Pruritus Flashcards
Describe sensation in the skin
- Sensory nerves can be myelinated or unmyelinated. Conduction speeds of the former are faster
-Some unmyelinated nerves are found extending into the epidermis. Fibres mediating itch fibres are found in the epidermis as well as the dermis)
-Loss of sensation may lead to the development of trophic ulceration from repeated trauma. Examples would include foot ulcers in advanced diabetes, or pressure sores in anaesthetic areas
-It is possible that cutaneous sensory nerves have some sort of trophic role — that is, if they are damaged, surrounding tissue does not grow properly or repair itself properly
Describe the effector nerve supply
-Only effector nerves in skin are sympathetic nerves —there is no parasympathetic supply to skin —of both cholinergic and adrenergic post-ganglionic varieties.
-Two important effector roles are: control of vascular tone, and eccrine sweating. Both of these are key elements of thermoregulatory control
Thermoregulation of the skin
-More blood flows through skin than the brain, and the ability to vary heat loss by changing blood flow patterns is critical.
-This is achieved by opening and closing of a variety of shunts in skin that determine how superficially blood flows.
-This function may be deranged in cases of widespread skin disease (erythroderma), because the inflammatory processes drive increased blood flow.
-The result is that patients ‘overcool’ themselves, resulting in central hypothermia, but because they are ‘red all over’, they look ‘hot’ (i.e. they are vasodilated)
Describe eccrine sweat glands
-Largely under the function of post ganglionic cholinergic fibres (but) of the sympathetic nervous system.
-Neurological damage to sweat glands in one body site leads to compensatory increases in sweating at other sites.
Describe arrector pili smooth muscles
-Under sympathetic control, and they cause your hairs to ‘stand on end’ (goosebumps).
-In mammals with a dense coat of fur, this is a useful means of trapping air under the fur.
Describe the itch pathway
-Itch receptors found in dermis and very superficially in the epidermis.
-Itch is principally conducted along unmyelinated C fibres that conduct at rates of ~5cm/ sec (i.e. slowly).
-These fibres have large receptive fields (i.e. they may cover a large area of skin).
-The fibres cross over in the spinothalamic tract in the spinal cord and synapse with ascending fibres and intermediate neurones that mediate the itch-scratch reflex.
-Many cortical areas ‘light up’ in neuroimaging studies when itch is elicited — some of the signal in these cortical areas changes when the area is then scratched.
-There is no single ‘itch centre’ in the brain.
-Itch receptors respond to a variety of different signals The most well know is histamine.
=Histamine applied superficially to skin that has been abraded elicits a sensation of pure itch.
=This signalling can be blocked or diminished by pharmacological H1 blockade.
=By contrast, if histamine is injected deeper in skin, pain rather than itch is elicited: clearly location is important.
-There are however non-histamine mediated pathways — most likely, due to a variety of mediators.
=Proteases can activate Proteinase Activated Receptors (PAR)on nerves. Some of the fibres conducting itch respond in addition to different non-itch stimuli (e.g. mechanical) and, as we shall see next, the sensation of itch may arise from other types of ‘non-itch’ fibres
What is alloknesis?
-If you induce an area of skin to itch, using histamine, the itch within this focus is conducted along C fibres.
-However, the term alloknesis describes how skin around the central focus also may appear itchy when it is lightly touched.
=This latter sensation reflects a reinterpretation of light touch as itch, at the level of the spinal cord: it is conducted along subtypes of A fibres, not C fibres. (An analogous phenomenon(allodynia) occurs in the context of pain sensation)
Interactions between pain and itch
-When people scratch vigorously, itch often appears to be replaced by pain — and most patients prefer pain to itch
-Opioids diminish pain but may provoke itch. This action is not just due to opioids causing mast cell degranulation, but seems to reflect reciprocal inhibitory pathways at the level of the spinal cord
-Both itch and pain travel as crossed modalities in the spinothalamic tract up to the thalamus and onward to a cortical representation
Chronic response to itch
-An exaggeration of the normal skin markings, and hyperplasia of the skin, across large areas (lichenification)
-By contrast you may see focal changes and scratching centred around individual nodules, so called nodular prurigo.
=Both are due to scratching in response to itch
Why do we scratch itch?
-Itch provokes the desire to scratch, and scratch removes any offending parasite.
-The ‘reward’ that ‘drives’ the reflex, is therefore freedom from itch. For instance, scabies infestation can, and still does occasionally, lead to a secondary streptococcal systemic infection and death.
-Itch, provokes scratch that removes this parasite, and the reward is freedom from itch (and a reduction in the chance of secondary infection).
Mechanisms for why scratching resolves itch
-Itch fibres are remarkably superficial in the skin (some within 50μ of the surface) and they may be damaged by scratch such that they no longer function. In keeping with this hypothesis, as the damage heals, the itch becomes apparent again presumably as these fibres start working
-Pain from scratch may inhibit itch via inhibitory mechanisms at the level of the spinal cord (“gate theory”), analogous to the way rubbing may help pain
How do we inhibit itch?
-No specific blockers of itch (only) propagation along the neural pathway (with the possible exception of some classes of opioid receptor subtype blockers).
=Limited to blocking the causes of the itch.
-Most skin diseases are not mediated by histamine, but sedative antihistamines are employed therapeutically.
=some antihistamines are sedatives due to central CNS effects.
=Sedation, from whatever cause, results in less scratching.
=The therapeutic effect is not due to peripheral histamine blockade, but sedation (‘you are not conscious enough to scratch’).
=Similar therapeutic effects are seen with other sedatives such as benzodiazepines or some neuroleptics.
Conditions associated with itch
-Liver disease
-Iron deficiency anaemia
-Polycythemia
-Chronic kidney disease
-Lymphoma
-Thyroid problems
-Diabetes
-Pregnancy
-Urticaria
