A Comparison of the Cellular and Molecular Atlases of the Macaque and Mouse Dorsal Horns

2021 ◽  
Author(s):  
Cynthia Mary Arokiaraj ◽  
Michael Kleyman ◽  
Alexander Chamessian ◽  
Stephanie Shiers ◽  
Byungsoo Kang ◽  
...  
Keyword(s):  
Dorsal Horns

Spatiotemporal CCR1, CCL3(MIP-1α), CXCR4, CXCL12(SDF-1α) expression patterns in a rat spinal cord injury model of posttraumatic neuropathic pain

2011 ◽  
Vol 14 (5) ◽  
pp. 583-597 ◽  
Author(s):  
Friederike Knerlich-Lukoschus ◽  
Beata von der Ropp-Brenner ◽  
Ralph Lucius ◽  
Hubertus Maximilian Mehdorn ◽  
Janka Held-Feindt
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuropathic Pain ◽  
Substance P ◽  
Time Course ◽  
Behavioral Testing ◽  
Dorsal Horns ◽  
Cord Injury ◽  
Dorsal Columns ◽  
Spinal Cord Contusion

Object Central neuropathic pain is a frequent challenging complication after spinal cord injury (SCI), and specific therapeutic approaches remain elusive. The purpose of the present investigations was to identify potential key mediators of these pain syndromes by analyzing detailed expression profiles of important chemokines in an experimental SCI paradigm of posttraumatic neuropathic pain in rats. Methods Expression of CCR1, CCL3(MIP-1α), CXCR4, and CXCL12(SDF-1α) was investigated in parallel with behavioral testing for mechanical and thermal nociceptive thresholds after standardized SCI; 100-kdyn (moderate injury) and 200-kdyn (severe injury) force-defined thoracic spinal cord contusion lesions were applied via an Infinite Horizon Impactor at the T-9 level. Sham controls received laminectomies. Hindlimb locomotor function as well as mechanical and thermal sensitivities were monitored weekly by standardized behavioral testing after SCI. Chemokine expression was analyzed by real-time reverse transcriptase polymerase chain reaction in the early (7 days postoperatively) and late (42 days postoperatively) time courses after SCI, and immunohistochemical analysis (anatomical and quantitative) was performed 2, 7, 14, and 42 days after lesioning. Double staining with cellular markers and pain-related peptides (substance P and CGRP) or receptors (TRPV-1, TRPV-2, VRL-1, and TLR-4) was performed. Based on data obtained from behavioral testing, quantified immunohistochemical chemokine expressions in individual animals were correlated with the respective mechanical and thermal sensitivity thresholds 6 weeks after SCI. Results After 200-kdyn lesions, the animals exhibited prolonged reduction in their nociceptive thresholds, while 100-kdyn groups showed pain-related behaviors only in the early time course after SCI. Investigated chemokines were widely induced after SCI, involving cervical, thoracic, and lumbar spinal cord levels far beyond the lesion core. CCR1 and CCL3 were induced significantly in the dorsal horns 2 days after lesioning and remained at high levels after SCI with significantly higher intensities after 200-kdyn than 100-kdyn contusions. CXCR4 and CXCL12 levels continuously increased from 2 to 42 days after moderate and severe lesions. Additionally, chemokines were induced significantly in dorsal columns, with highest density levels 42 days after 200-kdyn lesions. In dorsal horns, CCR1 was coexpressed with TRPV-1 while CXCR4 and CXCL12 were partially coexpressed with substance P and CGRP. In dorsal columns, CCL3/CCR1 colabeled with GFAP, TRPV-2, TRPV-1, TLR-4; CXCR4/CXCL12 coexpressed with GFAP, CD68/ED1, and TLR4. Chemokine immunoreactivity density levels, especially CCL3 and its receptor, correlated in part significantly with nociceptive thresholds. Conclusions The authors report lesion grade–dependent upregulation of different chemokines/chemokine receptors after spinal cord contusion lesions in pain-processing spinal cord regions in a clinically relevant model of traumatic SCI in rats. Prolonged chemokine induction further correlated with below-level pain development in the delayed time course after severe SCI and was coexpressed with pain-associated peptides and receptors, suggesting that chemokines play a crucial role in chronic central pain mechanisms after SCI.

scholarly journals Propofol Alleviates Neuropathic Pain Induced by Chronic Contractile Injury by Regulating the Spinal glun2b-p38mapkepac1 Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Wen Li ◽  
Chenguang Qin ◽  
JianYong Yan ◽  
Qian Zhao ◽  
Lu You ◽  
...  
Keyword(s):  
Mechanical Allodynia ◽  
Underlying Mechanism ◽  
Histopathological Analysis ◽  
Immunofluorescence Analysis ◽  
Withdrawal Threshold ◽  
Analgesic Effects ◽  
Isoflurane Group ◽  
Dorsal Horns ◽  
Patients Experience ◽  
Thigh Region

Background. Propofol acts as an intravenous anesthetic cure which is widely used as a therapy for the craniocerebral injury that comprised surgical anesthesia as well as the sedation done in the intensive care units. Propofol is one of the most commonly used and efficient anesthetics where the painful effects are followed by an injection of propofol. In many cases, patients experience pain followed by anxiety, boredom, fear, and even myocardial ischemia. Objective. This study was performed to investigate the underlying mechanism of propofol and its effect on regulating spinal glun2b-p38mapkepac1 pathways in chronic contractile injury. Material and Methods. Contractile injury was performed by ligation around the nerve of the thigh region postanesthesia. Rats were divided into three groups to analyze the changes like mechanical allodynia by the paw withdrawal threshold and histopathological analysis for assessing cellular degradation. L4-L6 from the spinal dorsal horns were isolated and harvested for studying protein expression, by the method of western blotting and immunofluorescence analysis. Results. The pain caused due to mechanical allodynia in the paw region was highest at 1 hour postinduction and lasted for three days postinjury. Pain was significantly less in the group receiving propofol when compared with the isoflurane group for the first two hours of injury. In the propofol group, EPAC1, GluN2B, and p38 MAP K were significantly lower. Conclusion. In the rat model of induced chronic contractile injury, postsurgery there was a suppression of the GluN2B-p38MAPK/EPAC1 signaling pathway in the propofol group. As the p38MAPK/EPAC pathway has a significant role in the postoperative hyperalgesia, thus our experiment suggests that propofol has analgesic effects.

Quantitative analysis of dorsal horn cell receptive fields following limited deafferentation

1995 ◽  
Vol 74 (5) ◽  
pp. 2065-2076 ◽  
Author(s):  
H. R. Koerber ◽  
P. B. Brown
Keyword(s):  
Dorsal Horn ◽  
Receptive Fields ◽  
Afferent Input ◽  
Width Ratio ◽  
Survival Times ◽  
Long Survival ◽  
Dorsal Horns ◽  
Length Width ◽  
Low Threshold ◽  
And Control

1. To test the hypothesis that subtotal deafferentation of dorsal horn cells can stimulate plastic changes in their receptive fields (RFs), diffuse deafferentation of the cat hindlimb dorsal horn was produced by transection of L7 or L6 and L7 dorsal roots. The following single-unit cutaneous low-threshold mechanoreceptor RF properties were compared between operated and control dorsal horns: 1) distance of RF center from tips of toes, 2) RF length-width ratio; and 3) RF area. 2. In both L7 and L6-L7 rhizotomized animals there was an increased incidence of silent electrode tracks in the most deafferented portion of the hindlimb map (the foot and toe representation). In the rhizotomized L6-L7 animals, there was also an increased incidence of symmetrically placed tracks in deafferented and control dorsal horns, in which cell RFs had no mirror-symmetrical components. In addition, cells in the lateral half of the L6 and L7 dorsal horns exhibited a proximal shift in the location of their RFs. In the rhizotomized L7 animals there was a distal shift of RFs in the L5 segment at long survival times. RFs had lower length-width ratios in L5 and L6 at short survival times and in L6 at long survival times. 3. In intact preparations, dorsal horn cells normally respond to inputs via single or small numbers of low-threshold cutaneous mechanoreceptors. Because these rhizotomies do not remove all inputs from any given area of skin, the deafferentations would produce only patchy loss of input from individual receptors. Therefore observed changes cannot be accounted for entirely by loss of afferent input, suggesting that some reorganization of dorsal horn cell RFs occurred. We conclude that the threshold stimulus for plastic change is less than total deafferentation of dorsal horn cells. At least some of the mechanisms underlying these changes may be active in normal animals in the maintenance of the somatotopic map or in conditioning.

Inhibition and facilitation of different nocifensor reflexes by spatially remote noxious stimuli

1994 ◽  
Vol 72 (3) ◽  
pp. 1152-1160 ◽  
Author(s):  
M. M. Morgan ◽  
M. M. Heinricher ◽  
H. L. Fields
Keyword(s):  
Conditioning Stimulus ◽  
Hot Water ◽  
Noxious Stimulus ◽  
Tail Flick ◽  
Withdrawal Reflex ◽  
Dorsal Horns ◽  
Electrophysiological Studies ◽  
Noxious Stimuli ◽  
Evoked Activity ◽  
Lumbar Spinal

1. Noxious stimuli have been shown to produce a diffuse inhibition of nociresponsive neurons in the spinal and trigeminal dorsal horns. The present study sought to extend these electrophysiological studies of diffuse noxious inhibitory controls (DNIC) by determining the effect of a spatially remote noxious stimulus on behavioral measures of nociception. Changes in latency for hindpaw withdrawal and tail flick reflexes were measured in lightly halothane-anesthetized or awake, spinally transected rats before, during, and after application of a spatially remote noxious stimulus. 2. Surprisingly, in no case did application of a spatially remote noxious stimulus inhibit the hindpaw withdrawal reflex. The latency for this reflex was either reduced or did not change when the tail or contralateral hindpaw was placed in hot water (50 degrees C) or when a noxious pinch was applied to the ear. In contrast, the latency for the tail flick reflex was consistently increased when the hindpaw was placed in hot water. Both the hindpaw reflex facilitation and the tail flick reflex inhibition produced by a noxious conditioning stimulus were attenuated in spinally transected rats indicating supraspinal modulation of both reflexes. 3. In addition, and consistent with the work of others, placing the tail in hot water reduced the evoked activity of convergent neurons in both the trigeminal and lumbar spinal dorsal horns. Thus inhibition of the activity of nociresponsive neurons in the dorsal horn is consistent with inhibition of the tail flick reflex, but not with facilitation of the hindpaw withdrawal reflex.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals GABAergic Inhibition of Spinal Cord Dorsal Horns Contributes to Analgesic Effect of Electroacupuncture in Incisional Neck Pain Rats

2020 ◽  
Vol Volume 13 ◽  
pp. 1629-1645
Author(s):  
Jun-ying Wang ◽  
Wan-zhu Bai ◽  
Yong-hui Gao ◽  
Jian-liang Zhang ◽  
Cheng-lin Duanmu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neck Pain ◽  
Analgesic Effect ◽  
Gabaergic Inhibition ◽  
Dorsal Horns ◽  
Spinal Cord Dorsal

scholarly journals Study on the Mechanism Underlying the Regulation of the NMDA Receptor Pathway in Spinal Dorsal Horns of Visceral Hypersensitivity Rats by Moxibustion

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
L. D. Wang ◽  
J. M. Zhao ◽  
R. J. Huang ◽  
L. Y. Tan ◽  
Z. H. Hu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Irritable Bowel Syndrome ◽  
Visceral Pain ◽  
Intrathecal Injection ◽  
Visceral Hypersensitivity ◽  
Regulatory Function ◽  
Visceral Hyperalgesia ◽  
Spinal Dorsal ◽  
Dorsal Horns ◽  
Irritable Bowel

Visceral hypersensitivity is enhanced in irritable bowel syndrome (IBS) patients. Treatment of IBS visceral pain by moxibustion methods has a long history and rich clinical experience. In the clinic, moxibustion on the Tianshu (ST25) and Shangjuxu (ST37) acupoints can effectively treat bowel disease with visceral pain and diarrhea symptoms. To investigate the regulatory function of moxibustion on the Tianshu (ST25) and Shangjuxu (ST37) acupoints on spinal cord NR1, NR2B, and PKCεprotein and mRNA expression in irritable bowel syndrome (IBS) visceral hypersensitivity rats, we did some research. In the study, we found that moxibustion effectively relieved the IBS visceral hyperalgesia status of rats. Analgesic effect of moxibustion was similar to intrathecal injection of Ro 25-6981. The expression of NR1, NR2B, and PKCεin the spinal dorsal horns of IBS visceral hyperalgesia rats increased. Moxibustion on the Tianshu and Shangjuxu acupoints might inhibit the visceral hypersensitivity, simultaneously decreasing the expression of NR1, NR2B, and PKCεin spinal cord of IBS visceral hyperalgesia rats. Based on the above experimental results, we hypothesized NR1, NR2B, and PKCεof spinal cord could play an important role in moxibustion inhibiting the process of central sensitization and visceral hyperalgesia state.

FURTHER EXPERIMENTAL STUDIES OF PNEUMOSTRONGYLUS TENUIS IN CERVIDS

1966 ◽  
Vol 44 (5) ◽  
pp. 851-861 ◽  
Author(s):  
Roy C. Anderson ◽  
Murray W. Lankester ◽  
Uta R. Strelive
Keyword(s):  
Grey Matter ◽  
Mule Deer ◽  
Experimental Studies ◽  
Clinical Signs ◽  
Odocoileus Hemionus ◽  
Eastern North America ◽  
Dorsal Horns ◽  
The Central Nervous System ◽  
Histopathologic Findings ◽  
Traumatic Damage

Two young wapiti (Cervus canadensis nelsoni) and a female mule deer fawn (Odocoileus hemionus hemionus) were infected experimentally with Pneumostrongylus tenuis from white-tailed deer (Odocoileus virginianus borealis). The male wapiti showed only slight clinical signs after infection, and first-stage larvae appeared in its faeces 92 days later. The female wapiti showed severe neurological signs that terminated in general paralysis on the 54th day. The mule deer showed severe neurologic signs and died of paralysis on the 62nd day. Numerous worms were found in the subdural space and neural parenchyma, especially in the dorsal horns of grey matter, of the female wapiti and the mule deer. Traumatic damage in the dorsal horns was extensive, especially in the wapiti. Histopathologic findings were similar to those reported earlier in moose calves (Alces americana americana) infected with P. tenuis. Study of worms recovered from experimentally infected cervids indicates that P. tenuis develops similarity in white-tailed deer, moose, wapiti, and mule deer although in the first species it causes little damage to the central nervous system. The possibility that P. tenuis could become established in wapiti introduced into eastern North America is noted.

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