The Role of Alph alpha Synuclein in Mouse Models of Acute, Inflammatory and Neuropathic Pain

(1) Alph alpha Synuclein (alpha Syn) is a synaptic protein which is expressed in the nervous system and has been linked to neurodegenerative diseases, in particular Parkinson's disease (PD). Symptoms of PD are mainly due to overexpression and aggregation of alpha Syn and include pain. However, the interconnection of alpha Syn and pain has not been clarified so far. (2) We investigated the potential effects of a alpha Syn knock-out on the nociceptive behaviour in mouse models of acute, inflammatory and neuropathic pain. Furthermore, we assessed the impact of alpha Syn deletion on pain-related cellular and molecular mechanisms in the spinal cord in these models. (3) Our results showed a reduction of acute cold nociception in alpha Syn knock-out mice while responses to acute heat and mechanical noxious stimulation were similar in wild type and knock-out mice. Inflammatory nociception was not affected by alpha Syn knock-out which is also mirrored by unaltered inflammatory gene expression. In contrast, in the SNI model of neuropathic pain, alpha Syn knock-out mice showed decreased mechanical allodynia as compared to wild type mice. This effect was associated with reduced proinflammatory mechanisms and suppressed activation of MAP kinase signalling in the spinal cord while endogenous antinociceptive mechanisms are not inhibited. (4) Our data indicate that alpha Syn plays a role in neuropathy and its inhibition might be useful to ameliorate pain symptoms after nerve injury.