**Conflict of interest**

**7. Is optogenetics the future of noninvasive brain stimulation?**

**8. Conclusion**

114 Transcranial Magnetic Stimulation in Neuropsychiatry

**Acknowledgements**

in the area of pain and neurostimulation.

Optogenetic techniques, where light-activated ion channels from microbial opsins are expressed in neurons enabling their activity to be controlled remotely by light, are rapidly increasing our understanding of neural circuits [95, 96]. In animal models, the technique has been used to investigate pain processing pathways; for instance, optogenetic activation of the prefrontal cortex has been found to lead to antinociceptive effects. This study highlighted the importance of a previously unexplored prefrontal to nucleus accumbens pathway that may in the future provide insights into treatment interventions for intractable pain [97]. As the field expands, optogenetic techniques are likely to lead to substantial increases in our understanding of pain processing by their use in animal models. In addition to the contribution to basic science, optogenetics has been predicted to have translational potential as a therapeutic neuromodulatory intervention for neurological disorders. One of the current limitations of the use of this technology in humans will be in how to safely deliver the channelrhodopsin (ChR2) gene to the targeted neuronal population. Nonetheless, it is likely that progress will occur very rapidly in this field due to its vast therapeutic potential [98].

The use of the NIBS for the relief of pain is a relatively new field and provides an exciting opportunity for neuromodulatory interventions to move to targeting cortical areas rather than traditional spinal cord stimulation. NIBS opens up the opportunity to fully probe the contributions of the widespread brain areas that are thought to be associated with pain processing in the pain neuromatrix. With the associated risk factor of mental health difficulties in chronic pain patients, this is particularly interesting as NIBS introduces the possibility of targeting cognitive-evaluative aspects of pain. Further NIBS allows experimental studies in healthy participants, as well as patient intervention, allowing the investigation of the neuromodulation of pain processing in health and disease. Taken together, these studies provide the potential for greater understanding of the role of descending modulation in pain perception and how this modulation is influenced by chronic pain. There is a clear need to look toward NIBS for future therapeutic interventions for chronic pain as there are currently a number of challenging chronic pain syndromes that are often refractory to conventional pharmacological therapy [3]. With the increasing numbers seeking treatment to pain associated with chronic disease and injury, the development of safe and effective forms of treatment is

Experimental work in my laboratory examining pain and neurostimulation has been conducted by Dr. Tonya Moloney, Dr. Eissa Al –Hashessi, Niamh O'Connor, Eoin Devy-Gray, Lucy O'Donoghue, Clive Drakeford, Victor Rodrigues, Brendan Grafe, Hannah Ashe, and Louisa-May Hanrahan. All have provided valuable contributions to discussions on literature

crucial in terms of both public health and the economy.

Funding has been provided by Trinity College, Dublin.

The author has no conflict of interest.
