An antiinflammatory effect of lidocaine?

Local anaesthetics (LA) block impulse propagation in nerve fibres by acting on voltage-gated sodium channels. However, clinically used LA exert other effects as well, such as reduction of neuronal transmitter release by an impaired activation of presynaptic calcium channels. LA may also modify postsynaptic receptors and consequent inhibition of the nicotinic acetylcholine receptor has been reported (1). The neurokinin-1 receptor, the target for the tachykinin substance P, can be non-competitively blocked (2). The extensively studied dihydropyridine receptor, involved in the transmembrane fluxes of the calcium ion, is antagonised by LA (1). There is also a lengthy list of effects of LA on membrane-associated enzymes and cytoplasmatic second-messenger systems. There are reports on modification of adenylate cyklase, guanylatecyklase, calmodulin-sensitive proteins, phospholipase A2 and C, Na+/K+ ATPase and Ca++/Mg++ ATrase. Of clinical importance, in the heart, LA, apart from blocking the voltage dependent Na+ currents, also reduce K + and Ca++ currents (1). The niucosa of the gastrointestinal tract constitutes man’s largest area of exposure against the exterior. In spite of its involvement in secretion and uptake of nutrients, i t should also function as an adequate barrier against the contaminated luminal contents. Processes such as motility, secretion, absorption and regulation of blood flow are controlled by nerve cells, the majority of which are entirely located intramurally, and by more or less locally acting hormones. In man, the number of neurons in the intramural nervous system has been estimated to be only slightly lower than that in the spinal cord. The intramural neurons are mainly located in two plexa, the submucosal and the myenteric plexa, of which the latter is situated between the two muscular layers. These neurons may not only contain the classical neurotransmitters, acetylcholine and norepinephrine, but also polypeptides with a proposed neurotransmitter function. Colocalization of putative transmitters in the same neuron is the rule rather than the exception. The numerous neurons in the gastrointestinal wall receive an external input of only 1 /300 as many efferents from the central nervous system. The bulk of evidence suggests that the enteric nervous system can operate independently and that external denervation has surprisingly small effect on gastrointestinal function. For instance, the local nerve system exerts a complex control of the myogenously active gut muscle. Intestinal blood flow is markedly increased by mechanical stimulation of the mucosa, a reflex which is mediated by the local nervous system and may be involved in the postprandial regulation of intestinal circulation (3). Several observations iiz vivo suggest that intrinsic nervous reflexes can influence secretion. This is the case even for the copious secretion evoked by cholera toxin which can be opposed by the sodium channel blocker tetrodotoxin, lidocaine or the ganglionic blocker, hexamethonium. Similar findings have been made with various intraluminally applied secretagouges such as E. coli toxin or sodium deoxycholate. Even agents on the serosal side can elicit secretion. If hydrochloric acid or bile are applied on the serosa, secretion ensues which can be subsequently inhibited by the same blockers (3). It is well known that intestinal obstruction is accompanied by a profuse secretion in the segment above the occlusion. This fluid movement cannot be accounted for by ischaemic damage to epithelium; rather, local blood flow is increased. In this issue, Nellgird et al. present evidence for the involvement of nervous mechanisms in this secretory response (4). In rats, the jejunum was ligated, the abdomen closed and 18 h later the obstructed intestine was exteriorized, with intact circulation and innervation and the luminal secretion was monitored gravimetrically. The fact that secretion went on for 2.5 h in the intestine, now relieved of the previous obstruction, indicates that the functional state of the intestine had been changed in a long-lasting manner. The secretion was