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The Two Faces of Capsaicin
Published OnlineFirst April 12, 2011; DOI: 10.1158/0008-5472.CAN-10-3756 Cancer Review Research The Two Faces of Capsaicin Ann M. Bode and Zigang Dong Abstract Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is the principal pungent component in hot peppers, including red chili peppers, jalapeños, and habaneros. Consumed worldwide, capsaicin has a long and convoluted history of controversy about whether its consumption or topical application is entirely safe. Conflicting epidemiologic data and basic research study results suggest that capsaicin can act as a carcinogen or as a cancer preventive agent. Capsaicin is unique among naturally occurring irritant compounds because the initial neuronal excitation evoked is followed by a long-lasting refractory period, during which the previously excited neurons are no longer responsive to a broad range of stimuli. This process is referred to as desensitization and has been exploited for its therapeutic potential. Capsaicin-containing creams have been in clinical use for many years to relieve a variety of painful conditions. However, their effectiveness in pain relief is also highly debated and some adverse side effects have been reported. We have found that chronic, long-term topical application of capsaicin increased skin carcinogenesis in mice treated with a tumor promoter. These results might imply that caution should be exercised when using capsaicin-containing topical applications in the presence of a tumor promoter, such as, for example, sunlight. Cancer Res; 71(8); 2809–14. Ó2011 AACR. Introduction tion of gastric juice. The structure of capsaicin was partially solved by Nelson in 1919 (5), and the compound was originally Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide; Fig. -
Topical Analgesics: Expensive and Avoidable
TOPICAL ANALGESICS: EXPENSIVE AND AVOIDABLE FAST FOCUS Some very expensive topical creams and gels are creeping into the workers’ compensation Close management of custom compounds prescription files. Previously, the issue of custom compounds was highlighted and the has decreased their prevalence in workers’ attention to these prescriptions has resulted in a decrease in the number of prescriptions compensation. But private-label topicals and homeopathic products have filled the void. seen. However, the price of these compounds has increased significantly. Neither is FDA-approved. Both warrant close monitoring because of their high costs and In addition to the compounds that are still being prescribed, other topical products are lack of proven efficacy. increasingly seen in the workers’ compensation setting. In this article, a spotlight is turned on to expose more expensive topicals — private-label analgesics and homeopathic products. 24 | RxInformer FALL 2013 SUMMARY OF PRIMARY ISSUES Issue Custom Compounds Private-Label Analgesics Homeopathic Products NDCs Available FDA-approved Proven clinical benefit Prepared by compounding — — pharmacy for a specific patient Contain high levels of NSAIDs — — Contain 2-3x the FDA-approved concentration of methyl salicylate — and/or menthol Can cause skin burns — Prescribers unaware of compound ingredients Prescribers unaware of high costs Expiration dating required — — TOPICAL PRIVATE-LABEL PRODUCTS FINANCIAL CONCERNS There are private-label companies marketing products similar to inexpensive, over- When compared with comparable over-the- the-counter products, but with catchy names, inflated claims and prices. Private-label counter (OTC) preparations, the private-label topical compounds are products containing OTC ingredients such as high-potency products’ prices are stunning. -
Inhibitory Effects of Monoterpenes on Human TRPA1 and the Structural Basis of Their Activity
J Physiol Sci (2014) 64:47–57 DOI 10.1007/s12576-013-0289-0 ORIGINAL PAPER Inhibitory effects of monoterpenes on human TRPA1 and the structural basis of their activity Masayuki Takaishi • Kunitoshi Uchida • Fumitaka Fujita • Makoto Tominaga Received: 26 July 2013 / Accepted: 2 September 2013 / Published online: 12 October 2013 Ó The Author(s) 2013. This article is published with open access at Springerlink.com Abstract TRPA1, one of the transient receptor potential on these identified TRPA1 antagonists could lead to new channels, has been reported to be involved in nociception pain therapeutics. and inflammatory pain, suggesting that this molecule could be a promising target for the development of analgesic Keywords Monoterpene Á Pain relief Á TRPA1 Á agents. We screened several monoterpene analogs of Hydroxyl group camphor, which is known to inhibit human (h) TRPA1, to identify more effective naturally occurring TRPA1 antag- onists. Borneol, 2-methylisoborneol, and fenchyl alcohol Introduction exhibited higher inhibitory effects on hTRPA1 activity than either camphor or 1,8-cineole. Our results revealed Transient receptor potential (TRP) channels respond to a further that the S873, T874, and Y812 residues of hTRPA1 wide variety of sensory stimuli, including temperature, were involved in the inhibitory effects, suggesting that the nociceptive compounds, touch, osmolarity, and phero- hydroxyl group in the six-membered ring of the inhibitors mones [1–3]. TRPA1, one of the TRP channels, functions may be interacting with these amino acids. Further research as a receptor that responds to noxious cold temperatures and pungent compounds, including allyl isothiocyanate (AITC), a component of mustard oil [4–8]. -
Avoiding Medication Mayhem
Avoiding Medication Mayhem Penny Miller, BSc.(Pharm.), M.A. Senior Instructor, Faculty of Pharmaceutical Sciences and Department of Family Practice, UBC Pharmacotherapeutic Consultant, Lifemark Health Chronic pain Program Disclosure I have nothing to disclose concerning possible financial or personal relationships with commercial entities that may have a direct or indirect interest in the subject matter of this presentation. Goal: Provide the clinician with practical information to support the medication management of patients with chronic pain. Learning Objectives: At the end of this session, the clinician will demonstrate improved abilities to: 1. Describe the rationale, efficacy, benefits and risks associated with non-steroidal anti-inflammatory agents, opioids, antidepressants and anticonvulsants in the treatment of chronic pain. 2. Identify appropriate combinations of medications. 3. Outline the important reasons for slow upward titrations and slow tapers off medications. 4. Discuss effective monitoring for the efficacy and side effects of drugs to meet the outcomes of increased functioning, improved sleep and reduced pain. Case of Ben 45 y.o., construction worker • Low back pain x 7 months after a fall at work • Constant throbbing ache in low back • Radiates down right buttock & thigh, at times extends to right ankle (burning, shooting, electric pain) • Pain level on good day 5/10, on bad day 8/10, average 7/10 (over past week) • Sleep 3 hours nightly interrupted 3 times. • Diagnosis: Lumbar radiculopathy (neuropathy with nerve root -
Thymol, Menthol and Camphor from Indian Sources
THYMOL, MENTHOL AND CAMPHOR IN INDIA : CHOPRA & MUKHERJEE 361 ' sweetmeats, in pan supari' (betel leaf) mix- Articles tures, etc. The ajowan plant has, therefore, Original been grown to a greater or lesser extent all /over India. It is particularly abundant in Bengal, Central India (Indore) and Hyderabad THYMOL, MENTHOL AND CAMPHOrf (Deccan). 7,000 to 8,000 acres of land FROM INDIAN SOURCES Nearly are under cultivation each year in the Nizam's By R. N. CHOPRA, m.a., m.d. (Cantab.) Dominions alone and similar large areas are LIEUTENANT-COLONEL, I.M.S. also stated to be under cultivation in the and the United Provinces. i and Punjab Large quantities also find their way into India through B. m.b. MUKHERJEE, (Cal.) the inland routes from Afghanistan, Baluchistan Indigenous Drugs Enquiry, I. R. F. A., Series No. 35 and Persia. It can in fact be grown in any of the Indian Peninsula and the (From the Department of Pharmacology, School of part country Tropical Medicine, Calcutta) has possibilities of being a rich source of raw material for the of Indeed Thymol, menthol and camphor are well production thymol. this source has been the known in the materia medica of western already exploited by manufacturers as will be seen from the medicine as well as in that of the foreign indigenous of seeds from India between medicine in India. Thymol has been considered quantities exported 1911 and 1918 :? important on account of its powerful antiseptic, Value of germicidal and anthelmintic properties. One T otal the quantity seed of its chief uses in recent years has been in the in cwts. -
Efficacy of Paracetamol for Acute Low-Back Pain Postherpetic
NEW ZEALAND MEDICAL JOURNAL http://www.nzma.org.nz/journal/read-the-journal/all-issues/2010-2019/2014/vol-127-no-1407/6398 METHUSELAH Efficacy of paracetamol for acute low-back pain Regular paracetamol is the recommended first-line analgesic for acute low-back pain; however, no high-quality evidence supports this recommendation. This report concerns a randomised trial concerning this hypothesis. 1652 patients with acute low-back pain were randomly assigned to receive regular doses of paracetamol, as needed doses of paracetamol, or placebo. The median time to recovery was 17 days in the regular group, 17 days in the as-needed group, and 16 days in the placebo group. Adverse effects were reported in 18.5%, 18.7%, and 18.5% in the 3 groups. No differences were noted in secondary outcomes (short-term pain relief between 1 and 12 weeks, disability, function, global rating of symptom change, sleep, or quality of life) between the 3 groups. All patients received advice to remain active, avoid bed rest, and were reassured of a favourable outcome. At 12 weeks about 85% of participants had recovered. The researchers concluded that regular or as-needed dosing with paracetamol does not affect recovery time compared with placebo in low-back pain, and question the universal endorsement of paracetamol in this patient group. Lancet 2014;384:1586–96. Postherpetic neuralgia Approximately a fifth of patients with herpes zoster report some pain at 3 months after the onset of symptoms, and 15% report pain at 2 years. Approximately 6% have a score for pain intensity of at least 30 out of 100 at both time points. -
Determining Non-Cigarette Tobacco, Alcohol, and Substance Use
Cohn et al. Tobacco Induced Diseases (2017) 15:5 DOI 10.1186/s12971-017-0111-5 RESEARCH Open Access Determining non-cigarette tobacco, alcohol, and substance use typologies across menthol and non-menthol smokers using latent class analysis Amy Cohn1,2*, Amanda Johnson1,JenniferPearson1,3, Shyanika Rose1, Sarah Ehlke1, Ollie Ganz1 and Raymond Niaura1,3 Abstract Background: Substance use and mental health are robustly associated with smoking and poor cessation outcomes, but not often examined in combination with menthol cigarette smoking, which is also associated with lower quit rates. This study identified classes of Black and White menthol and non-menthol cigarette smokers based on demographics, alcohol, drug, and other tobacco use behaviors. Methods: Using screening data from two studies, latent class analysis (LCA) was conducted to classify n = 1177 menthol and non-menthol cigarette smokers on demographic characteristics, heavy smoking, alcohol and drug use, desire to quit smoking, other tobacco product use, and use of psychotropic medication. Results: Three latent classes were identified that differentiated smokers on substance use, menthol cigarette smoking, and other tobacco use behavior. One class consisted primarily of young adults who used a wide array of other tobacco products, reported the highest prevalence of other drug use, and showed the lowest desire to quit smoking cigarettes in the next 6-months. Class 2 comprised primarily of Black male menthol smokers, all of whom used cigarillos in addition to cigarettes, and who displayed moderate drug use. The third class was categorized as primarily older cigarette smokers, who engaged in very little other tobacco use or drug use, but who were most likely to self-report being prescribed psychotropic medication. -
The Effects of a Co-Application of Menthol and Capsaicin on Nociceptive Behaviors of the Rat on the Operant Orofacial Pain Assessment Device
The Effects of a Co-Application of Menthol and Capsaicin on Nociceptive Behaviors of the Rat on the Operant Orofacial Pain Assessment Device Ethan M. Anderson1,2*, Alan C. Jenkins3, Robert M. Caudle1,2, John K. Neubert3 1 Department of Oral and Maxillofacial Surgery, University of Florida College of Dentistry, Gainesville, Florida, United States of America, 2 Department of Neuroscience, University of Florida College of Medicine, McKnight Brain Institute, Gainesville, Florida, United States of America, 3 Department of Orthodontics, University of Florida, Gainesville, Florida, United States of America Abstract Background: Transient receptor potential (TRP) cation channels are involved in the perception of hot and cold pain and are targets for pain relief in humans. We hypothesized that agonists of TRPV1 and TRPM8/TRPA1, capsaicin and menthol, would alter nociceptive behaviors in the rat, but their opposite effects on temperature detection would attenuate one another if combined. Methods: Rats were tested on the Orofacial Pain Assessment Device (OPAD, Stoelting Co.) at three temperatures within a 17 min behavioral session (33uC, 21uC, 45uC). Results: The lick/face ratio (L/F: reward licking events divided by the number of stimulus contacts. Each time there is a licking event a contact is being made.) is a measure of nociception on the OPAD and this was equally reduced at 45uC and 21uC suggesting they are both nociceptive and/or aversive to rats. However, rats consumed (licks) equal amounts at 33uC and 21uC but less at 45uC suggesting that heat is more nociceptive than cold at these temperatures in the orofacial pain model. When menthol and capsaicin were applied alone they both induced nociceptive behaviors like lower L/F ratios and licks. -
Antioxidant and Anti-Inflammatory Properties of Capsicum
Journal of Ethnopharmacology 139 (2012) 228–233 Contents lists available at SciVerse ScienceDirect Journal of Ethnopharmacology jo urnal homepage: www.elsevier.com/locate/jethpharm Antioxidant and anti-inflammatory properties of Capsicum baccatum: From traditional use to scientific approach a,b a a a Aline Rigon Zimmer , Bianca Leonardi , Diogo Miron , Elfrides Schapoval , c a,∗ Jarbas Rodrigues de Oliveira , Grace Gosmann a Programa de Pós-Graduac¸ ão em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ipiranga 2752, Porto Alegre, RS, 90610-000, Brazil b Laboratório de Farmacologia Aplicada, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Av. Ipiranga 6681, Porto Alegre, RS, 90619-900, Brazil c Laboratório de Biofísica Celular e Inflamac¸ ão, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Av. Ipiranga 6681, Porto Alegre, RS, 90619-900, Brazil a r t i c l e i n f o a b s t r a c t Article history: Ethnopharmacological relevance: Peppers from Capsicum species (Solanaceae) are native to Central and Received 27 July 2011 South America, and are commonly used as food and also for a broad variety of medicinal applications. Received in revised form 29 October 2011 Aim of the study: The red pepper Capsicum baccatum var. pendulum is widely consumed in Brazil, but Accepted 2 November 2011 there are few reports in the literature of studies on its chemical composition and biological properties. Available online 9 November 2011 In this study the antioxidant and anti-inflammatory activities of Capsicum baccatum were evaluated and the total phenolic compounds and flavonoid contents were determined. -
Topical Pain Relief
TOPICAL PAIN RELIEF- methyl salicylate, menthol, capsaicin cream Two Hip Consulting, LLC Disclaimer: Most OTC drugs are not reviewed and approved by FDA, however they may be marketed if they comply with applicable regulations and policies. FDA has not evaluated whether this product complies. ---------- ACTIVE INGREDIENTS Methyl salicylate 20% (16gm) Menthol 5% (4 gm) Capsaicin 0.035% (0.3gm) PURPOSE TOPICAL ANALGESIC USES For the temporary relief of minor aches and pains of muscles and joints associated with arthritis, simple backache, strains, sprains, muscle soreness and stiffness. This product does not cure any diseases. WARNINGS Warnings: For external use only. Use only as directed. Avoid contact with eyes and mucous membranes. Do not use with heating devices or pads. Do not cover or bandage tightly. If swallowed, call poison control. If contact does occur with eyes rinse with cold water and call a doctor. Discontinue use and consult a physician if condition worsens or irritation develops. Pain persists for more than 7 days. If pain clears up and then redevelops. Do not use: on cuts or infected skin, on children less than 12 years old, in combination with other topical pain products, if allergic to any ingredients, PABA, aspirin products, or sulfa. Do not use if you are pregnant or nursing. Store below 90 degrees F/32 degrees C. See USP Controlled Temperature. KEEP OUT OF REACH OF CHILDREN. DIRECTIONS Use only as directed. Prior to first use, test skin sensitivity by applying a small amount. Apply and massage directly to affected area. Do not use more than 4 times a day. -
Dose-Dependent Effects of Smoked Cannabis on Capsaicin- Induced Pain and Hyperalgesia in Healthy Volunteers Mark Wallace, M.D.,* Gery Schulteis, Ph.D.,* J
Ⅵ PAIN AND REGIONAL ANESTHESIA Anesthesiology 2007; 107:785–96 Copyright © 2007, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc. Dose-dependent Effects of Smoked Cannabis on Capsaicin- induced Pain and Hyperalgesia in Healthy Volunteers Mark Wallace, M.D.,* Gery Schulteis, Ph.D.,* J. Hampton Atkinson, M.D.,† Tanya Wolfson, M.A.,‡ Deborah Lazzaretto, M.S.,§ Heather Bentley, Ben Gouaux,# Ian Abramson, Ph.D.** Background: Although the preclinical literature suggests that nents of clinical pain makes it difficult to study these cannabinoids produce antinociception and antihyperalgesic ef- features in isolation, in terms of identifying potentially fects, efficacy in the human pain state remains unclear. Using a human experimental pain model, the authors hypothesized responsive components. Using models of experimentally that inhaled cannabis would reduce the pain and hyperalgesia induced pain in human volunteers, however, permits induced by intradermal capsaicin. simplified stimulus conditions, crossover designs, and Methods: In a randomized, double-blinded, placebo-con- comparisons between human and animal models to de- trolled, crossover trial in 15 healthy volunteers, the authors fine in parallel the physiology and pharmacology of pain evaluated concentration–response effects of low-, medium-, and high-dose smoked cannabis (respectively 2%, 4%, and 8% 9-␦- states. Therefore, one is able to investigate the sensory tetrahydrocannabinol by weight) on pain and cutaneous hyper- components of pain processing in concert with assess- algesia induced by intradermal capsaicin. Capsaicin was in- ment of analgesic efficacy. Another difficulty in some jected into opposite forearms 5 and 45 min after drug exposure, previous cannabinoid research lies in the uncertain rela- and pain, hyperalgesia, tetrahydrocannabinol plasma levels, tion of traditional experimentally induced human pain and side effects were assessed. -
International Olympic Committee Consensus Statement on Pain
Consensus statement Br J Sports Med: first published as 10.1136/bjsports-2017-097884 on 21 August 2017. Downloaded from International Olympic Committee consensus statement on pain management in elite athletes Brian Hainline,1 Wayne Derman,2 Alan Vernec,3 Richard Budgett,4 Masataka Deie,5 Jiří Dvořák,6 Chris Harle,7 Stanley A Herring,8 Mike McNamee,9 Willem Meeuwisse,10 G Lorimer Moseley,11 Bade Omololu,12 John Orchard,13 Andrew Pipe,14 Babette M Pluim,15 Johan Ræder,16 Christian Siebert,17 Mike Stewart,18 Mark Stuart,19 Judith A Turner,20 Mark Ware,21 David Zideman,22 Lars Engebretsen4 ► Additional material is ABSTRact This consensus paper fulfils the IOC charge by published online only. To view Pain is a common problem among elite athletes and is addressing the multifaceted aspects of pain physi- please visit the journal online ology and pain management in elite athletes through (http:// dx. doi. org/ 10. 1136/ frequently associated with sport injury. Both pain and bjsports- 2017- 097884). injury interfere with the performance of elite athletes. the lenses of epidemiology, sports medicine, pain There are currently no evidence-based or consensus- medicine, pain psychology, pharmacology and For numbered affiliations see based guidelines for the management of pain in elite ethics. end of article. athletes. Typically, pain management consists of the provision of analgesics, rest and physical therapy. Correspondence to PREVALENCE OF USE OF PHARMACOLOGICAL Dr Brian Hainline, National More appropriately, a treatment strategy should AND NON-PHARMACOLOGICAL TREATMENTS Collegiate Athletic Association address all contributors to pain including underlying TO MANAGE PAIN IN ELITE atHLETES (NCAA), Indianapolis, Indiana pathophysiology, biomechanical abnormalities and Elite athletes commonly use prescription and over- 46206, US; bhainline@ ncaa.