ABSTRACT
Inspired by the marine mussel's ability to adhere to surfaces underwater, an aqueous catechol-based dip coating platform was developed. Using a catechol-functionalized polyacrylamide binder in combination with inorganic nanoparticles enables the facile fabrication of robust composite coatings via a layer-by-layer process. This modular assembly of well-defined building blocks provides a versatile alternative to electrostatic driven approaches with layer thickness and refractive indices being readily tunable. The platform nature of this approach enables the fabrication of hierarchically ordered nano-materials such as Bragg stacks.
ABSTRACT
To establish the afferent receptive properties of lumbosacral dorsal root ganglion (DRG) neurones that express calcitonin gene-related peptide (CGRP), intracellular recordings were made with fluorescent dye-filled electrodes in deeply anaesthetised young guinea-pigs. After determination of neuronal functional properties, dye was injected into the soma. CGRP-like immunoreactivity (CGRP-LI) was examined on histological sections of dye-marked neurones. Fourteen of 34 C-fibre neurones showed CGRP-LI. These included 10/21 C-fibre nociceptive neurones. All C-polymodal nociceptors in glabrous (n = 4) but none in hairy skin (n = 4) were positive. Positive C-fibre high threshold mechanoreceptive (HTM) units had receptive fields in dermal or deeper tissue. Four (n = 6) unresponsive or unidentified C-fibre units were positive. Neither C-fibre cooling sensitive (n = 4) nor C-fibre low threshold mechanoreceptive (LTM) units (n = 3) had CGRP-LI. Six of 23 A-fibre nociceptive cells were positive including one Aalpha/beta unit. Three of these positive cells had epidermal and three had dermal/deep receptive fields. Three of 36 A-fibre LTM units exhibited CGRP-LI; all were Aalpha/beta-fibre G hair units. All glabrous skin and muscle spindle units and in hairy skin slowly adapting and field units, and some G-hair units lacked CGRP-LI. CGRP-LI stained fibres were found in tissues containing receptive fields of positive DRG neurones: glabrous skin, near hair follicles and in skeletal muscle. A few substance P-labelled neurones did not exhibit CGRP-LI and vice versa. Thus CGRP expression was detected in under half the nociceptive neurones, was not limited to nociceptive neurones and apart from receptive properties was also related to location/depth in the tissues of a DRG neurone's peripheral terminals.
Subject(s)
Afferent Pathways/physiology , Calcitonin Gene-Related Peptide/analysis , Ganglia, Spinal/physiology , Neurons/physiology , Afferent Pathways/cytology , Animals , Electrophysiology/methods , Ganglia, Spinal/cytology , Guinea Pigs , Immunohistochemistry , Nerve Fibers/physiology , Nerve Fibers/ultrastructure , Neural Conduction/physiology , Neurons/cytologyABSTRACT
Relationships between the morphology of individual neurones of the spinal superficial dorsal horn (SDH), laminae I and II, and their electrophysiological properties were studied in spinal cord slices prepared from anaesthetized, free-ranging hamsters. Tight-seal, whole-cell recordings were made with pipette microelectrodes filled with biocytin to establish electrophysiological characteristics and to label the studied neurones. Neurones were categorized according to location and size of the somata, the dendritic and axonal pattern of arborization, spontaneous synaptic potentials, evoked postsynaptic currents, pattern of discharge to depolarizing pulses and current-voltage relationships. Data were obtained for 170 neurones; 13 of these had somata in lamina I and 157 in lamina II. Stimulation of the segmental dorsal root evoked a prompt excitatory response in almost every neurone sampled (161/166) with nearly 3/4 displaying putative monosynaptic EPSCs. The majority of neurones (133/170) fitted one of several distinctive morphological categories. To a considerable extent, neurones with a common morphological configuration and neurite disposition shared electrophysiological characteristics. Five of the 13 lamina I neurones were relatively large with extensive dendritic arborization in the horizontal dimension and a prominent axon directed ventrally and contralaterally. These presumptive ventrolateral projection neurones differed structurally and electrophysiologically from the other lamina I neurones, which had ipsilateral, locally arborizing axons and/or branches entering the dorsal lateral funiculus. One hundred and twenty lamina II neurones fitted one of five morphological categories: islet, central, medial-lateral, radial or vertical. Central cells were further divided into three groups on functional features. We conclude that the spinal SDH comprises many types of neurones whose morphological characteristics are associated with specific functional features implying diversity in functional organization of the SDH and in its role as a major synaptic termination for thin primary afferent fibres.
Subject(s)
Excitatory Postsynaptic Potentials/physiology , Lysine/analogs & derivatives , Posterior Horn Cells/physiology , Posterior Horn Cells/ultrastructure , Action Potentials/physiology , Animals , Cell Size/physiology , Cricetinae , Dendrites/physiology , Patch-Clamp Techniques , Staining and LabelingABSTRACT
Much attention has been given to the pelvic nerve afferent innervation of the urinary bladder; however, reports differ considerably in descriptions of afferent receptor types, their conduction velocities, and their potential roles in bladder reflexes and sensation. The present study was undertaken to do a relatively unbiased sampling of bladder afferent fibers of the pelvic nerve in adult female rats. The search stimulus for units to be studied was electrical stimulation of both the bladder nerves and the pelvic nerve. Single-unit activity of 100 L(6) dorsal root fibers, activated by both pelvic and bladder nerve stimulation, was analyzed. Sixty-five units had C-fiber and 35 units had Adelta-fiber conduction velocities. Receptive characteristics were established by direct mechanical stimulation, filling of the bladder with 0.9% NaCl at a physiological speed and by filling the bladder with solutions containing capsaicin, potassium, or turpentine oil. The majority (61) of these fibers were unambiguously excited by bladder filling with 0.9% NaCl and were classified as mechanoreceptors. All mechanoreceptors with receptive fields on the body of the bladder had low pressure thresholds (=10 mmHg). Receptive fields of units with higher thresholds were near the ureterovesical junction, on the base of the bladder or could not be found. Neither thresholds nor suprathreshold responses could be related to conduction velocity. Bladder compliance and mechanoreceptor thresholds were influenced by the stage of the estrous cycle: both were lowest in proestrous rats and highest in metaestrous rats. Mechanoreceptors innervating the body of the bladder and the region near the ureterovesical junction showed two patterns of responsiveness to slow bladder filling. One group of units exhibited increasing activity with increasing pressure up to 40 mmHg, while the other group showed a peak in activity at pressures below 40 mmHg followed by a plateau or decrease in activity with increasing pressure. It is proposed that differences in stimulus transduction relate to the different response patterns. Thirty-nine units failed to respond to bladder filling. Eight of these were excited by intravesical potassium or capsaicin and were classified as chemoreceptors. The remaining 31 units were not excited by any stimulus tested. Chemoreceptors and unexcited units had both Adelta and C afferent fibers. We conclude that the pelvic nerve sensory innervation of the rat bladder is complex, may be sensitive to hormonal status, and that the properties of individual sensory receptors are not related in an obvious manner to the conduction velocity of their fibers.
Subject(s)
Nerve Fibers/physiology , Sensation/physiology , Urinary Bladder/innervation , Animals , Capsaicin/pharmacology , Chemoreceptor Cells/drug effects , Chemoreceptor Cells/physiology , Electrophysiology , Female , Mechanoreceptors/physiology , Neurons, Afferent/physiology , Potassium Chloride/pharmacology , Rats , Rats, Sprague-DawleyABSTRACT
Control of expression of molecular receptors for chemical messengers and modulation of these receptors' activity are now established as ways to alter cellular reaction. This paper extends these mechanisms to the arena of pathological pain by presenting the hypothesis that increased expression of alpha-adrenergic receptors in primary afferent neurons is part of the etiology of pain in classical causalgia. It is argued that partial denervation by lesion of peripheral nerve or by tissue destruction induces a change in peripheral nociceptors, making them excitable by sympathetic activity and adrenergic substances. This excitation is mediated by alpha-adrenergic receptors and has a time course reminiscent of experimental denervation supersensitivity. The change in neuronal phenotype is demonstrable after lesions of mixed nerves or of the sympathetic postganglionic supply. Similar partial denervations also produce a substantial increase in the number of dorsal root ganglion neurons evidencing the presence of alpha-adrenergic receptors. The hypothesis proposes the increased presence of alpha-adrenergic receptors in primary afferent neurons to result from an altered gene expression triggered by cytokines/growth factors produced by disconnection of peripheral nerve fibers from their cell bodies. These additional adrenergic receptors are suggested to make nociceptors and other primary afferent neurons excitable by local or circulating norepinephrine and epinephrine. For central pathways, the adrenergic excitation would be equivalent to that produced by noxious events and would consequently evoke pain. In support, evidence is cited for a form of denervation supersensitivity in causalgia and for increased expression of human alpha-adrenergic receptors after loss of sympathetic activity.
Subject(s)
Causalgia/physiopathology , Neurons, Afferent/physiology , Pain/physiopathology , Receptors, Adrenergic/physiology , Animals , Denervation , Humans , Receptors, Adrenergic, alpha/physiologyABSTRACT
Advances in our understanding of the activation of peripheral damage-sensing neurons (nociceptors) over the past year have been complemented by electrophysiological and imaging studies of central nervous system pain-related centres. The manipulation of gene expression in a reversible and cell type specific way combined with imaging and electrophysiological studies holds promise for helping us to identify the spatial and molecular substrates of pain perception with increasing precision and gives hope for improved analgesic therapies.
Subject(s)
Pain/physiopathology , Analgesics/chemical synthesis , Analgesics/therapeutic use , Animals , Brain/anatomy & histology , Brain/diagnostic imaging , Genetic Therapy , Humans , Neurokinin A/physiology , Neurons, Afferent/physiology , Pain/diagnostic imaging , Pain Management , Radionuclide ImagingABSTRACT
1. Immunocytochemistry with polyclonal antibodies directed against specific fragments of intracellular loops of alpha2A- and alpha2C-adrenergic receptors (alpha2A-AR, alpha2C-AR) was used to explore the possibility that expression of these receptors in dorsal root ganglion (DRG) neurones of rat alters as a result of peripheral nerve injury or localized inflammation. 2. Small numbers of neurones with positive alpha2A-AR immunoreactivity (alpha2A-AR-IR) were detected in DRG from normal animals or contralateral to nerve lesions. In contrast, after complete or partial sciatic nerve transection the numbers of ipsilateral L4 and L5 DRG somata expressing alpha2A-AR-IR sharply increased (>5-fold). There was no discernible change in the number of DRG neurones exhibiting alpha2A-AR-IR innervating a region in association with localized chemically induced inflammation. 3. After nerve injury, double labelling with Fluoro-Gold, a marker of retrograde transport from transected fibres, or by immunoreactivity for c-jun protein, an indicator of injury and regeneration, suggested that many of the neurones expressing alpha2A-AR-IR were uninjured by the sciatic lesions. 4. In general the largest proportionate increase in numbers of neurones labelled by alpha2A-AR-IR after nerve lesions appeared in the medium-large diameter range (31-40 microm), a group principally composed of cell bodies of low threshold mechanoreceptors. The number of small diameter DRG neurones labelled by alpha2A-AR-IR, a category likely to include somata of nociceptors, also increased but proportionately less. 5. Relatively few DRG neurones exhibited alpha2C-AR-IR; this population did not appear to change after either nerve lesions or inflammation. 6. These observations are considered in relation to effects of nerve injury on excitation of primary afferent neurones by sympathetic activity or adrenergic agents, sympathetically related neuropathy and reports of sprouting of sympathetic fibres in DRG.
Subject(s)
Neuritis/metabolism , Neurons, Afferent/metabolism , Receptors, Adrenergic, alpha/metabolism , Sciatic Nerve/injuries , Wounds, Penetrating/metabolism , Animals , Female , Ganglia, Spinal/metabolism , Ganglia, Spinal/pathology , Isomerism , Male , Rats , Rats, WistarABSTRACT
Many neurons of spinal laminae I and II, a region concerned with pain and other somatosensory mechanisms, display frequent miniature "spontaneous" EPSCs (mEPSCs). In a number of instances, mEPSCs occur often enough to influence neuronal excitability. To compare generation of mEPSCs to EPSCs evoked by dorsal root stimulation (DR-EPSCs), various agents affecting neuronal activity and Ca2+ channels were applied to in vitro slice preparations of rodent spinal cord during tight-seal, whole-cell, voltage-clamp recordings from laminae I and II neurons. The AMPA/kainate glutamate receptor antagonist CNQX (10-20 microM) regularly abolished DR-EPSCs. In many neurons CNQX also eliminated mEPSCs; however, in a number of cases a proportion of the mEPSCs were resistant to CNQX suggesting that in these instances different mediators or receptors were also involved. Cd2+ (10-50 microM) blocked evoked EPSCs without suppressing mEPSC occurrence. In contrast, Ni2+ (=100 microM), a low-threshold Ca2+ channel antagonist, markedly decreased mEPSC frequency while leaving evoked monosynaptic EPSCs little changed. Selective organic antagonists of high-threshold (HVA) Ca2+ channels, nimodipine, omega-Conotoxin GVIA, and Agatoxin IVA partially suppressed DR-EPSCs, however, they had little or no effect on mEPSC frequency. La3+ and mibefradil, agents interfering with low-threshold Ca2+ channels, regularly decreased mEPSC frequency with little effect on fast-evoked EPSCs. Increased [K+]o (5-10 mM) in the superfusion, producing modest depolarizations, consistently increased mEPSC frequency; an increase suppressed by mibefradil but not by HVA Ca2+ channel antagonists. Together these observations indicate that different Ca2+ channels are important for evoked EPSCs and mEPSCs in spinal laminae I and II and implicate a low-threshold type of Ca2+ channel in generation of mEPSCs.
Subject(s)
Calcium Channels/metabolism , Excitatory Postsynaptic Potentials , 6-Cyano-7-nitroquinoxaline-2,3-dione/pharmacology , Animals , Cadmium/pharmacology , Calcium Channel Blockers/pharmacology , Cricetinae , Excitatory Amino Acid Antagonists/pharmacology , Excitatory Postsynaptic Potentials/drug effects , Ganglia, Spinal/metabolism , In Vitro Techniques , Nickel/pharmacology , Patch-Clamp Techniques , Potassium/pharmacology , Potassium/physiology , Rats , Rats, Sprague-Dawley , Tetrodotoxin/pharmacologyABSTRACT
A planar 6 x 6 array of iridium electrodes with four reference electrodes has been developed for use with neural tissue preparations. Precise knowledge of the relative locations of the array elements allows for spatial neurophysiological analyses. The 10 microns diameter platinized iridium electrodes on a 100 microns pitch have been used to stimulate acutely prepared slices of spinal cord from free-ranging rodents. An intracellular recording from a single neuron in the substantia gelatinosa (SG) using the whole-cell, tight-seal technique allowed low noise, high resolution studies of excitatory or inhibitory electrical responses of a given neuron to inputs from the primary afferent fibers or from stimulation by individual electrodes of the array. The resulting maps of responses provide an indication of the interconnectivity of neural processes. The pattern emerging is that of limited interconnectivity in the SG from areas surrounding a recorded neuron but with strong excitatory or inhibitory effects from those oriented in a longitudinal (rostral-caudal) direction relative to the neuron. The observations to date suggest the neurons of the SG are arranged in sets of independent networks, possibly related to sensory modality and input from particular body regions.
Subject(s)
Microelectrodes , Nerve Net , Spinal Cord/physiology , Animals , Cricetinae , Electric Stimulation , In Vitro Techniques , Video RecordingABSTRACT
1. The relationship between the afferent properties and substance P-like immunoreactivity (SP-LI) of L6 and S1 dorsal root ganglion (DRG) neuronal somata was examined in anaesthetized guinea-pigs. Glass pipette microelectrodes filled with fluorescent dyes were used to make intracellular recordings and to label DRG somata. The dorsal root conduction velocity (CV) and the afferent receptive properties of each unit were categorized according to criteria established in other species. Categories included a variety of low threshold mechanoreceptive classes, innocuous thermoreceptive and several nociceptive classes. Nociceptive units were further subdivided on the basis of CV and the locus of the receptive field (superficial cutaneous, deep cutaneous or subcutaneous). 2. SP-LI was determined using the avidin-biotin complex method and the relative staining intensity determined by image analysis. The possible significance of labelling intensity is discussed. Clear SP-LI appeared in twenty-nine of 117 dye-labelled neurones. All SP-LI positive units with identified receptive properties were nociceptive but not all categories of nociceptors were positive. The intensity of SP-LI labelling varied, often systematically, in relation to afferent properties. There was a tendency for nociceptive neurones with slower CVs and/or smaller cell bodies to show SP-LI. 3. Nineteen of fifty-one C fibre neurones showed SP-LI. Fewer than half the C polymodal nociceptors (CPMs) were positive. The most intensely labelled units were the deep cutaneous nociceptors and some of the CPMs in glabrous skin. C low threshold mechanoreceptors and cooling-sensitive units did not show SP-LI. 4. Ten of sixty-six A fibre neurones exhibited SP-LI, including eight of sixteen A delta nociceptors and two of fifteen A alpha/beta nociceptors. A fibre neurones exhibiting SP-LI included seven of eight deep cutaneous mechanical nociceptors and some superficial cutaneous mechano-heat nociceptors of hairy skin. In contrast, none of twenty superficial cutaneous A high threshold mechanoreceptor units or the thirty-five A fibre low threshold units (D-hair and other units) showed detectable SP-LI. 5. We conclude that SP-LI labelling in guinea-pig DRG neurones is related to (a) afferent receptive properties, (b) the tissue in which the peripheral receptive terminals are located, (c) the CV and (d) the soma size.
Subject(s)
Ganglia, Spinal/physiology , Neurons, Afferent/physiology , Nociceptors/physiology , Substance P/physiology , Action Potentials , Animals , Cell Size , Electrophysiology , Fluorescent Dyes , Guinea Pigs , Immunohistochemistry , Microscopy, Fluorescence , Nerve Fibers/chemistry , Nerve Fibers, Myelinated/chemistry , Neurons, Afferent/chemistry , Skin/innervation , Substance P/analysis , Substance P/immunologyABSTRACT
This article explores the clinical, systemic, and interpersonal dynamics of conflict between therapists on a treatment team. It considers treatment implications in regard to how therapists handle conflicts with one another, and focuses attention on the pressure they experience to resolve differences and reach consensus. Specifically, the author suggests that the therapist's ability to tolerate a lack of consensus, and to understand and accept conflicting perspectives with respect to a given patient, can help that patient begin to tolerate and integrate his or her own ambivalent feelings. Such integrative efforts may enable the patient to eventually deal with conflicting affects more directly within a single therapeutic relationship.
Subject(s)
Conflict, Psychological , Patient Care Team , Adult , Female , Humans , Professional-Patient RelationsABSTRACT
Psychological distress measured by the Talbieh Brief Distress inventory was compared between two groups of immigrants: consumers of supported housing (N = 302) and non-consumers living in community settings (N = 419), matched by sex, age and education level. Overall, distress level was found to be significantly lower in consumers of supported housing than in non-consumers. Consumers also exhibited significant lower hostility, obsessive-compulsive and paranoid ideation symptoms, but they were similar to nonconsumers on level of depression, anxiety and sensitivity. The results suggest that supported housing protects recent immigrants from environmental stresses to a greater extent than community residence.
Subject(s)
Emigration and Immigration/statistics & numerical data , Housing , Mental Disorders/epidemiology , Adolescent , Adult , Civil Rights , Female , Financial Support , Housing/economics , Humans , Israel/epidemiology , Life Change Events , Male , Mental Disorders/diagnosis , Middle Aged , Personality Inventory , Public Policy , Residence Characteristics , Social Justice , Stress, Psychological/diagnosis , Stress, Psychological/epidemiologyABSTRACT
The effects of partial division of the great auricular nerve of adult rabbits were evaluated on the responsiveness of cutaneous C-fiber polymodal nociceptors (CPMs) to sympathetic stimulation (SS), close-arterial injections of epinephrine (EPI) and other alpha-adrenergic agonists. In normal unanesthetized rabbits, the two ears were usually at the same temperature. Two to 4 weeks after partial nerve lesions, however, the operated ear was cooler by 1-3 degrees C in the majority of animals, suggestive of increased vasoconstriction and possible denervation supersensitivity. Neither SS nor EPI (50 ng) excited CPM units (n = 23) from intact anesthetized animals. In contrast, 14-27 days after partial nerve lesions, SS (8 out of 38 units) and EPI (12 out of 38 units) were excitatory for a class of CPMs. There was notable variability in the response of different units and of a given unit between first and second trials. Responses consisted of 1-22 impulses for SS and 1-23 impulses for EPI in the 60 s following a trial. Arterial occlusion did not activate responsive units, suggesting that the excitation was not caused by vascular or temperature changes. Selective alpha2-adrenoceptor blockade with yohimbine (0.6-1.0 mg/kg i.v.) or rauwolscine (1.0 mg/kg i.v.) reversibly antagonized the effects of SS and EPI. EPI-responsive units were also excited by norepinephrine (50 ng) and guanabenz (10 microg) but not by clonidine (3 microg) or B-HT 933 (3 microg). The results suggest that circulating EPI, acting via an alpha-adrenoceptor subtype, can play a part in the development and/or maintenance of aberrant pain syndromes such as causalgia and other sympathetically related dystrophies.
Subject(s)
Epinephrine/pharmacology , Nerve Fibers/drug effects , Nociceptors/drug effects , Sympathetic Nervous System/injuries , Animals , Female , Male , Nerve Fibers/physiology , RabbitsABSTRACT
OBJECTIVE: The authors examined the efficacy of lithium carbonate for treating conduct disorder in adolescents. METHOD: The subjects were 33 inpatients aged 12-17 years. Lithium or placebo was administered in a double-blind fashion for 2 weeks. RESULTS: On several measures of clinical change the groups showed no significant differences. Of the patients who completed the study, 8.3% of those receiving placebo (one of 12) versus 21.4% (three of 14) of those receiving lithium were considered responders. CONCLUSIONS: Lithium does not appear beneficial for this indication.
Subject(s)
Child Behavior Disorders/drug therapy , Lithium Carbonate/therapeutic use , Adolescent , Age Factors , Aggression/drug effects , Child , Child Behavior Disorders/psychology , Double-Blind Method , Humans , Male , Placebos , Treatment OutcomeABSTRACT
Opiates in general, and heroin in particular, are known to induce compulsive drug-seeking and drug-taking behavior. Addiction is accompanied by psychobiological processes which may distort perception of sensory stimuli. Gustatory and olfactory stimuli are hedonically polarized and therefore most appropriate for the assessment of the organism's reactivity to "useful" and "harmful" chemosensory events. Previous studies revealed that psychophysical self-estimates and reflectory facial expressions mirror with comparable reliability the hedonics of the perceived taste and odor sensations. In the present study both cognitive verbal and reflectory facial expressions of a group of: a) heroin addicts were recorded and compared to those of a group of b) detoxified former addicts and to c) a group of matching controls. Results show that all three groups differentiate between pleasant, indifferent and aversive tastes and odors. Active addicts estimated sweet taste and savory smells as being somewhat more pleasant, and bitter and sour tastes and a putrid odor as less unpleasant than did the other two groups. The reflectory facial displays of addicts were less expressive and discriminative than those of the two other groups. Taste- and odor-induced facial displays are known to be controlled primarily by the brainstem. The findings indicate that heroin-addiction affects brain-mechanisms, which mirror taste- and odor-hedonics. Modulation of the phylogenetically ancient, sensory-motor coordinations was found to be of a different pattern than that of the cortically-controlled cognitive reactions.
Subject(s)
Heroin Dependence/psychology , Smell/drug effects , Taste/drug effects , Adult , Brain Stem/drug effects , Facial Expression , Female , Heroin Dependence/rehabilitation , Humans , Male , Middle Aged , Perceptual Distortion/drug effects , Sensory Thresholds/drug effectsSubject(s)
Independent Practice Associations/organization & administration , Practice Management, Medical/organization & administration , Efficiency, Organizational , Family Practice/economics , Family Practice/organization & administration , Independent Practice Associations/economics , Investments , Ownership , Physicians , Practice Management, Medical/economics , Rate Setting and Review , United StatesABSTRACT
One hundred and nine physician-initiated consultations were directed to a clinical pharmacist over a 1-year period. Two hundred and three (88.2%) recommendations out of 229 were adopted. Major question types included preventive measures, non-response, side-effects and mixed factors. The global effectiveness of pharmacist interventions suggests that 67.9% of patients exhibited a very satisfactory or satisfactory response. While our study suggests that a clinical pharmacist may favourably contribute to the quality of patient care, a control-group study is required to confirm our results.
Subject(s)
Pharmacists , Pharmacy Service, Hospital/statistics & numerical data , Referral and Consultation/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , Child , Hospitals, Psychiatric , Humans , Middle AgedABSTRACT
1. The effects of ipsilateral removal of the superior cervical ganglion on the subsequent responsiveness of C-fiber polymodal nociceptors (CPMs) of the ear to close-arterial injections of norepinephrine (NE) were evaluated in adult, anesthetized rabbits. 2. In normal unanesthetized rabbits, the two ears were usually at the same temperature. Immediately after the ganglionectomy, the ipsilateral ear was warmer; however, at the time of electrophysiological recordings (4-23 days) the majority of animals had the ipsilateral ear cooler by > or = 1 degree C, suggestive of denervation supersensitivity. 3. NE (50 ng) did not activate any CPMs (n = 28) from intact animals. 4. Seven of 22 CPMs recorded from sympathectomized ears were activated by NE (50 ng). The responses varied considerably but typically consisted of 2-4 impulses in the 60 s after the NE injection. In some instances, repetitive activity continued for many minutes. Such prolonged discharge differs from the adrenergic responses seen after partial nerve damage. 5. The induction of adrenergic excitability in CPMs by sympathectomy is suggested to be a counterpart to postsympathectomy neuralgia in human beings and a possible part of the mechanism leading to sympathetically related pain states.
Subject(s)
Adrenergic Fibers/physiology , Nerve Fibers/physiology , Nociceptors/physiology , Skin/innervation , Superior Cervical Ganglion/physiology , Sympathetic Nervous System/physiology , Animals , Ear, External/innervation , Female , Male , Norepinephrine/physiology , Patch-Clamp Techniques , Rabbits , Skin Temperature/physiology , Sympathectomy , Synaptic Transmission/physiologyABSTRACT
The cutaneous sensory units labeled C-fiber polymodal nociceptors have a broadly coherent set of responsive characteristics. These include; (a) elevated thresholds to mechanical stimulation and to heat; (b) excitation by irritant and algesic chemicals; and (c) sensitization by injury or algesic substances. These characteristics and the match between the signals produced by C-polymodal nociceptors to pain-causing stimuli and human reports of pain indicate a probable causal connection. Nevertheless, there are indications that this population of sensory units may contain functionally-distinct subtypes. Some human C-polymodal nociceptors have been reported to be excited by histamine at low concentrations, whereas much of the population lacks such responsiveness. Further, in vitro studies of the effects of non-steroidal anti-inflammatory agents and low pH on sensitization suggest distinctions in the responsiveness of different elements whose general characteristics place them into the C-polymodal category. The enhanced responsiveness of C-polymodal nociceptors after heat stimulation or exposure to acidity has a probable relationship to the primary hyperalgesia produced after injury to hairy skin or in the presence of inflammation. Furthermore, the alterations of C-polymodal nociceptor characteristics after partial nerve injury and sympathectomy imply a change in phenotype of neurons spared by denervation and are suggestive of a possible relationship to sympathetically related pain and post-sympathetic neuralgias. These evidences of plasticity in responsiveness of a set of sense organs putatively associated with cutaneous pain represent lessons in the adaptability of biological mechanisms, and clues to the pathophysiology of pain.