Exploitation of Thermal Sensitivity and Hyperalgesia in a Mouse Model of Dystonia

Abstract

Neuropathic pain is characterized by mechanical allodynia and thermal hyperalgesia to heat, and it affects some 20% of European population. Patients suffering from several neurologic diseases experience neuropathic pain, often finding no relief in therapy. Transgenic mice expressing the gene encoding the human mutant (hMT) or the human wild-type (hWT) torsin A represent a preclinical model of DYT1 dystonia which is the most common form of early-onset inherited dystonia. Baseline thermal sensitivity and hyperalgesia to heat have never been studied in models of dystonia. Therefore, the aim of this research has been to characterize thermal sensitivity in baseline conditions and hyperalgesia to heat after the induction of neuropathic pain through the spinal nerve ligation (SNL) model in mice overexpressing human wild-type and mutated torsin A in comparison to non-transgenic C57BL/6 mice. According to our results, the paw withdrawal latency time to heat in the Hargreaves’ test is significantly lower in the hMT mice (Kruskal–Wallis test = 6.933; p = 0.0312*; hMT vs. hWT p = 0.0317*). On the other hand, no significant differences in SNL-induced thermal hyperalgesia was found among the three strains (Friedman test = 4.933; p = 0.1019). Future studies are needed to better understand the role of torsin A in sensory processing of heat stimuli.

Transgenic Mice for the Translational Study of Neuropathic Pain and Dystonia

“…In conflict with mechanical sensitivity, baseline thermal sensitivity was increased in hMT mice, although no statistically significant differences in hyperalgesia induced by SNL were observed; only a trend towards decreased heat thresholds was found in the hWT and hMT mice [ 111 ]. Since GABA-ergic inhibitory control is needed to avoid aberrant processing within the dorsal horn after nerve injury [ 112 ], these results suggest that the transgenic murine model of dystonia exhibited delayed recovery from the sensitization process because of the role of torsinA in the activity of GABA-ergic and glutamatergic interneurons, the development of abnormalities in the neuronal nuclear membrane [ 113 ] and synaptogenesis [ 44 ].…”