Since starting to take 2.4g of capsaicin a day and sometimes up to 3g a day I have found the spasticity in my leg improved, my bladder function improved and my bowel function rather too loose! Here's maybe why:
1: J Spinal Cord Med. 2008;31(2):157-65.Links
Neurotoxin treatments for urinary incontinence in subjects with spinal cord injury or multiple sclerosis: a systematic review of effectiveness and adverse effects.MacDonald R, Monga M, Fink HA, Wilt TJ.
Center for Chronic Disease Outcomes Research, Minneapolis Veterans Affairs Medical Center, Minneapolis, Minnesota, 55417, USA.
roderick.macdonald@va.gov
BACKGROUND/OBJECTIVE: The objective was to evaluate the effectiveness of neurotoxin treatments of urinary incontinence (UI) in individuals with spinal cord injury (SCI) or multiple sclerosis (MS). METHODS: Studies were included if published in English, presented randomized adults with SCI or MS, and reported UI outcomes. RESULTS: Ten trials randomizing 288 subjects with SCI (43%), MS (52%), or other spinal conditions (5%) and UI refractory to oral antimuscarinics were included. The overall mean age was 41 years, and 46% were women. Study durations ranged from 1 to 18 months. Treatments included botulinum toxin-A (BTX-A, 2 trials) and 2 vanilloid compounds, capsaicin (6 trials) and resiniferatoxin (4 trials). BTX-A was superior to placebo and resiniferatoxin in reducing daily UI episodes, mainly in individuals with SCI, although significant reductions vs placebo were not evident throughout the study duration. There were 1.1 fewer daily UI episodes in the BTX-A 200 unit group vs 0.1 fewer for the placebo group at the final week 24 assessment.
Capsaicin was generally superior to placebo. The weighted difference between capsaicin and placebo in a pooled analysis of 2 trials enrolling subjects with either paraplegia or tetraplegia (n = 32) was -3.8 daily UI episodes [95% Cl -4.7 to -2.9] after 30 days. Capsaicin was comparable to resiniferatoxin. Pelvic pain and facial flushing were associated with capsaicin. CONCLUSION: Neurotoxins may improve refractive UI in adults with SCI or MS, although trial results were inconsistent. Trials were small in size and relatively short in duration. Further studies are needed to determine the efficacy and tolerability of long-term application.
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1: Neurourol Urodyn. 2006;25(7):752-7. Links
Intravesical glucidic capsaicin versus glucidic solvent in neurogenic detrusor overactivity: a double blind controlled randomized study.de Sèze M, Gallien P, Denys P, Labat JJ, Serment G, Grise P, Salle JY, Blazejewski S, Hazane C, Moore N, Joseph PA.
Physical Medicine and Neurorehabilitation Unit, Bordeaux University Hospital, Bordeaux, France.
marianne.de-seze@chu-bordeaux.fr
AIMS: Many studies report the use of alcoholic capsaicin instillation to treat neurogenic detrusor overactivity (NDO) in spinal cord injured (SCI) and multiple sclerosis (MS) patients. However, poor tolerability due to the irritative effect of the ethanol solvent limits its use. Our study aimed to evaluate the efficacy and tolerability of a new formulation of capsaicin in a glucidic solution in a multicenter clinical trial. MATERIALS AND METHODS: Thirty-three patients (26MS/7SCI) suffering from urinary incontinence due to refractory NDO were prospectively enrolled in a double-blind placebo controlled study and randomized to capsaicin group (CG, N = 17) or solvent group (SG, N = 16). They respectively received an intravesical instillation of 100 ml capsaicin diluted in glucidic solvent (CG) or glucidic solvent alone (SG). Efficacy (voiding chart, maximum cystometric capacity (MCC)) and tolerability were evaluated on days 0 (D0), 30 and 90. RESULTS: On D0, groups were homogeneous. On D30, significant improvement of overactive bladder syndrome and an increase in MCC were shown in CG, whereas there were no improvement in SG. No significant improvement was shown on D90 in both groups. There were no significant differences between groups regarding prevalence, duration, or intensity of side effects, except for short duration pubic pain during instillation more often reported in CG (58.8%) than in SG (12.5%) (P < 0.01). CONCLUSION: This placebo controlled study using glucidic capsaicin confirms its short-term efficacy in NDO patients. Global tolerance of glucidic capsaicin appeared satisfactory. Long-term efficacy and tolerance of repeated glucidic capsaicin instillations need to be evaluated. (c) 2006 Wiley-Liss, Inc.
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1: J Neuroimmunol. 2006 Feb;171(1-2):110-9. Epub 2005 Oct 18. Links
Arvanil inhibits T lymphocyte activation and ameliorates autoimmune encephalomyelitis.Malfitano AM, Matarese G, Pisanti S, Grimaldi C, Laezza C, Bisogno T, Di Marzo V, Lechler RI, Bifulco M.
Dipartimento di Scienze Farmaceutiche, Universita' di Salerno, Via Ponte don Melillo 84084 Fisciano (Salerno), Italy.
This study examined the immunomodulatory effect of arvanil, a synthetic capsaicin-anandamide hybrid. Arvanil inhibits lymphocyte proliferation and IFN-gamma production. The phenotype of activated CD4+T cells treated with arvanil shows a down-regulation of T cell activation markers such as CD25, HLA-DR and CD134/OX40. Arvanil and anandamide do not induce apoptosis on CD4+T cells. Arvanil blocks the G1/S phase transition of the cell cycle in stimulated peripheral blood mononuclear cells, inducing activation of p21waf-1/cip-1 and phosphorylation of Akt/PKB. In vivo, arvanil ameliorates experimental autoimmune encephalomyelitis in the SJL/J mouse. Our findings have relevance for the use of arvanil and related compounds as a novel immunotherapeutic approach in the treatment of multiple sclerosis.
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1: Eur J Pharmacol. 2002 Mar 29;439(1-3):83-92. Links
Arvanil-induced inhibition of spasticity and persistent pain: evidence for therapeutic sites of action different from the vanilloid VR1 receptor and cannabinoid CB(1)/CB(2) receptors.Brooks JW, Pryce G, Bisogno T, Jaggar SI, Hankey DJ, Brown P, Bridges D, Ledent C, Bifulco M, Rice AS, Di Marzo V, Baker D.
Pain Research Group, Department of Anaesthetics, Faculty of Medicine, Imperial College, Chelsea and Westminster Hospital Campus, London, UK.
Activation of cannabinoid receptors causes inhibition of spasticity, in a mouse model of multiple sclerosis, and of persistent pain, in the rat formalin test. The endocannabinoid anandamide inhibits spasticity and persistent pain. It not only binds to cannabinoid receptors but is also a full agonist at vanilloid receptors of type 1 (VR1). We found here that vanilloid VR1 receptor agonists (capsaicin and N-N'-(3-methoxy-4-aminoethoxy-benzyl)-(4-tert-butyl-benzyl)-urea [SDZ-249-665]) exhibit a small, albeit significant, inhibition of spasticity that can be attenuated by the vanilloid VR1 receptor antagonist, capsazepine. Arvanil, a structural "hybrid" between capsaicin and anandamide, was a potent inhibitor of spasticity at doses (e.g. 0.01 mg/kg i.v.) where capsaicin and cannabinoid CB(1) receptor agonists were ineffective. The anti-spastic effect of arvanil was unchanged in cannabinoid CB(1) receptor gene-deficient mice or in wildtype mice in the presence of both cannabinoid and vanilloid receptor antagonists. Likewise, arvanil (0.1-0.25 mg/kg) exhibited a potent analgesic effect in the formalin test, which was not reversed by cannabinoid and vanilloid receptor antagonists. These findings suggest that activation by arvanil of sites of action different from cannabinoid CB(1)/CB(2) receptors and vanilloid VR1 receptors leads to anti-spastic/analgesic effects that might be exploited therapeutically.
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Stat 3 blockade by capsaicin may be helpful in MS:
1: Clin Cancer Res. 2007 May 15;13(10):3024-32. Links
Capsaicin is a novel blocker of constitutive and interleukin-6-inducible STAT3 activation.Bhutani M, Pathak AK, Nair AS, Kunnumakkara AB, Guha S, Sethi G, Aggarwal BB.
Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
PURPOSE: Capsaicin, a constituent of green and red peppers, has been linked with suppression of tumorigenesis through a mechanism that is not well understood. Because the transcription factor signal transducer and activator of transcription 3 (STAT3) has been closely linked with tumorigenesis, we investigated the effect of this vanilloid on the STAT3 pathway in human multiple myeloma cells. EXPERIMENTAL DESIGN: The effect of capsaicin on both constitutive and interleukin-6-induced STAT3 activation, associated protein kinases, and STAT3-regulated gene products involved in proliferation, survival and angiogenesis, cellular proliferation, and apoptosis in multiple myeloma cells was investigated. RESULTS: We found that capsaicin inhibited constitutive activation of STAT3 in multiple myeloma cells in a dose- and time-dependent manner, with minimum effect on STAT5. Capsaicin also inhibited the interleukin-6-induced STAT3 activation. The activation of Janus-activated kinase 1 and c-Src, implicated in STAT3 activation, was also inhibited by the vanilloid, with no effect on extracellular signal-regulated kinase 1/2 activation. Pervanadate reversed the capsaicin-induced down-regulation of STAT3, suggesting the involvement of a protein tyrosine phosphatase. Capsaicin down-regulated the expression of the STAT3-regulated gene products, such as cyclin D1, Bcl-2, Bcl-xL, survivin, and vascular endothelial growth factor. Finally, capsaicin induced the accumulation of cells in G(1) phase, inhibited proliferation, and induced apoptosis, as indicated by caspase activation. Capsaicin also significantly potentiated the apoptotic effects of Velcade and thalidomide in multiple myeloma cells. When administered i.p., capsaicin inhibited the growth of human multiple myeloma xenograft tumors in male athymic nu/nu mice. CONCLUSION: Overall, these results suggest that capsaicin is a novel blocker of the STAT3 activation pathway, with a potential role in the prevention and treatment of multiple myeloma and other cancers.
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1: J Immunol. 2008 May 1;180(9):6070-6. Links
Loss of STAT3 in CD4+ T cells prevents development of experimental autoimmune diseases.Liu X, Lee YS, Yu CR, Egwuagu CE.
Section of Molecular Immunology, Laboratory of Immunology, National Eye Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.
Th17 cells are implicated in CNS autoimmune diseases. We show that mice with targeted-deletion of Stat3 in CD4(+) T cells (CD4(Stat3)(-/-)) do not develop experimental autoimmune uveoretinitis (EAU) or experimental autoimmune encephalomyelitis. Defective Th17 differentiation noted in CD4(Stat3)(-/-) mice is compensated by exaggerated increases in Foxp3-, IL-10-, IL-4-, and IFN-gamma-expressing T cells, suggesting critical roles of STAT3 in shaping Ag-specific CD4(+) T cell repertoire. In mice with EAU, a high percentage of IL-17-expressing T cells in their peripheral lymphoid organs also secrete IFN-gamma while these double-expressors are absent in CD4(Stat3)(-/-) and wild-type mice without EAU, raising the intriguing possibility that uveitis maybe mediated by Th17 and IL-17-expressing Th1 cells. Resistance of Stat3-deficient mice to EAU derives in part from an inability of uveitogenic Th17 and Th1 cells to enter eyes or brain of the CD4(Stat3)(-/-) mouse because of the reduction in the expression of activated alpha4/beta1 integrins on CD4(Stat3)(-/-) T cells. Adoptive transfer of activated interphotoreceptor retinoid-binding protein-specific uveitogenic T cells induced in CD4(Stat3)(-/-) mice a severe EAU characterized by development of retinal folds, infiltration of inflammatory cells into the retina, and destruction of retinal architecture, underscoring our contention that the loss of STAT3 in CD4(+) T cells results in an intrinsic developmental defect that renders CD4(Stat3)(-/-) resistant to CNS inflammatory diseases. STAT3 requirement for IL-17 production by Th17, generation of double positive T cells expressing IL-17 and IFN-gamma, and for T cell trafficking into CNS tissues suggests that STAT3 may be a therapeutic target for modulating uveitis, sceritis, or multiple sclerosis.
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not sure if pSTAT3 is the same as STAT3, I suspect it just means phosphorylated STAT3:
1: J Neurosci Res. 2006 Oct;84(5):1027-36. Links
pSTAT1, pSTAT3, and T-bet expression in peripheral blood mononuclear cells from relapsing-remitting multiple sclerosis patients correlates with disease activity.Frisullo G, Angelucci F, Caggiula M, Nociti V, Iorio R, Patanella AK, Sancricca C, Mirabella M, Tonali PA, Batocchi AP.
Institute of Neurology, Department of Neuroscience, Catholic University, Rome, Italy.
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, and it is considered to be a T helper 1 (Th1) cell-mediated autoimmune disease. T-bet has been identified as a key transcription factor for the development of Th1 cells and the induction of interferon (IFN)-gamma production. T-bet is induced during T-cell activation by the IFN-gamma signal transducer and activator of transcription (STAT)-1 signalling pathway. In this study we found an up-regulation of T-bet and pSTAT1 in peripheral blood CD4+ and CD8+ T cells and monocytes from relapsing-remitting MS patients in relapse compared with patients in remission and with healthy subjects. The increased expression of pSTAT1 strongly correlated with T-bet expression in CD4+ and CD8+ cells and monocytes from patients in relapse and was associated with an increased production of IFN-gamma by peripheral blood mononuclear cells (PBMCs). pSTAT3 was also up-regulated in CD4+ and CD8+ cells and monocytes from patients in relapse and was associated with an increased production of interleukin (IL)-10 but not of IL-6. pSTAT1, pSTAT3, and T-bet expression strongly correlated with Gd-DTPA-enhanced lesions on brain and spinal cord magnetic resonance imaging. Our data show for the first time that there is an up-regulation of type 1 immunity-correlated transcription factors such as STAT1 and T-bet in peripheral blood subpopulations of MS patients in the active phase of disease. The evaluation of T-bet and pSTAT1 expression in peripheral blood CD4+, CD8+ T cells and monocytes could be used as a marker of disease activity in relapsing-remitting MS. Copyright 2006 Wiley-Liss, Inc.
PMID: 16865709 [PubMed - indexed for MEDLINE]
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