Itch is the most common chief complaint in patients visiting
dermatology clinics and is analogous to cough and also sneeze of
the lower and upper respiratory tract, all three of which are host
actions trying to clear noxious stimuli. The pathomechanisms of
these symptoms are not completely determined. The itch can
originate from a variety of etiologies. Itch originates following the
activation of peripheral sensory nerve endings following damage
or exposure to inflammatory mediators. More than one sensory
nerve subtype is thought to subserve pruriceptive itch which
includes both unmyelinated C-fibers and thinly myelinated Aδ
nerve fibers. There are a lot of mediators capable of stimulating
these afferent nerves leading to itch. Cough and itch pathways are
mediated by small-diameter sensory fibers. These cough and itch
sensory fibers release neuropeptides upon activation, which leads
to inflammation of the nerves. The inflammation is involved in the
development of chronic conditions of itch and cough. The aim of
this review is to point out the role of sensory nerves in the
pathogenesis of cough and itching. The common aspects of itch
and cough could lead to new thoughts and perspectives in both
fields.
An excessive, irritable, productive or non-productive coughing
associated with airway inflammation belongs to pathological
cough. Increased activation of airway vagal nociceptors in
pathological conditions results from dysregulation of the neural
pathway that controls cough. A variety of mediators associated
with airway inflammation overstimulate these vagal airway fibers
including C-fibers leading to hypersensitivity and hyperreactivity.
Because current antitussives have limited efficacy and unwanted
side effects there is a continual demand for the development of
a novel more effective antitussives for a new efficacious and safe
cough treatment. Therefore, inhibiting the activity of these vagal
C-fibers represents a rational approach to the development of
effective antitussive drugs. This may be achieved by blocking
inflammatory mediator receptors or by blocking the generator
potential associated with the specific ion channels. Because
voltage-gated sodium channels (NaVs) are absolutely required for
action potentials initiation and conduction irrespective of the
stimulus, NaVs become a promising neural target. There is
evidence that NaV1.7, 1.8 and 1.9 subtypes are predominantly
expressed in airway cough-triggering nerves. The advantage of
blocking these NaVs is suppressing C-fiber irrespective to stimuli,
but the disadvantage is that by suppressing the nerves is may
also block beneficial sensations and neuronal reflex behavior. The
concept is that new antitussive drugs would have the benefit of
targeting peripheral airway nociceptors without inhibiting the
protective cough reflex.