Role of central dopaminergic circuitry in pain processing and nitroglycerin-induced hyperalgesia

Experimental evidence shows that dopaminergic transmission within the basal ganglia is involved in the modulation of nociceptive information. Epidemiological studies show that in some disease states inherent pathophysiological mechanisms that involve degenerative changes (Parkinson's disease; PD) can also impact negatively on other unrelated functional systems (i.e. nociception). Delayed Fos expression in response to nitroglycerin (NTG) administration is a procedure used to identify the neuroanatomical substrates of the migraine condition. In this study, we investigated the influence of dopaminergic nigrostriatal denervation, obtained by intrastriatal injection of 6-hydroxydopamine (6-OHDA), on this response in Sprague-Dawley rats. We also explored the effects on the NTG-induced hyperalgesic response to painful stimuli (formalin and tail-flick tests). Nigrostriatal lesion prevented the neuronal activation typically induced by NTG in sub-cortical areas involved in pain perception, autonomic control and neuroendocrine functions, such as hypothalamic nuclei, periaqueductal grey, parabrachial nucleus and the medullary nuclei. In addition, 6-OHDA-induced lesion inhibited NTG-induced hyperalgesia. Our data show that integrity of central dopaminergic neurotransmission is required for the NTG-induced activation of sub-cortical areas involved in the expression of migraine symptoms, as well as for the hyperalgesic response to painful stimuli elicited by the drug.