Abstract
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-1 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.
Highlights
Intracerebral hemorrhage, mainly caused by trauma and stroke in humans, is one of the principal causes of incapacitation and death in the population of industrialized countries (Reilly and Bullock, 1997; Graham and Gennarelli, 1997)
Cerebrovascular accidents often cause an intracerebral hemorrhage leading to severe and debilitating neurological symptoms and they are the 3rd cause of mortality in the United States, following cardiovascular disease and cancer (Reilly and Bullock, 1997)
Following the collection of baseline data, rats were injected intracerebrally with 3 μL of a collagenase solution (0.5 U 2 μL−1) to produce a hematoma centered in basal ganglia of the right cerebral hemisphere
Summary
Intracerebral hemorrhage, mainly caused by trauma and stroke in humans, is one of the principal causes of incapacitation and death in the population of industrialized countries (Reilly and Bullock, 1997; Graham and Gennarelli, 1997). Cerebrovascular accidents often cause an intracerebral hemorrhage leading to severe and debilitating neurological symptoms and they are the 3rd cause of mortality in the United States, following cardiovascular disease and cancer (Reilly and Bullock, 1997). Nuclear magnetic resonance has shown that dogs may suffer from cerebrovascular accidents leading to brain hemorrhage (Platt and Garosi, 2003). Primary and secondary hypertension in dogs predisposing to intracranial hemorrhage (Dukes, 1992) is known to occur with hypothyroidism and hyperlipoproteinemia (Thomas, 1996). Diseases such as sepsis, coagulopathy, neoplasia and heartworms are associated with cerebral infarction in dogs (Platt and Garosi, 2003).
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