Title A systematic review of the literature of the effects of laser irradiation on peripheral mammalian nerves: implications for the analgesic effects of low-level laser therapy. Introduction Early studies of the effects of laser irradiation (LI) on peripheral nerves used an injury model to study stimulation of repair processes. The focus on stimulation was consistent with research in other domains of tissue repair where inhibition was seen as an unwanted response. In parallel, many authors described laser-induced neural inhibition, in particular of nociceptor activity, which led to the hypothesis that neural inhibition was central to laser-induced analgesia. Aim We sought to systematically evaluate the effects of LI in peripheral mammalian nerve models and to develop hypotheses for mechanisms of laser-induced pain modulation based on the review findings. Methods We searched computerized databases using key words for studies of LI of any wavelength to peripheral mammalian nerves. We excluded studies of non-mammalian nerves, experimentally injured nerves, studies in which LI was used as a noxious stimulus and studies without a control. Results We identified 41 studies suitable for evaluation, of pre and post-laser irradiation effects within nerves or neurons induced by visible and infrared wavelengths of LI in i) electrical activity; ii) functional activity and iii) morphology. Visible and infrared wavelengths caused inhibitory effects on electrical and functional neural activities. Morphological changes were seen with infrared LI. Specific anti-nociceptor and pain modulating effects were seen predominantly with infrared wavelengths. Conclusion Inhibition of neural activity is seen in many, but not all, studies of LI of peripheral nerves. Specificity for inhibitory effects increases when small diameter A? and C fibres are targeted. As these fibres mediate pain perception, a mechanism by which LI reduces clinical pain, both acutely and in the long term, by direct inhibition of nociceptors, is proposed.