Differential effects of morphine and clonidine on visceral and cutaneous spinal nociceptive transmission in the rat

1989 ◽  
Vol 62 (1) ◽  
pp. 220-230 ◽  
Author(s):  
T. J. Ness ◽  
G. F. Gebhart
Keyword(s):  
Spontaneous Activity ◽  
Dorsal Horn ◽  
Short Latency ◽  
Base Line ◽  
Neuronal Responses ◽  
Colorectal Distension ◽  
Nociceptive Transmission ◽  
Dorsal Horn Neurons ◽  
Spinal Segments ◽  
Dose Dependent

1. The effect of morphine or clonidine administered systemically on visceral and cutaneous spinal nociceptive transmission was examined in 45 dorsal horn neurons in spinalized, decerebrate rats: 17 "cutaneous" dorsal horn neurons located in the L3-L5 spinal segments were excited by heating the glabrous skin of the hindpaw (48 degrees C, 15 s) and 28 "visceral" dorsal horn neurons located in the T13-L2 spinal segments were excited by colorectal distension (80 mmHg, 20 s). The 28 visceral dorsal horn neurons were subclassified as 18 short-latency abrupt neurons (SL-A), which were excited by colorectal distension at short latency (less than 1 s) and whose activity abruptly returned to base line following termination of the distending stimulus, and as 10 short-latency-sustained (SL-S) neurons, which also were excited at short latency (less than 1 s) by colorectal distension, but whose activity was sustained above base line for 4-31 s following termination of the distending stimulus. 2. Morphine produced a dose-dependent, naloxone-reversible inhibition of both spontaneous activity and/or neuronal responses during heating or colorectal distension of 8 SL-A, 7 SL-S, and 11 cutaneous dorsal horn neurons. Comparison of the effective doses of morphine to produce a 50% reduction in the response of the neurons (ED50s) during colorectal distension or heating demonstrated that, at the intensities of distension and heating employed, SL-S neurons were affected at the least dosage (ED50 = 0.46 mumol/kg), followed by SL-A neurons (ED50 = 1.95 mumol/kg) and cutaneous neurons (ED50 = 6.12 mumol/kg). Effects on spontaneous activity were variable: at low doses morphine produced an increase in the spontaneous activity of 2 SL-A and 5 cutaneous neurons; greater doses (up to 42 mumol/kg) inhibited in all of the SL-A and SL-S neurons, but not three cutaneous neurons studied. With the exclusion of these three neurons, the ED50s for inhibition of spontaneous activity were comparable to the ED50s for inhibition of neuronal responses during colorectal distension or heating of the hindpaw in all three neuronal groups. 3. Clonidine produced a dose-dependent, yohimbine- or phentolamine-reversible inhibition of both spontaneous activity and neuronal responses during heating or colorectal distension of 10 SL-A, 3 SL-S, and 6 cutaneous dorsal horn neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

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

1988 ◽  
Vol 60 (4) ◽  
pp. 1419-1438 ◽  
Author(s):  
T. J. Ness ◽  
G. F. Gebhart
Keyword(s):  
Neuronal Response ◽  
Receptive Fields ◽  
Short Latency ◽  
Base Line ◽  
Colorectal Distension ◽  
Stimulus Response ◽  
C Fibers ◽  
Spinal Segments ◽  
Intact Rats

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)

Spinal pathways mediating tonic, coeruleospinal, and raphe-spinal descending inhibition in the rat

1987 ◽  
Vol 58 (1) ◽  
pp. 138-159 ◽  
Author(s):  
S. L. Jones ◽  
G. F. Gebhart
Keyword(s):  
Spontaneous Activity ◽  
Dorsal Horn ◽  
Unit Activity ◽  
Tail Flick ◽  
Descending Inhibition ◽  
Nociceptive Transmission ◽  
Dorsal Horn Neurons ◽  
C Fibers ◽  
Electrophysiological Studies ◽  
Evoked Activity

1. The contribution of midline medullary bulbospinal neurons to descending inhibition from the locus coeruleus (LC) and the funicular trajectories of coeruleo- and raphe-spinal fibers mediating inhibition of spinal nociceptive transmission were examined in different experiments. Extracellular recordings of lumbar dorsal horn neurons were made in deeply pentobarbital-anesthetized, paralyzed rats. All units studied responded to electrical stimulation of the ipsilateral tibial nerve at intensities supramaximal to activate A-alpha-delta- and C-fibers and to mechanical and heat (50 degrees C) stimuli of the glabrous skin of the ipsilateral hind foot. Parallel studies were done in lightly pentobarbital-anesthetized rats utilizing the nociceptive tail-flick (TF) reflex. 2. To examine the contribution of bulbospinal neurons in the nucleus raphe magnus (NRM) to descending coeruleospinal inhibition, lidocaine microinjections were made into the NRM to produce a time-limited, reversible block. Lidocaine microinjections into the NRM effectively blocked NRM stimulation-produced inhibition of the TF reflex (prelidocaine stimulation thresholds were increased two to three times), but did not affect stimulation-produced inhibition from the LC. 3. In parallel electrophysiological studies, stimulation in the NRM inhibited heat-evoked dorsal horn unit activity to 31% of control, whereas stimulation in the LC/SC inhibited heat-evoked activity of the same units to 30% of control. Following NRM lidocaine microinjections, stimulation at the same intensity in the NRM no longer inhibited heat-evoked activity (93% of control), confirming the efficacy of the lidocaine block. LC stimulation-produced inhibition, however, was not affected by blockage of the NRM; heat-evoked unit activity was inhibited by LC stimulation to 39% of control. 4. The effects of ipsilateral and bilateral ventrolateral funiculus (VLF) lidocaine microinjections on spontaneous and heat-evoked unit activity were examined in other experiments. Spontaneous activity increased following ipsilateral VLF lidocaine microinjections for 13/18 units; decreases and no change in spontaneous activity were observed for three and two units, respectively. Heat-evoked unit activity was increased significantly following ipsilateral VLF lidocaine microinjections.(ABSTRACT TRUNCATED AT 400 WORDS)

Differential Processing of Noxious Colonic Input by Thoracolumbar and Lumbosacral Dorsal Horn Neurons in the Rat

2005 ◽  
Vol 94 (6) ◽  
pp. 3788-3794 ◽  
Author(s):  
Gexin Wang ◽  
Bin Tang ◽  
Richard J. Traub
Keyword(s):  
Dorsal Horn ◽  
Single Cells ◽  
Male Rats ◽  
Colonic Inflammation ◽  
Dorsal Horn Neurons ◽  
Inflammatory Stimuli ◽  
Before And After ◽  
Spinal Segments ◽  
Colorectal Distention ◽  
Multiple Cells

Previous studies suggest the lumbosacral (LS) spinal cord processes acute colorectal stimuli whereas the thoracolumbar (TL) and LS spinal segments process inflammatory stimuli. In this study, the effects of colorectal distention (CRD) on TL and LS dorsal horn neuronal activity were recorded in Nembutal-anesthetized male rats both with and without colonic inflammation. Both single cells (before and after inflammation) and populations (multiple cells from noninflamed or inflamed rats) were studied. CRD-responsive neurons had excitatory Abrupt (on–off with stimulus) or Sustained (prolonged after discharge) responses or were Inhibited by CRD. In noninflamed rats, a significantly greater percentage of LS neurons (63% Abrupt, 27% Sustained) were excited by CRD than TL neurons (61% Abrupt, 3% Sustained). The remaining cells were Inhibited (10% LS, 36% TL). LS Abrupt neurons had lower thresholds and greater response magnitudes to CRD compared with TL Abrupt neurons. After colonic inflammation, TL neurons became more excitable: the percentage of Inhibited neurons decreased, the response magnitude of Abrupt neurons increased, and the threshold decreased. In contrast, in single-cell recordings, the response of LS Sustained neurons increased, whereas LS Abrupt neurons decreased. These data suggest that in noninflamed rats, the net response to CRD of TL visceroceptive spinal sensory neurons is less than that of LS neurons. Colonic inflammation increases the net response of TL neurons and differentially modulates the response of LS neurons. These differences may contribute to the functional dichotomy between the TL and LS spinal segments in processing acute and inflammatory colorectal pain.

scholarly journals Regulating nociceptive transmission by VGluT2-expressing spinal dorsal horn neurons

2018 ◽  
Vol 147 (4) ◽  
pp. 526-540 ◽  
Author(s):  
Li Wang ◽  
Shao-Rui Chen ◽  
Huijie Ma ◽  
Hong Chen ◽  
Walter N. Hittelman ◽  
...  
Keyword(s):  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Nociceptive Transmission ◽  
Dorsal Horn Neurons ◽  
Spinal Dorsal ◽  
Spinal Dorsal Horn Neurons

Quantitative comparison of inhibition of visceral and cutaneous spinal nociceptive transmission from the midbrain and medulla in the rat

1987 ◽  
Vol 58 (4) ◽  
pp. 850-865 ◽  
Author(s):  
T. J. Ness ◽  
G. F. Gebhart
Keyword(s):  
Spinal Cord ◽  
Gain Control ◽  
Neuronal Responses ◽  
Spinal Neurons ◽  
Descending Inhibition ◽  
Colorectal Distension ◽  
Mean Intensity ◽  
Nociceptive Transmission ◽  
Plantar Surface ◽  
The Mean

1. The descending inhibition of neuronal responses by focal electrical stimulation or glutamate microinjections in the periaqueductal gray (PAG) or rostral ventromedial medulla (RVM) was quantitatively studied on 61 spinal neurons in halothane-N2O-anesthetized paralyzed rats. Thirty-six neurons were located in the medial L6-S1 spinal cord and were consistently and reproducibly excited by distension of the descending colon and rectum (75 mmHg). Twenty-five other neurons were located in the dorsal horn of spinal segments L3-L5 and were consistently and reproducibly excited by radiant heating (50 degrees C) of the glabrous skin of the plantar surface of the left (ipsilateral) hind foot. 2. The inhibition of neuronal responses to colorectal distension by stimulation in the PAG or RVM differed quantitatively when examined on the same spinal neurons. Inhibition of neuronal responses to distension occurred at a lower mean threshold of stimulation in the RVM than in the PAG. The mean intensity of stimulation in the RVM producing an attenuation to 50% of the control response to colorectal distension (75 mmHg, 20 s) was significantly lower than the mean intensity of stimulation in the PAG producing a 50% attenuation of the same spinal units. The mean magnitude of inhibition produced by stimulation in the RVM was significantly greater than that produced on the same spinal units by the same intensity of stimulation in the PAG. However, stimulation in the RVM and PAG produced the same mean percent change in inhibition per 25-microA increase in the intensity of stimulation. Thus the slopes of the lines of recruitment of descending inhibition from the PAG and RVM as a function of increasing intensities of stimulation are the same; the lines of recruitment of inhibition are parallel. These findings are virtually identical to those found by others in studies of modulation of neuronal responses to noxious heating of the skin. 3. Neuronal intensity coding to both graded heating of the hindfoot and graded colorectal distension was montonus and accelerating and could be expressed as linear stimulus-response functions (SRFs) in the temperature and pressure ranges studied (46-52 degrees C, 25-100 mmHg). Stimulation in the PAG modulated the SRFs differently than did stimulation in the RVM. Stimulation in the PAG decreased the slope of the SRFs without affecting the units' thresholds of response, thus influencing the gain control of both cutaneous and visceral nociception in the spinal cord.(ABSTRACT TRUNCATED AT 400 WORDS)

Changes in Properties of Spinal Dorsal Horn Neurons and Their Sensitivity to Morphine after Spinal Cord Injury in the Rat

2005 ◽  
Vol 102 (1) ◽  
pp. 152-164 ◽  
Author(s):  
Jungang Wang ◽  
Mikito Kawamata ◽  
Akiyoshi Namiki
Keyword(s):  
Spinal Cord ◽  
Spontaneous Activity ◽  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
High Threshold ◽  
Dorsal Horn Neurons ◽  
Spinal Dorsal ◽  
Cord Injury ◽  
Spinal Dorsal Horn Neurons ◽  
Wdr Neurons

Background To gain a better understanding of spinal cord injury (SCI)-induced central neuropathic pain, the authors investigated changes in properties of spinal dorsal horn neurons located rostrally and caudally to the lesion and their sensitivity to morphine in rats after SCI. Methods The right spinal cord of Sprague-Dawley rats was hemisected at the level of L2. At 10 to 14 days after the SCI, when mechanical hyperalgesia/allodynia had fully developed, spontaneous activity and evoked responses to mechanical stimuli of wide-dynamic-range (WDR) and high-threshold neurons rostral and caudal to the lesion were recorded. Effects of cumulative doses of systemic (0.1-3 mg/kg) and spinal (0.1-5 microg) administration of morphine on spontaneous activity and evoked responses to the stimuli of the neurons were evaluated. Results Spontaneous activity significantly increased in WDR neurons both rostral and caudal to the SCI site, but high-frequency background discharges with burst patterns were only observed in neurons rostral to the SCI site. Significant increases in responses to the mechanical stimuli were seen both in WDR and high-threshold neurons located both rostrally and caudally to the lesion. The responses to nonnoxious and noxious stimuli were significantly greater in caudal WDR neurons than in rostral WDR neurons. In contrast, the responses to pinch stimuli were significantly higher in rostral high-threshold neurons than those in caudal high-threshold neurons. Systemically administered morphine had a greater effect on responses to nonnoxious and noxious stimuli of rostral WDR neurons than those of caudal WDR neurons. Spinally administered morphine significantly suppressed responses of WDR neurons in SCI animals to nonnoxious stimuli compared with those in sham-operated control animals. Conclusions The findings suggest that changes in properties of spinal dorsal horn neurons after SCI are caused by different mechanisms, depending on the classification of the neurons and their segmental locations.

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