Ph.D Thesis

Ph.D StudentTreister Roi
SubjectGenetic, Psychophysical and Pharmacological Evidence for
Dopamine and Serotonin Involvement in Pain
Perception and Modulation in Healthy
DepartmentDepartment of Medicine
Supervisors PROF. Elon Eisnberg
DR. Dorit Pud
Full Thesis textFull thesis text - English Version


According to the bio-psychosocial approach, the experience of pain consists of complex and dynamic interactions between the biological, socio-cultural, and psychological domains. The current dissertation presents the results of two genetic association studies in which the relations between pain perception, pain modulation, personality traits, and candidate genes were investigated.

Several lines of results were generated from these studies. The most prominent line of evidence was on the relation between dopamine and pain. The results of the first study revealed significant associations between cold pain tolerance and the dopamine transporter (DAT-1) and monoamine oxidase-A (MAO-A) gene polymorphisms. These associations imply that low dopaminergic activity can be associated with high pain sensitivity and vice versa. In the second study, the dopamine agonist apomorphine was found to affect pain in a complex manner, evoking both hyperalgesia and analgesia. Associations were found between the analgesic effect of apomorphine and dopamine (DAT-1) and serotonin (5-HTTLPR) transporter polymorphisms.

Another line of results focused on the relation between the ability to modulate pain by different modes of Endogenous Analgesia (EA). Different EA conditions seem to be related to each other, and predictors for these EA measures were identified. In addition, a genetic association was found between the 5-HTTLPR and the ability to inhibit pain in the nonpainful Conditioned Pain Modulation (CPM) mode.

Finally, a third line of evidence involved the relation between pain and personality traits. More specifically, a cluster analysis was used to identify subgroups of subjects by their pain and personality characteristics. This method of sub-grouping may be useful for identifying the mechanisms underlying individual variability in the sensitivity to pain and may point to groups at risk for experiencing high levels of clinical pain.

The analgesic effect of dopamine, which was demonstrated for the first time in humans in this research, can lead to new diagnostic and therapeutic strategies. In addition, the search for associations between response to drugs and genetic markers can promote the utilization of “individualized pain therapy” in accordance with a patient’s “pain profile.” The results of these studies highlight the importance of further investigating the relations between pain perception, personality traits, and genetic factors.