title: Pain sensitivity following loss of cholinergic basal forebrain (CBF) neurons in the rat.
abstract: Flexion/withdrawal reflexes are attenuated by spinal, intracerebroventricular (ICV) and systemic delivery of cholinergic agonists. In contrast, some affective reactions to pain are suppressed by systemic cholinergic antagonism. Attention to aversive stimulation can be impaired, as is classical conditioning of fear and anxiety to aversive stimuli and psychological activation of stress reactions that exacerbate pain. Thus, in contrast to the suppressive effects of cholinergic agonism on reflexes, pain sensitivity and affective reactions to pain could be attenuated by reduced cerebral cholinergic activation. This possibility was evaluated in the present study, using an operant test of escape from nociceptive thermal stimulation (10 °C and 44.5 °C) before and after destruction of basal forebrain cholinergic neurons. ICV injection of 192 IgG-saporin produced widespread loss of basal forebrain cholinergic innervation of the cerebral cortex and hippocampus. Post-injection, escape from thermal stimulation was decreased with no indication of recovery for upto 19 weeks. Also, the normal hyperalgesic effect of sound stress was absent after ICV 192-sap. Effects of cerebral cholinergic denervation or stress on nociceptive licking and guarding reflexes were not consistent with the effects on operant escape, highlighting the importance of evaluating pain sensitivity of laboratory animals with an operant behavioral test. These results reveal that basal forebrain cholinergic transmission participates in the cerebral processing of pain, which may be relevant to the pain sensitivity of patients with Alzheimer's disease who have prominent degeneration of basal forebrain cholinergic neurons.
authors.affiliation: Department of Neuroscience, McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL, USA. Electronic address: vierck@mbi.ufl.edu.
authors.forename: C J
authors.initials: CJ
authors.lastname: Vierck
authors.affiliation: Pain Research and Intervention Center of Excellence, Department of Orthodontics, University of Florida College of Dentistry, Gainesville, FL, USA.
authors.forename: R P
authors.initials: RP
authors.lastname: Yezierski
authors.affiliation: Laboratory of Experimental Neurology, VA TVHS, Nashville, TN, USA; Departments of Neurology and Pharmacology, Vanderbilt University, Nashville, TN, USA.
authors.forename: R G
authors.initials: RG
authors.lastname: Wiley
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000633:toxicity; D066187:Basal Forebrain / Q000187:drug effects / Q000473:pathology*; D018678:Cholinergic Agents / Q000633:toxicity; D059329:Cholinergic Neurons / Q000187:drug effects / Q000473:pathology*; D003216:Conditioning, Operant; D004195:Disease Models, Animal; D005260:Female; D017288:Pain Threshold / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans; D054789:Ribosome Inactivating Proteins, Type 1 / Q000633:toxicity; D000076985:Saporins
chemical_list: C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; D018678:Cholinergic Agents; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins
keywords: 192-saporin; ACh; cholinergic decline with aging; cholinergic forebrain; pain sensitivity; stress