Central Pain Following a Collagenase-Induced Hematoma in the Basal Ganglia and Thalamus Can Be Reversed with Gabapentin

Abstract

The objective of this study was to evaluate pain sensitization in rats following the induction of an intracerebral haemorrhage located in the basal ganglia and/or thalamus using the Rosenberg model (intracerebral injection of collagenase). Thirty male Sprague-Dawley rats weighing between 175-300 g were used. In a first experiment, 3 groups of 6 animals were used to evaluate pain threshold using the Hargreaves test (thermal sensitivity). Following 3 days of behavioural testing (baseline values), animals in each group were injected intracerebrally either with 0.5, 1 or 2 μL of a collagenase solution (0.5 U/2 μL Type VII collagenase) which induced a hematoma in the right caudoputamen nucleus and/or thalamus. They were then tested for the next 9 consecutive days. No pain-related behavioural changes were observed following injections with 0.5 and 1 μL of collagenase. However with 2 μL, reaction times were significantly faster on days 3, 4, 5, 6 (p < 0.0001) and 7 (p < 0.006) in the right and left hind paws compared to baseline values. The lesion was localized only in the caudoputamen nucleus for animals receiving 0.5 and 1 μL of collagenase whereas lesions extended in the ipsilateral thalamic nuclei (lateral-dorsal and lateral-posterior nuclei) for animals receiving 2 μL of collagenase. In a second experiment, gabapentin reversed mechanical allodynia, evaluated with von Frey filaments, and hyperalgesia, evaluated with Hargreaves test, in rats (n=6) following a collagenase-induced (3 μL) hematoma. In conclusion, these preliminary results suggest that central pain was induced in rats with a collagenase-induced intracerebral haemorrhage localized in the caudoputamen nuclei most probably associated with lesions to the thalamus, and concurrent allodynia and hyperalgesia were reduced with gabapentin treatment.