Segmental organization of visceral and somatic input onto C3-T6 spinothalamic tract cells of the monkey.

1. Referred pain of visceral origin has three major characteristics: visceral pain is referred to somatic areas that are innervated from the same spinal segments as the diseased organ; visceral pain is referred to proximal body regions and not to distal body areas; and visceral pain is felt as deep pain and not as cutaneous pain. The neurophysiological basis for these phenomena is poorly understood. The purpose of this study was to examine the organization of viscerosomatic response characteristics of spinothalamic tract (STT) neurons in the rostral spinal cord. Interactions were determined among the following: 1) segmental location, 2) effects of input by cardiopulmonary sympathetic, greater splanchnic, lumbar sympathetic, and urinary bladder afferent fibers, 3) location of excitatory somatic field, e.g., hand, forearm, proximal arm, or chest, 4) magnitude of response to hair, skin, and deep mechanoreceptor afferent input, and 5) regional specificity of thalamic projection sites. 2. A total of 89 STT neurons in segments C3-T6 were characterized for responses to visceral and somatic stimuli. Neurons were activated antidromically from the contralateral ventroposterolateral oralis or caudalis nuclei of the thalamus. Cell responses to visceral and somatic stimuli were not different on the basis of the thalamic site of antidromic activation. Recording sites for 61 neurons were located histologically; 87% of lesion sites were located in laminae IV-VII or X. There was no relationship between response properties of the neurons and spinal laminar location. 3. Different responses to visceral stimuli were observed in three zones of the rostral spinal cord: C3-C6, C7-C8, and T1-T6. In C3-C6, urinary bladder distension (UBD) and electrical stimulation of greater splanchnic and lumbar sympathetic afferent fibers inhibited STT cells. Electrical stimulation of cardiopulmonary sympathetic afferents increased cell activity in C5 and C6 and either excited or inhibited STT cells in C3 and C4. In the cervical enlargement (C7-C8), STT cells generally were either inhibited or showed little response to stimulation of visceral afferent fibers. In T1-T6, input from greater splanchnic and cardiopulmonary sympathetic afferent nerves increased activity of STT cells. Lumbar sympathetic afferent input inhibited cells in T1-T2 and had little effect on cells in T3-T6, whereas UBD decreased cell activity in all segments studied. 4. In general, stimulation of somatic structures increased activity of STT neurons in segments that received primary afferent innervation from the excitatory somatic receptive field or in the segments immediately adjacent to these segments. Only input from the forelimb, especially the hand, markedly excited cells in C7 and C8.+     

Spinal inhibitory effects of cardiopulmonary afferent inputs in monkeys: neuronal processing in high cervical segments

Noxious stimulation of spinal afferents inhibits primate spinothalamic tract (STT) neurons in segments distant from the region of afferent entry. Inhibitory effects of cardiopulmonary sympathetic afferent (CPSA) stimulation remain after C(1) transection but disappear with spinal transection between C(3) and C(7). We hypothesized that spinal inhibitory effects produced by CPSA stimulation are processed by neurons in C(1)-C(3) segments. One purpose of this study in anesthetized monkeys was to determine whether chemical activation of high cervical neurons reduced sacral STT cell responses to colorectal distension (CRD) and urinary bladder distension (UBD). First, effects and interactions of pelvic and cardiopulmonary visceral afferent inputs were determined in 10 monkeys on extracellular activity of sacral STT neurons recorded in deep dorsal horn. CRD and UBD increased activity in 95 and 91% of sacral STT neurons, respectively. CPSA and cardiopulmonary vagal stimulation decreased activity in 84 and 56% of STT neurons, respectively. CPSA stimulation decreased CRD-evoked activity in six of eight sacral STT neurons and decreased UBD-evoked activity in five of eight STT neurons tested. Excitatory amino acid application at C2 segment decreased CRD-evoked responses in 7 of 10 sacral STT neurons and decreased UBD-evoked responses in 9 of 12 STT neurons. The second purpose of this study was to examine responses of C(1)-C(3) descending propriospinal neurons to stimulation of cardiopulmonary afferent fibers. If C(1)-C(3) neurons process CPSA input to suppress STT transmission, then CPSA stimulation should excite C(1)-C(3) neurons with descending projections. Effects of thoracic vagus nerve stimulation also were examined. Vagal stimulation inhibits STT neurons in segments below C(3) but excites C(1)-C(3) STT neurons; we theorized that vagal inhibition of sensory transmission might relay in high cervical segments and, therefore, excite C(1)-C(3) descending propriospinal neurons. Extracellular discharge rate was recorded for C(1)-C(3) neurons antidromically activated from thoracic or lumbar spinal cord in 24 monkeys. CPSA stimulation increased activity of 16 of 45 neurons and inhibited one cell. Thoracic vagus stimulation increased activity of 20 of 43 neurons and inhibited one cell; stimulation of abdominal vagus fibers did not affect activity of six of six cells that were excited by thoracic vagal input. Mechanical stimulation of somatic fields excited 30 of 41 neurons tested. All neurons activated by visceral input received convergent somatic input from noxious pinch of somatic receptive fields that generally included the neck and upper body; 11 C(1)-C(3) propriospinal neurons did not respond to any afferent input examined. Results of these studies were consistent with the idea that modulation of spinal nociceptive transmission might involve neuronal connections in high cervical segments.     

Responses and afferent pathways of superficial and deeper c(1)-c(2) spinal cells to intrapericardial algogenic chemicals in rats

Electrical stimulation of vagal afferents or cardiopulmonary sympathetic afferent fibers excites C(1)--C(2) spinal neurons. The purposes of this study were to compare the responses of superficial (depth <0.35 mm) and deeper C(1)--C(2) spinal neurons to noxious chemical stimulation of cardiac afferents and determine the relative contribution of vagal and sympathetic afferent pathways for transmission of noxious cardiac afferent input to C(1)--C(2) neurons. Extracellular potentials of single C(1)--C(2) neurons were recorded in pentobarbital anesthetized and paralyzed male rats. A catheter was placed in the pericardial sac to administer a mixture of algogenic chemicals (0.2 ml) that contained adenosine (10(-3) M), bradykinin, histamine, serotonin, and prostaglandin E(2) (10(-5) M each). Intrapericardial chemicals changed the activity of 20/106 (19%) C(1)--C(2) spinal neurons in the superficial laminae, whereas 76/147 (52%) deeper neurons responded to cardiac noxious input (P < 0.01). Of 96 neurons responsive to cardiac inputs, 48 (50%) were excited (E), 41 (43%) were inhibited (I), and 7 were excited/inhibited (E-I) by intrapericardial chemicals. E or I neurons responsive to intrapericardial chemicals were subdivided into two groups: short-lasting (SL) and long-lasting (LL) response patterns. In superficial gray matter, excitatory responses to cardiac inputs were more likely to be LL-E than SL-E neurons. Mechanical stimulation of the somatic field from the head, neck, and shoulder areas excited 85 of 95 (89%) C(1)--C(2) spinal neurons that responded to intrapericardial chemicals; 31 neurons were classified as wide dynamic range, 49 were high threshold, 5 responded only to joint movement, and no neuron was classified as low threshold. For superficial neurons, 53% had small somatic fields and 21% had bilateral fields. In contrast, 31% of the deeper neurons had small somatic fields and 46% had bilateral fields. Ipsilateral cervical vagotomy interrupted cardiac noxious input to 8/30 (6 E, 2 I) neurons; sequential transection of the contralateral cervical vagus nerve (bilateral vagotomy) eliminated the responses to intrapericardial chemicals in 4/22 (3 E, 1 I) neurons. Spinal transection at C(6)--C(7) segments to interrupt effects of sympathetic afferent input abolished responses to cardiac input in 10/10 (7 E, 3 I) neurons that still responded after bilateral vagotomy. Results of this study support the concept that C(1)-C(2) superficial and deeper spinal neurons play a role in integrating cardiac noxious inputs that travel in both the cervical vagal and/or thoracic sympathetic afferent nerves.     

Viscerosomatic neurons in the lower thoracic spinal cord of the cat: excitations and inhibitions evoked by splanchnic and somatic nerve volleys and by stimulation of brain stem nuclei

Single-unit electrical activity has been recorded from 95 viscerosomatic neurons in the T9 and T11 segments of the cat's spinal cord. These neurons were excited by electrical and/or natural stimulation of visceral and somatic afferent fibers. The excitatory and inhibitory effects on these neurons of volleys in somatic and visceral afferent fibers and of electrical and chemical stimulation of the nucleus raphe magnus (NRM) and adjacent areas of the reticular formation (Ret. F.) have been studied. Electrical stimulation of the splanchnic nerve produced, after the initial excitation of the neurons, a period of inhibition lasting for up to 1 s. This inhibition reduced the responsiveness of the neurons to all inputs, somatic and visceral, and was still present after spinalization of the animals with cold block, which indicates a segmental organization of the inhibition. Electrical stimulation of afferent fibers within the somatic receptive field of the neurons produced, after the initial excitation, a period of inhibition similar to that induced by visceral afferent volleys. During this period of inhibition all inputs to the neurons were reduced. Reversible spinalization of the animals with cold block did not abolish this inhibition. On the basis of the effects of reversible spinalization on the visceral input to viscerosomatic neurons, two types of neurons were distinguished: 1) neurons whose visceral responses increased in the spinal state (neurons under tonic descending inhibition) and 2) neurons whose visceral responses were decreased or abolished in the spinal state (neurons subject to descending excitation). Neurons under tonic descending inhibition were inhibited by electrical stimulation of locations within the NRM and Ret. F. This inhibition lasted for less than 100 ms and could be evoked at intensities of stimulation of 100 microA or less. Neurons under descending excitation were also inhibited by electrical stimulation in the NRM and Ret. F. but, in addition, the inhibition was preceded by an excitation in 75% of these neurons. Chemical stimulation with DL-homocysteic acid (DLH) of locations within the NRM and Ret. F. was used to activate cell bodies, but not axons, located in these brain stem sites. The only effect observed following injections of DLH into the NRM and Ret. F. was inhibition of viscerosomatic neurons including those with descending excitation as well as those with descending inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)     

Characterization of neuronal responses to noxious visceral and somatic stimuli in the medial lumbosacral spinal cord of the rat

The cutaneous receptive fields, long ascending projections, and responses to colorectal distension (20-100 mmHg) and tail movement of 252 neurons in spinal segments L6-S1 were characterized in pentobarbital- or halothane-N2O anesthetized, physiologically intact male rats. Seventeen additional neurons were studied in spinalized rats. Neurons studied were located within 0.5 mm of the midline at depths 0.2-1.4 mm from the spinal cord dorsum and included the area immediately dorsal and lateral to the central canal. Colorectal distension and/or antidromic invasion from the contralateral ventral quadrant of the cervical spinal cord were used as search stimuli. One hundred seventeen neurons responded to noxious colorectal distension; many had long ascending projections and convergent somatic input from deep joint receptors, ipsilateral perianal/scrotal cutaneous receptive fields, or both. Stimulus-response functions (SRFs) of 45 neurons to graded colorectal distension were linear, allowing extrapolation of threshold distending pressures to neuronal response. Neurons responsive to colorectal distension were subdivided into four classes based on their initial response colorectal distension (75-80 mmHg, 20 s). Short-latency abrupt (SL-A) neurons were excited at short latency by colorectal distension; activity abruptly returned to base line following termination of distension. Most SL-A neurons had long ascending projections, convergent somatic receptive fields, and 4/6 tested were excited by bradykinin administered intraarterially. The threshold distending pressure, estimated from the SRFs of 19 SL-A neurons, extrapolated to 2.7 mmHg. Short-latency sustained (SL-S) neurons were also excited at short latency by colorectal distension, but responses were sustained for 4-120 s following termination of distension. Most SL-S neurons had long ascending projections, convergent somatic receptive fields, and 18/20 tested were excited by intraarterial bradykinin. The threshold distending pressure, estimated from the SRFs of 20 SL-A neurons, extrapolated to 17.0 mmHg. Long-latency (LL) neurons were excited by colorectal distension at long latency following the onset of distension. No LL neurons had demonstrable long ascending projections, and few had convergent excitatory somatic fields. Three of five LL neurons were excited by intraarterial bradykinin. The threshold distending pressure, estimated from the SRFs of six LL neurons, extrapolated to 9.8 mmHg. Inhibited (INHIB) neurons were spontaneously active and were inhibited by colorectal distension.(ABSTRACT TRUNCATED AT 400 WORDS)     

Characteristics of spinoreticular and spinothalamic neurons with renal input

Spinoreticular (SRT) and spinothalamic (STT) neurons were studied for responses to renal and somatic stimuli in 34 cats that were anesthetized with alpha-chloralose. SRT cells were antidromically activated from the medial medullary reticular formation near the gigantocellular tegmental field contralateral (35 cells), ipsilateral (15 cells), or both contralateral and ipsilateral (11 cells) to the recording site. Collision tests showed that activation from two electrodes resulted from stimulation of separate axonal branches and not from current spread. Twenty STT cells were activated from the spinothalamic tract just medial to the medial geniculate nucleus. SRT cells were located in laminae I, V, VII, and VIII of the T12-L2 segments. Most cells were located in lamina VII. STT cells were found in laminae I, V, and VII. The axons of 12 SRT cells were located in the ventrolateral or ventral quadrants of the upper cervical spinal cord. Antidromic conduction velocities of SRT cells averaged 48.7 +/- 3.7 m/s. No differences in conduction velocity were found between cells projecting to different reticular sites. In addition conduction velocity did not vary with the type of somatic or renal input. Antidromic conduction velocities of STT cells averaged 46.4 +/- 4.7 m/s. Renal nerve stimulation excited 58 and inhibited 3 SRT cells. All 20 STT cells were excited. Thirty SRT cells were excited only by A-delta input, 26 received both A-delta- and C-fiber inputs, and 2 cells received only C-fiber input. Ten STT cells received A-delta input only and 10 received both A-delta- and C-fiber inputs. All cells with renal input also received somatic input. Thirty-six SRT cells (59%) were classified as high threshold, 12 (20%) as wide dynamic range, and 10 (16%) as deep. Ten STT cells were classified as high threshold and 10 as wide dynamic range. Somatic receptive fields of STT cells were usually simple and invariably included the left flank region, although many of the fields extended to the left hindlimb or abdomen. Eighteen of the 20 were restricted to the ipsilateral side. In contrast, somatic receptive fields of SRT cells were primarily bilateral (71%). While all but two receptive fields included the left flank area, most extended to one or both hindlimbs, the abdomen, or the right flank. Inhibitory receptive fields were found for 33% of the SRT cells and 20% of the STT cells.(ABSTRACT TRUNCATED AT 400 WORDS)     

Vagal afferent inhibition of primate thoracic spinothalamic neurons

Spinothalamic (ST) neurons in the C8-T5 segments of the spinal cord were examined for responses to electrical stimulation of the left thoracic vagus nerve (LTV). Seventy-one ST neurons were studied in 39 anesthetized monkeys (Macaca fascicularis). Each neuron could be excited by manipulation of its somatic field and by electrical stimulation of cardiopulmonary sympathetic afferent fibers. LTV stimulation resulted in inhibition of the background activity of 43 (61%) ST neurons. Nine (13%) were excited, 3 (4%) were excited and then inhibited, while 16 (22%) did not respond. There was little difference among these groups in terms of the type of somatic or sympathetic afferent input although inhibited cells tended to be more prevalent in the more superficial laminae. The degree of inhibition resulting from LTV stimulation was related, in a linear fashion, to the magnitude of cell activity before stimulation. LTV inhibition of background activity was similar among wide dynamic range, high threshold, and high-threshold cells with inhibitory hair input. Any apparent differences in LTV inhibitory effects among these groups were accounted for by the differences in ongoing cell activity as predicted by linear regression analysis. LTV stimulation inhibited responses of 32 of 32 ST cells to somatic stimuli. In most cases the stimulus was a noxious pinch; however, LTV stimulation also inhibited responses to innocuous stimuli such as hair movement. Bilateral cervical vagotomy abolished the inhibitory effect of LTV stimulation on background activity (six cells) or responses to somatic stimuli (seven cells). Stimulation of the cardiac branch of the vagus inhibited activity of three cells to a similar degree as LTV stimulation, while stimulation of the vagus below the heart was ineffective in reducing activity of 10 cells. We conclude that LTV stimulation alters activity of ST neurons in the upper thoracic spinal cord. Vagal inhibition of ST cell activity was due to stimulation of cardiopulmonary vagal afferent fibers coursing to the brain stem, which appear to activate descending inhibitory spinal pathways. Vagal afferent activity may participate in processing of somatosensory information as well as information related to cardiac pain.     

Electrophysiological characteristics of primate spinothalamic neurons with renal and somatic inputs

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

Cardiopulmonary sympathetic afferent excitation of lower thoracic spinoreticular and spinothalamic neurons

1. Responses of spinoreticular (SRT) and spinothalamic (STT) neurons located in the T7-T9 segments to cardiopulmonary sympathetic afferent (CPS) stimuli were studied in 27 cats that were anesthetized with alpha-chloralose. 2. CPS stimulation excited 32 SRT and 10 STT neurons. Each neuron was also excited by stimulation of the left greater splanchnic nerve (SPL) and had a somatic receptive field that was most commonly located on the upper abdomen and over the lower rib cage. An additional 12 SRT and 3 STT neurons received input from SPL and somatic structures but failed to respond to CPS stimulation. 3. CPS stimulation evoked early responses (23 cells) or both early and late responses (19 cells) that had average latencies of 12.7 +/- 1.8 and 88.2 +/- 13.1 (SE) ms, respectively. Latencies of responses to SPL stimulation were significantly shorter and averaged 8.1 +/- 0.9 and 46.1 +/- 7.1 ms. Magnitudes of early responses to SPL stimulation were significantly greater than responses to CPS stimulation; however, late responses were not different. 4. Responses to CPS stimulation were inhibited by a prior conditioning stimulus applied to SPL. Greatest inhibition occurred at a conditioning-test interval of 40 ms, and inhibition lasted for at least 300 ms. Inhibition of responses to SPL stimulation could be evoked by conditioning stimuli applied to CPS; however, the inhibition was significantly less than that evoked by SPL stimulation on responses to CPS stimulation. 5. Thirty-eight neurons were tested for responses to injection of bradykinin (4 micrograms/kg) into the left atrium. Discharge rate of 17 cells increased from 5 +/- 2 to 12 +/- 4 Hz. Four cells were tachyphylactic to repeated injections. Injections of bradykinin into the thoracic aorta did not significantly alter cell activity. Bilateral cervical vagotomy had no effect on responses to intracardiac bradykinin. 6. The results indicate that lower thoracic SRT and STT neurons are excited by CPS stimuli including noxious stimulation of the heart. However, comparison of these responses with previously reported responses of upper thoracic SRT and STT neurons indicate that there is a decrease in effectiveness of CPS stimuli from upper to lower thoracic segments. Convergence of CPS and abdominal inputs onto lower thoracic pain pathways could explain abdominal pain that is occasionally associated with cardiac disease.     

Evidence that C1 and C2 propriospinal neurons mediate the inhibitory effects of viscerosomatic spinal afferent input on primate spinothalamic tract neurons.

1. Lumbosacral spinothalamic tract (STT) neurons can be inhibited by noxious pinch of the contralateral hindlimb or either forelimb and by electrical stimulation of cardiopulmonary sympathetic, splanchnic, and hypogastric afferents. A previous study found that spinal transections between C2 and C4 sometimes abolished the inhibitory effect of spinal afferent input and sometimes left it intact. This suggested that propriospinal neurons in the C1 and C2 segments might mediate this effect. To test whether neurons in the C1 and C2 segments were involved in producing this inhibitory effect, the magnitude of the reduction in neural activity was measured in the same STT neuron before and after spinal transection at C1 or between C3 and C7. 2. All neurons were antidromically activated from the contralateral thalamus and thoracic spinal cord. For us to accept a neuron for analysis, the characteristics of the somatic input and the latency and shape of the antidromatic spike produced by spinal cord stimulation had to be the same before and after the spinal transection. Also, spinal transection often causes a marked increase in spontaneous cell activity, which may affect the magnitude of an inhibitory response. To avoid this confounding problem, a cell was accepted for analysis only if it showed marked inhibition of high cell activity evoked by somatic pinch before spinal transection. For analysis 13 STT neurons met these criteria: 6 neurons were in monkeys with C1 transections, and 7 neurons were in animals with transections between C3 and C7.(ABSTRACT TRUNCATED AT 250 WORDS)     

An iontophoretic study of single somatosensory neurons in rat granular cortex serving the limbs: a laminar analysis of glutamate and acetylcholine effects on receptive-field properties

1. Glutamate, acetylcholine (ACh), and bicuculline were delivered by iontophoretic pipettes to the 545 neurons described in the preceding paper. Their response properties were examined to determine the effect of these compounds on the behavior of neurons in rat somatosensory cortex. 2. The responses to glutamate covered a broad range. Some cells were completely depolarized by small amounts of this excitatory amino acid, whereas others were extremely insensitive requiring in excess of 100 nA to be excited. This range of sensitivities was seen throughout all cortical layers. 3. Glutamate was most effective in uncovering new receptive fields or in enhancing preexisting somatic responses in the bottom of layer II/III and in layer IV. Receptive fields uncovered by glutamate had properties comparable to receptive fields observed without drugs. Overall, glutamate enhanced the ability of afferent inputs to drive 39% of the neurons tested. 4. In 61% of the cells tested with glutamate there was no evidence of somatic input even during excitation with glutamate. Of 50 cells displaying receptive fields, only two were enlarged by treatment with glutamate. For 36 other cells receptive fields of normal dimensions were uncovered during glutamate administration. 5. Bicuculline uncovered more somatic inputs than either glutamate or ACh, leaving only 37% of 86 cells tested without evidence of excitatory inputs from the skin. Bicuculline produced an average receptive-field enlargement of 8.7 times in 11 of 56 cells tested. This drug acted uniformly throughout the cortical layers. 6. ACh excited 36.9% of the 360 cells tested. Those excited tended to be located in laminae Vb and VIb. The effects of ACh on afferent response properties could not be predicted from its ability to excite a cell. The magnitude of the response to 100 nA of ACh varied with the laminar position of the cell being tested, being weakest in layer II/III and greatest in layer Vb. 7. Overall, 34.2% of 263 cells showed changes in afferent drive during ACh treatment. ACh enhanced the responses to somatic stimulation most frequently in laminae IV and V. 8. Of the 90 neurons tested for long-term effects, 27% displayed effects of ACh that significantly outlasted the duration of the ACh administration. In 18% of these, changes lasted for greater than 5 min, sometimes remaining altered for the duration of the time that the cell was studied. These long-term changes in excitability were generally produced by administration of ACh during the time that the cell was excited by glutamate or by somatic stimulation.     

Characterization of neurons responsive to noxious colorectal distension in the T13-L2 spinal cord of the rat

1. One-hundred thirty-two neurons responsive to colorectal distension in the dorsal horn of the T13-L2 spinal segments of 35 spinalized and 7 intact, deeply pentobarbital-sodium-anesthetized rats were characterized for convergent cutaneous receptive fields, long ascending projections and responses to the intra-arterial administration of the algesic peptide bradykinin. All but 9 neurons had an identifiable excitatory cutaneous receptive field; all receptive fields were located on the lower abdomen, flank, and dorsal body surface. Electrical stimulation in the cutaneous fields of 28 neurons demonstrated that neurons responsive to colorectal distension receive afferent information carried by A- and C-fibers. Stimulus-response functions (SRFs) of 52 neurons excited by graded colorectal distension (20-100 mmHg, 20 s) were monotonic and accelerating, allowing extrapolation of threshold distending pressures to neuronal response. Neurons were subdivided into four classes based upon their response to an 80-mmHg, 20-s colorectal distension search stimulus. 2. Short-latency abrupt [SL-A] neurons (spinalized, n = 46; intact, n = 9) were excited at short latency; activity abruptly returned to base line on termination of distension. Six of 9 neurons in intact rats had long ascending projections as demonstrated by antidromic invasion from the contralateral, ventrolateral caudal medulla. Responses of SL-A neurons to colorectal distension were significantly greater in spinalized than in intact rats. Fifty-three of 55 SL-A neurons had convergent excitatory cutaneous receptive fields and most were responsive to both noxious and nonnoxious stimuli. Ten of 13 neurons tested were excited by intra-arterial bradykinin. The threshold distending pressure, determined from the SRFs of 29 neurons in both the spinalized and intact states, extrapolated to near 0 mmHg. 3. Short-latency sustained (SL-S) neurons (spinalized, n = 31; intact, n = 11) were also excited at short latency in response to colorectal distension, but responses were sustained for 4-50 s following termination of the distending stimulus. Nine of 11 SL-S neurons in intact rats had long ascending projections. All 42 SL-S neurons were spontaneously active and 41 of 42 had convergent excitatory cutaneous receptive fields, excited exclusively by noxious stimuli (n = 29) or excited by both noxious and nonnoxious stimuli (n = 12). Responses to colorectal distension and spontaneous activity were significantly greater in spinalized rats. Twelve of 12 neurons tested were excited by intra-arterial bradykinin.(ABSTRACT TRUNCATED AT 400 WORDS)     

Intracellular records of the effects of primary afferent input in lumbar spinoreticular tract neurons in the cat

1. The afferent-evoked synaptic input to lumbar spinal cord (L5-S1) neurons that were activated antidromically from the medial pontomedullary reticular formation (nucleus reticularis gigantocelluaris and vicinity) was investigated with the use of intracellular recordings in pentobarbital sodium-anesthetized cats. 2. Spinoreticular tract (SRT) neurons (n = 33) were categorized into three types ("deep-inhibited," "deep-complex," and "intermediate") on the basis of their locations and of their responses to natural and electrical stimulation. 3. The deep-inhibited-type neurons, located in the medial part of the deeper laminae (approximately VI-VIII), comprised a large component of the sample (20/33). They had no demonstrable excitatory receptive field (RF). However, electrical stimulation of low-threshold cutaneous afferents of hindlimb nerves evoked inhibitory postsynaptic potentials (IPSPs) via an oligosynaptic linkage. High-threshold cutaneous and muscle afferents also evoked IPSPs. 4. In the deep-complex-type neurons (8/33), electrical stimulation of low-threshold cutaneous afferents evoked complex IPSP-excitatory postsynaptic potential (EPSP) sequences. With intense stimuli, long-latency C-fiber-like EPSPs were evoked. Two of these eight neurons were characterized as wide-dynamic-range (WDR) neurons with large, excitatory and inhibitory cutaneous RFs. 5. Intermediate-type neurons (5/33) were concentrated in the lateral spinal gray and relatively superficially (approximately lamina V). These neurons had convergent low- and high-threshold cutaneous inputs (WDR neurons). Electrical stimulation of low-threshold cutaneous afferent fibers from within the excitatory RF evoked mono- or disynaptic EPSPs followed by IPSPs. High-threshold muscle and cutaneous afferents also evoked EPSPs. 6. These results show that SRT neurons have a variety of response characteristics resulting from various degrees of spatial and temporal summation of primary afferent input. Neurons with widespread inhibitory responses but no excitatory drive from the periphery comprise a surprisingly large component of the SRT: the function of these cells is unknown. It is apparent that the spinoreticular projection has considerable functional heterogeneity.     

Effects of reversible spinalization on the visceral input to viscerosomatic neurons in the lower thoracic spinal cord of the cat

Single-unit electrical activity has been recorded from 122 viscerosomatic neurons in the T9 and T11 segments of the cat's spinal cord. These neurons were excited by electrical and/or natural stimulation of visceral and somatic afferent fibers. The majority of viscerosomatic neurons (72%) received somatic nociceptive inputs, either exclusively or together with low-threshold somatic inputs. Many of these neurons were excited most strongly by intense mechanical stimulation of subcutaneous tissues, particularly by pinching or squeezing muscle. Twelve viscerosomatic neurons were excited by distensions of the biliary system at levels of biliary pressure greater than 25 mmHg. These intensities of biliary stimulation evoked transient increases in blood pressure, which suggest that the visceral stimuli were of nociceptive nature. The effects of reversible spinalization by cold block were tested on 98 viscerosomatic neurons. Three subgroups of viscerosomatic neurons were distinguished depending on whether their responses to visceral afferent stimulation were increased, decreased, or unchanged in the spinal state. Forty percent of all neurons tested increased the intensity of their responses to visceral stimulation in the spinal state. In addition, many of these neurons developed or increased their background activity and increased their somatic responses in the spinal state. It is concluded that these neurons were subjected to tonic descending inhibition of both somatic and visceral afferent inputs. More than 40% of the neurons in this group were located in or close to lamina V of the dorsal horn. In 44% of all neurons tested the response to visceral stimulation was reduced or abolished by spinalization. The background activity was not affected in the same manner and sometimes even increased during spinalization. The responses to somatic stimuli were fully tested in 11 neurons of this group and were found to be decreased, but not abolished, in nine neurons, unchanged in one cell, and increased in another one. Many of the neurons in this group were located in the ventral horn (laminae VII and VIII). Sixteen percent of all viscerosomatic neurons tested showed no change in their responses to visceral stimulation during spinalization. It is concluded that the visceral input to viscerosomatic neurons in the lower thoracic spinal cord is under considerable descending control, which includes excitation as well as tonic inhibition of visceral afferent information. This may represent part of the widespread effects of visceral nociceptive stimulation.     

Chemical activation of cervical cell bodies: effects on responses to colorectal distension in lumbosacral spinal cord of rats

We have shown that stimulation of cardiopulmonary sympathetic afferent fibers activates relays in upper cervical segments to suppress activity of lumbosacral spinal cells. The purpose of this study was to determine if chemical excitation (glutamate) of upper cervical cell bodies changes the spontaneous activity and evoked responses of lumbosacral spinal cells to colorectal distension (CRD). Extracellular potentials were recorded in pentobarbital-anesthetized male rats. CRD (80 mmHg) was produced by inflating a balloon inserted in the descending colon and rectum. A total of 135 cells in the lumbosacral segments (L(6)-S(2)) were activated by CRD. Seventy-five percent (95/126) of tested cells received convergent somatic input from the scrotum, perianal region, hindlimb, and tail; 99/135 (73%) cells were excited or excited/inhibited by CRD; and 36 (27%) cells were inhibited or inhibited/excited by CRD. A glutamate (1 M) pledget placed on the surface of C(1)-C(2) segments decreased spontaneous activity and excitatory CRD responses of 33/56 cells and increased spontaneous activity of 13/19 cells inhibited by CRD. Glutamate applied to C(6)-C(7) segments decreased activity of 10/18 cells excited by CRD, and 9 of these also were inhibited by glutamate at C(1)-C(2) segments. Glutamate at C(6)-C(7) increased activity of 4/6 cells inhibited by CRD and excited by glutamate at C(1)-C(2) segments. After transection at rostral C(1) segment, glutamate at C(1)-C(2) still reduced excitatory responses of 7/10 cells. Further, inhibitory effects of C(6)-C(7) glutamate on excitatory responses to CRD still occurred after rostral C(1) transection but were abolished after a rostral C(6) transection in 4/4 cells. These data showed that C(1)-C(2) cells activated with glutamate primarily produced inhibition of evoked responses to visceral stimulation of lumbosacral spinal cells. Inhibition resulting from activation of cells in C(6)-C(7) segments required connections in the upper cervical segments. These results provide evidence that upper cervical cells integrate information that modulates activity of distant spinal neurons responding to visceral input.     

Urinary bladder and hindlimb afferent input inhibits activity of primate T2-T5 spinothalamic tract neurons

1. Extracellular recordings were made from 41 spinothalamic tract (STT) neurons on the left side of the T2-T5 spinal segments of 20 monkeys (Macaca fascicularis) anesthetized with alpha-chloralose. Manipulation of the left triceps-chest region and electrical stimulation of cardiopulmonary sympathetic afferent fibers excited these cells. 2. Isotonic urinary bladder distensions (UBD) to pressures between 20 and 80 cmH2O reduced the spontaneous activity in 33 of 41 cells. Cell activity was significantly reduced by UBD at 20 cmH2O. Distensions to 40, 60, and 80 cmH2O produced progressively greater reductions in spontaneous discharge. Activity was decreased throughout distension in 29 cells (tonic inhibition) and at the onset of distension in 3 neurons (phasic inhibition). In one cell, inhibition followed a brief excitation at the onset of distension (phasic excitation-tonic inhibition). Spontaneous bladder contractions also inhibited STT cell activity. 3. Inhibition by UBD was observed in STT cells characterized as wide dynamic range, high threshold, and high threshold inhibitory. No correlation existed between cell type or laminar location and inhibition by urinary bladder distension. Cells excited by cardiopulmonary sympathetic afferent A delta- and C-fibers had a significantly greater tendency to be inhibited by UBD (17 of 18) than cells activated by A delta- but not C-fibers (13 of 20). 4. Urinary bladder distension and pinch of the hindlimbs also reduced activity of STT cells excited by input from cardiopulmonary sympathetic afferents and from the proximal forelimb. 5. Urinary bladder distension to 40, 60, or 80 cmH2O produced a greater absolute but smaller relative reduction in the firing frequency of STT cells as spontaneous activity increased. Thus the magnitude of this inhibitory effect may depend on whether the inhibitory effect is measured as an absolute or relative change in cell activity. 6. Convergent inhibitory input from somatic regions also was observed. Noxious pinch of the hamstring region of the right hindlimb decreased activity in 32 of 39 cells. Left hindlimb pinch inhibited 21 of 38 cells, and 15 of 29 cells were inhibited by right triceps pinch. 7. Convergent inhibitory input from the hamstring region of the hindlimbs and from the urinary bladder to upper thoracic STT cells may be important for coding the intensity and location of noxious visceral and somatic stimuli and for organizing the appropriate sequence of motor responses when multiple noxious stimuli are present.     

Sacral spinal cord neurons responsive to bladder pelvic and perineal inputs in cats

In chloralose-anesthetized or decerebrate male cats, 70% of 73 sacral spinal cord neurons activated from the bladder branch of the pelvic nerve also received excitatory inputs from urethra and/or perineal cutaneous nerves (sensory pudendal in 55% and superficial perineal in 84% of neurons). Only 29% of these neurons were excited by the hindlimb skin and muscle nerves tested. The pelvic nerve-responsive neurons received monosynaptic urethral/perineal input in 25% of cases and required temporal summation of this input in 47% of cases. Of 211 neurons responding to superficial perineal nerve stimulation, 101 were not excited by the other nerves tested. Neurons activated by superficial perineal nerve stimulation were found predominantly in S2. It is likely that the superficial perineal nerve represents an important pathway whereby perineal stimulation influences bladder function.     

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.     

Responses of feline medial medullary reticulospinal neurons to cardiac input

1. Responses of medial medullary reticulospinal (RS) neurons to electrical stimulation of cardiac sympathetic afferents, probing the epicardium and epicardial application of bradykinin, were determined in cats anesthetized with alpha-chloralose. Conduction velocity of RS cells averaged 67 m/s; these neurons were probably part of the RS motor pathway and the bulbospinal pathway that modulates ascending information. Fifty-three RS neurons had unilateral projections and 18 neurons bilateral projections to the thoracic spinal cord. 2. Maximal electrical stimulation of the left stellate ganglion excited 69% of 97 RS neurons with a mean latency of 15 +/- 1.0 ms. Mean spike discharge rate increased from 4 +/- 1.2 to 93 +/- 8.0 spikes/s for responsive neurons. 3. Epicardial bradykinin (0.04 mg) excited 34%, inhibited 2%, and did not affect 64% of 44 RS cells tested. Excited neurons increased their mean discharge rate from 12.3 +/- 3.6 to 18.2 +/- 4.3 spikes/s, with a latency of 24 +/- 3.0 s, in response to bradykinin. Response duration averaged 43 +/- 2.3 s. Neurons responsive to bradykinin had greater spontaneous discharge rates than unresponsive neurons. Thirteen of 16 RS cells excited by bradykinin were located in the gigantocellular tegmental field (FTG); the other three cells were in the paramedian nucleus (PR). 4. Epicardial bradykinin often elicited changes in aortic pressure. Although some neurons responded to altered blood pressure alone, these responses could not account for responses to bradykinin. Furthermore, the percentage of responsive neurons was similar in experiments with intact nerves as well as those with vagotomy and barodenervation. 5. Touching the epicardium with a blunt probe excited 19 of 60 (32%) RS neurons, and visceral receptive fields were mapped for 12 of these cells. Neurons responded with one to three spikes to probing. RS neurons responsive to probing were scattered throughout the medial reticular formation. 6. RS cells were also tested for somatic, auditory, and visual input. Of 63 neurons responsive to sympathetic afferent stimulation, only one did not receive convergent input from at least one of these sources; 51% received input from each tested source. Neurons responsive to bradykinin were more likely to receive visual input than the general population of neurons. RS neurons unresponsive to sympathetic afferent stimulation were less likely to receive convergent inputs from other sensory modalities.(ABSTRACT TRUNCATED AT 400 WORDS)     

Responses and afferent pathways of C1-C2 spinal neurons to cervical and thoracic esophageal stimulation in rats

Because vagal and sympathetic inputs activate upper cervical spinal neurons, we hypothesized that stimulation of the esophagus would activate C(1)-C(2) neurons. This study examined responses of C(1)-C(2) spinal neurons to cervical and thoracic esophageal distension (CED, TED) and afferent pathways for CED and TED inputs to C(1)-C(2) spinal neurons. Extracellular potentials of single C(1)-C(2) spinal neurons were recorded in pentobarbital-anesthetized male rats. Graded CED or TED was produced by water inflation (0.1-0.5 ml) of a latex balloon. CED changed activity of 48/219 (22%) neurons; 34 were excited (E), 12 were inhibited (I), and 2 were E-I. CED elicited responses for 18/18 neurons tested after ipsilateral cervical vagotomy, for 12/14 neurons tested after bilateral vagotomy and for 9/11 neurons tested after bilateral vagotomy and C(6)-C(7) spinal cord transection. TED changed activity of 31/190 (16%) neurons (28E, 3 I). Ipsilateral cervical vagotomy abolished TED-evoked responses of 5/12 neurons. Bilateral vagotomy eliminated responses of 2/4 neurons tested, and C(6)-C(7) spinal transection plus bilateral vagotomy eliminated responses of 2/2 neurons. Thus inputs from CED to C(1)-C(2) neurons most likely entered upper cervical dorsal roots, whereas inputs from TED were dependent on vagal pathways and/or sympathetic afferent pathways that entered the thoracic dorsal roots. These results supported a concept that C(1)-C(2) spinal neurons play a role in integrating visceral information from cervical and thoracic esophagus.