Experimental neurology
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Experimental neurology · Sep 2007
Comparative StudyThe high affinity peripheral benzodiazepine receptor ligand DAA1106 binds specifically to microglia in a rat model of traumatic brain injury: implications for PET imaging.
Traumatic brain injury (TBI) is a significant cause of mortality, morbidity, and disability. Microglial activation is commonly observed in response to neuronal injury which, when prolonged, is thought to be detrimental to neuronal survival. Activated microglia can be labeled using PK11195, a ligand that binds the peripheral benzodiazepine receptor (PBR), receptors which are increased in activated microglia and sparse in the resting brain. ⋯ Further, increased [(3)H]DAA1106-specific binding positively correlated with the degree of microglial activation, and to a lesser degree with reactive astrocytosis. Finally, in vivo administration of each ligand in rats with TBI showed greater retention of [(11)C]DAA1106 compared to [(11)C](R)-PK11195 at the site of the contusion as assessed by ex vivo autoradiography. These results in a rat model of TBI indicate that [(11)C]DAA1106 binds with higher affinity to microglia when compared with PK11195, suggesting that [(11)C]DAA1106 may represent a better ligand than [(11)C](R)-PK11195 for in vivo PET imaging of activated microglia in TBI.
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Experimental neurology · Sep 2007
Segmental hypersensitivity and spinothalamic function in spinal cord injury pain.
The mechanisms underlying central pain following spinal cord injury (SCI) are unsettled. The purpose of the present study was to examine differences in spinothalamic tract function below injury level and evoked pain in incomplete SCI patients with neuropathic pain below injury level (central pain) versus those without such pain. A clinical examination, quantitative sensory testing and magnetic resonance imaging (MRI) were performed in 10 SCI patients with below-level pain and in 11 SCI patients without neuropathic pain. ⋯ SCI patients with central pain had sensory hypersensitivity in dermatomes corresponding to the lesion level more frequently than SCI patients without pain, but this may in part be explained by the exclusion of at-level spontaneous pain in the pain-free group. The rostral-caudal extent of the lesion measured by MRI did not differ between the two patient groups, and there were no statistically significant differences in any of the predefined areas of interest on the axial plane images. This study suggests that neuronal hyperexcitability plays a key role in central SCI pain and furthermore - in contrast to previous findings - that loss of spinothalamic functions does not appear to be a predictor for central neuropathic pain in spinal cord injury.
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Experimental neurology · Aug 2007
Activation of phosphatidylinositol 3-kinase and protein kinase B/Akt in dorsal root ganglia and spinal cord contributes to the neuropathic pain induced by spinal nerve ligation in rats.
Several lines of evidence indicate that phosphatidylinositol 3-kinase (PI3K) and PI3K-protein kinase B/Akt (PKB/Akt) signal pathway mediate the pain hypersensitivity induced by intradermal injection of capsaicin or nerve growth factor. However, the role of PI3K and PI3K-PKB/Akt signal pathway activation in neuropathic pain is still unclear. Using L5 spinal nerve ligation (L5 SNL) and immunohistochemistry, we found that the numbers of phospho-PKB/Akt-immunoreactive (p-PKB/Akt IR) positive neurons were significantly increased in ipsilateral L5 dorsal root ganglia (DRG) and adjacent L4 DRG started at 12 h after surgery and maintained to the 3rd day. ⋯ Whereas the inhibitory effect of Akt inhibitor IV on established neuropathic pain was observed only in those rats that received the drug treatment started at the 1st day. Immunohistochemistry revealed that intrathecal injection of wortmannin significantly inhibited the activation of PKB/Akt in L5 DRG and L5 spinal cord. The data suggested that PI3K and PI3K-PKB/Akt signal pathway activation might contribute to the development of neuropathic pain.
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Experimental neurology · Aug 2007
Spinal pathways involved in the control of forelimb motor function in rats.
There is increasing interest in developing rodent models for cervical spinal cord injury (SCI) and techniques to assess forelimb motor function. Previously, we demonstrated that in rats, complete unilateral hemisection at cervical level five (C5) permanently eliminated the ability to grip and caused severe impairments in food retrieval by the forepaw ipsilateral to the lesion [Anderson, K. D., Gunawan, A., Steward, O., 2005. ⋯ In contrast, rats with lateral lesions exhibited deficits, but the majority (7/10) recovered the ability to grip by 43 days post-injury. Interestingly, when tested on the food retrieval task, rats with medial lesions exhibited deficits that recovered; rats with lateral lesions exhibited more permanent deficits. These results suggest that different spinal circuits are involved in recovery of grip strength vs. recovery of skilled reaching.
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Autotomy behavior is frequently observed in rats and mice in which the nerves of the hindlimb are severed, denervating the paw. This is the neuroma model of neuropathic pain. A large body of evidence suggests that this behavior reflects the presence of spontaneous dysesthesia and pain. ⋯ Moreover, the heritable across strains predisposition to spontaneous pain behavior in this new proximal denervation model (SNN) was highly correlated with pain phenotype in the neuroma model suggesting that the pain mechanism in the two models is the same. Relative reproducibility of strain predispositions across laboratories was verified. These data indicate that the neural substrate for spontaneous pain is present in the Chung-SNL model, and perhaps in the other partial nerve injury models as well, but that spontaneous pain is not expressed as autotomy in these models because there is protective nociceptive sensory cover.