Förderzeitraum 2020
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Background
High doses of capsaicin are recommended for the treatment of neuropathic pain. However, low doses evoke mechanical hypersensitivity. Activation of the capsaicin chemosensor transient receptor potential vanilloid 1 (TRPV1) induces neurogenic inflammation. In addition to the release of pro-inflammatory mediators, reactive oxygen species are produced. These highly reactive molecules generate oxidised phospholipids and 4-hydroxynonenal (4-HNE) which then directly activate TRP ankyrin 1 (TRPA1). The apolipoprotein A-I mimetic peptide D-4F neutralises oxidised phospholipids. Here, we asked whether D-4F ameliorates neurogenic hypersensitivity in rodents by targeting reactive oxygen species and 4-HNE in the capsaicin-evoked pain model.
Results
Co-application of D-4F ameliorated capsaicin-induced mechanical hypersensitivity and allodynia as well as persistent heat hypersensitivity measured by Randell–Selitto, von Frey and Hargreaves test, respectively. In addition, mechanical hypersensitivity was blocked after co-injection of D-4F with the reactive oxygen species analogue H2O2 or 4-HNE. In vitro studies on dorsal root ganglion neurons and stably transfected cell lines revealed a TRPA1-dependent inhibition of the calcium influx when agonists were pre-incubated with D-4F. The capsaicin-induced calcium influx in TRPV1-expressing cell lines and dorsal root ganglion neurons sustained in the presence of D-4F.
Conclusions
D-4F is a promising compound to ameliorate TRPA1-dependent hypersensitivity during neurogenic inflammation.
Introduction
We characterized dermal innervation in patients with fibromyalgia syndrome (FMS) as potential contribution to small fiber pathology.
Methods
Skin biopsies of the calf were collected (86 FMS patients, 35 healthy controls). Skin was immunoreacted with antibodies against protein gene product 9.5, calcitonine gene-related peptide, substance P, CD31, and neurofilament 200 for small fiber subtypes. We assessed two skin sections per patient; on each skin section, two dermal areas (150 x 700 mu m each) were investigated for dermal nerve fiber length (DNFL).
Results
In FMS patients we found reduced DNFL of fibers with vessel contact compared to healthy controls (p<0.05). There were no differences for the other nerve fiber subtypes.
Discussion
We found less dermal nerve fibers in contact with blood vessels in FMS patients than in controls. The pathophysiological relevance of this finding is unclear, but we suggest the possibility of a relationship with impaired thermal tolerance commonly reported by FMS patients.
The clinical picture of depressive disorders is characterized by a plethora of somatic symptoms, psychomotor retardation, and, particularly, anhedonia. The number of patients with residual symptoms or treatment resistance is high. Touch is the basic communication among humans and animals. Its application professionally in the form of, e.g., psychoactive massage therapy, has been shown in the past to reduce the somatic and mental symptoms of depression and anxiety. Here, we investigated the effects of a specially developed affect-regulating massage therapy (ARMT) vs. individual treatment with a standardized relaxation procedure, progressive muscle relaxation (PMR), in 57 outpatients with depression. Patients were given one ARMT or PMR session weekly over 4 weeks. Changes in somatic and cognitive symptoms were assessed by standard psychiatric instruments (Hamilton Depression Scale (HAMD) and the Bech–Rafaelsen–Melancholia–Scale (BRMS)) as well as a visual analogue scale. Furthermore, oral statements from all participants were obtained in semi-structured interviews. The findings show clear and statistically significant superiority of ARMT over PMR. The results might be interpreted within various models. The concept of interoception, as well as the principles of body psychotherapy and phenomenological aspects, offers cues for understanding the mechanisms involved. Within a neurobiological context, the significance of C-tactile afferents activated by special touch techniques and humoral changes such as increased oxytocin levels open additional ways of interpreting our findings.