The influence of adrenergic stimulation, adrenergic blockade and sympathectomy on crypt cell cycle time and mitotic time in rat jejunum was studied. Alpha adrenergic stimulation by noradrenaline was found to shorten both cell cycle and mitotic times, whereas beta adrenergic stimulation by adrenaline or isoprenaline was found to prolong both cell cycle and mitotic times. Conversely, alpha adrenergic blockade by phentolamine prolonged cell cycle time and beta adrenergic blockade by propranolol or practolol shortened cell cycle time but not mitotic time. Both chemical and surgical sympathectomy inhibited crypt cell proliferation. Chemically sympathectomized animals manifested supersensitivity to exogenous noradrenaline.

The effects of surgical denervation, capsaicin, and 6-Hydroxydopamine pretreatment on the inflammatory response to thermal injury have been investigated in the rat. Surgical denervation and capsaicin pretreatment reduced the cellular and exudative reactions to the injury. 6-Hydroxydopamine appeared to have a selective effect on the exudative reaction only. The effects of surgical denervation are partly explained by local and systemic effects of the procedure.

Summary. Primary afferent iinmyetinated nerves modulate ihe intlammatory response to injury through a process known as neurogenic inflammation. The undecapeptide Substance P is contained in many of these nerves and therefore may be an important mediator of the response. Treatment of neonatal rats with capsaicin permanently destroys primary afferent unmyelinated nerves and depletes (he skin and other organs of Substance P. These animals have a reduced capacity to mount an inflammatory response to injury. We examined the ability of Substance P to chemo-attract neutrophils from normal rats and rats treated a.s neonates with capsaicin. Substance P was shown to cause normal rat neutrophils to chemotact at an optimum concentration of 5 x 10 -' ' M. Equivalent chemotaxis was observed in neutrophils from rats pretreated as neonates with capsaicin. Substance P did not increase chemokinesis. These in vitro results support the view that the reduced neurogenic inflammatory response seen in capsaicin-pretreated rats is not due to a direct toxic effect of capsaicin on neutrophils, but may be due to a decreased availability of neurally derived Substance P a£ the site of injury.

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The function of cutaneous primary afferent unmyelinated nerves (C-fibres) was assessed by measuring axon reflex vasodilatation in the skin over the arms and feet of 15 elderly patients with chronic venous ulcers using a laser Doppler flowmeter. Dilatation of skin microvasculature in response to nerve-independent stimuli was also assessed. Results were compared with those of control subjects matched for age and sex. The chronic venous ulcer group showed reduced axon reflex vasodilatation in the feet but not the arms. Response to nerve-independent vasodilators was similar in both ulcer patients and controls in arms and feet. Local impairment of C-fibre function may partly explain the increased incidence and resistance to healing of leg ulcers in old people.