Artikel
CB1 Cannabinoid receptor and related C-C chemokine expression changes in brain areas underlying circuitry of chronic pain conditions after experimental spinal cord injuries in rats
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Autoren
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F. Knerlich-Lukoschus
- Department of Neurosurgery, University of Schleswig-Holstein Medical Center, Kiel, Germany; Department of Anatomy, University of Kiel, Kiel, Germany
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M. Noack
- Department of Neurosurgery, University of Schleswig-Holstein Medical Center, Kiel, Germany
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B. von der Ropp-Brenner
- Department of Neurosurgery, University of Schleswig-Holstein Medical Center, Kiel, Germany
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R. Lucius
- Department of Anatomy, University of Kiel, Kiel, Germany
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H.M. Mehdorn
- Department of Neurosurgery, University of Schleswig-Holstein Medical Center, Kiel, Germany
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J. Held-Feindt
- Department of Neurosurgery, University of Schleswig-Holstein Medical Center, Kiel, Germany
| Veröffentlicht: | 28. April 2011 |
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Gliederung
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Objective: Central neuropathic pain is a frequent intricate complication after spinal cord injury (SCI) and specific therapeutic approaches remain elusive. In order to develop effective therapeutic strategies, the whole neuraxis – in particular specific brain regions – must be considered and investigated for SCI-induced pain syndromes. Due to their involvement in neuromodulatory processes, we investigated putative changes in the endogenous cannabinoid and chemokine system in a rat SCI paradigm of posttraumatic neuropathic pain.
Methods: Adult male Long Evans rats were used. After laminectomy on T8 100kdyn or 200kdyn impact lesions were applied by the Infinite-Horizon-Impactor device (PSI, Lexington, KY). Controls received laminectomy (sham operation). Animals were tested weekly for locomotor function and mechanical and thermal nociceptive thresholds for 6 weeks. Expression profiles of cannabinoid receptor Type-1 (CB1), CCL2, CCL3, and their main receptors were investigated in pain, emotion, learning, and memory-related brain regions. CB1, CCL2, CCR2, CCL3, CCR1 immunoreactivities (IR) were investigated 7 d and 42 d after surgery. Hippocampal (HC) subregions, amygdaloid complex, anterior cingulate cortex (ACC), periaqueductal gray (PAG), and thalamic nuclei were analyzed densitometrically. Double staining of CB1 with cellular markers, chemokines, TRPV1 and its phosphorylated active form TRPV1-P was performed.
Results: Dependent on the applied lesion force, survival time point, and anatomical region, CB1 IR density levels changed after SCI with prolonged significant downregulation in the PAG, ACC, and amygdaloid complex in animals, which exhibited prolonged pain-related behavior after 200kdyn sc lesion application. In contrast, there was an upregulation in thalamic nuclei and HC subregions in these animals. CB1 was partially co-expressed or co-localized with CCL2/CCR2, and CCL3/CCR1, which were strongly induced in the delayed phase after severe sc lesion in thalamic nuclei, PAG, and HC subregions. CB1 IR was also co-expressed with TRPV1-P in severely lesioned animals that exhibited prolonged neuropathic pain related behavior.
Conclusions: Interactions of CB1, C-C chemokines, and TRPV1 are likely to play a role in SCI-induced plastic changes on the brain level, underlying emotional-affective pain responses and central pain development after sc lesions.
