Hypothesis: Initiating new paths to study mechanisms of anxiety disorders and chronic pain for novel treatment development.
Authors: Cunha Catarina 
Published: February 2019

Prominent scientists classified mental health drugs and its research as a disappointment or even a failure, which lead to the decision of some drug companies to draw away their money from psychiatric drug treatment research, while mental health disorders now claim more lives than automobile accidents each year. Furthermore, because of the expeditious rise in mental health disorders worldwide, the economic health of developing and developed nations will depend on controlling the growth and the costs of mental illnesses.There have been many attempts to explain how we ended up in this situation. Many of these theories boil down to the hypothesis that the lack of the concept of a “self” in research animals means that they can’t consciously experience fear, and are therefore not an adequate model to investigate mental health drugs. We hypothesize that the lack of consciousness in animals is not a hurdle to study anxiety and chronic pain mechanisms for effective treatment development, because it is not exclusive to humans. Based on evolutionary data we theorize, that the first step to generate a multicellular organism was introspection and self-awareness. The first multicellular organisms were Ediacara. They lived in a time when no competition or predators existed, and based on research they show no evidence of interactions with each other, or engagement with their environment. Their challenge was the organization and compartmentalization of different cell functions in order to become a functioning whole organism, which requires inner awareness to perform intentional self-monitoring. Excluding consciousness as an obstacle for effective treatments, we propose that two main problems are not addressed correctly in current research: 1) accurate dissection of acute vs chronic states of disorders, 2) specific to anxiety we need to examine pain free fear memory in more detail. We propose experiments and mechanisms that should be examined in order to develop novel effective treatments. Addressing the first point we suggest alternative fear-inducing stimuli to examine anxiety disorders mechanisms in rats with and without pain receptor knockdown (Nav1.7 knockout) after the chronic state of anxiety is established. To addresses chronicpain under exclusion of acute pain, we propose to first induce chronic pain and after its establishment, one needs to knock down pain receptors such as Nav1.7 to examine mechanisms that became independent of an acute painful input. Additionally, one should examine if pain-free knock out mice have different or no fear memory induced by other anxiety generating stimuli than pain. We propose that one should examine epimutations and identify epigenetic biomarkers for these chronic disorders in which biotechnologies analyzing genome-wide detection of disorder related patterns of DNA methylation and histone modifications should be used. Novel research using epigenetic drugs for mental health disorder treatments are showing promising results. Therefore, designing accurate strategies with novel approaches will enable us to develop more chronic specific, and effective treatments, that will hopefully regain hope, trust and funding for our important undertaking.