Background: Non-coding RNAs (lncRNAs) are a group of non-coding RNAs that act as regulators of gene expression; they are implicated in various human diseases and have been reported to be involved in the modulation of pain. We aimed to study whether: (a) lncRNAs modifications could be found in an experimental model of pain; (b) there was a correlation between lncRNA changes and laser evoked potential (LEP) amplitude/laser-pain rating. Methods: Laser evoked potentials were recorded from 11 healthy subjects to both left hand and perioral region stimulation. Three consecutive averages were calculated for each stimulation site in order to investigate the LEP amplitude habituation. Blood samples were obtained immediately before LEP recording (pre-pain) and 30-min after the recording of the last LEP average (post-pain). Eighty-four lncRNAs, involved in autoimmunity and human inflammatory response, were screened. The criteria used for lncRNAs analysis were fold change >2 and p <.05. By Real-Time PCR, we identified two lncRNAs up-regulated at the post-pain time, as compared to the pre-pain time: RP11-819C21.1 (fold change = 8.2; p =.038) and ZNRD1 antisense RNA 1 non-protein coding (ZNRD1-AS; fold change = 6.3; p =.037). Results: The ZNRD1-AS up-regulation was directly correlated with the N1 amplitude, while the RP11-819C21.1 increase after pain showed a correlation with the reduced N2/P2 amplitude and laser-pain habituation. Conclusion: IncRNA changes in a human experimental phasic pain model. The correlation between lncRNA changes and LEP amplitude and habituation suggests that RP11-819C21.1 and ZNRD1-AS could be involved in the pathophysiology of painful diseases characterized by abnormal excitability of the cerebral cortex. Significance: Long non-coding RNAs are upregulated after experimental pain. RP11-819C21.1 and ZNRD1 could be involved in the pathophysiology of diseases characterized by reduced habituation to pain.