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The distribution of alpha 2 (alpha 2)-adrenoceptors along cervical, thoracic, lumbar, and sacral segments of the spinal cord of normal rats has been studied by quantitative autoradiography using the specific alpha 2-antagonist [3H]rauwolscine as a ligand. In addition, the influence of noradrenergic (NA) denervation [obtained either by complete transection of the spinal cord at vertebrae level T8-T9 or by selective lesion of NA spinal cord system carried out by intracisternal injection of 6-hydroxydopamine (6-OHDA)] on eventual variations of alpha 2-adrenoceptor density at spinal cord target cells was studied in parallel. In control rats, the quantitative analysis of alpha 2-adrenoceptor densities revealed the presence of these receptors throughout the whole gray matter with a preferential location in the superficial dorsal horn. This pattern was the same at all rostro-caudal levels of the cord and appeared very well correlated with the distribution of NA terminals revealed by immunohistochemistry, particularly in the superficial layers of the dorsal horn. After total transection of the spinal cord (caudally to the section) and 6-OHDA-induced lesion, an increase of alpha 2-adrenoceptor density was mainly observed within the distal dorsal horn thus evidencing supersensitivity in this area, while modifications were not detectable in other regions of the spinal gray matter, except at the lumbar level where other dorsal, central, and intermediate zones were significantly enriched.

We aimed to characterize neuronal and corticotrophin-releasing (CRF) pathways in a model of somato-visceral pain in rats. Male rats received an intraperitoneal (i.p.) injection of either vehicle (controls) or acetic acid (AA) and were sacrificed 1, 2, 3, 4, or 6 h later. Coronal frozen sections of the brain were cut and mRNAs encoding the rat c-fos, CRF(1), CRF(2 alpha,beta) receptors were assayed by in situ hybridisation histochemistry. Localization of these transcripts within CRF-immunoreactive (i.r.) neurons of the paraventricular nucleus (PVN) of the hypothalamus was also determined. AA i.p. induced c-fos mRNA expression in brain nuclei involved in the autonomic, behavioural and neuroendocrine response to pain. Some of these nuclei are involved in the control of digestive motility, as represented by the PVN, locus coeruleus and nucleus tractus solitarius. CRF pathways, in particular in the PVN, are activated in this model. Indeed, a robust signal of c-fos and CRF(1) transcripts was observed in the PVN and numerous CRF-i.r. neurons expressed c-fos or CRF(1) transcripts in the PVN of AA-treated animals. In contrast, no expression of CRF(2) transcripts was observed in the PVN either in basal conditions or after AA i.p. These data argue for an activation of CRF pathways within the PVN in this model of somato-visceral pain. The use of CRF antagonists, particularly of the CRF(1) type, should have an interest in somato-visceral pain pathology.

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