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Article: Targeting TRPV1 for Cancer Pain Relief: Can It Work?

Szallasi, Arpad

2024 Volume 16, Issue 3

Abstract: Chronic intractable pain affects a large proportion of cancer patients, especially those with metastatic bone disease. Blocking sensory afferents for cancer pain relief represents an attractive alternative to opioids and other drugs acting in the CNS in ... ...

Abstract	Chronic intractable pain affects a large proportion of cancer patients, especially those with metastatic bone disease. Blocking sensory afferents for cancer pain relief represents an attractive alternative to opioids and other drugs acting in the CNS in that sensory nerve blockers are not addictive and do not affect the mental state of the patient. A distinct subpopulation of sensory afferents expresses the capsaicin receptor TRPV1. Intrathecal resiniferatoxin, an ultrapotent capsaicin analog, ablates TRPV1-expressing nerve endings exposed to the cerebrospinal fluid, resulting in permanent analgesia in women with cervical cancer metastasis to the pelvic bone. High-dose capsaicin patches are effective pain killers in patients with chemotherapy-induced peripheral neuropathic pain. However, large gaps remain in our knowledge since the mechanisms by which cancer activates TRPV1 are essentially unknown. Most important, it is not clear whether or not sensory denervation mediated by TRPV1 agonists affects cancer progression. In a murine model of breast cancer, capsaicin desensitization was reported to accelerate progression. By contrast, desensitization mediated by resiniferatoxin was found to block melanoma growth. These observations imply that TRPV1 blockade for pain relief may be indicated for some cancers and contraindicated for others. In this review, we explore the current state of this field and compare the analgesic potential of TRPV1 antagonism and sensory afferent desensitization in cancer patients.
Language	English
Publishing date	2024-02-02
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers16030648
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The Vanilloid (Capsaicin) Receptor TRPV1 in Blood Pressure Regulation: A Novel Therapeutic Target in Hypertension?

Szallasi, Arpad

International journal of molecular sciences

2023 Volume 24, Issue 10

Abstract: Today's sedentary lifestyle with excess food and little exercise increases the number of people with hypertension, a major risk factor for stroke. New knowledge of treatments in this field is of utmost importance. In animal experiments, the activation by ...

Abstract	Today's sedentary lifestyle with excess food and little exercise increases the number of people with hypertension, a major risk factor for stroke. New knowledge of treatments in this field is of utmost importance. In animal experiments, the activation by capsaicin of TRPV1-expressing sensory afferents evokes a drop in blood pressure by triggering the Bezold-Jarisch reflex. In hypertensive rats, capsaicin reduces blood pressure. Conversely, genetic ablation of the TRPV1 receptor results in elevated nocturnal (but not diurnal) blood pressure. These observations imply a therapeutic potential for TRPV1 activation in hypertensive patients. Indeed, in a major epidemiological study involving 9273 volunteers, dietary capsaicin was found to lower the risk for hypertension. New research indicates that the mechanism of action of capsaicin on blood pressure regulation is far more complex than previously thought. In addition to the well-recognized role of capsaicin-sensitive afferents in blood pressure regulation, TRPV1 seems to be expressed both in endothelial cells and vascular smooth muscle. This review aims to evaluate the therapeutic potential of TRPV1-targeting drugs in hypertensive patients.
MeSH term(s)	Animals ; Rats ; Blood Pressure ; Capsaicin/pharmacology ; Capsaicin/therapeutic use ; Endothelial Cells ; Hypertension/drug therapy ; TRPV Cation Channels/genetics ; Humans
Chemical Substances	Capsaicin (S07O44R1ZM) ; TRPV Cation Channels ; Trpv1 protein, rat
Language	English
Publishing date	2023-05-15
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24108769
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Resiniferatoxin: Nature's Precision Medicine to Silence TRPV1-Positive Afferents.

Szallasi, Arpad

International journal of molecular sciences

2023 Volume 24, Issue 20

Abstract: Resiniferatoxin (RTX) is an ultrapotent capsaicin analog with a unique spectrum of pharmacological actions. The therapeutic window of RTX is broad, allowing for the full desensitization of pain perception and neurogenic inflammation without causing ... ...

Abstract	Resiniferatoxin (RTX) is an ultrapotent capsaicin analog with a unique spectrum of pharmacological actions. The therapeutic window of RTX is broad, allowing for the full desensitization of pain perception and neurogenic inflammation without causing unacceptable side effects. Intravesical RTX was shown to restore continence in a subset of patients with idiopathic and neurogenic detrusor overactivity. RTX can also ablate sensory neurons as a "molecular scalpel" to achieve permanent analgesia. This targeted (intrathecal or epidural) RTX therapy holds great promise in cancer pain management. Intra-articular RTX is undergoing clinical trials to treat moderate-to-severe knee pain in patients with osteoarthritis. Similar targeted approaches may be useful in the management of post-operative pain or pain associated with severe burn injuries. The current state of this field is reviewed, from preclinical studies through veterinary medicine to clinical trials.
MeSH term(s)	Humans ; Precision Medicine/adverse effects ; Urinary Bladder, Overactive/etiology ; Diterpenes/adverse effects ; Pain/drug therapy ; TRPV Cation Channels/genetics
Chemical Substances	resiniferatoxin (A5O6P1UL4I) ; Diterpenes ; TRPV Cation Channels ; TRPV1 protein, human
Language	English
Publishing date	2023-10-10
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms242015042
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: "ThermoTRP" Channel Expression in Cancers: Implications for Diagnosis and Prognosis (Practical Approach by a Pathologist).

Szallasi, Arpad

International journal of molecular sciences

2023 Volume 24, Issue 10

Abstract: Temperature-sensitive transient receptor potential (TRP) channels (so-called "thermoTRPs") are multifunctional signaling molecules with important roles in cell growth and differentiation. Several "thermoTRP" channels show altered expression in cancers, ... ...

Abstract	Temperature-sensitive transient receptor potential (TRP) channels (so-called "thermoTRPs") are multifunctional signaling molecules with important roles in cell growth and differentiation. Several "thermoTRP" channels show altered expression in cancers, though it is unclear if this is a cause or consequence of the disease. Regardless of the underlying pathology, this altered expression may potentially be used for cancer diagnosis and prognostication. "ThermoTRP" expression may distinguish between benign and malignant lesions. For example, TRPV1 is expressed in benign gastric mucosa, but is absent in gastric adenocarcinoma. TRPV1 is also expressed both in normal urothelia and non-invasive papillary urothelial carcinoma, but no TRPV1 expression has been seen in invasive urothelial carcinoma. "ThermoTRP" expression can also be used to predict clinical outcomes. For instance, in prostate cancer, TRPM8 expression predicts aggressive behavior with early metastatic disease. Furthermore, TRPV1 expression can dissect a subset of pulmonary adenocarcinoma patients with bad prognosis and resistance to a number of commonly used chemotherapeutic agents. This review will explore the current state of this rapidly evolving field with special emphasis on immunostains that can already be added to the armoire of diagnostic pathologists.
MeSH term(s)	Transient Receptor Potential Channels/genetics ; Transient Receptor Potential Channels/metabolism ; Humans ; Neoplasms/diagnosis ; Neoplasms/metabolism ; Neoplasms/pathology ; Prognosis ; Temperature ; Thermosensing
Chemical Substances	Transient Receptor Potential Channels
Language	English
Publishing date	2023-05-22
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24109098
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Book ; Online: Transient Receptor Potential (TRP) Channels in Drug Discovery: Old Concepts & New Thoughts

Szallasi, Arpad / Huang, Susan M.

2018

Abstract: The year 2017 marks the 20th anniversary of the molecular cloning of the long sought-after capsaicin receptor, now known as TRPV1 (Transient Receptor Potential Vanilloid 1). This seminal discovery has opened up a "hot" new field of basic research and ... ...

Abstract	The year 2017 marks the 20th anniversary of the molecular cloning of the long sought-after capsaicin receptor, now known as TRPV1 (Transient Receptor Potential Vanilloid 1). This seminal discovery has opened up a "hot" new field of basic research and launched drug discovery efforts into the large family (by the latest count, 28 mammalian members and 27 in humans) of TRP ion channels. Indeed, it took less than a decade for the first potent, small molecule TRPV1 antagonists to enter phase 1 clinical trials, closely followed by TRPA1 and TRPM8 antagonists. The literature on TRP channels is immense. TRPV1 alone is a keyword in over 5000 publications searchable in PubMed. Clearly, it is not possible to capture the entire literature in a single thematic issue. Consequently, the selection of articles presented in this book represents a sampling of the literature, and is admittedly subjective. We tried to survey the wide range of human diseases in which TRP channels have been implicated, ranging from chronic pain through asthma and diabetes to cancer, and highlight the channels that appear to hold the greatest promise for therapeutic targeting. With this book, we hope to convince readers that TRP channels constitute a formidable family of potential therapeutic targets that will likely continue to demand attention
Keywords	Therapeutics. Pharmacology
Size	1 electronic resource (VI, 250 p.)
Publisher	MDPI - Multidisciplinary Digital Publishing Institute
Document type	Book ; Online
Note	English ; Open Access
HBZ-ID	HT020098744
ISBN	9783038426387 ; 9783038426394 ; 3038426385 ; 3038426393
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article: Capsaicin and cancer: Guilty as charged or innocent until proven guilty?

Szallasi, Arpad

Temperature (Austin, Tex.)

2022 Volume 10, Issue 1, Page(s) 35–49

Abstract: With an estimated 2 billion chili pepper connoisseurs worldwide, the human exposure to capsaicin is enormous. Therefore, the question whether nutritional capsaicin is a cancer causing or cancer preventive agent is of utmost importance. The gamut of human ...

Abstract	With an estimated 2 billion chili pepper connoisseurs worldwide, the human exposure to capsaicin is enormous. Therefore, the question whether nutritional capsaicin is a cancer causing or cancer preventive agent is of utmost importance. The gamut of human epidemiology studies suggests that capsaicin in modest, "restaurant-like" doses is not only safe to eat, but it may even provide health benefits, such as lower cancer-related death rate. Very "hot" food is, however, probably better avoided. Importantly, no increased cancer risk was reported in patients following topical (skin or intravesical) capsaicin therapy. Aberrant capsaicin receptor TRPV1 expression was noted in various cancers with potential implications for cancer therapy, diagnosis and prognostication. Indeed, capsaicin can kill cancer cells by a combination of on- and off-target mechanisms, though it remains unclear if this can be exploited for therapeutic purposes. The literature on capsaicin and cancer is vast and controversial. This review aims to find answers to questions that are relevant for our daily life and medical practice.
Language	English
Publishing date	2022-01-11
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2332-8940
ISSN	2332-8940
DOI	10.1080/23328940.2021.2017735
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Article ; Online: Dietary Capsaicin: A Spicy Way to Improve Cardio-Metabolic Health?

Szallasi, Arpad

Biomolecules

2022 Volume 12, Issue 12

Abstract: Today's sedentary lifestyle with too much food and too little exercise has made metabolic syndrome a pandemic. Metabolic syndrome is a major risk factor for type-2 diabetes and cardiovascular disease. New knowledge of medical and nutraceutical ... ...

Abstract	Today's sedentary lifestyle with too much food and too little exercise has made metabolic syndrome a pandemic. Metabolic syndrome is a major risk factor for type-2 diabetes and cardiovascular disease. New knowledge of medical and nutraceutical intervention in the early stages of metabolic syndrome is central to prevent these deadly complications. People who eat chili pepper on a regular basis seem to stay healthier and live longer than those who do not. Animal experiments suggest a therapeutic potential for dietary capsaicin, the active principle in hot chili pepper, to reduce the risk of developing metabolic syndrome. This is an attractive theory since capsaicin has been a culinary staple for thousands of years, and is generally deemed safe when consumed in hedonically acceptable doses. The broad expression of the capsaicin receptor TRPV1 in metabolically active tissues lends experimental support to this theory. This review critically evaluates the available experimental and clinical evidence for and against dietary capsaicin being an effective dietary means to improve cardio-metabolic health. It comes to the conclusion that although a chili pepper-rich diet is associated with a reduced risk of dying due to cardiovascular disease, dietary capsaicin has no clear effect on blood glucose or lipid profiles. Therefore, the reduced mortality risk may reflect the beneficial action of digested capsaicin on gut microbiota.
Language	English
Publishing date	2022-11-29
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom12121783
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Article: Capsaicin for Weight Control: "Exercise in a Pill" (or Just Another Fad)?

Szallasi, Arpad

Pharmaceuticals (Basel, Switzerland)

2022 Volume 15, Issue 7

Abstract: Medical management of obesity represents a large unmet clinical need. Animal experiments suggest a therapeutic potential for dietary capsaicin, the pungent ingredient in hot chili peppers, to lose weight. This is an attractive theory since capsaicin has ... ...

Abstract	Medical management of obesity represents a large unmet clinical need. Animal experiments suggest a therapeutic potential for dietary capsaicin, the pungent ingredient in hot chili peppers, to lose weight. This is an attractive theory since capsaicin has been a culinary staple for thousands of years and is generally deemed safe when consumed in hedonically acceptable, restaurant-like doses. This review critically evaluates the available experimental and clinical evidence for and against capsaicin as a weight control agent and comes to the conclusion that capsaicin is not a magic "exercise in a pill", although there is emerging evidence that it may help restore a healthy gut microbiota.
Language	English
Publishing date	2022-07-11
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2193542-7
ISSN	1424-8247
ISSN	1424-8247
DOI	10.3390/ph15070851
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Targeting TRP Channels for Pain, Itch and Neurogenic Inflammation.

Koivisto, Ari-Pekka / Szallasi, Arpad

International journal of molecular sciences

2023 Volume 25, Issue 1

Abstract: Transient receptor potential (TRP) channels are multifunctional signaling molecules with important roles in health and disease [ ... ]. ...

Abstract	Transient receptor potential (TRP) channels are multifunctional signaling molecules with important roles in health and disease [...].
MeSH term(s)	Humans ; Neurogenic Inflammation ; Transient Receptor Potential Channels ; Pain ; Pruritus
Chemical Substances	Transient Receptor Potential Channels
Language	English
Publishing date	2023-12-25
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25010320
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Article: János Szolcsányi and capsaicin research - from the early years to his legacy.

Barthó, Lóránd / Szallasi, Arpad

Temperature (Austin, Tex.)

2023 Volume 10, Issue 1, Page(s) 3–8

Language	English
Publishing date	2023-05-11
Publishing country	United States
Document type	Journal Article
ISSN	2332-8940
ISSN	2332-8940
DOI	10.1080/23328940.2023.2179820
Database	MEDical Literature Analysis and Retrieval System OnLINE

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