The role of ascending neuronal pathways in stress-induced release of noradrenaline in the hypothalamic paraventricular nucleus of rats

Central catecholaminergic pathways carrying pain-related signals to the hyp othalamic paraventricular nucleus (PVN) were investigated in laboratory rat s. Four per cent formalin injected subcutaneously was employed as a stressf ul stimulus. Neuronal activity in brainstem catecholaminergic and paraventr icular neurones was assessed by Fos immunohistochemistry. Stress-induced no radrenaline (NE) release from nerve terminals in the PVN was measured in ex tracellular fluid by in-vivo microdialysis. Within 30 min, formalin elicite d a four- to sixfold increase in plasma ACTH and corticosterone concentrati ons and intense Fos-like activity was seen in the superficial zones of the lumbar spinal cord ipsilateral to the side of the formalin injection. In br ainstem catecholaminergic neurones, the PVN, and midline thalamic nuclei, f ormalin-induced Fos-immunopositivity was equally present in the ipsi- and c ontralateral sides of the injection. An immediate elevation (4-5 times high er than baseline levels) of NE levels was measured in both the right and le ft PVN after a formalin injection into the right paw. Unilateral surgical t ransections at the medulla-spinal cord junction failed to affect formalin-i nduced elevations in NE levels in the PVN independently of the side of the formalin injection or the knife cut. Thus, this observation clearly shows t hat fibres carrying pain-evoked signals ascend bilaterally from the spinal cord to the brainstem and forebrain. Hemisections of the medulla oblongata between the level of A1-A2 NE cell groups and the locus coeruleus reduced b ut did not eliminate formalin-induced NE release from the PVN ipsilateral t o the knife cut. This effect was independent of the side of the formalin in jection. In the contralateral PVN, high and similar NE levels were measured in response to a formalin injection into the right or the left leg. The pr esent study indicates that formalin-induced pain signals are carried by sen sory fibres to the ipsilateral spinal cord. From there, axons of different dorsal horn neurones reach noradrenergic cells on both sides of the medulla oblongata, The majority of noradrenergic fibers ascend on the same side an d innervate the ipsilateral PVN. Since formalin administration resulted in a moderate elevation of NE levels in the PVN on the operated side, the role of other ascending noradrenergic (from the locus coeruleus) or noncatechol aminergic fibres that could modulate NE release from the PVN should be cons idered.