Effects of ageing on sensory nerve function in rat skin

Khalil, Zeinab; Ralevic, Vera; Bassirat, Maryam; Dusting, GJ; Helme, Robert D.

doi:10.1016/0006-8993(94)90153-8

Cited by 67 publications

(44 citation statements)

References 31 publications

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“…The current study shows that the vascular response to electrical stimulation of the sciatic nerve at parameters known to stimulate C-fibres (20 V, 5 Hz, 2 msec) [19] was inhibited by hemorphin-7 in a dose-dependent manner (Fig. 1).…”

Section: Discussionsupporting

confidence: 51%

Modulation of peripheral inflammation by locally administered hemorphin-7

1998

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The results of this study suggest that hemorphins might play a role in inhibiting the inflammatory response in acute, but not in recurrent or chronic injury conditions. Evidence is also provided that the modulatory inhibitory effect of hemorphin-7 is mediated via activation of opioid receptor(s). The significance of this study in conjunction with our previous work, is that it raises the possibility that different endogenous inhibitory mechanisms may operate under different injury conditions - endogenous hemorphins and opioids may modulate acute and chronic inflammation, respectively.

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Section: Discussionsupporting

confidence: 51%

Modulation of peripheral inflammation by locally administered hemorphin-7

1998

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“…Studies from our group [40][41][42] showed that EDRF (NO) plays an important role in inflammation and contributes to the increase in local blood flow in response to the released sensory peptide and local tissue factors at the site of tissue injury. However, it has been proposed that endothelins modulate the release and action of EDRF (NO) [33].…”

Section: Discussionmentioning

confidence: 99%

Effect of chronic sciatic nerve lesion on the neurogenic inflammatory response in intact and acutely injured denervated rat skin

1996

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A supersensitivity to the neuropeptide substance P (SP) has been shown to develop in post-terminal membranes of many denervated tissues. This study examined changes in the sensitivity of post-terminal vascular receptors to SP and calcitonin gene-related peptide (CGRP) in rat skin microvasculature following sciatic nerve section. In anaesthetised rats, 0.5 cm of sciatic nerve in the right mid-thigh region was removed. Two weeks later, SP (100 microM) and sodium nitroprusside (SNP, 1 mM), a direct smooth muscle vasodilator, were introduced into denervated intact footpad skin, via the electrophoresis technique. Laser doppler flowmeter was used to record changes in relative blood flow in the rat hind footpad. The results showed a significant increase in SP response over controls and slight increase in smooth muscle reactivity as determined by an increase in the vascular response to SNP. In another set of experiments, the sensitivity of post-terminal receptors was examined over a 4 weeks period in an acutely injured footpad skin of sciatic nerve lesioned rats. A vacuum-induced blister was raised on the hind footpad and SP, CGRP (each at 1 microM) or SNP (100 microM) were superfused over the blister base. In nerve lesioned rats, using the acutely injured footpad skin model, the results showed a reduction in the vascular responses to SP, CGRP and SNP. The response to SP continued to decrease over time reaching 22% of control values by 4 weeks. Responses to SNP and CGRP were reduced to 53% and 45% respectively by 2 weeks and then improved to 75% of control values by 4 weeks. Possible contributions of sympathetic efferents and the saphenous nerve to these reduced responses in acutely injured skin of nerve lesioned rats were examined using guanethidine (50 mg/kg i.p.) or sectioned saphenous nerve respectively. These procedures did not significantly modify the reduced vascular responses in the blister base of lesioned rats. Possible activation of endogenous opioids and/or the release of endothelin due to blister induction in nerve lesioned rats was examined using naloxone and the endothelin receptor antagonist, BQ-123, respectively. Treatment with naloxone increased SP response in lesioned rats to 41% of control value with no change in smooth muscle reactivity. BQ-123 significantly increased the responses to SP and SNP to 51% and 100% of their own control values respectively. It is concluded that supersensitivity of post-terminal vascular receptors develops in intact skin following chronic nerve lesion. On the other hand, acute injury of the denervated skin area induces activation of endogenous inhibitory modulatory mechanisms that masks this supersensitivity.

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“…The vasodilatation evoked by substance P and acetylcholine in this preparation was partly dependent on the release of nitric oxide ( fig. 3), as was the plasma extravasation induced by substance P [73,74], Interestingly, the contribution of nitric oxide to substance-P-induced vasodilatation increased with the age of the rats [75]. In contrast, CGRP did not stimulate the release of nitric oxide, but elicited vasodilatation directly [73], as it does in rat aorta [45], Hughes et al [76] have also shown that nitric oxide contributes to the vasodilata tion and oedema formation elicited by substance P and capsaicin in rabbit skin.…”

Section: Vasodilatation Elicited By a Utonomic And Sensory Nervesmentioning

confidence: 98%

Nitric Oxide in Cardiovascular Disorders

Dusting

1995

J Vasc Res

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102

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Nitric oxide derived from the vascular endothelium and other cells of the cardiovascular system has important roles in physiological regulation of blood flow and may have pathophysiological functions in cardiovascular disease. Nitric oxide can be synthesised from L-arginine by any of three isoforms of nitric oxide synthase (NOS), and its interaction with prostacyclin, its proposed mechanisms of action and cytotoxicity are briefly reviewed in the context of cardiovascular function. Although nitric oxide can hyperpolarize vascular smooth muscle, activation of the endothelium can induce hyperpolarization and vasodilatation by other means. Nitric oxide has important roles in the physiological regulation of local blood flow and blood pressure, especially during exercise and in response to shear stresses and other local factors in arterioles. Nitric oxide is also involved in neurogenic control of the microcirculation through autonomic efferent nerves and it contributes to vasodilatation and inflammation associated with activation of sensory nerves. In pathological circumstances, excess nitric oxide produced by inducible NOS compromises circulatory function in septic shock, during transplant rejection, and during myocardial ischaemia and reperfusion injury. Immunosuppressant drugs like cyclosporin A inhibit the expression of NOS through complex intracellular intermediates. Disturbances in the activity of constitutive and inducible NOS in the artery wall accompany the development of atherosclerosis, vasospasm and thrombosis, and may contribute to some forms of hypertension and diabetic vascular disease. Reversing the nitric oxide defect with therapeutic agents including angiotensin-converting enzyme inhibitors offers promise in protecting against some manifestations of vascular disease.

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Effects of ageing on sensory nerve function in rat skin

Cited by 67 publications

References 31 publications

Modulation of peripheral inflammation by locally administered hemorphin-7

Modulation of peripheral inflammation by locally administered hemorphin-7

Effect of chronic sciatic nerve lesion on the neurogenic inflammatory response in intact and acutely injured denervated rat skin

Nitric Oxide in Cardiovascular Disorders

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