Reflex Vasodilator Response Research Articles

A novel human surrogate model of noninjurious sharp mechanical pain.

We propose a blade as a noninjurious nociceptive stimulus modeling sharp mechanical pain and yielding acute pain and hyperalgesia responses with closer proximity to incision-induced pain/hyperalgesia than punctate or blunt pressure mechanical pain models. Twenty-six healthy men and women were investigated to compare a small incision in the left forearm with noninvasive stimuli of different shapes and modalities to the right forearm. The magnitude and time course of incisional and blade-induced pain were assessed by numerical rating scales. Affective vs sensory components of pain experience were differentiated using a pain sensation questionnaire. The magnitude and time course of the axon reflex vasodilator response and of secondary hyperalgesia following a 7-second blade application were assessed. The maximum blade or incisional pain was similar (visual analogue scale [mean ± SD]: 32.9 ± 22.5 [blade] vs. 33.6 ± 29.8 [incision]), and both time courses matched closely in the first 10 seconds (paired t test; P = 0.5-1.0), whereas incision but not blade was followed by a second phase of pain, probably related to the tissue injury (decrease to half maximum pain 8 ± 2 vs. 33 ± 35 seconds; P < 0.01). Affective pain scores were significantly lower than sensory scores for all stimuli (P < 0.001). Comparing blade and incision, patterns of affective and sensory pain descriptors exhibited a remarkably similar pattern. Hence, we suggest the blade as novel model of sharp mechanical pain, which will be useful in investigating postoperative/mechanical pain and the role of self-injurious behavior in, eg, patients with borderline personality disorder.

Cutaneous Responses to Endothelin-1 and Histamine in Patients with Vibration White Finger

Vibration white finger (VWF) is the episodic blanching of the fingers that occurs in response to cold in those who work with hand-held vibrating tools. Clinically the condition differs from primary Raynaud's phenomenon as persistent pain and paresthesia are common in the hands and arms and occur independently of the "white attacks." We have previously reported a decrease in protein gene product 9.5 and calcitonin gene-related peptide-immunoreactive nerve fibers in the digital skin of individuals with VWF. In this study, we have sought to determine whether this deficit of immunoreactive sensory-motor nerves has a functional counterpart in vivo. Histamine produces a rapid wheal and flare response following intradermal injection, whereas endothelin-1 (ET-1) produces a central area of pallor with a surrounding neurogenic flare. In contrast, calcitonin gene-related peptide produces a non-neurogenic erythema. In this study, histamine and ET-1 were injected into the dorsum of the middle phalanx and the local neurovascular response was assessed by measuring the area of the visible flare or pallor. Basal finger blood flow was also measured by laser Doppler flowmetry in each of the digits prior to intradermal injection. The experiments were performed at 21 degrees C and 4 degrees C. Patients with VWF and asymptomatic vibration-exposed workers had significantly lower resting skin blood flow at both 21 degrees C and 4 degrees C than heavy manual workers with no vibration exposure. The size of the histamine- and ET-1-induced flares at both 21 degrees C and 4 degrees C was significantly smaller in patients with VWF when compared with the asymptomatic vibration-exposed workers and heavy manual workers. The size of the ET-1-induced pallor was smaller in patients with VWF when compared with the heavy manual workers at both 21 degrees C and 4 degrees C. In contrast, the area of erythema induced by intradermal injection of calcitonin gene-related peptide at both 21 degrees C and 4 degrees C was of a similar size in patients with VWF and in heavy manual workers. These results indicate that the neuroneal deficit identified by immunohistochemistry in the digital skin of patients with VWF has a functional counterpart in vivo and is evident as a reduced ability to propagate an axon-reflex vasodilator response when challenged with histamine and ET-1. Furthermore, these results enable patients with VWF to be differentiated from both asymptomatic vibration-exposed workers, in whom the histamine- and ET-1-induced flares are normal, and those with primary Raynaud's disease, in whom the ET-1 flare is reduced and the histamine-induced flare is normal.

Effects of clonidine and yohimbine on parasympathetic reflex salivation and vasodilatation in cat SMG.

The present experiments were designed to examine the site of action of the alpha 2-adrenoceptor agonist, clonidine, and the alpha 2-antagonist, yohimbine, on the salivary secretion response to parasympathetic and sympathetic stimulation in the cat submandibular gland (SMG). The parasympathetic reflex salivary secretion was significantly affected by both clonidine and yohimbine (clonidine reduced and yohimbine increased the amount of saliva secreted) while the reflex vasodilator response was not affected by either agent. No degree of methacholine-induced salivation was affected by prior treatment with either clonidine or yohimbine. The salivation elicited by facial nerve root stimulation was markedly reduced by clonidine but potentiated by yohimbine. Prior treatment with scopolamine completely abolished the salivary secretion induced by either methacholine or facial nerve root stimulation. Clonidine and yohimbine had no effect on SMG salivation elicited by sympathetic stimulation. These results indicate that the alpha 2-agonist and antagonist act specifically on parasympathetic salivary fibers but have no effect on parasympathetic vasodilator fibers. They thus suggest that postganglionic parasympathetic innervation is differentiated into salivary and vasodilator fibers.

The parasympathetic vasodilator fibers in the trigeminal portion of the distal lingual nerve in the cat tongue

Electrical stimulation of the peripheral and central cut ends of the chorda tympani nerve (CTN) caused an increase in ipsilateral tongue blood flow in anesthetized cats. Both blood flow increases were markedly reduced by pretreatment with the autonomic ganglionic blocker hexamethonium (1.0 mg/kg). Electrical stimulation of the central cut ends of the CTN, inferior alveolar nerve, and vagus nerve as well as of the upper buccal gingiva also caused the vasodilator responses in the sympathectomized cat tongue. These vasodilatations were notably reduced by hexamethonium pretreatment, and were almost completely abolished by the section of the distal lingual nerve (DLN) and the lingual nerve proper but not by section of the CTN. The present data suggest that the parasympathetic vasodilator fibers in the CTN are not involved in somatoautonomic reflex vasodilatation in the cat tongue and that the major part of the somatoautonomic reflex vasodilator response is mediated by parasympathetic fibers running together with the trigeminal portion of the DLN as vasodilator fibers in the cat tongue. This also implies that there are two groups of parasympathetic vasodilator fibers, that is, one originates from the CTN (the facial nerve) and other from the trigeminal portion of the DLN (probably via the glossopharyngeal nerve).

Reflex vasodilatation in the cat lip evoked by stimulation of vagal afferents

In 36 cats under nembutal anaesthesia, stimulation of the central end of the cut vagus nerve caused blood flow to increase in only the ipsilateral side in six cats (17%) and in the bilateral sides in 30 cats (83%) in the lower lips. Pretreatment with hexamethonium to block nicotinic synapses in autonomic ganglia resulted in a time-dependent reduction of the reflex vasodilator response, while phentolamine, propranolol (α-, β-adrenoreceptor antagonists) and tripelennamine (histamine receptor antagonist) had no effect. Pretreatment with atropine (muscarinic receptor antagonist) showed a slight, but not statistically insignificant attenuation of the reflex vasodilation. Ipsilateral section of either the glossopharyngeal nerve root or the inferior alveolar nerve completely abolished the reflex vasodilator response elicited by central vagal stimulation. The reflex vasodilator response induced by stimulation of the central end of the cut vagus nerve was abolished by topical capsaicin application on the central cut ends of the vagus nerve but not by capsaicin on the inferior alveolar nerve. These results suggest that there is a cutaneous reflex vasodilator system that can be activated via capsaicin-sensitive afferent fibres in the vagus nerve. Parasympathetic vasodilator fibres of this system emerge from the brain stem with the glossopharyngeal nerve and reach the blood vessels in the cat mandibular lip via the inferior alveolar nerve.

Somatosensory stimulation causes autonomic vasodilatation in cat lip.

1. Electrical stimulation of the infra-orbital nerve and the maxillary buccal gingiva caused an increase in ipsilateral lip blood flow in a stimulus intensity-dependent manner in anaesthetized cats. 2. The reflex vasodilator response was resistant to blockade by antimuscarinic (atropine), antiadrenergic (phentolamine and propranolol) and antihistaminergic (tripelennamine) but sensitive to ganglionic blocking agent (hexamethonium). 3. The reflex vasodilator response was unaffected by section of the ipsilateral cervical sympathetic trunk and facial nerve root, but was completely abolished by ipsilateral section of the glossopharyngeal nerve root. 4. The vasodilator response elicited by stimulation of the facial and glosso-pharyngeal nerves was never affected by lesion of the ipsilateral pterygopalatine ganglion. 5. Local anaesthesia or section of the inferior alveolar nerve abolished the vasodilator effects of stimulation of the facial and the glossopharyngeal nerves. 6. These results suggest that there is a somato-autonomic reflex vasodilator system mediated via final neurons that are not cholinergic, and that the parasympathetic vasodilator fibres emerge from the brain stem with the glossopharyngeal nerve and reach the blood vessels via the otic ganglion and the inferior alveolar nerve in the cat mandibular lip.

Effects of vasopressin on the circulation and its baroreflex control in healthy men.

Information on the hemodynamic effects of vasopressin (AVP) in healthy humans is very limited despite its known importance in body fluid homeostasis and release in pathologic states such as hemorrhage and trauma. Although it is a potent vasoconstrictor in vitro, it does not cause the expected rise in arterial pressure when given systemically to animals with intact baroreflexes. It has been proposed that this is because AVP facilitates baroreflex control of the circulation. In this study, we assessed the effect of infusion of AVP on resting circulatory variables and on the baroreflex control of forearm vascular resistance and heart rate in healthy men. AVP in a dose of 0.4 ng/kg/min, which raised plasma level of AVP to 24 +/- 4 pg/ml, a value known to have a significant antidiuretic effect, had little hemodynamic effect, producing only mild bradycardia and a slight increase in central venous pressure. Reflex changes in heart rate during neck suction (-15 and -30 mm Hg) and neck pressure (+15 and +30 mm Hg) were not altered. Reflex responses to lower body negative pressure and to its release were also unchanged by this dose of AVP. In contrast, a higher dose of AVP (4 ng/kg/min), which raised plasma levels to 290 +/- 41 pg/ml, a concentration known to occur as a result of hemorrhagic hypotension and circulatory stresses, did cause hemodynamic changes. There was tachycardia (from 63 +/- 2 to 68 +/- 2 beats/min), a decrease in pulse pressure (from 62 +/- 2 to 53 +/- 2 mm Hg), an increase in central venous pressure (from 2.6 +/- 0.5 to 4.1 +/- 0.4 mm Hg), and surprisingly in view of the known vasoconstrictor effect of AVP, an increase in forearm flow (from 4.4 +/- 0.7 to 5.9 +/- 1.2 ml/min/100 ml tissue) and a decrease in forearm vascular resistance (from 24 +/- 4 to 18 +/- 3 U); there was no significant change in mean arterial pressure (from 83 +/- 2 to 83 +/- 3 mm Hg). Reflex changes in heart rate were unaltered. The maximal vasoconstrictor response in the forearm attained during lower body negative pressure was not influenced by AVP, but the reflex vasodilator response to the sudden release of lower body negative pressure was significantly augmented, vascular resistance falling to 23 +/- 4 U before and 13 +/- 2 U during AVP. The unanticipated findings in this study include the biphasic changes in heart rate with increasing doses of AVP, the absence of a pressor response, and the vasodilatation in forearm vessels.(ABSTRACT TRUNCATED AT 400 WORDS)

Comparison of reflex vasodilator responses in hindlimb of dog and cat.

Comparison of reflex vasodilator responses in hindlimb of dog and cat.

EFFECT OF SOME DRUGS ON REFLEX VASODILATATION OF HAND PRODUCED BY RADIANT HEATING OF TRUNK.

The effect of some drugs on reflex vasodilatation in the hand was studied. Bretylium tosylate and phenoxybenzamine abolished the reflex vasodilator response in the hand caused by cradle heating of the chest. Alpha methyl dopa, nethalide, and atropine had no effect on this response. It is suggested that the tonic constriction of hand vessels maintained by sympathetic fibers and alpha adrenergic constrictor receptors is temporarily interrupted by 40 sec cradle heating of the chest and that this produces the observed increase in hand blood flow. The reflex increase in hand blood flow with short cradle heating of the chest appears to utilize a common efferent pathway with the vasodilator response produced in the hand by prolonged heating of the legs. On the afferent side, however, these reflexes use different mechanisms. afferent and efferent pathways; alpha methyl dopa; nethalide; atropine; receptors on hand vessels; bretylium tosylate; phenoxybenzamine Submitted on February 24, 1964

THE EFFECT OF SYMPATHECTOMY ON THE VASOMOTOR CAROTID SINUS REFLEXES OF THE CAT

The carotid sinus is a sensory zone where vasomotor, cardiac and respira. tory reflexes arise. The vasomotor and cardiac reflexes have a common afferent pathway; pressure changes within the carotid sinus stimu1at.c stretch receptors in the arterial wall, initiating impulses which are conducted by the carotid sinus nerve to the glossopharyngeal nerve and thencci to the vasomotor and cardiac centers of the medulla. The efferent components of the cardiac portion of the carotid sinus reflex are formed by the vagus and cardioaccelerator nerves which function reciprocally (Heymans, Bouckaert and Regniers, 1933). The efferent arc of the vasomotor portion of the reflex is less clearly defined. The sympathetic vasoconstrictors constitute one important pathway; does the reflex traverse separate vasodilator pathways as well? Reflex vasodilatation of blood vessels has been obtained in sympathectomized regions (Bayliss, 1902; Fofanow and Tschalussow, 1913; Bishop, Heinbecker and O’Leary, 1933). Freeman and Rosenblueth (1931) elicited reflex vasodilator responses in completely sympathectomizcd cats by stimulation of the vago-depressor trunk and various sensory nerves. Rosenblueth and Cannon (1934) concluded that the dilator fibers in the dorsal roots of the spinal nerves were probably the efferent paths of these dilator reflexes observable in sympathectomized cats. The efferent components of the vasomotor reflexes which originate in the arch of the aorta and in the carotid sinuses are supposedly identical. It was thought, therefore, that vasodilator responses might be obtained in completely sympathectomized cats by raising the pressure within an artificially perfused carotid sinus. We believed that such a technique would enable us to elicit possible reflexes by physiological stimulation of sensory endings and would be preferable to direct mechanical or electrical stimulation of nerves. The results reported here were obtained while testing this hypothesis. METHOD. The thoracic and abdominal sympathetic chains of adult cats were removed in two stages by the method of Cannon, Newton,