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Anti-Inflammatory
& Anti-Allergy Agents in Medicinal Chemistry
ISSN: 1871-5230
Anti-Inflammatory
& Anti-Allergy Agents in Medicinal Chemistry
Volume 10, Number 1, February 2011
Contents
Hot-Topic
Anti-inflammatory and Anti-Allergy Functions of Capsaicin
in Association with its Actions on Primary Sensory Neurons
Guest Editor: Akio Hiura & Gábor Jancsó
Editorial Pp.1
An Overview of the Actions of Capsaicin and Its Receptor,
TRPV1, and Their Relations to Small Primary Sensory Neurons
Pp. 2-9
Akio Hiura and Hiroshi Nakagawa
[Abstract] [Purchase
Article]
Anatomical and Functional Relationships Between Sensory
Nerves and Mast Cells Pp. 10-17
Fatma Tore and Nese Tuncel
[Abstract] [Purchase
Article]
TRPV1 and TRPA1 in Pulmonary Vagal Afferents and their
Relations to Airway Sensitivity Pp.18-30
Hiroyuki Watanabe, Takayoshi Ohba, Kazuhiro Satoh, Masaaki
Sano, Takanobu Shioya and Hiroshi Ito
[Abstract] [Purchase
Article]
Capsaicin-Sensitive Nociceptive Innervation of the
Dura Mater: Implications for the Pathomechanism of Headache
Pp. 31-42
Mária Dux, Judit Rosta and Gábor Jancsó
[Abstract] [Purchase
Article]
Pain Alleviation in Anti-Inflammatory and Anti-Allergic
Conditions Pp. 43-51
Ceng Luo, Rou-Gang Xie and San-Jue Hu
[Abstract] [Purchase
Article]
The Capsaicin Paradox: Pain Relief by an Algesic Agent
Pp. 52-65
Gábor Jancsó, Orsolya Oszlács
and Péter Sántha
[Abstract] [Purchase
Article]
General Article
Anti-inflammatory Lipid Mediators Derived from
ω-6
and ω-3
Polyunsaturated Fatty Acids as a Treatment Option for IBD
Pp. 66-71
Shin Nishiumi, Izumi Kure, Tsukasa Ishida, Makoto Ooi,
Tomoo Yoshie, Hiromu Kutsumi, Takeshi Azuma and Masaru
Yoshida
[Abstract] [Purchase
Article]
Abstracts
[Back to top]
Editorial: Anti-inflammatory and Anti-allergy Functions
of Capsaicin in Association with its Actions on Primary Sensory
Neurons
Capsaicin and its analogs induce anti-inflammatory and anti–allergic
functions as well as causing inflammation and allergy, principally
acting on the small primary sensory neurons. This special
issue is focused on capsaicin-sensitive (chemo-sensitive)
somatic and visceral C-fibers responsible for inflammation
and allergy, resulting in the trigger of hyperalgesia, headache,
airway sensitivity (cough and hypersensitivity), and itching
sensation. Especially, non Ca++-selective,
a molecular integrator of nociception, TRPV1 and TRPA1 receptors
are highlighted to explain the relationships between inflammatory
diseases and efferent functions of chemo-sensitive C fiber
terminals. Furthermore, causal interactions (autocrine and
paracrine functions) in milieu of C fiber terminals and mast
cells are considered for inflammation and allergy in the itch.
The direct or indirect mediators participating in inflammation
and allergy, such as neuropeptids (especially, calcitonin
gene-related peptide), decomposed neuropeptids by protease
(their protease-activated receptors as well), prostaglandins,
histamine, growth factors, nuclear factor-kappa B (NF-κB)
and some cytokines are brought up for discussion of the complicated
vital phenomenon. Vanilloid agonists, exerting anti-nociceptive,
anti-allergic and anti-inflammatory agents, are surveyed from
experimental studies of the topical, perineural and subarachnoidal
applications for their available therapeutic use.
Akio Hiura
(Guest Editor)
Department of Oral Histology, School of Dentistry,
University of Tokushima
Tokushima, Japan
Tel: +81-88-633-9121
Fax: +81-88-633-7342
E-mail: hiuraaki@dent.tokushima-u.ac.jp
Gábor Jancsò
(Guest Editor)
Department of Physiology, Faculty of Medicine,
University of Szeged
Hungary
Tel: 00-36-62-545101; 00-36-62-545099
Fax: 00-36-62-545842
E-mail: Jancsó@phys.szote.u-szeged.hu
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Article]
An Overview of the Actions of Capsaicin and Its Receptor,
TRPV1, and Their Relations to Small Primary Sensory Neurons
Akio Hiura and Hiroshi Nakagawa
The specific actions of capsaicin on the small primary afferent
neurons with regard to neurogenic inflammation and plasma
extravasation are examined in this review. First, a short
history of the study of capsaicin is introduced from the viewpoint
of the efferent function of capsaicin-sensitive nerve fibers.
Agonist (resiniferatoxin) and antagonists (capsazepine and
ruthenium red) of capsaicin are referred, to better understand
the action of the drug. The significance of the discovery
of capsaicin receptor, TRPV1, and its characteristic features
(polymodal receptor) are discussed based on recent reports,
although the sensitization or desensitization mechanisms are
not yet resolved. This review also briefly deals with the
therapeutic use of capsaicin and its agonist and antagonist
for relief pain. Whether or not capsaicin-sensitive nerve
fibers are involved in itching is examined by a recent literature
survey. TRPV1- expressing nerve fibers were recently reported
to be responsible for the itching sensation. Three possible
itching pathways were raised. The participation of pure sensory
nerve fibers which exclusively transmit itchiness has not
been found, as yet.
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Anatomical and Functional Relationships Between
Sensory Nerves and Mast Cells
Fatma Tore and Nese Tuncel
Mast cell and sensory nerve relationships fall into three
categories: proximity, communication and a shared fate. Mast
cells are found in all tissues of the human body, especially
located closely to nerves. Mast-nerve membrane to membrane
contact is a highly common configuration. This should be by
design rather than by accident since such spatial distributions
generally indicate a functional relationship. Mast cells associated
to sensory nerves contain abundant neuropeptides and also
a range of neuropeptide receptors enabling nerve to mast cell,
mast cell to nerve and reciprocal communications which form
the basis of neuroimmune interfacing. Wondering about the
possible effects of this intimacy and communication potential
on several physiological and pathophysiological events, specifically
on diseases with low success rates of therapy and mysterious
mechanisms, scientists have uncovered many aspects of mast-nerve
interactions. In light of these studies, from a focal point
between the nervous and immune systems, mast cells highlight
the concept of collaboration as an indispensable building
block of the neuroimmune system.
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Article]
TRPV1 and TRPA1 in Pulmonary Vagal Afferents
and their Relations to Airway Sensitivity
Hiroyuki Watanabe, Takayoshi Ohba, Kazuhiro Satoh, Masaaki
Sano, Takanobu Shioya and Hiroshi Ito
In the last 15 years, studies of transient receptor potential
(TRP) channels have significantly extended our knowledge about
the molecular basis of sensory function in pulmonary vagal
afferents. In particular, TRPV1 and TRPA1 channels are unique
cellular sensors for a wide range of inflammatory mediators
and noxious irritants. These channels act as the molecular
integrator of multiple nociceptive stimuli and are involved
in multiple cellular functions, ranging from transduction
of sensory signals to the release of neuropeptides in pulmonary
vagal afferents. Increased activity of TRPV1 channels is now
recognized as a cause of airway hypersensitivity in inflammatory
airway diseases. In this review, we summarize current knowledge
about the activation mechanisms of TRPV1 and TRPA1, and discuss
the possible functional implications of TRPV1 and TRPA1 in
human physiology and pathophysiology, such as the cough reflex
and hypersensitivity.
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Article]
Capsaicin-Sensitive Nociceptive Innervation of the
Dura Mater: Implications for the Pathomechanism of Headache*
Mária Dux, Judit Rosta and Gábor Jancsó
This review focuses on the critical pathophysiological
significance of capsaicin-sensitive trigeminal primary afferent
neurons in the mechanisms of neurovascular responses in animal
models of cranial pain and their possible relevance for primary
headaches. In the rat dura mater, neurogenic sensory vasodilator
responses elicited by activation of the transient receptor
potential vanilloid type 1 (TRPV1) receptor are mediated by
the release of calcitonin gene-related peptide (CGRP) from
sensory nerves, which suggests that similar mechanisms may
operate in man during migraine attacks, when an increased
concentration of CGRP is measured in the jugular venous blood.
Capsaicin-sensitive trigeminal afferent nerves also contribute
to the vasodilatory responses induced by the activation of
protease-activated receptor 2 (PAR-2), which involves the
release of CGRP from capsaicin-sensitive afferent nerves.
Importantly, the activation of PAR-2 has been shown to sensitize
the TRPV1 receptor. Demonstration of the colocalization of
PAR-2 and TRPV1 receptors in the meningeal axons lends further
support to this mechanism. Neurogenic vasodilatory responses
mediated by capsaicinsensitive afferent nerves may serve a
protective function via the elimination of inflammatory mediators
from the tissue, a mechanism which may play a role in the
resolution of headaches. Pathological conditions such as diabetes
mellitus may compromise this protective mechanism through
decreases in the expression of TRPV1 and the release of CGRP.
These observations indicate an important role of capsaicin-sensitive
meningeal afferent nerves in the pathophysiology of headaches
and suggest that pharmacological manipulation of the TRPV1
receptor may offer a promising approach to the management
of headaches.
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Article]
Pain Alleviation in Anti-Inflammatory and Anti-Allergic
Conditions
Ceng Luo, Rou-Gang Xie and San-Jue Hu
Pain and inflammation are considered strongly associated.
The greater pain behavior was demonstrated in animals with
greater amount of inflammation. Tissue or nerve injury results
in the release of various inflammatory mediators such as prostaglandins,
bradykinin, proinflammatory cytokines, chemokines, histamine,
serotonin and nerve growth factors from the site of injury.
These inflammatory mediators play a critical role in both
integrating the inflammatory response and mediating pain hypersensitivity.
This review highlights the role of prostaglandins and proinflammatory
cytokines in the pain sensitization and its underlying mechanisms,
emphasizing the evidence that these molecules are potential
targets to develop novel drugs and therapies for the treatment
of both inflammation and pain in clinic.
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Article]
The Capsaicin Paradox: Pain Relief by an Algesic Agent
Gábor Jancsó, Orsolya Oszlács
and Péter Sántha
Chemosensitive primary sensory neurones expressing the
TRPV1 receptor, a molecular integrator of diverse noxious
stimuli, play a fundamental role in the sensation of pain.
Capsaicin, the archetypical ligand of the TRPV1 receptor,
is one of the most painful chemical irritants, and its acute
administration onto the skin and mucous membranes elicits
severe pain. However, repeated or high-dose applications of
capsaicin, and/or its administration through specific routes
dramatically decreases the sensitivity of the innervated tissues
to noxious chemical and heat stimuli. This review surveys
the mechanisms of the antinociceptive, anti-inflammatory and
anti-hyperalgesic effects of vanilloid agonists applied topically,
or perineurally, or injected into the subarachnoid space in
animal experiments and to put these data into a clinical perspective.
The great body of available experimental evidence indicates
that vanilloid agonists exert their antinociceptive actions
through TRPV1 receptor-mediated selective neurotoxic/neurodegenerative
effects directed against somatic and visceral C-fibre nociceptive
primary afferent fibres. It is expected that vanilloid agonists
will broaden the palette of analgesic drugs which do not cause
addiction and tachyphylaxis.
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Article]
Anti-inflammatory Lipid Mediators Derived from ω-6
and ω-3
Polyunsaturated Fatty Acids as a Treatment Option for IBD
Shin Nishiumi, Izumi Kure, Tsukasa Ishida, Makoto Ooi,
Tomoo Yoshie, Hiromu Kutsumi, Takeshi Azuma and Masaru
Yoshida
Lipoxins and resolvins are endogenous lipid mediators derived
from ω-6
and ω-3
polyunsaturated fatty acids (PUFAs), respectively. Lipoxins,
such as lipoxin A4 (LXA4) and lipoxin B4 (LXB4), are known
as the first proresolving mediators, and their appearance
leads to the resolution of inflammation. In addition, resolvins,
such as D series resolvins (RvD) and E series resolvins (RvE),
play important roles in the resolution of inflammation. So
far, the anti-inflammatory effects of lipoxins and resolvins
have been revealed in various experimental models of inflammatory
disorders, and much attention has been paid to PUFAs and lipid
mediators derived from PUFAs as a therapeutic strategy for
inflammatory disorders including inflammatory bowl diseases
(IBD). Recent studies using animal experimental models demonstrated
that lipoxins; aspirin-triggered lipoxins; and their stable
analogues, such as LXA4 and aspirin-triggered 15-epi-LXA4,
were able to attenuate colitis. Resolvins, such as RvE1, were
also demonstrated to protect against colitis. Moreover, it
has been proposed that the biological abilities of endogenous
anti-inflammatory lipid mediators are induced via their corresponding
receptors, for example, FPR2/ALX for LXA4 and ChemR23 for
RvE1, and the expression levels of their receptors were reported
to be increased in macrophages and intestinal epithelium stimulated
with exogenous antigens such as lipopolysaccaride. In this
paper, the anti-inflammatory effects of lipid mediators derived
from PUFAs, especially LXA4 and RvE1, are outlined, and the
possibility of their use as a therapeutic strategy for IBD
is discussed.
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