scholarly journals Extracranial injections of botulinum neurotoxin type A inhibit intracranial meningeal nociceptors’ responses to stimulation of TRPV1 and TRPA1 channels: Are we getting closer to solving this puzzle?

Cephalalgia ◽  
2016 ◽  
Vol 36 (9) ◽  
pp. 875-886 ◽  
Author(s):  
XiChun Zhang ◽  
Andrew M Strassman ◽  
Victor Novack ◽  
Mitchell F Brin ◽  
Rami Burstein
Keyword(s):  
Chronic Migraine ◽  
Mechanical Response ◽  
Receptive Fields ◽  
Chemical Stimulation ◽  
Response Threshold ◽  
Mustard Oil ◽  
Peripheral Tissues ◽  
C Fibers ◽  
Ability To Act ◽  
Stimulation Of

Background Administration of onabotulinumtoxinA (BoNT-A) to peripheral tissues outside the calvaria reduces the number of days chronic migraine patients experience headache. Because the headache phase of a migraine attack, especially those preceded by aura, is thought to involve activation of meningeal nociceptors by endogenous stimuli such as changes in intracranial pressure (i.e. mechanical) or chemical irritants that appear in the meninges as a result of a yet-to-be-discovered sequence of molecular/cellular events triggered by the aura, we sought to determine whether extracranial injections of BoNT-A alter the chemosensitivity of meningeal nociceptors to stimulation of their intracranial receptive fields. Material and methods Using electrophysiological techniques, we identified 161 C- and 135 Aδ-meningeal nociceptors in rats and determined their mechanical response threshold and responsiveness to chemical stimulation of their dural receptive fields with TRPV1 and TRPA1 agonists seven days after BoNT-A administration to different extracranial sites. Two paradigms were compared: distribution of 5 U BoNT-A to the lambdoid and sagittal sutures alone, and 1.25 U to the sutures and 3.75 U to the temporalis and trapezius muscles. Results Seven days after it was administered to tissues outside the calvaria, BoNT-A inhibited responses of C-type meningeal nociceptors to stimulation of their intracranial dural receptive fields with the TRPV1 agonist capsaicin and the TRPA1 agonist mustard oil. BoNT-A inhibition of responses to capsaicin was more effective when the entire dose was injected along the suture lines than when it was injected into muscles and sutures. As in our previous study, BoNT-A had no effect on non-noxious mechanosensitivity of C-fibers or on responsiveness of Aδ-fibers to mechanical and chemical stimulation. Discussion This study demonstrates that extracranial administration of BoNT-A suppresses meningeal nociceptors’ responses to stimulation of their intracranial dural receptive fields with capsaicin and mustard oil. The findings suggest that surface expression of TRPV1 and TRPA1 channels in dural nerve endings of meningeal nociceptors is reduced seven days after extracranial administration of BoNT-A. In the context of chronic migraine, reduced sensitivity to molecules that activate meningeal nociceptors through the TRPV1 and TRPA1 channels can be important for BoNT-A’s ability to act as a prophylactic.

scholarly journals Mechanisms of the adenosine A2Areceptor-induced sensitization of esophageal C fibers

2016 ◽  
Vol 310 (3) ◽  
pp. G215-G223 ◽  
Author(s):  
M. Brozmanova ◽  
L. Mazurova ◽  
F. Ru ◽  
M. Tatar ◽  
Y. Hu ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Mechanical Response ◽  
Kinase Inhibitor ◽  
Ex Vivo ◽  
Receptor Potential ◽  
P2x Receptor ◽  
C Fibers ◽  
C Fiber ◽  
Transient Receptor ◽  
Stimulation Of

Clinical studies indicate that adenosine contributes to esophageal mechanical hypersensitivity in some patients with pain originating in the esophagus. We have previously reported that the esophageal vagal nodose C fibers express the adenosine A2Areceptor. Here we addressed the hypothesis that stimulation of the adenosine A2Areceptor induces mechanical sensitization of esophageal C fibers by a mechanism involving transient receptor potential A1 (TRPA1). Extracellular single fiber recordings of activity originating in C-fiber terminals were made in the ex vivo vagally innervated guinea pig esophagus. The adenosine A2Areceptor-selective agonist CGS21680 induced robust, reversible sensitization of the response to esophageal distention (10–60 mmHg) in a concentration-dependent fashion (1–100 nM). At the half-maximally effective concentration (EC50: ≈3 nM), CGS21680 induced an approximately twofold increase in the mechanical response without causing an overt activation. This sensitization was abolished by the selective A2Aantagonist SCH58261. The adenylyl cyclase activator forskolin mimicked while the nonselective protein kinase inhibitor H89 inhibited mechanical sensitization by CGS21680. CGS21680 did not enhance the response to the purinergic P2X receptor agonist α,β-methylene-ATP, indicating that CGS21680 does not nonspecifically sensitize to all stimuli. Mechanical sensitization by CGS21680 was abolished by pretreatment with two structurally different TRPA1 antagonists AP18 and HC030031 . Single cell RT-PCR and whole cell patch-clamp studies in isolated esophagus-specific nodose neurons revealed the expression of TRPA1 in A2A-positive C-fiber neurons and demonstrated that CGS21682 potentiated TRPA1 currents evoked by allylisothiocyanate. We conclude that stimulation of the adenosine A2Areceptor induces mechanical sensitization of nodose C fibers by a mechanism sensitive to TRPA1 antagonists indicating the involvement of TRPA1.

Electrophysiological characteristics of primate spinothalamic neurons with renal and somatic inputs

1989 ◽  
Vol 61 (6) ◽  
pp. 1121-1130 ◽  
Author(s):  
W. S. Ammons
Keyword(s):  
Nerve Stimulation ◽  
Receptive Fields ◽  
High Threshold ◽  
Spinothalamic Tract ◽  
Renal Nerve ◽  
C Fibers ◽  
Afferent Fibers ◽  
Renal Nerve Stimulation ◽  
Somatic Receptive Fields ◽  
Stimulation Of

1. Spinothalamic tract (STT) neurons in the T10-L3 segments were studied for responses to renal and somatic stimuli. A total of 90 neurons was studied in 25 alpha-chloralose anesthetized monkeys (Macaca fascicularis). All neurons were antidromically activated from the ventral posterior lateral nucleus of the thalamus. 2. Sixty-two cells were excited by renal nerve stimulation and six inhibited. Probability of locating cells with renal input was greatest in T11-L1. Cells were located in laminae I and IV-VII; however, most were located in laminae V-VII. Antidromic latencies averaged 4.61 +/- 0.32 (SE) ms, whereas antidromic conduction velocities averaged 43.23 +/- 9.03 m/s. 3. Cells with excitatory renal input received A delta input only (36 cells) or A delta- and C-fiber inputs (26 cells). Stimulation of A delta renal afferent fibers evoked bursts of 1-10 spikes/stimulus [mean 3.6 +/- 0.9 spikes/stimulus] with onset latencies of 10.7 +/- 0.5 ms. Stimulation of C-fibers evoked 1.3 +/- 0.5 spikes/stimulus with onset latencies of 61.7 +/- 11.1 ms. Magnitude of responses to A delta-fiber stimulation was greatest in T12 and decreased both rostrally and caudally. Inhibitory responses to renal nerve stimulation required activation of renal C-fibers. 4. All cells that responded to stimulation of renal afferent fibers received convergent inputs from somatic structures. Forty-four cells were classified as wide dynamic range, 10 were high threshold, 12 were high-threshold cells with inhibitory input from hair, 2 were deep, and 2 were low threshold. Somatic receptive fields were large and located on the flank and abdomen and/or the upper hindlimb. Fourteen cells had inhibitory receptive fields located on the contralateral hindlimb or one of the forearms. 5. It is concluded that T11-L1 STT cells in the monkey respond reliably to renal nerve stimulation. Thoracolumbar STT cells may thus play a role in pain that results from renal disease. The locations of the somatic receptive fields of the cells suggest that they are responsible for the referral of renal pain to the flank and abdomen.

Chemical Stimulation of the Intracranial Dura Induces Enhanced Responses to Facial Stimulation in Brain Stem Trigeminal Neurons

1998 ◽  
Vol 79 (2) ◽  
pp. 964-982 ◽  
Author(s):  
Rami Burstein ◽  
Hiroyoshi Yamamura ◽  
Amy Malick ◽  
Andrew M. Strassman
Keyword(s):  
Brain Stem ◽  
Dynamic Range ◽  
Chemical Activation ◽  
Receptive Fields ◽  
Chemical Stimulation ◽  
Slow Heating ◽  
High Threshold ◽  
Antidromic Activation ◽  
Trigeminal Neurons ◽  
Stimulation Of

Burstein, Rami, Hiroyoshi Yamamura, Amy Malick, and Andrew M. Strassman. Chemical stimulation of the intracranial dura induces enhanced responses to facial stimulation in brain stem trigeminal neurons. J. Neurophysiol. 79: 964–982, 1998. Chemical activation and sensitization of trigeminal primary afferent neurons innervating the intracranial meninges have been postulated as possible causes of certain headaches. This sensitization, however, cannot explain the extracranial hypersensitivity that often accompanies headache. The goal of this study was to test the hypothesis that chemical activation and sensitization of meningeal sensory neurons can lead to activation and sensitization of central trigeminal neurons that receive convergent input from the dura and skin. This hypothesis was investigated by recording changes in the responsiveness of 23 [16 wide-dynamic range (WDR), 5 high threshold (HT), and 2 low threshold (LT)] dura-sensitive neurons in nucleus caudalis to mechanical stimulation of their dural receptive fields and to mechanical and thermal stimulation of their cutaneous receptive fields after local application of inflammatory mediators or acidic agents to the dura. Responses to brief chemical stimulation were recorded in 70% of the neurons; most were short, lasting the duration of the stimulus only. Twenty minutes after chemical stimulation of the dura, the following changes occurred: 1) 95% of the neurons showed significant increases in sensitivity to mechanical indentation of the dura: their thresholds to dural indentation changed from 1.57 to 0.49 g (means, P < 0.0001), and the response magnitude to identical stimuli increased by two- to fourfold; 2) 80% of the neurons showed significant increases in cutaneous mechanosensitivity: their responses to brush and pressure increased 2.5- ( P < 0.05) and 1.6-fold ( P < 0.05), respectively; 3) 75% of the neurons showed a significant increase in cutaneous thermosensitivity: their thresholds to slow heating of the skin changed from 43.7 ± 0.7 to 40.3 ± 0.7°C ( P < 0.005) and to slow cooling from 23.7 ± 3.3 to 29.2 ± 1.8°C ( P < 0.05); 4) dural receptive fields expanded within 30 min and cutaneous receptive fields within 2–4 h; and 5) ongoing activity developed in WDR and HT but not in LT neurons. Application of lidocaine to the dura abolished the response to dural stimulation but had minimal effect on the increased responses to cutaneous stimulation (suggesting involvement of a central mechanism in maintaining the sensitized state). Antidromic activation (current of <30 μA) of dura-sensitive neurons revealed projections to the hypothalamus, thalamus, and midbrain. These findings suggest that chemical activation and sensitization of dura-sensitive peripheral nociceptors could lead to enhanced responses in central neurons and that this central sensitization therefore could result in extracranial tenderness (mechanical and thermal allodynia) in the absence of extracranial pathology. The projection targets of these neurons suggest a possible role in mediating the autonomic, endocrine, and affective symptoms that accompany headaches.

Characterization of Aδ- and C-Fibers Innervating the Plantar Rat Hindpaw One Day After an Incision

2002 ◽  
Vol 87 (2) ◽  
pp. 721-731 ◽  
Author(s):  
Esther M. Pogatzki ◽  
G. F. Gebhart ◽  
Timothy J. Brennan
Keyword(s):  
Spontaneous Activity ◽  
Mechanical Response ◽  
Tissue Injury ◽  
Mechanical Stimulus ◽  
Response Threshold ◽  
Mechanical Stimuli ◽  
Median Response ◽  
Sham Procedure ◽  
C Fibers ◽  
Afferent Fibers

Primary hyperalgesia after tissue injury is suggested to result from sensitization of primary afferent fibers, but sensitization to mechanical stimuli has been difficult to demonstrate. In the companion study, sensitization of mechano-responsive Aδ- and C-fibers did not explain pain behaviors 45 min after an incision in the rat hindpaw. In the present study, we examined mechanical response properties of Aδ- and C-fibers innervating the glabrous skin of the plantar hindpaw in rats 1 day after an incision or sham procedure. In behavioral experiments, median withdrawal thresholds to von Frey filaments were reduced from 522 mN before to 61 mN 2 and 20 h after incision; median withdrawal thresholds after sham procedure were stable (522 mN). Responses to a nonpunctate mechanical stimulus were increased after incision. In neurophysiological experiments in these same rats, 67 single afferent fibers were characterized from the left tibial nerve 1 day after sham procedure ( n = 39) or incision ( n = 28); electrical stimulation was used as the search stimulus to identify a representative population of Aδ- and C-fibers. In the incision group, 11 fibers (39%) had spontaneous activity with frequencies ranging from 0.03 to 39.3 imp/s; none were present in the sham group. The median response threshold of Aδ-fibers was less in the incision (56 mN, n = 13) compared with sham (251 mN, n = 26) group, mainly because the proportion of mechanically insensitive afferents (MIAs) was less (8 vs. 54% after sham procedure). Median C-fiber response thresholds were similar in incised (28 mN, n = 15) and sham rats (56 mN, n = 13). Responsiveness to monofilaments was significantly enhanced in Aδ-fibers 1 day after incision; stimulus response functions of C-fibers after incision and after sham procedure did not differ significantly. Only Aδ-fibers but not C-fibers sensitized to the nonpunctate mechanical stimulus. The size of receptive fields was increased in Aδ- and C-fibers 1 day after incision. The results indicate that sensitization of Aδ- and C-fibers is apparent 1 day after incision. Because sensitization of afferent fibers to mechanical stimuli correlated with behavioral results, sensitization may contribute to the reduced withdrawal threshold after incision. Spontaneous activity in Aδ- and C-fibers may account for nonevoked pain behavior and may also contribute to mechanical hyperalgesia by amplifying responses centrally.

Recordings From Brain Stem Neurons Responding to Chemical Stimulation of the Subarachnoid Space

1997 ◽  
Vol 77 (6) ◽  
pp. 3122-3133 ◽  
Author(s):  
A. Ebersberger ◽  
M. Ringkamp ◽  
P. W. Reeh ◽  
H. O. Handwerker
Keyword(s):  
Brain Stem ◽  
Inflammatory Mediators ◽  
Subarachnoid Space ◽  
Receptive Fields ◽  
Chemical Stimulation ◽  
Response Patterns ◽  
Stimulus Period ◽  
Artificial Cerebrospinal Fluid ◽  
Base Of The Skull ◽  
Stimulation Of

Ebersberger, A., M. Ringkamp, P. W. Reeh, and H. O. Handwerker. Recordings from brain stem neurons responding to chemical stimulation of the subarachnoid space. J. Neurophysiol. 77: 3122–3133, 1997. The subarachnoid space at the base of the skull was perfused continuously with artificial cerebrospinal fluid in anesthetized rats. A combination of inflammatory mediators consisting of histamine, bradykinin, serotonin, and prostaglandin E2 (10−5 M) at pH of 6.1 was introduced into the flow for defined periods to stimulate meningeal primary afferents. Secondary neurons in the caudal nucleus of the trigeminal brain stem were searched by electrical stimulation of the cornea. Of the units receiving oligosynaptic input from the cornea, 44% were excited by stimulation of the meninges with inflammatory mediators. Most of these units had small receptive fields including cornea and the periorbital region, and their responsiveness was restricted to stimuli of noxiuos intensity. Three types of responses to stimulation of the meninges with algogenic agents were encountered: responses that did not outlast the stimulus period, responses outlasting the stimulus period for several minutes, and oscillating response patterns containing periods of enhanced and suppressed activity. The response pattern of a unit was reproducible, however, upon repetitive stimulation at 20-min intervals; the response magnitude showed tachyphylaxis upon stimulus repetition. The preparation presented mimics pathophysiolocial states normally accompanied by headache, e.g., subarachnoidal bleeding. Responsiveness of neurons in the caudal nucleus of the trigeminal brain stem to inflammatory mediators may play a role in the generation and maintenance of headache, e.g., migraine.

Ventromedial hypothalamic stimulation enhances peripheral glucose uptake in anesthetized rats

1991 ◽  
Vol 261 (3) ◽  
pp. E298-E303 ◽  
Author(s):  
M. Sudo ◽  
Y. Minokoshi ◽  
T. Shimazu
Keyword(s):  
Adipose Tissue ◽  
Electrical Stimulation ◽  
Glucose Uptake ◽  
Rate Constant ◽  
Skeletal Muscles ◽  
Plasma Insulin ◽  
Chemical Stimulation ◽  
Peripheral Tissues ◽  
Anesthetized Rats ◽  
Stimulation Of

Effects of electrical and chemical stimulation of the ventromedial (VMH) and lateral hypothalamic (LH) nuclei on glucose uptake in peripheral tissues were studied by the 2-deoxy-D-[3H]glucose (2-[3H]DG) method in anesthetized rats. Electrical stimulation of the VMH increased the rate constant of glucose uptake in brown adipose tissue (BAT; 8 times), heart (3 times), and skeletal muscles (1.5 times) but not in white adipose tissue, diaphragm, and brain, without detectable changes in plasma insulin levels. Chemical stimulation of the VMH by microinjection of L-glutamate also enhanced the rate constant of glucose uptake in BAT, heart, and skeletal muscles preferentially, which indicates that the enhancement of glucose uptake in these tissues is derived from activation of VMH neurons. The increased rate of glucose uptake in BAT in response to VMH stimulation was effectively suppressed by surgical sympathetic denervation, suggesting a mediation of the sympathetic nerve in this effect. On the other hand, electrical stimulation of the LH had no appreciable effect on 2-[3H]DG uptake in any tissues. It is concluded that glucose uptake in certain peripheral tissues is accelerated selectively by activation of VMH neurons, the action of which is independent of plasma insulin but which is probably via the sympathetic nervous system.

Involvement of Dorsal Column Nucleus Neurons in Nociceptive Transmission in Aged Rats

2005 ◽  
Vol 94 (6) ◽  
pp. 4178-4187 ◽  
Author(s):  
Junichi Kitagawa ◽  
Yoshiyuki Tsuboi ◽  
Akiko Ogawa ◽  
Ke Ren ◽  
Suzuro Hitomi ◽  
...  
Keyword(s):  
Mechanical Response ◽  
Dynamic Range ◽  
Receptive Fields ◽  
Mechanical Stimulus ◽  
Dorsal Column ◽  
Response Threshold ◽  
Aged Rats ◽  
Adult Rats ◽  
Antidromic Activation ◽  
Nociceptive Transmission

To clarify the functional role of the dorsal column nucleus (DCN) in nociception in rats with advancing age, single neuronal activity and substance P–like immunoreactivity (SP-LI) of the gracile nucleus (GN) were studied in aged rats (29 to 34 mo old) and adult rats (9 to 12 mo old). A total of 122 neurons [aged: 34 wide-dynamic-range (WDR), two nociceptive-specific (NS), and 32 low-threshold mechanical (LTM) neurons; adult: 22 WDR and 32 LTM neurons] were recorded from GN. For WDR neurons, the latency to antidromic activation of the ventral posterior lateral nucleus of the thalamus showed no difference between the aged and adult rats. Sciatic nerve stimulation with C-fiber intensity induced responses of GN with significantly longer latency in aged rats than in adults, whereas there was no difference in the response latency to A-fiber intensity stimulation. Background activity and afterdischarges were significantly higher in the aged rats than those in the adult rats. Responses to noxious mechanical and thermal stimuli were significantly greater in the aged rats during application of graded stimuli. There were no significant differences in responses to nonnoxious mechanical stimulus, mechanical response threshold, and the size of the receptive fields between neurons in the aged and adult rats. The area occupied by SP-LI fibers in the GN and the size of SP-LI dorsal root ganglia neurons were significantly larger in aged rats than in adults. The present findings suggest that the hyperexcitability of GN neurons could be involved in abnormal noxious pain sensations with advancing age.

Sensory receptors with unmyelinated (C) fibers innervating the skin of the rabbit's ear

1985 ◽  
Vol 54 (3) ◽  
pp. 491-501 ◽  
Author(s):  
V. K. Shea ◽  
E. R. Perl
Keyword(s):  
Mechanical Stimulation ◽  
Receptive Fields ◽  
High Threshold ◽  
Cutaneous Stimulation ◽  
Great Auricular Nerve ◽  
C Fibers ◽  
C Fiber ◽  
Back Ground ◽  
Low Threshold ◽  
Stimulation Of

The cutaneous receptive properties of unmyelinated (C) fibers of the rabbit's great auricular nerve were determined by single-unit recordings. The majority of C-fiber units could be excited by cutaneous stimulation, and such sensory units fell into three major categories on the basis of responses to mechanical and thermal stimulation of their cutaneous receptive fields: low-threshold mechanoreceptors, nociceptors, or specific thermoreceptors. The majority of afferent elements were nociceptive, and all nociceptors responded to strong mechanical stimulation. Three types of nociceptors could be distinguished by their responses to thermal stimuli. Polymodal nociceptors responded to heat with thresholds of 40-55 degrees C and typically displayed enhanced responses or sensitization after noxious heating of their receptive fields. High-threshold mechanoreceptors failed to respond promptly to heat before noxious cutaneous stimulation which, however, elicited subsequent back-ground activity or sensitivity to heat. A third type of nociceptor responded to cold but not to heat. Low-threshold mechanoreceptors were identified by their brisk responses to very gentle, slowly moving mechanical stimulation of their receptive fields, and were readily distinguished from any element classified as nociceptive by their lower mechanical thresholds. Rapid innocuous warming or cooling excited some of the low-threshold mechanoreceptors. Specific thermoreceptors, both warming and cooling types, were rare, insensitive to mechanical stimulation, and responded to very slight changes in temperature. In contrast to the sensitization to heat, which was characteristic of most nociceptors, specific warming receptors displayed depressed thermal responses after noxious heating of their receptive fields. These results provide further evidence of the similarity of C-fiber receptors innervating hairy skin of different species. Some differences from past reports and additional features are described.

Discharge patterns of human C-fibers induced by itching and burning stimuli

1991 ◽  
Vol 66 (1) ◽  
pp. 307-315 ◽  
Author(s):  
H. O. Handwerker ◽  
C. Forster ◽  
C. Kirchhoff
Keyword(s):  
Receptive Fields ◽  
Radiant Heat ◽  
Single Units ◽  
Mustard Oil ◽  
Burning Pain ◽  
C Fibers ◽  
Discharge Rates ◽  
Histamine Response ◽  
Multiunit Recording ◽  
Discharge Patterns

1. The aim of this investigation was to study the peripheral neural mechanisms of the C-fiber-mediated modalities of burning pain and itch by the use of microneurography of human unmyelinated afferents. 2. Sixteen stable recordings of single C-fibers and 6 multiunit recordings were obtained from the superficial radial nerves of volunteers. All units were excited by stimulating their receptive fields with von Frey bristles (range 10-600 mN), and all but four units were also driven by radiant heat stimulation. 3. Histamine was iontophoretically applied to the receptive fields of these units for 20 or 30 s and was found to provoke itching sensations lasting several minutes, together with wheal and flare responses. Subsequently a solution containing 20 or 30% mustard oil was applied to the receptive field of the respective unit, which provoked a sensation of burning pain. 4. One-half of the units were excited by histamine, and the median discharge rates derived from interspike intervals ranged from approximately 0.1 to 0.8 Hz. Mustard oil-induced activity was observed in all histamine-sensitive units and also in three single units and in one multiunit recording that revealed no histamine response. Median interval-derived discharge rates ranged from 0.2 to 1.2 Hz. 5. Analysis of the interspike interval distribution and of the autocorrelation function derived from the chemically induced discharges of single units provided no evidence for an encoding of itch and burning pain in different discharge patterns of units responding to histamine and to mustard oil.(ABSTRACT TRUNCATED AT 250 WORDS)

Failure of sympathetic stimulation to affect responsiveness of rabbit polymodal nociceptors

1985 ◽  
Vol 54 (3) ◽  
pp. 513-519 ◽  
Author(s):  
V. K. Shea ◽  
E. R. Perl
Keyword(s):  
Impulse Activity ◽  
Receptive Fields ◽  
Testing Temperature ◽  
Maximum Temperature ◽  
Sympathetic Stimulation ◽  
Great Auricular Nerve ◽  
C Fibers ◽  
Cervical Sympathetic ◽  
Polymodal Nociceptor ◽  
Stimulation Of

The responses of polymodal nociceptors with unmyelinated (C) fibers of the rabbit's great auricular nerve were examined with and without intermittent stimulation of the ipsilateral cervical sympathetic trunk. The receptive field of each polymodal nociceptor was heated twice in a stepwise manner from 30 to 50 or 55 degrees C in 5 degree C steps. For each unit, one heating trial was a control trial and the other was accompanied by sympathetic stimulation. The order of the control and sympathetic stimulation trials and the maximum testing temperature were varied systematically among the units examined. The initial responses of polymodal nociceptors in the first heating trial in the presence of sympathetic stimulation were similar to the responses of units whose first heating was a control trial. Units whose receptive fields were tested to a maximum temperature of 50 degrees C in the first trial displayed enhanced responses to heat in their second trial (sensitization), while units tested initially to 55 degrees C responded less briskly during their second heating trial (depression). However, the occurrence of sympathetic stimulation in the second heating trials had no apparent effect on the responses to heat of sensitized or depressed elements. Alterations in the numbers of impulses, instantaneous frequency, or pattern of impulse activity of individual units could not be attributed to sympathetic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

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