Effects of fentanyl on pain and motor behaviors following a collagenase-induced intracerebral hemorrhage in rats

Purpose: Intracerebral hemorrhage (IH) and cephalalgia are common consequences of traumatic brain injury. One of the primary obstacles for patient recovery is the paucity of treatments to support an appropriate analgesic protocol. The present study aimed to assess pain and motor behaviors following different doses of fentanyl on a rat model of IH. Methods: Twenty-one male Sprague Dawley rats underwent a stereotaxic surgery to produce a collagenase-induced IH in the right caudoputamen nucleus. The control group (n=6) received saline subcutaneously (SC), and experimental groups received either 5 (n=6), 10 (n=6), or 20 (n=3) mu g/kg of fentanyl SC, 2 hours following surgery and on 2 subsequent days. Only 3 animals received 20 mu g/kg because this dose caused catalepsy for 15-20 minutes following the injection. The rat grimace scale, a neurological examination, balance beam test, and rotarod test were performed for 5 consecutive days postoperatively to evaluate pain and motor performance. At the end of the experimentation, the brains were evaluated to determine hematoma volume, and the number of reactive astrocytes and necrotic neurons. Results: When compared to controls, the grimace scale showed that 5 mu g/kg fentanyl significantly alleviated pain on day 2 only (P<0.01) and that 10 mu g/kg alleviated pain on days 1 (P<0.01), 2 (P<0.001), and 3 (P<0.01). For the rotarod test, only the 10 mu g/kg group showed significant decreases in performance on days 5 (P<0.05) and 6 (P<0.02). The neurological examination was not significantly different between the groups, but only the hopping test showed poor recuperation for the 5 and 10 mu g/kg fentanyl group when compared to saline (P<0.01). No differences were found between the groups for the balance beam test, the histopathological results. Conclusion: Fentanyl, at a dose of 10 mu g/kg SC, provides substantial analgesia following a collagenase-induced IH in rats; however, it can alter motor performance following analgesic treatments.