PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Spinothalamic Tracts”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources

Inhibition of primate spinothalamic tract neurons by stimulation in ipsilateral or contralateral ventral posterior lateral (VPLc) thalamic nucleus.

The effects of stimulation in the ventral posterior lateral (VPLc) thalamic nuclei on the activity of primate spinothalamic tract neurons were investigated. All 19 cells studied were strongly inhibited by conditioning trains of stimuli delivered to either ipsilateral or contralateral VPLc. Both background discharges and activity evoked by innocuous or noxious cutaneous stimulation were inhibited.

Animals↗

Comparative study of viscerosomatic input onto postsynaptic dorsal column and spinothalamic tract neurons in the primate.

The purpose of the present investigation was to examine, in the primate, the role of the postsynaptic dorsal column (PSDC) system and that of the spinothalamic tract (STT) in viscerosensory processing by comparing the responses of neurons in these pathways to colorectal distension (CRD). Experiments were done on four anesthetized male monkeys (Macaca fascicularis). Extracellular recordings were made from a total of 100 neurons randomly located in the L(6)-S(1) segments of the spinal cord. Most of these neurons had cutaneous receptive fields in the perineal area, on the hind limbs or on the rump. Forty-eight percent were PSDC neurons activated antidromically from the upper cervical dorsal column or the nucleus gracilis, 17% were STT neurons activated antidromically from the thalamus, and 35% were unidentified. Twenty-one PSDC neurons, located mostly near the central canal, were excited by CRD and three were inhibited. Twenty-four PSDC neurons, mostly located in the nucleus proprius, did not respond to CRD. Of the 17 STT neurons, 7 neurons were excited by CRD, 4 neurons were inhibited, and 6 neurons did not respond to CRD. Of the unidentified neurons, 23 were excited by CRD, 7 were inhibited, and 5 did not respond. The average responses of STT and PSDC neurons excited by CRD were comparable in magnitude and duration. These results suggest that the major role of the PSDC pathway in viscerosensory processing may be due to a quantitative rather than a qualitative neuronal dominance over the STT.

Animals↗

Effects of iontophoretically released amino acids and amines on primate spinothalamic tract cells.

The effects of glutamate (Glu), gamma-aminobutyric acid (GABA), glycine (Gly), serotonin (5-HT), norepinephrine (NE), dopamine (DA), and acetylcholine (ACh) were examined in this study by iontophoretic application onto primate spinothalamic tract (STT) neurons identified antidromically by stimulation in the contralateral thalamus. Drugs were tested for effects on background activity, Glu-induced firing, and activity evoked by pinching of the skin. Whereas Glu excited STT cells and was thus used for tests of the other compounds, the amino acids GABA and Gly inhibited Glu- and pinch-induced activity in all STT cells examined. STT cells were also inhibited by 5-HT, NE, and DA. Only two cases of excitation by 5-HT were seen (of 58 cells tested). ACh also had inhibitory actions on STT cells, although 3 of 21 cells exhibited some enhancement of activity. The effects of these compounds on identified STT cells resemble previous demonstrations of the effects of these drugs on dorsal horn interneurons. The results suggest that GABA, Gly, 5-HT, NE, and DA may be inhibitory neurotransmitters on nociceptive STT cells.

Acetylcholine↗

Collaterals of spinothalamic tract cells to the periaqueductal gray: a fluorescent double-labeling study in the rat.

Spinothalamic tract (STT) cells were investigated in the rat to determine the distribution of STT cells with terminals in both the ventrobasal (VB) thalamus and the lateral periaqueductal gray (PAG). Two retrogradely transported fluorescent dyes (Diamidino yellow and Granular blue) were injected into each animal. The distribution of single- and double-labeled cells was mapped in the cervical, thoracic, lumbar and sacral spinal cord. An average of 1.4% of all STT cells and 6.2% of PAG cells projected to both VB thalamus and PAG. Double-labeled cells were observed only in cervical and lumbar levels of the spinal cord, with the greatest number found in the cervical enlargement. The double-labeled cells were located in laminae I and V and also in the lateral spinal nucleus (LSN). The number of double-labeled cells found in each of these 3 areas varied depending on the spinal cord level. This population of neurons exhibiting collaterals provide an anatomical mechanism by which noxious stimuli activate neurons not only in the thalamus but also in the PAG, which is an area involved in stimulation-produced analgesia (SPA).

Animals↗

Convergence of phrenic and cardiopulmonary spinal afferent information on cervical and thoracic spinothalamic tract neurons in the monkey: implications for referred pain from the diaphragm and heart.

1. Spinothalamic tract (STT) neurons in the C3-T6 spinal segments were studied for their responses to stimulation of phrenic and cardiopulmonary spinal afferent fibers. A total of 142 STT neurons were studied in 44 anesthetized, paralyzed monkeys (Macaca fascicularis). All neurons were antidromically activated from the ventroposterolateral nucleus and/or medial thalamus. 2. Electrical stimulation of phrenic afferent fibers (PHR) excited 43/58 (74%), inhibited 2/58 (3%), and did not affect 13/58 (13%) of cervical STT neurons. Neurons with excitatory somatic fields confined to the proximal limb or encompassing the whole limb were excited to a significantly greater extent by electrical stimulation of PHR than were neurons with somatic fields confined to the distal limb. Mechanical stimulation of PHR by probing the exposed diaphragm excited 11/22 (50%), inhibited 3/22 (14%), and did not affect 8/22 (36%) cervical STT neurons. 3. The technique of minimum afferent conduction velocity (MACV) was used to obtain information about the identity of the PHR that excited 35 cervical STT neurons. Evidence was obtained for excitation of these neurons by group II and III PHR. The mean +/- SE MACV for all neurons was 14 +/- 2 m/s. 4. Electrical stimulation of cardiopulmonary spinal afferent fibers excited 41/57 (72%), inhibited 8/57 (14%), and did not affect 8/57 (14%) of cervical STT neurons. Neurons with excitatory somatic fields confined to the proximal limb or encompassing the whole limb were excited to a significantly greater extent by electrical stimulation of cardiopulmonary spinal afferents than were neurons with somatic fields confined to the distal limb. 5. Excitatory convergence of PHR and cardiopulmonary spinal afferent input was observed for 36/57 (63%) cervical STT neurons. 6. Electrical stimulation of PHR excited 36/84 (43%), inhibited 25/84 (30%), and did not affect 23/84 (27%) of thoracic STT neurons. All of these neurons received excitatory cardiopulmonary spinal afferent input. 7. Neurons were more likely to be excited by electrical stimulation of PHR if they were located in C3-C6 spinal segments. Furthermore, the net excitatory effect of PHR input decreased in more caudal segments, such that thoracic STT neurons were weakly excited relative to cervical STT neurons. 8. We conclude that cervical STT neurons with excitatory somatic fields that include or are restricted to proximal sites are excited by electrical or mechanical stimulation of PHR. Those effects demonstrate a physiological substrate for pain referred from the diaphragm to the shoulder in patients with pleural effusions or subphrenic abscesses.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

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.

Animals↗

Position of spinothalamic tract axons in upper cervical spinal cord of monkeys.

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 microA) 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.

Action Potentials↗

Role of GABA receptor subtypes in inhibition of primate spinothalamic tract neurons: difference between spinal and periaqueductal gray inhibition.

1. gamma-Aminobutyric acid (GABA) is thought to inhibit both pre- and postsynaptically the transfer of nociceptive signals from primary afferent fibers to spinal dorsal horn sensory cells, including spinothalamic tract (STT) neurons. The inhibition can be mediated by both GABAA and GABAB receptors. We now attempt to characterize the synaptic inhibition of STT cells by spinal GABAA and GABAB receptors in anesthetized monkeys and to analyze the roles of these two receptor subtypes in the inhibition of STT cellular activity produced by stimulation in the periaqueductal gray (PAG). 2. Iontophoretic release of GABA or muscimol (a selective GABAA receptor agonist) onto STT cells elicited a profound and dose-related inhibition of the responses of all cells tested to noxious cutaneous stimuli. Only four cells (16.7%) were found to be inhibited when baclofen (a selective GABAB receptor agonist) was applied iontophoretically. However, a strong and dose-dependent inhibition of the responses to cutaneous mechanical and thermal stimuli was obtained in all cells examined when baclofen was administered into the dorsal horn through a microdialysis fiber. The inhibitory effects were mainly on nociceptive inputs. 3. The inhibition of cellular activity by GABAA and GABAB agonists could be selectively antagonized by specific antagonists applied through a microdialysis fiber. 4. The excitatory responses evoked by pulsed release of glutamic acid (GLUT) were also inhibited in a dose-related manner by iontophoretic application of GABA and muscimol, but not by baclofen. A high dose of baclofen administered by microdialysis resulted in only a small decrease in GLUT-evoked excitatory responses. 5. Infusion of GABAA and GABAB antagonists into the dorsal horn by microdialysis caused an increase in both background activity and responses to cutaneous stimuli, suggesting that there is a tonic GABAergic inhibition of STT cells. 6. The inhibition of responses to mechanical and thermal stimulation of the cutaneous excitatory receptive field resulting from stimulation in PAG was significantly antagonized in most of the STT cells tested when the GABAA antagonist bicuculline was infused into the spinal dorsal horn through a microdialysis fiber. In contrast, the inhibition produced by PAG stimulation in most of the cells examined was not significantly antagonized by the GABAB antagonists phaclofen or 3-amino-propyl(diethoxymethyl)phophinic acid (CGP35348) administered into the spinal dorsal horn by microdialysis. 7. Our results support the contention that GABAergic mechanisms in the spinal dorsal horn normally exert a tonic modulation of nociceptive inputs through both GABAA and GABAB receptors. The evidence provided here indicates that GABAA receptors located on primate STT neurons contribute to a postsynaptic inhibitory effect on the transmission of peripheral nociceptive inputs. A possible presynaptic GABAA action was not investigated. Our finding of a GABAB-receptor-mediated inhibition is consistent with the view that both pre- and postsynaptic GABAB receptors are involved in inhibitory modulation of spinal nociceptive transmission. Finally, it is suggested from this study that primate spinal GABAA, but not GABAB receptors, are involved in mediating the descending inhibition induced by PAG stimulation.

Animals↗

Effects of capsaicin applied to a peripheral nerve on the responses of primate spinothalamic tract cells.

Capsaicin is a neurotoxin that appears to affect unmyelinated nociceptive sensory fibers selectively. We examined the effects of capsaicin applied topically to the sural nerve on peripheral nerve volleys and on the responses of neurons belonging to the spinothalamic tract (STT) in the monkey. The responses examined included those following electrical stimulation of the sural nerve and also those produced by more natural forms of noxious and innocuous stimuli applied to the skin. Capsaicin (1% solution) applied onto the sural nerve for 15 min resulted in a reduction of the sizes of A delta- and C-fiber afferent volleys. These changes paralleled the reduction of A- and C-fiber responses of the STT cells elicited by electrical stimulation of the sural nerve. During capsaicin application onto the sural nerve, the background activity of STT cells increased for 5-10 min. After capsaicin treatment, the responses of STT cells to innocuous mechanical stimuli applied to the cutaneous receptive field were increased, whereas the responses to noxious mechanical stimuli were decreased. However, topical capsaicin application almost eliminated the responses of STT cells to noxious heat stimuli. The results of the present study suggest that topical capsaicin application onto a peripheral nerve produces a transient nociceptive response followed by a decrease in sensitivity to noxious stimuli, particularly to noxious heat. These changes are due to conduction block of the nerve fibers at the site of capsaicin application.

Animals↗

Neurokinin 1 and 2 antagonists attenuate the responses and NK1 antagonists prevent the sensitization of primate spinothalamic tract neurons after intradermal capsaicin.

1. Activation of neurokinin receptors contributes to the excitation of many dorsal horn neurons by cutaneous sensory stimuli, particularly noxious stimuli. In the present study we investigate the role of neurokinin receptors in the activation of primate spinothalamic tract (STT) neurons by cutaneous mechanical stimuli and by intradermal injection of capsaicin. This was done by testing the responses of these neurons to a battery of cutaneous stimuli before and during infusion by microdialysis of antagonists selective for NK1 and NK2 receptors. 2. The NK1 receptor antagonists cis-3-(2-methoxybenzyl-amino-2-benzhydrylquinuclidine (CP96345) and D-Pro9-[Spiro-y-lactam]-Leu10,Trp11)-Physalaemin(1-11) (GR82334) did not significantly reduce the responses of STT cells to mechanical stimulation of the skin. Both NK1 antagonists did, however, produce a significant reduction in the responses of STT neurons to an intradermal injection of capsaicin. Finally, despite having no effects on responses to mechanical stimuli, both NK1 antagonists prevented the sensitization of the responses to cutaneous stimuli that is usually observed after intradermal injections of capsaicin. 3. The NK2 selective antagonists PhCO-Ala-Ala-D-Trp-Phe-D-Pro-Pro-Nle-NH2 (GR98400) and [Tyr5,D-Trp6,8,9,Lys10]-NKA (4-10) (MEN10376) had effects very similar to those of the NK1 antagonists, but with an important difference. Neither NK2 antagonist affected the responses of STT neurons to noxious or innocuous mechanical stimulation of the skin, but they did reduce the responses to intradermal capsaicin injections. These compounds failed to prevent capsaicin-induced sensitization. In fact, cells exposed to GR98400 or MEN10376 showed unusually sustained increases in the responses to mechanical stimuli after the first capsaicin injection, suggesting that these compounds actually induced sensitization. 4. These results support the contention that both neurokinin receptors participate in the processing of nociceptive information in the dorsal horn, especially responses to strong stimuli such as intradermal injection of capsaicin. NK1 receptors are also involved in the sensitization of STT neurons after peripheral injury. A clearer understanding of the role of NK2 receptors in sensitization requires further studies with improved antagonists.

Animals↗

Nitric oxide mediates the central sensitization of primate spinothalamic tract neurons.

Nitric oxide (NO) has been proposed to contribute to the development of hyperalgesia by activating the NO/guanosine 3',5'-cyclic monophosphate (cGMP) signal transduction pathway in the spinal cord. We have examined the effects of NO on the responses of primate spinothalamic tract (STT) neurons to peripheral cutaneous stimuli and on the sensitization of STT cells following intradermal injection of capsaicin. The NO level within the spinal dorsal horn was increased by microdialysis of a NO donor, 3-morpholinosydnonimine (SIN-1). SIN-1 enhanced the responses of STT cells to both weak and strong mechanical stimulation of the skin. This effect was preferentially on deep wide dynamic range STT neurons. The responses of none of the neurons tested to noxious heat stimuli were significantly changed when SIN-1 was administered. Intradermal injection of capsaicin increased dramatically the content of NO metabolites, NO-2/NO-3, within the dorsal horn. This effect was attenuated by pretreatment of the spinal cord with a nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester (L-NAME). Sensitization of STT cells induced by intradermal injection of capsaicin was also prevented by pretreatment of the dorsal horn with the NOS inhibitors, L-NAME or 7-nitroindazole. Blockade of NOS did not significantly affect the responses of STT cells to peripheral stimulation in the absence of capsaicin injection. The data suggest that NO contributes to the development and maintenance of central sensitization of STT cells and the resultant mechanical hyperalgesia and allodynia after peripheral tissue damage or inflammation. NO seems to play little role in signaling peripheral stimuli under physiological conditions.

Animals↗

Conduction velocity of the spinothalamic tract following CO2 laser stimulation of C-fibers in humans.

Pain-related somatosensory-evoked potential following CO(2) laser stimulation (laser-evoked potential (LEP)) is now used not only for research objectives, but also for clinical applications. Estimating the conduction velocity (CV) of the spinothalamic tract (STT) by analyzing LEP following activation of Adelta-fibers (Adelta-CVSTT) by CO(2) laser stimulation has been performed previously, but estimating the CV of STT following activation of C-fibers (C-CVSTT) has not. This is the first report to estimate the C-CVSTT in humans; by using the novel method of CO(2) laser stimulation applied to tiny skin areas. The calculation method was based on that of Kakigi and Shibasaki (Electroenceph clin Neurophysiol 80 (1991) 39) who measured Adelta-CVSTT by conventional CO(2) laser stimulation. The C-CVSTT ranged between 1.4 and 4.0 m/s, and its mean+/-SD was 2.9+/-0.8 m/s. This C-CVSTT was significantly slower than the Adelta-CVSTT, which ranged approximately from 10 to 21 m/s. The nociceptive signal of the C-fibers in STT is probably conveyed by unmyelinated axons of projection neurons to reach the thalamus. Our findings provide the first physiological evidence of the signals ascending through unmyelinated axons in the spinal cord in humans. In addition, estimating C-CVSTT and Adelta-CVSTT combined with conventional methods to measure the CV of the posterior column using electrical stimulation should be useful and have important clinical applications, particularly in patients with spinal cord lesions showing various kinds of sensory disturbances.

Adult↗

Physiological study of the spinothalamic tract conduction in multiple sclerosis.

This is the first paper to study the physiological function of the spinothalamic tract in multiple sclerosis (MS) using pain-related somatosensory evoked potentials (pain SEPs) following CO2 laser stimulation. Among 12 patients with MS, hand- and foot-stimulated pain SEPs were significantly delayed or absent in 3 and 7, respectively. These results were totally consistent with clinical impairment of pain-temperature sensation. In contrast, the results of conventional electrically-stimulated SEPs were compatible with impairment of vibration sensation. Therefore, the examination of both pain and electric SEPs is very useful to evaluate the physiological function of the ascending spinal tract in patients with MS.

Adult↗

Combined application of excitatory amino acids and substance P produces long-lasting changes in responses of primate spinothalamic tract neurons.

Sensitization of dorsal horn neurons following injury may underlie the generation of secondary hyperalgesia and so the chemical basis of sensitization is now receiving considerable attention. The present study used microiontophoretic applications of excitatory amino acids (EAA's) and substance P (SP) to test their roles in the sensitization of primate spinothalamic tract (STT) neurons. Of 70 STT cells examined in laminae I-VI of the dorsal horn, 40 showed an increase in responses to one or more EAA's following their co-application with SP. The increased responses were usually specific to either N-methyl-D-aspartate (NMDA) or to the non-NMDA agonists, quisqualate (QUIS) or D,L-alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA). The enhancement of EAA responses was long-lasting (> 15 min) in 18 cases, was accompanied by similarly long-lasting increases in responses to mechanical stimulation of the receptive field in 14 cases and was accompanied by an increase in responses to either glutamate (Glu) or aspartate (Asp) in eleven cases. A global decrease in all EAA responses tested was produced in 26 other STT neurons. The inhibition, unlike the increases, was generalized to both NMDA and non-NMDA ligands, was long-lasting in only six cases and was never accompanied by a change in the responses to mechanical stimuli. The excitatory and inhibitory effects of SP on the responses to NMDA were uniformly reversed by the NK-1 receptor selective antagonist, CP96345. In contrast, only the inhibitory effects of SP on the responses to QUIS or AMPA were reversed by CP96345. The long-lasting enhancement of EAA responses by SP may follow the combined synaptic release of the natural ligands in vivo, resulting in the sensitization of dorsal horn neurons and secondary hyperalgesia. However, the reductions in EAA responses produced by SP are problematic for this hypothesis and need further elucidation.

Amino Acids↗

Dextrorphan attenuates responses of spinothalamic tract cells in normal and nerve-injured monkeys.

Spinal cord N-methyl-D-aspartate (NMDA) receptors play an important role in the transmission of acute and chronic pain. The present study investigated the ability of dextrorphan (DEX), a metabolite of dextromethorphan and a clinically safe NMDA antagonist, to attenuate the responses of nociceptive spinothalamic tract (STT) neurons in anesthetized monkeys. The STT cells were recorded extracellularly in the lumbosacral enlargement and were identified by antidromic activation from the ventral posterior lateral thalamic nucleus. DEX administered through a microdialysis fiber inserted into the dorsal horn inhibited the responses of STT cells in normal animals to noxious pinch and heat stimuli. In monkeys made neuropathic by tight ligation of the L7 or S1 spinal nerve, DEX significantly attenuated the responses of STT cells to noxious pinch and heat, as well as to innocuous brushing, pressure and von Frey filament stimuli. These findings strongly suggest that DEX should be considered a potentially useful therapeutic agent for the treatment of neuropathic pain in humans.

Animals↗

Vagal, sympathetic and somatic sensory inputs to upper cervical (C1-C3) spinothalamic tract neurons in monkeys.

1. Myocardial ischemia activates vagal and sympathetic cardiac afferent fibers. The purpose of this study was to determine a neuro physiological basis for cardiac pain referred to C1-C3 somatic dermatomes. We hypothesized that afferent fibers traveling in vagal or sympathetic nerves transmit nociceptive information to C1-C3 spinothalamic tract (STT) neurons. 2. Electrical stimulation of the left stellate ganglion to excite cardiopulmonary sympathetic afferent fibers increased extracellular activity of 44 of 77 C1-C3 STT neurons examined in 33 anesthetized male monkeys (Macaca fascicularis); responses increased as stimulus strength increased. Additionally, this stimulus inhibited 5 cells, increased/decreased activity of 2 cells, and did not affect 26 cells. 3. Electrical stimulation of the left (ipsilateral) thoracic vagus nerve excited 41 of 78 C1-C3 STT neurons, inhibited 4 neurons, increased/decreased activity of 2 neurons, and did not affect 31 neurons. Responses increased with increasing stimulus strength Contralateral vagal stimulation excited 7 of 39 cells tested, inhibited 4 cells and did not affect 28 cells. 4. Effects of stimulating one or more vagal branches were examined on 22 C1-C3 STT neurons excited by input from left thoracic vagus nerve. Stimulation of the cardiac branch excited 11 of 16 cells tested; stimulation of the recurrent laryngeal nerve excited 11 of 18 cells; stimulation of vagal fibers just rostral to the diaphragm excited 8 of 19 cells. 5. Excitatory somatic receptive fields ranged from small ipsilateral fields to large, sometimes bilateral or noncontinuous fields. Many fields included the ipsilateral neck and/or inferior jaw. Thirty-nine of 74 neurons examined were wide dynamic range (WDR), 21 were high threshold (HT), 6 were low threshold (LT), and 8 did not respond to brushing or noxious pinching of somatic tissues. Most (38 of 39) WDR cells responded to stimulation of the stellate ganglion or vagal fibers, as did 18 of 21 HT cells, 3 of 6 LT cells, and 2 of 8 cells unresponsive to brush or pinch stimuli. 6. Results of this study supported the concept that vagal and/ or sympathetic afferent activation of C1-C3 STT neurons might provide a neural mechanism for referred pain that originates in the heart or other visceral organs but is perceived in the neck and jaw region. Additionally, C1-C3 STT neurons processed sensory information from widespread regions of the body.

Adrenergic Fibers↗

Effects of protein kinase a activation on the responses of primate spinothalamic tract neurons to mechanical stimuli.

Behavioral and anatomical studies by our group have suggested that the protein kinase A (PKA) signal transduction cascade contributes to long-term changes in nociceptive processing at the spinal cord level. In this study, we have examined the effects of activation of the PKA cascade on the responses of spinothalamic tract (STT) neurons to peripheral mechanical stimuli in anesthetized and paralyzed monkeys. PKA in the spinal cord was activated by intra-spinal infusion of forskolin, an activator of adenylate cyclase, by microdialysis. There was a consistent increase in responses to mechanical pressure and pinch stimuli in all STT cells tested when forskolin was administered. Enhanced responses remained at relatively high levels when forskolin had been washed out for 30 min. However, in most STT cells tested (65%), the responses to brushing stimuli were not obviously changed when forskolin was given. Background activity was slightly increased when forskolin was administered. An inactive isomer of forskolin, D-forskolin, did not produce significant effects on cellular activity. The sensitization of STT cells to noxious mechanical stimuli produced by forskolin could be blocked by pretreatment of the spinal cord with the PKA inhibitor, N-[2-((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamine (H89). The same dose of H89 did not affect the enhanced responses to mechanical stimuli produced by activation of protein kinase G by intra-spinal infusion of 8-bromo-cGMP, indicating that the effect of forskolin was selective. The present data suggest that activation of PKA can preferentially enhance the responses of STT cells to noxious mechanical stimuli without producing an increase in responses to innocuous brushing stimuli. We speculate that the PKA signal transduction cascade may contribute more to secondary mechanical hyperalgesia than to secondary mechanical allodynia.

Animals↗

GABA-immunoreactive terminals synapse on primate spinothalamic tract cells.

Gamma-aminobutyric acid (GABA) is a putative inhibitory neurotransmitter in the vertebrate nervous system. Several lines of evidence suggest that GABA plays an important role in the processing and modulation of sensory input in the spinal cord dorsal horn. In the present study, the relationship between GABA-immunoreactive (GABA-IR) terminals and spinothalamic tract (STT) cells in the monkey lumbar cord was investigated. Physiologically characterized STT cells, one located in lamina V and two located in lateral lamina IV, were intracellularly injected with horseradish peroxidase (HRP). A fourth STT cell, located in lamina I, was retrogradely labeled following injection of HRP into the contralateral thalamus. Immunogold labeling of ultrathin sections through the cell bodies and proximal dendrites of the STT neurons demonstrated that the percentage of the GABA-IR terminals in contact with these profiles was 24.7% and 36%, respectively. The average STT surface length contacted by GABA-IR terminals for cell bodies and proximal dendrites was 18.2% and 26.7%, respectively. For the lamina I cell, 7 out of 35 (20%) of the terminals were GABA-IR and they covered 9.6% of the surface analyzed. These data demonstrate that GABA-IR terminals synapse directly on STT cells, constituting a substantial proportion of the terminal population on these cells. Furthermore, compared to the cell bodies, a greater percentage of the input on the proximal dendrites is GABAergic. These anatomical data are consistent with the findings of a previously published iontophoretic study that demonstrated that GABA can exert a strong inhibitory influence on STT cells. These findings are discussed in relation to GABAergic involvement in tonic and phasic inhibition of STT neurons.

Animals↗