PubMed Health⌕ Search

Biomedical subjects

R P Tuckett

Publications and source records attributed to R P Tuckett.

At least 19 recordsLinked to original sources

C-fiber modulation of the rat type I slowly adapting mechanoreceptor.

Effects of C-fiber activation on type I slowly adapting mechanoreceptor responses were investigated in a rat in vitro nerve-skin preparation using controlled mechanical stimuli. Two changes in behavior were evoked by antidromic C-fiber stimulation: (1). The type I response to mechanical stimuli was modulated in a graded fashion by antidromic C-fiber activation. The average decrease in mechanoresponse from baseline discharge was 53% at 20-Hz, 51% at 5-Hz, and 30% at 1-Hz stimulation rate. The type I response recovered to baseline levels following termination of antidromic electrical stimulation. (2). Antidromic C-fiber activation generated a spontaneous ongoing activity in many skin units; this was independent of mechanical stimulation and outlasted electrical stimulation. The fact that neither antidromic electrical stimulation of the crushed nerve trunk nor selective A-fiber activation elicited these reactions suggests that they were mediated via action potentials of slowly conducting (C-fiber) axons. Immunohistochemical staining revealed both substance P- and calcitonin gene-related peptide-like immunoreactivity in small unmyelinated nerve fibers entering the touch dome. These results support the concepts that (1). the type I slowly adapting mechanoreceptor in rat receives input from nociceptive terminals within the touch dome. (2). The function of type I slowly adapting mechanoreceptors is modulated by axon reflex activation of nociceptor terminals, which may play a role in altering the type I response during states of mechanical allodynia and have paracrine and autocrine influences on maintenance of touch dome structure.

Action Potentials↗

Characterization of a behavioral model for peripherally evoked itch suggests platelet-activating factor as a potent pruritogen.

The studies described herein characterize animal behavioral models for conjunctival and cutaneous itch. Histamine was used as the reference stimulus for model development because it is firmly established as a pruritogen in both conjunctiva and skin. Itching evokes the desire to scratch in human subjects, so hind limb scratching at the afflicted area was used to identify pruritogenic stimuli. Under optimized environmental conditions, hind limb scratching behavior yielded substantial and highly reproducible responses. The conjunctival itch-scratch response was delineated from pain and foreign body sensations by using appropriate stimuli. Examination of a large and diverse variety of autocoids revealed that only histamine, platelet-activating factor (PAF) and arachidonic acid and its cyclooxygenase metabolite prostaglandin E2 possessed meaningful pruritogenic activity. PAF-induced ocular pruritus did not involve histamine release, according to studies with appropriate antagonists. Thus PAF-induced ocular pruritus was unaffected by the histamine H1-receptor antagonist pyrilamine but was substantially attenuated by the PAF antagonists WEB 2086 and CV-6209 and was virtually abolished by E-6123. Similar itch-scratch behaviors were quantified in hairless guinea pig skin following the application of cowhage or the iontophoretic administration of histamine and PAF. Findings from these newly developed itching models suggest that PAF could be an important mediator of the pruritic sensation by activating a population of nerve endings responsible for encoding the itch sensation.

Animals↗

Response of sensory units with unmyelinated fibres to mechanical, thermal and chemical stimulation of the cat's cornea.

1. In the cat anaesthetized with sodium pentobarbitone, electrical activity was recorded from single unmyelinated sensory fibres innervating the cornea. 2. Based on their response to mechanical (calibrated aesthesiometer), chemical (10 mM acetic acid or 616 mM NaCl) and thermal (cooling from 35 to 5 degrees C; heating to 51 degrees C) stimuli, corneal unmyelinated fibres were classified as polymodal (71%) or 'cold' nociceptors (29%). 3. Polymodal units responded to mechanical indentation of the cornea and developed fatigue after repeated stimulation. They were excited by temperatures over 37 degrees C and exhibited sensitization to repeated heating. 4. Corneal polymodal units were also activated by topical application of 10 mM acetic acid and hypertonic NaCl (616 mM). Capsaicin (0.33 mM) elicited a discharge of impulses that was followed by inactivation to mechanical, chemical and thermal stimuli. 5. 'Cold' nociceptors had small receptive fields, preferentially located at the periphery of the cornea. They were excited by small temperature decreases of the corneal surface in a range between 30 and 8 degrees C, but were not responsive to noxious heat. 6. 'Cold' nociceptors encoded temperature changes between 35 and 23 degrees C. The discharge was proportional to the velocity of the temperature drop; sustained temperatures were not signalled by changes in static frequency values. 'Cold' nociceptive fibres responded to hypertonic NaCl (616 mM) and weakly to 10 mM acetic acid. Capsaicin (0.33 mM) first excited and then inactivated 'cold' nociceptors. 7. Thermoreceptive fibres were found in the episclera. They fired in bursts and responded to small temperature decreases, but were insensitive to irritant chemical and capsaicin.

Acetates↗

Serotonin-like immunoreactivity in Merkel cells and their afferent neurons in touch domes from the hairy skin of rats.

Immunoreactivity to serotonin was observed in Merkel cells as well as the afferent type I nerves terminating upon them in touch domes excised from the belly skin of rats. Type I nerves were strongly immunoreactive and could be traced through the dermis of the domal papilla. Merkel cell immunoreactivity was sometimes seen in the entire cell, but was often localized in the Merkel cell cytoplasm adjacent to nerve terminals and may have been in the terminals themselves. Domes were fixed by immersion in 4% paraformaldehyde-lysine-sodium-m-periodate (PLP) fixative at 4 degrees C for 2.5-3 hours and cryoprotected in 30% sucrose overnight. Sections were processed with the avidin-biotin complex peroxidase (ABC), peroxidase-antiperoxidase (PAP), and indirect immunofluorescence techniques with rabbit antiserum generated against serotonin.

Afferent Pathways↗

Tactile function in skin-equivalent grafts.

Cultured grafts are excellent wound covers; however, their somatosensory capabilities are unknown. This is a preliminary report of a study which determined whether grafts of cultured skin become innervated and also examined whether seeding grafts with target tissue improved nerve growth or functional recovery. Autologous skin for grafting was generated from adult rat biopsy tissue. Dissociated keratinocytes were seeded on top of fibroblast-contracted collagen gels (skin-equivalents). Some animals received grafts composed entirely of skin-equivalents. Others had grafts with 2-mm punch biopsies (normal skin or touch domes) inserted into them. Prior to sacrifice, whole nerve recordings of the cutaneous nerves supplying the grafts were made following tactile mechanical stimulation of the graft surfaces. Tissue was processed for light and electron microscopy as well as silver stained. Nerve fibers were present in the dermis (generated from the fibroblast contracted collagen gels) of all animals and often extended to the epidermis. Light brushing of the cultured areas of the grafts produced little or no activity in the cutaneous nerves; however, afferent impulses were generated after rubbing the skin with a glass rod or pinching it with fine forceps. The implanted regions within the skin-equivalents varied from this pattern. Lightly brushing their surface resulted in vigorous activity in the nerves. Elements in the skin therefore seemed to enhance nerve regeneration and function. However, the quality of the engraftment was also important. Implanted regions of grafts experiencing poor "takes" had compromised innervation.

Animals↗

Functional innervation of cultured skin grafts.

The aims of the present study were to determine 1) if grafts of cultured skin become innervated; and 2) whether tactile function of these grafts could be improved by implanting target tissue into them. Autologous skin equivalents were generated in vitro (30 d) for individual adult Sprague-Dawley rats. Some animals received pure skin equivalent grafts; others had target tissue consisting of 2-mm punch biopsies (normal skin or touch domes) inserted into their skin equivalents at the time of grafting. After 83 d, physiologic recordings were obtained from afferent nerves innervating the grafts. Tissue was processed for histology at various intervals. Silver staining of the tissues demonstrated many isolated nerve fibers in the dermis of cultured areas of skin as well as in implant zones. When grafts were rubbed with a glass rod or pinched with watchmaker forceps, impulses were evoked in nerves innervating both implant and cultured regions. In contrast, the afferent response to gently stroking grafts with a camel hair brush was severely reduced in cultured areas but was vigorous in implanted skin. Neuronal activity characteristic of type I neurons innervating touch domes was only found in cutaneous nerves innervating implants originally possessing domal tissue. Furthermore, grafts with good takes had better return of sensory function than grafts undergoing episodes of crusting. These results suggest that structural components or trophic factors present in implants enhanced the return of neural function related to the sensory modality of light touch; and this was also affected by the engraftment quality.

Action Potentials↗

Response of cat ventrolateral spinal axons to an itch-producing stimulus (cowhage).

A comparison was made between different categories of mechanically sensitive, ventrolateral spinal axons to assess their sensitivity to the itch-producing substance cowhage. Of 52 wide-dynamic-range (WDR) units, 17 had contralateral, 22 had ipsilateral, and 13 had bilateral receptive fields. Of the 5 low-threshold units, 1 had an ipsilateral receptive field and the remainder were bilateral. Among the high-threshold units, 10 were contralateral, 6 ipsilateral, and 5 bilateral. Although there was no evidence of cowhage sensitivity in either low- or high-threshold spinal axons, neurons with WDR properties were reactive to cowhage. WDR neurons were subclassified on the basis of their resting discharge pattern as having intermittent, continuous, or no resting discharge. WDR units with an intermittent pattern of resting discharge demonstrated a significant sensitivity to active cowhage and hence might be regarded as pruritogen-responsive spinal axons. Inactive cowhage was used as a control stimulus. In some WDR units with large receptive fields, there were observations suggesting convergence of chemoreceptive and mechanoreceptive inputs, which produced inhibitory as well as excitatory effects.

Afferent Pathways↗

Response to an itch-producing substance in cat. I. Cutaneous receptor populations with myelinated axons.

The purpose of this study was to determine which myelinated cutaneous receptor populations in cat are responsive to a stimulus (cowhage) that produces unambiguous pruritus in human subjects. Initial experiments using electrocutaneous stimuli demonstrated that fibers conducting as slowly as 1.5 m/s could be recorded from small fascicles of cutaneous nerves. Multiunit recordings from fascicles and nerve filaments revealed small, but significant changes in nerve firing following application of cowhage. A sample of all known myelinated receptor populations showed that each gave a response that was less than its response to adequate intensities of mechanical stimulation (n = 118). It was concluded that the slight changes in multunit discharge induced by cowhage could be accounted for by changes in mechanoreceptor behavior and hence there was no evidence to support the possibility that an unknown population of myelinated sensory fibers exists that signals pruritus. The possibility that itch is signaled by coactivation of myelinated mechanoreceptive and C-polymodal nociceptive neurons was discussed.

Animals↗

Response to an itch-producing substance in cat. II. Cutaneous receptor populations with unmyelinated axons.

Within the sampled population of cutaneous unmyelinated afferent neurons (n = 94), only the C-polymodal nociceptor population was reactive to the pruritogen cowhage. Of 62 C-polymodal neurons tested, 11 were unresponsive to cowhage. No C-polymodal neurons were more responsive to inactive, than to active, cowhage (n = 17) and all were responsive to mechanical (n = 62) stimuli and noxious heat (n = 24). The range of conduction velocities obtained by single-unit recording techniques was similar to that found by signal averaging the activity from larger strands of nerve. Hence, it is concluded that our recording technique was capable of recording from the smallest afferent fibers in a cutaneous nerve and it was unlikely that we would have missed finding a slowly conducting, pruritus-signaling neuron due to sampling bias. A search of slowly conducting afferents (n = 314) using electrocutaneous stimulation gave no evidence to suggest the existence of an unknown population of unmyelinated fibers that might signal pruritus. A number of alternative mechanisms by which the sensation of itch might be encoded were discussed, the most favored being the activation of a subset of the C-polymodal nociceptive population.

Animals↗

Rapid displacements of the skin lack clear positional information.

Rapid skin indentations can produce strong tap-like sensations that contain little information about skin indentation depth. Although slower stimuli produce weaker sensations, subjects can more accurately identify how the position of the skin surface changes with respect to the deeper tissues. This dissociation between intensity and depth information suggests that intensity and depth are served by different neural circuits.

Humans↗

The neural signal for the intensity of a tactile stimulus.

The effect of indenting the skin at different rates on the perceived intensity of the stimulus was studied by indenting the skin of the fingertip with two triangular waveforms, given as a pair. The subjects were asked to judge which member of the pair was more intense. Perceived intensity was found to increase both with the depth and the speed of the indentation. In contrast, changes in the rate of skin indentation had little influence on perceived skin indentation depth. This suggests that intensity and depth are different attributes of tactile sensibility. Since the skin is viscous, a rapid indentation is more forceful than a slow indentation of the same depth, raising the possibility that perceived intensity is related to stimulus force. Even though intensity judgments were more closely correlated with the force of a stimulus than with the indentation it produced, a rapidly increasing force was felt as more intense than one that increased more slowly but attained the same final magnitude. When mechanoreceptors in the palmar aspect of the monkey's hand were excited with triangular stimuli like those used in the psychophysical studies, their discharge frequency increased with the rate of skin indentation. However, the receptors were distinctly more rate sensitive than the human judgments of stimulus intensity, suggesting that impulse summation in the central nervous system summates (integrates in the mathematical sense) the receptor input so as to enhance, relatively, the perceived intensity of the slower stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The neural signal for skin indentation depth. II. Steady indentations.

The glabrous skin of the monkey's hand was stimulated with a waveform that indented the skin at a rate of 0.4 mm/sec, held the skin steadily or nearly steadily indented for 12 sec or longer, and then retracted back to the starting position. Recordings were made of activity in single afferent fibers in response to these stimuli. The average discharge frequency of 21 slowly adapting mechanoreceptors declined 38% during the first 12 sec of a steady indentation when the amplitude of the displacement was 0.65 mm and 36% when the displacement was 1.3 mm. When the plateau was not steady but the indentation depth gradually decreased by 15% during the 12-sec plateau period, the average decline was 47% for the 0.65-mm indentation and 46% for the 1.3-mm stimulus. When the indentation depth gradually increased by 15% during the 12-sec plateau, the discharge declined an average of 26% during the 0.65-mm indentation and 22% during the 1.3-mm displacement. To determine the effect of receptor adaptation on the perception of skin indentation depth, 13 human subjects had the skin of their fingertips indented 1 mm with similar trapezoidal waveform and were asked whether the indentation depth increased or decreased during the plateau portion of the stimulus. Ten of the 13 subjects thought that the indentation depth was increasing when the plateau was steady. The method of limits was then used to determine how much the stimulus had to change for the subject to feel the depth during the plateau as unchanging; i.e., a "perceptual zero."(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Boring's formulation: a scheme for identifying functional neuron groups in a sensory system.

In 1935 Edwin Boring proposed that each attribute of sensation reflects the activity of a different neural circuit. If this idea is valid, it could facilitate both psychophysical and neurophysiological research on sensory systems. We think it likely that Boring's formulation is correct for three reasons: 1) Different sensory attributes reflect conscious information about different parameters of a stimulus. To be measured by any device, each of these parameters must be individually computed. Different neural circuits would appear to be necessary for the nervous system to carry out these different computations. 2) Perceived information about different sensory attributes can be made to diverge by appropriate manipulations of the stimuli. If there is a rigorous relationship between conscious sensory experience and neural activity, such a divergence implies that different sensory attributes are served by different neural circuits. 3) Accurate information about a sensory attribute requires that a human observer's attention be focused on that attribute. Changes in direction of attention are thought to involve a process of switching from one neural circuit to another, and provide another way to cause perceived information about different sensory attributes to diverge.

Fingers↗

The neural signal for skin indentation depth. I. Changing indentations.

Psychophysical tests on human subjects showed that judgments of skin indentation depth made when the fingertip was indented at rates from 0.2 to 16 mm/sec were quite insensitive to changes in indentation velocity. Similar results were obtained on the forearm at indentation velocities of 0.4 to 16 mm/sec. Recordings were made from mechanoreceptors in the monkey's hand that were able to respond over the same range of velocities and at comparable depths to determine how skin indentation depth might be signaled (coded) at the receptor level and to examine the rate sensitivity of the possible depth codes. It was found that most of the receptors with foci under the stimulator were recruited relatively early during an indentation, especially at velocities of 1.6 mm/sec and higher, making it improbable that the full range of indentation depths is signaled by the "subsurface" recruitment of different receptors at different indentation depths. A subsurface recruitment code involving subcutaneous receptors is not likely since subjects could feel virtually none of the stimuli after skin anesthesia. Progressive recruitment with depth of receptors whose foci lie further and further away from the stimulator ("lateral" recruitment) was considered an unlikely depth code because changing the area of the stimulator had little effect on its perceived depth. Also, it was shown that subjects could sense the curvature of the indentation (the profile of the depth at right angles to the skin surface), which requires information about the depth of individual patches of skin beneath the stimulator. There is no obvious way that a lateral recruitment code can provide this information. Thus it is probable that the discharge rate of some or all of the receptors excited by the indentation is involved in indicating its depth. Both impulse frequency and receptor recruitment at any given depth increased as the velocity of the indentation increased. The demonstrated reliability of information about skin indentation depth in humans indicates that the central neural circuitry responsible for judgments of skin indentation depth is able to compensate for the rate-sensitive receptor signals.

Adult↗

Innervation patterns of cutaneous hair receptors in cat.

Cat hair receptors were studied to determine whether they could be distinguished by the following receptive field characteristics: thickness of innervated guard hairs, distance between innervated follicles and receptive field size. Initially the receptors were classified as G1, GI, G2 or D on the basis of their velocity requirements for excitation, their degree of linear directionality, their vibrational sensitivity, and whether they were activated by movement of down hairs. It was found that the thickest guard hairs on the posterior aspect of a cat's hindleg were usually 4-5 times thicker than the thinnest guard hairs from the same area and that G1, GI and G2 neurons innervated the full range of guard hair thicknesses available. Although there was a tendency for thicker guard hairs to be more heavily innervated, none of the neurons studied innervated thick guard hairs exclusively. While movement of the down hair and most guard hairs within D-mechanoreceptive fields easily evoked activity, a few guard hairs were regularly found for which mechanical displacement did not elicit a discharge even though they were well within the receptive field. Receptive field sizes and nearest neighbor distances between innervated follicles were smaller for D than for G1, GI and G2 receptors and greater for G1 than GI and G2 receptors.

Animals↗

Itch evoked by electrical stimulation of the skin.

Psychophysical experiments were done to test the possibility that a single receptor population signals both itch and pain by generating different patterns of activity for each type of stimulus. Electrical stimulation of hairy skin evoked pruritus in 92% of the subjects tested, and for the majority the pruritus elicited by electrical stimulation felt the same as that provoked by cowhage. The intensity of pruritus increased with the frequency of stimulation with no change in the quality of the sensation from itch to pain. Electrical stimulation of human skin with response patterns obtained from individual cat polymodal nociceptive neurons to pain- and itch-producing stimuli caused no differences in the quality of the evoked pruritic sensations. These results do not support the idea that the same population of primary sensory neurons can produce both itch and pain by changing their pattern of discharge.

Animals↗