Neuropathic pain after thoracotomy: Tracking signs and symptoms before and at monthly intervals following surgery.

BACKGROUND: As the development of neuropathic symptoms contributes to pain severity and chronification after surgery, their early prediction is important to allow targeted treatment. OBJECTIVES: We longitudinally investigated trajectories of signs and symptoms in patients undergoing thoracotomy and assessed whether and at which time they were related to the development of neuropathic pain symptoms 6 months after surgery. METHODS: Presurgical and 6 monthly postsurgical assessments included questionnaires for mental and physical well-being (e.g., depression/anxiety, pain catastrophizing, sleep quality, neuropathic pain symptoms), and quantitative sensory testing (QST). RESULTS: QST trajectories indicated nerve impairment of the surgery site with predominant loss of function. Signs of recovery towards the end of the assessment period were observed for some tests. Unsupervised cluster analysis with NPSI scores 6 months after surgery as clustering variable identified one group with no/low levels of neuropathic symptoms and one with moderate levels. The two groups differed w.r.t. several signs and symptoms already at early time points. Notably, neuropathic pain anywhere in the body differed already preoperatively and sleep impairment differentiated the two groups at all time points. Regression analysis revealed three factors that seemed particularly suited to predicted 6 months NPSI scores, namely preoperative neuropathic pain symptoms, with contributions from sleep impairment 1 month after surgery and the presence of dynamic mechanical allodynia 3 months after surgery. CONCLUSIONS: Clinical routine should focus on the individual's physiological state, including pre-existing neuropathic pain and sleep quality to identify patients early who might be at risk to develop chronic post-surgical neuropathic pain. SIGNIFICANCE: Development of neuropathies contributes to pain severity and pain chronification after surgery. Here we demonstrate trajectories of quantitative sensory tests (assessed at monthly intervals for 6 months after surgery) that reveal accurate time courses of gain/loss of nerve function following thoracotomy. Independent of the degree of neuropathic signs after surgery, the main predictors for post-surgical neuropathic pain are self-reported neuropathic pain before surgery and sleep quality shortly after surgery.

Postthoracotomy Ipsilateral Shoulder Pain: A Literature Review on Characteristics and Treatment.

Context. Postthoracotomy Ipsilateral Shoulder Pain (IPS) is a common and sometimes intractable pain syndrome. IPS is different from chest wall pain in type, origin, and treatments. Various treatments are suggested or applied for it but none of them is regarded as popular accepted effective one. Objectives. To review data and collect all present experiences about postthoracotomy IPS and its management and suggest future research directions. Methods. Search in PubMed database and additional search for specific topics and review them to retrieve relevant articles as data source in a narrative review article. Results. Even in the presence of effective epidural analgesia, ISP is a common cause of severe postthoracotomy pain. The phrenic nerve has an important role in the physiopathology of postthoracotomy ISP. Different treatments have been applied or suggested. Controlling the afferent nociceptive signals conveyed by the phrenic nerve at various levels-from peripheral branches on the diaphragm to its entrance in the cervical spine-could be of therapeutic value. Despite potential concerns about safety, intrapleural or phrenic nerve blocks are tolerated well, at least in a selected group of patient. Conclusion. Further researches could be directed on selective sensory block and motor function preservation of the phrenic nerve. However, the safety and efficacy of temporary loss of phrenic nerve function and intrapleural local anesthetics should be assessed.

Subcostal transversus abdominis plane phenol injection for abdominal wall cancer pain.

A subcostal transversus abdominis plane (TAP) phenol injection was performed on a patient with refractory cancer pain due a metastatic involvement of the abdominal wall. A diagnostic block with local anesthetic was performed under ultrasound guidance (USG), resulting in a decrease of 80% and 100% in dynamic and static visual analog scale (VAS) for pain, respectively, for 20 hours. A phenol injection was then performed under USG. The patient reported 70% and 100% reduction in the dynamic and static VAS for pain and had a 50% decrease in the opioid requirement that was maintained for 2 months. TAP blocks offer an interesting tool for either diagnosis or therapeutic purpose in chronic pain management. USG provides an optimal approach to soft-tissue lesions where fluoroscopy techniques are not useful.

Vertebroplasty and kyphoplasty: new evidence adds heat to the debate.

PURPOSE OF REVIEW: Cement bone augmentation has become very popular worldwide in treating painful noncomplicated spine fractures. Controversy about the effectiveness was raised by two randomized trials in 2009. Recent new evidence contradicts those findings giving credit to vertebroplasty/kyphoplasty. RECENT FINDINGS: Well designed prospective clinical trials in cancer and noncancer vertebral fractures as well as an excellent meta-analysis showed that painful vertebral compression fractures have better and faster pain relief, better functional outcomes, and with low complication rate when treated with percutaneous cement than conservatively. SUMMARY: The saga is unfinished. The treatment of vertebral compression fractures with cement augmentation is still in its infancy. The potential for development with new materials and the injection of biologic and active bone cements or anticancer products, in metastatic disease, will revolutionize the treatment of this condition.

Methylene blue in the treatment of discogenic low back pain.

BACKGROUND: The personal and societal impact of chronic low back pain is considerable. The intervertebral disc is considered the etiologic source in up to 40% of patients, with considerable previous efforts directed at developing reliable and efficacious treatments. Recent publications, including a double-blind, randomized, placebo-controlled trial, using a one-time treatment of methylene blue, showed statistically significant, clinically relevant improvements in pain and function in the treatment groups. The postulated mechanism of action of methylene blue is denervation of small nociceptive fibers that grow into the annulus fibrosis, which are implicated in discogenic pain. STUDY DESIGN: Retrospective case series. SETTING: Academic pain management center. OBJECTIVES: To examine the outcomes for a cohort of patients treated with methylene blue for discogenic pain, discuss potential differences in selection and administration protocols and briefly review other proposed treatments for discogenic pain (e.g. intradiscal electrothermy therapy, intradiscal steroids, intradiscal biaccuplasty, rami communicans radiofrequency thermocoagulation, and chymopapain). METHODS: This case series examines the pain and functional outcomes in 8 patients treated with a one-time administration of methylene blue for discogenic back pain. Follow-up information was available between 2 months and over one year, depending on the patient. RESULTS: Application of this treatment for these 8 patients for discogenic pain diagnosed by provocation discography showed only one clinical success at our center. Four patients had a time-limited clinical response in pain and/or function between 2 weeks and 5 months. Patient specific data are outlined in detail herein. CONCLUSIONS: Low back pain ascribed to a discogenic source continues to be an elusive clinical entity to treat. We have reserved further treatment of methylene blue for discogenic pain until other controlled trials have been published. LIMITATIONS: A case series.

Microencapsulation to reduce mechanical loss of microspheres: implications in myocardial cell therapy.

OBJECTIVE: Previous regenerative studies have demonstrated massive cell losses after intramyocardial cellular delivery. Therefore, efforts at reducing mechanical losses may prove more successful in optimising cellular therapy. In this study, we hypothesized that escalating mesenchymal stem cells (MSCs) dose will not produce corresponding improvement in cardiac function due to washout of the small cells in microcirculation. Using microspheres similar in size to MSCs, that are encapsulated in alginate-poly-l-lysine-alginate (APA), we tested the hypothesis that size is an important factor in early losses. METHODS: In experiment I, five groups of rats (n=9 each) underwent coronary ligation; group I had no treatment; the other groups received escalating 0.5 × 10(6), 1.5 × 10(6), 3 × 10(6) and 5 × 10(6) of MSCs each. Echocardiogram was performed at baseline, 2 days and 7 weeks after surgery. In experiment II, cell-sized microspheres (10 µm) were encapsulated in APA microcapsules. In group I (n=16), rats received bare microspheres, group II (n=16) microspheres within 200 µm microcapsules and in group III (n=16), microspheres within 400 µm microcapsules. After 20 min, hearts were quantified for the amount retained. RESULTS: Myocardial function did not improve further with escalating cell doses beyond an initial response at 1.5 × 10(6) cells. Encapsulated microspheres in 200 µm and 400 µm microcapsules demonstrated a fourfold increase in retention rate compared with 10 µm microspheres. CONCLUSION: We concluded that suboptimal functional improvement in this animal model starts at 1.5 × 10(6) cells and does not respond to escalating cell doses. Improving mechanical retention is possible by increasing the size of the injectate. Microencapsulation could be used to encapsulate donor cells and facilitate functional improvement in cellular heart failure therapy.

Marrow stromal cells for cell-based therapy: the role of antiinflammatory cytokines in cellular cardiomyoplasty.

BACKGROUND: The mechanism by which marrow stromal cells (MSCs) improve cardiac function after myocardial infarction (MI) is still unclear. Because MI patients with lower circulating proinflammatory/antiinflammatory cytokine ratios have been reported to have a better prognosis and in vitro studies showed that MSCs express antiinflammatory cytokines, we hypothesized that changes in cytokine ratios in the infarct microenvironment after MSC therapy may play a role in improving early cardiac function after MI. METHODS: Sixty-three rats that survived left coronary artery ligations were injected with culture media (group M) or MSCs (group C). Cardiac functional changes were assessed with echocardiography. Cytokine gene expressions of interleukin (IL)-1beta, IL-6, IL-8, (proinflammatory) and IL-10 (antiinflammatory) were quantified by real-time polymerase chain reaction. Extracellular matrix deposition, injury score, and the matrix metallopeptidase 2/tissue inhibitor of metallopeptidase 1 ratio were also analyzed. RESULTS: The ratio of proinflammatory/antiinflammatory cytokine gene expression was decreased in group C at various times, particularly in the early postoperative period. In group C, the matrix metallopeptidase 2/tissue inhibitor of metallopeptidase 1 gene expression ratio was significantly lower than group M at the early phase (12 hours), which in group C was translated into significantly lower extracellular matrix deposition at 24 hours, 1, and 2 weeks. Functional recovery was also significantly better in cell therapy group C. CONCLUSIONS: Our data demonstrate that MSC therapy decreases the proinflammatory/antiinflammatory cytokine ratio in the microenvironment early after MI. This is associated with subsequent less scar formation and improved cardiac function.

Marrow stromal cells as universal donor cells for myocardial regenerative therapy: their unique immune tolerance.

BACKGROUND: Recently rodent and porcine bone marrow stromal cells (MSCs) have been reported to be uniquely immune tolerant. To confirm these findings in human cells, we tested whether human MSCs are also immune tolerant, such that they can be used as universal donor cells for myocardial regenerative therapy. METHODS: Immunocompetent female rats underwent coronary ligations (n = 90). In group I, lacZ-labeled male human MSCs were implanted into the peri-infarcted area. In groups II, III, and IV, isogeneic rat MSCs, culture medium, or human fibroblasts were injected, respectively. Echocardiography was carried out to assess cardiac function, and the specimens were examined serially for up to 8 weeks with immunohistochemistry, fluorescent in situ hybridization, and polymerase chain reaction to examine MSCs survival and differentiation. RESULTS: Human MSCs survived within the rat myocardium for more than 8 weeks without immunosuppression. Furthermore, the implanted MSCs significantly contributed to the improvement in ventricular function and attenuated left ventricular remodeling. No cellular infiltration characteristic of immune rejection was noted in contrast to group IV. CONCLUSIONS: Human MSCs survived within this xenogeneic environment, and contributed to the improvement in cardiac function. Our findings support the feasibility of using these cells as universal donor cells for xenogeneic or allogeneic cell therapy, as they can be prepared and stored well in advance for urgent use. Allogeneic MSCs from healthy donors may be particularly useful for severely ill or elderly patients whose own MSCs could be dysfunctional.

Effect of a continuous peripheral nerve block on the inflammatory response in knee arthroplasty.

BACKGROUND AND OBJECTIVES: Experimental nerve block in animals inhibits the inflammatory response. The purpose of this study was to determine to what extent a 48-hour local anesthetic block of all afferent and efferent nerve fibers of the knee area has an impact on postoperative inflammatory response. METHODS: Twelve patients scheduled for primary total knee arthroplasty received spinal anesthesia, and then were randomly allocated to either patient-controlled analgesia with morphine (n = 6) or a combination of continuous lumbar plexus and sciatic nerve blocks (continuous peripheral nerve block; CPNB) with ropivacaine 0.2% for 48 hours. Blood samples were collected before surgery and at 3, 8, 24, and 48 hours after surgical incision to measure plasma glucose, serum insulin and cortisol, C-reactive protein, interleukin-6, and leukocyte count. Pain visual analog scale at rest and on knee flexion were recorded and complications classified. RESULTS: Visual analog scale was lower in the CPNB group at rest and on knee flexion on postoperative days 1 and 2 (P < .05). There were no differences in circulating levels of glucose, insulin, and cortisol. C-reactive protein and leukocyte count were lower in the CPNB group (P < .05). There was a positive correlation between the peak leukocyte count and the inflammatory markers (P < .03). Three patients in the patient-controlled analgesia group and one in the CPNB group had complications requiring conservative management. CONCLUSIONS: Continuous lumbar plexus and sciatic nerve blocks with ropivacaine contribute to the attenuation of the postoperative inflammatory response.

Intraoperative esmolol infusion in the absence of opioids spares postoperative fentanyl in patients undergoing ambulatory laparoscopic cholecystectomy.

BACKGROUND: The use of opioids during ambulatory surgery can delay hospital discharge or cause unexpected hospital admission. Preliminary studies using an intraoperative continuous infusion of esmolol in place of an opioid have inconsistently reported a postoperative opioid-sparing effect. In this study, we compared esmolol versus either intermittent fentanyl or continuous remifentanil on postoperative opioid-sparing, side effects, and time of discharge. METHODS: Ninety patients (consisting of three groups) were enrolled in this prospective, randomized, and observer-blinded study. The control group (n = 30) received intermittent doses of fentanyl, the esmolol group (n = 30) received a continuous infusion of esmolol (5-15 microg x kg(-1) x min(-1)) and no supplemental opioids during surgery, and the remifentanil group (n = 30) received a continuous infusion of remifentanil (0.1-0.5 mixrog x kg(-1) x min(-1)). General anesthesia was standardized, and adjuvant medications included acetaminophen, ketorolac, local anesthetics in the skin incisions, dexamethasone, and droperidol. Postoperative analgesia included fentanyl. RESULTS: The amount of fentanyl in the postanesthesia care unit was significantly less in the esmolol group, 91.5 +/- 42.7 microg, compared with the other two groups, remifentanil, 237.8 +/- 54.7 microg, control, 168.1 +/- 96.8 microg (P < 0.0001). The incidence of nausea was more frequent in the control (66.7%) and remifentanil (67.9%) groups compared with the esmolol group (30%) (P < 0.01). The esmolol group reached the White-Song score of 12 of 14 faster than the remifentanil group (P < 0.01), and left the hospital 45-60 min earlier (P < 0.004). CONCLUSIONS: Intraoperative IV infusion of esmolol contributes to a significant decrease in postoperative administration of fentanyl and ondansetron and facilitates earlier discharge.

Opioids: other routes for use in recovery room.

Opioids remain the main pharmacological tools for pain control in the postoperative patient. Recent concerns about chronic use of non-steroidal anti-inflammatory drugs have put extra pressure on health care workers to device and develop new medications and delivery methods to provide patients with appropriate pain relief after surgery. New technologies and better understanding of the pharmacology of the opioids administered by non-traditional ways will be reviewed in this manuscript. Understanding the anatomy of the nose cavity is important to use the inhaled way to deliver fentanyl, sufentanyl or butorphanol in surgical patients. High concentration and small volume are keys to good absorption and effect by nasal administration. Transdermal delivery of fentanyl has been used in chronic pain for some years. A new fentanyl self-administration method is in advanced trials for clinical use. It has a huge potential in giving good pain relief with lower side effects and more patient independence because of its reduced size and lack of tubing attached to it. Day surgery patients could be great candidates for this therapeutic alternative. Finally, oral transmucosal fentanyl is also in the market. Better suited to be used in controlling breakthrough pain in chronic settings, it has been so far marketed in the perioperative period. Side effects are a concern in its use for preoperative sedation in children. Large studies are now required for drugs approval and for new indications at regulatory agencies level. Good clinical judgment is more relevant now than ever before to avoid complications and new withdraw of old good medications inappropriately prescribed from the market place.

Vertebroplastía percutánea en el manejo del dolor de las fracturas vertebrales por compresión / Percutaneous cement vertebral augmentation in vertebral compression fractures: an update

Las fracturas vertebrales por compresión son de alta prevalencia y se relacionan principalmente a osteoporosis y cáncer. Frecuentemente tienen consecuencias devastadoras en la calidad de vida de los pacientes. Aquellos pacientes que no responden al tratamiento conservador se pueden beneficiar de una técnica mínimamente invasiva, la vertebroplastía, para reforzar la vértebra fracturada con cemento y así controlar el dolor. La vertebroplastía es un procedimiento ambulatorio con baja tasa de efectos colaterales cuando la realiza un médico con experiencia y el entrenamiento adecuado. Su tasa de éxito va del 65 al 95 por ciento, dependiendo de la indicación. Sólida evidencia científica se requiere aún para apoyar su amplio uso clínico.

Vertebral compression fractures are highly prevalent. Osteoporosis and cancer are the main causes. As a consequence patients endure excruciating breakthrough pain and debilitating experience that affect their quality of life. Those individuals that do not respond to classic treatment might benefit of vertebral cement augmentation. This is a totally ambulatory procedure aimed to control pain and stabilize the bone. Percutaneous approach is usually undertaken. Long lasting pain relief results in 65 to 95 percent of patients with a very low profile of complications when the procedure is done by experienced practitioners. Randomized, blinded and prospective studies are still required.