An Induced Hematoma in Caudoputamen Nuclei in Rats Causes Central Pain when the Thalamus is also Implicated and the Central Sensitization is Reversed with Gabapentin

Problem statement: The objective of this study was to evaluate pain sensitisation in rats following the induction of an intracerebral hemorrhage by injecting a collagenase solution in the caudoputamen nucleus of the right basal ganglia and to evaluate gabapentin as an analgesic for central pain. Approach: 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) only. Following 3 days of behavioral 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) inducing a hematoma in the right caudoputamen nucleus and/or thalamus. They were then tested for the next 9 consecutive days. In a second experiment, gabapentin was evaluated for the reversal of thermal hyperalgesia and mechanical allodynia (using von Frey filaments) following the intracerebral injection of 3 μL of the collagenase solution. Results: No pain-related behavioral changes were observed following injections with 0.5 and 1 μL of the collagenase solution. However with 2 μL, reaction times were significantly faster on days 3-7 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. Gabapentin reversed mechanical allodynia and thermal hyperalgesia in animals with caudoputamen and thalamic lesions. Conclusion: These preliminary results suggest that central pain was induced in rats with a collagenase-induced intracerebral hemorrhage localized in the thalamus and that mechanical allodynia and thermal hyperalgesia were reduced with gabapentin treatment. Keys words: Central pain, ganglia and thalamus, intracerebral hematoma, Sprague-Dawley rats, gabapentin treatment, intracerebral hemorrhage, collagenase solution, caudoputamen nucleus, thermal hyperalgesia, mechanical allodynia, thalamic lesions