PMPS) is a common postoperative condition for breast cancer, but has been ignored. The aim of this study was to investigate the prevalence of PMPS and the risk factors in women submitted to surgical treatment for breast cancer. The study included 532 postoperative breast cancer patients in a hospital for five consecutive years period, of whom 473 were considered eligible and included in the study. A total of 420 people completed a questionnaire survey, which revealed that 152 (36.2%) had ever suffered from PMPS and 18 (11.8%) sought treatment. Of the patients with PMPS, 34 (22.4%) had a history of chronic pain. Patients with PMPS were younger than patients without PMPS (50.5 ± 10.4 vs 53.5 ± 11.1). Univariate analysis showed that age, history of chronic pain, tumor staging, number of lymphadenectomy were significantly different between the two groups. Multivariate analysis shows that age and history of chronic pain were independent risk factors. The incidence of PMPS in postoperative breast cancer patients can reach 36.2%, and age as well as previous history of pain are independent risk factors for PMPS. The combination of prevention and treatment may be an effective way to reduce PMPS.

Post-mastectomy pain syndrome (PMPS) is a syndrome broadly applied to the development of chronic pain after surgical breast intervention (i.e., lumpectomy and mastectomy). The incidence of PMPS is likely underreported, and this has contributed to a paucity of high-level evidence related to the treatment of the aforementioned condition. A drive to reduce the burden of opioid use has led to pain management physicians trialing a variety of strategies to help patients manage PMPS. This review discusses the latest evidence behind treatment options for PMPS, exploring medications as well as interventional techniques (e.g., nerve blocks, radiofrequency ablation, neuromodulation, and intrathecal drug delivery systems). Recent advances in neuromodulation technology are of particular interest heredue to the well-localized nature of PMPS-related pain and the specificity with which modern neuromodulation techniques can generate an effect. Finally, the review proposes a framework with which to approach the care of patients with PMPS, with a specific emphasis on the early consideration of neuromodulation techniques along with functional and physical therapy to reduce patient medication burden and improve overall quality of life.

Objective: To investigate the effects of multi-day low dose ketamine infusion for postmastectomy pain syndrome (PMPS) after breast cancer surgery. Methods: This study was a prospective randomized controlled trial. From June 2015 to May 2016 in Affiliated Yiwu Hospital of Wenzhou Medical University, 66 patients with breast cancer surgery were randomly divided into control group (group C) and ketamine group (group K). Patients in group K were infused with 0.5 mg/kg of ketamine mixed in 250 ml of 0.9% normal saline in 1 h daily for 7 days. Patients in group C were infused the same dose of 0.9% normal saline. Anesthesia induction in both groups were given intravenous midazolam, sufentanil, propofol, vecuronium and intermittent positive pressure ventilation after tracheal intubation, anesthesia was maintained with propofol and remifentanil. After awakening, all patients were monitored in postanesthesia care unit (PACU) and given patient-controlled intravenous analgesia(PCIA). Pain scores were assessed using visual analogue scales (VAS) during PACU, 4 h, 24 h and 2-5 d after surgery, simultaneously analgesic requirement were recorded. Patients were evaluated Hospital Anxiety and Depression Scale (HADS) 5 d after surgery . The patients were followed up for 6 months. At 3 m, 6 m after surgery, the incidence of PMPS, the level of pain, pain site and HADS scale were assessed. Results: The VAS score uring PACU, 4 h, 24 h and 2-5 d after surgery in group K( (2.5±0.8), (2.4±0.5), (2.4±0.5), (2.0±0.4), (1.5±0.5), (1.0±0.4), 1(1), respectively) was lower than those in group C ((2.9±1.0), (2.9±0.6), (2.6±0.5), (2.3±0.5), (1.8±0.6), (1.5±0.5), 1(0), respectively). There was statistically difference between the two groups (all P<0.05). The consumption of analgesics required at each time postoperation in group K were also lower than that of group C(all P<0.05). Followed up for 6 months, 2 lost in group C, 1 lost in group K. The incidence of PMPS in group K at 3 months and 6 months after surgery was significantly lower(25% and 22%) than that in group C(52% and 45%)(χ(2)=4.729, 3.842, all P<0.05). There were no significant difference in pain level and site between two groups of PMPS patients (all P>0.05). There were no significant difference of HADS scale preoperative and 5 d after surgery between two groups (all P>0.05); and HADS scale in group K at 3 m and 6 m after surgery was significantly lower than that in group C(all P<0.05). Conclusion: Perioperative continuous multi-day low dose ketamine infusion can effectively reduce the incidence of PMPS after breast cancer surgery.

Literature on Post mastectomy pain in the Indian population is scarce. Most literature is from the West. The current study aimed to identify the incidence of post-mastectomy pain syndrome (PMPS), pain severity, and its impact on quality of life in Indian patients. Prospective observational study of 120 women undergoing mastectomy between March and December 2017, followed until 6 months after surgery. The Brief Pain Inventory (BPI) questionnaire and the quality of life questionnaire (QLQ) by the European Organization for Research and Treatment of Cancer (EORTC) and known as (EORTC-QLQ 30) were used to identify the impact on function and quality of life. A 35.8% PMPS incidence was identified at 6 months after mastectomy. Pain was located in the anterior chest wall (41.8%), axilla (32.6%), and medial upper arm (25.6%). Most (48.8%) patients described it as dull aching and of mild intensity (55.8%). No significant association of age, BMI, surgery, Intercostobrachial nerve (ICBN) dissection, postoperative pain severity, pain history {dysmenorrhea, headache}, and postoperative radiotherapy with PMPS was found. Pain interfered with daily activities and quality of life in those with PMPS, as deduced from BPI and EORTC-QLQ. PMPS is very much a problem affecting the quality of life in our set of patients. Most women tried to cope and accept the pain as part of the treatment process. This shows the need for creating awareness about PMPS among healthcare providers and patients alike. Early identification and treatment of post mastectomy pain should be an essential aspect of patient care.

Perioperative use of ketamine has been discussed widely in many kinds of surgery. The aim of our study was to evaluate the short-term and long-term benefits and safety of ketamine after breast surgery. We performed a quantitative systematic review. We included randomized controlled trials that compared intravenous administration of ketamine to a placebo control group, or compared bupivacaine in combination with ketamine to bupivacaine alone in thoracic paravertebral blocks or pectoral blocks among patients undergoing breast surgery. The primary outcome was postoperative pain intensity. Secondary outcomes included cumulative opioid consumption during the 0- to 24-hour postoperative period, the effect on postmastectomy pain syndrome, the effect on postoperative depression, and the adverse events associated with the use of ketamine. Thirteen randomized controlled trials with 1,182 patients were included for analysis. Compared with placebo, intravenous ketamine was effective in reducing wound pain intensity during the first 6hours after surgery (weighted mean difference [WMD]-0.83; 95% confidence interval [CI]-1.65, -0.01; P=0.048) and during the first 24hours after surgery (WMD-0.65; 95% CI -0.95, -0.35; P<0.001), and in decreasing opioid consumption (WMD-4.14; 95% CI-8.00, -0.29; P=0.035) during the first 24hours after surgery, without increasing the risks for gastrointestinal and central nervous system adverse events. Adding ketamine to bupivacaine in thoracic paravertebral blocks was also effective in reducing postoperative wound pain during the first 6hours after surgery (WMD-0.59; 95% CI, -1.06, -0.12; P=0.014) and during the first 24hours after surgery (WMD-0.90; 95% CI -1.27, -0.53; P<0.001), and in decreasing opioid consumption (WMD-4.59; 95% CI-5.76, -3.42; P<0.001) during the first 24hours after surgery. Perioperative use of ketamine was associated with improved postoperative depression symptoms (standardized mean difference-0.80; 95% CI-1.34, -0.27; P=0.003) and less incidence of postmastectomy pain syndrome (relative risk 0.79; 95% CI 0.63, 0.99; P=0.043). Ketamine is an effective and safe multimodal analgesic in patients undergoing breast surgery, administered both intravenously and when added to bupivacaine in paravertebral blocks. In addition, ketamine showed a long-term benefit for preventing postoperative depression and postmastectomy pain syndrome.

Postmastectomy pain syndrome (PMPS) affects nearly half of patients who undergo mastectomy to treat breast cancer. As the survival rate of breast cancer increases with advancements in treatment, the incidence of PMPS is also increasing. Patients with PMPS can experience unrelenting, chronic pain refractory to traditional management with oral pharmacotherapy in conjunction with nonpharmacologic treatment (physical therapy, transcutaneous electrical nerve stimulation (TENS)). Neuromodulation is an emerging treatment modality for numerous chronic pain conditions. This case report highlights the tremendous success of spinal cord stimulator placement for a patient with PMPS.

Postmastectomy pain syndrome (PMPS) has been reported following procedures involving complete lymph node dissection (CLND). Since the triggering event is probably related to nerve injury, sentinel lymph node dissection (SLND) should decrease the incidence of PMPS. The purpose of this report is to determine the impact of SLND on the number of patients referred to the pain clinic for PMPS treatment. The records of all breast surgical patients with a diagnosis of PMPS referred to the Moffitt Cancer Center pain clinic were reviewed. The criterion for diagnosis of PMPS was a history of postoperative pain in the upper anterior chest wall, upper extremity, axilla, and/or shoulder in the absence of recurrent disease. A total of 55 patients with a diagnosis of PMPS were seen in the pain clinic since 1991. Treatments included local anesthetics/corticosteroid injection, stellate ganglion block, and tricyclic antidepressants. A decrease from 15 patients in 1991 to 3 in 1998 was observed. All but one of the 55 patients with PMPS had CLND, and none referred to the pain clinic had undergone SLND. PMPS is a complication of CLND. The increased use of SLND in our center has reduced the number of referrals to the pain clinic for treatment of PMPS. This benefit of SLND reduces suffering in the postoperative breast patient.

Background: Post-mastectomy pain syndrome (PMPS) affects up to 60% of women undergoing mastectomy. Standard perioperative multimodal analgesia remains only moderately effective in preventing PMPS, and many patients continue to rely on opioids for their chronic pain. In the context of the opioid overdose crisis, alternative interventions are urgently needed. Ketamine targets risks factors for PMPS including acute pain and negative mood, making it an ideal candidate for the prevention of PMPS. Trial Design: This is a multisite, three-arm, double-blind, RCT to test the effectiveness of ketamine in reducing PMPS in women undergoing mastectomy for oncologic indication. Arm 1 consists of continuous perioperative ketamine infusion that begins during surgery and continues for 2 hours in the post-anesthesia care unit (PACU). Arm 2 consists of a single-dose of ketamine in the PACU given over 50-60 minutes. Arm 3 consists of placebo. Standard surgical and postsurgical care remain unchanged across all arms. Eligibility Criteria: Inclusion criteria are: women ≥18 years of age undergoing total mastectomy for oncologic indication +/- lymph node dissection and +/- immediate or delayed reconstruction with no distant metastases. Exclusion criteria include: (1) history of cognitive impairment (2) past ketamine or phencyclidine misuse or abuse, (3) schizophrenia or history of psychosis, (4) history of post-traumatic stress disorder, (5) known sensitivity or allergy to ketamine, (6) liver or renal sufficiency, (7) uncontrolled hypertension, chest pain, cardiac arrhythmia, stroke, head trauma, intracranial mass or hemorrhage, glaucoma, porphyria, uncontrolled thyroid disease, or other contraindication to ketamine, (8) lamotrigine alfentanil, physostigmine, or 4-aminopyridine use, (9) currently pregnant, (10) body mass index greater than 35, (11) non-English or non-Spanish speaker, (12) currently participating in another pain interventional trial, (13) patient has started or undergone hormone therapy for gender transition into male, or (14) patient is scheduled for bilateral (or greater) flap reconstruction. Specific Aims: The primary outcome is pain intensity on the Brief Pain Inventory short form scale at the surgical site three months after mastectomy. Secondary outcomes include pain severity and interference at the surgical site, incidence of PMPS, anxiety, and depression over 12 months after surgery. Tertiary outcomes include neuropathic symptoms, fatigue, sleep, physical function, and opioid use. Statistical Methods: We will test the differences in the primary outcome between 1) the continuous ketamine infusion and the control; and 2) the single-dose ketamine and the control, each at 0.025 significance level (adjusted for multiple comparisons using the Bonferroni correction), based on the two-sample t-tests (allowing unequal variances) if outcome variables are approximately normal, or Wilcoxon’s rank-sum tests otherwise. Accrual: The target accrual for this study is ~750. Recruitment began January 2022. Recruitment is expected to be complete by October 2025. As of July 14, 2022, 43 participants have been enrolled across all sites. If interested in the KALPAS Study, please contact kalpas@nyulangone.org, jing.wang@nyulangone.org, or lisa.doan@nyulangone.org This research is supported by the National Institutes of Health through the NIH HEAL Initiative under UH3CA261067. It is also supported by the NCATS Trial Innovation Network under award numbers U24TR001608 (CCC), U24TR001597 (DCC), U24TR001609 (SSC), U24TR001579 (RIC) Citation Format: Lisa Doan, Raven Perez, Jeana Chun, Randy Cuevas, Pabel Miah, Amber Guth, Karen Hiotis, Freya Schnabel, Michele Curatolo, Robert Edwards, Hyung Park, John Rotrosen, Deborah Axelrod, Jing Wang. Ketamine Analgesia for Long Lasting Pain Relief after Surgery (KALPAS) Study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT3-20-01.

Breast cancer is the most common female malignancy worldwide. Breast surgery and adjuvant oncological therapies are often required to increase survival. Treatment-related pain may persist and evolve into postmastectomy pain syndrome (PMPS) in a significant subset of breast cancer survivors. In this retrospective investigation, we will present our experience in applying an interventional algorithmic approach to treat PMPS. A retrospective study. An academic cancer hospital. Adult females with PMPS diagnosis. We reviewed 169 records with the diagnosis of PMPS from 2015 to 2019 within our health system. Pre- and post-injection pain scores, relief duration, and medication usage changes were collected. The decision to perform each procedure was based on the anatomic location of the painful area with the corresponding peripheral sensory innervation. Decision-making flow diagrams were created to present our experience in managing PMPS beyond peripheral nerve blocks. Ultrasound-guided peripheral nerve block results (n=350) were analyzed. The mean baseline pain score was 7, compared with the post-treatment mean score of 3 (95% confidence interval: 3.58 to 3.98, P = 0.0001). Among the responders, the mean pain relief duration was 45 days, with a median of 84 days. Opioid medication consumption was reduced by 11% (t = 0.72, P = 0.47). Ultrasound-guided nerve blocks of this area could be performed safely and effectively after breast surgeries. We also present our proposed algorithm to provide a stepwise application for selecting the appropriate therapies in the management of more complex PMPS.

Chronic Pain Syndrome After Breast Cancer Surgery, defined as Postmastectomy Pain Syndrome (PMPS), is a condition in which, according to statistics, about 60% of patients experience low-intensity pain for three to six months after surgery in the intervention area, while 15-25% of patients suffer from moderate or high-intensity pain. The objective of this review is to analyze literature sources containing relevant data on anesthesia and analgesia methods used to prevent PMPS, as well as studies on new perioperative and postoperative PMPS prevention techniques. The authors conducted a search and review of literature in the PubMed, Ovid MEDLINE, Google Scholar, and ScienceDirect databases. The review included studies published between 2014 and 2024, where the study population consisted of adult female patients who underwent mastectomy for breast cancer treatment or prophylactic risk reduction, as well as data on pharmacological and regional anesthesia methods for PMPS prevention over 3 months or more after surgery. Regional nerve blocks as a method of intraoperative anesthesia demonstrated high efficacy and good analgesic effects during mastectomy, reducing the need for opioid analgesics. However, data on their effectiveness in preventing PMPS remain inconclusive. Studies on the efficacy of Pectoral Nerve Block (PECSII) in reducing post-breast cancer surgery pain found no statistically significant differences in PMPS incidence at 3 and 6 months post-surgery between patient groups. Compared to ketamine and lidocaine, pregabalin showed greater efficacy in preventing chronic pain syndrome, though its benefits were primarily short-term, and long-term effects require further research. Physiotherapy methods did not lead to significant improvements compared to traditional approaches, which may be due to small sample sizes in the studies. Psychotherapeutic interventions, such as cognitive-behavioral therapy (CBT) and hypnosis, proved effective in reducing pain perception and stress levels during the perioperative period.

Background:Postmastectomy pain syndrome (PMPS) is defined as a chronic (continuing for 3 or more months) neuropathic pain affecting the axilla, medial arm, breast, and chest wall after breast cancer surgery. The prevalence of PMPS has been reported to range from 20% to 68%. In this study, we aimed to determine the prevalence of PMPS among mastectomy patients, the severity of neuropathic pain in these patients, risk factors that contribute to pain becoming chronic, and the effect of PMPS on life quality.Methods:This cross-sectional study was approved by the Sakarya University, Medical Faculty Ethical Council and included 146 patients ranging in age from 18 to 85 years who visited the pain clinic, general surgery clinic, and oncology clinic and had breast surgery between 2012 and 2014. Patients were divided into two groups according to whether they met PMPS criteria: pain at axilla, arm, shoulder, chest wall, scar tissue, or breast at least 3 months after breast surgery. All patients gave informed consent prior to entry into the study. Patient medical records were collected, and pain and quality of life were evaluated by the visual analog scale (VAS) for pain, a short form of the McGill Pain Questionnaire (SF-MPQ), douleur neuropathique-4 (DN-4), and SF-36.Results:Patient mean age was 55.2 ± 11.8 years (33.0–83.0 years). PMPS prevalence was 36%. Mean scores on the VAS, SF-MPQ, and DN-4 in PMPS patients were 1.76 ± 2.38 (0–10), 1.73 ± 1.54 (0–5), and 1.64 ± 2.31 (0–8), respectively. Of these patients, 31 (23.7%) had neuropathic pain characteristics, and 12 (9.2%) had phantom pain according to the DN-4 survey. Patients who had modified radical mastectomy were significantly more likely to develop PMPS than patients who had breast-protective surgery (P = 0.028). Only 2 (2.4%) of PMPS patients had received proper treatment (anticonvulsants or opioids).Conclusions:PMPS seriously impacts patients’ emotional situation, daily activities, and social relationships and is a major economic burden for health systems. We conclude that the rate of PMPS among patients receiving breast cancer surgery in Turkey is 64.1% and that challenges to the proper treatment of these patients deserve further investigation.

Pectoserratus plane block (PSPB) leads to lower postoperative pain intensity. We examined whether PSPB could also reduce the incidence of post-mastectomy pain syndrome (PMPS) in women undergoing breast cancer surgery. We performed an extension study of a randomized trial that compared PSPB versus control in women undergoing mastectomy. The primary outcome was any chronic pain at the surgical site or adjacent areas, defined as persistent/recurrent pain lasting ≥3 months. Secondary outcomes included neuropathic pain (score ≥4 in the Douleur Neuropathique 4 questionnaire), use of analgesic/anti-inflammatory drugs, pain intensity via the short-form McGill Pain Questionnaire, and type, frequency and location of the pain. Of the 60 patients that completed the 24-hour follow-up (short-term trial), 53 (88%) completed the long-term follow-up (27 in the PSPB group and 26 in the placebo group). Six of 27 patients (22%) in the PSPB group and 17 of 26 patients (65%) in the placebo group reported any chronic pain (relative risk [RR], 0.34; 95% confidence interval [95% CI]=0.16-0.73, P=0.005). The risk of neuropathic pain was also lower in the PSPB group than in the placebo group (18.5% vs. 54%, respectively; RR, 0.34; 95% CI=0.14-0.82, P=0.02). There were no differences regarding all other pain-related outcomes considering the patients who developed PMPS. The results suggest that, in the long-term, PSPB-treated participants were associated with a statistically significantly lower risk of PMPS than those who received standard general anesthesia. ClinicalTrials.gov (NCT03966326).

This narrative review explores the role of the erector spinae plane block (ESPB) as an alternative strategy for managing acute and chronic pain following breast surgeries. The focus is on its potential to reduce opioid consumption and the incidence of postmastectomy pain syndrome (PMPS), which remain significant postoperative concerns. A structured literature search was conducted across PubMed, Google Scholar, Medline, and ScienceDirect using keywords including: Erector Spinae Plane Block, ESPB, postoperative analgesia, opioid reduction, breast surgery, mastectomy, and postmastectomy pain syndrome. Studies included randomized controlled trials, cohort studies, and case series published within the last 10 years. The quality of evidence was assessed based on study design, sample size, and reported outcomes. ESPB has shown promise in reducing postoperative pain and opioid requirements in breast surgeries, including mastectomies, lumpectomies, reconstruction, and axillary dissections. By delivering local anesthetic into the fascial plane deep to the erector spinae muscle, ESPB provides multi-dermatomal analgesia with a favorable safety profile. Compared to other regional techniques such as pectoralis nerve blocks and paravertebral blocks, ESPB is often easier to perform and associated with comparable or improved analgesia. Some studies also report earlier ambulation and shorter hospital stays. The ESPB has been shown to reduce the incidence of postmastectomy pain syndrome and opioid consumption following breast surgery. Current evidence indicates that both the ESPB and paravertebral blocks are both safe and effective in their analgesic purposes but there is no significant evidence favoring one block over the other.

This study assesses the role of pregabalin in the prevention of postmastectomy pain syndrome (PMPS). Chronic PMPS affects 20%–40% of breast cancer patients undergoing surgery. This has the potential to negatively affect the quality of life of this patient population with chronic postsurgical pain. The study is a randomized controlled trial of 200 patients with breast cancer who received pregabalin or placebo for 1 week at the time of elective breast surgery. The incidence of PMPS was significantly lower in the pregabalin group (P &amp;lt; .001, relative risk: 0.26, 95% CI: 0.12–0.56). In addition, this study demonstrated that the use of perioperative pregabalin significantly lowered the incidence of neuropathic pain measured by the Grading System for Neuropathic Pain and pain intensity measured by a visual analog scale at 4, 12, and 24 weeks. Therefore, the use of perioperative oral pregabalin could reduce the frequency of PMPS.