The effect of splanchnic nerve stimulation and neuropeptide Y on cholera secretion and release of vasoactive intestinal polypeptide in the feline small intestine

The effect of sympathetic nerve stimulation and intra-arterial infusion of neuropeptide Y (NPY) on net fluid secretion and release of vasoactive intestinal polypeptide (VIP) was studied in the cat small intestine during a secretion due to cholera toxin. Activation of the splanchnic nerves (4 Hz, 5 ms, 5 V) decreased net fluid secretion to 57 +/- 10% of control. Concomitantly, the release of VIP was reduced to less than 50%. Furthermore, close i.a. infusion of NPY (estimated increase in plasma concentration 75 nmol l-1) reduced the net fluid secretion and VIP release to 27 +/- 5 and 28 +/- 4% of the pre-stimulatory value. The correlation between the decrease in net fluid secretion and reduction in VIP release showed a strong positive correlation (r = 0.83). These results strongly indicate that the antisecretory effect of sympathetic nerve stimulation during cholera diarrhoea is mediated by inhibition of secretory VIP neurons in the intestinal mucosa. A similar mechanism is also proposed for the intravascularly administered NPY.     

Pelvic afferent reflex control of rectal motility and lumbar colonic efferent discharge mediated by the pontine sympatho-inhibitory region in guinea pigs

Rectal motility and the efferent discharge of lumbar colonic nerves (LCED) have previously been shown to be affected by reflex activity activated by rectal stimulation. The sensory limb of this reflex is represented by afferent fibers in pelvic nerves. The present study revealed that this reflex is modulated by supraspinal sympatho-inhibitory regions. Pelvic afferent stimulation led to rectal contraction through the withdrawal of a tonic inhibitory influence of lumbar colonic nerves. The supraspinal region responsible for this antagonism ofthe rectal-inhibitory colonic nerve activity was localized to the pons. Neither the intravenous administration of atropine nor that of guanethidine (and Eisai compound 865–123, another adrenergic neuron blocking agent) effected the ability of pelvic afferent stimulation to inhibit tonic discharge of lumbar colonic efferent nerves; nervertheless, both agents eliminated the mechanical response of the rectum to stimulation of pelvic afferents. These observations suggest that lumbar sympathetic nerves may tonically inhibit the release of acetylcholine from excitatory neurons in the rectal myenteric plexus. We conclude that descending fibers from the pons are activated as a result of pelvic afferent nerve stimulation. These descending pontine fibers in turn inhibit the firing of sympathetic lumbar colonic nerves. Removal of this tonic restraint leads to rectal contraction.     

Studies on the integrated extrinsic nervous control of rectal motility in the cat

The effect of sympathetic nervous activity on rectal motility induced by pelvic nerve stimulation (PNS) was studied in anaesthetized cats. Division of the sympathetic lumbar colonic and hypogastric nerves or alpha-adrenoreceptor blockade, both of which reduced rectal tone, also reversed a predominantly relaxatory pelvic nerve response into a pure contraction. Contractions to pelvic nerve stimulation were reduced by simultaneous lumbar colonic nerve stimulation. This lumbar colonic nerve-induced inhibition was augmented by alpha-adrenoceptor blockade and abolished by beta-blockade. Close intra-arterial injection of a beta-adrenergic agonist reduced contractions to PNS, while an alpha-adrenergic agonist had no effect. Stimulation of the hypogastric nerves enhanced rectal contractions to simultaneous PNS. The apparent similarity with the arrangement of extrinsic nervous control of the internal anal sphincter suggests that the rectum is functionally involved in continence mechanisms.     

Reflex responses of neurons in the inferior mesenteric ganglion to mechanical stimulation of the colon, rectum, anal canal, and urinary bladder in the dog

Unitary discharges were recorded from the inferior mesenteric ganglion of decerebrate dogs. Eighty-one units were identified as sympathetic postganglionic neurons innervating the colon and rectum by collision test performed by stimulation of the lumbar colonic nerve. Discharges of four units were enhanced simultaneously with an increased outflow of the renal nerve by pinching a toe. Thus, those units were regarded as vasoconstrictors of colonic blood vessels. Sixty-five units whose discharges were depressed or not affected by the pinching were regarded as neurons innervating colonic smooth muscle or mucosa (colonic units). Discharges were enhanced in the majority of the colonic units by colonic, rectal, and vesical distension, and mechanical stimulation of the anal canal, while discharges were depressed in a few units by rectal and vesical distension, and the anal canal stimulation. The number and percentage of the depressed units increased not only after cutting the hypogastric nerves and descending branches of the lumbar colonic nerve but also after transection of the caudal pons. The reflex depressions disappeared after transection at the bulbospinal junction, but the reflex enhancements remained. These results indicate that the colonic units are enhanced through a spinal reflex by the inflows from the distal colon, rectum, anal canal, and urinary bladder through the lumbar colonic, hypogastric, pelvic, and pudendal nerves, while a few are inhibited through a supraspinal reflex by inflows through the pelvic and pudendal nerves.     

Non-nicotinic, non-adrenergic excitatory motor fibres in the preganglionic sympathetic supply to the feline colon. An axon reflex arrangement associated to thin sensory neurons, involving substance P?

Experiments were performed on chloralosed cats with ligated adrenals. The peripheral ends of the preganglionic sympathetic nerves to the colon were stimulated and colonic motility was monitored by a volumetric method. Electric nerve stimulation with various intensities elicited inhibitory motor responses and occasionally contractions. Hexamethonium and/or guanethidine blocked all inhibitory actions and revealed pure excitatory responses at high stimulation intensities. These colonic contractions were inhibited by atropine. However, atropine-resistant contractions were sometimes observed, predominantly in the colorectal region. Thoracic sympathetic nerves affected the motility in the proximal colon only, while lumbar sympathetic nerves acted on both proximal and distal parts. Strength-duration relationships and sensitivity to local heating suggest that the excitatory responses are due to an antidromic activation of thin, possibly afferent nerve fibres. Small doses of substance P injected close i.a. induced colonic contractions unchanged by hexamethonium and/or guanethidine but sensitive to atropine. The neurally-induced colonic contractions are suggested to be due to an antidromic activation of thin sensory neurons which in the periphery release substance P, in turn activating cholinergic motor neurons, thus constituting an axon reflex arrangement. The possibility of a similar axon reflex mechanism, associated to thin afferents, activating adrenergic inhibitory neurons at the prevertebral ganglionic level is discussed.     

Colonic Motility in the Cat IV. Peripheral Pathways Mediating the Effects Induced by Hypothalamic and Mesencephalic Stimulation

Rostad , H. Colonic motility in the cat. IV. Peripheral pathways mediating the effects induced by hypothalamic and mesencephalic stimulation. Acta physiol. scand. 1973. 89. 154–168. The peripheral pathways by which the hypothalamus and mesencephalon influence the motility of the colon have been studied by combining brain stimulation and peripheral nerve sectioning, and by use of autonomic blocking agents. Excitatory colonic effects induced from the hypothalamic sympatho-inhibitory area with concomitant blood pressure falls were found to be mediated through the sympathetic lumbar colonic nerves, whereas excitatory responses with associated blood pressure rises were conveyed through the latter as well as through the parasympathetic pelvic nerves. On the other hand, the augmentatory colonic effects usually associated with blood pressure rise evoked from the mesencephalon were conveyed through the lumbar colonic nerves only. The responses through the lumbar colonic and pelvic nerves were blocked by guanethidine and atropine, respectively. The augmentatory colonic responses from the hypothalamic sympatho-inhibitory area were blocked by the beta-adrenergic blocking agent propranolol, whereas the effects from the other responsive hypothalamic areas, transmitted through the lumbar colonic nerves, were blocked by alpha-blocker (phenoxybenzaminc), but not by propranolol. This finding support the presence of alpha-excitatory receptors in the colonic wall. Inhibition of colonic motility induced by hypothalamic and mesencephalic stimulation, weir found to be mediated through the lumbar colonic as well as through the splanchnic nerves. The effects were blocked by guanethidine, and those from the responsive hypothalamic zones were also blocked by propranolol.     

Neuropeptide Y may mediate effects of sympathetic nerve stimulations on colonic motility and blood flow in the cat

The present study investigated sympathetic mechanisms involved in the regulation of colonic motility and blood flow in the cat. Infusion of neuropeptide Y (NPY) close i.a. produced an inhibition of colonic motility and a vasoconstriction of long duration but no post-infusion vasodilatation. In contrast to NPY, porcine pancreatic polypeptide did not evoke any vascular or motility response. On a molar basis, NPY was 25 times more potent than noradrenaline in producing 50% reduction of the colonic blood flow. These vascular and motility effects of NPY were resistant to guanethidine, phentolamine, phenoxybenzamine and propranolol. Thus, the action of NPY on vascular and colonic smooth muscle did not seem to be mediated via adrenergic receptors. Noradrenaline administered close i.a. produced inhibition of colonic motility, and vasoconstriction followed by a rapid vasodilatation. These effects were completely blocked by combined alpha- and beta-adrenoceptor blockade. Electrical stimulation of the splanchnic and lumbar colonic nerves produced an overall inhibition of colonic motility, and vasoconstriction of the proximal and distal colon, respectively, with a rapid post-stimulatory vasodilatation. After combined alpha- and beta-adrenoceptor blockade the inhibitory effect of the nerve stimulations on colonic motility partly remained together with a marked vasoconstriction, which was most pronounced upon lumbar colonic nerve stimulation. All vascular effects of sympathetic nerve stimulation were eradicated by guanethidine, which also abolished the inhibitory motility response to splanchnic nerve stimulation. However, lumbar colonic nerve stimulation elicited a colonic contraction, possibly due to stimulation of afferent C-fibres. The present findings indicate the existence of a sympathetic nonadrenergic neuronal mechanism mediating vasoconstriction and inhibition of colonic motility in the cat. Thus, NPY may be released from noradrenergic neurons to act on colonic smooth muscle and vessels.     

Role and localization of a region in the pons which has a descending inhibitory influence on sympathetically mediated inhibition of the recto-rectal reflex of guinea pigs

The present study revealed the site of origin and the possible function of a supraspinal descending-inhibitory influence over the lumbar sympathetic component of the recto-rectal reflex of guinea pigs. The recto-rectal reflex contraction was not changed by suprapontine transection. It completely disappeared after subpontine transection, but returned immediately after additional section of the colonic nerves, which contain the sympathetic inhibitory outflow to the rectum, i.e., subpontine transection with the lumbar colonic nerves transected did not suppress the recto-rectal reflex. These results indicate that a descending pathway which can inhibit the lumbar sympathetic component of the reflex may originate in the pons. On stimulation at sites within the pons of animals which had been spinalized at L4 we were able to evoke an increase of rectal motility and an inhibition of the lumbar colonic efferent discharges, thus producing a response which is comparable to the reflex response produced by afferent stimulation of the rectum. The sites from which this effect could be evoked were mainly located in a band running rostrocaudally through the lateral reticular formation of the rostral part of the pons, medial to the sensory nucleus of the trigeminal nerve.     

Studies of vasoactive intestinal polypeptide expression in injured peripheral neurons using capsaicin, sympathectomy and mf mutant rats

The increased expression of vasoactive intestinal polypeptide (VIP) in injured peripheral neurons was studied. In contrast to substance P, there was a marked increase, and maintained fast axonal transport, of VIP in rat sciatic nerve after peripheral axotomy. Local capsaicin application to the nerve trunk failed to inhibit the injury-induced VIP increase, and capsaicin even increased VIP levels when applied locally to uninjured nerves. Pharmacological sympathectomy showed that some of the peripheral VIP increase may occur in post-ganglionic sympathetic fibres. The VIP increase after injury appeared unaffected in the mf mutant rat, in spite of its loss of lumbar dorsal root ganglion cells. VIP-staining fibres in the epi- and peri-neurium and perivascular plexuses of sciatic nerve showed an increase in number in parallel with the changes of the nerve VIP content. These findings suggest that sensory and sympathetic nerve fibres expressing VIP after injury play a role in the regulation of blood flow to nerves, and in the pathophysiological processes in nerve and dorsal spinal cord which follow peripheral nerve injury.     

Cardiopulmonary sympathetic afferent influences on renal nerve activity.

Cardiopulmonary sympathetic afferent nerves may affect renal control of intravascular volume by influencing renal sympathetic nerve activity. This influence was evaluated in alpha-chloralose anesthetized, vagotomized, sino-aortic denervated cats. When the afferent nerves were activated with a single electrical stimulus, the renal nerve responded with an excitatory burst of activity followed by a long period of inhibition. This response had characteristics of a supraspinal reflex. Repetitive stimulation of the sympathetic afferent nerve either inhibited or excited renal nerves and increased or decreased systemic blood pressure. The direction of these changes depended on stimulus parameters. No obligatory correlation in the direction of change of nerve activity and blood pressure was observed. Activation of cardiopulmonary sympathetic afferent nerves by intravascular volume expansion inhibited renal nerve discharge. Inhibition was elminated by sectioning the sympathetic afferent nerves. Volume expansion had no effect on lumbar sympathetic discharge monitored simultaneously with renal nerve activity. This observation suggests specificity of reflex influences of these afferent nerves on the kidney. In conclusion, cardiopulmonary sympathetic afferent nerves can reflexly alter renal nerve activity, and therefore may affect renal control of intravascular volume.     

Effects of sympathetic stimulation on C-fibre response after peripheral nerve compression: an experimental study in the rabbit common peroneal nerve

Non-myelinated C-fibre responses during sympathetic trunk stimulation were studied in rabbit common peroneal nerve 2 weeks after the nerve had been subjected to compression at 400 mmHg for 30 min. Our previous studies have demonstrated that during sympathetic trunk stimulation the compound action potential of uninjured somatic C-fibres is characterized by a reduced amplitude and an increased latency. In the present study, nerve compression changed the C-fibre response to sympathetic stimulation. Three out of eight nerves reacted to nerve compression by increased C-fibre compound action potential amplitude in response to sympathetic stimulation. In three other rabbits with compressed nerves the C-fibre action potential amplitude was unchanged, and in the remaining two rabbits the action potential amplitude was decreased during sympathetic stimulation. The action potential latency increased in all tested compressed C-fibres. The phenomenon of increased C-fibre amplitude during sympathetic activation has not been observed in uninjured nerves. As in uninjured nerves, noradrenaline infusion produced an increased C-fibre action potential amplitude and latency in six animals. Sympathetic stimulation did not affect the A-fibre response. These results indicate that sympathetic activity influences the conduction properties in C-fibres of somatic origin and that the response can be changed after a nerve injury. The findings may be of importance for the understanding of pain aggravation in different types of nerve injuries during increased sympathetic activity.     

Blockade of substance P receptors inhibits non-nicotinic, non-adrenergic colonic contractions induced by stimulation of the lumbar sympathetic nerves to the feline large intestine

Experiments were performed on chloralosed cats, pretreated with guanethidine and hexamethonium and with ligated adrenals. The motility of an arterially isolated colonic segment was monitored by a volumetric method. Colonic contractions were induced either by electric stimulation of the centrally cut lumbar splanchnic nerves, or by close i.a. injections of acetylcholine (ACh). Close i.a. injections of substance P (SP) were performed in order to test the degree of SP-receptor blockade. Blockade of colonic SP-receptors, either by close i.a. administration of large amounts of SP itself or by Spantide, a competitive SP-receptor antagonist, markedly reduced or abolished the neurally induced colonic contractions, while responses to ACh were unchanged. These results indicate a role for SP, or a closely related peptide, as an intermediate neurotransmitter in the neurally induced colonic responses. Thus, the present study gives support to the hypothesis that non-nicotinic, non-adrenergic colonic contractions, in response to electric stimulation of sympathetic nerves, are due to an antidromic activation of sensory neurons with peripheral excitatory collaterals which release SP, in turn activating the colonic smooth muscle, mainly via a muscarinic mechanism.     

Complementary role of vasoactive intestinal polypeptide (VIP) and acetylcholine for cat submandibular gland blood flow and secretion I. VIP release

The effects of parasympathetic and sympathetic nerve stimulation on VIP release in relation to blood flow and secretion were studied in the cat submandibular salivary gland. Parasympathetic nerve stimulation caused a marked VIP overflow (over thousand fold increase in VIP output) into the venous effluent from the gland which was simultaneous with profuse salivation and an about 10–15 fold increase in blood flow. The VIP output was dependent on the stimulation frequency, the duration of the stimulation period as well as the glandular blood flow. At 15 Hz maximal VIP output (about 4 fmol per impulse) was obtained after about 5 min of stimulation simultaneously with the maximum of the maintained phase of vasodilation. About 50 pmol VIP was recovered in the venous effluent from the gland during 1 h of maximal nerve stimulation. The VIP output after 1 h, was only about 20% of maximal, however, suggesting that the storage reserves and/or resupply of VIP might be running out. Under physiological conditions (frequencies ≤ 6 Hz) it was estimated that the axonal transport mechanism should be sufficient for replacement of VIP. At lower frequencies (2 and 6 Hz) the VIP output was parallel to vasodilation and secretion, while at a high frequency (15 Hz) a much more pronounced VIP output was seen. The increased overflow at 15 Hz may either be due to an actual increase in release or to a saturation of local VIP inactivating mechanisms. When stimulated simultaneously, the parasympathetic vasodilator mechanism seemed much more potent than sympathetic vasoconstriction. Since VIP may be present in cholinergic neurons, data from the literature concerning acetylcholine release are discussed in relation to the observed VIP output.     

Interaction between antisecretory opioid and sympathetic mechanisms in the rat small intestine

The putative existence of an endogenous opioid antisecretory mechanism in the small intestine was tested in anaesthetized Sprague-Dawley rats. Cholera secretion was elicited with cholera toxin and net fluid secretion was measured in vivo using a gravimetric technique allowing on line registrations. Opioid blockade with naloxone (10 mg kg-1 i.v.) increased the cholera secretion significantly but had no effect on control absorption. Pretreatment with phentolamine (2 mg kg-1 i.v.) eliminated the effect of opioid blockade indicating an interaction between the opioid and the adrenergic mechanisms. The effect of naloxone on cholera secretion was unchanged after acute division of the sympathetic nerves to the intestine and removal of the adrenals. Chronic sympathetic denervation of the small intestine, on the other hand, abolished the effect of opiate blockade on the secretion. The antisecretory effect of sympathetic nerve stimulation was unchanged by opiate blockade. Conclusion: An intrinsic antisecretory opioid mechanism has been demonstrated in the small intestine of the rat. This endogenous opioid mechanism seems to decrease secretion indirectly via peripheral activation of the sympathetic antisecretory system.     

On the sympathetic innervation to the cat's liver and its role for hepatic glucose release

Morphology and function of the adrenergic innervation of the liver were studied in cats. Fluorescence microscopy revealed a dense network of adrenergic nerve fibres in association with interlobular vessels and a sparse, but unequivocal innervation of the hepatocytes. These parenchymal adrenergic nerve fibres were more frequent in kittens (2 months old) than in adult cats. Electrical stimulation of the hepatic sympathetic nerves in the adult adrenalectomized cat evoked a small but insignificant increment (1–2 mM) of arterial plasma glucose concentration. When both hepatic and pancreatic sympathetic nerves were stimulated simultaneously, arterial plasma glucose concentration increased significantly by about 6 mM. We conclude that the pronounced hyperglycemic effect of activation of the sympathetic nervous system in the cat is mediated mainly via an adrenergic influence on the release of insulin and glucgon from the pancreas. The sympathetic innervation of the cat liver parenchyma seems to contribute to the hyperglycemia to a minor extent only.     

Efferent sympathetic nervous control of rectal motility in the cat

The sympathetic nervous control of rectal motility was studied in anesthetized cats. Division of the sympathetic nerves, i.e. the hypogastric nerves and the lumbar colonic nerves and alpha-adrenergic blockade reduced rectal tone indicating that these nerves are tonically active. Efferent electrical stimulation of the nerves at high intensities caused an immediate and sustained contraction which was inhibited after phentolamine but unaffected by hexamethonium suggesting a direct alpha-adrenergic effect on the rectal smooth muscle. However when prevailing rectal tone was high beta-adrenergic inhibitory responses unaffected by hexamethonium were observed. In addition the hypogastric nerves seem to convey cholinergic excitatory fibres to the rectum. The results imply that the sympathetic nerves are integrated in the nervous regulation of rectal motility in a fashion similar to the nervous control of the internal anal sphincter.     

The effect of oxytocin and adrenaline on blood flow in the hind limb of the dog following chronic lumbar sympathectomy

1. In a number of dogs the last two lumbar ganglia were removed unilaterally. At various dates up to the 56th day after operation the dogs were anaesthetized and the effect of oxytocin and adrenaline on hind-leg blood flow studied. Oxytocin alone reduced leg flow in all dogs after operation.

2. Until approximately day 11 after operation oxytocin given during an infusion of adrenaline increased leg blood flow, as it does in normal dogs not given adrenaline infusion. After that date it reduced the flow even during adrenaline infusion. The timing of this change suggests that the normal response to adrenaline depends on the presence of undegenerated nerve fibres.

3. In one animal the sympathetic nerves were crushed between the last two lumbar ganglia and beyond the last, and hind-leg blood flow frequently measured by means of venous occlusion plethysmography until day 204, when the animal was anaesthetized and acute observations made. Electrical stimulation of the sympathetic chain above the site of crushing caused a reduction in leg flow, indicating that at least some of the nerve supply had regenerated. However, oxytocin reduced leg flow when used alone and exerted no apparent effect in the presence of adrenaline.

4. It is suggested that sympathetic nerves to vascular smooth muscle have a function or functions other than transmitter release and that when crushed nerves regenerate the functions do not recover at the same rate.

     

Colonic Motility in the Cat

Rostad , H. Colonic motility in the cat. V. Influence of telencephalic stimulation and the peripheral pathways mediating the effects. Acta physiol. scand. 1973. 89. 169–181. The cerebral cortex and intracerebral structures were stimulated in lightly anesthetized cats while colonic motility was recorded using extraluminal strain gage transducers. Excitatory colonic responses were produced from the anterior ectosylvian gyrus (the second somatic sensory-motor area) and from a small zone around the anterior end of the lateral sulcus. These effects were shown to be mediated through the vagal nerves. Colonic inhibition resulted from stimulation of three separate cortical zones, the anterior sigmoid, the orbital and the anterior cingulate gyrl These effects were mediated mainly through the lumbar colonic nerves. Stimulation of the amygdaloid nuclei produced excitatory colonic effects mediated through the lumbar colonic nerves. Inhibitory effects were not obtained from the amygdala. Finally, weak colonic contractions resulted from stimulation of the olfactory bulb and tract and were found to be conveyed through the parasympathetic vagal and pelvic nerves.     

Effect of apamin on release of vasoactive intestinal polypeptide (VIP) from the cat intestines

The effect of apamin, a polypeptide from bee venom, on the release of vasoactive intestinal polypeptide (VIP) during active neurogenic vasodilatation in the intestines was studied in vivo in anesthetized cats. Three non-adrenergic, non-cholinergic mechanisms were investigated, i.e. the vasodilatation seen upon transmural electrical field stimulation, pelvic nerve activation and stimulation of the intramural nerves with 5-hydroxytryptamine (5-HT) infused i.a. Apamin given close i.a. abolished the three vasodilator responses. Concomitantly, the increase of VIP release was also markedly diminished although apamin increased the rate of VIP release seen in the "resting" control period. The results are in agreement with the hypothesis that VIP is the neurotransmitter in the three investigated vasodilator mechanisms.     

Influence on plasma levels of somatostatin, gastrin, glucagon, insulin and VIP-like immunoreactivity in peripheral venous blood of anaesthetized cats induced by low intensity afferent stimulation of the sciatic nerve

The objective of the present study was to investigate whether gastrointestinal hormones can be released in response to low intensity afferent activation of the sciatic nerve. Experiments were performed on anaesthetized cats in which the sciatic nerve was stimulated electrically at 3 Hz, to V and 0.2 ms. Blood samples were collected in a peripheral vein and the plasma levels of somatostatin, gastrin, glucagon, insulin and VIP-like immunoreactivity (below referred to as somatostatin, gastrin, glucagon, insulin and VIP) were recorded by radioimmunoassay. Afferent stimulation of the sciatic nerve caused immediate (approximately 15 min long) changes of the levels of all the above mentioned peptides. Somatostatin, gastrin and glucagon levels rose significantly, whereas in the case of insulin and VIP a significant relationship between the effect of sciatic nerve stimulation and basal levels was established. Thus, insulin and VIP levels decreased when basal levels were high and increased when basal levels were low. The secretion of gastrointestinal and pancreatic hormones is in part regulated by the autonomic nervous system. It is suggested that afferent stimulation of the sciatic nerve causes a reflex activation of the vagal and/or the splanchnic nerves, which in turn affects the release rate of the above-mentioned hormones. In conclusion, these data show that the release of gastrointestinal hormones can be influenced by low intensity stimulation of the sciatic nerve. The physiological trigger of these responses may be touching of the skin.