Perspectives and Trends in Pharmacological Approaches to the Modulation of Pain

Pharmacological approaches to our understanding and treatment of pain have had a long history and have traditionally relied on very few drugs that either have significant side effects and abuse liability, such as the nonsteroidal anti-inflammatory drugs or the opioids, respectively, or those that have been developed for other conditions such as the tricyclic antidepressants. The pathophysiology of pain is undoubtedly complex, complicated in part by the fact that it is not a singular condition, and has a variety of etiologies and a number of associated comorbidities that make treatment interventions challenging. Moreover, there are changes in the central nervous system during the course of the development of chronic pain that, in a manner parallel to neurodegenerative disorders, likely require different pharmacological approaches in the early stages of acute pain compared to those that would be effective when pain has become chronic. This chapter reviews the current status of the field of pain research focusing on some relatively underdeveloped areas, such as pain and its associated comorbidities, and the use of transgenic animals and drug self-administration procedures in the context of analgesic assessment. This chapter also incorporates more recent developments and emerging trends in the area of epigenetics, biomarkers, and the use of induced pluripotent stem cells for pharmacological evaluation, target identification, and validation. Recent progress in the study of "organs-on-a-chip" will also be included in this overview, setting expectations for future progress that integrates these advances for deeper insights into mechanisms, novel treatments, and facilitated efforts in drug discovery.