Curcumin Is Emerging as One of the Most Potent Natural Cancer Treatments

Over the last decade, research into curcumin (Curcuma longa, a constituent of turmeric that gives the curry spice its yellow-orange color) has demonstrated potent chemoprotective and chemopreventive effects, as well as use as an anti-cancer therapy.

Curcumin produces anti-cancer effects through several different channels:

• Inhibits the proliferation of tumor cells
• Decreases inflammation
• Inhibits the transformation of cells from normal to tumor
• Inhibits the synthesis of a protein thought to be instrumental in tumor formation
• Helps your body destroy mutated cancer cells so they cannot spread throughout your body
• Prevents the development of additional blood supply necessary for cancer cell growth (angiogenesis) 

One of the issues with curcumin as a drug is that it is poorly absorbed in its raw form, with some estimates suggesting that only 1-3% of the curcuminoids are absorbed. Importantly, turmeric itself is not an adequate source of curcumin, with only an approximate 3% concentration of curcumin.

Most supplement manufacturers have developed a standardized 95-percent concentration of curcumin, and even with that level of concentration, it takes 2-3 grams of curcumin each day to get therapeutic benefits.

One way to increase absorption is to include black pepper extract (piperine) in the product. Piperine has been shown to inhibit CYP 450 enzymes that are crucial in metabolizing drugs. Research on using piperine with curcumin has demonstrated a 2000% increase in absorption {1}.

[As an aside, piperine may enhance the pharmacokinetic parameters of resveratrol by inhibiting glucuronidation, which slows its metabolism {2}.]

In an interview at Dr. Mercola's site, Dr. William LaValley made the following observation:

I found that a way to change that, to dramatically increase the bioavailability, is actually a very simple process of bringing water to a boil, putting those capsules or some dry powder (I use it by the teaspoon), and boiling it for 10 to 12 minutes. That increases the amount of curcumin dissolved in water from that one-percent amount up to 12 percent or so. That amount is a vast number of curcumin molecules that are now in a bioavailable or absorbable form.

It turns out that curcumin is a fat-loving or lipophilic molecule, which suggests taking curcumin with some sort of oil or fat might improve its absorption and bioavailability. According to Dr. LaValley, incorporating a lipid-based delivery system may promote a seven to eight times higher absorption rate than the 95-percent-concentration of dry powder.

As researchers continue to seek more effective delivery systems, the approaches are becoming much more sophisticated. In a 2014 article from PLoS ONE, researchers are directly targeting the mitochondria as a delivery method {3}.

Mitochondrial-Targeted Curcuminoids: A Strategy to Enhance Bioavailability and Anticancer Efficacy of Curcumin

Abstract


Although the anti-cancer effects of curcumin has been shown in various cancer cell types, in vitro, pre-clinical and clinical studies showed only a limited efficacy, even at high doses. This is presumably due to low bioavailability in both plasma and tissues, particularly due to poor intracellular accumulation. A variety of methods have been developed to achieve the selective targeting of drugs to cells and mitochondrion. We used a novel approach by conjugation of curcumin to lipophilic triphenylphosphonium (TPP) cation to facilitate delivery of curcumin to mitochondria. TPP is selectively taken up by mitochondria driven by the membrane potential by several hundred folds. In this study, three mitocurcuminoids (mitocurcuminoids-1, 2, and 3) were successfully synthesized by tagging TPP to curcumin at different positions. ESI-MS analysis showed significantly higher uptake of the mitocurcuminoids in mitochondria as compared to curcumin in MCF-7 breast cancer cells. All three mitocurcuminoids exhibited significant cytotoxicity to MCF-7, MDA-MB-231, SKNSH, DU-145, and HeLa cancer cells with minimal effect on normal mammary epithelial cells (MCF-10A). The IC₅₀ was much lower for mitocurcuminoids when compared to curcumin. The mitocurcuminoids induced significant ROS generation, a drop in ΔØm, cell-cycle arrest and apoptosis. They inhibited Akt and STAT3 phosphorylation and increased ERK phosphorylation. Mitocurcuminoids also showed upregulation of pro-apoptotic BNIP3 expression. In conclusion, the results of this study indicated that mitocurcuminoids show substantial promise for further development as a potential agent for the treatment of various cancers.

Presented below are some recent studies (all from 2014) on the therapeutic uses of curcumin, primarily as a cancer treatment or chemoprotective.

Citations for the section above

1. Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS (1998, May). Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med.; 64 (4): 353–6. doi:10.1055/s-2006-957450. PMID 9619120.

2. Johnson, J. J.; Nihal, M; Siddiqui, I. A.; Scarlett, C. O.; Bailey, H. H.; Mukhtar, H; Ahmad, N (2011). Enhancing the bioavailability of resveratrol by combining it with piperine. Molecular Nutrition & Food Research; 55 (8): 1169–76. doi:10.1002/mnfr.201100117. PMC 3295233. PMID 21714124 

3. Reddy, CA, Somepalli, V, Golakoti, T,  Koteswara, A, Kanugula, R, Karnewar, S, Rajendiran, K, Vasagiri, N, Prabhakar, S, Kuppusamy, P, Kotamraju, P, Kutala, VK. (2014, Mar 12). Mitochondrial-Targeted Curcuminoids: A Strategy to Enhance Bioavailability and Anticancer Efficacy of Curcumin. PLoS ONE; 9(3): e89351. DOI: 10.1371/journal.pone.0089351 

2014 Research on Curcumin Presented in PLoS ONE

For each article I am sharing the citation and the abstract - these are all open access articles.

Citation:  
Seo BR, Min K-j, Cho IJ, Kim SC, Kwon TK. (2014, Apr 17). Curcumin Significantly Enhances Dual PI3K/Akt and mTOR Inhibitor NVP-BEZ235-Induced Apoptosis in Human Renal Carcinoma Caki Cells through Down-Regulation of p53-Dependent Bcl-2 Expression and Inhibition of Mcl-1 Protein Stability. PLoS ONE 9(4): e95588. doi: 10.1371/journal.pone.0095588

AbstractThe PI3K/Akt and mTOR signaling pathways are important for cell survival and growth, and they are highly activated in cancer cells compared with normal cells. Therefore, these signaling pathways are targets for inducing cancer cell death. The dual PI3K/Akt and mTOR inhibitor NVP-BEZ235 completely inhibited both signaling pathways. However, NVP-BEZ235 had no effect on cell death in human renal carcinoma Caki cells. We tested whether combined treatment with natural compounds and NVP-BEZ235 could induce cell death. Among several chemopreventive agents, curcumin, a natural biologically active compound that is extracted from the rhizomes of Curcuma species, markedly induced apoptosis in NVP-BEZ235-treated cells. Co-treatment with curcumin and NVP-BEZ235 led to the down-regulation of Mcl-1 protein expression but not mRNA expression. Ectopic expression of Mcl-1 completely inhibited curcumin plus NVP-NEZ235-induced apoptosis. Furthermore, the down-regulation of Bcl-2 was involved in curcumin plus NVP-BEZ235-induced apoptosis. Curcumin or NVP-BEZ235 alone did not change Bcl-2 mRNA or protein expression, but co-treatment reduced Bcl-2 mRNA and protein expression. Combined treatment with NVP-BEZ235 and curcumin reduced Bcl-2 expression in wild-type p53 HCT116 human colon carcinoma cells but not p53-null HCT116 cells. Moreover, Bcl-2 expression was completely reversed by treatment with pifithrin-α, a p53-specific inhibitor. Ectopic expression of Bcl-2 also inhibited apoptosis in NVP-BE235 plus curcumin-treated cells. In contrast, NVP-BEZ235 combined with curcumin did not have a synergistic effect on normal human skin fibroblasts and normal human mesangial cells. Taken together, combined treatment with NVP-BEZ235 and curcumin induces apoptosis through p53-dependent Bcl-2 mRNA down-regulation at the transcriptional level and Mcl-1 protein down-regulation at the post-transcriptional level.

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Citation:  
Das L, Vinayak M. (2014, Jun 16). Long Term Effect of Curcumin in Regulation of Glycolytic Pathway and Angiogenesis via Modulation of Stress Activated Genes in Prevention of Cancer. PLoS ONE 9(6): e99583. doi: 10.1371/journal.pone.0099583

AbstractOxidative stress, an important factor in modulation of glycolytic pathway and induction of stress activated genes, is further augmented due to reduced antioxidant defense system, which promotes cancer progression via inducing angiogenesis. Curcumin, a naturally occurring chemopreventive phytochemical, is reported to inhibit carcinogenesis in various experimental animal models. However, the underlying mechanism involved in anticarcinogenic action of curcumin due to its long term effect is still to be reported because of its rapid metabolism, although metabolites are accumulated in tissues and remain for a longer time. Therefore, the long term effect of curcumin needs thorough investigation. The present study aimed to analyze the anticarcinogenic action of curcumin in liver, even after withdrawal of treatment in Dalton's lymphoma bearing mice. Oxidative stress observed during lymphoma progression reduced antioxidant enzyme activities, and induced angiogenesis as well as activation of early stress activated genes and glycolytic pathway. Curcumin treatment resulted in activation of antioxidant enzyme super oxide dismutase and down regulation of ROS level as well as activity of ROS producing enzyme NADPH:oxidase, expression of stress activated genes HIF-1α, cMyc and LDH activity towards normal level. Further, it lead to significant inhibition of angiogenesis, observed via MMPs activity, PKCα and VEGF level, as well as by matrigel plug assay. Thus findings of this study conclude that the long term effect of curcumin shows anticarcinogenic potential via induction of antioxidant defense system and inhibition of angiogenesis via down regulation of stress activated genes and glycolytic pathway in liver of lymphoma bearing mice.

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Citation:  
Shakibaei M, Buhrmann C, Kraehe P, Shayan P, Lueders C, et al. (2014, Jan 3). Curcumin Chemosensitizes 5-Fluorouracil Resistant MMR-Deficient Human Colon Cancer Cells in High Density Cultures. PLoS ONE 9(1): e85397. doi: 10.1371/journal.pone.0085397

Abstract 

Objective
Treatment of colorectal cancer (CRC) remains a clinical challenge, as more than 15% of patients are resistant to 5-Fluorouracil (5-FU)-based chemotherapeutic regimens, and tumor recurrence rates can be as high as 50–60%. Cancer stem cells (CSC) are capable of surviving conventional chemotherapies that permits regeneration of original tumors. Therefore, we investigated the effectiveness of 5-FU and plant polyphenol (curcumin) in context of DNA mismatch repair (MMR) status and CSC activity in 3D cultures of CRC cells.

Methods
High density 3D cultures of CRC cell lines HCT116, HCT116+ch3 (complemented with chromosome 3) and their corresponding isogenic 5-FU-chemo-resistant derivative clones (HCT116R, HCT116+ch3R) were treated with 5-FU either without or with curcumin in time- and dose-dependent assays.

Results
Pre-treatment with curcumin significantly enhanced the effect of 5-FU on HCT116R and HCR116+ch3R cells, in contrast to 5-FU alone as evidenced by increased disintegration of colonospheres, enhanced apoptosis and by inhibiting their growth. Curcumin and/or 5-FU strongly affected MMR-deficient CRC cells in high density cultures, however MMR-proficient CRC cells were more sensitive. These effects of curcumin in enhancing chemosensitivity to 5-FU were further supported by its ability to effectively suppress CSC pools as evidenced by decreased number of CSC marker positive cells, highlighting the suitability of this 3D culture model for evaluating CSC marker expression in a close to vivo setting.

Conclusion
Our results illustrate novel and previously unrecognized effects of curcumin in enhancing chemosensitization to 5-FU-based chemotherapy on DNA MMR-deficient and their chemo-resistant counterparts by targeting the CSC sub-population.

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Citation: 
Meng J, Li Y, Camarillo C, Yao Y, Zhang Y, et al. (2014, Jan 7). The Anti-Tumor Histone Deacetylase Inhibitor SAHA and the Natural Flavonoid Curcumin Exhibit Synergistic Neuroprotection against Amyloid-Beta Toxicity. PLoS ONE 9(1): e85570. doi: 10.1371/journal.pone.0085570

AbstractWith the trend of an increasing aged population worldwide, Alzheimer's disease (AD), an age-related neurodegenerative disorder, as one of the major causes of dementia in elderly people is of growing concern. Despite the many hard efforts attempted during the past several decades in trying to elucidate the pathological mechanisms underlying AD and putting forward potential therapeutic strategies, there is still a lack of effective treatments for AD. The efficacy of many potential therapeutic drugs for AD is of main concern in clinical practice. For example, large bodies of evidence show that the anti-tumor histone deacetylase (HDAC) inhibitor, suberoylanilidehydroxamic acid (SAHA), may be of benefit for the treatment of AD; however, its extensive inhibition of HDACs makes it a poor therapeutic. Moreover, the natural flavonoid, curcumin, may also have a potential therapeutic benefit against AD; however, it is plagued by low bioavailability. Therefore, the integrative effects of SAHA and curcumin were investigated as a protection against amyloid-beta neurotoxicity in vitro. We hypothesized that at low doses their synergistic effect would improve therapeutic selectivity, based on experiments that showed that at low concentrations SAHA and curcumin could provide comprehensive protection against Aβ_25–35-induced neuronal damage in PC12 cells, strongly implying potent synergism. Furthermore, network analysis suggested that the possible mechanism underlying their synergistic action might be derived from restoration of the damaged functional link between Akt and the CBP/p300 pathway, which plays a crucial role in the pathological development of AD. Thus, our findings provided a feasible avenue for the application of a synergistic drug combination, SAHA and curcumin, in the treatment of AD.

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Citation:  
Radhakrishnan VM, Kojs P, Young G, Ramalingam R, Jagadish B, et al. (2014, Jan 22). pTyr421 Cortactin Is Overexpressed in Colon Cancer and Is Dephosphorylated by Curcumin: Involvement of Non-Receptor Type 1 Protein Tyrosine Phosphatase (PTPN1). PLoS ONE 9(1): e85796. doi: 10.1371/journal.pone.0085796

AbstractCortactin (CTTN), first identified as a major substrate of the Src tyrosine kinase, actively participates in branching F-actin assembly and in cell motility and invasion. CTTN gene is amplified and its protein is overexpressed in several types of cancer. The phosphorylated form of cortactin (pTyr⁴²¹) is required for cancer cell motility and invasion. In this study, we demonstrate that a majority of the tested primary colorectal tumor specimens show greatly enhanced expression of pTyr⁴²¹-CTTN, but no change at the mRNA level as compared to healthy subjects, thus suggesting post-translational activation rather than gene amplification in these tumors. Curcumin (diferulolylmethane), a natural compound with promising chemopreventive and chemosensitizing effects, reduced the indirect association of cortactin with the plasma membrane protein fraction in colon adenocarcinoma cells as measured by surface biotinylation, mass spectrometry, and Western blotting. Curcumin significantly decreased the pTyr⁴²¹-CTTN in HCT116 cells and SW480 cells, but was ineffective in HT-29 cells. Curcumin physically interacted with PTPN1 tyrosine phosphatases to increase its activity and lead to dephosphorylation of pTyr⁴²¹-CTTN. PTPN1 inhibition eliminated the effects of curcumin on pTyr⁴²¹-CTTN. Transduction with adenovirally-encoded CTTN increased migration of HCT116, SW480, and HT-29. Curcumin decreased migration of HCT116 and SW480 cells which highly express PTPN1, but not of HT-29 cells with significantly reduced endogenous expression of PTPN1. Curcumin significantly reduced the physical interaction of CTTN and pTyr⁴²¹-CTTN with p120 catenin (CTNND1). Collectively, these data suggest that curcumin is an activator of PTPN1 and can reduce cell motility in colon cancer via dephosphorylation of pTyr⁴²¹-CTTN which could be exploited for novel therapeutic approaches in colon cancer therapy based on tumor pTyr⁴²¹-CTTN expression.
  

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Citation:  
Zhu W, Cromie MM, Cai Q, Lv T, Singh K, et al. (2014, Mar 24). Curcumin and Vitamin E Protect against Adverse Effects of Benzo[a]pyrene in Lung Epithelial Cells. PLoS ONE 9(3): e92992. doi: 10.1371/journal.pone.0092992

AbstractBenzo[a]pyrene (BaP), a well-known environmental carcinogen, promotes oxidative stress and DNA damage. Curcumin and vitamin E (VE) have potent antioxidative activity that protects cells from oxidative stress and cellular damage. The objectives of the present study were to investigate the adverse effects of BaP on normal human lung epithelial cells (BEAS-2B), the potential protective effects of curcumin and VE against BaP-induced cellular damage, and the molecular mechanisms of action. MTT assay, flow cytometry, fluorescence microplate assay, HPLC, qRT-PCR, and western blot were performed to analyze cytotoxicity, cell cycle, reactive oxygen species (ROS), BaP diol-epoxidation (BPDE)-DNA adducts, gene expression, and protein expression, respectively. Curcumin or VE prevented cells from BaP-induced cell cycle arrest and growth inhibition, significantly suppressed BaP-induced ROS levels, and decreased BPDE-DNA adducts. While CYP1A1 and 1B1 were induced by BaP, these inductions were not significantly reduced by curcumin or VE. Moreover, the level of activated p53 and PARP-1 were significantly induced by BaP, whereas this induction was markedly reduced after curcumin and VE co-treatment. Survivin was significantly down-regulated by BaP, and curcumin significantly restored survivin expression in BaP-exposed cells. The ratio of Bax/Bcl-2 was also significantly increased in cells exposed to BaP and this increase was reversed by VE co-treatment. Taken together, BaP-induced cytotoxicity occurs through DNA damage, cell cycle arrest, ROS production, modulation of metabolizing enzymes, and the expression/activation of p53, PARP-1, survivin, and Bax/Bcl-2. Curcumin and VE could reverse some of these BaP-mediated alterations and therefore be effective natural compounds against the adverse effects of BaP in lung cells.

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Citation:  
Zheng L, Sun X, Zhu X, Lv F, Zhong Z, et al. (2014, Mar 27). Apoptosis of THP-1 Derived Macrophages Induced by Sonodynamic Therapy Using a New Sonosensitizer Hydroxyl Acetylated Curcumin. PLoS ONE 9(3): e93133. doi: 10.1371/journal.pone.0093133

AbstractCurcumin is extracted from the rhizomes of the traditional Chinese herb Curcuma longa. Our previous study indicated curcumin was able to function as a sonosensitizer. Hydroxyl acylated curcumin was synthesized from curcumin to eliminate the unstable hydroxy perssad in our group. The potential use of Hydroxyl acylated curcumin as a sonosensitizer for sonodynamic therapy (SDT) requires further exploration. This study investigated the sonodynamic effect of Hydroxyl acylated curcumin on THP-1 macrophage. THP-1 macrophages were cultured with Hydroxyl acylated curcumin at a concentration of 5.0 μg/mL for 4 hours and then exposed to pulse ultrasound irradiation (0.5 W/cm² with 1.0 MHz ) for 5 min, 10 min and 15 min. Six hours later, cell viability decreased significantly by CCK-8 assay. After ultrasound irradiation, the ratio of apoptosis and necrosis in SDT group was higher than that in control, Hydroxyl acylated curcumin alone and ultrasound alone. Moreover, the apoptotic rate was higher than necrotic rate with the flow cytometry analysis. Furthermore, Hydroxyl acylated curcumin-SDT induced reactive oxygen species (ROS) generation in THP-1 macrophages immediately after the ultrasound treatment while ROS generation was reduced significantly with the scavenger of singlet oxygen Sodium azide (NaN₃). Hydroxyl acylated curcumin-SDT led to a conspicuous loss of mitochondrial membrane potential (MMP) compared with other groups, while MMP was increased significantly with the scavenger of singlet oxygen Sodium azide (NaN₃), ROS inhibitor N-acetyl cysteine (NAC) and Mitochondrial Permeability Transition Pore (MPTP) inhibitor Cyclosporin A (CsA). The cytochrome C, cleaved-Caspase-9, cleaved-Caspase-3 and cleaved-PARP upregulated after SDT through Western blotting. These findings suggested that Hydroxyl acylated curcumin under low-intensity ultrasound had sonodynamic effect on THP-1 macrophages via generation of intracellular singlet oxygen and mitochondria-caspase signaling pathway, indicating that Hydroxyl acylated curcumin could be used as a novel sonosensitizer in SDT for atherosclerosis.

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Citation: 
Kumar B, Yadav A, Hideg K, Kuppusamy P, Teknos TN, et al. (2014, Mar 27). A Novel Curcumin Analog (H-4073) Enhances the Therapeutic Efficacy of Cisplatin Treatment in Head and Neck Cancer. PLoS ONE 9(3): e93208. doi: 10.1371/journal.pone.0093208

AbstractChemotherapy constitutes the standard modality of treatment for localized head and neck squamous cell carcinomas (HNSCC). However, many patients fail to respond and relapse after this treatments due to the acquisition of chemo-resistance. Therefore, there is an urgent need to develop novel drugs that could reverse the resistant phenotype. Curcumin, the constituent of the spice turmeric has been shown to have anti-inflammatory, anti-oxidant and anti-proliferative properties in several tumor types. However, use of curcumin has been limited due to its poor bio-absorption. Recently, a novel class of curcumin analogs, based on diarylidenylpiperidones (DAP), has been developed by incorporating a piperidone link to the beta-diketone structure and fluoro substitutions on the phenyl groups. In this study, we evaluated the effectiveness of H-4073, a parafluorinated variant of DAP, using both in vitro and in vivo head and neck cancer models. Our results demonstrate that H-4073 is a potent anti-tumor agent and it significantly inhibited cell proliferation in all the HNSCC cell lines tested in a dose-dependent manner. In addition, pretreatment of cisplatin-resistant HNSCC cell lines with H-4073 significantly reversed the chemo-resistance as observed by cell viability assay (MTT), apoptosis assay (Annexin V binding) and cleaved caspase-3 (Western blot). H-4073 mediated its anti-tumor effects by inhibiting JAK/STAT3, FAK, Akt and VEGF signaling pathways that play important roles in cell proliferation, migration, survival and angiogenesis. In the SCID mouse xenograft model, H-4073 significantly enhanced the anti-tumor and anti-angiogenesis effects of cisplatin, with no added systemic toxicity. Interestingly, H-4073 inhibited tumor angiogenesis by blocking VEGF production by tumor cells as well as directly inhibiting endothelial cell function. Taken together, our results suggest that H-4073 is a potent anti-tumor agent and it can be used to overcome chemotherapy resistance in HNSCC.

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Citation: 
Malhotra A, Nair P, Dhawan DK (2014, Apr 4). Study to Evaluate Molecular Mechanics behind Synergistic Chemo-Preventive Effects of Curcumin and Resveratrol during Lung Carcinogenesis. PLoS ONE 9(4): e93820. doi: 10.1371/journal.pone.0093820

Abstract

Background
The combination approach is the future of the war against cancer and the present study evaluated molecular mechanics behind the synergistic effects of curcumin and resveratrol during lung carcinogenesis.

MethodsThe mice were segregated into five groups which included normal control, Benzo[a]pyrene[BP] treated, BP+curcumin treated, BP+resveratrol treated and BP+curcumin+resveratrol treated.

ResultsThe morphological analyses of tumor nodules confirmed lung carcinogenesis in mice after 22 weeks of single intra-peritoneal[i.p] injection of BP at a dose of 100 mg/Kg body weight. The BP treatment resulted in a significant increase in the protein expressions of p53 in the BP treated mice. Also, a significant increase in the protein expression of phosphorylated p53[ser15] confirmed p53 hyper-phosphorylation in BP treated mice. On the other hand, enzyme activities of caspase 3 and caspase 9 were noticed to be significantly decreased following BP treatment. Further, radiorespirometric studies showed a significant increase in the ¹⁴C-glucose turnover as well as ¹⁴C-gulcose uptake in the lung slices of BP treated mice. Moreover, a significant rise in the cell proliferation was confirmed indirectly by enhanced uptake of ³H-thymidine in the lung slices of BP treated mice. Interestingly, combined treatment of curcumin and resveratrol to BP treated animals resulted in a significant decrease in p53 hyper-phosphorylation, ¹⁴C glucose uptakes/turnover and ³H-thymidine uptake in the BP treated mice. However, the enzyme activities of caspase 3 and caspase 9 showed a significant increase upon treatment with curcumin and resveratrol.

ConclusionThe study, therefore, concludes that molecular mechanics behind chemo-preventive synergism involved modulation of p53 hyper-phosphorylation, regulation of caspases and cellular metabolism enzymes.

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Citation: 
Kalinski T, Sel S, Hütten H, Röpke M, Roessner A, et al. (2014, Jun 5). Curcumin Blocks Interleukin-1 Signaling in Chondrosarcoma Cells. PLoS ONE 9(6): e99296. doi: 10.1371/journal.pone.0099296

AbstractInterleukin (IL)-1 signaling plays an important role in inflammatory processes, but also in malignant processes. The essential downstream event in IL-1 signaling is the activation of nuclear factor (NF)-κB, which leads to the expression of several genes that are involved in cell proliferation, invasion, angiogenesis and metastasis, among them VEGF-A. As microenvironment-derived IL-1β is required for invasion and angiogenesis in malignant tumors, also in chondrosarcomas, we investigated IL-1β-induced signal transduction and VEGF-A expression in C3842 and SW1353 chondrosarcoma cells. We additionally performed in vitro angiogenesis assays and NF-κB-related gene expression analyses. Curcumin is a substance which inhibits IL-1 signaling very early by preventing the recruitment of IL-1 receptor associated kinase (IRAK) to the IL-1 receptor. We demonstrate that IL-1 signaling and VEGF-A expression are blocked by Curcumin in chondrosarcoma cells. We further show that Curcumin blocks IL-1β-induced angiogenesis and NF-κB-related gene expression. We suppose that IL-1 blockade is an additional treatment option in chondrosarcoma, either by Curcumin, its derivatives or other IL-1 blocking agents.

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These last two studies are not cancer-related - one looks at pain and the other looks at spinal cord injury.

Citation:  
Zhu X, Li Q, Chang R, Yang D, Song Z, et al. (2014, Mar 6). Curcumin Alleviates Neuropathic Pain by Inhibiting p300/CBP Histone Acetyltransferase Activity-Regulated Expression of BDNF and Cox-2 in a Rat Model. PLoS ONE 9(3): e91303. doi: 10.1371/journal.pone.0091303

AbstractThe management of neuropathic pain is still a major challenge because of its unresponsiveness to most common treatments. Curcumin has been reported to play an active role in the treatment of various neurological disorders, such as neuropathic pain. Curcumin has long been recognized as a p300/CREB-binding protein (CBP) inhibitor of histone acetyltransferase (HAT) activity. However, this mechanism has never been investigated for the treatment of neuropathic pain with curcumin. The aim of the present study was to investigate the anti-nociceptive role of curcumin in the chronic constriction injury (CCI) rat model of neuropathic pain. Furthermore, with this model we investigated the effect of curcumin on P300/CBP HAT activity-regulated release of the pro-nociceptive molecules, brain-derived neurotrophic factor (BDNF) and cyclooxygenase-2 (Cox-2). Treatment with 40 and 60 mg/kg body weight curcumin for 7 consecutive days significantly attenuated CCI-induced thermal hyperalgesia and mechanical allodynia, whereas 20 mg/kg curcumin showed no significant analgesic effect. Chromatin immunoprecipitation analysis revealed that curcumin dose-dependently reduced the recruitment of p300/CBP and acetyl-Histone H3/acetyl-Histone H4 to the promoter of BDNF and Cox-2 genes. A similar dose-dependent decrease of BDNF and Cox-2 in the spinal cord was also observed after curcumin treatment. These results indicated that curcumin exerted a therapeutic role in neuropathic pain by down-regulating p300/CBP HAT activity-mediated gene expression of BDNF and Cox-2.

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Citation:  
Ormond DR, Shannon C, Oppenheim J, Zeman R, Das K, et al. (2014, Feb 18). Stem Cell Therapy and Curcumin Synergistically Enhance Recovery from Spinal Cord Injury. PLoS ONE 9(2): e88916. doi: 10.1371/journal.pone.0088916

AbstractAcute traumatic spinal cord injury (SCI) is marked by the enhanced production of local cytokines and pro-inflammatory substances that induce gliosis and prevent reinnervation. The transplantation of stem cells is a promising treatment strategy for SCI. In order to facilitate functional recovery, we employed stem cell therapy alone or in combination with curcumin, a naturally-occurring anti-inflammatory component of turmeric (Curcuma longa), which potently inhibits NF-κB. Spinal cord contusion following laminectomy (T9–10) was performed using a weight drop apparatus (10 g over a 12.5 or 25 mm distance, representing moderate or severe SCI, respectively) in Sprague-Dawley rats. Neural stem cells (NSC) were isolated from subventricular zone (SVZ) and transplanted at the site of injury with or without curcumin treatment. Functional recovery was assessed by BBB score and body weight gain measured up to 6 weeks following SCI. At the conclusion of the study, the mass of soleus muscle was correlated with BBB score and body weight. Stem cell therapy improved recovery from moderate SCI, however, it had a limited effect on recovery after severe SCI. Curcumin stimulated NSC proliferation in vitro, and in combination with stem cell therapy, induced profound recovery from severe SCI as evidenced by improved functional locomotor recovery, increased body weight, and soleus muscle mass. These findings demonstrate that curcumin in conjunction with stem cell therapy synergistically improves recovery from severe SCI. Furthermore, our results indicate that the effect of curcumin extends beyond its known anti-inflammatory properties to the regulation of stem cell proliferation.

Empathy for Social Exclusion Involves the Sensory-Discriminative Component of Pain

 

In a new article in the journal Social, Cognitive, Affective Neuroscience has identified the mechanism by which we tend to feel pain when we empathize with those who have been socially excluded. Here is a brief summary of the research:

[A]n ecologically valid experience of social exclusion recruits areas coding the somatosensory components of physical pain (posterior insular cortex, and secondary somatosensory cortex). Furthermore, we show that this pattern of activation not only holds for directly experienced social pain, but also during empathy for social pain. Finally, we report that subgenual cingulate cortex is the only brain area conjointly active during empathy for physical and social pain.

The authors feels that this new finding supports recent theories that affective processing and homeostatic regulation are at the core of empathic responses.

The original article is available online as a PDF, and below I have posted the abstract and then a summary of the research from Medical News Today.

Full Citation:
Novembre G, Zanon M, and Silani G. (2014, Feb 21). Empathy for social exclusion involves the sensory-discriminative component of pain: a within-subject fMRI study. Social Cognitive Affective Neuroscience. [Epub ahead of print]

Empathy for social exclusion involves the sensory-discriminative component of pain: a within-subject fMRI study

G Novembre, M Zanon, and G Silani

To whom correspondence should be addressed. Dr. Giorgia Silani, Cognitive Neuroscience Sector, International School for Advanced Studies, SISSA-ISAS, Via Bonomea 265, 34136, Trieste, Italy, Tel. +39 040 3878 611, Email: gsilani@sissa.it

Abstract

Recent research has shown that experiencing events that represent a significant threat to social bonds activates a network of brain areas associated with the sensory-discriminative aspects of pain (Kross et al., 2011). In the present study we investigated whether the same brain areas are involved when witnessing social exclusion threats experienced by others. Using a within-subject design, we show that an ecologically valid experience of social exclusion recruits areas coding the somatosensory components of physical pain (posterior insular cortex, and secondary somatosensory cortex). Furthermore, we show that this pattern of activation not only holds for directly experienced social pain, but also during empathy for social pain. Finally, we report that subgenual cingulate cortex is the only brain area conjointly active during empathy for physical and social pain. This supports recent theories that affective processing and homeostatic regulation are at the core of empathic responses.

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Feeling of social pain or empathy for others 'causes physical pain'

Written by Honor Whiteman
Monday 3 March 2014

We all have friends that we cherish. Some can be as close to us as our own family. Now, new research suggests that if a bond with a friend is threatened or lost, we see a friend in distress, or we become excluded socially, these experiences can cause us to feel physical pain.

This is according to a study published in the journal Social Cognitive and Affective Neuroscience.

The research team, from the International School for Advance Studies (SISSA) in Italy, conducted a series of experiments on a group of participants, during which their brain activity was measured using functional magnetic resonance imaging (fMRI).

The investigators say the way they conducted this study is innovative, compared with previous research looking at the association between social and physical pain.

"Classic experiments used a stylized procedure in which social exclusion situations were simulated by cartoons. We suspected that this simplification was excessive and likely to lead to systematic biases in data collection, so we used real people in videos," explains study author Giorgia Silani.

One of the experiments involved a game in which subjects tossed a ball to each other, but one of the players was deliberately excluded by the others. Either a player was excluded his or herself, or a friend was excluded to trigger a condition of social pain.

In another experiment, a participant or the friend of a participant received a mildly painful stimulus. Each participant was a witness to their friend's experience and this triggered the condition of physical pain.

Social pain in ourselves and others triggers physical pain

The researchers found that both conditions activated the posterior insular cortex of the brain - the region linked to the sensory processing of physical pain. Interestingly, this region of the brain was activated whether a person experienced the social or physical pain conditions themselves, or witnessed a friend experiencing both conditions.

According to the investigators, the feeling of social pain guides our behavior. They explain that a person's ultimate goal is to "prioritize escape, recovery and healing," which is why we feel social pain and are able to empathize when others experience it.

Commenting on the research, study author Giorgia Silani says:

"Our findings lend support to the theoretical model of empathy that explains involvement in other people's emotions by the fact that our representation is based on the representation of our own emotional experience in similar conditions."

This is not the first study to suggest that we can feel the pain of others. Last year, Medical News Today reported on a study showing that when a spouse experiences chronic pain, the other spouse may be affected by lack of sleep and may even develop health problems. 

Gee, ya think?

In my experience, almost all addictions begin as attempts to self-medicate pain, sometimes physical but often emotional. This is why I don't buy into the "disease model" of addiction.

However, what these researchers are suggesting is a little different. After the first high, which if you ask most addicts was the best high, they are no longer seeking a high as much as trying to avoid the pain of not being high. What they don't mention here is that over time it takes more and more drug to get near the desired original high, but it's nearly impossible to ever reach that state again because the brain is forever altered with the first administration of the drug.

Anyway, this is still interesting research.

Full Citation: 
Peraile, I, Granado, N, Torres, E, Gutiérrez-López, MD, Moratalla, R, Colado, MI, O’Shea, E. (2013, Nov). Cocaine potentiates MDMA-induced oxidative stress but not dopaminergic neurotoxicity in mice: implications for the pathogenesis of free radical-induced neurodegenerative disorders. Psychopharmacology, 230 (1): 125 DOI: 10.1007/s00213-013-3142-5

Addicts May Be Seeking Relief from Emotional Lows More Than Euphoric Highs

Nov. 6, 2013 — Cocaine addicts may become trapped in drug binges -- not because of the euphoric highs they are chasing but rather the unbearable emotional lows they desperately want to avoid.

In a study published today online in Psychopharmacology, Rutgers University Behavioral and Systems Neuroscience Professor Mark West, and doctoral student David Barker in the Department of Psychology, in the School of Arts and Sciences, challenge the commonly held view that drug addiction occurs because users are always going after the high. Based on new animal studies, they discovered that the initial positive feelings of intoxication are short lived -- quickly replaced by negative emotional responses whenever drug levels begin to fall.

If these animal models are a mirror into human addiction, Rutgers researchers say that addicts who learned to use drugs to either achieve a positive emotional state or to relieve a negative one are vulnerable to situations that trigger either behavior.

"Our results suggest that once the animals started a binge, they may have felt trapped and didn't like it," said West. "This showed us that negative emotions play an equal, if not more important role in regulating cocaine abuse."

In their study, Rutgers researchers detected high-pitched calls made by laboratory rats when they had the opportunity at the beginning of the six-hour drug binge to self-administer cocaine and rapidly raise their internal drug levels. After that, positive and negative emotions collided and the high-pitched euphoric calls emitted in the beginning of the experiment were absent even though the cocaine usage continued at the same level for several hours. The only time during the rest of the binge that researchers detected any calls was when drug level fell below the level animals wanted, which triggered lower-pitched calls associated with negative feelings.

"We see all the positive, high-pitched calls in the first 35-40 minutes," said Barker. "Then if the animals are kept at their desired level you don't observe either positive or negative calls. But as soon as the drug level starts to fall off, they make these negative calls."

The Rutgers researchers say this animal study may lead to a better understanding of human addiction -- alcohol, tobacco and food -- as well as substance abuse. The reason animal studies are critical in addiction research, they say, is that human responses are not always reliable. Individuals may be too embarrassed to answer truthfully or may just tell the scientist what they think he or she wants to hear.

"It's not that human studies aren't important, they certainly are," said West. "But with these animal studies it is clear that we should be placing just as much importance on the negative as being a trigger for drug abuse and deal with that as well."

Here is the full abstract of the article (which seems to not have been at all about way addiction occurs - the findings discussed above are provenance):

Abstract

Rationale

The drugs of abuse 3,4-methylenedioxymethamphetamine (MDMA; “ecstasy”) and cocaine both increase the generation of free radicals, and in the case of MDMA, this increase in oxidative stress is involved in the dopaminergic neurotoxicity produced by the drug in mice. Oxidative stress processes are also involved in the pathogenesis of several neurodegenerative diseases.

Objectives

We aimed to determine the consequences of the combined administration of MDMA and cocaine on oxidative stress and dopaminergic neurotoxicity.

Methods

Mice received MDMA (20 mg/kg, i.p.; two doses separated by 3 h) followed by cocaine 1, 3, 6, or 24 h after the second MDMA dose. Mice were killed between 1 h and 7 days after cocaine injection.

Results

MDMA decreased dopamine transporter density and dopamine concentration 7 days later. Cocaine did not alter this neurotoxicity. MDMA produced an increase in the concentration of 2,3-dihydroxybenzoic acid in striatal microdialysis samples and an increase in lipid peroxidation in the striatum which were potentiated by cocaine. MDMA and cocaine given together also increased nitrate and 3-nitrotyrosine levels compared with either drug given alone. On the other hand, MDMA increased superoxide dismutase activity and decreased catalase activity, changes which were prevented by cocaine administration. In addition, cocaine administration produced an increase in glutathione peroxidase (GPx) activity in both saline-treated and MDMA-treated mice.

Conclusions

Cocaine potentiates MDMA-induced oxidative stress but does not produce an increase in the neurotoxicity produced by MDMA, and this lack of potentiation may involve an increase in GPx activity.

A Randomized Controlled Trial of Internal Family Systems-based Psychotherapy for Rheumatoid Arthritis

In a first-of-its-kind "Proof-of-Concept" study, a group of therapists (including IFS founder Richard Schwartz) implemented Internal Family Systems therapy with people who have rheumatoid arthritis. Participants (N=39, 40 controls) were assessed every three months for the length of the study (9 months) and then one year later. They were assessed for self-assessed joint pain (RA Disease Activity Index joint score), Short Form-12 physical function score, visual analog scale for overall pain, and mental health status (Beck Depression Inventory, and State Trait Anxiety Inventory).

The results demonstrated post-treatment improvements for the IFS group (more than the control group) in overall pain [mean treatment effects –14.9 (29.1 SD); p = 0.04], and physical function [14.6 (25.3); p = 0.04]. Post-treatment improvements were still present one year later in self-assessed joint pain [–0.6 (1.1); p = 0.04], self-compassion [1.8 (2.8); p = 0.01], and depressive symptoms [–3.2 (5.0); p =0.01].

These are promising results that demonstrate a psychotherapeutic intervention for auto-immune disorders may be ad effective (or more so) than pharmacological interventions, which tend to have serious and somethings disastrous side effects.

The article is being offered Open Access by the Journal of Rheumatology.


Full Citation:
Shadick, NA, Sowell, NF, Frits, ML, Hoffman, SM, et al. (2013, Aug 15). A Randomized Controlled Trial of an Internal Family Systems-based Psychotherapeutic Intervention on Outcomes in Rheumatoid Arthritis: A Proof-of-Concept Study. Journal of Rheumatology, 40(9), 11 pgs. doi:10.3899/jrheum.121465 Clinical Trials.gov identifier: NCT00869349. 

A Randomized Controlled Trial of an Internal Family Systems-based Psychotherapeutic Intervention on Outcomes in Rheumatoid Arthritis: A Proof-of-Concept Study

Nancy A. Shadick, Nancy F. Sowell, Michelle L. Frits, Suzanne M. Hoffman, Shelley A. Hartz, Fran D. Booth, Martha Sweezy, Patricia R. Rogers, Rina L. Dubin, Joan C. Atkinson, Amy L. Friedman, Fernando Augusto, Christine K. Iannaccone, Anne H. Fossel, Gillian Quinn, Jing Cui, Elena Losina, and Richard C. Schwartz 

ABSTRACT

Objective
 
To conduct a proof-of-concept randomized trial of an Internal Family Systems (IFS)
psychotherapeutic intervention on rheumatoid arthritis (RA) disease activity and psychological status.

Methods
 
Patients with RA were randomized to either an IFS group for 9 months (n = 39) or an education (control) group (n = 40) that received mailed materials on RA symptoms and management. The groups were evaluated every 3 months until intervention end and 1 year later. Self-assessed joint pain (RA Disease Activity Index joint score), Short Form-12 physical function score, visual analog scale for overall pain and mental health status (Beck Depression Inventory, and State Trait Anxiety Inventory) were assessed. The 28-joint Disease Activity Score-C-reactive Protein 4 was determined by rheumatologists blinded to group assignment. Treatment effects were estimated by between-group differences, and mixed model repeated measures compared trends between study arms at 9 months and 1 year after intervention end.
 
Results

Of 79 participants randomized, 68 completed the study assessments and 82% of the IFS group completed the protocol. Posttreatment improvements favoring the IFS group  occurred in overall pain [mean treatment effects –14.9 (29.1 SD); p = 0.04], and physical function [14.6 (25.3); p = 0.04]. Posttreatment improvements were sustained 1 year later in self-assessed joint pain [–0.6 (1.1); p = 0.04], self-compassion [1.8 (2.8); p = 0.01], and depressive symptoms [–3.2 (5.0); p =0.01]. There were no sustained improvements in anxiety, self-efficacy, or disease activity.
 
Conclusion
 
An IFS-based intervention is feasible and acceptable to patients with RA and may complement medical management of the disease. Future efficacy trials are warranted.


Despite effective pharmacotherapy, many individuals with rheumatoid arthritis (RA) suffer ongoing pain and disability. Living with RA can lead to depression, anxiety, isolation, an overall impaired quality of life [1,2], and increased healthcare resource use [3]. Psychotherapeutic interventions that improve disease activity, pain-related symptoms, and psychological function would be helpful to patients living with this disease. 

A number of psychobehavioral interventions have been shown to be effective in improving coping efficacy and other outcomes in patients with RA [4-11]. Cognitive behavioral interventions, in particular, have reduced pain, joint inflammation, physical disability, and depression [5,6,9,10]. The improvements are variable according to the type of intervention, tend to be most effective in newly diagnosed patients, and have limited sustainability [6,9]. For example, effect sizes (ES) for pain and disability in 2 metaanalyses of psychological interventions for RA were modest [12,13]. Also, joint inflammation and swelling were reduced by several interventions, but these results were mostly seen in patients with illness of shorter duration [13]. In a Cochrane review assessing the effectiveness of educational programs for RA, there were positive effects on disability, joint counts, patient global assessments, psychological status, and depression, but the improvements were short-lived [14]. A sustainable intervention that affects disease activity in individuals with longer-term illness could improve patients’ lives. 

The Internal Family Systems (IFS) model is a rapidly emerging individual psychotherapeutic modality developed by Schwartz [15] that teaches patients to attend to and interact with their internal experience mindfully. The model actively recruits self-compassion toward an individual’s parts, conceptualized as subpersonalities that are manifested by strong feelings, judgments, or physical sensations. By fostering an internal dialogue with polarized thinking, IFS reduces emotional intensity and dysregulation; elements that have been shown to increase pain perception [16] and disease activity in RA [4,17]. IFS also uses nonjudgmental noticing and active mindfulness.  Mindfulness-based interventions have been helpful in a number of painful conditions including RA [4,7,18]. To date, more than 2200 therapists worldwide have been trained in the IFS modality [19]. This technique is increasingly being used as adjunctive therapy for certain medical conditions, with anecdotal benefit reported in migraines, back pain, and multiple sclerosis. To our knowledge, our study is the first to evaluate the IFS model’s feasibility, acceptability, and potential efficacy in a randomized trial.

New Research in Psychopathy, Moral Decision-Making, and Empathy

Two new studies offer deeper insight into psychopathy, both from the open access journal, Frontiers in Human Neuroscience.

The first one suggests that people high in psychopathic traits - specifically, those related to affective deficit - do not lack moral judgment, but they tend to exhibit greater utilitarianism in choice of action.

Here is their definition of psychopathy, just to set the stage for these two studies:

Psychopathy is a personality disorder characterized by emotional dysfunction, callousness, manipulativeness, reduced guilt, remorse and empathy, egocentricity, and antisocial behavior including impulsivity and poor behavioral control. Moreover, psychopaths frequently engage in morally inappropriate behavior, including taking advantage of others, lying, cheating, and abandoning relationships (Cleckley, 1941; Hare, 1999).

The authors believe that their study lends support to the idea that moral judgment and moral choice/action operate in different brain circuits.

The second study looks at two different types of psychopathy - primary and secondary - and how these traits are correlated (or not) with somatosensory resonance with others pain and with empathic response to that pain.

Primary psychopathy has been designated as the heritable traits of emotional detachment commonly reported as a lack of compassion and guilt, callous misuse of others for personal gain and failure to form close interpersonal attachment (Levenson et al., 1995; Poythress and Skeem, 2006). Secondary psychopathy usually refers to poor behavioral control, hostility and antisociality (Levenson et al., 1995).

The shared neural representations between the perception of pain in self and other (somatosensory resonance) may be the result of an "automatic resonance mechanism (Jackson et al., 2006)" that might be seen as "the lower-level of a vicarious pain response on which higher order process operate to develop empathy (Han et al., 2009; Vachon-Presseau et al., 2011)."

They investigated the impact of psychopathic traits [measured with Levenson's Self-Report Psychopathy Scale (LSRP)] on the relationship between sensorimotor resonance to other's pain and self-reported empathy. These researchers have previously shown that "a steady-state response to non-painful stimulation is modulated by the observation of other people's bodily pain. This change in somatosensory response was interpreted as a form of somatosensory gating (SG)."

Somatosensory gating is the term for how the body-brain filters relevant information out of the flood of sensory data available at any given time. They found that observing pain in others more likely triggered somatosensory gating in male college students with high psychopathic traits compared to students with low psychopathic traits.

Here is the complex part of this:

The study of Fecteau et al. (2008), in which a community sample of men was exposed to visual stimuli depicting hands in painful and non-painful scenarios, was the first to show a positive correlation between suppression of motor evoked potentials (MEPs) and the score of their participants on the Coldheartedness subscale of the psychopathic personality inventory (PPI; Lilienfeld and Andrews, 1996). This result seemed counter-intuitive because increased sensorimotor resonance to the pain of others had been positively associated with self-reported empathy (Avenanti et al., 2009). However, it was also suggested that this automatic neural response could trigger distress (Decety, 2011) and threat related networks (Ibáñez et al., 2011), therefore advocating for an alternative or concomitant view to automatic pain resonance that simply implies arousal. This would also support the view that regulation processes of sensorimotor responses are required in order to respond empathically to the pain of others (Han et al., 2009). Together, these results suggest that sensorimotor resonance to the pain of others is not a direct path to empathy and further investigation on the role of psychopathic traits could be useful to better understand this relationship.

[Emphasis added.]

As I see it, and this applies to both studies, the use of self-report empathy with correctional sample (prison inmates) is more than likely compromised in its usefulness due to the deception, manipulation, and grandiose sense of self-worth that are defining characteristics of psychopathy.

Even so, these are interesting studies - both of which can be read or downloaded by following the title link.

High levels of psychopathic traits alters moral choice but not moral judgment

Sébastien Tassy, Christine Deruelle, Julien Mancini, Samuel Leistedt, and Bruno Wicker

04 June 2013

Psychopathy is a personality disorder frequently associated with immoral behaviors. Previous behavioral studies on the influence of psychopathy on moral decision have yielded contradictory results, possibly because they focused either on judgment (abstract evaluation) or on choice of hypothetical action, two processes that may rely on different mechanisms. In this study, we explored the influence of the level of psychopathic traits on judgment and choice of hypothetical action during moral dilemma evaluation. A population of 102 students completed a questionnaire with ten moral dilemmas and nine non-moral dilemmas. The task included questions targeting both judgment (“Is it acceptable to … in order to …?”) and choice of hypothetical action (“Would you … in order to …?”). The level of psychopathic traits of each participant was evaluated with the Levenson Self-Report Psychopathy (LSRP) scale. Logistic regression fitted with the generalized estimating equations method analyses were conducted using responses to the judgment and choice tasks as the dependent variables and psychopathy scores as predictor. Results show that a high level of psychopathic traits, and more specifically those related to affective deficit, predicted a greater proportion of utilitarian responses for the choice but not for the judgment question. There was no first-order interaction between the level of psychopathic traits and other potential predictors. The relation between a high level of psychopathic traits and increased utilitarianism in choice of action but not in moral judgment may explain the contradictory results of previous studies where these two processes were not contrasted. It also gives further support to the hypothesis that choice of action endorsement and abstract judgment during moral dilemma evaluation are partially distinct neural and psychological processes. We propose that this distinction should be better taken into account in the evaluation of psychopathic behaviors.

Full Citation: 

Tassy S, Deruelle C, Mancini J, Leistedt S and Wicker B. (2013). High levels of psychopathic traits alters moral choice but not moral judgment. Frontiers in Human Neuroscience; 7:229. doi: 10.3389/fnhum.2013.00229

* * * * *

The modulation of somatosensory resonance by psychopathic traits and empathy

Louis-Alexandre Marcoux, Pierre-Emmanuel Michon, Julien I. A. Voisin, Sophie Lemelin, Etienne Vachon-Presseau, and Philip L. Jackson 

19 June 2013

A large number of neuroimaging studies have shown neural overlaps between first-hand experiences of pain and the perception of pain in others. This shared neural representation of vicarious pain is thought to involve both affective and sensorimotor systems. A number of individual factors are thought to modulate the cerebral response to other's pain. The goal of this study was to investigate the impact of psychopathic traits on the relation between sensorimotor resonance to other's pain and self-reported empathy. Our group has previously shown that a steady-state response to non-painful stimulation is modulated by the observation of other people's bodily pain. This change in somatosensory response was interpreted as a form of somatosensory gating (SG). Here, using the same technique, SG was compared between two groups of 15 young adult males: one scoring very high on a self-reported measure of psychopathic traits [60.8 ± 4.98; Levenson's Self-Report Psychopathy Scale (LSRP)] and one scoring very low (42.7 ± 2.94). The results showed a significantly greater reduction of SG to pain observation for the high psychopathic traits group compared to the low psychopathic traits group. SG to pain observation was positively correlated with affective and interpersonal facet of psychopathy in the whole sample. The high psychopathic traits group also reported lower empathic concern (EC) scores than the low psychopathic traits group. Importantly, primary psychopathy, as assessed by the LSRP, mediated the relation between EC and SG to pain observation. Together, these results suggest that increase somatosensory resonance to other's pain is not exclusively explained by trait empathy and may be linked to other personality dimensions, such as psychopathic traits.

Full Citation: 

Marcoux L-A, Michon P-E, Voisin JIA, Lemelin S, Vachon-Presseau E and Jackson PL. (2013). The modulation of somatosensory resonance by psychopathic traits and empathy. Frontiers in Human Neuroscience; 7:274. doi: 10.3389/fnhum.2013.00274

Dr. Fernando Cervero - Pain is a Complex Emotional and Sensory Experience (BSP 93)

In part one of a two-part interview, Dr. Ginger Campbell, host of the Brain Science Podcast, speaks with Dr. Fernando Cervero about his new book, Understanding Pain: Exploring the Perception of Pain. Here is the publisher's blurb to give you a sense of what you will be listening to in this interesting podcast:

If you touch something hot, it hurts. You snatch your hand away from the hot thing immediately. Obviously. But what is really happening, biologically--and emotionally? In Understanding Pain, Fernando Cervero explores the mechanisms and the meaning of pain. You touch something hot and your brain triggers a reflex action that causes you to withdraw your hand, protecting you from injury. That kind of pain, Cervero explains, is actually good for us; it acts as an alarm that warns us of danger and keeps us away from harm. 

But, Cervero tells us, not all pain is good for you. There is another kind of pain that is more like a curse: chronic pain that is not related to injury. This is the kind of pain that fills pain clinics and makes life miserable. Cervero describes current research into the mysteries of chronic pain and efforts to develop more effective treatments. Cervero reminds us that pain is the most common reason for people to seek medical attention, but that it remains a biological enigma. It is protective, but not always. Its effects are not only sensory but also emotional. There is no way to measure it objectively, no test that comes back positive for pain; the only way a medical professional can gauge pain is by listening to the patient's description of it. The idea of pain as a test of character or a punishment to be borne is changing; prevention and treatment of pain are increasingly important to researchers, clinicians, and patients. Cervero's account brings us closer to understanding the meaning of pain.

Sounds like a good book - and one that will be of interest to anyone who works with clients who may experience chronic pain, whether in a medical setting, or psycho-therapeutic setting, or in a personal training/rehab setting.

Pain is a Complex Emotional and Sensory Experience (BSP 93)
GINGER CAMPBELL, MD

Friday, January 25, 2013 at 4:00 AM

Dr. Fernando Cervero 

Dr. Fernando Cervero of McGill University has been studying pain since the beginning of his career back in the 1960's. These decades have seen tremendous advances in our neuroscientific understanding of what causes different types of pain as well as changing attitudes. Pain was once regarded as something that most people had to endure, but now most of us demand adequate pain relief, sometimes even to the point of not tolerating minor pain. Dr. Cevero's new book Understanding Pain provides an accessible account of both the history of pain research and a thoughtful consideration of the challenges facing the field.

The latest episode of the Brain Science Podcast (BSP 93) is an interview with Dr. Cervero. This is Part 1 of a planned two part series.

Listen to Episode 93

Episode Transcript (Free PDF)

Subscribe to the Brain Science Podcast:

References:

• Understanding Pain: Exploring the Perception of Pain by Fernando Cervero
• International Association for the Study of Pain
• Life Before Death (video)

Meet Dr. Campbell in Person: 

• Downtown Atlanta, Georgia February 19-21, 2013
• South by SouthWest: March 7-10, 2013 (Austin, TX, USA)
• Johannesburg, South Africa April 8,9 2013

I would love to have some listener meetups, so please drop me an email at gincampbell at mac dot com, if you will be at any of these places on the right days.

Other Announcements:

• Coming Very Soon! Completely new Brain Science Podcast website!
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Reminders:

• The earliest episodes of the Brain Science Podcast are now disappearing from iTunes but they remain freely available here. They are also available within the Brain Science Podcast app for mobile devices. By the way the mobile app has been updated and I need users to post new reviews.
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Fit Bits - Fitness News You Can Use from Exercise Etc.

Fit Bits is a monthly newsletter sent to subscribers from the folks at Exercise Etc., providers of high quality, cost effective continuing education programs to personal trainers, athletic trainers, group fitness instructors, dietitians and physical therapists, since 1993.

This is the Fit Bits research summary for August 15th, 2012.

Personal Training Careers Strong During Tough Economy

The economy is tough right now, but one career that seems be doing well despite the dismal news is personal training. From 2001 to 2011 the number of trainers working out in the field grew by 44% while the overall numbers in other field dropped by 1%.

With the obesity rate climbing, potential clients should be readily available. Fitness centers and health clubs have added about 10 million members since the recession began in 2007. However, the field has its cons. While some like a job that is not 9-5, the hours can be erratic and sparse. The median hourly wage is currently less than $15 per hour, so the pay can be a challenge. The field is not as closely regulated, so the variety in knowledge one trainer has as compared to another can vary greatly. Some states, such as New Jersey, Washington DC, Maryland, and Georgia are actually pushing for licensing laws that would require a 4 year degree in Exercise Science in order to personal train.

Right now, there are many options, but one thing to consider is that personal training is a customer service field. Human skills are important as well as the knowledge of the field.

Rampell, Catherine, "A Jobs Boom Built on Sweat in an Age of Belt-Tightening." New York Times Online. June 30, 2012.

* * * * *

Special Considerations for Exercise During Pregnancy

The biggest risk factor for maternal and fetal complications that obstetric physicians notice is being overweight during pregnancy. The mother's extra pounds increase the possibility of fetal distress, congenital abnormalities, and the need to being admitted to neonatal intensive care.

American College of Obstetrics and Gynecology (ACOG) recommends the best time for a pregnant overweight client to begin exercising is the 2nd trimester. The warm up should last 10-15 minutes of gentle activities such as stretching or slow walking. Aerobic and resistance training should follow if cleared by her physician followed by a 10-15 minute cool down.

For cardio intensity, the RPE should be 12-14 on the 6-20 Borg scale, and the frequency and intensity for the obese pregnant client should be less than the ACOG guidelines with gradual progression to the recommendations. This means to begin with 15-25 minutes of aerobic exercise 3 days per week as tolerated.Indoor activities are best to decrease fetal stress due to environmental conditions. Although the pool is fine, these women will get more metabolic benefit from weight bearing activities since the goal is to control obesity during this time frame.

Strength training should include core, lumbar, pelvis, and overall body strength although very little research has been done in this area. However the research currently out there suggests that about 15-30 minutes of strength training is beneficial especially in the control of gestational diabetes. Follow the recommendations of the physician for sets and reps.

And finally, remember to modify exercises as the pregnancy progresses and the body continues to change.

May, Linda, PhD., "Part 3: Special Considerations for Exercise During Pregnancy." American College of Sports Medicine Certified News, April – June, 2012, Vol. 22, Issue 2, pp. 4 –-5.

* * * * *

Comparisons of Clinical Pilates vs. General Exercise for Low Back Pain

With chronic low back pain (CLB) being one of the highest health care expenses, it makes sense to find ways to help clients improve pain and function.Unfortunately, the most effective type of exercise still remains elusive.

One question is, do those clients with CLB need specific exercises or will general exercises be just as effective? Researchers in Australia investigated that very thing. With 87 clients participating with a mean age of 40, each was randomly placed in a group. On group participated in Pilates where they received individualized direction-specific exercise programs prescribed by a physiotherapist. The other group participated in a general exercise program receiving generic sets of exercises that were non-specific.

Interestingly, the individualized Pilates group reported similar benefits as the general exercise group. So, Pilates is beneficial, but so are other exercises. So, it all boils down to what the client will do, what they will stick with, and what they enjoy that may benefit their back pains.

Wajswelner, H. et al., "Clinical Pilates vs. General Exercise for Chronicle Low Back Pain: Randomized Trial." ACSM Medicine and Science in Sports and Exercise, Vol. 44, No. 7, July 2012, pp. 1197-1205.

* * * * *

The Mind Body Connection: Exercise and Cognitive Function

Many of us fitness professionals try to help our clients with balance and gait to improve walking. However, more and more studies are showing that gradual deficiencies in gait can be a sign of early stage of dementia or Alzheimer's.

Researchers at the University of Calgary found that higher levels of aerobic fitness in older adults are associated with improved cognition, better ability of the oxygen to perfuse into the brain, and the blood vessels of the brain to respond to these stimuli... bottom line, better blood circulation to the brain leading to better oxygen circulation.

All of this is interesting since less than 5% of North Americans older than 60 years of age are getting the recommended 30 minutes of exercise 3-5 days per week. As the researchers state, exercise may be the least expensive, most practical way to stave off dementia while helping with other disease control as well.

So, keep an eye on your clients whose gait is changing, take a look at their activity and pay attention to their ability to remember and communicate.Exercise could be the best medicine!

Catharine Paddock PhD. (2012, July 16). "Gait Changes May Signal Cognitive Decline, Presage Alzheimer's." Medical News Today. Retrieved fromhttp://www.medicalnewstoday.com/articles/247862.php.