Spinal Mechanisms Underlying Persistent Pain and Referred Hyperalgesia in Rats With an Experimental Ureteric Stone

1998 ◽  
Vol 79 (4) ◽  
pp. 1603-1612 ◽  
Author(s):  
Carolina Roza ◽  
Jennifer M. A. Laird ◽  
Fernando Cervero

Roza, Carolina, Jennifer M. A. Laird, and Fernando Cervero. Spinal mechanisms underlying persistent pain and referred hyperalgesia in rats with an experimental ureteric stone. J. Neurophysiol. 79: 1603–1612, 1998. Spinal neurons processing information from the ureter have been characterized in rats 1–4 days after the implantation of an experimental ureteric stone and compared with those of normal rats. The effects of a conditioning noxious stimulation of the ureter in the presence of the hyperalgesia evoked by the calculosis also were examined. Extracellular recordings were performed at the T12–L1 segments of the spinal cord. In rats with calculosis, more neurons expressed a ureter input (53 vs. 42% in normal rats); such cells being more likely to show background activity, at a higher rate than normals (6.6 ± 1.2 vs. 3.2 ± 0.9 spikes/s; mean ± SE) and increasing with the continuing presence of the stone. The threshold pressure for a ureteric response was higher than in normal rats (79 ± 5 vs. 54 ± 4 mmHg) but the neurons failed to encode increasing intensities of stimulation. Thirty-five percent of the neurons with exclusively innocuous somatic receptive fields had a ureter input in rats with calculosis, whereas none were seen in normal rats. A noxious ureteric distention applied to neurons with ureter input evoked a complex mixture of increases and decreases in somatic receptive field size and/or somatic input properties markedly different from the generalized increases in excitability seen when such a stimulus was applied to normal animals. We conclude that the presence of a ureteric stone evokes excitability changes of spinal neurons (enhanced background activity, greater number of ureter-driven cells, decreased threshold of convergent somatic receptive fields), which likely account for the referred hyperalgesia seen in rats with calculosis. However, further noxious visceral input occurring in the presence of persistent hyperalgesia produces selective changes that cannot be explained by a generalized excitability increase and suggest that the mechanisms underlying maintenance of hyperalgesia include alteration of both central inhibitory and excitatory systems.

1988 ◽  
Vol 60 (6) ◽  
pp. 1967-1981 ◽  
Author(s):  
W. S. Ammons

1. Studies were done to characterize responses of spinal neurons backfired from the ventrolateral medulla to renal and somatic stimuli. Experiments were performed on 31 cats that were anesthetized with alpha-chloralose. Sixty-six spinal neurons were antidromically activated from the area of the lateral reticular nucleus or the ventrolateral reticular formation just rostral to the lateral reticular nucleus contralateral to the recording site. These cells could not be backfired from the medial reticular formation or from the spinothalamic tract just caudal to the thalamus. 2. Cells were located in laminae I, V, and VII of the T12-L2 segments. Antidromic conduction velocities averaged 35.9 +/- 7.2 m/s. Conduction velocities were unrelated to the projection site or laminar location of the cells. Termination sites of 21 cells were located in antidromic mapping experiments. Terminals were localized to the ventrolateral reticular formation, including the lateral reticular nucleus. 3. Responses to electrical stimulation of the renal nerves were always excitatory. Stimulation of renal A-delta-fibers excited 33 cells. These cells failed to respond to stimulation of renal C-fibers. The other 33 cells responded to both A-delta- and C-fiber stimulation. Latencies to A-delta-fiber stimulation averaged 9 +/- 2 ms, whereas latencies to C-fiber stimulation averaged 57 +/- 10 ms. 4. Renal mechanoreceptors were activated by occlusion of the renal vein or upper portion of the ureter. Renal vein occlusion excited 14 of 32 cells tested. Activity increased from 6 +/- 2 to 14 +/- 4 spike/s. Ureteral occlusion increased activity of 19 of 32 cells from 7 +/- 2 to 16 +/- 5 spikes/s. Cells responding to one of the mechanical stimuli were significantly more likely to receive A-delta-and C-fiber input compared with nonresponding cells. Nonresponders were more likely than responders to receive only A-delta input. 5. All cells received somatic input in addition to renal input. Twelve cells were classified as wide dynamic range, 46 as high threshold, and 8 as Deep. Somatic receptive fields most often included skin and muscle of the left flank and abdomen. Thirty-two cells had bilateral receptive fields, and 22 had inhibitory fields in addition to excitatory fields. 6. These data show that spinal neurons projecting to the ventrolateral medulla receive convergent inputs from the kidney and somatic structures. These cells may participate in a variety of functions including autonomic reflexes of renal origin.


1994 ◽  
Vol 266 (1) ◽  
pp. R268-R276 ◽  
Author(s):  
E. W. Akeyson ◽  
L. P. Schramm

The rostral cervical spinal cord is increasingly being considered the source of important propriospinal regulation. To better understand the substrate for this function, we investigated the effects of stimulation of the greater splanchnic nerve (GSN) and both thoracic and cervical somatic afferents on the activity of cervical spinal neurons. Extracellular single-neuron recordings were made in the C2-C5 spinal segments of chloralose-anesthetized, paralyzed, and artificially ventilated rats. Neurons were classified according to their responses to GSN stimulation. Neurons were inhibited by this stimulation as frequently as they were excited. We then studied the characteristics of cervical and thoracic convergent somatic input to each class of neurons. Although all cervical neurons that responded to GSN stimulation responded to electrical stimulation of the iliohypogastric nerve (IHN), only the few neurons that exhibited whole body receptive fields (RF) responded to natural thoracic somatic stimuli. Responses to electrical stimulation of the GSN and IHN were similar for most neurons; most exhibited nociceptive cutaneous RFs in cervical dermatomes. These data indicate that input from cervical somatic afferents and from both thoracic visceral and thoracic somatic afferents converge on individual splanchnic-receptive cervical neurons. Although these neurons exhibited the predicted cervical somatic RFs, responses from thoracic levels did not exhibit discrete RFs, requiring instead more synchronous or more spatially convergent input.


1986 ◽  
Vol 250 (3) ◽  
pp. R435-R443 ◽  
Author(s):  
W. S. Ammons

Responses of 65 thoracolumbar spinal neurons to electrical stimulation of the left renal nerves were examined in 19 cats anesthetized with alpha-chloralose. Cells were found primarily in laminae V and VII of the T12-L2 segments on the left side of the spinal cord. Renal nerve stimulation excited 55 and inhibited 10 cells. Excitatory responses were characterized either by short latency or both short and long latency responses (means +/- SE: 13 +/- 1 and 68 +/- 7 ms). Recordings of the compound action potential in the least splanchnic nerve indicated that early responses resulted from A delta-renal afferent input and long latency responses from C-fiber renal input. Maximal responses to A delta-renal input (3.3 +/- 0.5 spikes/stimulus) were significantly greater than maximal responses to C-fiber renal input (1.5 +/- 0.3 spikes/stimulus). Inhibitory responses were best demonstrated by repetitive stimuli; however, responses of five cells to single stimuli showed that these responses had long latencies to onset (36 +/- 6 ms). All cells were excited or inhibited by somatic stimuli. Excitatory somatic receptive fields invariably included the left flank region and lower abdomen, occasionally included the left hindlimb, and in a few cases included the right hindlimb. Thirteen cells had both excitatory and inhibitory somatic receptive fields. The results show that thoracolumbar spinal neurons receive renal A delta- and C-fiber input that converges with input from somatic structures. These cells may participate in renal pain which is referred to somatic structures or reflexes initiated by renal afferent fibers.


1996 ◽  
Vol 76 (5) ◽  
pp. 3025-3037 ◽  
Author(s):  
K. Ren ◽  
R. Dubner

1. The role of descending brain stem modulatory systems in the development of persistent behavioral hyperalgesia and dorsal horn hyperexcitability was studied in rats with unilateral hindpaw inflammation. Inflammation was induced by intraplantar injection of complete Freund's adjuvant (CFA, 0.05 ml of an 1:1 oil/saline emulsion, 25 micrograms Mycobacterium), or lambda carrageenan (1 mg/ 0.1 ml saline). Thermal hyperalgesia was assessed by testing paw withdrawal latency (PWL) to a noxious heat stimulus. Superficial dorsal horn nociceptive (nociceptive specific, NS, and wide dynamic range, WDR) neuronal activity in the lumbar spinal cord was recorded extracellularly in chloralose-anesthetized rats. 2. Bilateral lesions of the dorsolateral funiculus (DLFX) at the T10 level were made in 13 rats, and the development of thermal hyperalgesia in these rats was compared with sham-operated or nonoperated control rats. In rats receiving a 0.05-ml CFA injection, a similar magnitude of hyperalgesia developed in the inflamed paw in DLFX (n = 7) and control (n = 8) rats. In addition, there appeared to be a contralateral hyperalgesia that was most apparent between 2 and 24 h after injection of CFA in DLFX rats. The CFA-induced contralateral effects were significantly different (P < 0.05) from the control rats at 2 and 6 h. 3. The intensity of the thermal stimulus was reduced and a low dose of carrageenan (1 mg) was injected into one hindpaw to further reveal the potentiation of hyperalgesia in DLFX rats. Throughout the 0.5- to 4-h time period after the injection of carrageenan, the PWL of the inflamed paws in DLFX rats (n = 6) was significantly shorter than that of control rats (n = 10; 2-way analysis of variance, F1,14 = 14.04, P < 0.01), suggesting the enhancement of hyperalgesia in DLFX rats. A hyperalgesia on the noninflamed paws was also more apparent in this experiment in DLFX rats, when compared with control rats. DLFX did not affect the baseline PWL of the rats. 4. A reversible spinalization was produced by application of a local anesthetic, lidocaine (2%, 0.1 ml), onto the dorsal surface of the thoracic cord (T10-12). This procedure produced thoracic spinal block that lasted for 90 min. The effects of thoracic lidocaine block on nociceptive neuronal activity were studied in 11 neurons (NS = 7, WDR = 4) in CFA-inflamed rats and 10 neurons (NS = 6, WDR = 4) in noninflamed naive rats. After the thoracic lidocaine block, rats showed increases in background activity, expansion of the receptive fields, and increased responses to noxious thermal, mechanical, and electrical stimuli. 5. Quantitative comparison revealed that the mean change in background firing rate of dorsal horn neurons was greater in inflamed [NS: 18.3 +/- 0.4 Hz, (mean +/- SE) n = 7; WDR: 10.9 +/- 0.7 Hz, n = 4] than that in noninflamed (NS: 2.3 +/- 0.3 Hz, n = 6; WDR: 3.3 +/- 0.4 Hz, n = 4) rats (P < 0.01, t-test) after thoracic lidocaine block. Thoracic saline application produced a 2.8 +/- 0.4 Hz decrease in background activity (2 NS and 2 WDR units). The expansion of the receptive fields after thoracic lidocaine block was also greater in inflamed (NS: 141 +/- 9% control, n = 6; WDR: 240 +/- 36% control, n = 4) than in noninflamed (NS: 114 +/- 9% control, n = 6; WDR: 167 +/- 21% control, n = 4) rats (P < 0.05, t-test). Thoracic saline did not produce a significant change in the receptive field size (105 +/- 9%, n = 4). The increases in responses to noxious thermal and mechanical stimuli after thoracic lidocaine block were also significantly greater in inflamed than in noninflamed rats (P < 0.01). There was no significant difference in the increase in responses to electrical stimulation of the sciatic nerve after lidocaine between inflamed and noninflamed rats.(ASTRACT TRUNCATED)


1996 ◽  
Vol 76 (5) ◽  
pp. 3239-3248 ◽  
Author(s):  
J. M. Laird ◽  
C. Roza ◽  
F. Cervero

1. Stimulation of the ureter in humans evokes only painful sensations. A large proportion of ureteric afferents show high activation thresholds to ureter pressure increases and encode stimuli within the noxious range. However, little is known about how these properties are reflected in the central processing of ureteric information. In this study, dorsal horn neurons recorded in the left side of the T12-L1 spinal cord of anesthetized rats have been tested for responses to innocuous and noxious pressure stimuli applied to the ipsilateral ureter. 2. Single-unit recordings were made from 76 neurons with somatic receptive fields on the left flank, of which 57 were fully characterized and tested by raising the ureter pressure to 80 mmHg for 30 s. Of these 57 neurons, 24 (42%) were influenced by the ureter stimulus, as follows: 18 were excited, 2 were inhibited, and 4 showed changes in background activity and/or in somatic receptive field area, without a time-locked change in firing rate. The remaining 33 cells (58%) showed no changes in firing rate, background activity, somatic receptive field area, or input properties as a result of ureter stimulation. 3. Neurons responding to the 80-mmHg stimulus were further tested with a range of ureter pressures (5-100 mmHg). No responses were evoked by stimuli of < 20 mmHg, and responses observed were proportional to stimulus intensity. Excitatory responses showed a long onset latency (median = 23 s) and long afterdischarges (median = 145 s). 4. All neurons with ureter input had nociceptive somatic inputs. When compared with neurons without ureter input, cells with ureter input were more likely to show background activity (80 vs. 27%) and more likely to have bilateral somatic receptive fields (30 vs. 6%). Neurons with ureter input had higher rates of background activity and larger somatic receptive fields. Ureter stimulation also produced changes in the somatic receptive field area of neurons excited or inhibited by the stimulus, indicating a high degree of plasticity in the ureteric nociceptive pathway. 5. We conclude that the characteristics of the responses of dorsal horn neurons with ureter input to noxious and innocuous ureter stimulation indicate that they receive ureteric input mainly from high-threshold afferents, and that their response properties correlate well with ureteric pain sensation in humans.


1993 ◽  
Vol 90 (23) ◽  
pp. 11142-11146 ◽  
Author(s):  
S Bisti ◽  
C Trimarchi

Prenatal unilateral enucleation in mammals causes an extensive anatomical reorganization of visual pathways. The remaining eye innervates the entire extent of visual subcortical and cortical areas. Electrophysiological recordings have shown that the retino-geniculate connections are retinotopically organized and geniculate neurones have normal receptive field properties. In area 17 all neurons respond to stimulation of the remaining eye and retinotopy, orientation columns, and direction selectivity are maintained. The only detectable change is a reduction in receptive field size. Are these changes reflected in the visual behavior? We studied visual performance in cats unilaterally enucleated 3 weeks before birth (gestational age at enucleation, 39-42 days). We tested behaviorally the development of visual acuity and, in the adult, the extension of the visual field and the contrast sensitivity. We found no difference between prenatal monocularly enucleated cats and controls in their ability to orient to targets in different positions of the visual field or in their visual acuity (at any age). The major difference between enucleated and control animals was in contrast sensitivity:prenatal enucleated cats present a loss in sensitivity for gratings of low spatial frequency (below 0.5 cycle per degree) as well as a slight increase in sensitivity at middle frequencies. We conclude that prenatal unilateral enucleation causes a selective change in the spatial performance of the remaining eye. We suggest that this change is the result of a reduction in the number of neurones with large receptive fields, possibly due to a severe impairment of the Y system.


2005 ◽  
Vol 93 (6) ◽  
pp. 3537-3547 ◽  
Author(s):  
Chong Weng ◽  
Chun-I Yeh ◽  
Carl R. Stoelzel ◽  
Jose-Manuel Alonso

Each point in visual space is encoded at the level of the thalamus by a group of neighboring cells with overlapping receptive fields. Here we show that the receptive fields of these cells differ in size and response latency but not at random. We have found that in the cat lateral geniculate nucleus (LGN) the receptive field size and response latency of neighboring neurons are significantly correlated: the larger the receptive field, the faster the response to visual stimuli. This correlation is widespread in LGN. It is found in groups of cells belonging to the same type (e.g., Y cells), and of different types (i.e., X and Y), within a specific layer or across different layers. These results indicate that the inputs from the multiple geniculate afferents that converge onto a cortical cell (approximately 30) are likely to arrive in a sequence determined by the receptive field size of the geniculate afferents. Recent studies have shown that the peak of the spatial frequency tuning of a cortical cell shifts toward higher frequencies as the response progresses in time. Our results are consistent with the idea that these shifts in spatial frequency tuning arise from differences in the response time course of the thalamic inputs.


1996 ◽  
Vol 75 (6) ◽  
pp. 2441-2450 ◽  
Author(s):  
D. D. Rasmusson

1. Single neurons in the ventroposterior lateral thalamic nucleus were studied in 10 anesthetized raccoons, 4 of which had undergone amputation of the fourth digit 4-5 mo before recording. Neurons with receptive fields on the glabrous skin of a forepaw digit were examined in response to electrical stimulation of the “on-focus” digit that contained the neuron's receptive field and stimulation of an adjacent, “off-focus” digit. 2. In normal raccoons all neurons responded to on-focus stimulation with an excitation at a short latency (mean 13 ms), whereas only 63% of the neurons responded to off-focus digit stimulation. The off-focus responses had a longer latency (mean 27.2 ms) and a higher threshold than the on-focus responses (800 and 452 microA, respectively). Only 3 of 32 neurons tested with off-focus stimulation had both a latency and a threshold within the range of on-focus values. Inhibition following the excitation was seen in the majority of neurons with both types of stimulation. 3. In the raccoons with digit removal, the region of the thalamus that had lost its major peripheral input (the “deafferented” region) was distinguished from the normal third and fifth digit regions on the basis of the sequence of neuronal receptive fields within a penetration and receptive field size as described previously. 4. Almost all of the neurons in the deafferented region (91%) were excited by stimulation of one or both adjacent digits. The average latency for these responses was shorter (15.3 ms) and the threshold was lower than was the case with off-focus stimulation in control animals. These values were not significantly different from the responses to on-focus stimulation in the animals with digit amputation. 5. These results confirm that reorganization of sensory pathways can be observed at the thalamic level. In addition to the changes in the somatotopic map that have been shown previously with the use of mechanical stimuli, the present paper demonstrates an improvement in several quantitative measures of single-unit responses. Many of these changes suggest that this reorganization could be explained by an increased effectiveness of preexisting, weak connections from the off-focus digits; however, the increase in the proportion of neurons responding to stimulation of adjacent digits may indicate that sprouting of new connections also occurs.


1994 ◽  
Vol 11 (4) ◽  
pp. 703-720 ◽  
Author(s):  
Ming Sun ◽  
A. B. Bonds

AbstractThe two-dimensional organization of receptive fields (RFs) of 44 cells in the cat visual cortex and four cells from the cat LGN was measured by stimulation with either dots or bars of light. The light bars were presented in different positions and orientations centered on the RFs. The RFs found were arbitrarily divided into four general types: Punctate, resembling DOG filters (11%); those resembling Gabor filters (9%); elongate (36%); and multipeaked-type (44%). Elongate RFs, usually found in simple cells, could show more than one excitatory band or bifurcation of excitatory regions. Although regions inhibitory to a given stimulus transition (e.g. ON) often coincided with regions excitatory to the opposite transition (e.g. OFF), this was by no means the rule. Measurements were highly repeatable and stable over periods of at least 1 h. A comparison between measurements made with dots and with bars showed reasonable matches in about 40% of the cases. In general, bar-based measurements revealed larger RFs with more structure, especially with respect to inhibitory regions. Inactivation of lower cortical layers (V-VI) by local GABA injection was found to reduce sharpness of detail and to increase both receptive-field size and noise in upper layer cells, suggesting vertically organized RF mechanisms. Across the population, some cells bore close resemblance to theoretically proposed filters, while others had a complexity that was clearly not generalizable, to the extent that they seemed more suited to detection of specific structures. We would speculate that the broadly varying forms of cat cortical receptive fields result from developmental processes akin to those that form ocular-dominance columns, but on a smaller scale.


Cephalalgia ◽  
2020 ◽  
pp. 033310242097046
Author(s):  
Michael Koch ◽  
Julika Sertel-Nakajima ◽  
Karl Messlinger

Background The pathophysiology of headaches associated with rhinosinusitis is poorly known. Since the generation of headaches is thought to be linked to the activation of intracranial afferents, we used an animal model to characterise spinal trigeminal neurons with nociceptive input from the dura mater and paranasal sinuses. Methods In isoflurane anaesthetised rats, extracellular recordings were made from neurons in the spinal trigeminal nucleus with afferent input from the exposed frontal dura mater. Dural and facial receptive fields were mapped and the paranasal cavities below the thinned nasal bone were stimulated by sequential application of synthetic interstitial fluid, 40 mM potassium chloride, 100 µM bradykinin, 1% ethanol (vehicle) and 100 µm capsaicin. Results Twenty-five neurons with input from the frontal dura mater and responses to chemical stimulation of the paranasal cavities were identified. Some of these neurons had additional receptive fields in the parietal dura, most of them in the face. The administration of synthetic interstitial fluid, potassium chloride and ethanol was not followed by significant changes in activity, but bradykinin provoked a cluster of action potentials in 20 and capsaicin in 23 neurons. Conclusion Specific spinal trigeminal neurons with afferent input from the cranial dura mater respond to stimulation of paranasal cavities with noxious agents like bradykinin and capsaicin. This pattern of activation may be due to convergent input of trigeminal afferents that innervate dura mater and nasal cavities and project to spinal trigeminal neurons, which could explain the genesis of headaches due to disorders of paranasal sinuses.


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