the-sciatic-nerve-cuffing-model-of-neuropathic-pain-in-mice

The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice

Neuropathic pain arises as a consequence of a lesion or a disease affecting the somatosensory system. This syndrome results from maladaptive changes in ...

Centre National de la Recherche Scientifique

université de strasbourg

Neuropeptide FF (NPFF) is a neurotransmitter known to modulate opioid functions. This study investigates the effects of RF9, a new antagonist of NPFF receptors, on the roles of NPFF1 and NPFF2 receptors in thermoregulation in mice. RF9 (10 nmol) injected into the third ventricle did not modify the body temperature as compared to saline, but it completely antagonized the hypothermic effects of 10 nmol NPVF, a NPFF1 selective agonist, as well as the hyperthermic actions of dNPA (5 nmol), a NPFF2 selective agonist. The use of a specific antagonist demonstrates here that central NPFF1 and NPFF2 receptors control in an opposite manner the body temperature in mice.

Opposite control of body temperature by NPFF1 and NPFF2 receptors in mice.

In addition to its neurotrophic role, brain-derived neurotrophic factor (BDNF) is involved in a wide array of functions, including anxiety and pain. The central amygdaloid nucleus (CeA) contains a high concentration of BDNF in terminals, originating from the pontine parabrachial nucleus. Since the spino-parabrachio-amygdaloid neural pathway is known to convey nociceptive information, we hypothesized a possible involvement of BDNF in supraspinal pain-related processes. To test this hypothesis, we generated localized deletion of BDNF in the parabrachial nucleus using local bilateral injections of adeno-associated viruses in adult floxed-BDNF mice. Basal thresholds of thermal and mechanical nociceptive responses were not altered by BDNF loss and no behavioural deficit was noticed in anxiety and motor tests. However, BDNF-deleted animals displayed a major decrease in the analgesic effect of morphine. In addition, intra-CeA injections of the BDNF scavenger TrkB-Fc in control mice also decreased morphine-induced analgesia. Finally, the number of c-Fos immunoreactive nuclei after acute morphine injection was decreased by 45% in the extended amygdala of BDNF-deleted animals. The absence of BDNF in the parabrachial nucleus thus altered the parabrachio-amygdaloid pathway. Overall, our study provides evidence that BDNF produced in the parabrachial nucleus modulates the functions of the parabrachio-amygdaloid pathway in opiate analgesia.

Florent Barthas

Institut des Neurosciences Cellulaires et Intégratives UPR3212

Centre National de la Recherche Scientifique

The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice

Florent Barthas

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Institut des Neurosciences Cellulaires et Intégratives UPR3212

Centre National de la Recherche Scientifique

The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice

Institut des Neurosciences Cellulaires et Intégratives UPR3212