5HT2A modulation attenuates pancreatic cancer induced pain mouse model by inhibiting HDAC.

PURPOSE: Patients have been severely suffered from cancer associated pain, and pancreatic cancer is the most severe form of cancer associated with pain. There are very few options available to manage it. The present report evaluated the effect of 5HT2A on pancreatic cancer associated pain. METHODS: Pancreatic cancer was induced by injecting SW 1,990 cells (~3×106 in a 20 µL suspension) into the pancreas and formed a 2-3-mm vesicle using an inoculator fitted with a 26-gauge needle in BALB/c-nu mice. Survival rate and body weight of the mice were observed. Pain behaviour testing was performed at the end of each week (third and fourth week) after surgery. Inflammatory mediators and HDAC 2 proteins were determined in the spinal tissue using quantitative real-time polymerase chain reaction. RESULTS: There was improvement in the survival rate and body weight in 5HT2A antagonist treated group than pancreatic cancer group of mice. Moreover, 5HT2A antagonist ameliorated the alteration in pain behaviour of pancreatic cancer mice. mRNA expression of HDAC2 and level of inflammatory cytokines were reduced in the spinal tissue of 5HT 2A antagonist treated group than pancreatic cancer group of mice. CONCLUSIONS: Data revealed that 5HT2A antagonist ameliorates pain associated with pancreatic cancer mice by HDAC inhibition and inflammatory cytokines. The result of investigation supports that modulation of 5HT2A receptor could be used clinically to protects neuropathic pain in pancreatic cancer.

Refractory cancer pain in young child at end-of-life: Can we alleviate the suffering?

Pain is a common and highly distressing symptom in children with advanced malignancies and it is often multifactorial at the end-of-life. The prognosis of cancer pain is reported to be worse in those with mixed pain type, high pain severity, daily opioid use, and poor emotional well-being. We describe a case of 13-year-old boy, known case of metastatic Ewing sarcoma right iliac bone, who presented to our palliative care ward with intractable pain and was finally discharged home for terminal care with high doses of morphine, ketamine, and midazolam infusion through elastomeric pump attached to a peripherally inserted central catheter (PICC line). The suffering of imminently dying children should be reduced, and judicious dose escalation of opioids along with adjuvants is appropriate and often necessary.

The nonreceptor protein tyrosine kinase Src participates in every step of cancer-induced bone pain.

Cancer-induced bone pain (CIBP) is a refractory form of pain that has a high incidence in advanced tumors. Src protein tyrosine kinase is mainly composed of six domains, with two states of automatic inhibition and activation. The modular domain allows Src to conveniently regulate by and communicate with a variety of proteins, directly or indirectly participate in each step of the CIBP process. Src is beneficial to the growth and proliferation of tumor cells, and it can promote the metastases of primary tumors to bone. In the microenvironment of bone metastasis, it mainly mediates bone resorption, activates related peripheral receptors to participate in the formation of pain signals, and may promote the generation of pathological sensory nerve fibers. In the process of pain signal transmission, it mainly mediates NMDAR and central glial cells to regulate pain signal intensity and central sensitization, but it is not limited to these two aspects. Both basic experimentation and clinical research have shown encouraging potential, providing new ideas and inspiration for the prevention and treatment of CIBP.

MiR-135-5p Alleviates Bone Cancer Pain by Regulating Astrocyte-Mediated Neuroinflammation in Spinal Cord through JAK2/STAT3 Signaling Pathway.

Bone cancer pain (BCP) was associated with microRNA dysregulation. In this study, we intended to clarify the potential role of miR-135-5p in a BCP mouse model, which was established by tumor cell implantation (TCI) in the medullary cavity of the mouse femur. The BCP-related behaviors were tested, including the paw withdrawal mechanical threshold (PWMT) and number of spontaneous flinches (NSF). The miRNA expression profiles in astrocytes of the sham and tumor groups were compared, and miRNA microarray and quantitative real-time PCR (qRT-PCR) assays confirmed that the amount of expression of miR-135-5p was significantly decreased in astrocytes of the tumor group. Gain- and loss-of-function studies showed that miR-135-5p could inhibit astrocyte activation and inflammation cytokine (TNF-α and IL-1ß) expression. The relation between miR-135-5p and JAK2 was detected by bioinformatic analysis and dual luciferase reporter gene assay. By conducting in vitro experiments, it was shown that the miR-135-5P mimics lowered the level of JAK2/STAT3 proteins and inflammatory factors in astrocytes. Moreover, in vivo analysis on BCP mice model indicated that the miR-135-5p agonist could sufficiently increase PWMT and decrease NSF. Meanwhile, reduced activation of astrocytes in the spinal cord, as well as decreased expression of JAK2/STAT3 and inflammatory mediators, were found after miR-135-5p agonist treatment. Collectively, the results showed that miR-135-5p could potentially reduce BCP in mice through inhibiting astrocyte-mediated neuroinflammation and blocking of the JAK2/STAT3 signaling pathway, indicating that the upregulation of miR-135-5P could be a therapeutic focus in BCP treatment.

Medical Cannabis in Oncology: a Valuable Unappreciated Remedy or an Undesirable Risk?

OPINION STATEMENT: The use of the cannabis plant by cancer patients has been rising significantly in the past few years worldwide, primarily driven by public demand. There is an obvious need for more reliable scientific data, pharmacology information, a better understanding of its mode of action, and available clinical evidence supporting its robust use. Physicians must complete a thorough medical assessment, screening for potential drugs, or treatment contraindications before allowing its consumption. In light of the growing popularity of cannabis usage, it is highly essential that, in the near future, the medical community will be able to provide practical recommendations and explicit guidelines, including doses, and that cannabinoid concentrations in the used products are defined regarding its prescription before any medical procedure involving its usage is authorized. Here, we review and describe the favorable outcomes demonstrating the benefits of cannabis as an adjunctive treatment to conventional medicines for chemotherapy-induced nausea, vomiting, and cancer-related pain (primarily refractory chronic or neuropathic pain). Although not yet substantial enough, the treatment of anorexia, insomnia, depression, and anxiety is also seemingly favorable. To date, reports regarding its anti-neoplastic effects or its potent immunosuppressive properties influencing response to immunotherapy are still very conflicting and controversial. Thus, with the current state of evidence, cannabis use is not advisable as initial treatment, as an adjunct or an advanced line of care. In the coming years, we expect that preclinical data and animal models will shift to the clinical arena, and more patients will be recruited for clinical trials, and their reports will advance the field. Thus, physicians should prescribe cannabis only if careful clarification and consideration is provided together with a follow-up response evaluation.

Effects of Mefenamic Acid in Pain Control during Loop Electrical Excision Procedure:A Prospective Double-Blind Randomized Control Trial.

OBJECTIVE: To investigate the effectiveness of pre-procedural oral mefenamic acid compared with placebo in women undergoing Loop Electrosurgical Excision Procedure (LEEP) with intracervical lidocaine injection. STUDY DESIGNS: A prospective double-blinded randomized control trial. Materials, Setting, Methods: Women undergoing LEEP for any indications were asked to participate in the study. The participants were randomly allocated into two groups. In group 1 (oral mefenamic acid), the participants were offered oral mefenamic acid (500 mg) for 30 minutes before procedures. In group 2 (placebo), the patients were given oral placebo (identical tablet) for 30 minutes before operation. All participants received immediate 10 mL of 2% lidocaine with 1:100,000 of epinephrine intracervical injection before undergoing the LEEP. All participants were excised in one piece of LEEP. No top-hat excision in this study.  The patients graded their pain on a 10-cm visual analog scale (VAS) at different points during the procedure, including speculum insertion, at starting excision, and 30 minutes post excision. Primary outcomes revealed the difference of VAS during all steps of LEEP by generalized estimating equations procedure. RESULTS: Sixty participants (30 in mefenamic group and 30 in placebo group) participated in this study. The study did not find differences of VAS during all steps of LEEP and analgesic drug requirement at 30 minutes after LEEP procedure. All patients reported no immediate complications and no intervention-related adverse events were observed. CONCLUSION: Using pre-procedural oral mefenamic acid before LEEP procedure was not associated with pain reduction during all steps of excision.
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Efficacy of pectoral nerve block type II versus thoracic paravertebral block for analgesia in breast cancer surgery.

BACKGROUND: Ultrasound-guided pectoral nerve block type II is a recently proposed technique for postoperative analgesia after breast cancer surgery. The thoracic paravertebral block is widely used for this purpose by decades. The presented study compares the efficacy of these two techniques for postoperative analgesia. MATERIALS AND METHODS: Sixty adult women were undergoing unilateral radical mastectomy or quadrantectomy with axillary dissection. The patients were randomized to receive either pectoral nerve block with 30ml ropivacaine 0.375% (Pecs group) or thoracic paravertebral block with 20ml ropivacaine 0.5% (TPVB group). The evaluated variables included pain intensity by the numerical rating scale at 0, 2, 4, 6, 12, 18 and the 24 hours, 24-hour postoperative opioid (promedol) and nonopioid (ketoprofen) consumption and the time to first rescue analgesia. RESULTS: There were no statistically significant differences between both groups in the pain intensity after surgery. Ten (33%) patients from Pecs group and nine (30%) patients from TPVB group did not require any analgesia within the first 24 hours (P = 0.793). The mean postoperative ketoprofen consumption was lower in Pecs group: 63.3 (± 66.87) mg vs. 90.0 (± 84.49) mg (Р = 0.283). The number of patients who required promedol was 6 (20%) vs. 8 (27%) in Pecs and TPVB groups, respectively (Р = 0.542). The time to first analgesic request was longer in Pecs group, 550 (400.0-600.0) min vs. 510 (360.0-600.0) min (Р = 0.506) in TPVB group. CONCLUSIONS: In breast cancer surgery, the pectoral nerve block type II with ropivacaine 0.375% can provide postoperative analgesia that is comparable to the single-level thoracic paravertebral block.

Local treatment with deep percutaneous electrochemotherapy of different tumor lesions: pain relief and objective response results from an observational study.

OBJECTIVE: The aim of this investigation focuses on the evaluation of the efficacy of deep-seated Electrochemotherapy (ECT) in terms of pain relief and local objective response, in pre-treated patients with neither further available pharmacological treatments nor eligible for surgery. PATIENTS AND METHODS: Deep percutaneous ECT has been performed in 20 patients subjected to systemic anaesthesia. Bleomycin was administrated intravenously before the application of the electrical pulses on the target area, employing multiple single needles depending on the size and location of the target tumor. RESULTS: Pain assessment based on Visual Analogue Scale showed significant pain relief one month after treatment in all patients, reducing from 7.5 to 3 as a median value (p-value at Wilcoxon test <0.001). Local symptom-free survival median value was 5.5 months. At the first follow-up (1-2 months), a local disease control rate (LDCR) was observed in 19/20 (95%) patients: complete responses in 2 (10%), partial responses in 8 (40%) and stable disease in 9 (45%). Local progression-free survival median value was 5.7 months. Overall, no major adverse effects were observed. CONCLUSIONS: Our study indicates that deep percutaneous ECT can produce a significant pain reduction and a high LDCR in different tumor lesions, for anatomical site or histotype. In particular, ECT has demonstrated to be effective in various histotypes and deep-seated tumor lesions never treated before by this approach giving a new chance to physicians for reducing oncological pain in patients not eligible to other therapeutic routes. The innovative peculiarity of our study was the successful application of deep percutaneous ECT on adrenal metastasis, malignant pleural mesothelioma, uterine leiomyosarcoma and the uncommon case of a male müllerian tumor.

Randomized Pilot Study of 20 Gy in 5 Fractions versus 27 Gy in 3 Fractions Radiotherapy for Treating Painful Bone Metastases: A Single Institution Experience.

PURPOSE: Radiotherapy is a very effective tool in the treatment of painful bone metastases. The aim of this study was to compare the palliative effect of radiotherapy between the standard fractionation schedule 20 Gy over 5 fractions (20Gy/5fr) and the high biological dose schedule 27 Gy over 3 fractions (27Gy/3fr) which is frequently used in Stereotactic body radio-surgery (SBRT). METHODS: Patients were randomized to receive (20Gy/5fr)or (27Gy/3fr). The primary aim of the study was pain relief using the numeric rating scale (NRS), after three months of radiation therapy. Secondary end points include pain relief immediately after finishing radiation therapy (within one week), and narcotic relief after three months of radiation therapy. RESULTS: Twenty-two patients with painful bone metastases were included. 12 patients received (20Gy/5fr) and 10 patients received (27Gy/3fr). Male patients were predominant on both arms (81.8%) with a mean age of 58 years [ranging between 19-72 years]. For pain relief after three months of radiation therapy, partial pain relief was documented in 9 patients (75%) with (20Gy/5fr) and in 8 patients (80%) with (27Gy/3fr) with a p- value of 0.6. Additionally, narcotic relief after three months was equal for both groups. For immediate pain relief, partial pain relief was seen in one patient (8%) with (20Gy/5fr) versus seven patients (70%) with (27Gy/3fr) with a p value of 0.06. The increase in immediate pain relief in the 27Gy arm was numerically but not statistically significant. CONCLUSION: SBRT and standard fractionation radiation therapy had equal effectiveness for pain relief, when the assessment was done after three months of radiation therapy. Interestingly, SBRT had a better immediate pain relief. 
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Dexamethasone for the Prevention of a Pain Flare After Palliative Radiation Therapy for Painful Bone Metastases: The Multicenter Double-Blind Placebo-Controlled 3-Armed Randomized Dutch DEXA Study.

PURPOSE: After radiation therapy for painful bone metastases, up to 44% of patients report a pain flare (PF). Our study compared 2 dose schedules of dexamethasone versus placebo to prevent PF. METHODS AND MATERIALS: This double-blind, randomized, placebo-controlled trial allocated patients with painful bone metastases from solid tumors randomly to receive 8 mg dexamethasone before radiation therapy followed by 3 daily doses (group A), 8 mg dexamethasone followed by 3 doses of placebo (group B), or 4 doses of placebo (group C). Patients reported worst pain scores, study medication side effects, and opioid intake before treatment and thereafter daily for 14 days and on day 28. PF was defined as at least a 2-point increase on a 0 to 10 pain scale with no decrease in opioid intake or a 25% or greater increase in opioid intake with no decrease in pain score, followed by a return to baseline or lower. The primary analysis was by intention to treat with patients who had missing data classified as having a PF. RESULTS: From January 2012 to April 2016, 295 patients were randomized. PF incidence was 38% for group A, 27% for group B, and 39% for group C (P = .07). Although patients in group B had the lowest PF incidence, a relatively high percentage did not return to baseline pain levels, indicating pain progression. The mean duration of PF was 2.1 days for group A, 4.5 days for group B, and 3.3 days for group C (P = .0567). Dexamethasone postponed PF occurrence; in group A 52% occurred on days 2 to 5 versus 73% in group B and 99% in group C (P = .02). Patients in group A reported lower mean pain scores on days 2 to 5 than those in group B or C (P < .001). Side effects were similar. CONCLUSIONS: There was insufficient evidence that dexamethasone reduced the incidence of radiation-induced PF. However, dexamethasone postponed the occurrence of PF and led to lower mean pain scores on days 2 to 5.

Antinociceptive activity of Schinus terebinthifolia leaf lectin (SteLL) in sarcoma 180-bearing mice.

ETHNOPHARMACOLOGY RELEVANCE: Schinus terebinthifolia Raddi leaves have been used in folk medicine due to several properties, including antitumor and analgesic effects. The variable efficacy and adverse effects of analgesic drugs have motivated the search for novel antinociceptive agents. It has been reported that the S. terebinthifolia leaf lectin (SteLL) has antitumor activity against sarcoma 180 in mice. AIM OF THE STUDY: This work aimed to evaluate whether SteLL would reduce cancer pain using an orthotopic tumor model. MATERIALS AND METHODS: A sarcoma 180 cell suspension was inoculated into the right hind paws of mice, and the treatments (150 mM NaCl, negative control; 10 mg/kg morphine, positive control; or SteLL at 1 and 2 mg/kg) were administered intraperitoneally 24 h after cell inoculation up to 14 days. Spontaneous nociception, mechanical hyperalgesia, and hot-plate tests were performed. Further, the volume and weight of the tumor-bearing paws were measured. RESULTS: SteLL (2 mg/kg) improved limb use during ambulation. The lectin (1 and 2 mg/kg) also inhibited mechanical hyperalgesia and increased the latency time during the hot-plate test. Naloxone was found to reverse this effect, indicating the involvement of opioid receptors. The tumor-bearing paws of mice treated with SteLL exhibited lower volume and weight. CONCLUSION: SteLL reduced hyperalgesia due to sarcoma 180 in the paws of mice, and this effect can be related to its antitumor action.

CXCL10 and CCL21 Promote Migration of Pancreatic Cancer Cells Toward Sensory Neurons and Neural Remodeling in Tumors in Mice, Associated With Pain in Patients.

BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma (PDAC) is frequently accompanied by excruciating pain, which has been associated with attraction of cancer cells and their invasion of intrapancreatic sensory nerves. Neutralization of the chemokine CCL2 reduced cancer-associated pain in a clinical trial, but there have been no systematic analyses of the highly diverse chemokine families and their receptors in PDAC. METHODS: We performed an open, unbiased RNA-interference screen of mammalian chemokines in co-cultures of mouse PDAC cells (K8484) and mouse peripheral sensory neurons, and confirmed findings in studies of DT8082 PDAC cells. We studied the effects of chemokines on migration of PDAC cell lines. Orthotopic tumors were grown from K8484 cells in mice, and mice were given injections of neutralizing antibodies against chemokines, antagonists, or control antibodies. We analyzed abdominal mechanical hypersensitivity and collected tumors and analyzed them by histology and immunohistochemistry to assess neural remodeling. We collected PDAC samples and information on pain levels from 74 patients undergoing resection and measured levels of CXCR3 and CCR7 by immunohistochemistry and immunoblotting. RESULTS: Knockdown of 9 chemokines in DRG neurons significantly reduced migration of PDAC cells towards sensory neurons. Sensory neuron-derived CCL21 and CXCL10 promoted migration of PDAC cells via their receptors CCR7 and CXCR3, respectively, which were expressed by cells in orthotopic tumors and PDAC specimens from patients. Neutralization of CCL21 or CXCL10, or their receptors, in mice with orthotopic tumors significantly reduced nociceptive hypersensitivity and nerve fiber hypertrophy and improved behavioral parameters without affecting tumor infiltration by T cells or neutrophils. Increased levels of CXCR3 and CCR7 in human PDAC specimens were associated with increased frequency of cancer-associated pain, determined from patient questionnaires. CONCLUSIONS: In an unbiased screen of chemokines, we identified CCL21 and CXCL10 as proteins that promote migration of pancreatic cancer cells toward sensory neurons. Inhibition of these chemokines or their receptors reduce hypersensitivity in mice with orthotopic tumors, and patients with PDACs with high levels of the chemokine receptors of CXCR3 and CCR7 had increased frequency of cancer-associated pain.

Optimization of opioid utility in cancer pain populations.

In this era of crisis and controversy surrounding opioid therapy, we must remember that cancer patients entrust us with supporting them through what might be the most difficult, and oftentimes final, period of their life. The factors that affect the benefits and risks of opioid use in cancer patients and the non-cancer population are quite different. In fact, opioid-associated deaths are 10 times less likely in the former than the latter population, suggesting that a reluctance to initiate opioids in cancer patients can risk under treatment of complex pain. In this review, we outline the considerations and evidence-based practices required to manage the clinical situations that challenge the judicious use of opioids in patients with cancer. A comprehensive review that enable us to better understand and quantify the root causes of variability in pain control, as well as risks of opioid misuse or abuse, would arm healthcare providers with the tools they need to implement multi-modal approaches to treatment planning.

The Critical Role of Parents in Pediatric Cancer-Related Pain Management: a Review and Call to Action.

PURPOSE OF REVIEW: Even with optimized medical management, pain remains an inevitable part of pediatric cancer care. The most effective interventions for nonpharmacologic pain management within pediatric psychology include parent skills training. This review specifically explored the role of parents in cancer-related pain management with the goal of defining a set of evidence-based skills that could translate to improved pediatric cancer pain management. RECENT FINDINGS: Pain is now widely understood to be both a sensory and emotional experience. As a result, within pediatric non-cancer pain management there is increasing application of the biopsychosocial model for pain management, inclusive of evidence-based psychological intervention. This review, specifically focusing on the role of parent training in cancer-related pain management, finds few interventions that systematically included parents. There is a need for continued evidence-based innovation and knowledge dissemination in this area of care. This paper highlights a critical gap in translational science within pediatric cancer pain management, namely, that parents who have a child with cancer are not reliably gaining access to well-established, evidence-based psychological skills training that can help to mitigate pain and pain-related stress. Based on the literature, the authors provide recommendations for generating adaptable, evidence-informed interventions that support and empower parents to help their child with pain management through all phases of cancer treatment.

Telephone Follow-up Design and Practice for Advanced Cancer Pain Patients.

To describe the design of a telephone follow-up protocol and to evaluate the feasibility of this protocol for advanced cancer pain patients. A series of nine telephone follow-up calls was implemented with 40 advanced cancer pain patients within 3 months after their discharge from the Department of Chemotherapy. Cancer pain information and the pain-related knowledge of the patients were collected by nurses using pain follow-up information sheets and the Patient Pain Questionnaire (PPQ); pain self-efficacy and the quality of life were reported by patients using the Chronic Pain Self-Efficacy Scale (CPSS) Chinese version and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC-QLQ-C30) Chinese version. The average score assessed by advanced cancer pain patients of the need for pain care from nurses was 24.28 (SD = 4.90). Twenty-one and eight patients completed all nine telephone follow-up calls and seven self-reported questionnaires, respectively. The pain intensity of patients at the time of follow-up was mild, but there had been breakthrough pain in the previous week. All patients were satisfied with the nurses' pain follow-up practices. There was a highly positive correlation between the time of follow-up and the patients' pain-related knowledge scores (r = 0.963**, p < 0.01). Patients' pain self-efficacy scores and quality of life scores varied across different dimensions. The baseline pain self-efficacy subscales were associated with all dimensions of quality of life (p < 0.05 or p < 0.01). Telephone follow-up can be an effective method of transitional care. For advanced cancer pain patients, it is still necessary to further explore the cost effectiveness of this method, including the appropriate follow-up duration, endpoints, and outcome measures based on government requirements and policies.

Pain Flare-Effect Prophylaxis With Corticosteroids on Bone Radiotherapy Treatment: A Systematic Review.

BACKGROUND: Radiotherapy for metastatic bone pain can induce a transitory increase in pain known as pain flare. Several studies have described the use of prophylactic corticosteroids to prevent pain flare. However, the role and efficacy of corticosteroids to prevent pain flare remain unclear. PURPOSE: To summarize the available evidence with regard to the efficacy and toxicity of prophylactic corticosteroids for the prevention of pain flare. METHODS: This was a systematic review (PROSPERO protocol CRD42018090351) of peer-reviewed studies published in the Cochrane, Medline, and Scopus databases through September 2018. Studies carried out in adult patients treated with radiotherapy for bone metastases who received prophylactic corticosteroids to prevent pain flare were eligible for inclusion. The Cochrane Collaboration tool was used to assess risk of bias. The evidence grade was determined according to the GRADEpro tool. RESULTS: A total of 4,407 studies were identified. Of these, 4 clinical trials (CT) and 1 prospective cohort study met the inclusion criteria. The overall incidence of pain flare was 28%, and 21% vs. 37% in the prophylaxis vs. non-prophylaxis groups; the relative risk reduction was 43%. In the 3 studies that compared corticosteroids to placebo, the relative risk reductions were 25%, 67%, and 72%. The most common treatment regimen was oral dexamethasone at 8 mg once daily from the first day of radiotherapy for 5 days. One study administered methylprednisolone. No severe toxicity was reported in any of the studies. CONCLUSIONS: Overall, the findings of this systematic review indicate that glucocorticoids appear to be an effective prophylactic treatment to prevent pain flare in patients undergoing radiotherapy for bone metastases. New CT are needed to confirm these results and to determine the optimal dose of dexamethasone.

Intrathecal administration of SRT1720 relieves bone cancer pain by inhibiting the CREB/CRTC1 signalling pathway.

Bone cancer pain (BCP) caused by primary or metastatic bone tumours significantly interferes with the quality of life of patients. However, the relief of BCP remains a major challenge. Our previous study demonstrated that intrathecal administration of the Sirtuin 1 (SIRT1) activator SRT1720 attenuated BCP in a murine model. Nevertheless, the underlying mechanisms have not been fully clarified. Previous studies demonstrated that the activation of the cAMP response element binding (CREB) protein played a critical role in BCP. Furthermore, SIRT1 can also regulate the balance between glucose and lipid metabolism through CREB deacetylation. In this study, we measured the analgesic effects of different intrathecal doses of SRT1720 on BCP in a murine model and further examined whether SRT1720 attenuated BCP by suppressing CREB/CREB-regulated transcription coactivator 1 (CRTC1) signalling pathway. Our results demonstrated that the BCP mice developed significant mechanical allodynia and spontaneous flinching, which were accompanied by the upregulation of phospho-Ser133 CREB (p-CREB) and CRTC1 expression in the spinal cord. SRT1720 treatment produced a dose-dependent analgesic effect on the BCP mice and downregulated the expression of p-CREB and CRTC1. These results suggest that intrathecal administration of SRT1720 reverses BCP likely by inhibiting the CREB/CRTC1 signalling pathway.

The Role of Ablation in Cancer Pain Relief.

PURPOSE OF REVIEW: The purpose of this article is to describe the concepts of ablation techniques for pain relief in symptomatic oncologic patients. Controversies concerning techniques and products will be addressed. RECENT FINDINGS: Despite conventional pain palliative techniques, cancer patients often endorse unresolved somatic and neuropathic pain that can present as a great burden to quality of life. In non-operative patients, several techniques have been applied to minimize opioid dependence. While radiotherapy is often considered as a non-invasive option, percutaneous ablation has been advanced as a minimally-invasive alternative with clear procedural and outcome advantages. Similar to radiation therapy, percutaneous ablation techniques can act either upon nerve structures responsible for pain mediation signals (neurolysis) or directly upon the tumor to relieve tumor-mediated inflammation and decompress tumor compression of adjacent structures. Percutaneous ablation provides valuable neurolysis and tumor-directed pain palliative effects to be incorporated into clinical guidelines for pain reduction in oncologic patients. Selection among different ablation techniques should be based upon an individually tailored approach, to include consideration of all treatment modalities.