Wiley RG, Yezierski R, Vierck Jr CJ (2016) Cerebral cholinergic mechanisms in pain: CBF lesions vs systemic scopolamine. Neuroscience 2016 Abstracts 525.15 / SS2. Society for Neuroscience, San Diego, CA.
Summary: Cholinergic inputs to the cerebral cortex and limbic system, originating primarily from the cholinergic basal forebrain (CBF), play an important role in cortical sensory processing, largely through modulation of inhibitory interneurons. Cholinergic agonists given spinally, intracerebroventricularly (ICV) or systemically depress reflex nocifensive responses, but systemic cholinergic antagonists also depress some affective responses to pain and impair attention to aversive stimuli and stress reactions. In the present study, we determined the effects of selective cerebral cholinergic denervation, using ICV microinjection of 4 ug of 192-saporin in 10 μl (Advanced Targeting Systems, San Diego, CA) on operant thermal escape responses to aversive thermal stimuli (10° C, 44.5° C) and hyperalgesic effect of sound stress (ten X 30 sec bursts of 100 dB white noise over a 15 min period, 20 mins prior to thermal escape testing) in normal and CBF-lesioned rats compared to effects of systemic cholinergic antagonism (0.1 mg/kg, i.p., scopolamine, 20 minutes prior to thermal escape testing) in intact, normal rats. All rats were on the thermal escape task prior to either scopolamine, or sound stress testing and prior to ICV 192-saporin. At the conclusion of behavioral testing, choline acetyltransferase immunohistochemistry confirmed that 192-sap produced 62-81% loss of CBF cholinergic neurons. CBF-lesioned rats showed decreased thermal escape responses to both temperatures (10°C and 44.5°C) for >19 weeks. There also was no increase in escape responding (hyperalgesia) after sound stress as seen in normal rats. Scopolamine in normal rats produced decreased thermal escape responses to cold (2° C, 6°C and 10° C) and to heat (44.5° C). These results suggest that systemic scopolamine mimics the effects of CBF destruction on pain and together the overall results are interpreted to indicate an important role for the CBF in cerebral pain processing. These findings may be relevant to clinical pain care in patients with cerebral cholinergic dysfunction, such as Alzheimer’s disease.
Related Products: 192-IgG-SAP (Cat. #IT-01)