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 subservepruriceptive itch which includes both unmyelinated C-fibers and thinly myelinated Adelta 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.
- MeSH
- agonisté histaminu škodlivé účinky MeSH
- histamin škodlivé účinky MeSH
- kapsaicin škodlivé účinky MeSH
- kašel chemicky indukované patofyziologie MeSH
- látky ovlivňující senzorický systém škodlivé účinky MeSH
- lidé MeSH
- nervová vlákna myelinizovaná účinky léků fyziologie MeSH
- nervová vlákna nemyelinizovaná účinky léků fyziologie MeSH
- nervové receptory účinky léků fyziologie MeSH
- neurony aferentní účinky léků fyziologie MeSH
- periferní nervy účinky léků patofyziologie MeSH
- pruritus chemicky indukované patofyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- agonisté histaminu MeSH
- histamin MeSH
- kapsaicin MeSH
- látky ovlivňující senzorický systém MeSH
Topically applied camphor elicits a sensation of cool, but nothing is known about how it affects cold temperature sensing. We found that camphor sensitizes a subpopulation of menthol-sensitive native cutaneous nociceptors in the mouse to cold, but desensitizes and partially blocks heterologously expressed TRPM8 (transient receptor potential cation channel subfamily M member 8). In contrast, camphor reduces potassium outward currents in cultured sensory neurons and, in cold nociceptors, the cold-sensitizing effects of camphor and menthol are additive. Using a membrane potential dye-based screening assay and heterologously expressed potassium channels, we found that the effects of camphor are mediated by inhibition of Kv7.2/3 channels subtypes that generate the M-current in neurons. In line with this finding, the specific M-current blocker XE991 reproduced the cold-sensitizing effect of camphor in nociceptors. However, the M-channel blocking effects of XE991 and camphor are not sufficient to initiate cold transduction but require a cold-activated inward current generated by TRPM8. The cold-sensitizing effects of XE991 and camphor are largest in high-threshold cold nociceptors. Low-threshold corneal cold thermoreceptors that express high levels of TRPM8 and lack potassium channels are not affected by camphor. We also found that menthol--like camphor--potently inhibits Kv7.2/3 channels. The apparent functional synergism arising from TRPM8 activation and M-current block can improve the effectiveness of topical coolants and cooling lotions, and may also enhance TRPM8-mediated analgesia.
- MeSH
- kafr farmakologie MeSH
- kationtové kanály TRPM genetika metabolismus MeSH
- menthol farmakologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nervová vlákna nemyelinizovaná účinky léků metabolismus MeSH
- nízká teplota MeSH
- nociceptory metabolismus fyziologie MeSH
- signální transdukce účinky léků fyziologie MeSH
- spinální ganglia účinky léků metabolismus MeSH
- termoreceptory metabolismus fyziologie MeSH
- vnímání teploty účinky léků fyziologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- kafr MeSH
- kationtové kanály TRPM MeSH
- menthol MeSH
- TRPM8 protein, mouse MeSH Prohlížeč
The growth-associated protein 43 (GAP-43) is known as a marker of regenerating nerve fibers and their continuous remodeling in the adult human skin. The purpose of this pilot study was to investigate a possible role for GAP-43 in the detection of the early stages of small-fiber neuropathy in patients with type 2 diabetes mellitus (DM2) as compared with a well- established and validated parameter - intra-epidermal nerve fiber density (IENFD) of protein gene product 9.5 (PGP 9.5) immunoreactive intra-epidermal C fibers. In a group of 21 patients with DM2 within three years of diagnosis (13 men, 8 women; mean age 53.9±12.8; range 30-74) and a group of 17 healthy volunteers (8 men, 9 women; mean age 55.8±8.5; range 45-70 years), skin punch biopsies were taken from a distal calf and double immunostained with both PGP 9.5 and GAP-43. In healthy controls, 96.8% of 629 PGP 9.5 immunoreactive fibers were immunostained with GAP-43; the proportion of PGP 9.5 intra-epidermal nerve fibers immunoreactive for GAP-43 in control subjects ranged from 86.5 to 100%. In DM2 patients, IENFD was significantly lower compared to controls (median, 1.5 vs. 11.2/mm; p<0.001). The proportion of GAP-43 immunoreactive intraepidermal nerve fibers was significantly lower in DM2 patients compared to healthy controls (73.6% of 337 PGP 9.5 positive fibers; p<0.001); ranged from 0 to 98.1%. In conclusion, these results show that impaired regeneration of intra-epidermal C fibers in the early stages of type 2 diabetes mellitus, as indicated by GAP-43, might be a marker of incipient diabetic neuropathy.
- MeSH
- diabetes mellitus 2. typu genetika metabolismus patofyziologie MeSH
- diabetické neuropatie genetika metabolismus patofyziologie MeSH
- dospělí MeSH
- kůže inervace metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- nervová vlákna nemyelinizovaná patologie fyziologie MeSH
- nervová vlákna fyziologie MeSH
- pilotní projekty MeSH
- protein GAP-43 biosyntéza genetika MeSH
- regenerace nervu genetika MeSH
- regulace genové exprese * MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- protein GAP-43 MeSH
The role of L-DOPA in spinal nociceptive reflex activity has been re-evaluated. In high spinal cats, with supraspinal loops being excluded, the onset of reflex facilitation induced by noxious radiant heat is delayed after injection of L-DOPA by 4 to 10 s, i.e. the early component of nociceptive reflex facilitation is blocked, while the late component persisted. Further investigations have shown that the early component of reflex facilitation induced by noxious radiant heat is mediated by Adelta-fibres and the late component by C-fibres. Therefore, it can be assumed that L-DOPA, like opioids, preferentially blocks the transmission in nociceptive reflex pathways from Adelta-fibres.
- MeSH
- kočky MeSH
- levodopa farmakologie MeSH
- měření bolesti účinky léků metody MeSH
- mícha účinky léků fyziologie MeSH
- nervová vlákna myelinizovaná účinky léků fyziologie MeSH
- nervová vlákna nemyelinizovaná účinky léků fyziologie MeSH
- nociceptory fyziologie MeSH
- reflex účinky léků fyziologie MeSH
- zvířata MeSH
- Check Tag
- kočky MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- levodopa MeSH
OBJECTIVES: There is a lot of variability between the results of studies reporting the pattern of gray matter volume changes in schizophrenia. Methodological issues may play an important role in this heterogeneity. The aim of the present study was to replicate the better performance of multivariate "source-based morphometry" (SBM) over the mass-univariate approach. EXPERIMENTAL DESIGN: Voxel-based morphometry of Jacobian-modulated gray matter volume images, using voxel and cluster level inference, and SBM were performed in a group of first-episode schizophrenia patients (N = 49) and healthy controls (N = 127). RESULTS: Using SBM we were able to find a significant reduction of gray matter volume in fronto-temporo-cerebellar areas whereas no significant results were obtained using voxel-based morphometry. CONCLUSION: Multivariate analysis of gray matter volume seems to be a suitable method for characterization of the pattern of changes at the beginning of the illness in schizophrenia subjects.
- MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- mladý dospělý MeSH
- mozek patologie MeSH
- multivariační analýza MeSH
- nervová vlákna nemyelinizovaná patologie MeSH
- počítačové zpracování obrazu metody MeSH
- schizofrenie patologie MeSH
- velikost orgánu MeSH
- Check Tag
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH