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Background and Purpose: Vascular 'denervation' hyper-reactivity has generally been investigated 1-2 weeks after administration of chemicals that temporarily prevent transmitter release, but do not necessarily inactivate the neuronal noradrenaline transporters (NETs). We have investigated the reactivity of rat tail arteries over longer periods after removing the terminals by surgical denervation.Experimental Approach: Two and 7 weeks after denervation, myography was used to assess contractions of isolated arterial segments to phenylephrine, methoxamine, clonidine, vasopressin and angiotensin II (AII). Denervation was confirmed by lack of tyrosine hydroxylase immunoreactive nerve terminals.Key Results: The NET inhibitor, desmethylimipramine, increased the pEC(50) for phenylephrine in control, but not denervated arteries after both 2 and 7 weeks. Relative to controls, pEC(50)s for phenylephrine (with desmethylimipramine), methoxamine, clonidine and vasopressin were increased at 2 but not 7 weeks after denervation. The pEC(50) for phenylephrine in the absence of desmethylimipramine was greater than control after both 2 and 7 weeks' denervation. The maximum contraction to vasopressin was larger than in controls at 2 but not 7 weeks after denervation, whereas contractions to AII were markedly enhanced at both time points.Conclusions and Implications: Increased vascular reactivity to alpha(1)- and alpha(2)-adrenoceptor agonists, and vasopressin is transient following denervation. After 7 weeks, increased reactivity to phenylephrine can be entirely accounted for by the loss of NETs. Maintained supersensitivity to AII indicates that denervation differentially and selectively affects vascular reactivity to circulating vasoconstrictor agents. This might explain persistent vasoconstriction in denervated skin of humans after nerve injuries. [ABSTRACT FROM AUTHOR]

To determine whether peripheral nerve injury has similar effects on all functional types of afferent neuron, we retrogradely labeled populations of neurons projecting to skin and to muscle with FluoroGold and lesioned various peripheral nerves in the rat. Labeled neurons were counted after different periods and related to immunohistochemically identified ectopic terminals and satellite cells in lumbar dorsal root ganglia. After 10 weeks, 30% of cutaneous afferent somata labeled from transected sural nerves had disappeared but, if all other branches of the sciatic nerve had also been cut, 60% of cutaneous neurons were lost. Small-diameter sural neurons preferentially disappeared. In contrast, the number of muscle afferent somata was not affected by transection of various nerves, p75 was downregulated in axotomized cutaneous neurons but in not axotomized muscle neurons. Conversely, p75 was upregulated in satellite cells around cutaneous but not muscle neurons. Consistent with this, perineuronal rings containing tyrosine hydroxylase, calcitonin gene-related peptide, galanin, or synaptophysin were formed preferentially around cutaneous neurons. Selective lesions of predominantly cutaneous nerves triggered the formation of rings, but none were detected after selective lesions of muscle nerves. We conclude that cutaneous neurons are both more vulnerable and more associated with ectopic nerve terminals than muscle neurons in dorsal root ganglia after transection and ligation of peripheral nerves. [ABSTRACT FROM AUTHOR]