Psyconeurodermatology Flashcards
Which growth factor is involved in supporting survival and outgrowth of sensory fibers?
Neurotrophin-4
There an increase in intraepidermal fibers in both atopic humans and dogs.
The skin is equipped with a dense network of highly specialized afferent ____ and efferent _____ nerve braches that can be found in all skin layers.
sensory
autonomic
What are the main functions of the cutaneous nervous system?
Sensory: touch, heat, cold, pressure, pain and itch
Motor: control vasomotor tonus, regulate the secretory activities of glands
What is the general anatomy of the cutaneous nervous system?
- Cutaneous nerve trunks carry myelinated postganglionic sympathetic fibers
- Stained by methylene blue staining, metallic impregnation
Dermatome
the area of skin supplied by the branches of one spinal nerve
Describe autonomic nervous innervation?
- Autonomic (sympathetic) nerves represent only a minority of cutaneous fibers innervating eccrine, apocrine, and sebaceous glands, hair follicles, hair erector muscles, and blood vessels.
- On activation, they release acethylocholine (Ach) and norepinephrine, which activate the target cells via muscarinic and catecholamine receptors.
Cutaneous sensation consists of?
Sensory nerves and receptors.
Sensory nerves surround hair follicles as well as encapsulated structures such as Pacini’s corpuscle, Meissners corpuscle, and Ruffinis corpuscle
Sensory nerves are derived from _____ and are present in all parts of the skin
dorsal root ganglion neurons
What are pencillate nerve endings?
Sensory nerves that end as free nerve endings
Arise from the terminal Schwann cell in the dermis as tuftlike structures and give rise to an arborizating network of fine nerves, and they terminate either subepidermnally or intraepidermally
• Unmyelinated
• Limited to the skin, mucous membranes, and cornea
On the basis of properties of afferent units, somatosensory activity can be subdivided into what three categories?
nociceptors, thermoreceptors, and mechanoreceptors:
Nociceptors:
involved in itch and pain; supplied by A, and C fibers
Mechanoreceptor units
4 types with A axons in most skin regions
Pacinian corpuscles
Rapidly adapting units
Within haired skin
Slowly adapting Type I endings
Neuropeptides
- Neuropeptides released by cutaneous nerves in response to a variety of noxious stimuli can activate a number of target cells such as keratinocytes, mast cells and endothelial cells (upregulating VCAM – 1, expression and causing secretion of IL-8).
- Synthesized and released predominantly by a subpopulation of small neurofilament-poor (unmyelinated) afferent neurons (C fibers) designated as C-polymodal nociceptors.
Mechanoreceptor units - within haired skin
many afferent units that are excited by hair movement and have both A and A axons.
• Units driven from large hairs: A β axons
• Units driven from down hairs have A δ units
• These axons provide the major tactile input from such regions
• Guard and down hairs receive many nerve terminations of the lanceolate types
Slowly adapting Type I endings
from Merkel’s cell complexes signal about steady pressure
Slowly adapting Type II units
Associated with Ruffini endings show directional sensitivity in response to skin stretch and may play a role in propioception
List 7 neuropeptides?
substance P*(more information in pruritus)
neurokinin A
calcitonin gene-related peptide
vasoactive intestinal peptide
neuropeptide Y
somatostatin
pituitary adenylate cyclase activity peptide
Neurohormones
such as alpha-melanocyte-stimulating hormone (α-MSH) are capable of modulating a range of cellular activities; can be detected in peripheral nerves and are produced by different cell types in the skin
What is the general function of neutropeptides and neurohormones?
Function of both neuropeptides and neurohormones include: the modulation of cell proliferation, cytokine production, and cellular adhesion molecule expression
What are the 3 main neuropeptide receptors and their functions?
different types of neuropeptide receptors have been identified on the neuronal and non-neuronal cells in the skin
- NK (3 principal neurokinin receptors): bind with high affinity to substance P, NK A, and NK B; seven-transmembrane G protein-coupled peptides; detected keratinocytes and dermal endothelial cells
- CGRP (2 subtypes): Dermal microvascular endothelial cells and Langerhans cells have been reported to respond specifically to CGRP
- Melanocortin (MC) receptors: a group of 5 G protein-coupled receptors with 7 transmembrane domains; epidermal and dermal cells as well as inflammatory and immunocompetent cells exhibit high affinity for αMSH.
NK (3 principal neurokinin receptors)
bind with high affinity to substance P, NK A, and NK B; seven-transmembrane G protein-coupled peptides; detected keratinocytes and dermal endothelial cells
CGRP (2 subtypes)
Dermal microvascular endothelial cells and Langerhans cells have been reported to respond specifically to CGRP
Melanocortin (MC) receptors
a group of 5 G protein-coupled receptors with 7 transmembrane domains; epidermal and dermal cells as well as inflammatory and immunocompetent cells exhibit high affinity for αMSH.
What are two neuropeptide-degrading enzymes
Neutral endopeptidase (NEP, CD10) Carboxypeptidase angiotensin-converting enzyme (ACE):
Neutral endopeptidase (NEP, CD10)
cell membrane associated protease capable of degrading neurokinins; an important regulator in terminating neurogenic inflammation
Carboxypeptidase angiotensin-converting enzyme (ACE):
biologic effects similar to those of NEP
Neurogenic inflammation
the inflammatory response in the skin by direct electrical stimulation of sensory nerves or by stimulation of these nerves by chemical irritants, such as capsaicin, mustard oil, formalin, xylene, or hypertonic solutions.
Major consequences of neuro-inflammatory responses include vasodilatation, increased vascular permeability, and plasma leakage.
What are the two hallmarks of neurogenic inflammation?
vasodilatation and plasma leakage
Neuroanatomy species differences
Cat haired skin: unmyelinated axon, the C mechanoreceptor Equine epitrichial (apocrine) sweat glands are controlled by a β adrenergic control Small animal epitrichial sweat glands do not appear to be innervated
What are the different classifications of itch? There are 9.
- Epicritic itch a spontaneous, sharp, well-demarcated pruritus.
- Protopathic itch pruritus that is poorly localized and possesses a burning quality.
- Spontaneous itch well-localized itch at the site of itch stimulation that persists briefly after the stimulus is removed.
- Itchy skin a poorly localized area adjacent to the site of the itch stimulation that doesn’t itch spontaneously, but is hyperresponsive when exposed to a minor stimulus such as light touch
- Physiologic itch a short-lived response in skin to the common environmental stimuli that may or may not provoke scratching.
- Pathologic itch an intense skin response occurring with pathologic changes that provoke severe scratching.
- Scattered itch multiple distant areas of pruritus present in the skin following the previous stimulation of itch at one primary site.
- Referred itch development of a focal area of pruritus during scratching of the primary pruritic site. Similar to scattered itch.
- Conversion itch the change of a normal cutaneous sensory experience (like touch) to pruritus.
Pruritoceptive
induced by stimulation of the free nerve endings of the specialized C-fibers by one or more of a range of pruritogens.
Pruriceptive primary afferents-
Pruritoceptive
induced by stimulation of the free nerve endings of the specialized C-fibers by one or more of a range of pruritogens.
Pruriceptive primary afferents
When stimulated by a pruritogen, a subset of specialized unmyelinated C-fibers (originating superficially in the skin) conveys impulses to the dorsal horn of the spinal cord and then via the spinothalamic tract to the thalamus, and on to the somatoseonsory cortex.
C-fibers
- Anatomically identical to those associated with pain BUT functionally distinct
- C-fibers that mediate itch comprise about 5% of the afferent C-fibers in human skin nerves
- Respond to histamine and other pruritogens but are insensitive to mechanical stimuli.
Aδ fibers
Myelinated
Carry sensations of pain, tactile temperature, and epicritic itch (spontaneous, well-localized itch)
List itch-producing mediators in the skin
Histamine Aceytlcholine Serotonin Endopeptidase Neuropeptides Eiconsanoids Cytokines
Histamine
- Directly stimulates histamine type 1 (H1) rececptors on itch-specific C-fibers
- Causes rapid tachyphylaxis with respect to vasodilation and increased vascular permeability – as a result of the secondary release of vasoactive substances from collateral axons (specifically calcitonin gene-related peptide (CGRP) and substance P)5
- Important mediator in short-lived wheal-and-flare reactions of the urticarial type
Aceytlcholine
• Stimulates histamine-sensitive and histamine-insensitive C-fibers
Endopeptidase
• Trypsin, papain (present in the spicules of Mucuna pruriens) – cause itch
• Tyrpsin: an important component of dermal mast cells; secreted upon mast cell activation
Recent studies (2000): suggest that mast cell-dervied tryptase, by its action on proteinase-actived receptor-2 (PAR-2) contained in adjacent C neuron terminals, evokes release of pruritogenic neuropeptides by the same terminals additional pathway of itch?
• Kallikrein: a kinin-forming enzyme, the best known product of which is bradykinin
Causes predominately pain rather than itch, by a peripheral action.
Eiconsanoids
Arachidonic acid transformation products (prostaglandins, leukotrienes, and other hydroxyl fatty acids) possess powerful pro-inflammatory properties, but are not directly pruritic.
Lipoxygenase pathway – results in the formation of leukotrienes
• LTD4 and LTE4 – may cause transient burning on injection, but not pruritus.
• LTB4 – one of the most potent neutrophil chemoattractants and may cause pruritus due to recruitment of leukocytes and potentiation of other mediators.
Acts in synergy with PGD2 as mediators of inflammation.
Cyclooxygenase pathway - results in the formation of prostaglandins
• PGE1 – unable to cause pruritus by itself, but significantly lowers the pruritus threshold in human skin.
• PGE2 and PGH2 – both capable of producing pruritus but PGE2 is more potent.
Eiconsanoids
Arachidonic acid transformation products (prostaglandins, leukotrienes, and other hydroxyl fatty acids) possess powerful pro-inflammatory properties, but are not directly pruritic.
Lipoxygenase pathway – results in the formation of leukotrienes
• LTD4 and LTE4 – may cause transient burning on injection, but not pruritus.
• LTB4 – one of the most potent neutrophil chemoattractants and may cause pruritus due to recruitment of leukocytes and potentiation of other mediators.
Acts in synergy with PGD2 as mediators of inflammation.
Cyclooxygenase pathway results in the formation of prostaglandins
• PGE1 – unable to cause pruritus by itself, but significantly lowers the pruritus threshold in human skin.
• PGE2 and PGH2 – both capable of producing pruritus but PGE2 is more potent.
PGE enhance itching due to other mediators. Pretreatment of human skin by low concentrations of PGE1 lowered the threshold the treated skin to itch produced by subsequent intradermal injection of histamine at the same sites.
Apart from a subset of HIV+ patients and polycythaemia vera, NSAIDS generally have no effect on itching; benefit may relate to blocking cytokine-induced PGE2 production
Cutaneous nerves of the somatic sensory generate _____ and thus influence development, sprouting and survival of nerve fibers.
neutrotrophins.
In general, cutaneous nerve fibers are associated with what structures?
- blood vessels
- tylotrich pads
- Pacini corpuscles
- Meissner corpuscles
- Ruffini corpuscles
- Sebaceous glands
- hair follicles
- arrestor pili muslces
The motor innervation of skin is attributed to ______ fibers for the _____ nervous system.
sympathetic fibers
autonomic nervous system
Small, hairless, knoblike innervated structures are present in the haired skin of cats and dogs these are called ____ and serve as slow-adapting mechanoreceptors.
tylotrich pads
Allodynia
touch evoked pain
Alloknesis
touch-evoked itch, itchy skin
End organ
The specialized terminals of peripheral afferent nerves that transducer sensory stimuli into action potentials.
Epicritic itch
Itch that is sharp and well localized; transmitted by aδ fibers (myelinated)
Nociceptor
A somatosensory neuron activated by noxious mechanical, thermal or chemical stimuli.
Protopathic itch
Itch that is poorly localized and may have a burning quality, transmitted by C fibers (non-myelinated)
Pruritoceptive
Itching resulting from activation of peripheral nerves
Pruriceptor
A somatosensory neuron activated by pruritus stimuli
Punctuate hyperkinesis
Skin prick inducing intense itch sensation
Rapid-adapting receptor
Light-touch receptor that responds robustly at the onset of a sustained mechanical stimulus.
Slow-adapting receptor
Light-touch receptor that fires at a low level throughout a sustained mechanical stimulus.
Meissner corpuscles
Rapid adapting mechanoreceptor
Located in superficial dermis, layers of cells enfold the large leaflike ending of two to six afferent nerves, responds to vibration
Merkel cell
Slow-adapting type 1 mechanoceptor
Located in basal layer of epidermis, unmyelinated ending of afferent service, is a touch receptor and respond to pressure, edges and curves.
Pacinian corpuscle
rapid adapting mechanoreceptor
Large, layered, onion like structure enclosing a afferent neuron, sensitive to pressure and vibration
Ruffini corpuscle
slow-adapting type II mechanoreceptor
Located in connective tissue of dermis, large spindle shaped structure interconnects with collagen matrix, sensitive to skin stretch
Sinus hairs
Slow-adapting mechanoreceptor
Longer, thicker, and stiffer than normal hairs and have an endothelium-line blood sinus located between the external root sheath of the follicle nd the outer connective tissue capsule.
Pancinain corpuscles are located close to the sinus hair follicle.
Tylotrich hair
Rapid-adapting mechanoreceptor
Specialized hair that is large primary follicle surrounded by a ring of neurovascular tissue. Associated with a tylotrich pad.
Tylotrich pad
Slow-adapting mechanoreceptor
A local area of epidermal thickening with a layer of highly vascular and well-innervated connective tissue under it.
Acetycholine
Source: Autonomic cholinergic nerves, keratinocytes, lymphocytes, melanocytes
Receptor: nicotinergic and muscarinergic acetylcholine receptors.
Function: keratinocyte differentiation and function, regulation of skin circulation, sweat gland secretion
Calcitonin gene-related peptide (CGRP)
Source: sensory nerve fibers (dorsal root ganglion)
Receptor: CRGP receptors
Function: keratinocyte and endothelial cell proliferation, stimulate cytokine production
Neurokinin A
Source: sensory nerve fiber
Receptor: tachykinin receptors
Function: up regulates keratinocyte expression of nerve growth factor
Noradrenaline
Source: sympathetic nerves, keratinocytes, melanocytes
Receptor: adrenergic receptors
Function: Innervation of blood vessels, arrestor pili muscles, affects activity of natural killer cells, monocytes, lymphocytes, keratinocyte migration
Pituitary adenylate cyclase-activating polypeptide
Source: autonomic and sensory nerves, lymphocytes, endothelial cells
Receptor: VPAC receptors
Function: vasodilation, immunomodulation, nociception.
Pro-opiomelanocortin
Source: melanocytes, keratinocytes, endothelial cells, Langerhans cells, mast cells, fibroblasts, monocytes, macrophages.
Receptor: Melanocortin receptors
Function: immunomodulation (decreases inflammation)
Substance P
Source: sensory nerve fiber
Receptor: Tachykinin receptor (NK-1)
Function: inflammation, up regulation of cell adhesion molecules
Vasoactive intestinal peptide
Source: sensory nerve fiber, Merkel cells
Receptor: VPAC receptors
Function: vasodilation, proliferation and migration of keratinocytes, histamine release from mast cells
What are the three. types of rapidly adapting mechanoreceptors?
- tylotrich hairs
- Pacinian corpuscle unites
- Meissner corpuscles
What are the three types of slow-adapting mechanoreceptors?
- Merkel cell type 1 nerve endings
- Ruffini corpuscles with type II nerve endings
- Tylotrich pads
Guard and down hairs receive many nerve terminations of the ____ type?
lanceolate type - such units can be subdivided into two major cases
- those excited by only movement of large guard or tylotrich (G and T hair units-fast)
- those excited by movement of all hairs, but especially by fine hairs (D units - slow)
**units driven by large hairs almost always have ab axons; those driven from down hairs have ag axons.
A characteristic class of mechanoreceptor, is frequently encountered in ___ haired skin.
cat
Most nociceptor units fall into what two categories?
Delta high threshold mechanoreceptors units with delta axons and polymodal nociceptor units with C axons.
The later afferents are classic pain receptors, responding to intense mechanical and thermal stimuli and irritant chemicals.
What nociceptor units are involved with hyperalgesia and pruritus and flare around skin injuries?
Polymodal C fibers
Autonomic nerves in the skin are primarily ____ neurons, with fewer______ ones. These nerves are located in the dermis and innervate blood vessels, arteriovenous anastomoses, lymphatic vessels, arrestor pili muscles, hair follicles, and sweat glands.
sympathetic
parasympathetic
Some sympathetic nerve fibers release _____ and ______ to mediate vasoconstriction.
noradrenalin
neuropeptide Y
Parasympathetic nerves mediate vasodilation through the release of ______, ______ and _______.
acetylcholine
vasoactive intestinal peptide
peptide histidine methionine
Where in the brain is pruritus processed?
prefrontal cortex
promoter areas
primary somatosensory cortex
anterior cingulate cortex
What nerves are present in the spinothalamic tract in cats that DO NOT respond to mechanical stimuli?
histamine-sensitive nerves
Cowhage (mucuna pruriens)
this is an example of a pruritogen that induces itching without producing a flare. It has been demonstrated that response to cowhide is transmitted by nerves that are distinct from those responding to histamine.
What is histamine?
histamine is a potent biogenic amine that has long been recognized as one of the causes of pruritus. There are at least four different histamine receptors.
** study showed that H4 agonist induced wheal formation in dog
Increased levels of what substance lead to sprouting and growth of epidermal nerve fibers? in humans, the level of this substance is correlated with severity of atopic dermatitis in humans.
neutrotrophins (nerve growth factor)
** keratinocytes and mast cells are important sources of nerve growth factor
Alkaline skin pH enhances what enzyme that may increase the reception of pruritus?
serine proteases
Acetylcholine
Source: Autonomic cholinergic nerve fibers, keratinocytes, lymphocytes, melanocytes, fibroblasts, endothelial cells
Receptor: Nicotinergic and muscarinergic Act receptors
Comments: Causes pruritus in atopic dermatitis
calcitonin gene-related
peptide
Source: sensory nerve fibers
Receptor: CRGP
Comments: Sensitizes receptor endings, keratinocyte and endothelial cell proliferation
corticotropin-releasing hormone
Source: hypothalamous
Receptor: keratinocytes and mast cells
Comments: Induces mast cell release of cytokines, histamine, TNFa and VEGF
endocannabinoids
Source: Neurons and keratinocytes
Receptor: Cannabinoid receptors
Comments: Antipruritic in the skin
Endothelins
Source:endothelial cells and mast calls
Receptor: endothelia receptors (ETa and ETb)
Comments: directly pruritic (burning itch)
Endovanilloids
Source: heat, acidosis, eiconsanoids, histamine, bradykinin, extracellular adenosine triphophate, prostaglandins, various neurotrophins.
Receptor: Transient receptor, potential vanilloid 1 receptor
Comments: Induce pain and itch, affect epidermal proliferation and differentiation.
histamine
Source: Sensory fibers, mast cells
Receptor: Histamine receptors H1R and H4R
Comments: H1 and H4 agonists stimulate flare, H1 agonists induce itch
IL-2
Source: T cells
Comments: Causes pruritus
IL-31
Source: Helper T cells and macrophages
Receptor: GP 130-like receptor, OSMR
Comments: causes pruritus, increased expression in atopic dermatitis
Kallikreins, proteases
Source: Leukocytes, keratinocytes, mast cells, endothelial cells and platelets
Receptor: Protease-activated receptors, tryptic enzymes
Comments: pruritic through protease activated receptor 2
Kinins
Source: endothelial cells
Receptor:Bradykinin receptors B1R and B2R
Comments: Induce pain in normal skin, itch in sensitized skin
Leukotriene B
Source:leukocytes, mast cells
Receptor: leukotriene receptors
Comments: induces itch and inflammation
Neurokinin A
Source: nerve fibers
Receptor: tachykinin receptors
Comments: Upregulates keratinocyte nerve growth factor expression
Nerve growth factor
Source: keratinocytes, mast cell, fibroblasts, eosinophils
Receptor: tyrosine receptor kinase A (type 1)
Comments: peripheral sensitization potentiates itching - upregulates TRPV1)
Opioids
Source: Neurons, keratinocytes and mast cells
Receptor: u, k and delta opioid receptors
Comments: u-opioid is pruritic at spinal level, k-opioids are antipruritic
Pituitary adenylate cyclase-activating polypeptide
Source: autonomic and sensory nerve fibers, lymphocytes, dermal endothelial cells
Receptor: VPAC receptors
Comments: vasodilation, immunomodulation and pain (nociception)
Pro-opiomelanocortin
Source: melanocytes, keratinocytes, endothelial cells, Langerhan cells, mast cells, fibroblasts, monocytes, macrophages
Receptor: melanocortin receptors
Comments: antagonizes pro inflammatory cytokines, induces histamine release from mast cells inhibits nuclear factor kB (decreases inflammation)
Prostaglandin E
Source: nerve fibers, keratinocytes, mast cells
Receptor: prostanoid receptors
Comments: causes pruritus
Substance P
Source: sensory nerve fibers and keratinocytes
Receptor: NK-1 receptor
Comments: priming of mast cells, causes pruritus in some species by histamine-dependent and histamine independent mechanisms
Thromboxane A2
Source: keratinocytes and nerve fibers
Comments: causes pruritus
Typtase
Source: mast cells
Receptor: protease activated receptor 2
Comments: causes pruritus
Vasoactive intestinal peptide
Source: sensory nerve fibers, merkel cells
Receptor: VPAC receptors
Comments: vasodilation, histamine release from mast cells
Activated nerves can release what substances that can modulate immune cells and their responses during inflammation in AD?
substance P
calcitonin gene–related protein
neurotrophins (eg, nerve growth factor)
The receptors to which cytokine have most recently been found on sensory C-fibers and in the dorsal root ganglia in rodents where they likely contribute to the transduction of pruritus signals?
IL-31
What binds to neurokinin-1 receptors present on a variety of immune cells such as neutrophils, lymphocytes, macrophages, lymphocytes, and mast cells, leading to their activation.
Substance P
***Neurokinin-1 receptors have also been found on neurons within the dorsal horn, and recently, these neurons have been shown to mediate scratching be- havior in mice.
In AD, itch signals are detected through relevant itch receptors present cutaneous itch-selective sensory nerves residing in the epidermis and dermis. The signals then travel along _______ and are received by the ________ and the ______ within the dorsal horn of the spinal cord. The itch signal finally reaches the brain through ______ neurons
unmyelinated nervefibers
dorsal root ganglia
lamina I region
spinothalamic tract neurons
What is a serine protease that may play a key role in urticaria, inducing edema through an increase in vascular permeability, mast cell activation and degranulation, and production of the anaphylotoxin C5a.
Thrombin
Acute stress is associated with increases in interleukin ___ and ___, suggesting activation of inflammatory pathways.
IL-6 and C-reactive protein
TCAs act primarily by increasing NTs ___ and ____ by blocking their reuptake by the presynaptic neuronal membrane, which effectively increases their NT activity.
serotonin and norepinephrine
Amitryptykube and dose-in are potent ___ blockers which may contribute to some of the beneficial effects seen, particularly if there is an underlying allergy present.
H1
SSRIs (fluoxetine) ar emoe selective than TCAs, with their effected limited to only blocking reuptake of ____; therefore, other effects including many fox eh side effects of TCASs are not seen.
serotoninin
Fluoxetine is a potent inhibitor of what enzyme? So caution must be taken when prescribing using it concurrently with other drugs.
Cytochrome P-450
Neither SSRI or TCAs should be administered concurrently with _____ inhibitors (amitraz, selegiline) or L-Tryptophan.
Monoamine oxidase inhibitors
What drug blocks serotonin presynaptic and postsynaptic receptors AND has dopamine agonist activity.
Buspirone
It is a serotonin 5-HT1A receptor agonist.
What idiopathic disease does diazepam cause in cats?
idiosyncratic hepatoxicosis
What breeds are predisposed to developing acral lick dermatitis?
Dobermans, Labrador Retrievers, Great Danes, Irish Setter, Golden Retrievers, boxer, Weimaraner and GSD.
What are the common histopathologic findings in acral lick dermatitis?
Moderate to marked, frequently papillated acanthosis
Erosion or ulceration with exudation
Occasional neutrophilic serocellular crusts
Hyperkeratosis
Dermal fibrosis in a vertical streaking pattern
Thickened and elongated follicles
Dermal infiltrate of lymphocytes, neutrophils, macrophages, and plasma cells in a perivascular, perifollicular, or diffuse pattern
Dilatation, hypertrophy of epitrichial glands, often with retained secretions
Perihidradenitis and hidradenitis with occasional gland rupture
Folliculitis and furunculosis
What is a chili pepper extract, contains analgesic properties and has been shown to be effective in reducing neuropathic pain?
Capsaicin
What contains serotonin neurons that provide most of the serotonergic input to forebrain structures involved in complex emotional response regulation to stress?
the dorsal raphe nucleus
Antidepressants are the most effective in treating acral ick dermatitis. In general, what two drugs appear to be the most effective?
fluoxetine and clomipramine
What antihistamine used for the treatment of acral lick dermatitis his a piperazine-durative antihistamine with other effects and has been helpful in some cases (especially associated with allergy).
hydroxyzine
What breed is predisposed to tail dock neuroma?
Cocker spaniels
Flank sucking is most commonly seen in what breed of dog?
Dobermann Pinchers
What breed is predisposed to anal licking?
Poodles
What breeds of cats are predisposed to psychogenic alopecia and dermatitis?
Siamese and the other oriental breeds
**clomipramine is the drug of choice
Sinus hairs are located on the muzzle, lips, eyes, face and throat and palmar aspect of the campus of cats. Where is the endothelium blood sinus located?
Between the external root sheath of the hair follicle (ORS) and outer connective tissue capsule.
What rapid-adapting mechanoreceptor structures are located close to the sinus hair follicles (slow-adapting mechanoreceptors)?
Pancinian corpuscles - onion like structures enclosing on afferent neuron.
What is mediated by free nerve endings of nonmyelinated nerve fibres that are located at the dermo-epidermal junction and within the epidermis?
pruritus
What is a specific receptor in the posterior root of the spinal cord which is exclusively responsible for transmitting the perception of pruritus but not pain or temperature perception?
gastrin-releasing peptide receptor
Gastrin-releasing peptide (GRP) receptors in the superficial dorsal horn of the spinal cord are also drawing attention as a novel pathway of itch-selective neural transmission
What is the proposed theory for why there is an antipruritic effect of the pain induced by scratching?
The gate-control theory suggests that pruritus is suppressed by mechanical or electrical stimulation of rapid-transmitting myelinated A-fibres at the spinal level in favor of transmitting pain sensation
The pruritogenic effect of endogenous opioids depends, however, on the activation of specific opioid receptors. While the activation of ___-receptors causes pruritus, the ___ receptor can lead to inhibition of pruritus
U
K
What was often used to describe pruritus of primary noninflamed skin?
pruritus sine materia
Among all species of domestic animals, chronic urticaria is most frequently observed in what species?
horses
What drug is the only oral opioid receptor antagonist with a long-lasting, selective blockade of u-opiate receptors?
Naltrexone
Itch signals reach the brain traveling along what fibers to reach which neurons?
Itch signals are detected through relevant itch receptors present on cutaneous itch-selective sensory nerves residing in the epidermis and dermis.
The signals then travel along unmyelinated C nerve fibers and are received by the dorsal root ganglia and the lamina I region within the dorsal horn of the spinal cord.
The itch signal finally reaches the brain through spinothalamic tract neutrons.
Proteases, such as trypsin, tryptase, cathepsins, and kal- likreins, also work as pruritogens in inflammatory skin dis- eases. What receptor do they activate?
PAR2
___ and ___ nerves are mainly involved in the conduction of thermal and pain/itch sensation, whereas ___ nerves conduct tactile sensation
AG, C
AB
