Plasticity in somatic receptive fields after nerve injury

Devor and Wall, in a pioneering electrophysiological study, examined the change in somatic receptive fields in the dorsal horn of the spinal cord after nerve injury. Rather than the anticipated loss of an area of electrophysiological perception, the system demonstrated ‘plasticity’ whereby novel receptive fields, remote to the corresponding area of damage, were evident. The authors postulated that this neuroplasticity occurred via a hitherto undefined spinal mechanism, which lead to an explosion of interest and research to elucidate the mechanisms of central plasticity. In this truly landmark paper, the idea of the nervous system being an inherently ‘hard-wired’ structure was made redundant and the concept of neuroplasticity was given robust form.

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

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.

Spinal dorsal horn neurons responding to noxious distension of the ureter in anesthetized rats

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.

Projections from the pelvic nerve to the periphery of the cat's thalamic ventral posterolateral nucleus and adjacent regions of the posterior complex

1. Mapping experiments were performed in the region of the ventral posterolateral nucleus of the lateral thalamus in pentobarbitone-anesthetized cats with the aim to locate foci with input from the electrically stimulated pelvic nerve. The locations of the recording sites were verified in Nissl-stained histological sections with reference to electrolytic lesions. 2. Of the 68 visceroceptive thalamic neurons identified, 63% were located in the periphery of the ventral posterolateral nucleus (VPLp) and 34% in the dorsal, lateral, and medial aspects of the posterior complex (POd, POl, and POm, respectively) directly adjacent to VPLp. The region surrounding the middle and caudal part of the ventral posterolateral nucleus (VPL) received a much denser input from the pelvic nerve than that around the rostral pole of VPL. 3. The response latencies of the thalamic neurons to pelvic nerve stimulation ranged from 10 to 65 ms (median: 16 ms; interquartile distance: 12–20 ms) indicating a transmission of information from the pelvic space via small and large diameter myelinated fibers. 4. Seventy-nine percent of the visceroceptive neurons tested (n = 58), in addition, had low threshold somatic receptive fields that were located in 67% of the cases in regions of the lower back, the thigh, the tail and/or the heel and in 26% of the cases on the hindfoot. None of the 40 visceroceptive neurons tested with noxious mechanical stimulation of the skin responded to this kind of stimulus.(ABSTRACT TRUNCATED AT 250 WORDS)

Characterization of responses of T2-T4 spinal cord neurons to esophageal distension in the rat

1. Three hundred fifty neurons in the T2-T4 spinal segments of 38 intact, pentobarbital sodium-anesthetized, pancuronium-paralyzed male rats were examined for somatic receptive fields and responses to midthoracic esophageal distension (ED). Recordings were made at a depth of 0.1–1.45 mm from the dorsal spinal cord surface and from the midline to approximately 1.0 mm lateral. 2. Fifty-six of the 350 total neurons (16%) responded to ED, produced by air inflation of a latex balloon (0.5–1.5 ml). Most of these 56 neurons (84%) were excited by ED, and all except one were excited at a short latency (< 2 s) to stimulus onset. The response to ED in about one-half of all excited neurons terminated abruptly with termination of the stimulus; the other neurons exhibited an afterdischarge of 5 to > 80 s. Repeated ED at a constant intensity (1.25 ml, 30 s every 6 min) produced stable and reproducible responses of neurons excited by ED. Twenty-one percent of neurons that responded to ED were antidromically invaded from the spinomedullary junction. 3. Graded ED (0.5–1.5 ml, 30 s every 6 min) produced linear and accelerating stimulus-response functions in the 29 neurons tested. The mean threshold for distension, determined with a least-squares regression analysis, was extrapolated to near 0.5 ml of distending volume, and no difference in response threshold was found between neuronal groups with or without after-discharge. 4. The spontaneous activity of 7 of the 56 neurons (12.5%) that responded to ED was inhibited by the stimulus. Stimulus-response functions for four neurons inhibited by ED were intensity dependent. The spontaneous activity of these neurons was inhibited to a mean of 24.5% of the prestimulus control by 1.25 ml ED. 5. Two neurons of the total sample of 56 (3.5%) responded to ED (1.50 ml) in a biphasic excitatory-inhibitory manner. The excitatory component of excitatory-inhibitory neurons encoded the intensity of ED; the inhibitory component during the second half of ED was apparent only at greater distending volumes (1.25–1.5 ml). 6. Somatic receptive fields were found for 303/350 neurons, and 98% were located on the thorax and proximal forearm (all ipsilateral). Five neurons in T2–T4 spinal segments had their cutaneous receptive fields located on caudal parts of the body (tail, hindleg, scrotum).(ABSTRACT TRUNCATED AT 400 WORDS)

Responses of neurons in and near the thalamic ventrobasal complex of the rat to stimulation of uterus, cervix, vagina, colon, and skin

1. Previous studies in the rat and other species have shown that neurons in and near the ventrobasal complex (VB) can be activated by various visceral as well as somatic stimuli. 2. This study examined the responses of 84 single neurons in and near the rostral 2/3 of VB in 19 adult female rats in estrus to mechanical stimulation of the skin (brush, pressure, noxious pinch) and 4 different visceral stimuli, as follows: distension of both uterine horns, mechanical probing of the vagina, gentle pressure against the cervix, and distension of the colon. The rats were studied while under moderate gaseous anesthesia (33% O2-67% N2O + 0.5% halothane) and paralyzed (pancuronium bromide). 3. Of 77 neurons tested with both somatic and visceral stimuli, 70 were responsive to one type and/or the other. Responses to somatic stimuli were immediate with brief afterdischarges to the pinch stimuli. In contrast, responses to visceral stimuli were delayed an average of 9 s with long afterdischarges averaging 2 min. Most viscerally responsive neurons (74%) had somatic receptive fields, often (44%) to noxious pinch. 4. Of the 70 responsive neurons, 43 (61%) responded to 1 or more of the 4 visceral stimuli, primarily with excitation. Most of these 43 neurons (71%) were responsive to uterine distension, whereas fewer responded to stimulation of the cervix (45%), vagina (29%), or colon (34%). 5. Viscerally responsive neurons were preferentially located in regions bordering or near VB. Only 6 of 22 neurons within the core of VB (27%) responded to visceral stimuli, in contrast with 37 of 48 neurons bordering or near VB (77%). 6. The six viscerally responsive neurons within VB all had somatic receptive fields located primarily on the caudal part of the body and were responsive to only one or two of the four visceral stimuli, usually the uterus. The 37 viscerally responsive neurons bordering or near VB were of 3 types. Neurons of the first type (n = 15) were scattered throughout the areas bordering VB and responded to both somatic and visceral stimuli much like VB neurons, except that they showed more visceral convergence. Neurons of the second type (n = 11) were concentrated at the rostral and dorsal borders of VB and responded only to visceral stimuli, mainly the uterus. Neurons of the third type (n = 11) were concentrated ventrally and had very complex, long-lasting and history-dependent response characteristics to both visceral and somatic stimuli.(ABSTRACT TRUNCATED AT 400 WORDS)

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.

Spinoreticular cell responses to intrarenal injections of bradykinin

Thirty cats were anesthetized with alpha-chloralose, paralyzed, and artificially ventilated. Extracellular unit activity was recorded from 63 spinoreticular tract (SRT) neurons in the T12-L2 segments. All cells were excited by renal nerve stimulation and had somatic receptive fields. Intrarenal injection of bradykinin (4 micrograms/kg) increased activity of 36 cells from 7 +/- 1 to 23 +/- 5 spikes/s. Latency to onset of responses averaged 11 +/- 2 s and latencies to peak were 26 +/- 5 s. Intrarenal injection of isotonic saline vehicle or intravenous injection of the same dose of bradykinin failed to alter activity. Responses increased as dosage increased from 2 to 12 micrograms/kg. Seventeen cells exhibited tachyphylaxis to repeated injections. Cells most likely to respond to bradykinin received both A delta- and C-fiber renal inputs and/or were located in lamina V of the spinal gray matter. Mechanical pressure applied to the renal capsule excited eight of the cells that responded to bradykinin. These results show that activation of renal afferent fibers with bradykinin leads to activation of T12-L2 SRT neurons. These cells may participate in the ascending limb of supraspinal reflexes initiated by renal receptors.

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)