Endogenous peripheral pain regulatory systems in orofacial pain patients

Abstract

Introduction: Initiation of pulpal pain begins with the release of bacterial toxins and inflammatory mediators that either activate or sensitize nociceptors thereby activating the trigeminal pain pathway. In addition, pain perception quickly triggers inhibitory signals that are often mediated by endogenously produced analgesic substances such as opioid peptides. The balance between inflammatory mediators and endogenously released analgesics may contribute to clinical conditions such as symptomatic versus asymptomatic pulpitis. We hypothesized that patients with asymptomatic periradicular pathosis have increased levels of the opioid peptides compared to patients with symptomatic periradicular pathosis. In addition, we also proposed to study the immune cell type that is responsible for the release the opioid peptides in periradicular lesions. Material and method: Fifty tissue biopsy samples obtained from patients who have received endodontic microsurgery and assigned to either symptomatic and asymptomatic groups (n = 25/group) based on their pre-operative clinical periradicular testings. Immunohistochemistry, enzyme-linked immunosorbent assay (ELISA) and Fluorescence-Activated Cell Sorting (FACS) were performed to determine the expressions, levels and the cellular sources of opioid peptides, namely; β-endorphin (END), met-enkephalin (ENK) and dynorphin A (DYN), respectively. Radioimmunoassay (RIA) was performed to determine the functional role of conditioned media (CM) from asymptomatic and symptomatic patients on regulation of trigeminal (TG) neuronal activity in vitro. Results: Compared to symptomatic group, patients with asymptomatic lesions showed 3-fold increase in END levels only. Macrophages showed the highest expression of END, DYN and ENK. This study shows that the application of CM from asymptomatic and symptomatic patients triggered differential regulation of TG neuronal activity. Conclusion: Endogenous opioid peptides are present in periapical lesions. The higher level of endogenous opioid peptides in asymptomatic periapical lesions could explain the lack of symptoms in asymptomatic lesions.