pruritus

Question 1

define pruritus

Answer 1

unpleasant sensation that elicits the desire or reflex to scratch, rub, lick, chew

Question 2

how does pruritus commonly manifest in dogs

Answer 2

• scratch
• rub
• nibble
• lick
• temperament changes

Question 3

how does pruritus often manifest in cats

Answer 3

• often secretive and not noticed by owner
• overgrooming (sometimes bilateral symmetrical alopecia not caused by endocriopathy)
• hair plucking (resulting in hair balls, tufts of hair around house and hair in feces)

Question 4

what are the 2 classifications of pruritus

Answer 4

• pruriceptive pruritus
• neuropathic pruritus

Question 4

how does pruritus often manifest in horses

Answer 4

• rubbing
• stamping
• biting
• scratching
• bucking/kicking
• temperament changes

Question 5

what is pruriceptive pruritus

Answer 5

due to stimulation of peripheral receptors in skin (in presence of a healthy nervous system) usually due to a skin disease

originates from the skin

Question 6

what is neuropathic pruritus

Answer 6

generated in the CNS in response to:
- anatomical lesion of PNS or CNS
- circulating pruritogens
- pharmacological mediators

Question 6

what receptors are responsible for sensation of itch

Answer 6

nociceptors

Question 7

what nerve fibres conduct itch

Answer 7

• unmyelinated slow-conducting C fibres
• A-delta fibres

Question 8

what other itch receptors are in the skin

Answer 8

• fine network of free nerve endings at dermo-epidermal junction and within epidermis contain itch-associated receptors
• epidermis with free C-neuron receptors act as main itch receptor in skin

Question 9

what is the main itch receptor type

Answer 9

free C-neuron receptors within the epidermis

Question 10

what chemical mediators are involved in cutaneous itch

Answer 10

a lot of different mediators
- various proteases/leukotrienes/neurotropins
- peptides
- prostaglandins
- cytokines
- histamine

Question 11

where do chemical mediators involved in itch originate

Answer 11

• keratinocytes (leukotrine, cannabinoids, thymic stromal lymphopoietin)
• mast cells (histamine, LTB-4, IL-2, NGF)
• Skin leucocytes (T-cells produce IL-31 and eosinophils which produce NGF)

Question 12

how do chemical mediators act to cause itch

Answer 12

• direct stimulation of intraepidermal nerve fibres
• stimulate mast cells
• stimulate other mediators/transduction cascades

Question 13

why is IL-31 important

Answer 13

• produced by activated T-cells in allergic skin disease
• binds to receptors on surface neurons in skin and activates JAK enzymes to stimulate pruritic nerve impulse to brain
• important focus of therapy for allergic skin disease in dogs (apoquel and cytopoint)

Question 14

describe the neural pathway for itch

Answer 14

1. sensory afferent from skin (mainly via C-neurons which are slow conducting)
2. dorsal nerve root to spinal cord
3. dorsal horn and synapse with spinal interneurons (some inhibitory, some activatory)
4. cross and ascend in lateral spinothalamic tract
5. thalamus to internal capsule
6. sensory cortex (left hemisphere dominance)

itch perception can be altered by emotiuonal factors and competing cutaneous sensations

Question 15

sensory fibres from thehead carry itch sensations via which cranial nerves

Answer 15

• trigeminal (V)
• facial (VII)
• Glossopharyngeal (IX)
• Vagus (X)

Question 16

discuss neuronal regulatory mechanisms

Answer 16

multiple factors on/in skin can also suppress/exacerbate pruritus
- physical factors (painful heat/cold supresses while moderate cold exacerbates)
- mechanical factors (rubbing/scratching causes pain) induces brief suppression of itch
- distraction

NB a truly pruritic animal (one that is severely itchy) cannot be distracted and will itch even while eating

Question 17

how does scratching work to inhibit itchy sensations

Answer 17

scratch
1. fast conducting A-beta neurons stimulated
2. activation of inhibitory neuronal circuits
3. results in widespread surround inhibition of sensation

Question 18

how does distraction work to prohibit sensations of itch

Answer 18

1. increased activity in descending pathways from reticular formation
2. activation of inhibitory circuits in dorsal horns of spinal cord
3. closes gated mechanism
4. diminishes afferent itch messages

Question 19

discuss how sensitisation in chronic pruritus works

Answer 19

not well studied in animals but in man:
peripheral sensitisation: scratching leads to increased local inflammation, leading to production of pruritogens by inflammatory cells leading to increased C-fibre responsiveness
central sensitisation: chronic inflammation of skin leads to altered perception of gentle mechanical/other stimuli which is the perceived as pruritus (allokinesis)

Question 20

list and discuss some therapeutic interventions for pruritus

Answer 20

• reduction of skin inflammation (steroids/ciclosporin)
• blocking of peripheral inflammatory mediators (cytopoint and antihistamines)
• moisturiser (dry skin is itchy)
• topical cooling preparations (calamine and menthol)

Question 21

why are some treatments for pruritus preferred over others

Answer 21

pathogenesis of pruritus involves a variety of cells/mediators/neurological pathways which can vary between species and individuals
- a single drug is unlikely to uniformly be effective in all cases
- narrowly targeted treatments generally give less side effects than those with a broader action (steroids) but will be effective in a lower % of patients
- treatments that affect a target that is only present for a short time are less likely to be effective than those in which the target is long term