Referred pain in headache

A technique consisting of the application of digital pressure to posterior neck muscles was applied at the time of headache to 82 neuropsychiatric patients observed at a Veterans Administration Mental Hygiene Clinic. Results indicated correlation between sustained muscular contraction of neck muscles and pain in the head. Certain commonalities among the Minnesota Multiphasic Personality Inventory profiles of the patients were noted and a new scale of items was developed which may prove useful in identifying headache-prone persons and their psychological characteristics. Repression was not found to be higher than the populational mean.     

The neurobiology of itch

The neurobiology of itch, which is formally known as pruritus, and its interaction with pain have been illustrated by the complexity of specific mediators, itch-related neuronal pathways and the central processing of itch. Scratch-induced pain can abolish itch, and analgesic opioids can generate itch, which indicates an antagonistic interaction. However, recent data suggest that there is a broad overlap between pain- and itch-related peripheral mediators and/or receptors, and there are astonishingly similar mechanisms of neuronal sensitization in the PNS and the CNS. The antagonistic interaction between pain and itch is already exploited in pruritus therapy, and current research concentrates on the identification of common targets for future analgesic and antipruritic therapy.     

The physiology of itch

The perception of itch is associated with many parasites and their vectors, especially following penetration of the skin by the parasites themselves, as in cercarial dermatitis of schistosome infections, or penetration of arthropod mouthparts during blood feeding. Many ectoparasites such as scabies, lice and fleas, provoke sensations of itch - even when the insects are no longer (or have never been) present, giving rise to the phenomenon of delusory parasitosis. Itch, and the host 'grooming' responses with which it is associated, is increasingly recognized as an important factor in modulating vector feeding behaviour, which can have profound effects on the transmission dynamics of vector borne parasites. As a background to future reviews of this developing subject, we asked John Alexander, author of the classic Arthropods and Human Skin (Springer-Verlag, 1984), to explain what is itch, and to discuss what is known about its underlying Physiology.     

A basophil-neuronal axis promotes itch

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Cowhage-induced itch as an experimental model for pruritus. A comparative study with histamine-induced itch

Background

Histamine is the prototypical pruritogen used in experimental itch induction. However, in most chronic pruritic diseases, itch is not predominantly mediated by histamine. Cowhage-induced itch, on the other hand, seems more characteristic of itch occurring in chronic pruritic diseases.

Objectives

We tested the validity of cowhage as an itch-inducing agent by contrasting it with the classical itch inducer, histamine, in healthy subjects and atopic dermatitis (AD) patients. We also investigated whether there was a cumulative effect when both agents were combined.

Methods

Fifteen healthy individuals and fifteen AD patients were recruited. Experimental itch induction was performed in eczema-free areas on the volar aspects of the forearm, using different itch inducers: histamine, cowhage and their combination thereof. Itch intensity was assessed continuously for 5.5 minutes after stimulus application using a computer-assisted visual analogue scale (COVAS).

Results

In both healthy and AD subjects, the mean and peak intensity of itch were higher after the application of cowhage compared to histamine, and were higher after the combined application of cowhage and histamine, compared to histamine alone (p<0.0001 in all cases). Itch intensity ratings were not significantly different between healthy and AD subjects for the same itch inducer used; however AD subjects exhibited a prolonged itch response in comparison to healthy subjects ( p<0.001).

Conclusions

Cowhage induced a more intense itch sensation compared to histamine. Cowhage was the dominant factor in itch perception when both pathways were stimulated in the same time. Cowhage-induced itch is a suitable model for the study of itch in AD and other chronic pruritic diseases, and it can serve as a new model for testing antipruritic drugs in humans.     

The cell biology of acute itch

IntroductionThe average human is covered in 1.8 to 2.0 m² of skin (Ogden et al., 2004). With such a large surface area, a sensory modality we call itch has evolved to alert us to potentially dangerous external stimuli. Unlike the sensation of pain, where an organism will actively try and withdraw from an unpleasant stimuli, itch compels the affected to seek out the source and respond with a scratch. Acute itch serves us well in guarding against environmental threats; however, chronic or severe itch (pruritus) is a burdensome illness that affects millions every year (Nutten, 2015). Fortunately, great strides have been made over the past few decades in understanding the cellular biology that underlies both acute and chronic itch, providing hope for new medical treatments.Compared with its sensory cousin, pain, the understanding of itch is still nascent. New discoveries within the past few years have brought excitement, however. Work uncovering receptors, agonists, and the interplay of different cell types has begun to widen the field and offer new avenues for study. In this review, we will look at the cell biology of itch, with an emphasis on the receptors, cell types, and pruriceptors that are involved in the processing of itch, focusing on the periphery and how itch is coded in the spinal cord.KeratinocytesAs the primary cell type found in skin, keratinocytes are capable of producing a variety of defenses against pathogens. In response to noxious stimuli, keratinocytes can release a host of inflammatory mediators, including nerve growth factor, IL-6, and serotonin, sensitizing peripheral neurons (Luo et al., 2015). Keratinocytes have also been shown to directly activate neurons via the release of the cytokine thymic stromal lymphopoietin, triggering itch behavior (Fig. 1; Wilson et al., 2013). Keratinocytes interact with the immune system via the release of chemoattractants, such as monocyte chemoattractant protein 1, chemokine ligand 5, and IL-8, recruiting immune cells to the site of injury or pruritinergic stimuli. These chemokines were found to be elevated in patients with atopic dermatitis and psoriasis, implicating keratinocytes in the pathology of itch (Giustizieri et al., 2001).Open in a separate windowFigure 1.Multiple cell types contribute to peripheral itch. Prurinergic stimuli, here a mosquito bite, generates itch via the interaction of a variety of cell types. Keratinocytes release endogenous pruritogens, including thymic stromal lymphopoietin (TSLP), contributing directly to itch sensation by activating the TSLP receptor (TSLPR) on peripheral afferent neurons (Wilson et al., 2013). Keratinocytes also release chemoattractants that recruit immune cells, including mast cells. Histamine released from stored granules in mast cells binds H1 receptors, activating pruriceptors and transmitting itch signals to the spinal cord. Along with histamine, other pruritogens, including serotonin, proteases, and IL-6, are released by resident immune cells such as T cells and dendritic cells (Schmelz et al., 2003). The blue squares at the nerve endings represent the receptor for itchy substances.ConclusionProgress has been made in identifying distinct receptors and sensory neurons that encode itch, which was formerly thought to be a submodality of pain. Characterization of primary afferents expressing Mrgprs and GRP, as well as those spinal neurons that are positive for GRPR, BNP, and NPY, have broadened our understanding of the cell types underlying itch. The focus of this review has been acute itch, and questions still remain about whether pathological or chronic itch alters the expression and molecular underpinnings of the mechanisms outlined in this review. However, the research outlined here provides hope for the future, as the identification of unique itch pathways will aid in the development of novel clinical therapies for those suffering from debilitating pruritus.     

Palaeontology: the 165-million-year itch

New flea-like fossils from China provide a rare, tantalizing glimpse of bizarre insects in the Cretaceous and Jurassic. Possibly the oldest flea-like animals known, they provide a challenge to the functional morphologist to infer which animals they may have targeted.     

The parasitism of the itch mite Sarcoptes scabiei (Acariformes: Sarcoptidae)]

The life cycle of the itch mite Sarcoptes scabiei (L.), an intracutaneous parasite of man and animals, has been studied. The paper concerns morphological adaptations, embryonal and postembryonal development, life cycle pattern, scabious passage as a reproductive formation, invasive stages, feeding, reproduction and topical relationships with the host, distribution and survival in the environment.