Somatosensory response properties of contralaterally projecting spinothalamic and nonspinothalamic neurons in the second cervical segment of the cat

1991 ◽  
Vol 66 (1) ◽  
pp. 83-102 ◽  
Author(s):  
M. V. Smith ◽  
A. V. Apkarian ◽  
C. J. Hodge
Keyword(s):  
Dynamic Range ◽  
Cervical Spinal Cord ◽  
Average Distance ◽  
Whole Body ◽  
High Threshold ◽  
Average Depth ◽  
Spinothalamic Tract ◽  
Antidromic Activation ◽  
Response Properties ◽  
Electrolytic Lesions

1. The upper cervical spinal cord contains over one-third of the cells of the spinothalamic tract (STT). This study investigated response properties of contralaterally projecting STT neurons in C2 of the cat by the use of single-unit, microelectrode recordings. Standard antidromic stimulation and collision techniques were used to identify STT units projecting to the contralateral thalamus. Once an STT unit was found, its receptive field (RF) and responses to cutaneous stimuli such as touch, pressure, deep muscle squeeze, tap, noxious pinch, and heat were characterized. C2 units that were not activated from the contralateral thalamus (non-STT units) were also characterized. The locations of thalamic stimulation electrodes and spinal recording sites were reconstructed from electrolytic lesions. 2. A total of 48 STT and 68 non-STT units were well characterized. RF sizes were classified as small, intermediate, large, or whole body. Each unit was also classified as having one of two possible response types: simple units were those with homogeneous responses within the RF and were classified as low threshold (LT), high threshold (HT), wide dynamic range (WDR), deep, or tap. Complex units were those that responded differently in different regions of the RF. 3. The average depth of non-STT units subdivided by RF size was 2.1 +/- 0.6 (SD) mm for cells with small RFs, 2.4 +/- 0.8 mm for cells with intermediate RFs, 2.8 +/- 0.3 mm for cells with large RFs, and 2.7 +/- 0.5 mm for cells with whole-body RFs. The average depth of non-STT units based on response type was 2.0 +/- 0.5 mm for LT, 2.3 +/- 0.7 mm for HT, 2.1 +/- 0.7 mm for WDR, 2.6 +/- 0.9 mm for deep, 2.6 +/- 0.5 mm for tap, and 2.4 +/- 0.2 mm for complex. 4. A somatotopic organization along the rostrocaudal length of C2 and upper C3 was observed for non-STT units with small- and intermediate-size RFs. The average distance of the recording sites from the rostralmost dorsal rootlet of C2 was 3.8 +/- 2.1 mm for units with RFs on the face, 7.1 +/- 4.3 mm for units with RFs on the neck, and 11.9 +/- 5.1 mm for units with RFs on the forelimb. 5. The average threshold for antidromic activation of STT units was 175 +/- 120 microA. Most C2 STT units were activated from the ventroposterior region of the thalamus.(ABSTRACT TRUNCATED AT 400 WORDS)

Position of Spinothalamic Tract Axons in Upper Cervical Spinal Cord of Monkeys

2000 ◽  
Vol 84 (3) ◽  
pp. 1180-1185 ◽  
Author(s):  
Xijing Zhang ◽  
Christopher N. Honda ◽  
Glenn J. Giesler
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Dynamic Range ◽  
Cervical Spinal Cord ◽  
High Threshold ◽  
Spinothalamic Tract ◽  
Antidromic Activation ◽  
Lateral Funiculus ◽  
Upper Cervical ◽  
Low Threshold

Percutaneous upper cervical cordotomy continues to be performed on patients suffering from several types of severe chronic pain. It is believed that the operation is effective because it cuts the spinothalamic tract (STT), a primary pathway carrying nociceptive information from the spinal cord to the brain in humans. In recent years, there has been controversy regarding the location of STT axons within the spinal cord. The aim of this study was to determine the locations of STT axons within the spinal cord white matter of C2 segment in monkeys using methods of antidromic activation. Twenty lumbar STT cells were isolated. Eleven were classified as wide dynamic range neurons, six as high-threshold cells, and three as low-threshold cells. Eleven STT neurons were recorded in the deep dorsal horn and nine in superficial dorsal horn. The axons of the examined neurons were located at antidromic low-threshold points (<30 μA) within the contralateral lateral funiculus of C2. All low-threshold points were located ventral to the denticulate ligament, within the lateral half of the ventral lateral funiculus (VLF). None were found in the dorsal half of the lateral funiculus. The present findings support our previous suggestion that STT axons migrate ventrally as they ascend the length of the spinal cord. Also, the present findings indicate that surgical cordotomies that interrupt the VLF in C2 likely disrupt the entire lumbar STT.

Comparison of Responses of Primate Spinothalamic Tract Neurons to Pruritic and Algogenic Stimuli

2004 ◽  
Vol 91 (1) ◽  
pp. 213-222 ◽  
Author(s):  
Donald A. Simone ◽  
Xijing Zhang ◽  
Jun Li ◽  
Jun-Ming Zhang ◽  
Christopher N. Honda ◽  
...  
Keyword(s):  
Dynamic Range ◽  
Intradermal Injection ◽  
High Threshold ◽  
Mechanical Stimuli ◽  
Spinothalamic Tract ◽  
Wide Dynamic Range ◽  
Antidromic Activation ◽  
Lateral Nucleus ◽  
Maximal Time

We investigated the role of mechanosensitive spinothalamic tract (STT) neurons in mediating 1) the itch evoked by intradermal injection of histamine, 2) the enhanced sense of itch evoked by innocuous stroking (alloknesis), and 3) the enhanced pain evoked by punctate stimulation (hyperalgesia) of the skin surrounding the injection site. Responses to intradermal injections of histamine and capsaicin were compared in STT neurons recorded in either the superficial or the deep dorsal horn of the anesthetized monkey. Each neuron was identified by antidromic activation from the ventral posterior lateral nucleus of thalamus and classified by its initial responses to mechanical stimuli as wide dynamic range (WDR) or high-threshold (HT). Approximately half of the WDRs and one of the HTs responded weakly to histamine, some with a duration > 5 min, the maximal time allotted. WDRs but not HTs exhibited a significant increase in response to punctate stimulation after histamine consistent with their possible role in mediating histamine-induced hyperalgesia. Neither type of neuron exhibited significant changes in response to stroking, consistent with their unlikely role in mediating alloknesis. Furthermore, nearly all STT neurons exhibited vigorous and persistent responses to capsaicin, after which they became sensitized to stroking and to punctate stimulation. We conclude that the STT neurons in our sample are more likely to contribute to pain, allodynia, and hyperalgesia than to itch and alloknesis.

Spinothalamic and spinohypothalamic tract neurons in the cervical enlargement of rats. I. Locations of antidromically identified axons in the thalamus and hypothalamus

1994 ◽  
Vol 71 (3) ◽  
pp. 959-980 ◽  
Author(s):  
R. J. Dado ◽  
J. T. Katter ◽  
G. J. Giesler
Keyword(s):  
Dorsal Horn ◽  
Dynamic Range ◽  
Ventral Horn ◽  
Mechanical Stimuli ◽  
Spinothalamic Tract ◽  
Noxious Heat ◽  
Antidromic Activation ◽  
Posterior Thalamus ◽  
Electrolytic Lesions ◽  
Nociceptive Input

1. Seventy-seven neurons in the cervical enlargement of rats anesthetized with urethan were initially antidromically activated using currents < or = 30 microA from the contralateral posterior thalamus. A goal of these experiments was to determine the course of physiologically characterized spinal axons within the diencephalon. Therefore, in 38 cases, additional antidromic mapping was done throughout the mediolateral extent of the diencephalon at multiple anterior-posterior planes. 2. Electrolytic lesions marking the recording sites were recovered for 71 neurons. Thirty-one were located in the superficial dorsal horn (SDH); 39 were in nucleus proprius or the lateral reticulated area of the deep dorsal horn (DDH), and one was in the ventral horn. 3. Eight of 38 (21%) neurons that were tested for more anterior projections could only be antidromically activated with currents < or = 30 microA from sites in the contralateral posterior thalamus. Such neurons are referred to as spinothalamic tract (STT) neurons. Lesions marking the lowest threshold points for antidromic activation were located in or near the posterior thalamic group (Po). At more anterior levels, considerably higher currents were required for antidromic activation or it was not possible to activate the neurons with currents up to 500 microA. Four of these neurons were physiologically characterized and each responded preferentially to noxious mechanical stimuli (wide dynamic range, WDR). Each of the three neurons that were tested responded to noxious heat stimuli. These findings confirm anatomic studies that have shown that a number of STT axons terminate in Po and suggest that such axons that originate in the cervical enlargement carry nociceptive input from the upper extremity. 4. In 15 cases, electrode penetrations were made systematically throughout much of the contralateral ventrobasal complex (VbC). In 17 cases, penetrations were made throughout the intralaminar nuclei contralaterally, including the central lateral nucleus (CL). Surprisingly, only one of the examined axons was antidromically activated with low currents from CL and one from VbC, although both of these nuclei are known to receive sizeable inputs from the STT. 5. Many of the axons (27 of the 38 tested, 71%) that were initially antidromically activated from the contralateral posterior thalamus could also be antidromically activated with low currents (< or = 30 microA) and at increased latencies from sites located anteriorly in the contralateral hypothalamus. Such neurons are referred to as spinothalamic tract/spinohypothalamic tract (STT/SHT) neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Termination Zones of Functionally Characterized Spinothalamic Tract Neurons Within the Primate Posterior Thalamus

2008 ◽  
Vol 100 (4) ◽  
pp. 2026-2037 ◽  
Author(s):  
Steve Davidson ◽  
Xijing Zhang ◽  
Sergey G. Khasabov ◽  
Donald A. Simone ◽  
Glenn J. Giesler
Keyword(s):  
Dynamic Range ◽  
Lumbar Spinal Cord ◽  
High Threshold ◽  
Chemical Information ◽  
Thalamic Nuclei ◽  
Spinothalamic Tract ◽  
Noxious Heat ◽  
Antidromic Activation ◽  
Posterior Thalamus ◽  
Medial Geniculate

The primate posterior thalamus has been proposed to contribute to pain sensation, but its precise role is unclear. This is in part because spinothalamic tract (STT) neurons that project to the posterior thalamus have received little attention. In this study, antidromic mapping was used to identify individual STT neurons with axons that projected specifically to the posterior thalamus in Macaca fascicularis. Each axon was located by antidromic activation at low stimulus amplitudes (<30 μA) and was then surrounded distally by a grid of stimulating points in which 500-μA stimuli were unable to activate the axon antidromically, thereby indicating the termination zone. Several nuclei within the posterior thalamus were targets of STT neurons: the posterior nucleus, suprageniculate nucleus, magnocellular part of the medial geniculate nucleus, and limitans nucleus. STT neurons projecting to the ventral posterior inferior nucleus were also studied. Twenty-five posterior thalamus-projecting STT neurons recorded in lumbar spinal cord were characterized by their responses to mechanical, thermal, and chemical stimuli. Sixteen of 25 neurons were recorded in the marginal zone and the balance was located within the deep dorsal horn. Thirteen neurons were classified as wide dynamic range and 12 as high threshold. One-third of STT neurons projecting to posterior thalamus responded to noxious heat (50°C). Two-thirds of those tested responded to cooling. Seventy-one percent responded to an intradermal injection of capsaicin. These data indicate that the primate STT transmits noxious and innocuous mechanical, thermal, and chemical information to multiple posterior thalamic nuclei.

Primate nucleus gracilis neurons: responses to innocuous and noxious stimuli

1988 ◽  
Vol 59 (3) ◽  
pp. 886-907 ◽  
Author(s):  
D. G. Ferrington ◽  
J. W. Downie ◽  
W. D. Willis
Keyword(s):  
Conduction Velocity ◽  
Dynamic Range ◽  
Subcutaneous Tissue ◽  
Receptive Fields ◽  
High Threshold ◽  
Spinothalamic Tract ◽  
Sinusoidal Vibration ◽  
Nucleus Gracilis ◽  
Pressure Sensitive ◽  
Stimulation Of

1. Recordings were made from 67 neurons in the nucleus gracilis (NG) of anesthetized macaque monkeys. All of the cells were activated antidromically from the ventral posterior lateral (VPL) nucleus of the contralateral thalamus. Stimuli used to activate the cells orthodromically were graded innocuous and noxious mechanical stimuli, including sinusoidal vibration and thermal pulses. 2. The latencies of antidromic action potentials following stimulation in the VPL nucleus were significantly shorter for cells in the caudal compared with the rostral NG. The mean minimum afferent conduction velocity of the afferent conduction velocity of the afferent fibers exciting the NG cells was 52 m/s, as judged from the latencies of the cells to orthodromic volleys evoked by electrical stimulation of peripheral nerves. The overall conduction velocity of the pathway from peripheral nerve to thalamus was approximately 40 m/s. 3. Cutaneous receptive fields on the distal hindlimb usually occupied an area equivalent to much less than a single digit. However, a few cells had receptive fields up to or exceeding the area of the foot. 4. NG cells were classified by their responses to graded mechanical stimulation of the skin as low threshold (LT) or wide dynamic range (WDR). No high-threshold NG cells were found. A special subcategory of pressure-sensitive LT (SA) neurons was recognized. Many of these cells were maximally responsive to maintained indentation of the skin. The sample of NG cells differed from the population of primate spinothalamic and spinocervicothalamic pathways so far examined, in having a larger proportion of LT neurons and a smaller proportion of WDR cells. A few NG cells responded best to manipulation of subcutaneous tissue. 5. Discriminant analysis permitted the NG cells to be assigned to classes determined by a k-means cluster analysis of the responses of a reference set of 318 primate spinothalamic tract (STT) cells. There were four classes of cells based on normalized responses of individual neurons and another four classes based upon responses compared across the population of cells. The NG cells were allocated to the various categories in different proportions than either primate STT cells or spinocervicothalamic neurons, consistent with the view that the functional roles of these somatosensory pathways differ. 6. Some of the pressure-sensitive NG cells were excited when the skin was stretched, suggesting an input from type II slowly adapting (Ruffini) mechanoreceptors.(ABSTRACT TRUNCATED AT 400 WORDS)

Responses of primate T1-T5 spinothalamic neurons to gallbladder distension

1984 ◽  
Vol 247 (6) ◽  
pp. R995-R1002 ◽  
Author(s):  
W. S. Ammons ◽  
R. W. Blair ◽  
R. D. Foreman
Keyword(s):  
Chest Pain ◽  
Dynamic Range ◽  
Discharge Rate ◽  
Gallbladder Disease ◽  
High Rate ◽  
High Threshold ◽  
Spinothalamic Tract ◽  
Left Chest ◽  
Afferent Fibers ◽  
Upper Thoracic

Extracellular unit recordings were obtained from 44 spinothalamic tract (STT) neurons in the T1-T5 segments of 15 alpha-chloralose anesthesized monkeys (Macaca fascicularis). Each cell had a somatic receptive field in the left chest region and was excited by electrical stimulation of cardiopulmonary sympathetic afferent fibers. Gallbladder distension to pressures between 20 and 100 mmHg increased activity in 16 of 44 neurons. Responses usually consisted of bursts of activity associated with increased gallbladder pressure (phasic responses) followed by maintained activity during the distension (tonic responses). Magnitude of phasic responses was linearly related to the distending pressure and was consistently greater than magnitude of tonic responses. The gallbladder-responsive and nonresponsive groups included similar proportions of wide dynamic range, high threshold, and high-threshold inhibitory cells. Nine of 10 gallbladder-responsive cells and 11 of 21 gallbladder-nonresponsive cells increased their discharge rate after injection of 2 micrograms/kg bradykinin into left atrium. Activity of cells with gallbladder input increased from 14 +/- 4 to 33 +/- 4 spikes/s. Cells without gallbladder input increased their discharge rate to a significantly less degree (10 +/- 3-23 +/- 4 spikes/s). These results indicate that upper thoracic STT neurons may increase their activity during gallbladder distension. Convergence of afferent information from the chest and gallbladder may explain chest pain occurring during gallbladder disease. Furthermore the tendency of gallbladder-responsive cells to respond to bradykinin injections with a high rate of discharge could explain how this chest pain of gallbladder origin may closely mimic pain of angina pectoris.

Grouping of somatosensory neurons in the spinal cord and the gracile nucleus of the rat by cluster analysis

1994 ◽  
Vol 72 (6) ◽  
pp. 2590-2597 ◽  
Author(s):  
J. W. Leem ◽  
B. H. Lee ◽  
W. D. Willis ◽  
J. M. Chung
Keyword(s):  
Cluster Analysis ◽  
Dorsal Horn ◽  
Dynamic Range ◽  
High Threshold ◽  
Spinothalamic Tract ◽  
Wide Dynamic Range ◽  
Gracile Nucleus ◽  
Noxious Stimuli ◽  
Thermal Stimuli ◽  
Wide Dynamic Range Neurons

1. A set of 11 cutaneous stimuli defined previously to differentiate among different types of cutaneous sensory receptors in the rat hindpaw was also effective in differentially activating second-order sensory neurons in the dorsal horn and the gracile nucleus of rats. 2. All sampled units were responsive to more than 1 of the 11 stimuli. However, none responded to innocuous warming or cooling stimuli. Therefore further analysis was restricted to responses to nine of the selected stimuli. 3. Cluster analysis of the responses to nine selected innocuous and noxious mechanical stimuli and noxious thermal stimuli yielded seven classes that seemed functionally distinct from each other: a class of high-threshold neurons, three classes of convergent (wide dynamic range) neurons, a class of a mixture of poorly responsive neurons and neurons receiving Pacinian inputs, and two classes of low-threshold neurons. 4. High-threshold neurons responded predominantly to noxious mechanical and thermal stimuli and presumably received an input from both mechanically and thermally sensitive nociceptors. These cells were located in the dorsal horn, and some were spinothalamic tract cells. Wide dynamic range neurons were excited by innocuous and noxious stimuli, but better by noxious stimuli. These classes of cells were either in the dorsal horn (some were spinothalamic tract cells) or in the nucleus gracilis.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of primate spinothalamic tract neurons by stimulation in periaqueductal gray or adjacent midbrain reticular formation

1984 ◽  
Vol 51 (3) ◽  
pp. 450-466 ◽  
Author(s):  
K. D. Gerhart ◽  
R. P. Yezierski ◽  
T. K. Wilcox ◽  
W. D. Willis
Keyword(s):  
Spinal Cord ◽  
Reticular Formation ◽  
Dynamic Range ◽  
Periaqueductal Gray ◽  
Noxious Stimulation ◽  
Spinothalamic Tract ◽  
Antidromic Activation ◽  
Lateral Funiculus ◽  
C Fibers ◽  
Midbrain Reticular Formation

Recordings were made from spinothalamic tract (STT) cells in the lumbosacral enlargement of anesthetized monkeys. The cells were identified by antidromic activation from the contralateral ventral posterior lateral nucleus of the thalamus. Electrical stimulation at sites within the periaqueductal gray, the adjacent midbrain reticular formation, or the deep layers of the tectum were found to inhibit the activity of STT cells. In general, midbrain stimulation inhibited the background discharges and the responses of wide dynamic range cells evoked by innocuous and noxious cutaneous stimulation (29 of 37 cases). However, for six cells, midbrain stimulation preferentially inhibited the responses to noxious stimulation. The evoked responses of all 10 high-threshold cells were inhibited. In only two cases was midbrain stimulation ineffective, and no excitatory effects were observed. The mean latency to onset of inhibition resulting from midbrain stimulation was 24.9 +/- 7.2 ms (n = 35). The amount of inhibition produced by midbrain stimulation was graded with stimulus intensity. For example, trains of stimuli (333 Hz) at 50 microA produced a mean inhibition to 81.7 +/- 16.6% of control, while 200 microA resulted in a mean inhibition to 36.3 +/- 21.7%. Not only was the inhibition increased by the use of stronger current intensities, but the duration of inhibition was prolonged. Midbrain stimulation inhibited the responses of STT cells to volleys in both the A-fibers and the C-fibers of the sural nerve. However, there was a selective action in that the responses to C-fiber volleys were more strongly inhibited than were the responses to A-fiber volleys. Lesions placed in the white matter of the upper cervical spinal cord reduced the inhibition produced by stimulation in either the midbrain or the nucleus raphe magnus. The extent to which the inhibition was reduced was proportional to the extent of the cord lesions. However, even when there was an interruption of the entire lateral funiculus on the side of an STT cell and of the dorsal quadrant of the contralateral side, there was still substantial inhibition following stimulation in either brain stem site. It is concluded that while part of the inhibition is mediated by pathways descending in the dorsal lateral funiculus (DLF), at least some depends on pathways coursing through the ventral spinal cord. Inhibition of STT cells may contribute to the neuronal mechanism of the analgesia that results from stimulation in the periaqueductal gray matter in awake, behaving animals.

Inhibition of Primate Spinothalamic Tract Neurons by Spinal Glycine and GABA Is Modulated by Guanosine 3′,5′-Cyclic Monophosphate

1999 ◽  
Vol 81 (3) ◽  
pp. 1095-1103 ◽  
Author(s):  
Qing Lin ◽  
Jing Wu ◽  
Yuan Bo Peng ◽  
Minglei Cui ◽  
William D. Willis
Keyword(s):  
Signal Transduction ◽  
Dorsal Horn ◽  
Central Sensitization ◽  
Dynamic Range ◽  
Cgmp Level ◽  
High Threshold ◽  
Descending Inhibition ◽  
Spinothalamic Tract ◽  
Cyclic Monophosphate ◽  
Deep Layers

Inhibition of primate spinothalamic tract neurons by spinal glycine and GABA is modulated by guanosine 3′,5′-cyclic monophosphate. Our recent work has suggested that the nitric oxide/guanosine 3′,5′-cyclic monophosphate (NO/cGMP) signal transduction system contributes to central sensitization of spinothalamic tract (STT) neurons in part by influencing the descending inhibition of nociception resulting from stimulation in the periaqueductal gray. This study was designed to examine further whether activation of the NO/cGMP cascade reduces the inhibition of the activity of STT neurons mediated by spinal inhibitory amino acid (IAA) receptors. Responses of STT cells to noxious cutaneous stimuli were inhibited by iontophoresis of glycine and GABA agonists in anesthetized monkeys. Administration of 8-bromoguanosine-3′,5′-cyclophosphate sodium (8-bromo-cGMP), a membrane permeable analogue of cGMP, either by microdialysis or by iontophoresis reduced significantly the IAA-induced inhibition of wide dynamic range (WDR) STT cells in the deep layers of the dorsal horn. The reduction in inhibition lasted for up to 1–1.5 h after the cessation of drug infusion. In contrast, IAA-induced inhibition of WDR STT cells in the superficial dorsal horn and high-threshold (HT) cells in superficial or deep layers was not significantly changed during 8-bromo-cGMP infusion. Iontophoresis of 8-bromo-cGMP onto STT cells produced the same actions as produced by microdialysis of this agent, but the effect was not as long-lasting nor as potent. Finally, an attenuation of the IAA receptor–mediated inhibition of STT cells produced by iontophoretic release of a NO donor, 3-morpholinosydnonimine, could be blocked by pretreatment of the spinal cord with a guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one. These results suggest that an increased spinal cGMP level contributes to the sensitization of WDR STT neurons in the deep dorsal horn in part by down-regulating spinal IAA receptors. However, no evidence is provided in this study that the NO/cGMP cascade regulates IAA receptors on HT and superficial WDR neurons. Combined with the preceding studies, our data support the view that NO and cGMP function in the same signal transduction cascade and play an important role in central sensitization.

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.

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