C-fiber Activation Research Articles

Physiological and pharmalogical properties of the three subsystems constituting the aortic nerve-renal sympathetic reflex in rabbits

Electrical stimulation of the aortic nerve of anesthetized rabbits reflexly evoked both excitation and inhibition of renal nerve activity. The excitatory component of the reflex, observed in about 75% of the animals, was elicited by activation of aortic C-fibers. It was selectively suppressed by chronic treatment of the animal with capsaicin. Intracisternal injection of either [ d-ala 2]-met-enkephalinamide or beta-endorphin markedly attenuated this excitatory component, although neither affected the excitatory component mediated by chemoreceptor fibers in response to stimulation of the carotid sinus nerve. It seems most likely that nociceptive C-fibers of the rabbit's aortic nerve were responsible for the excitatory component. On the other hand, the inhibitory component was reflexly elicited by stimulation of the aortic A- or C-fiber group activated separately or in combination. In agreement with previous reports, the sympatho-inhibitory action of C-fibers was more powerful and longer-lasting than that of A-fibers. We found that the inhibitory component induced by C-fibers was markedly attenuated by the two opioid peptides mentioned above, but was resistant to pentobarbital. On the contrary, the component mediated by A-fibers was suppressed by pentobarbital but was relatively resistant to the opioid peptides. Thus, the rabbit's aortic nerve-renal sympathetic reflex consists of the following 3 subsystems characterized by different physiological and pharmacological properties: sympatho-inhibitory systems activated by barosensory A- or C-fibers and a sympatho-excitatory system attributable to C-fibers probably of nociceptive modality.

Resetting of aortic baroreceptors with non-myelinated afferent fibers in spontaneously hypertensive rats.

The phenomenon of resetting and the possible mechanisms responsible for it were investigated in aortic baroreceptors having unmyelinated axons. Recordings were obtained from 31 aortic baroreceptor C-fibers in 20 normotensive Wistar Kyoto rats (WKY) and 37 baroreceptor C-fibers in 11 spontaneously hypertensive rats (SHR). The recordings were obtained from the left aortic nerve of an in vitro aortic nerve-aortic arch preparation. The thresholds for activation of baroreceptor C-fibers were not different between SHR's and WKY's at 16 weeks of age (139 +/- 7 and 133 +/- 5 mmHg, respectively). However, the thresholds for activation in SHR at 36 weeks of age were considerably higher (163 +/- 4 mmHg) indicating resetting of the receptors in the older rats. The pressure-discharge curves were not different between SHR's and WKY's at 16 weeks of age and WKY's at 35 weeks of age, but were shifted to the right for SHR's at 36 weeks of age. The receptors showed greater responses to pulsatile pressures than to steady state pressures at the same mean level of pressure. We found that aortic C-fibers were not reset during the early established phase of hypertension in SHR's because of enhanced receptor strain sensitivity. This is likely to be of importance for tonic vasomotor control at this time. In later stages of hypertension and despite enhanced strain sensitivity the endings were reset to higher pressures probably due to an increased collagen content in the aortic wall.

Effect of anodal blockade of myelinated fibers on vagal C-fiber afferents.

The effects of monopolar cathodal, monopolar anodal, and bipolar anodal polarizing currents on vagal A- and C-fiber activity were studied in anesthetized dogs. Monopolar cathodal polarization consistently produced excitation of spontaneous and evoked A- and C-fibers. Monopolar anodal and bipolar anodal polarizations differentially blocked A-fibers as a function of fiber diameter. The specific purpose of this study was to compare the effects of monopolar anodal and bipolar anodal currents on C-fiber excitability. Small fiber preparations were dissected from the vagal trunk, cut centrally, and placed on recording electrodes. A constant-current stimulus pulse was applied to the nerve at various distances from the blocking electrodes. The stimulus current strength was increased until an isolated C-fiber spike was observed. This value was defined as 100% of threshold. The stimulus current was then reduced to zero, the blocking current was increased slowly to 100 microA, and the procedure repeated. Threshold data obtained in this manner for each set of stimulation electrodes was plotted as a function of distance from the blocking electrode(s) for both modes of anodal blockade. No significant change in C-fiber excitability was observed with bipolar anodal blockade, whereas excitability was significantly (P less than or equal to 0.05) decreased using the monopolar technique. Thus, monopolar anodal block may reduce the possibility of asynchronous C-fiber discharge, which has been associated with a bipolar block of A-fibers.

II. Effect of CO 2 on afferent vagal endings in the canine lung

We have attempted to identify the afferent endings responsible for the pulmonary-CO 2 ventilatory reflex. We recorded afferent vagal impulses arising from the left lung in anesthetized dogs with separately ventilated lungs. When the left pulmonary artery was occluded, left lung P CO 2 fell to 3 mm Hg and slowly-adapting pulmonary stretch receptor activity increased 46%. Firing declined to its original intensity when left lung P CO 2 was raised in steps by administration of CO 2, firing decreasing most between 2 and 19 mm Hg, and least between 30 and 50 mm Hg. Irritant receptor activity also increased (from 2.8 to 7.4 impulses/sec) after pulmonary arterial occlusion, the effect being reversed by administration of CO 2. These procedures caused trivial changes in pulmonary and bronchial C-fiber activity. Effects on both slowly-adapting stretch receptors and irritant receptors appeared to result from a direct action of CO 2 on the endings themselves, rather than from mechanical changes in the lung. Changes in slowly-adapting stretch receptor activity provide an adequate explanation for the pulmonary CO 2 ventilatory reflex, the relationship between impulse frequency and lung P CO 2 suggesting that these afferents may have a role in limiting CO 2 loss under conditions causing hypocapnia, but be less effective in stimulating breathing during hypercapnia.

Comparison of responses of warm and nociceptive C-fiber afferents in monkey with human judgments of thermal pain

1. Radiant-heat stimuli of different intensities were delivered every 28 s to the thenar eminence of the hand of human subjects and to the receptive fields (RFs) of 58 "mechanothermal nociceptive" and 16 "warm" C-fibers, most of which innervated the glabrous skin of the monkey hand. A CO2 infrared laser under control via a radiometer provided a step increase in skin temperature to a level maintained within +/- 0.1 degrees C over a 7.5-mm-diameter spot. 2. Human subjects categorized the magnitude of warmth and pain sensations evoked by stimuli that ranged in temperature from 40 to 50 degrees C. The scale of subjective thermal intensity constructed from these category estimates showed a monotonically increasing relation between stimulus temperature and the magnitude of warmth and pain sensations. 3. The mechanothermal fibers had a mean RF size of 18.9 +/- 3.2 mm2 (SE), a mean conduction velocity of 0.8 +/- 0.1 m/s, mean thresholds of 43.6 +/- 0.6 degrees C for radiant heat and 5.95 +/- 0.59 bars for mechanical stimulation, and no spontaneous activity. In contrast, warm fibers had punctate RFs, a mean conduction velocity of 1.1 +/- 0.1 m/s, heat thresholds of less than 1 degrees C above skin temperature, no response to mechanical stimulation, and a resting level of activity in warm skin that was suppressed by cooling. 4. The cumulative number of impulses evoked during each stimulation in the nociceptive afferents increased monotonically as a function of stimulus temperature over the range described by humans as increasingly painful (45-50 degrees C). Nociceptive fibers showed little or no response to stimulus temperatures less than 45 degrees C that elicited in humans sensations primarily of warmth but not pain. In contrast, the cumulative impulse count during stimulation of each warm fiber increased monotonically with stimulus temperature over the range of 39-43 degrees C. However, for stimuli of 41-49 degrees C the cumulative impulse count in warm fibers was nonmonotonic with stimulus temperature. Warm-fiber response to stimuli of 45 degrees C or greater usually consisted of a short burst of impulses followed by cessation of activity. 5. The subjective magnitude of warmth and pain sensations in humans and the cumulative impulse count evoked by each stimulus in warm and nociceptive afferents varied inversely with the number, delivery rate, and intensity of preceding stimulations. 6. The results of these experiments suggest the following: a) that activity in the mechanothermal nociceptive C-fibers signals the occurrence of pain evoked by radiant heat, and that the frequency of discharge in these fibers may encode the intensity of painful stimulation; b) that activity in warm fibers may encode the intensity of warmth at lower stimulus temperatures, but is unlikely to provide a peripheral mechanism for encoding the intensity of painful stimulation at higher stimulus temperatures.

Anodal block of medullated cardiopulmonary vagal afferents in cats.

In anesthetized cats examination was made of the conditions under which the application of DC current to a mixed nerve permits determination of whether a reflex response is mediated by medullated or nonmedullated afferents. The following precautions should be observed. The nerve must be stripped of its sheath and bleeding avoided. The anode should be 6 mm distant from the cathode. The temperature of the mineral oil surrounding the nerve should be 30-32 degrees C to avoid activation of nonmedullated fibers during the block. The major limitation is a time- and frequency-dependent block of nonmedullated fibers which makes the technique suitable only for differentiating between medullated fibers and nonmedullated fibers with low frequency traffic. Observing these criteria, anodal block of the cervical vagus in sino-aortic denervated cats resulted in a mean rise in aortic pressure of 8 Torr; subsequent cold block caused a further mean rise of 30 Torr. Thus 80% of the total increase in aortic pressure could be ascribed to interruption of vagal C-fiber activity.

C-fiber activity in feline tooth pulp afferents

C-fiber activity in feline tooth pulp afferents

Selective activation of C-fibers.

A polarizing current applied transiently to a nerve selectively blocks conduction in the A-fibers, whereas the C-fibers remain unaffected. The block is reversible. Stimulation of A-fibers by the polarizing current is prevented by appropriately adjusting its slope of rise.

Functional organization of hairy skin in response to sensory stimuli

The cross correlation methods previously developed for the analysis of peripheral nerve activity in response to natural stimuli were used to study the functional organization of hairy skin. Histological methods were used to supplement these findings. Measurements of peak velocity, distribution of fiber speeds and temporal dispersion confirmed previous findings that for the myelinated fiber groups, the innervation to the caudal area of skin conducts faster than the innervation to the rostral end. From the physiological and histological data it can be concluded that the skin contains two specific mechanoreceptors. The first is to the hair, is rapid adapting and responds to movement of the hairs. These receptors are innervated by the A, alpha-beta group (high sensitivity) and the A, delta-gamma group (low sensitivity). The second type of receptor is to the skin between the hair shafts and responds to touching the skin; these receptors are not as rapidly adapting and are innervated primarily by the A, delta-gamma group. The C-fiber activity is associated with nonspecific activity in response to various mechanical stimuli. Within each sub-area there is considerable time sharing of myelinated fibers by receptors. Cutaneous sensibility consists of specific mechanoreceptors which are supplied by myelinated fibers and subserve the basic modality of touch (hair and pressure). Nonspecific activity in response to C-fiber activity subserve the sensations of pain and temperature which are not basic modalities but the result of pattern recognition of specific and non-specific activities.

Cutaneous nerve activity in response to temperature changes of the cat's skin

Cutaneous nerve activity was recorded in response to changes in skin temperature. The presence of activity from the number of receptors which theoretically should be present in the area of skin innervated by the cutaneous nerve could be detected by the method of cross-correlation even if from small myelinated or unmyelinated fibers. No specific response in the small myelinated or unmyelinated afferents was detected in response to skin temperature changes in the range of 15–45 C. Activity recorded from the A, alpha-beta and A, delta-gamma groups in response to mechanical stimulation was not altered by skin temperature ranging from 15 to 45 C. With the temperature below this, the activity in both groups was markedly depressed. Above 45 C, there was some suppression of the A, alpha-beta, but more of the A, delta-gamma groups activity. Above 50 C, irreversible damage to the tissue occurred. Unmyelinated fiber activity in response to mechanical stimuli was increased above and below skin temperature deviating from room temperature. Below 7 C, the response was suppressed. Above 50 C, there is a large amount of C-fiber activity which occurs during the rapid change in skin temperature and this adapts out and C-fiber activity in response to mechanical stimuli is suppressed. The data derived from this study would support the spatial-temporal pattern of cutaneous sensibility as expounded by the “Oxford” group.