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R H LaMotte

Publications and source records attributed to R H LaMotte.

At least 19 recordsLinked to original sources
PubMed2006

MCP-1 enhances excitability of nociceptive neurons in chronically compressed dorsal root ganglia.

Previous experimental results from our laboratory demonstrated that monocyte chemoattractant protein-1 (MCP-1) depolarizes or increases the excitability of nociceptive neurons in the intact dorsal root ganglion (DRG) after a chronic compression of the DRG (CCD), an injury that upregulates neuronal expression of both MCP-1 and mRNA for its receptor CCR2. We presently explore the ionic mechanisms underlying the excitatory effects of MCP-1. MCP-1 (100 nM) was applied, after CCD, to acutely dissociated small DRG neurons with nociceptive properties. Under current clamp, the proportion of neurons depolarized was similar to that previously observed for CCD-treated neurons in the intact ganglion, although the magnitude of depolarization was greater. MCP-1 induced a decrease in rheobase by 44 +/- 10% and some cells became spontaneously active at resting potential. Action potential width at a voltage equal to 10% of the peak height was increased from 4.94 +/- 0.23 to 5.90 +/- 0.47 ms. In voltage clamp, MCP-1 induced an inward current in 27 of 50 neurons held at -60 mV, which increased with concentration over the range of 3 to 300 nM (EC(50) = 45 nM). The MCP-1-induced current was not voltage dependent and had an estimated reversal potential of -27 mV. In addition, MCP-1 inhibited a voltage-dependent, noninactivating outward current, presumably a delayed rectifier type K(+) conductance. We conclude that MCP-1 enhances excitability in CCD neurons by, at least, two mechanisms: 1) activation of a nonvoltage-dependent depolarizing current with characteristics similar to a nonselective cation conductance and 2) inhibition of a voltage-dependent outward current.

Action Potentials↗
PubMed2006

Effects of a chronic compression of the dorsal root ganglion on voltage-gated Na+ and K+ currents in cutaneous afferent neurons.

A chronic compression of the dorsal root ganglion (CCD) produces ipsilateral cutaneous hyperalgesia that is associated with an increased excitability of neuronal somata in the compressed ganglion, as evidenced by spontaneous activity and a lower rheobase. We searched for differences in the properties of voltage-gated Na+ and K+ currents between somata of CCD- and control (unoperated) rats. CCD was produced in adult rats by inserting two rods through the intervertebral foramina, one compressing the L4, and the other, the ipsilateral, L5 dorsal root ganglion (DRG). After 5-9 days, DRG somata were dissociated and placed in culture for 16-26 h. Cutaneous neurons of medium size (35-45 microm), Fluorogold-labeled from the hindpaw, were selected for whole cell patch-clamp recording of action potentials and ion currents. In comparison with control neurons, CCD neurons had steady-state activation curves for TTX-sensitive (TTX-S) Na+ currents that were shifted in the hyperpolarizing direction, and CCD neurons had enhanced TTX-resistant (TTX-R) current. CCD neurons also had smaller, fast-inactivating K+ currents (Ka) at voltages from -30 to 50 mV. The reduction in Ka, the hyperpolarizing shift in TTX-S Na+ current activation, and the enhanced TTX-R Na+ current may all contribute to the enhanced neuronal excitability and thus to the pain and hyperalgesia associated with CCD.

Animals↗
PubMed2001

Fine-scale organization of SI (area 3b) in the squirrel monkey revealed with intrinsic optical imaging.

Optical imaging of intrinsic cortical activity was used to study the somatotopic map and the representation of pressure, flutter, and vibration in area 3b of the squirrel monkey (Saimiri sciureus) cortex under pentothal or isoflurane anesthesia. The representation of the fingerpads in primary somatosensory cortex was investigated by stimulating the glabrous skin of distal fingerpads (D1-D5) with Teflon probes (3-mm diam) attached through an armature to force feedback-controlled torque motors. Under pentothal anesthesia, intrinsic signal maps in area 3b obtained in response to stimulation (trapezoidal indentation) of individual fingerpads showed focal activations. These activations (ranging from 0.5 to 1.0 mm) were discrete and exhibited minimal overlap between adjacent fingerpad representations. Consistent with previously published maps, a somatotopic representation of the fingerpads was observed with an orderly medial to lateral progression from the D5 to D1 fingerpads. Under isoflurane anesthesia, general topography was still maintained, but the representation of fingerpads on adjacent fingers had higher degrees of overlap than with pentothal anesthesia. Multi- and single-unit recordings in the activation zones confirmed the somatotopic maps. To examine preferential inputs from slowly adapting type I (SA) and rapidly adapting type I (RA) and type II (PC) mechanoreceptors, we applied stimuli consisting of sinusoidal indentations that produce sensations of pressure (1 Hz), flutter (30 Hz), and vibration (200 Hz). Under pentothal anesthesia, activation patterns to these different stimuli were focal and coincided on the cortex. Under isoflurane, activation zones from pressure, flutter, and vibratory stimuli differed in size and shape and often contained multiple foci, although overall topography was maintained. Subtraction and vector maps revealed cortical areas (approximate 250-microm diam) that were preferentially activated by the sensations of pressure, flutter, and vibration. Multi- and single-unit recordings aided in the interpretation of the imaging maps. In conclusion, the cortical signals observed with intrinsic signal optical imaging delineated a somatotopic organization of area 3b and revealed different topographical cortical activation patterns for pressure, flutter, and vibratory stimuli. These patterns were dependent on anesthesia type. Possible relationships of these anesthesia effects to somatosensory cortical plasticity are discussed.

Anesthesia↗
PubMed2000

Softness discrimination with a tool.

The abilities of humans to discriminate the softness of rubber objects of differing compliance with a hand-held tool (a stylus) was measured under experimental conditions that differed as to how the tool was used and the kind of sensory information available. When the subject actively tapped or pressed the compliant objects, they discriminated softness as well by means of a stylus as they did by contacting the objects directly with the fingerpad. Discrimination with the stylus was unaffected by whether the stylus was controlled by one or two fingers. While tapping or pressing a stylus held in a precision grip, the grip force increased before, reached a maximum at the same time as, and decreased in parallel with the compressional force. This relationship was suggestive of anticipatory motor control based on an internal model of the motor system and the physical properties of the object. Discrimination was significantly better when tapping as opposed to pressing the objects with the stylus. This was hypothesized as due to the presence of tactile cues generated by the rapid increase in force rate as the stylus struck and indented the object during tapping. During tapping, the magnitude and rate of compressional force produced by the stylus against the object were greater, the harder the object. An additional cue, possibly kinesthetic, during pressing and tapping was the magnitude of indentation of the specimen by the stylus that was greater, the softer the object. Subjects could discriminate differences on softness by tactile cues alone in the absence of kinesthetic when compliant objects were tapped at approximately the same velocity by the experimenter against a stylus in contact with the subject's passive fingerpad. Discrimination deteriorated if the softer specimen of a pair was tapped with a slightly greater velocity than the harder and not possible if the specimens were pressed against the stylus without generating tactile cues of mechanical contact. In contrast, discrimination was possible during active pressing and unaffected by variations in velocity during active tapping. It is concluded that during active movements, kinesthetic information and knowledge of central efferent commands provide useful cues that are not present during passive touch. These cues allow the observer to discriminate differences in object compliance not confounded by differences in applied velocity.

Acoustic Stimulation↗
PubMed1999

Mechanical and thermal hyperalgesia and ectopic neuronal discharge after chronic compression of dorsal root ganglia.

Chronic compression of the dorsal root ganglion (CCD) was produced in adult rats by implanting a stainless steel rod unilaterally into the intervertebral foramen, one rod at L(4) and another at L(5). Two additional groups of rats received either a sham surgery or an acute injury consisting of a transient compression of the ganglion. Withdrawal of the hindpaw was used as evidence of a nocifensive response to mechanical and thermal stimulation of the plantar surface. In addition, extracellular electrophysiological recordings of spontaneous discharges were obtained from dorsal root fibers of formerly compressed ganglia using an in vitro nerve-DRG-dorsal root preparation. The mean threshold force of punctate indentation and the mean threshold temperature of heating required to elicit a 50% incidence of foot withdrawal ipsilateral to the CCD were significantly lower than preoperative values throughout the 35 days of postoperative testing. The number of foot withdrawals ipsilateral to the CCD during a 20-min contact with a temperature-controlled floor was significantly increased over preoperative values throughout postoperative testing when the floor was 4 degrees C (hyperalgesia) and, to a lesser extent, when it was 30 degrees C (spontaneous pain). Stroking the foot with a cotton wisp never elicited a reflex withdrawal before surgery but did so in most rats tested ipsilateral to the CCD during the first 2 postoperative weeks. In contrast, the CCD produced no changes in responses to mechanical or thermal stimuli on the contralateral foot. The sham operation and acute injury produced no change in behavior other than slight, mechanical hyperalgesia for approximately 1 day, ipsilateral to the acute injury. Ectopic spontaneous discharges generated within the chronically compressed ganglion and, occurring in the absence of blood-borne chemicals and without an intact sympathetic nervous system, were recorded from neurons with intact, conducting, myelinated or unmyelinated peripheral nerve fibers. The incidence of spontaneously active myelinated fibers was 8.61% for CCD rats versus 0.96% for previously nonsurgical rats. We hypothesize that a chronic compression of the dorsal root ganglion after certain injuries or diseases of the spine may produce, in neurons with intact axons, abnormal ectopic discharges that originate from the ganglion and potentially contribute to low back pain, sciatica, hyperalgesia, and tactile allodynia.

Animals↗
PubMed1999

Enhanced excitability of sensory neurons in rats with cutaneous hyperalgesia produced by chronic compression of the dorsal root ganglion.

Pain and hyperalgesia can occur when the dorsal root ganglion (DRG) and its roots are deformed mechanically in association with injuries or diseases of the spine. To evaluate the electrophysiological changes that contribute to this sensory pathology, intracellular recordings were obtained in vitro from DRGs that had received a chronic mechanical compression [chronic compression of DRG (CCD)]. The compression was produced by inserting L-shaped rods ipsilaterally into the intervertebral foramina, one at L(4) and the other at L(5) in rats 1-14 days before the recording. Control rats received a sham operation. Postoperatively, the threshold force applied by punctate stimulation of the plantar surface of the hind paw decreased significantly on the foot ipsilateral to the CCD (mechanical hyperalgesia) but changed little on the contralateral foot or on either foot for control rats. DRG somata were viewed through a microscope during recording and classified as small, medium, and large according to their diameters. CCD cells in each size category were more excitable than those of comparable size from control rats as judged by the significantly lowered threshold currents and action potential voltage thresholds. Spontaneous activity was recorded in 11% of all the CCD cells tested. The spontaneous activity and/or changes in both the threshold currents and action potential thresholds were observed as early as one day after injury. The association of cutaneous hyperalgesia with changes in the electrophysiological properties of DRG cells suggests a possible role for intrinsic alterations in the membrane properties of compressed DRG cells in the production and persistence of chronic pain after certain spinal injuries or pathologies of the spine.

Animals↗
PubMed1998

Patch clamp recording from the intact dorsal root ganglion.

A method for patch-clamp recording from intact dorsal root ganglion (DRG) cells in rat is described. The L4 and L5 DRGs with sciatic nerve attached were excised from rats (10-15 days old) and placed in a recording chamber after removing the ganglion sheath and dissolving the connective tissue with dilute collagenase. The somata of individual cells were exposed by gentle surface cleaning through a perfusion micropipette. Somata were classified as Abeta, Adelta or C based on the cell size and the shape of the action potential (AP). Under current clamp, axonal conduction velocity (CV) was calculated from the distance between a stimulating electrode and the center of the ganglion divided by the latency of the AP elicited by stimulation of the sciatic nerve. CVs ranged from 0.2-0.8 m/s for C cells, 0.8-2.4 for Adelta and 3.2-5.0 for A/beta cells. AP threshold occurred at a significantly more positive potential in C cells than in Adelta and Abeta cells. Under voltage clamp, sodium currents were recorded from C cells. Both TTX-resistant (TTX-R) and TTX-sensitive (TTX-S currents) were demonstrated in the present study. The results demonstrate the feasibility of patch-clamp recording from intact, identified DRG cells in vitro.

Animals↗
PubMed1998

Raised object on a planar surface stroked across the fingerpad: responses of cutaneous mechanoreceptors to shape and orientation.

The representations of orientation and shape were studied in the responses of cutaneous mechanoreceptors to an isolated, raised object on a planar surface stroked across the fingerpad. The objects were the top portions of a sphere with a 5-mm radius, and two toroids each with a radius of 5 mm along one axis and differing radii of 1 or 3 mm along the orthogonal axis. The velocity and direction of stroking were fixed while the orientation of the object in the horizontal plane was varied. Each object was stroked along a series of laterally shifted, parallel, linear trajectories over the receptive fields of slowly adapting, type I (SA), and rapidly adapting, type I (RA) mechanoreceptive afferents innervating the fingerpad of the monkey. "Spatial event plots" (SEPs) of the occurrence of action potentials, as a function of the location of each object on the receptive field, were interpreted as the responses of a spatially distributed population of fibers. That portion of the plot evoked by the curved object (the SEPc) provided a representation of the shape and orientation of the two-dimensional outline of the object in the horizontal plane in contact with the skin. For both SAs and RAs, the major vector of the SEPc, obtained by a principal components analysis, was linearly related to the physical orientation of the major axis of each toroid. The spatial distribution of discharge rates [spatial rate surface profiles (SRSs), after plotting mean instantaneous frequency versus spatial locus within the SEPc] represented object shape in a third dimension, normal to the skin surface. The shape of the SA SRSs, well fitted by Gaussian equations, better represented object shape than that of the RA SRSs. A cross-sectional profile along the minor axis [spatial rate profile (SRP)] was approximately triangular for SAs. After normalization for differences in peak height, the falling slopes of the SA SRPs increased, and the base widths decreased with curvature of the object's minor axis. These curvature-related differences in slopes and widths were invariant with changes in object orientation. It is hypothesized that circularity in object shape is coded by the constancy of slopes of SA SRPs between peak and base and that the constancy of differences in the widths and falling slopes evoked by different raised objects encodes, respectively, the differences in their sizes and shapes regardless of differences in their orientation on the skin.

Action Potentials↗
PubMed1997

An in vitro study of ectopic discharge generation and adrenergic sensitivity in the intact, nerve-injured rat dorsal root ganglion.

A chronic, loose constriction of the sciatic nerve in rat produces behavioral signs of spontaneous pain and cutaneous hyperalgesia (Bennett and Xie, Pain, 33 (1988) 87-107) as well as an abnormal spontaneous activity and adrenergic sensitivity of certain dorsal root ganglion (DRG) cells with axons in the injured nerve (Kajander et al., Neurosci. Lett., 138 (1992) 225-228; Xie et al., J. Neurophysiol., 73 (1995)1811-1820). The present study investigated whether the spontaneous activity and adrenergic sensitivity were intrinsic properties of injured DRG cells and manifested in vitro, i.e., not dependent on intact blood circulation and an intact, functioning sympathetic nervous system. Two weeks after a loose constriction of the sciatic nerve, the L4 or L5 DRG with its ligated nerve and dorsal root attached was removed from the rat and placed in a chamber. Extracellular recordings were made from teased dorsal root fibers. Spontaneous activity (>0.05 imp/s in 3 min) originating within or close to the DRG was often found in C-, Adelta- and Abeta-fibers from nerve-injured rats, but was rare in fibers with peripheral axons from uninjured nerve. The incidence of various patterns of spontaneous discharge was similar to that previously recorded in vivo. Nineteen of 30 C-fibers, four of five Adelta- and three of seven Abeta-fibers from injured nerve responded to different doses of norepinephrine (NE) applied topically to the DRG. Five of seven C- and one of two Abeta -fibers from injured nerve responded to clonidine, a more selective alpha2 adrenergic agonist. The thresholds ranged from 500 to 10 microM, the lowest dose delivered. None of the fibers from uninjured nerve responded to NE or clonidine (500 microM). Since the experiments were carried out in vitro in the intact DRG, the existence of spontaneous activity in DRG cells in nerve-injured rats was independent of any blood borne chemicals, such as norepinephrine. We hypothesize that abnormal activity and adrenergic sensitivity in injured DRG neurons are due to an intrinsic alteration of the cell body membrane.

Action Potentials↗
PubMed1997

Tensile and compressive responses of nociceptors in rat hairy skin.

Mechanically sensitive nociceptor afferents were studied in a preparation of isolated skin from rat leg. Each neuron was studied while the skin was subjected to tensile and compressive loading. The experiment was designed to create highly uniform states of stress in both tension and compression. Tensile loads were applied by pulling on the edges of the sample. Applied loads were used to determine the tensile stresses. Surface displacements were used to determine tensile strains. Compressive loads were applied by indenting the surface of the skin with flat indenter tips applied under force control. The skin was supported by a flat, hard substrate. Compressive stresses were determined from the applied loads and tip geometry. Compressive strains were determined from skin thickness and tip excursions. All nociceptors were activated by both tensile and compressive loading. There was no interaction between the responses to compressive and tensile stimuli (i.e., the responses were simply additive). Responses of nociceptors were better related to tensile and compressive stresses than to strains. Nociceptors responded better to tensile loading than to compressive loading. Response thresholds were lower and sensitivities were higher for tensile stress than for compressive stress. The response to compression was better related to compressive stress than to other stimulus parameters (i.e., load/circumference or simply load). Indentations of intact skin over a soft substrate such as muscle would be expected to cause widespread activation of nociceptors because of tensile stresses.

Animals↗
PubMed1996

Abnormal spontaneous activity and responses to norepinephrine in dissociated dorsal root ganglion cells after chronic nerve constriction.

As a part of ongoing studies of the cellular mechanisms of sympathetically maintained pain, we investigated the effects of a peripheral nerve injury on the responses of dissociated dorsal root ganglion (DRG) cells to norepinephrine (NE). Whole-cell patch-clamp recordings under current clamp were obtained from L4 and L5 DRG cells from adult rats in acute culture 11-25 days after a loose or tight ligation of the sciatic nerve. Only small to medium-sized cells from normal (uninjured) nerves and from loosely ligated nerves were tested with NE. One of 15 cells obtained-from uninjured nerves responded to NE (500 microM, the highest dose, elicited a small depolarization without action potentials). In contrast, many cells from injured nerves responded to NE with a membrane depolarization, accompanied in some cases by the generation of action potentials. Fifty-two percent responded to 500 microM, while a significantly lower percentage responded to the lower doses of 100 microM (26%) and 10 microM (14%). Cells responsive to NE also responded to capsaicin. Spontaneous activity was observed in 14% and 21% of cells from loosely and tightly ligated nerves, respectively, but none of the cells from uninjured nerves. We conclude that the abnormal electrogenesis and responsiveness to NE in certain nerve-injured primary sensory neurons are due at least in part to changes in the membrane properties of the soma.

Adrenergic alpha-Agonists↗
PubMed1996

Neural encoding of shape: responses of cutaneous mechanoreceptors to a wavy surface stroked across the monkey fingerpad.

1. The role of cutaneous mechanoreceptors in the tactile perception of shape was investigated. Objects whose surfaces were shaped as a pattern of smooth, alternating convex and concave cylindrical surfaces of differing radii of curvature were constructed such that there were no discontinuities in the slope of the surface. These "wavy surfaces" were stroked across the fingerpad of the anesthetized monkey and electrophysiological responses of slowly adapting type I mechanoreceptive afferents (SAs) and rapidly adapting type I mechanoreceptive afferents (RAs) were recorded. 2. For both SAs and RAs, each convexity indenting the skin evoked a burst of impulses and each concavity of the same curvature that followed elicited a pause in response. "Spatial event plots" (SEPs) of the occurrence of action potentials as a function of the location of the object on the receptive field were obtained and interpreted as the responses of a spatially distributed population of fibers. With increasing magnitude of curvature (equivalently, decreasing radius of curvature) of convexity, the mean width of the burst in the SEPs for each fiber type (representing the width of a region of skin containing active fibers) decreased and the mean discharge rate during the burst increased. Over a range of velocities of stroking from 1 to 40 mm/s, the number of RAs activated increased with velocity, whereas SAs were active at all velocities. For both SAs and RAs, the burst rates increased with velocity, whereas the widths of the bursts and pauses remained approximately invariant. Thus the spatial measures of burst or pause width provide a robust representation of the size of a feature on the object surface. 3. For a given velocity of stroking, the spatially distributed pattern of averaged discharge rates (spatial rate profile, SRP) provided a representation of the shape of the wavy surface. The distance between neighboring peaks in the SRP for individual RAs and SAs was approximately the same as the distance between the peaks of the wavy surface. The averaged SRP for a population of SAs provided a better representation of shape than that for RAs. Whereas active regions in the SEP can be isomorphic to the two dimensional form of the stimulus "footprint" in contact with the skin surface, the SRP, which in addition encodes the features of the stimulus in the third dimension normal to the skin surface, is not isomorphic to the stimulus shape. 4. When the sizes as well as the shapes of objects are varied, it is hypothesized that a central processing mechanism extracts the invariant property of shape from the slopes of the rising and falling phases of an SRP that has been normalized for overall differences in discharge rates. These differences would be expected to occur with variations in the parameters of stimulation such as compressional force, stroke trajectory, and stroke velocity. It was shown that a common feature of the mean SRP for SAs evoked by each wavy surface convexity, regardless of its radius, was the constancy of the slope from the base to the peak and from the peak to the base. Thus a possible code for the constant curvature of a cylinder is the constancy of the slopes along the rising and declining phases of the triangular-shaped spatial response profile evoked in the SA population by the cylindrical convexity.

Animals↗
PubMed1995

Tactual discrimination of softness.

1. We investigated the ability of humans to tactually discriminate the softness of objects, using novel elastic objects with deformable and rigid surfaces. For objects with deformable surfaces, we cast transparent rubber specimens with variable compliances. For objects with rigid surfaces ("spring cells") we fabricated telescoping hollow cylinders with the inner cylinder supported by several springs. To measure the human discriminability and to isolate the associated information-processing mechanisms, we performed psychophysical experiments under three conditions: 1) active touch with the normal finger, where both tactile and kinesthetic information was available to the subject: 2) active touch with local cutaneous anesthesia, so that only kinesthetic information was available; and 3) passive touch, where a computer-controlled mechanical stimulator brought down the compliant specimens onto the passive fingerpad of the subject, who therefore had only tactile information. 2. We first characterized the mechanical behavior of the human fingerpad and the test objects by determining the relationship between the depth and force of indentation during constant-velocity indentations by a rigid probe. The fingerpad exhibited a pronounced nonlinear behavior in the indentation depth versus force trace such that compliance, as indicated by the local slope of the trace, decreased with increases in indentation depth. The traces for all the rubber specimens were approximately linear, indicating a constant but distinct value of compliance for each specimen. The fingerpad was more compliant than each of the rubber specimens. 3. All the human subjects showed excellent softness discriminability in ranking the rubber specimens by active touch, and the subjective perception of softness correlated one-to-one with the objectively measured compliance. The ability of subjects to discriminate the compliance of spring cells was consistently poorer compared with that of the rubber specimens. 4. For pairwise discrimination of a selected set of rubber specimens, kinesthetic information alone was insufficient. However, tactile information alone was sufficient, even when the velocities and forces of specimen application were randomized. In contrast, for discriminating pairs of spring cells, tactile information alone was insufficient, and both tactile and kinesthetic information were found to be necessary. 5. The differences in the sufficiency of tactile information for the discrimination of the two types of objects can be explained by the mechanics of contact of the fingerpad and its effect on tactile information. For objects with deformable surfaces, the spatial pressure distribution within the contact region depends on both the force applied and the specimen compliance.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Local↗
PubMed1995

Functional changes in dorsal root ganglion cells after chronic nerve constriction in the rat.

1. We studied the effects of a chronic nerve constriction on the evoked responses in dorsal root fibers in the rat to norepinephrine and to thermal stimuli applied either to the dorsal root ganglion (DRG) or the site of nerve injury. We recorded a total of 59 C fibers, 15 A delta-fibers, and 46 A beta-fibers from the L5 dorsal root of the rats 11-52 days after a loose ligation of the ipsilateral sciatic nerve. Most fibers were identified by the presence of spontaneous activity (SA) that originated partially at and/or proximal to the injury site. In addition, we recorded 20 C fibers, 1 A delta-fiber, and 28 A beta-fibers from the dorsal roots of normal, uninjured neurons. 2. In nerve-injured rats, the SA of some C fibers was generally increased by cooling and decreased by heating either site. In contrast, the SA of most A beta-fibers was increased by heating either the injury site or the DRG. Cooling the DRG decreased SA in A beta-fibers, whereas cooling the injury site typically had no effect. Excitatory responses were not evoked in any fiber group when the same thermal stimuli were applied to the nerve or DRG tested in normal, uninjured rats. 3. Norepinephrine (< 0.5 mM) applied either to the injury site or the DRG increased the SA of most C fibers and A delta-fibers but only a minority of A beta-fibers in previously injured nerves. The threshold concentration for excitation of the DRG somata of C fibers was 0.01 mM. No effects were found for fibers in uninjured nerves. 4. The effect of norepinephrine was blocked by a pretreatment with yohimbine, an alpha 2-blocker, but not with prazosin, an alpha 1-blocker. 5. Stimulation of the sympathetic trunk (L2-L3) excited most C fibers and a minority of A beta-fibers. In contrast, the SA of a minority of C fibers and A beta-fibers was depressed during sympathetic stimulation. 6. After a chronic nerve constriction the DRG becomes a source of abnormal activity modulated by sympathetically released norepinephrine acting on alpha 2 receptors in DRG somata. This neuropathic activity may contribute to cutaneous pain and hyperalgesia.

Animals↗
PubMed1994

Cutaneous neural codes for shape.

In the pursuit of peripheral neural representations of shape for the sense of touch, a series of two- and three-dimensional objects were stroked across the fingerpad of the anesthetized monkey and responses evoked in cutaneous mechanoreceptive primary afferent nerve fibers recorded. Responses of slowly adapting fibers (SAs) and rapidly adapting fibers (RAs) were recorded to the stroking of a cylinder, a sphere, several ellipsoids, and a pattern of alternating convex and concave cylindrical bars. The compressional force was maintained constant during a stroke, and the stroke velocities as well as orientations of the objects and stroke trajectories were varied between separate sets of trials. The major geometrical properties of the shapes were well represented in the spatiotemporal responses of the afferent fiber populations, particularly those of the SAs. Intensive parameters of shapes, such as the magnitude of change in skin curvature produced as a result of contact with the object surface, were encoded in the discharge rates of SAs and RAs, but this neural code was also influenced by changes in stroke velocity. Spatial parameters of shapes such as the extent of contact and the changes in contour that characterize a shape as belonging to a particular category (such as a sphere as opposed to a cylinder) are encoded in the spatially distributed discharge rates of the SA population. This spatial response profile provides a neural code that is probably invariant with moderate changes in the way the object comes in contact with the skin, such as the contact force or the orientation of the object.

Animals↗
PubMed1993

Responses of cutaneous mechanoreceptors to the shape of objects applied to the primate fingerpad.

The present study is one of a series whose aim is to determine how shape is represented in the activity of cutaneous mechanoreceptive peripheral nerve fibers. Cylindrical bars of varying curvature were indented into the receptive fields of slowly and rapidly adapting mechanoreceptive afferent nerve fibers (SAs and RAs respectively) supplying the fingerpad of the anesthetized monkey. The evoked pattern of nerve impulses in single nerve fibers was recorded electrophysiologically. SAs responded to differences in the curvature, both during the ramp and static phases of the skin indentation. RAs responded only during the ramp phase of the indentation, but their responses were not modulated by differences in curvature. Evidence from the present and previous studies is used to support the following hypotheses: Spatial parameters (such as the 'shapes' or 'widths' of responses rates plotted over the skin surface) of primarily SAs in a spatially distributed population of fibers govern the recognition of the overall object shape as a distribution of curvatures; Intensive parameters (such as the magnitude of discharge rates) of only SAs under static indentations, and both SAs and RAs under stroking, are important for discriminations of small differences in curvatures of objects belonging to the same category of shape.

Afferent Pathways↗
PubMed1993

Effect of protons on the inward current evoked by capsaicin in isolated dorsal root ganglion cells.

Capsaicin excites a subset of dorsal root ganglion (DRG) neurons by inducing an inward current. We have examined this inward current in response to high concentrations of protons in the external medium. The experiments were done in freshly dissociated DRG cells under whole-cell voltage-clamp conditions. The amplitude of the current evoked by capsaicin (200-300 nM) was increased with increasing concentrations of protons (pH 6.9-6.3). Increasing the acidification of the external medium from a physiological pH of 7.3 to 6.3 enhanced 7-fold the current induced by capsaicin (300 nM). Cells unresponsive to capsaicin in a physiological pH were also unresponsive to capsaicin in an acidic solution. There was a progressive decrease in the amplitude of the capsaicin-evoked current when the drug was repeatedly applied either at a physiological pH or an acidic pH of 6.3. Exposure of the cell to acidic solutions of capsaicin did not subsequently increase an evoked inward current when capsaicin was applied at a physiological pH nor did it lead to an inward current evoked by proton ions where there had been none. Our results suggest that increased proton concentrations in the extracellular medium could play an important modulatory role in the function of chemosensitive sensory neurons.

Animals↗