Transgenic Mice for the Translational Study of Neuropathic Pain and Dystonia

Abstract

Murine models are fundamental in the study of clinical conditions and the development of new drugs and treatments. Transgenic technology has started to offer advantages in oncology, encompassing all research fields related to the study of painful syndromes. Knockout mice or mice overexpressing genes encoding for proteins linked to pain development and maintenance can be produced and pain models can be applied to transgenic mice to model the most disabling neurological conditions. Due to the association of movement disorders with sensitivity and pain processing, our group focused for the first time on the role of the torsinA gene GAG deletion-responsible for DYT1 dystonia-in baseline sensitivity and neuropathic responses. The aim of the present report are to review the complex network that exists between the chaperonine-like protein torsinA and the baseline sensitivity pattern-which are fundamental in neuropathic pain-and to point at its possible role in neurodegenerative diseases.

Keywords: DYT1; dystonia; gabapentin; neurodegenerative diseases; pain; torsinA; transgenic mice.

Figure 1

Effect of the overexpression of human wild-type (hWT) and mutated (hMT) torsinA on locomotor activity with respect to non-transgenic littermates (control). The transgene-positive hMT mice fell off the rotarod sooner than the hWT mice (p < 0.05). Reproduced with permission from [57].

Figure 2

Time course of spinal nerve ligation (SNL)-induced mechanical allodynia in mice overexpressing human wild-type (hWT) and mutated (hMT) torsinA. Non-transgenic (NT), hWT and hMT mice did not show statistically significant differences in the development and maintenance of mechanical allodynia. However, hWT and hMT mice presented a delayed recovery from sensitization with longer lasting mechanical allodynia (two-way ANOVA F (32,374) = 1.561; p < 0.05 *; day 52 hWT vs. NT p < 0.01 **, hMT vs. NT p < 0.01 ^αα; day 59 hWT vs. NT p < 0.05 *, hMT vs. NT p < 0.01 ^αα; day 73 hWT vs. NT p < 0.05 *; day 86 hMT vs. NT p < 0.05 ^α). Data are expressed as mean ± SEM of the nociceptive reaction. p values < 0.05 were considered statistically significant. n: NT = 4; hWT = 10; hMT = 11. Reproduced with permission from [5].