**5. Conclusions**

Pain is a topic of grea<sup>t</sup> interest in the medical field because of the current opioid epidemic [6]. Medical providers in the 1990s trained with the establishment of "pain as the 5th vital sign" to improve the quality of patients' well-being [117]. Increasing pressure to treat pain was met with the availability to prescribe opioids. Although opioids interact with opioid receptors on nerves to block pain signaling, these drugs are problematic for a multitude of reasons, particularly tolerance and lethality. Future pain treatment modalities must be specific to pain but not as problematic for patients' quality of life as opioids have proven. We believe there is a viable target within the cerebrum based on the history of using DBS to treat pain; however, future work must systematically examine neural structures of interest, in space and time, to gain insight on how these networks interact.

We reviewed the evidence for the functional localization of the conscious perception of pain networks. Many of the gross anatomical correlates of pain are distributed and overlap with areas thought to be involved with interoception, a ffect, motivation, and cognition. This overlap motivates the need for novel approaches and techniques in understanding the neural mechanisms of pain [118]. The cerebral networks involved in pain are dynamic and distributed. Mapping these intracranial networks will require invasive neurosurgical techniques, such as ECoG and SEEG, to provide high-spatiotemporal-resolution recordings. We sugges<sup>t</sup> that these techniques, in conjunction with the TGI, will provide information on the neurophysiological response of pain. Use of this system also allows for simultaneous qualitative pain evaluation. Further studies on pain intensity in conjunction with neural recordings in the insula, thalamus, and ACC will provide functional considerations for targeted electrical pain therapy in the future.

**Author Contributions:** Conceptualization, E.H.S., R.M.C., T.S.D., and J.D.R.; data acquisition (literature search and study selection), E.H.S. and R.M.C.; analysis and interpretation of data (literature), E.H.S. and R.M.C.; thermal grill construction, T.S.D. and R.M.C.; drafting of the manuscript, E.H.S. and R.M.C.; writing—review and editing the manuscript, R.M.C., E.H.S., T.S.D., and J.D.R. All authors have read and agreed to the published version of the manuscript.

**Funding:** Rolston receives NIH/NINDS K23 NS114178 funding. Smith is supported by a Young Investigator Grant from the "Brain and Behavior Research Foundation." The other authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article.

**Conflicts of Interest:** The authors declare no conflict of interest.
