Chronic Post-thoracotomy Pain Research Articles

Retracted: Incidence and Influencing Factors of Chronic Postthoracotomy Pain in Lung Tumor Patients

Retracted: Incidence and Influencing Factors of Chronic Postthoracotomy Pain in Lung Tumor Patients

Ultrasound-guided continuous erector spinae plane block vs continuous thoracic epidural analgesia for the management of acute and chronic postthoracotomy pain: a randomized, controlled,double-blind trial.

Postthoracotomy pain (PTP) is a severe pain complicating thoracic surgeries and its good management decreases the risk of PTP syndrome (PTPS). This randomized controlled study evaluated the efficacy of ultrasound-guided continuous erector spinae plane block (ESPB) with or without dexmedetomidine compared with thoracic epidural analgesia (TEA) in managing acute postoperative pain and the possible emergence of PTPS. Ninety patients with chest malignancies planned for thoracotomy were randomly allocated into 3 equal groups. Group 1: TEA (20 mL of levobupivacaine 0.25% bolus, then 0.1 mL/kg/h of levobupivacaine 0.1%), group 2: ESPB (20 mL of levobupivacaine only 0.1% bolus every 6 hours), and group 3: ESPB (20 mL of levobupivacaine 0.25% and 0.5 μg/kg of dexmedetomidine Hcl bolus every 6 hours). Resting and dynamic visual analog scales were higher in group 2 compared with groups 1 and 3 at 6, 24, and 36 hours and at 8 and 12 weeks. Postthoracotomy pain syndrome incidence was higher in group 2 compared with groups 1 and 3 at 8 and 12 weeks, whereas it was indifferent between groups 1 and 3. The grading system for neuropathic pain score was higher in group 2 compared with groups 1 and 3 at 8 and 12 weeks, whereas it was indifferent between groups 1 and 3. Itching, pruritis, and urine retention were higher in group 1 than in ESPB groups. Ultrasound-guided ESPB with dexmedetomidine is as potent as TEA in relieving acute PTP and reducing the possible emergence of chronic PTPS. However, the 2 techniques were superior to ESPB without dexmedetomidine. Erector spinae plane block has fewer side effects compared with TEA.

Study protocol for a randomised controlled trial to investigate the effectiveness of thoracic epidural and paravertebral blockade in reducing chronic post-thoracotomy pain: 2 (TOPIC 2)

BackgroundThoracotomy is considered one of the most painful surgical procedures and can cause debilitating chronic post-surgical pain lasting months or years postoperatively. Aggressive management of acute pain resulting from thoracotomy may reduce the likelihood of developing chronic pain. This trial compares the two most commonly used modes of acute analgesia provision at the time of thoracotomy (thoracic epidural blockade (TEB) and paravertebral blockade (PVB)) in terms of their clinical and cost-effectiveness in preventing chronic post-thoracotomy pain.MethodsTOPIC 2 is a multi-centre, open-label, parallel group, superiority, randomised controlled trial, with an internal pilot investigating the use of TEB and PVB in 1026 adult (≥ 18 years old) patients undergoing thoracotomy in up to 20 thoracic centres throughout the UK. Patients (N = 1026) will be randomised in a 1:1 ratio to receive either TEB or PVB. During the first year, the trial will include an integrated QuinteT (Qualitative Research Integrated into Trials) Recruitment Intervention (QRI) with the aim of optimising recruitment and informed consent. The primary outcome is the incidence of chronic post-surgical pain at 6 months post-randomisation defined as ‘worst chest pain over the last week’ equating to a visual analogue score greater than or equal to 40 mm indicating at least a moderate level of pain. Secondary outcomes include acute pain, complications of regional analgesia and surgery, health-related quality of life, mortality and a health economic analysis.DiscussionBoth TEB and PVB have been demonstrated to be effective in the prevention of acute pain following thoracotomy and nationally practice is divided. Identification of which mode of analgesia is both clinically and cost-effective in preventing chronic post-thoracotomy pain could ameliorate the debilitating effects of chronic pain, improving health-related quality of life, facilitating return to work and caring responsibilities and resulting in a cost saving to the NHS.Trial registrationNCT03677856 [ClinicalTrials.gov] registered September 19, 2018. https://clinicaltrials.gov/ct2/show/NCT03677856. First patient recruited 8 January 2019.

Chronic post-thoracotomy pain after lung cancer surgery: a prospective study of preoperative risk factors.

The objective of this longitudinal cohort study was to investigate if preoperative pain mechanisms, anxiety, and depression increase risk of developing chronic post-thoracotomy pain (CPTP) after lung cancer surgery. Patients with suspected or confirmed lung cancer undergoing surgery by either video-assisted thoracoscopic surgery or anterior thoracotomy were recruited consecutively. Preoperative assessments were conducted by: quantitative sensory testing (QST) (brush, pinprick, cuff pressure pain detection threshold, cuff pressure tolerance pain threshold, temporal summation and conditioned pain modulation), neuropathic pain symptom inventory (NPSI), and the Hospital Anxiety and Depression Scale (HADS). Clinical parameters in relation to surgery were also collected. Presence of CPTP was determined after six months and defined as pain of any intensity in relation to the operation area on a numeric rating scale form 0 (no pain) to 10 (worst pain imaginable). A total of 121 patients (60.2 %) completed follow-up and 56 patients (46.3 %) reported CPTP. Development of CPTP was associated with higher preoperative HADS score (p=0.025), higher preoperative NPSI score (p=0.009) and acute postoperative pain (p=0.042). No differences were observed in relation to preoperative QST assessment by cuff algometry and HADS anxiety and depression sub-scores. High preoperative HADS score preoperative pain, acute postoperative pain intensity, and preoperative neuropathic symptoms were was associated with CPTP after lung cancer surgery. No differences in values of preoperative QST assessments were found. Preoperative assessment and identification of patients at higher risk of postoperative pain will offer opportunity for further exploration and development of preventive measures and individualised pain management depending on patient risk profile.

C3aR in astrocytes mediates post-thoracotomy pain by inducing A1 astrocytes in male rats

BackgroundAstrocyte activation, which is polarized into classical neurotoxic A1, neuroprotective A2, A-pan, etc., is thought to be involved in the transition from acute to chronic post-thoracotomy pain. The C3aR receptor associated with astrocyte-neuron and -microglia interactions is necessary for A1 astrocytes polarization. This study aimed to determine whether C3aR in astrocytes mediates post-thoracotomy pain by inducing A1 expression in a rat thoracotomy pain model. MethodsA rat thoracotomy pain model was employed. The mechanical withdraw threshold was measured to evaluate pain behavior. Lipopolysaccharide (LPS) was injected intraperitoneally to induce A1. Intrathecal injection of AAV2/9-rC3ar1 shRNA-GFAP was used to knock down in vivo C3aR expression in astrocytes. The expression of associated phenotypic markers before and after intervention was assessed by RT-PCR, western blot, co-immunofluorescence, and single-cell RNA sequencing. ResultsC3aR downregulation was found to inhibit LPS-induced A1 astrocytes activation, decrease the expression of C3aR, C3, and GFAP, which were activated from acute to chronic pain, and alleviate the mechanical withdrawal threshold and chronic pain incidence. In addition, more A2 astrocytes were activated in the model group that did not develop chronic pain. C3aR downregulation increased the number of A2 astrocytes upon LPS exposure. Knockdown of C3aR also decreased the activation of M1 microglia induced by LPS or thoracotomy. ConclusionsOur study confirmed that C3aR-induced A1 polarization contributes to chronic post-thoracotomy pain. Inhibition of A1 activation via C3aR downregulation increases anti-inflammatory A2 and decreases pro-inflammatory M1 activation, which may also be involved in the mechanism of chronic post-thoracotomy pain.

Sonic Hedgehog Signaling Pathway: ARole inPain Processing.

Pain, as one of the most prevalent clinical symptoms, is a complex physiological and psychological activity. Long-term severe pain can become unbearable to the body. However, existing treatments do not provide satisfactory results. Therefore, new mechanisms and therapeutic targets need to be urgently explored for pain management. The Sonic hedgehog (Shh) signaling pathway is crucial in embryonic development, cell differentiation and proliferation, and nervous system regulation. Here, we review the recent studies on the Shh signaling pathway and its action in multiple pain-related diseases. The Shh signaling pathway is dysregulated under various pain conditions, such as pancreatic cancer pain, bone cancer pain, chronic post-thoracotomy pain, pain caused by degenerative lumbar disc disease, and toothache. Further studies on the Shh signaling pathway may provide new therapeutic options for pain patients.

Nerve changes associated with post thoracotomy pain syndrome.

Chronic post-thoracotomy pain (PTPS) is a frequent complication of thoracic operations. Sometimes the pain is excruciating enough to impair activities of daily living (ADL). All thoracic procedures have the potential to cause trauma to the intercostal nerves due to retractor use, chest closure techniques, and or wound healing. In our study, we analyzed the microscopic aspects of the nerves involved in the healing process, to better understand the histopathology of chronic pain. 29 patients with PTPS underwent intercostal neurectomy to alleviate the symptoms. Microscopic specimens harvested during the surgeries were sent to our pathology unit for evaluation. The following data regarding the surgical procedures was collected: surgical approach, chest closure type, number of excised nerves, and time interval from previous surgery to neurectomy. A mean of 2.34±1.11 nerves were excised. Microscopy of the specimens revealed: fibrosis, hyalinization of the epineurium and perineurium, intense hyperemia of the blood capillaries, and interstitial edema. 7 cases presented with myxoid degeneration of epineurium and perineurium. In all the cases, endoneurium, myelin sheaths, and axons were interrupted. The endoneurium showed the presence of hyperemic dilated capillaries. The segmental cytoplasmic vacuolization of Schwann's cells with the total disappearance of axons was also noted. 60% of the examined specimens had intraneural myxoid degeneration, with highly dense irregular connective tissue around nerve fibers. The pathologic findings in the structure of the intercostal nerves obtained from the patients are indicative of the involvement of the wound healing mechanisms in PTPS. The negative impact of wound healing could be considered a key component in the development of intense chronic pain.

Incidence and Influencing Factors of Chronic Postthoracotomy Pain in Lung Tumor Patients.

Objectives To estimate the incidence of chronic postthoracotomy pain (CPTP) in lung tumor patients and to explore the influencing factors of the intensity of CPTP. Methods Lung tumor patients who underwent video-assisted thoracoscopic surgery (VATS) or thoracotomy were consecutively recruited from October 2016 to December 2017 at Yunnan Cancer Hospital. All the eligible patients were interviewed via telephone at the end of the third month after surgeries to identify the presence of CPTP. The potential influencing factors of CPTP, including pre-, intra-, and postoperative variables, were collected from medical records. A cumulative logit regression model was used to identify the independent influencing factors of the intensity of CPTP. Results Three hundred and forty-three patients completed a telephone interview. The estimated overall incidence of CPTP was 67.6% (95% of confidence interval, 95% CI: 62.4%, 72.6%) in lung tumor patients; 70.8% (95% CI: 63.8%, 77.1%) in benign patients and 63.5% (95% CI: 55.2%, 71.3%) in malignant patients; and 78.1% (95% CI: 66.0%, 87.5%) in open chest and 65.2% (95% CI: 59.3%, 70.8%) in VATS. Cumulative logit regression models (intensity order, NRS, 0 ⟶ 1–3 ⟶ 4-) revealed independent influencing factors of CPTP to be patients with diabetes (OR = 0.32; 95% CI: 0.14, 0.76), usage of VATS (OR = 0.47; 95% CI: 027, 0.82), and the amount of intraoperative blood loss (OR = 1.09; 95% CI: 1.00, 1.19). Conclusions A high incidence of CPTP is detected in lung tumor patients following the thoracic operation. Patients with diabetes and using VATS are the independent protective factors of the intensity of CPTP, and the increasing amount of intraoperative blood loss is an independent risk factor of the intensity of CPTP.

Ultrasound–guided serratus anterior plane block versus thoracic epidural analgesia for acute post–thoracotomy pain: a prospective randomized controlled study

Background: Post–thoracotomy pain can result not only in discomfort to the patient but also in pulmonary complications, due to ineffective coughing, which leads to retention of secretions. It can result into chronic post–thoracotomy pain in the long term. Many analgesic techniques are in use to control it, including continuous serratus anterior plane block (SAPB) and thoracic epidural analgesia (TEA). We compared the efficacy and safety of SAPB with continuous TEA in patients undergoing open lung resection.
 Methodology: This randomized, open–labeled, parallel–controlled trial was done in 60 patients aged 20 to 60 y with American Society of Anesthesiologists physical status II–III, who underwent elective thoracotomy for lung cancer surgery. Patients were randomly allocated according to analgesia either via a thoracic epidural catheter (10 ml levobupivacaine 0.25%, followed by 5 ml/h of 0.125%) or an ultrasound–guided SAPB (30 ml levobupivacaine 0.25% followed by 5 ml/h of 0.125%). Mean arterial pressure and heart rate were recorded during and after the surgery. Inj. fentanyl was used as rescue analgesia. Postoperatively VAS at rest and on coughing was used to assess the pain. Any complications were noted.
 Results: After excluding five patients, 27 and 28 patients were allocated to the TEA and SAPB groups, respectively. Intraoperatively and until 24 h after the end of surgery, the mean arterial pressure and heart rate were higher in the SAPB group than in the TEA group. Intraoperatively, the requirement for fentanyl was more in the SAPB group. Postoperatively, VAS at rest and cough were significantly higher in the SAPB group. The occurrence of nausea and vomiting, hypotension, and bradycardia were similar in the groups.
 Conclusions: In patients undergoing open lung resection for cancer, continuous serratus anterior plane block was less effective than thoracic epidural analgesia in controlling postoperative pain and presented similar adverse events.
 Key words: Serratus anterior plane block; Thoracic epidural, Continuous; Thoracotomy pain, Acute
 Abbreviations: PTP – Post–thoracotomy pain; TEA – Thoracic epidural analgesia; VAS – Visual analog scale; SAPB – Serratus anterior plane block; MAP – Mean arterial blood pressure; LA – Local anesthetics
 Preregistration: The study was registered in the institutional board ethical committee (201617026) and on www.clinicaltrials.gov (NCT03933592)
 Citation: Mostafa MM, Bakeer AH, Gamal RM. Ultrasound–guided serratus anterior plane block versus thoracic epidural analgesia for acute post–thoracotomy pain: a prospective randomized controlled study. Anaesth. pain intensive care 2021;25(6):733–740 ;
 DOI: 10.35975/apic.v25i6.1692
 Received: July 09, 2021, Reviewed: October 06, 2021, Accepted: October 09, 2021

Ror2 mediates chronic post-thoracotomy pain by inducing the transformation of A1/A2 reactive astrocytes in rats

Ror2 plays an important role in neuronal development, neuronal plasticity, and neuropathic pain. In our previous pilot study, we found that Ror2 and GFAP (a marker of astrocytes) protein levels increased in thoracic dorsal root ganglia from postoperative day (POD) 7 to POD 21 in rats with chronic post-thoracotomy pain (CPTP). In the present study, we aimed to further explore the roles of Ror2 and activated astrocytes during CPTP development. Ror2, c-JUN, and C3aR levels increased and the activated astrocytes were mainly expressed as the A1 phenotype in the spinal cord dorsal horn of the rats with CPTP. The knockdown of Ror2 in the spinal cord astrocytes alleviated thoracotomy-induced mechanical hyperalgesia and cold allodynia as well as reverted the A1/A2 ratio of the reactive astrocytes, downregulating the expression of c-JUN and C3aR in rats with CPTP. These results suggest that Ror2 in the spinal cord astrocytes mediates the transformation of A1/A2 reactive astrocytes via regulating the expressions of the c-JUN and C3aR in CPTP. Furthermore, the suppression of Ror2 could be utilized as a new strategy to help prevent CPTP.

New Thoracotomy Closure, a Simple Way to Decrease Chronic Post-Operative Pain in Selected Patients-Blinded Prospective Study.

Background and Objectives: Chronic post-thoracotomy pain syndrome (PTPS) is a very common and uncomfortable complication, occurring frequently after thoracic operations, leading to the necessity of further medication and hospitalizations. One important risk factor in developing chronic pain is the chest closure technique, which can lead to chronic intercostal nerve damage. This study proposes an alternative nerve-sparring closure technique to standard peri-costal sutures, aimed toward minimizing the risk of chronic pain in selected patients. Materials and Methods: We performed a prospective randomized study on 311 patients operated for various thoracic pathology over a period of 12 months, evaluating incision types, chest closure technique, and number of drains with drainage duration. The patients were divided into three groups: peri-costal (PC), proposed extra-costal (EC), and simple (SC) suture, respectively. Pain was measured on day 1, 2, 5, 7, and at 6 months post-operatively using the Visual Analogic Scale. Results: No significant differences in pain level were recorded in the first two post-operative days between the PC and EC groups. However, a significant decrease in pain level was observed on day 5 and at 6 months post-operatively, with a mean level of 3.5 ± 1.8, 1.2 ± 1 for the EC group compared to a mean value of 5.3 ± 1.6, 3.2 ± 1.5, respectively. No significant differences were observed regarding other evaluated variables. Conclusions: The lower recorded pain scores in patients with extra-costal chest closure are a strong argument to use this technique. Its ease of use is similar to the classic peri-costal closure, and the time needed to perform it is not significantly increased. The association of this technique with less invasive procedures and short drainage duration limits chronic post-operative pain. This procedure may represent an option for decreasing healthcare costs associated with the management of PTPS.

Serratus Anterior Plane Block as a Regional Analgesia Technique for Post Thoracotomy and Thoracoscopy Pain: Review Article

Background: Chest wall surgeries are accompanied by severe postoperative pain. Inadequate relief of this pain may lead to both pulmonary complications as lung atelectasis and infection and chronic post thoracotomy pain syndrome. Regional analgesic modalities are important portion of the multimodal therapeutic approach suggested for the management of post thoracotomy pain. Objective: To evaluate serratus anterior plane block as a regional analgesia technique for post thoracotomy and thoracoscopy pain. Recent Findings: Serratus anterior plane block (SAPB), a regional analgesic modality developed by Blanco et al. in 2013, has shown good analgesic effect after thoracotomy and thoracoscopy in many case reports and clinical trials. In such block, a local anesthetic is injected in the fascial plane deep or superficial to the serratus anterior muscle leading to block of lateral cutaneous branches of the intercostal nerves. This provides a sensory block of T2–T9 dermatomes. Conclusion:Serratus anterior plane block as a fascial plane block can be a preferred regional analgesia technique for both post-operative pain management with procedures involving anterolateral chest wall as thoracotomy, thoracoscopy and breast surgery and in cases of multiple rib fractures. This is owing to its easy technique, effective pain relief and potentially better side effects profile compared to other regional modalities and systemic opioids.

Incidence of Acute and Chronic Post-Thoracotomy Pain in Pediatric Patients

We studied acute and chronic pain in pediatric patients who underwent thoracotomy for benign disease with a follow-up of at least three months. A telephone interview investigated about the presence of pain and the analgesic therapy in progress. The results were compared with the anesthetic technique, postoperative pain and the adequacy of pain therapy, both during the first week after surgery and at the time of interview. Fifty-six families consented to the study. The mean age of the children at surgery was 2.9 ± 4.5 years, while at the time of the interview was 6.5 ± 4.4 years. We performed different anesthetic strategies: Group A: general anesthesia (36 pts); Group B: general anesthesia and thoracic epidural (10 pts); Group C: general anesthesia and intercostal nerve block (10 pts). During the immediate postoperative period, 21 patients (37.5%) had at least one painful episode. At the time of interview, 3 children (5.3%) had moderate chronic neuropathic (burning) pain on surgical scar. There was no statistically significant difference between the type of anesthesia and the incidence and severity of acute post-operative pain. Despite its limitations, this study confirms the low incidence of chronic post-thoracotomy pain syndrome in children.

Efficacy of Perioperative Intercostal Analgesia via a Multimodal Analgesic Regimen for Chronic Post-Thoracotomy Pain During Postoperative Follow-Up: A Big-Data, Intelligence Platform-Based Analysis.

BackgroundChronic post-thoracotomy pain is still an obstacle for lung-cancer patients even after less invasive surgical procedures. It is unclear whether intercostal analgesia is as useful in the prevention of postoperative chronic pain as it is for acute pain for video-assisted thoracoscopic surgery (VATS). The purpose of this study was to evaluate the efficacy of perioperative intercostal analgesia for chronic pain via a multimodal analgesic regimen for VATS during 6 months of postoperative follow-up.MethodsWe identified 837 cases of VATS from August 2016 to August 2018. Patients were treated by perioperative intercostal analgesia with 0.75% ropivacaine 50 mg through the intercostal catheter every 8 hours until chest tube extubation (INA group) or conventional analgesia with preoperative 0.75% ropivacaine 50 mg at incision once (CON group). Numerical rating scale (NRS) and neuropathic pain were evaluated in 6 months of post-surgery follow-up. Postoperative adverse effects were recorded.ResultsIn total, there were 419 patients in INA group and 418 patients in CON group. Scores of NRS with motion was lower in INA group at 3 postoperative days (P = 0.032). Occurrence of chronic pain was 28.4% in INA group and 32.8% in CON group at 6 postoperative months, 10.6% of patients experienced increasing pain from 3 to 6 months. Occurrence of considerable neuropathic pain (ID pain score ≥ 2) was 2.1% in INA group and 3.1% in CON group at 6 postoperative months. No differences were found between the two groups. Occurrence of numbness was lower in INA group (6.7% vs 10.5%, P = 0.031), and other pain symptoms did not differ between the groups. The incidence of dizziness, nausea, vomiting and atelectasis was not different between the two groups.ConclusionIn a multimodal analgesic regimen of VATS, perioperative intercostal analgesia with 0.75% ropivacaine infusion 50 mg three times in a day does not have an obvious effect on chronic post-thoracotomy pain.

Prevalence of chronic post-thoracotomy pain in patients with traumatic multiple rib fractures in South Korea: a cross-sectional study

Chronic post-thoracotomy pain is a debilitating condition after traumatic multiple rib fractures and surgery. We aimed to estimate the prevalence of chronic post-thoracotomy pain after traumatic multiple rib fractures in South Korea and explore factors associated with it. From October 2017 to June 2019, a cross-sectional survey of 100 adults, who had undergone thoracotomy due to traumatic fractures of two or more ribs 2 years to 3 months prior to the survey, was conducted in the regional trauma center in South Korea. In total, 80% and 65% patients reported any level and above moderate chronic pain, respectively. Quality of life was mostly below the normative value of the US general population. Forty-six percent patients had restrictive respiratory dysfunction, and 47% and 59% patients were classified as being at risk of above mild-level anxiety and depression, respectively. More than 70% of patients had a current opioid prescription. Multivariable logistic regression analysis showed weak evidence of association between acute, severe postoperative pain and chronic postsurgical pain (adjusted odds ratio 2.4, 95% confidence intervals 0.9 to 6.4). Collectively, chronic post-thoracotomy pain and associated incomplete recovery regarding respiratory, functional, and psychological outcomes were prevalent in patients with traumatic multiple rib fractures in South Korea.

Impact of regional analgesia techniques on the long-term clinical outcomes following thoracic surgery.

Continuous monitoring of clinical outcomes after thoracotomy is very important to improve medical services and to reduce complications. The use of regional analgesia techniques for thoracotomy offers several advantages in the perioperative period including effective pain control, reduced opioid consumption and associated side effects, enhanced recovery, and improved patient satisfaction. Postthoracotomy complications, such as chronic postthoracotomy pain syndrome, postthoracotomy ipsilateral shoulder pain, pulmonary complications, recurrence, and unplanned admission to the intensive care unit are frequent and may be associated with poor outcomes and mortality. The role of regional techniques to reduce the incidence of these complications is questionable. This narrative review aims to investigate the impact of regional analgesia on the long-term clinical outcomes after thoracotomy.

Mechanism of Toll-like Receptor 4 on Chronic Post-thoracotomy Pain Via Caspase-1 Activation.

Post-operative chronic post-thoracotomy pain (CPTP) has been linked to restrictions in mobility and daily activities. However, its potential causes and optimal therapy have not been well characterized. Here, the purpose of this study was to investigate the role of Toll-like receptor 4 (TLR4) in CPTP rats and its underlying mechanism. Initially, rat models of CPTP were established. Then, the mechanical withdrawal threshold (MWT) was measured after intrathecal injection of TLR4 antagonist (LPS-RS), TLR4 agonist (LPS-PG), or caspase-1 inhibitor (Ac-YVAD-CMK) in CPTP rats. Levels of TNF-α, IL-6 and IL-1β in the spinal dorsal horn (SDH) were measured by ELISA. TLR4 and caspase-1 were located by immunofluorescence double staining. TLR4 and caspase-1 levels were assessed by qRT-PCR and Western blot. TLR4 and caspase-1 were up-regulated in SDH of CPTP rats. Compared with Sham and non-CPTP groups, MWT was effectively decreased while TNF-α, IL-6 and IL-1β in SDH were increased in CPTP group. Moreover, intrathecal injection of TLR4 antagonist or caspase-1 inhibitor significantly elevated MWT expression and reduced levels of TNF-α, IL-6 and IL-1β in SDH. Additionally, high expression of TLR4 promoted mechanical hyperalgesia and inflammatory response, while intrathecal injection of a mixture of caspase-1 inhibitor and TLR4 agonist reversed the alleviation of caspase-1 inhibitor on the mechanical hyperalgesia and inflammatory response. TLR4 and caspase-1 were co-located in neurons. TLR4 aggravated CPTP in rats by mediating activation of caspase-1 in SDH.

Pre-emptive epidural analgesia for acute and chronic post-thoracotomy pain in adults: a systematic review and meta-analysis

Background and objectivesEpidural analgesia is the gold standard for post-thoracotomy pain management and can be started before or after surgical incision. This systematic review and meta-analysis investigated whether pre-emptive epidural...

Post-Thoracotomy Pain: Current Strategies for Prevention and Treatment.

Treating acute pain after thoracotomy surgery and preventing the development of chronic post-thoracotomy pain syndrome (PTPS) remain significant challenges in this surgical population. While appropriately treated acute thoracotomy pain often resolves, a significant number of patients develop PTPS, with up to 65% of patients experiencing some pain and 10% suffering life-altering, debilitating pain. Currently, there is very little known about specific molecular targets or novel therapeutic combinations that effectively prevent PTPS. Identifying modifiable clinical risk factors (procedure, physical and mental health, preoperative pain in the surgical area and another regions) seems to the most pragmatic approach for prevention for now. Effective acute pain management adopting a multimodal approach can result in a decreased incidence of PTPS. Interventional techniques such as paraverterbral blocks, intercostal blocks, and erector spinae blocks show some promise as well. Future research should be focused on minimally invasive surgeries and also the effect of ERAS protocols, including early mobilization, nutrition, and early removal of drains, on the development of PTPS.

Sonic Hedgehog Signaling Contributes to Chronic Post-Thoracotomy Pain via Activating BDNF/TrkB Pathway in Rats.

PurposeSome patients undergoing thoracotomy may suffer from chronic post-thoracotomy pain (CPTP). Treatment of CPTP has been a clinical challenge and the underlying mechanisms of CPTP remain elusive. Recently, sonic hedgehog (Shh) signaling has been shown to be associated with various pain states but its role in the pathogenesis of CPTP is still unclear.MethodsCPTP was induced in rats by thoracotomy. Rats were divided into CPTP group and non-CPTP group based on the mechanical withdrawal threshold (MWT). Rats were administered with Shh signaling inhibitor cyclopamine and activator smoothened agonist (SAG), and then evaluated by MWT and cold allodynia testing. The expressions of Shh signaling (Shh ligand, patched and smoothened receptor, Gli transcription factors), brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase receptor B (Trk-B), phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt) in rat T4-5 spinal cord dorsal horn (SDH) were detected by Western blotting and immunohistochemistry.ResultsThe expression of Shh signaling significantly increased and the BDNF/TrkB pathway was activated in T4-5 SDH of CPTP rats. Cyclopamine attenuated hyperalgesia and down-regulated the expressions of Gil1, BDNF, p-TrkB, p-PI3K and p-Akt in CPTP rats. SAG induced hyperalgesia in non-CPTP rats and elevated the expressions of Gil1, BDNF, p-TrkB, p-PI3K and p-Akt.ConclusionShh signaling may contribute to CPTP via activating BDNF/TrkB signaling pathway, and inhibition of Shh signaling may effectively alleviate CPTP.