Microinjection of calcitonin in midbrain periaqueductal gray attenuates hyperalgesia in a chronic constriction injury rat model

Objective(s): As heat, pain is one of the most common clinical symptoms. Generally, calcitonin (CT) is prescribed as an analgesic agent for the treatment of pain, especially for the pain caused by osteoporosis or primary and metastatic bone tumor. However, the detailed mechanism remains unknown.Materials and Methods: In this study, chronic constriction injury (CCI) rat model was created, and hot plate test and von frey filaments test were employed to evaluate thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT), respectively. Immunohistochemistry staining and western blot analyses were used to assess the distribution and expression of calcitonin receptor (CT-R) in the midbrain periaqueductal gray (PAG), which was a pivotal site in the modulatory system for the endogenous pain.Results: The TWL and MWT before the surgery (۱۹.۶±۱.۱۹ sec) were significantly longer than that at day ۲ (۱۲.۵±۱.۶۰ sec), and day ۱۴ (۷.۷۵±۰.۸۹ sec) (P< ۰.۰۱; P< ۰.۰۱), respectively. The TWL and MWT at day ۱۴ were significantly increased compared to that at day ۷ after microinjection of salmon calcitonin (sCT) with different doses. Interestingly, the expression of CT-R was up-regulated in neuropathic pain. Furthermore, the expression of CT-R was significantly up-regulated and algesia was remarkably relieved when CT was microinjected into PAG.Conclusion: These results suggested that an increased CT-R might be associated with hyperalgesia in CCI rat, and CT had a potent antinociceptive effect by the up-regulation of CT-R in the PAG. Thus, it might provide a potential approach for the treatment of bone pain.

Keywords:

Analgesia , Calcitonin , Calcitonin receptor , Pain , Periaqueductal gray