Long-term follow-up of intracerebroventricular injection of streptozotocin-inducing pain sensitization.

Abstract

Age is known to be the major risk factor for both pain sensation and sporadic Alzheimer's disease (sAD). Pain management in AD is a critical health condition. However, assessing pain in sAD patients is challenging. The intracerebroventricularly injected streptozotocin (icv-STZ) rat model of sAD has been brought to the fore as a hopefully suitable model that could mimic some features of sAD. However, the exact mechanism by which this agent may induce AD-like pathology is largely unknown. In some studies, analgesic drugs have been suggested as possible prevention of AD and icv-STZ-induced AD-like pathology. Therefore, this study used formalin and tail-flick tests to investigate whether different doses of icv-STZ injections could affect acute and inflammatory pain sensation and edema volume over time. Behavioral responses were observed at four testing time points (1, 2.5, 3.5, and 6 months postinjection). The results indicate that icv-STZ was able to significantly decrease the animals' formalin pain threshold in both a time- and dose-dependent manner. Formalin-induced acute and chronic pain scores of animals treated with streptozotocin 3 mg/kg (STZ3) increased dramatically 2.5 months after injection and persisted thereafter. The augmentation in pain score induced by streptozotocin 1 mg/kg (STZ1) was observed from 3.5 months after STZ injection. However, the effect of streptozotocin 0.5 mg/kg (STZ0.5) was NS until 6 months after injection. However, formalin-induced paw edema occurred with a longer delay and was not detectable in STZ0.5-treated animals. In addition, only STZ3-treated animals significantly reduced the thermal pain threshold of animals 6 months after injection. These observations indicate that icv-STZ can sensitize central and/or peripheral receptors to pain. The effect of STZ is dose- and time-dependent. AD-like pathology induced by icv-STZ could be partially activated via pain processing pathways. Therefore, anti-inflammatory agents could alleviate AD-like symptoms via pain treatments.