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Biomedical subjects

E R Perl

Publications and source records attributed to E R Perl.

At least 55 records · Page 3Linked to original sources
PubMed1983

Neurons in ventrobasal region of cat thalamus selectively responsive to noxious mechanical stimulation.

1. A survey was made of neurons located in the ventral posterior lateral nucleus of the cat thalamus and its immediate vicinity for elements with specifically nociceptive properties. 2. Pipette microelectrodes filled with a dye solution were used to obtain extracellular recordings of unitary activity in 34 animals anesthetized with chloralose. 3. The great majority of the over 1,000 different single units responding to sciatic nerve stimulation noted in this series of experiments could also be excited by innocuous mechanical stimulation of skin or subcutaneous tissues. An infrequent but consistently noted group of units excited by A-alpha beta delta sciatic nerve volleys did not respond to innocuous mechanical manipulation or A-alpha beta sciatic nerve volleys; they were excited only by either noxious levels of mechanical stimulation or when volleys included the activity of more slowly conducting myelinated fibers. The latencies of such "high-threshold" units to sciatic volleys were longer than those of the other units. 4. Histologically identified recording sites marked by dye were recovered for 17 high-threshold units. Twelve of the 17 could be excited by noxious manipulations of restricted parts of the contralateral hindlimb. Nine of the 12 had cutaneous receptive fields, whereas 3 responded only to stimulation of subcutaneous tissues. None of the 17 high-threshold units evidenced additional discharges that could be correlated with the C-fiber component of sciatic nerve volleys. 5. The high-threshold units typically exhibited a low level of irregular background activity, which increased on repeated noxious stimulation of the peripheral receptive fields. Tactile units of the same or adjacent penetrations usually had a much greater degree of ongoing activity, often marked by bursts at a relatively high frequency. 6. The recording sites for the 17 high-threshold neurons were located dorsal and ventrolateral to the core of the ventrobasal nuclei and were not found in the midst of the low-threshold, cutaneous, mechanoreceptive population. During vertical stereotaxic penetrations, high-threshold units were noted dorsal or ventral to the location of ventrobasal tactile units in a pattern consistent with the core's somatotopic arrangement. 7. These results support the concept that the cat ventrolateral thalamus receives a small but distinct selectively nociceptive projection. The nociceptive neurons appear to be located in a shell that surrounds the main tactile projection to the ventral posterior lateral nucleus and that retains at least part of the topographic arrangement characteristic of the tactile core. Presumably, this projection is part of an organization identifying and localizing noxious stimulation.

Animals↗
PubMed1982

Synaptic complexes formed by functionally defined primary afferent units with fine myelinated fibers.

The individual fine myelinated fibers of cutaneous mechanical nociceptors and "D-hair" receptors were identified by electrophysiological recording with micropipette electrodes in cats and monkeys. Their intraspinal terminations were labeled by iontophoresing horseradish peroxidase intracellularly and subsequent diaminobenzidine histochemistry. These terminations were examined with light and electron microscopy to determine the nature and organization of their synaptic contacts. Myelinated fibers of the mechanical nociceptors became unmyelinated before exhibiting many enlargements that made multiple synaptic contacts in the marginal zone (lamina I) and lamina V. Pre- or postsynaptic contacts were found only on enlargements. In the marginal zone of the cat, enlargements made simple axodendritic contacts or were scalloped, central terminals in glomeruli. In glomeruli, myelinated mechanical nociceptor enlargements were presynaptic to several dendritic appendages and postsynaptic to two different types of profiles. One type was interpreted as a presynaptic axon terminal, the other as a presynaptic, vesicle-containing, dendritic appendage. In lamina V of the cat the nociceptor synaptic complexes were similar, but simpler, and only axonal profiles were found to be presynaptic to them. In the monkey marginal zone and deep nucleus proprius, myelinated nociceptor terminations formed the central element of glomeruli, which consisted of postsynaptic dendritic appendages and presynaptic axon terminals. D-hair axons terminated in large numbers of enlargements in the nucleus proprius (laminae III and IV) and inner substantia gelatinosa (lamina IIi). Their large rounded enlargements formed the central terminals in glomeruli and were presynaptic to both ordinary and vesicle-containing dendritic appendages; the presynaptic dendritic profiles also often contacted each other. Profiles interpreted as axonal in origin were the only terminals presynaptic to the primary ending within the D-hair glomeruli. The results suggest that transfer of primary afferent information occurs only at enlargements of the primary fiber and that each primary fiber enters into more than one kind of synaptic arrangement. They also point out that synaptic glomeruli are common to functionally different types of primary afferent fibers and that the internal organization of glomeruli varies with the kind of primary fiber and the locus of the complex.

Afferent Pathways↗
PubMed1981

Fine structure of myelinated mechanical nociceptor endings in cat hairy skin.

High-threshold mechanoreceptors (mechanical nociceptors) with myelinated axons were electrophysiologically identified in hairy skin of the cat as described by Burgess and Perl ('67). Such elements possess receptive fields consisting of a number of punctate areas from which maximal firing can be elicited by intense (skin-damaging) mechanical stimuli. The spots of the receptive field are separated from each other by unresponsive regions, i.e., by skin areas from which responses cannot be evoked by stimuli effective at the spots. Fine steel pins were inserted to bracket closely a number of the spotlike responsive areas for each of several units. After aldehyde perfusion of the animal, osmification of the tissue and embedding in plastic, the marked skin zones were examined in semithin and ultrathin sections at the light and electron microscopic level. Near each delineated area, a thinly myelinated axon was found that could be traced to the papillary layer where it loses its myelin sheath. Unmyelinated axons accompanied by thin Schwann cell processes were then traced and found to penetrate the epidermal basal lamina in one of the papillae. At the epidermal penetration site, the axons contained both clear round, and large, dense core vesicles; at this level, the surrounding Schwann cell cytoplasm exhibited numerous pinocytotic vesicles. The zone of penetration may constitute the receptive apparatus. Some of these axons have been traced within the basal epidermal layer where they become surrounded by keratinocytes, lose their Schwann sheath, and apparently terminate. This overall morphological pattern was consistently present in the demarked areas of focal responsiveness, and was rare in the surrounding skin; this and its difference from other cutaneous neural endings suggest that the intraepidermal axon-Schwann cel complex constitutes the receptive structure for myelinated mechanical nociceptors. It is suggested that such complexes are the sense organs responsible for initiating the sensation of pricking pain produced by localized mechanical injury of the skin.

Afferent Pathways↗
PubMed1981

Sensory experiences in man evoked by intraneural electrical stimulation of intact cutaneous afferent fibers.

The response of slowly conducting myelinated and unmyelinated afferent units to natural types of cutaneous stimuli was recorded extracellularly with tungsten microelectrodes from intact human skin nerves. Seven fibers had characteristics of C-polymodal units (conduction velocity: 0.75-1.2 m/s) and two fit descriptions of myelinated high- threshold mechanoreceptors (conduction velocity of one: 19 m/s). Attempts were made to evoke a sensation in a subject by stimulating the impaled fascicles directly with electrical pulses of controlled amplitude, duration and frequency so as to try to correlate responsive properties of the sensory units and sensory experience. The subjective sensations evoked by natural stimuli to the skin surface were used as criteria for comparison.

Afferent Pathways↗
PubMed1979

Reexamination of the dorsal root projection to the spinal dorsal horn including observations on the differential termination of coarse and fine fibers.

Primary afferent fibers in the lumbar, sacral, and caudal spinal segments of several mammals (rat, cat, monkey) were stained by applying horseradish peroxidase to the proximal part of cut dorsal rootlets and reacting the tissue histochemically after several hours of survival. The stained fibers' pattern of termination in the dorsal horn was similar in all three species, with many bouton-like enlargements in the ipsilateral marginal zone, substantia gelatinosa, and nucleus proprius, as well as a few projections at each level to the dorsal commissure and contralaterally to the ventral border of the nucleus proprius. Partial lesions of dorsal rootlets in monkey revealed that the thin fibers comprising the lateral division end principally in the marginal zone and substantial gelatinosa, while the thick fibers of the medial division terminate in the nucleus proprius and deeper regions, contributing little to the substantia gelatinosa and marginal zone. On the basis of the termination patterns observed for whole and partly sectioned rootlets, the superficial dorsal horn can be divided into at least four regions. (1) The marginal zone (lamina I of cat) appears to receive terminations from intermediate (smaller myelinated) fibers; (2) the outer substantia gelatinosa (outer lamina II) receives many terminations from the very finest afferent fibers; (3) the inner substantia gelatinosa (inner lamina II) receives endings from some of the finest fibers and also from intermediate (smaller myelinated) fibers; and (4) the superficial part of the nucleus proprius (lamina III) receives endings from intermediate and large diameter dorsal root fibers.

Animals↗
PubMed1979

Spinal termination of functionally identified primary afferent neurons with slowly conducting myelinated fibers.

Single primary afferent myelinated fibers from cutaneous receptors of cat and monkey were functionally identified by recording from the spinal cord with micropipettes filled with horseradish peroxidase (HRP). Relatively slowly conducting fibers (less than 40 m/sec) from high threshold mechanoreceptors (mechanical nociceptors) and two types of low threshold mechanoreceptor (D-hair and field) were selected for staining. Iontophoresis of the HRP and subsequent histochemical reaction stained the axons recorded from and their collaterals, including terminations, for several millimeters. The termination patterns in the two species proved essentially identical. Ipsilaterally, the mechanical nociceptor fibers terminated principally in the dorsal horn's marginal zone and in the ventral parts of the nucleus proprius (lamina V in the cat). Some of these nociceptors also had terminals in the midline just dorsal to the central canal, contralaterally in the marginal zone, and at the base of the opposite nucleus proprius. In contrast, the D-hair primary afferent axons terminated in the dorsal part of the nucleus proprius overlapping into the innermost portion of the substantia gelatinosa. The field receptor fibers terminated predominantly in the middle part of the nucleus proprius. These results suggest that there is a highly specialized central projection of primary afferent endings which is related to sensory function and not to fiber diameter. The marginal zone and most dorsal parts of the substantia gelatinosa receive direct projections from cutaneous nociceptors but do not have direct input from cutaneous receptors transmitting activity initiated by innocuous stimulation.

Animals↗
PubMed1979

Morphological features of functionally defined neurons in the marginal zone and substantia gelatinosa of the spinal dorsal horn.

Functional characteristics of spinal neurons located in the marginal zone (lamina I) and substantia gelatinosa (lamina II) were compared to their structural features by intrcellularly staining the source of unitary potentials with horseradish peroxidase (HRP) in unanesthetized, spinal cats. The responses of postsynaptic units to graded electrical volleys in intact dorsal roots and to physiological stimulation revealed that the peripheral excitatory input to neurons of the region is dominated by slowly conducting afferent fibers; often, the input to a given element is largely from a particular class of receptors. One type commonly seen received its principal peripheral excitation from low threshold mechanoreceptors with A delta or C afferent fibers. Mechanoreceptive elements often exhibited a marked, prolonged habituation and many were not excited by afferent volleys. Other units were predominantly excited by nociceptors with myelinated or unmyelinated fibers, or by thermoreceptors with unmyelinated fibers. A few units (principally the thermoreceptive) showed substantial ongoing activity which was modulated by sensory stimulation, but most had little or none. The HRP staining revealed neuronal morphology in fine detail. No relationship between neuronal configuration and physiological response was discerned. Soma location was not always linked to afferent input, although the cell bodies of nociceptive and thermoreceptive neurons tended to be in lamina I or outer lamina II (SGo) while those of the innocuous mechanoreceptive meurons tended to be in inner lamina II (SGi). The locus of a neuron's major dendritic arborization was more closely related to the source(s) of peripheral excitation. Cells excited by nociceptors with myelinated fibers had major dendritic projections in the marginal zone. Cells excited by nociceptors or thermoreceptors with unmyelinated fibers had important dendritic branching in the SGo. Innocuous mechanoreceptive neurons had primary dendritic arborization in the SGi when the input derived from unmyelinated fibers, or in the SGi and extending into the outer nucleus proprius (lamina III) when the afferent drive came from A delta fibers. These findings support the concept that laminae I and II constitute a major termination region for thin primary afferent fibers, myelinated fibers from nociceptors ending principally in lamina I and unmyelinated fibers from nociceptors, thermoreceptors, and mechanoreceptros terminating predominantly in lamina II. Substantial integrative and distributive functions can be expected of such an afferent termination zone.

Animals↗
PubMed1979

Distribution of primary afferent fibers within the sacrococcygeal dorsal horn: an autoradiographic study.

The spinal segmental distribution and intersegmental course of primary afferent fibers were studied by injecting (by pressure or iontophoresis) tritiated amino acids (L-proline or L-leucine) into spinal ganglia of coccygeal and sacral segments and autoradiographically analyzing histological sections of the spinal cord, particularly those regions lying dorsal to the central canal. The results from eight cats and three monkeys are described. A heavy projection of primary afferent fibers to the marginal zone (lamina I), the substantia gelatinosa Rolandi (lamina II), and throughout the nucleus proprius (laminae III-IV) was demonstrated. The projections to these three areas appeared to be substantially independent. Primary afferent fibers were found to course rostrally and caudally within the marginal zone, in the midline dorsal to the central canal, in Lissauer's tract, and in the dorsal columns. A crossed projection passed by way of the dorsal commissure to the contralateral marginal zone and to a region ventrolateral to the contralateral nucleus proprius. There was a distinct medial-to-lateral shift in the termination of primary afferent fibers in the substantia gelatinosa and in the dorsal portion of the nucleus proprius. The most medial distribution occurred immediately caudal to the entry zone of the primary afferent fibers, and the most lateral at the cephalad end of the segment immediately rostral to the entry level. Small (iontophoretic) injections revealed circumscribed fields of termination, approximately 40 micrometers by 70 micrometers (dorsoventrally) by 400 micrometers or more (rostrocaudally) in the substantia gelatinosa.

Animals↗
PubMed1978

Excitation of marginal and substantia gelatinosa neurons in the primate spinal cord: indications of their place in dorsal horn functional organization.

Electrophysiological recordings were made from superficial parts of the spinal dorsal horn in monkeys, using dye-filled micropipette electrodes to permit iontophoretic marking of the recording sites for subsequent histological recovery. Focal field potentials and unitary activity evoked by dorsal root volleys including slowly-conducting components (both myelinated and unmyelinated) were found in the posteromarginal zone and the substantia gelatinosa (SG). Unitary potentials identified as being of the type recorded from cellular regions were separated into categories according to which group of slowly-conducting fibers and which kinds of cutaneous stimulation evoked the discharge. Recording locations for units excited by volleys in myelinated fibers conducting under 35 m/sec, by the types of skin stimulation activating either high-threshold mechanoreceptors (nociceptors) or cooling thermoreceptors, and giving no evidence of suprathreshold C-fiber excitation were centered on the posteromarginal zone. In contrast, recording loci for units exhibiting a strong C-fiber excitation and responses to cutaneous stimulation known to effectively excite C-fiber polymodal nociceptors or C-mechanoreceptors were centered in the SG. There appeared varying degrees of convergence of primary afferent input to the neuronal units, although most showed substantial specificity in their afferent excitation. On the bases of these results and consideration of existing morphological data, it is proposed that the marginal zone is a major synaptic termination region for the afferent fibers from high-threshold mechanoreceptors, cooling thermoreceptors, and perhaps other receptors with fine myelinated peripheral fibers. The SG, on the other hand, is suggested to be the terminal region for all types of unmyelinated primary afferent sensory neurons, and to have the complex role of integrating and distributing this input.

Afferent Pathways↗
PubMed1977

Failure of acupuncture to produce localized analgesia.

The pain sensitivity of 49 healthy volunteers has been tested both before and during electro-acupuncture at two or three widely separated places on the body surface. Test areas fell into two categories. The "target" areas were within the part of the body that experienced acupuncturists predicted would be most affected by acupuncture of specified traditional points. "Non-target" control areas fell outside this zone of predicted maximal effect. The subjects and the observers who administered the tests knew that acupuncture anesthesia was being studied, but they did not know which areas were the "targets". Each subject was tested using at least two sensory testing methods. Altogether 4 different tests of pain sensitivity (pinprick discrimination, cold pain ratings, heat pain thresholds and pinch pain thresholds) were used. Small, but statistically highly significant, decreases in pain sensitivity occurred with all 4 tests during acupuncture. However, pain sensitivity fell by the same amount at "target" and "non-target" areas. The variability of the data was sufficiently low that moderate differences between areas would have been detected. The mechanism of "acupuncture anesthesia" is discussed in the light of these negative findings.

Acupuncture Therapy↗