2 research outputs found
<Reviews> Dr. G. Sieben: Der Substanzwert der Unternehmung
The processing of pain undergoes several changes in aging that affect sensory nociceptive fibers and the endogenous neuronal inhibitory systems. So far, it is not completely clear whether age-induced modifications are associated with an increase or decrease in pain perception. In this study, we assessed the impact of age on inflammatory nociception in mice and the role of the hormonal inhibitory systems in this context. We investigated the nociceptive behavior of 12-month-old versus 6â8-week-old mice in two behavioral models of inflammatory nociception. Levels of TRP channels, and cortisol as well as cortisol targets, were measured by qPCR, ELISA, and Western blot in the differently aged mice. We observed an age-related reduction in nociceptive behavior during inflammation as well as a higher level of cortisol in the spinal cord of aged mice compared to young mice, while TRP channels were not reduced. Among potential cortisol targets, the NF-ÎșB inhibitor protein alpha (IÎșBα) was increased, which might contribute to inhibition of NF-ÎșB and a decreased expression and activity of the inducible nitric oxide synthase (iNOS). In conclusion, our results reveal a reduced nociceptive response in aged mice, which might be at least partially mediated by an augmented inflammation-induced increase in the hormonal inhibitory system involving cortisol
Cleavage of SNAPâ25 ameliorates cancer pain in a mouse model of melanoma
Background: Cancer pain is associated with increased pain sensitivity to noxious (hyperalgesia) and normally innocuous (allodynia) stimuli due to activation of nociceptors by tumourâderived mediators or tumour infiltration of nerves. The pain sensitization is accompanied by modifications in gene expression, but specifically regulated genes are largely unknown. The 25 kDa synaptosomalâassociated protein (SNAPâ25) is involved in chemical neurotransmission at the synaptic cleft. Its inhibition by Botulinum neurotoxin A (BoNT/A) has been associated with antinociceptive effects in migraine, inflammatory and neuropathic pain. However, its potential to reduce tumourâassociated pain remains to be clarified. Methods: We applied a melanoma model of tumour pain in C57BL/6 mice and investigated SNAPâ25 expression and regulation by qRTâPCR, Western Blot and immunofluorescence as well as tumourâassociated mechanical allodynia with and without BoNT/A treatment. Results: We found increased SNAPâ25 expression in the dorsal root ganglia and the sciatic nerve. Intraplantar injection of BoNT/A induced the cleavage of SNAPâ25 in these tissues and was associated with decreased mechanical allodynia after therapeutic treatment at early and late stages of tumour pain while the tumour size was not affected. Conclusions: Our data indicate that SNAPâ25 plays a role in tumour pain but has no influence on the initiation and progression of skin cancer. Its cleavage inhibits the development of allodynia in the mouse melanoma model and might be useful as new therapeutic approach for the treatment of cancer pain. What does this study add? SNAPâ25 is differentially regulated during melanomaâinduced tumour pain. Its cleavage by BoNT/A might be a suitable therapeutic option for tumour pain patients since tumourâassociated pain can be strongly and significantly reduced after preventive and therapeutic BoNT/A treatment, respectively