Behavioral responses and Fos activation following painful stimuli in a rodent model of Parkinson's disease.
In Parkinson's disease (PD), the motor dysfunction caused by degeneration of the nigrostriatal pathway is often associated with alterations of pain perception. This is likely related to the role that the nigrostriatal system may play in the processing of noxious, somatosensory stimuli. To further address this issue, we used a rodent model of PD, based on the unilateral, intrastriatal injection of neurotoxin 6-hydroxydopamine (6-OHDA). We investigated the effects of the nigrostriatal lesion on behavioral responses to pain tests designed to explore different aspects of nociception, such as the formalin test and the tail flick test; we also explored modifications in the expression of Fos protein, a marker of neuronal activation, in supraspinal nuclei involved in the integration of pain perception and stress-related behavior. Rats bearing the nigrostriatal lesion showed complex alterations in pain perception, including hyperalgesic responses to the tonic, inflammatory pain elicited by formalin injection, but only when the stimulus was delivered ipsilaterally to the lesion. This phenomenon was associated with delayed responses to the phasic, thermal stimulus induced by the tail flick test. The hyperalgesic response to the formalin test was accompanied by reduced Fos expression in the paraventricular nucleus of the hypothalamus, which is part of a network (the medial pain system) that mediates motivational-affective aspects of pain. Our results confirm that a unilateral alteration of central dopaminergic transmission disrupts the neural mechanisms underlying proper integration of painful stimuli, particularly in the hemibody ipsilateral to the dopaminergic denervation.
Tassorelli
Cristina
C
Laboratory of Pathophysiology of Integrative Autonomic Systems, Neurological Institute C Mondino, Pavia, Italy.
Armentero
Marie-Therese
MT
Greco
Rosaria
R
Fancellu
Roberto
R
Sandrini
Giorgio
G
Nappi
Giuseppe
G
Blandini
Fabio
F
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D003342:Corpus Striatum / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D006930:Hyperalgesia / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009434:Neural Pathways / Q000378:metabolism / Q000503:physiopathology; D016627:Oxidopamine; D010146:Pain / Q000378:metabolism* / Q000503:physiopathology; D010147:Pain Measurement; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism / Q000503:physiopathology; D010300:Parkinson Disease / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012678:Sensation Disorders / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D013378:Substantia Nigra / Q000378:metabolism / Q000503:physiopathology; D009435:Synaptic Transmission / Q000502:physiology
D015415:Biomarkers; D016760:Proto-Oncogene Proteins c-fos; D016627:Oxidopamine; D004298:Dopamine