Cat Dorsal Horn Research Articles

Effects of Electro-Acupuncture on IGF-I Expression in Spared Dorsal Root Ganglia and Associated Spinal Dorsal Horn in Cats Subjected to Adjacent Dorsal Root Ganglionectomies

The effects of electro-acupuncture (EA) on insulin-like growth factor-I (IGF-I) expression in the spared dorsal root ganglia (DRG) and associated spinal dorsal horns were explored in cats subjected to unilateral removal of L(1)-L(5) and L(7)-S(2) DRG, sparing the L(6) DRG. Immunohistochemistry revealed the presence of IGF-I immunoreactive products in the L(6) DRG neurons and some neurons and glial cells in the spinal cord. Western blot demonstrated that the level of IGF-I was significantly up-regulated both in the spared DRG and the dorsal horns of L(3) and L(6) cord segments at both 7 and 14 days post operation following EA. The present findings demonstrated the association between neuroplasticity and IGF-I expression, suggesting the possible role of IGF-I in EA promoted spinal cord plasticity.

RETRACTED: Effects of electro-acupuncture on NT-4 expression in spinal dorsal root ganglion and associated segments of the spinal dorsal horn in cats subjected to adjacent dorsal root ganglionectomy

It is well known that neuroplasticity occurs in the central nervous system in response to injury. Electro-acupuncture (EA) may also promote neuroplasticity. But little is known about the underlying molecular mechanisms for the beneficial effects of EA. This study investigated the effects of EA on neurotrophin-4 (NT-4) expression in L(6) spinal dorsal root ganglion (DRG) and associated segments of the spinal dorsal horn in cats subjected to unilateral removal of L(1)-L(5) and L(7)-S(2) DRG. NT-4 protein was normally present in the cytoplasm of the L(6) DRG neurons and L(3) and L(6) spinal dorsal horn neurons and glia. Adjacent ganglionectomy leads to a significant decrease in NT-4 expression in the L(6) DRG, but no change in the spinal dorsal horn. Following EA treatment a significant increase occurred in the L(6) DRG at 14 days post-operation (dpo) as well as the L(6) cord segment at 7 and 14 dpo. These findings pointed to a possible association between NT-4 expression and EA promoted spinal cord plasticity in adult cats subjected to partial ganglionectomy.

Electrophysiological evidence that neurokinin A acts via NK-1 receptors in the cat dorsal horn.

The aim of the present study was to investigate the effects of the non-peptide NK-2 receptor antagonist, SR 48968 on the responses of dorsal horn neurons to iontophoretic application of the endogenous NK-2 receptor ligand, neurokinin A, and on synaptically elicited responses in chloralose-anaesthetized cats. The effect of iontophoretic application of neurokinin A was tested on 51 dorsal horn neurons. Of these, 43 were wide dynamic range and the rest non-nociceptive neurons. Neurokinin A induced a slow, prolonged excitation of 25 of the wide dynamic range neurons. All remaining neurons were unaffected. SR 48968 (50 microg to 1.0 mg/kg, i.v.) did not affect the on-going basal activity (n = 8) or the slow excitation induced by neurokinin A in any of the nine wide dynamic range neurons tested. To eliminate the possibility that systemically administered SR 48968 may not be reaching central sites, SR 48968 was also applied iontophoretically (70-120 nA) to five neurons and tested against excitatory responses to iontophoretically applied neurokinin A. The on-going activity of these cells were unaffected by SR 48968. The responses to neurokinin A were also unaffected suggesting that neurokinin A did not mediate its effects via NK-2 receptors. SR 48968 also had no effect on the excitatory responses of seven neurons to iontophoretic application of the NK-1 receptor agonist, substance P indicating that substance P actions are not mediated via NK-2 receptors and that SR 48968 did not react with NK-1 receptors. Responses of the neurons to non-noxious (hair) stimulation (n = 10), noxious mechanical (n = 5) and noxious thermal (n = 8) stimulation of the receptive field were also unaffected by SR 48968, suggesting a lack of participation of NK-2 receptors in these responses. However, responses of wide dynamic range neurons to neurokinin A were totally blocked by i.v. administration (0.5 mg/kg) of the NK-1 receptor antagonists CP-96,345 (n = 7) and CP-99,994 (n = 5) but not by CP-96,344 (n = 4), the inactive enantiomer of CP-96,345. These data suggest that neurokinin A, like substance P may be acting via NK-1, rather than NK-2 receptors, to produce excitation of wide dynamic range neurons in the dorsal horn of the cat spinal cord.

Substance P analogues potentiate the pressor response to microinjection of l-glutamate into laminas I and II of the cat dorsal horn

Microinjection of a substance P analogue (1 mM; 7 or 10 nl) into laminae I and II of the L 7 dorsal horn of decerebrate cats significantly potentiated ( P<0.05) the increase in arterial pressure evoked by microinjection of l-glutamate (109 mM; 7 or 10 nl) into these spinal sites. Microinjection of the substance P analogues (i.e., GR73638 and [Sar 9,Met(O 2) 11]-substance P) which were selective NK-1 receptor agonists, had no impact on the cardioacceleration evoked by microinjection of l-glutamate ( P>0.05). In addition, microinjection of these analogues had no effect on the modest and non-significant increase in phrenic nerve discharge evoked by l-glutamate. We conclude that stimulation of NK-1 receptors in the superficial laminae of the dorsal horn potentiates the pressor responses to microinjection of l-glutamate.

Variation of dorsal horn cell dendritic spread with map scale.

Cells in laminae III, IV, and V of cat dorsal horn were injected with horseradish peroxidase or neurobiotin. Dorsal views of the dendritic domains were constructed in order to measure their lengths, widths, areas, and length/width ratios in the horizontal plane (the plane of the somatotopic map). Dendritic domain width and area in the horizontal plane were negatively correlated with fractional distance between the medial and lateral edges of the dorsal horn. These results are consistent with the hypothesis that dendritic domain width varies with map scale, which is maximal in the medial dorsal horn. This is similar to the variation in widths of primary afferent bouton distributions. The parallel variation of dorsal horn cell dendritic domain width and primary afferent bouton distribution width with map scale suggests that there is a causal relation between morphology and map scale in the dorsal horn representation of the hindlimb. This variation of adult morphology with map scale must reflect mechanisms responsible for the assembly of receptive fields.

Excitatory amino acid concentrations in the spinal dorsal horn of cats during muscle contraction

In anesthetized cats, static hindlimb muscle contraction reflexly increases mean arterial pressure (MAP) and heart rate (HR). Pharmacological and immunohistochemical evidence suggests that excitatory amino acids are involved in the spinal transmission of this reflex. Using microdialysis and high-performance liquid chromatography technology, we tested the hypothesis that static contraction of the triceps surae muscle increases the extracellular concentration of glutamate (Glu) and aspartate (Asp) at the L7 level of the dorsal horn of the spinal cord. With the exception of the L7 dorsal root, the L5-S2 dorsal and ventral roots were cut ipsilateral to the contracting muscle. After the insertion of microdialysis probes and a 3-h recovery period, a 2-min static contraction was electrically evoked. MAP and HR increased by 53 +/- 8 mmHg and 20 +/- 4 beats/min. The concentration of Glu increased from 324 +/- 59 to 857 +/- 80 nM, whereas Asp increased from 199 +/- 57 to 499 +/- 113 nM. These results were repeatable, in that Glu and Asp rose by similar amounts in two subsequent contractions. In both of these latter contractions, MAP and HR were also significantly increased. By contrast, in a subset of cats whose L7 dorsal roots were cut after the first contraction, neither MAP, HR, Glu, nor Asp was significantly increased over baseline levels. These data demonstrate that static contraction of the hindlimb increases the extracellular concentration of Glu and Asp in the dorsal horn. In summary, the results from this study are in agreement with previous findings suggesting that excitatory amino acids are involved in the spinal transmission of sensory information from the hindlimb muscle.

Intraaxonal injection of neurobiotin reveals the long-ranging projections of A beta-hair follicle afferent fibers to the cat dorsal horn.

1. The morphology and somatotopic organization of the spinal arborizations of identified A beta-hair follicle afferent fibers (HFAs) with receptive fields (RFs) on the digits have been investigated in the cat by the use of intraaxonal injection of the tracer n-(2 aminoethyl) biotinamide. 2. In three cats, the long-ranging projections of six HFAs were examined by selectively injecting afferents with RFs on digit 2, 4, or 5, directly over the digit 3 representation, and examining their collateral morphology in transverse sections of the spinal cord. The rostral and caudal boundaries of the digit 3 representation were determined by mapping the RFs of identified spinocervical tract (SCT) neurons. 3. In two more cats, three HFAs were injected at random rostrocaudal positions and their morphology was examined in parasagittal sections. In one animal (2 HFAs), the somatotopy of the digit representation was again determined by mapping the RFs of SCT neurons. In the remaining cat (1 HFA), the somatotopy of the dorsal horn was mapped from the RFs of unidentified dorsal horn neurons. 4. Hair follicle afferents emitted many more collaterals, over much greater rostrocaudal distances, than indicated by previous horseradish peroxidase studies, and all collaterals gave rise to synaptic boutons. 5. HFAs that have RFs confined to a small part of a digit give rise to bouton-bearing axonal branches throughout the entire rostrocaudal extent of the hindpaw representation.

NMDA receptor blockade in cat dorsal horn blunts reflex pressor response to muscle contraction and stretch.

The role of N-methyl-D-aspartate (NMDA) receptors in the reflex pressor response to static muscle contraction and passive stretch was examined by microdialyzing the NMDA receptor antagonist DL-2-amino-5-phosphonovalerate (AP-5) into the L7 or L6 and S1 levels of the dorsal horn of anesthetized cats. Contraction, elicited by electrical stimulation of the cut L7 and S1 ventral roots, increased mean arterial pressure (MAP) and heart rate (HR). Passive stretch at tensions similar to those generated by contraction also increased these variables. These cardiovascular changes were unaffected by dialyzing AP-5 (10 mM) into the dorsal horn at L7. Increasing the syringe concentration of AP-5 to 100 mM attenuated the pressor and HR responses from 62 +/- 8 to 31 +/- 6 mmHg and 18 +/- 4 to 12 +/- 4 beats/min, respectively. AP-5 blunted the increase in MAP (59 +/- 10 vs. 41 +/- 10 mmHg) evoked by muscle stretch. Simultaneously microdialyzing AP-5 (10 or 100 mM) into the dorsal horn at the L6 and S1 spinal levels also blunted the MAP and HR responses to contraction and stretch. These results suggest that NMDA receptors play a role in mediating the MAP and HR responses to static muscle contraction at the spinal level of the central nervous system. Furthermore, these data demonstrate that collaterals from muscle afferents partially mediate the reflex cardiovascular responses evoked by muscle contraction and stretch.

Gamma-aminobutyric Acid Is Released in the Dorsal Horn by Electrical Spinal Cord Stimulation

The mechanism underlying the beneficial effect of electrical stimulation of the posterior surface of the spinal cord in chronic pain states are unknown. The prolonged pain relief following a short stimulation period is believed to imply the activation of long-lasting neurochemical processes, mainly in the spinal cord, but possibly also involving other parts of the central nervous system. Previous studies have demonstrated that substance P and serotonin are released in the cat dorsal horn during spinal cord stimulation (SCS) with electrical parameters similar to those used in the clinic. However, gamma-aminobutyric acid (GABA) has also been hypothesized to play a role in the effect of SCS, but there have been no studies of the possible effects of SCS on GABA release. The authors applied SCS to anesthetized rats and monitored the extracellular concentration of GABA in the lumbar dorsal horns by microdialysis and a sensitive reverse-phase high-performance liquid chromatography technique. After 30 minutes of SCS, the GABA level increased significantly (by almost 270%) in comparison with the basal level recorded before stimulation, from 3.6 +/- 1.0 nmol/L to 13.1 +/- 2.2 nmol/L (mean +/- the standard error of the mean; P < 0.05). The peak release was delayed and appeared in the 30-minute fraction collected after stimulation. Also, perfusion of the dialysis probes with potassium (100 mmol/L) induced an increase of the GABA level. In control experiments without electrical stimulation, slowly decreasing GABA levels were observed throughout the experiments. The present results may suggest an involvement of GABA in the mechanism of SCS-induced pain relief.(ABSTRACT TRUNCATED AT 250 WORDS)

Gamma-aminobutyric Acid Is Released in the Dorsal Horn by Electrical Spinal Cord Stimulation&lt;subtitle&gt;An In Vivo Microdialysis Study in the Rat&lt;/subtitle&gt;

THE MECHANISMS UNDERLYING the beneficial effect of electrical stimulation of the posterior surface of the spinal cord in chronic pain states are unknown. The prolonged pain relief following a short stimulation period is believed to imply the activation of long-lasting neurochemical processes, mainly in the spinal cord, but possibly also involving other parts of the central nervous system. Previous studies have demonstrated that substance P and serotonin are released in the cat dorsal horn during spinal cord stimulation (SCS) with electrical parameters similar to those used in the clinic. However, gamma-aminobutyric acid (GABA) has also been hypothesized to play a role in the effect of SCS, but there have been no studies of the possible effects of SCS on GABA release. The authors applied SCS to anesthetized rats and monitored the extracellular concentration of GABA in the lumbar dorsal horns by microdialysis and a sensitive reverse-phase high-performance liquid chromatography technique. After 30 minutes of SCS, the GABA level increased significantly (by almost 270%) in comparison with the basal level recorded before stimulation, from 3.6 ± 1.0 nmol/L to 13.1 ± 2.2 nmol/L (mean ± the standard error of the mean; P < 0.05). The peak release was delayed and appeared in the 30-minute fraction collected after stimulation. Also, perfusion of the dialysis probes with potassium (100 mmol/L) induced an increase of the GABA level. In control experiments without electrical stimulation, slowly decreasing GABA levels were observed throughout the experiments. The present results may suggest an involvement of GABA in the mechanism for SCS-induced pain relief. A hypothetical role for GABA in the effect of SCS on the activity of wide dynamic range neurons and on symptoms of neuropathy is discussed on the basis of these observations and other recent experimental findings.

Morphology of A beta hair follicle afferent collaterals in dorsal horn of cats with neonatal chronic denervation of digits.

1. The effect of neonatal denervation of two adjacent hindpaw digits (digits 3 and 4) in the cat on the morphology of spinal collaterals of identified A beta hair follicle afferents (HFAs) with receptive fields (RFs) on the neighbouring digits has been investigated using intra-axonal injection of horseradish peroxidase. 2. The morphology of collaterals of HFAs innervating intact digits (digit 2 or digit 5) was examined within the neonatally and chronically deprived region of dorsal horn by selectively injecting the afferents directly over this region. 3. Of a total of nine injected axons, seven had RFs on the distal part of digit 2, whereas two had RFs on the distal part of digit 5. With the exception of one of the digit 5 afferents, all injected afferents gave rise to stained collaterals throughout the chronically deprived digit representation. 4. Many collaterals within the chronically deprived region of dorsal horn gave rise to arborizations having relatively large numbers of boutons when compared with previously described somatotopically inappropriate (SIA) collaterals in the normal adult cat. 5. It is suggested that neonatal denervation of digits in the cat may lead to collateral sprouting and bouton formation by SIA collaterals of A beta HFAs innervating adjacent intact digits. This morphological plasticity could explain the previously reported functional reorganization of the RFs of spinocervical tract neurons that occurs in these neonatally deafferented animals.

Precision and variability of hindlimb representation in cat dorsal horn and implications for tactile localization.

1. One hundred fifty-eight cells were recorded extracellularly in rows of tracks spanning both left and right dorsal horns, at segmental boundaries and midsegment in segments L5-S1, in six anesthetized cats. For each cell the low-threshold cutaneous mechano-receptive field was determined with the use of hand-held probes, and the recording site was marked with a microlesion. Recording sites were reconstructed, and the mediolateral (ML) and rostrocaudal (RC) locations of each cell were recorded along with the location of the cell's receptive field, expressed as distance from tips of toes (D). 2. Ninety-five percent of pairs of cells recorded from bilaterally symmetric locations (+/- 10%) in the same animal had receptive fields on opposite legs that had components that were mirror symmetric. Only 42% of cell pairs deviating from bilateral symmetry by approximately +/- 240 microns had receptive fields with overlapping components. This indicated that there was a substantial bilateral symmetry that was not simply due to large receptive fields. 3. The trajectories of receptive fields of cells in a single row of tracks were plotted in order of mediolateral recording site, going from medial to lateral, combining both sides. These trajectories followed a distoproximal course on the leg. Of 144 adjacent cells used to plot these trajectories, with an average spacing of approximately 120 microns, only 6 reversals of the distoproximal gradient polarity were observed within animals. 4. Data from individual animals were shifted rostrally and caudally, to obtain best agreement of mediolateral somatotopic gradients with the combined data from the other animals in the sample. Best agreement was obtained with shifts ranging from 0.3 segment rostral to 0.4 segment caudal, with an average absolute value shift of 0.22 segment. 5. By comparing cell pairs within the same dorsal horn, on opposite sides of the same animal, and across animals, variability in cell placement given the average map and the receptive field could be calculated. Interanimal variability and bilateral asymmetry were approximately +/- 60 microns, and within-dorsal horn variability was approximately +/- 35 microns. The interanimal variability is equivalent to a variability of distoproximal receptive-field location on the leg of +/- 13 mm, with a smaller variability in areas of high magnification (e.g., the toes), and a larger variability in areas with small magnification (e.g., the thigh). This degree of variability is consistent with the ability of animals with transected dorsal columns to localize tactile stimuli with a normal degree of precision.

The effects of neurokinin receptor antagonists on mustard oil-evoked activation of rat dorsal horn neurons

Previous evidence indicated that brief nociceptive responses of neurons in laminae IV V of both rat and cat dorsal horn are more readily inhibited by antagonists at NK 2 rather than at NK 1 neurokinin receptors. Further support for a role of spinal NK 2 receptors in nociception has been provided from experiments assessing modulation of the nociceptive flexor reflex by tachykinins and activation of dorsal horn neurons by brief application of capsaicin to afferents. The present experiments were designed to compare the contribution of NK 1 and NK 2 receptors in dorsal horn to the sustained neuronal activity induced by peripheral application of the chemical algogen mustard oil (reported to be a selective activator of C afferents). In nearly all of the multireceptive laminae IV V neurons tested, a selective NK 2 receptor antagonist L 659,874 inhibited previously established mustard oil-induced activity. In contrast, two selective NK 1 receptor antagonists L 668,169 and GR 82334 were only rarely effective. These results further underline the apparent importance of NK 2 receptors in spinal nociceptive processing. NK 1 receptors do not appear to play a major role in the present experimental protocol, but they may of course do so under different circumstances.

L-NAME blocks responses to NMDA, substance P and noxious cutaneous stimuli in cat dorsal horn.

The nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), administered i.v. (50 mg kg-1) or by iontophoresis, was tested on the responses of spinal dorsal horn neurones in cats anaesthetized with alpha-chloralose and spinally transected at the L1 level. Extracellular, single-unit recordings were obtained from functionally identified dorsal horn cells. All units included in this study were wide dynamic range neurones. L-NAME significantly reduced the responses of (i) twelve neurones to noxious thermal stimulation of the receptive field, (ii) nine neurones to noxious pinch, (iii) nine neurones to iontophoretic application of N-methyl-D-aspartate (NMDA) and (iv) ten neurones to iontophoretic application of substance P. The inhibition usually lasted for 50-70 min following i.v. administration and for 5-8 min after iontophoretic application of L-NAME. The responses of four neurones to iontophoretic application of quisqualate were not affected by L-NAME. The results suggest the possible involvement of nitric oxide in the mediation of the spinal effects of NMDA and substance P, and in the transmission of thermal and mechanical nociceptive imputs.

Dorsal column stimulation induces release of serotonin and substance P in the cat dorsal horn.

The neurohumoral mechanisms behind the pain-suppressing effect of dorsal column stimulation (DCS) still remain obscure. Experimental observations have indicated an inhibitory role for serotonin and, under certain conditions, also for substance P (SP), on nociceptive transmission in the spinal cord. Furthermore, some observations suggest that these substances might be involved in the effect of DCS. The present series of experiments was undertaken to investigate whether serotonin and SP are released in the dorsal horn by DCS. Twenty-one adult cats, in some experiments anesthetized, in others decerebrated at the midcollicular level, were used. Microdialysis probes were implanted bilaterally in lumbar dorsal horns (L5-L7) and perfused with Krebs' solution. Dialysates were analyzed for serotonin by high-performance liquid chromatography or for SP by radioimmunoassay. DCS was applied at the thoracolumbar junction with current parameters similar to those used clinically in humans. DCS induced a significant release of serotonin in the dorsal horn of decerebrated animals (173 +/- 83% increase; mean +/- standard error; n = 4; P less than 0.01), whereas the levels of the metabolite 5-hydroxyindoleacetic acid were not significantly influenced. In contrast, no release of SP could be recorded in response to DCS in the decerebrated preparation, although peripheral nociceptive stimulation (pinch) and noxious electric dorsal root stimulation induced an elevation of the SP levels. However, in intact animals DCS provoked a marked SP release in the dorsal horn (190 +/- 92% increase; n = 7; P less than 0.01). The release of serotonin and SP after DCS may indicate that these substances participate in the mediation of the pain alleviating effect of DCS.(ABSTRACT TRUNCATED AT 250 WORDS)

Dorsal Column Stimulation Induces Release of Serotonin and Substance P in the Cat Dorsal Horn

Dorsal Column Stimulation Induces Release of Serotonin and Substance P in the Cat Dorsal Horn

Central projections from the skin of the hand in squirrel monkeys

Central termination patterns of afferents from the hands of squirrel monkeys were studied after subdermal injections of wheat germ agglutinin conjugated with horseradish peroxidase (WGA-HRP) or cholera toxin subunit B conjugated to HRP (BHRP). WGA-HRP more effectively labeled axons terminating in the superficial dorsal horn of the spinal cord, while BHRP more effectively labeled axons terminating in the deeper layers. Injections of both tracers, when restricted to parts of glabrous digits, palm, or dorsal hand, revealed somatotopic patterns in the spinal cord and pars rotunda of the cuneate nucleus that were, in some respects, similar and, in other respects, quite different from those previously reported for macaque monkey (Florence et al., J. Comp. Neurol. 286:48-70, '89). As in macaques, injections in digits 1-5 produced a rostrocaudal sequence of foci of terminations in the cervical spinal cord. However, inputs from the palm were located medial to those from the digits, whereas the palm is represented lateral to the digits in macaque monkeys. Since inputs from the palm is also medial in the dorsal horn in cats (Nyberg and Blomqvist, J. Comp. Neurol. 242:28-39, '85), the condition in squirrel monkeys may be similar to the generalized state. In the cuneate nucleus, single injections in the hand produced dense label in the pars rotunda, and sparse label in the rostral and caudal poles. As in macaque monkeys, inputs from specific parts of the hand related to rostrocaudal clusters of cells that are cytochrome oxidase dense. The representation of the digits differed from macaques in that the digits were represented dorsal to the palm, rather that ventral to the palm as in macaques. Again, comparisons with cats suggest that squirrel monkeys have the more generalized pattern. Finally, inputs from the hair, dorsal surfaces of the digits terminated on the same clusters as the inputs from the glabrous, ventral surfaces, apparently overlapping somewhat. The proximity of these terminations from dorsal and ventral surfaces of the digits may be related to observations that cortical representations of the glabrous surfaces of digits become responsive to dorsal surfaces of the same digits when inputs from glabrous skin are chronically deactivated (e.g., Merzenich et al., Neuroscience 3:33-55, '83).

Influence of map scale on primary afferent terminal field geometry in cat dorsal horn

1. Thirty-one physiologically identified primary afferent fibers were labeled intracellularly with horseradish peroxidase (HRP). 2. A computer analysis was used to determine whether the distribution of cutaneous mechanoreceptive afferent terminals varies as a function of location within the dorsal horn somatotopic map. 3. An analysis of the geometry of the projections of these afferents has shown that 1) terminal arbors have a greater mediolateral width within the region of the foot representation than lateral to it, 2) terminal arbors have larger length-to-width ratios outside the foot representation than within it, and 3) the orientation of terminal arbors near the boundary of the foot representation reflects the angle of the boundary. Previous attribution of mediolateral width variations to primary afferent type are probably in error, although there appear to be genuine variations of longitudinal extent as a function of primary afferent type. 4. Nonuniform terminal distributions represent the first of a three-component process underlying assembly of the monosynaptic portions of cell receptive fields (RFs) and the somatotopic map. The other two components consist of the elaboration of cell dendritic trees and the establishment of selective connections. 5. The variation of primary afferent terminal distributions with map location is not an absolute requirement for development of the map; for example, the RFs of postsynaptic cells could be assembled with the use of a uniform terminal distribution for all afferents, everywhere in the map, as long as cell dendrites penetrate the appropriate portions of the presynaptic neuropil and receive connections only from afferent axons contributing to their RFs.(ABSTRACT TRUNCATED AT 250 WORDS)

Somatotopic organization of single primary afferent axon projections to cat spinal cord dorsal horn

Horseradish peroxidase injection of identified low threshold cutaneous mechanoreceptor (LTCM) primary afferent axons was used to assess the somatotopic organization of hindlimb projections to laminae III and IV of cat dorsal horn. Multiple injections in the same animals were used to assess bilateral symmetry and precision. Thirty-one axons were injected, with more than 1 axon injected in each of 8 animals (25 axons). Somatotopic relations between their receptive field (RF) centers and the centers of their dorsal horn projections were similar to the somatotopic relations between dorsal horn cell RF centers and cell locations. Very few reversals of mediolateral somatotopic gradients (proximodistal RF location as a function of mediolateral projection center) were observed. Two afferents with nearly identical RFs in 1 animal had nearly identical projections. These observations held for many different combinations of receptor types. A simple mathematical model was used to demonstrate that assembly of dorsal horn cell RFs via passive sampling of the presynaptic neuropil by dorsal horn cell dendrites cannot account for the sizes of dorsal horn cell LTCM RFs. Hypothesized mechanisms for assembly of dorsal horn cell RFs must take into account the functional selectivity of connections required to produce RFs smaller than those predicted by the passive assembly model.

The Antinociceptive Role of ??- and ??-Opiate Receptors and Their Interactions in the Spinal Dorsal Horn of Cats

This study was undertaken to examine the antinociceptive roles of different subtypes of opiate receptors and their interactions at the level of the spinal cord. We recorded extracellularly the activity of the single wide dynamic range neurons evoked by noxious radiant heat (51 degrees C) in decerebrate, spinally transected cats. The separate intrathecal administration of DAGO selective mu-agonist, n = 28), morphine (less selective mu-agonist, n = 22), DPDPE (selective delta-agonist, n = 25), and DADL (less selective delta-agonist, n = 17) produced statistically significant suppression of noxiously evoked activity in a time- and dose-dependent manner. In addition, intravenously administered naloxone (nonselective opiate antagonist) reversed the suppressive effects of all opiates studied. Intravenously administered ICI 174,864 (selective delta-antagonist) reversed the effects of DPDPE. These results, based on relative selectivity for opiate receptors, indicate that both mu- and delta-opiate receptors can modulate the input of nociceptive information in the spinal dorsal horn. To study interactions between mu- and delta-receptors at the level of the spinal cord, a combination of the above agonists was injected intrathecally--namely, an ineffective or slightly effective dose of DAGO (1 or 1.5 micrograms, respectively) that was combined with an ineffective dose of DPDPE (30 micrograms). The intrathecal combination of DAGO and DPDPE produced significant synergistic suppressive effects of noxiously evoked activity. These findings, again based on relative selectivity, suggest that drug combinations that include both selective mu- and delta-agonists may be a useful method of lowering the total amount of any one drug, thus decreasing the likelihood of side effects, while at the same time producing significant analgesia.(ABSTRACT TRUNCATED AT 250 WORDS)