Sympathetic activity in the recto-rectal reflex of the guinea pig

In the guinea pig, defecation is controlled by the myenteric plexus, whose activity is modulated by the sacral spinal and supraspinal centers. The purpose of this study is to clarify the control of defecation reflex by sympathetic nerves. The propulsive contractions of the rectum produced by rectal distension (recto-rectal excitatory reflex response) were abolished after transection of the Th 13 and/or the L 4 segment. This response was reproduced again after removal of the lumbar segments (L1-4), division of the lumbar dorsal roots (L1-4), the lumbar splanchnic nerves or lumbar colonic nerves (LCN). The frequency of efferent discharges of LCN was increased slightly by rectal distension and remarkably increased after Th 13 and/or L 4 transection. Thus, there occurs during the recto-rectal reflex not only mucosal intrinsic reflex and sacral excitatory reflex via the pelvic nerves but also a lumbar inhibitory reflex via the colonic nerves, whose center may be located in the upper lumbar segments.But, the activity of the inhibitory center was depressed by the supraspinal center, so that an excitatory reflex is produced more dominantly than an inhibitory one in normal animals. All these extrinsic reflexes coordinate the activity of the myenteric plexus in defecation reflex.     

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.     

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.     

Functional role of lumbar sympathetic nerves and supraspinal mechanism in the defecation reflex of the cat

The role of the lumbar sympathetic nerves and supraspinal mechanism in the defecation reflex was investigated in 30 adult cats and 6 kittens. One or two propulsive contractions, whose mean pressure evoked was more than about 90 cmH2O (adult cats) and 50 cmH2O (kittens), were induced in the rectum of all animals by rectal distension. These propulsive contractions could be generated at the descending and the transverse colons. The removal of the supraspinal influence by spinal transection at T13 or removal of pelvic afferents to the supraspinal center by spinal transection at L abolished the propulsive contractions. Successive lumbar sympathectomy restored the contractions. Lumbar sympathectomy and the successive removal of the supraspinal influence did not affect the propulsive contractions. In both cases, the final exclusion of the sacral segments by pithing of the spinal cord abolished the propulsive contractions. These results suggest that the sacral excitatory reflex mediated via pelvic nerves and the lumbar inhibitory reflex mediated via lumbar sympathetic nerves can function during rectal distension in spinal cats and that the lumbar inhibitory reflex is suppressed by the supraspinal sympathetic inhibitory reflex activated by pelvic afferents in intact cats, as in guinea pigs, resulting in propulsive contractions.     

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.     

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.     

Spinal and supraspinal components of the reflex discharges into lumbar and thoracic white rami

1. In chloralose anaesthetized cats reflex discharges in thoracic and lumbar white rami were elicited by single shock stimulation of intercostal, spinal and hind limb nerves.2. In animals with an intact neuraxis single stimuli of sufficient strength usually elicited a white rami mass discharge having two distinct components. Following spinal transection only the late reflex component disappeared.3. The early (spinal) reflex component had its largest amplitude if the afferent volley entered the spinal cord at the same or an adjacent segment of the white ramus under observation, whereas the size of the late (supraspinal) component was rather independent of the segmental level of the afferent input.4. It was concluded that somatic afferent volleys have a twofold action on the sympathetic nervous system: a more generalized action via the supraspinal sympathetic reflex centres and a more circumscribed action on the preganglionic neurones at the segmental level.     

Reflexogenic Contraction of the Ileo-Cecal Sphincter in the Cat Following Small or Large Intestinal Distension

The effect of distension of a small or large intestinal loop on the ileo-cecal sphincter (ICS) in the cat was studied with a flow-recording technique. Distension of a small or large intestinal loop, isolated from the adjacent intestine, but with its mesenteric vascular and nervous supply intact, elicited a contraction of the ICS concomitant with an inhibition of the adjacent large and small intestinal motility. Vagal and pelvic nerve section did not affect the response to distension of the ICS nor exclusion of the adrenal glands from the circulation. The sphincter reflex could be entirely or almost entirely eliminated by cutting both the splanchnic and lumbar colonic nerves, but not one or the other. Spinal anesthesia blocked the reflex response indicating a spinal reflex arc. The reflex persisted after atropine and propranolol, while both guanethidine and phenoxybenzamine completely abolished the reflex contraction of the sphincter. The present results indicate that the excitatory intestino-ileo-cecal sphincteric reflex is a spinal reflex with the main afferent and/or efferent fibres located within the major splanchnic and lumbar colonic nerves. The excitatory motor response in the sphincter is adrenergic and mediated viaα-receptors.     

Reflexogenic contraction of the ileo-cecal sphincter in the cat following small or large intestinal distension.

The effect of distension of a small or large intestinal loop on the ileo-cecal sphincter (ICS) in the cat was studied with a flow-recording technique. Distension of a small or large intestinal loop, isolated from the adjacent intestine, but with its mesenteric vascular and nervous supply intact, elicited a contraction of the ICS concomitant with an inhibition of the adjacent large and small intestinal motility. Vagal and pelvic nerve section did not affect the response to distension of the ICS nor exclusion of the adrenal glands from the circulation. The sphincter reflex could be entirely or almost entirely eliminated by cutting both the splanchnic and lumbar colonic nerves, but not one or the other. Spinal anesthesia bocked the reflex response indicating a spinal reflex arc. The reflex persisted after atropine and propranolol, while both guanethidine and phenoxybenzamine completely abolished the reflex contraction of the sphincter. The present results indicate that the excitatory intestino-ileo-cecal sphincteric reflex is a spinal reflex with the main afferent and/or efferent fibres located within the major splanchnic and lumbar colonic nerves. The excitatory motor response in the sphincter is adrenergic and mediated via alpha-receptors.     

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.     

The sympathetic innervation of the internal anal sphincter and rectum in the cat

The distribution of the sympathetic innervation to the internal anal sphincter (IAS) and rectum and the occurrence of different types of adrenergic receptors in the two organs were investigated in anaesthetized cats. Anal pressure and rectal motility were recorded by a manometric and a volumetric method respectively. Division of both the hypogastric nerves (HGN) and the lumbar colonic nerves (LCN) reduced the anal pressure by 46 +/- 6% of the resting pressure (40.9 +/- 6.4 mmHg) and consistently increased rectal motility. Efferent electrical stimulation of the HGN as well as the LCN elicited a contraction in the anus and the rectum, which, at maximal stimulation, caused the anal pressure to reach a similar level to that recorded before division of these nerves. After injection of phentolamine the anal contraction was abolished, whereas the rectal contraction was either abolished or converted to a beta-adrenergic relaxation. Propranolol caused increased rectal contraction in response to stimulation of the HGN and the LCN, whereas the anal contraction was unaffected. The results imply that the sympathetic nerves exert a tonic excitatory effect on the IAS and a dual effect on the rectum in the cat. The results also indicate that sympathetic fibres to the IAS are conveyed in both the HGN and the LCN. Inhibitory beta-adrenergic receptors seem to be of minor importance in regulating anal pressure.     

Cutaneous Mechanical Stimulation Regulates Ovarian Blood Flow via Activation of Spinal and Supraspinal Reflex Pathways in Anesthetized Rats

The reflex effects of noxious mechanical stimulation of a hindpaw or abdominal skin on ovarian blood flow, and the reflex pathways involved in those responses were examined in anesthetized rats. Blood flow in the left ovary was measured using a laser Doppler flowmeter, and the activity of the left ovarian sympathetic nerve and mean arterial pressure (MAP) of the common carotid artery were recorded. Stimulation of the left or right hindpaw for 30 s produced marked increases in ovarian sympathetic nerve activity and MAP. Ovarian blood flow slightly decreased during the stimulation and then slightly increased after the stimulation. After the left ovarian sympathetic nerves were severed, the same stimulus produced a remarkable monophasic increase in ovarian blood flow that was explained by passive vasodilation due to a marked increase in MAP. After spinal transection at the third thoracic (T3) level, the responses of MAP, ovarian sympathetic nerve activity, and ovarian blood flow to hindpaw stimulation were nearly abolished. Stimulation of the abdomen at the right or left side for 30 s produced slight increases in ovarian sympathetic nerve activity and MAP. Ovarian blood flow slightly decreased during the stimulation and then slightly increased after the stimulation. After the ovarian sympathetic nerves were severed, the response of the ovarian blood flow changed to a monophasic increase due to an increase in MAP. After spinal transection, stimulation of the left abdomen produced a moderate increase in MAP, a remarkable increase in ovarian sympathetic nerve activity and a slight decrease in ovarian blood flow during the stimulation. In contrast, stimulation of the right abdomen produced a smaller response in ovarian sympathetic nerve activity during the stimulation while it increased the MAP to a similar degree. Ovarian blood flow slightly increased after the end of stimulation, which was explained as passive vasodilation due to the increase in MAP. In conclusion, stimulation of somatic afferents affects ovarian blood flow by inducing changes in ovarian sympathetic nerve activities and blood pressure. When stimulation was applied to a hindpaw whose segment of afferent input is far from the segment of the ovarian sympathetic nerves, it took a supraspinal reflex pathway. However, when stimulation was applied to the abdomen whose spinal segment of the afferent is close to the segment of the ovarian sympathetic nerve output, there are spinal segmental reflex pathways. The present results demonstrate that spinal reflexes depend on the laterality of the stimulus, while supraspinal reflexes do not depend on the laterality of the stimulus.     

Physiological characterization of the renal-sympathetic reflex in rabbits

In urethane-anesthetized and vagotomized rabbits, electrical stimulation of the afferent renal nerve (RN) elicited reflex changes in renal nerve activity (RNA) and arterial pressure (AP). The responses were attributable mostly to excitation of nonmyelinated afferent fibers, although, in about 30% of the animals, they were contributed slightly by myelinated afferents. In about 70% of rabbits, the peristimulus time histogram (PTH) of RNA following stimulation of the RN consisted of a long-lasting inhibitory (I) component occasionally accompanied, during its recovery phase, by a transient excitatory (E) component. In these animals, tetanic stimulation of the RN resulted in a depressor response, either alone or, if an E component was present in the PTH, followed by a slight pressor response. In the remaining rabbits, the PTH was composed exclusively of an E component and tetanic stimulation caused a pressor response. Stimulation of the RN evoked reflex changes in cardiac sympathetic discharges comparable to that of RNA, whereas the change in cervical sympathetic discharges was much smaller. The sympathetic response remained intact after a total transection of the rostral medulla near the ponto-medullary junction; the I component was even augmented. However, it usually disappeared following a transection at the high cervical cord. Bilateral lesions of the nucl. tractus solitarius (NTS) near the obex failed to appreciably affect the response. Among chemical and mechanical stimuli examined, nociceptive stimulation of the kidney elicited a sympathetic response comparable to that following nerve stimulation. In conclusion, the renal-sympathetic reflex in rabbits (1) originates predominantly from nonmyelinated afferent renal fibers activated effectively by nociceptive stimulation applied to the kidney; (2) depends critically on medullary structures other than the NTS; and (3) evokes changes of the same temporal pattern but of nonuniform magnitude in sympathetic discharges to different organs.     

Sympathetic nerve activation decreases the release of vasoactive intestinal polypeptide from the feline intestine

The splanchnic nerves to the small intestine were stimulated in anaesthetized cats. Activation of the sympathetic nerves caused vasoconstriction, increased net fluid absorption and decreased release of vasoactive intestinal polypeptide (VIP) in the small intestine. In the colon, parasympathetic nerve stimulation elicited vasodilatation and increased release of VIP. Additional stimulation of the sympathetic lumbar colonic nerves decreased the colonic blood flow and inhibited the release of VIP. These effects of the stimulation of the lumbar colonic nerves were blocked by phentolamine. It is concluded that, in the feline intestine, sympathetic nerve stimulation presynaptically decreased the release of VIP via an alpha-adrenergic mechanism.     

Afferent electrical stimulation of mesenteric nerves inhibits duodenal HCO3- secretion via a spinal reflex activation of the splanchnic nerves in the rat

The experiments were performed on male Sprague-Dawley rats anaesthetized with chloralose. Duodenal HCO3- secretion was measured in situ by pH-stat titration. The nerves bundles surrounding two randomly chosen mesenteric vessels were electrically stimulated (3 Hz, supramaximal intensity) in the afferent direction. This was done in order to mimic the intestino-intestinal spinal reflex activation of the splanchnic sympathetic fibres. The procedure reduced duodenal HCO3- secretion by 20% together with an increase in mean arterial pressure and heart rate. Duodenal HCO3- secretion decreased similarly in control rats and in those subjected to a cervical cord transection, whereas animals with bilaterally cut splanchnic nerves did not respond to such mesenteric nerve stimulation. Pharmacological pretreatment with guanethidine or yohimbine, but not prazosin, inhibited the reduction in duodenal HCO3- secretion. Thus the data suggest that electrical stimulation of mesenteric afferent nerves inhibits duodenal HCO3- secretion via a spinal reflex activation of splanchnic sympathetic nerve fibres to the duodenum, and that the response is mediated via alpha 2 adrenoceptors.     

Pontomedullary transection attenuates central respiratory modulation of sympathetic discharge, heart rate and the baroreceptor reflex in the in situ rat preparation

Previous studies have indicated a major role for the pons in the genesis of the respiratory pattern. The respiratory rhythm is coupled to the cardiovascular system to ensure optimal matching of minute ventilation and cardiac output. Since much of this coupling results from cross-talk between brainstem circuits, we have assessed the role of the pons in both the co-ordination of respiratory and cardiovascular efferent activities and the baroreceptor reflex efficacy. Using the arterially perfused in situ rat preparation, we recorded neural activities from the left phrenic nerve, central end of the vagus nerve, thoracic sympathetic chain (T8-T10) and heart rate. Respiratory sinus arrhythmia, respiratory modulation of sympathetic nerve activity (and Traube-Hering waves in arterial pressure) and postinspiratory discharges recorded from vagal efferents were eliminated after pontine transection. We also found that although the sympathetic arterial baroreflex remained intact, respiratory gating of the baroreceptor reflex (i.e. both bradycardia and sympathoinhibition) was abolished after pontine removal. We propose that neural activity of the pons is essential for physiological coupling of centrally generated respiratory and cardiovascular efferent activities.     

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.     

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.     

Reflex firing in the lumbar sympathetic outflow to activation of vesical afferent fibres

1. Activation of vesical afferent fibres in the Aγδ range by electrical stimulation of the pelvic nerve or by bladder distension elicited reflex firing in hypogastric nerves and in preganglionic nerves to the inferior mesenteric ganglion.

2. The multisynaptic reflex was present in cats with an intact spinal cord and in acute and chronic spinal animals (transections at T10—T12). The reflex pathway was partially crossed in the sacral cord, and in the periphery at the level of the inferior mesenteric ganglia. In contrast, an inhibitory response to raised intravesical pressure was mediated by a supraspinal inhibitory mechanism which was activated in parallel with the micturition reflex.

3. Since enhancement as well as depression of sympathetic firing accompanied reflex micturition, it is concluded that at least two distinct populations of lumbar preganglionic neurones are responsive to vesical afferent activity: one population being excited, the other depressed, during micturition. The latter population may be involved in an inhibitory feed-back mechanism on to the bladder.

     

Sensory and sympathetic nerve contributions to the cutaneous vasodilator response from a noxious heat stimulus

We investigated the roles of sensory and noradrenergic sympathetic nerves on the cutaneous vasodilator response to a localized noxious heating stimulus. In two separate studies, four forearm skin sites were instrumented with microdialysis fibres, local heaters and laser-Doppler probes. Skin sites were locally heated from 33 to 42 °C or rapidly to 44 °C (noxious). In the first study, we tested sensory nerve involvement using EMLA cream. Treatments were as follows: (1) control 42 °C; (2) EMLA 42 °C; (3) control 44°C; and (4) EMLA 44 °C. At the EMLA-treated sites, the axon reflex was reduced compared with the control sites during heating to 42 °C (P < 0.05). There were no differences during the plateau phase (P > 0.05). At both the sites heated to 44 °C, the initial peak and nadir became indistinguishable, and the EMLA-treated sites were lower compared with the control sites during the plateau phase (P < 0.05). In the second study, we tested the involvement of noradrenergic sympathetic nerves in response to the noxious heating using bretylium tosylate (BT). Treatments were as follows: (1) control 42 °C; (2) BT 42 °C; (3) control 44 °C; and (4) BT 44 °C. Treatment with BT at the 42 °C sites resulted in a marked reduction in both the axon reflex and the secondary plateau (P < 0.05). At the 44 °C sites, there was no apparent initial peak or nadir, but the plateau phase was reduced at the BT-treated sites (P < 0.05). These data suggest that both sympathetic nerves and sensory nerves are involved during the vasodilator response to a noxious heat stimulus.