Alterations in the Anandamide Metabolism in the Development of Neuropathic Pain

Endocannabinoids (EC), particularly anandamide (AEA), released constitutively in pain pathways might be accountable for the inhibitory effect on nociceptors. Pathogenesis of neuropathic pain may reflect complex remodeling of the dorsal root ganglia (DRGs) and spinal cord EC system. Multiple pathways involved both in the biosynthesis and degradation of AEA have been suggested. We investigated the local synthesis and degradation features of AEA in DRGs and spinal cord during the development and maintenance of pain in a model of chronic constriction injury (CCI). All AEA synthesis and degradation enzymes are present on the mRNA level in DRGs and lumbar spinal cord of intact as well as CCI-treated animals. Deregulation of EC system components was consistent with development of pain phenotype at days 3, 7, and 14 after CCI. The expression levels of enzymes involved in AEA degradation was significantly upregulated ipsilateral in DRGs and spinal cord at different time points. Expression of enzymes of the alternative, sPLA2-dependent and PLC-dependent, AEA synthesis pathways was elevated in both of the analyzed structures at all time points. Our data have shown an alteration of alternative AEA synthesis and degradation pathways, which might contribute to the variation of AEA levels and neuropathic pain development.

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Melanocortin 4 Receptor Mediates Neuropathic Pain Through p38MAPK in Spinal Cord

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100013962 ◽

2012 ◽

Vol 39 (4) ◽

pp. 458-464 ◽

Cited By ~ 9

Author(s):

Haichen Chu ◽

Jiangling Xia ◽

Hongmei Xu ◽

Zhao Yang ◽

Jie Gao ◽

...

Keyword(s):

Spinal Cord ◽

Neuropathic Pain ◽

Time Course ◽

Lumbar Spinal Cord ◽

Enzyme Linked Immunosorbent Assay ◽

Melanocortin 4 Receptor ◽

Male Wistar Rats ◽

Underlying Mechanisms ◽

Lumbar Spinal ◽

Somatosensory Nervous System

Background:Neuropathic pain is characterised by spontaneous ongoing or shooting pain and evoked amplified pain responses after noxious or non-noxious stimuli. Neuropathic pain develops as a result of lesions or disease affecting the somatosensory nervous system either in the periphery or centrally. Melanocortin 4 receptor (MC4R) plays an important role in the initiation of neuropathic pain but the underlying mechanisms are still unclear.Methods:Adult male Wistar rats were given chronic constriction injury (CCI) or sham operations. Part of CCI rats were intrathecally treated with HS014 (MC4R antagonist) or SB203580 (p38MAPK inhibitor). On the third, seventh and fourteenth day, the thermal threshold of operated paws was tested. In addition, the MC4R or phosphorylated p38MAPK (p-p38MAPK) levels of lumbar spinal cord were tested with ELISA (enzyme-linked immunosorbent assay), western blot and immunohistochemistry.Results:Here we demonstrate that (1) both HS014 and SB203580 reduced CCI reduced hyperalgesia (2) p-p38MAPK was increased after CCI with a time course parallel to that of the MC4R change, (3) The p38 activation was prevented by blocking MC4R with an antagonist HS014, but MC4R-IR was not prevented by SB203580. (4) MC4R and p-p38MAPK were located in the same cells.Conclusion:The mechanisms of neuropathic pain mediated by MC4R is related to the inhibition of p38MAPK activation. P38MAPK may be a downstream of MC4R.

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(299) Therapeutic morphine prolongs neuropathic pain in Fischer 344 rats: a role for TLR4 and inflammasome signaling in the lumbar spinal cord

Journal of Pain ◽

10.1016/j.jpain.2014.01.209 ◽

2014 ◽

Vol 15 (4) ◽

pp. S50

Author(s):

P. Grace ◽

K. Strand ◽

E. Galer ◽

Y. Zhang ◽

L. Greene ◽

...

Keyword(s):

Spinal Cord ◽

Neuropathic Pain ◽

Lumbar Spinal Cord ◽

Fischer 344 Rats ◽

Fischer 344 ◽

Lumbar Spinal

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Cancer pain and neuropathic pain are associated with Aβ sensory neuronal plasticity in dorsal root ganglia and abnormal sprouting in lumbar spinal cord

Molecular Pain ◽

10.1177/1744806918810099 ◽

2018 ◽

Vol 14 ◽

pp. 174480691881009 ◽

Cited By ~ 4

Author(s):

Yong Fang Zhu ◽

Jacek M Kwiecien ◽

Wojciech Dabrowski ◽

Robert Ungard ◽

Kan Lun Zhu ◽

...

Keyword(s):

Spinal Cord ◽

Neuropathic Pain ◽

Cancer Pain ◽

Dorsal Root Ganglia ◽

Neuronal Plasticity ◽

Dorsal Root ◽

Lumbar Spinal Cord ◽

Lumbar Spinal

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31. Therapeutic morphine prolongs neuropathic pain in rats: A role for TLR4 and inflammasome signaling in the lumbar spinal cord

Brain Behavior and Immunity ◽

10.1016/j.bbi.2014.06.051 ◽

2014 ◽

Vol 40 ◽

pp. e9-e10

Author(s):

P.M. Grace ◽

K.A. Strand ◽

E.L. Galer ◽

Y. Zhang ◽

D. Berkelhammer ◽

...

Keyword(s):

Spinal Cord ◽

Neuropathic Pain ◽

Lumbar Spinal Cord ◽

Lumbar Spinal

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Changes in G proteins genes expression in rat lumbar spinal cord support the inhibitory effect of chronic pain on the development of tolerance to morphine analgesia

Neuroscience Research ◽

10.1016/j.neures.2005.06.020 ◽

2005 ◽

Vol 53 (3) ◽

pp. 250-256 ◽

Cited By ~ 14

Author(s):

Mohammad Javan ◽

Abolhassan Ahmadiani ◽

Fereshteh Motamadi ◽

Bahram Kazemi

Keyword(s):

Spinal Cord ◽

Chronic Pain ◽

G Proteins ◽

Inhibitory Effect ◽

Lumbar Spinal Cord ◽

Morphine Analgesia ◽

Genes Expression ◽

Lumbar Spinal ◽

Development Of Tolerance

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Differential Lumbar Spinal Cord Responses among Wild Type, CD4 Knockout, and CD40 Knockout Mice in Spinal Nerve L5 Transection-Induced Neuropathic Pain

Molecular Pain ◽

10.1186/1744-8069-8-88 ◽

2012 ◽

Vol 8 ◽

pp. 1744-8069-8-88 ◽

Cited By ~ 8

Author(s):

Ling Cao ◽

Holly Beaulac ◽

Adriana Eurich

Keyword(s):

Spinal Cord ◽

Neuropathic Pain ◽

Knockout Mice ◽

Spinal Nerve ◽

Lumbar Spinal Cord ◽

Wild Type ◽

Lumbar Spinal

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Morphine-induced Spinal Release of Adenosine Is Reduced in Neuropathic Rats

Anesthesiology ◽

10.1097/00000542-200112000-00026 ◽

2001 ◽

Vol 95 (6) ◽

pp. 1455-1459 ◽

Cited By ~ 29

Author(s):

Andreas Sandner-Kiesling ◽

Xinhui Li ◽

James C. Eisenach

Keyword(s):

Spinal Cord ◽

Neuropathic Pain ◽

Spinal Nerve ◽

Spinal Nerve Ligation ◽

Lumbar Spinal Cord ◽

Sprague Dawley ◽

Dorsal Spinal Cord ◽

Adenosine Release ◽

Sprague Dawley Rats ◽

Lumbar Spinal

Background Spinally administered opioids show decreased potency and efficacy in the treatment of neuropathic pain. As reported previously, morphine stimulates spinal opioid receptors to effect adenosine release, which acts at adenosine receptors to produce analgesia. The authors hypothesized that morphine induces less adenosine release in neuropathic compared with normal rats, explaining its reduced potency and efficacy. Methods Sprague-Dawley rats (200-250 g) were divided into three groups: no surgery (n = 52), sham surgery (n = 20), or left L5 and L6 spinal nerve ligation (n = 64). Two weeks after surgery, mechanical hypersensitivity of the left hind paw was verified. For each experiment, a crude synaptosomal P2 suspension was prepared by homogenizing cervical and lumbar dorsal spinal cord halves from four rats, followed by differential centrifugation, and aliquots incubated with morphine sulfate from 10(-8) to 10(-4) m alone or in presence of 10(-5) m dipyridamole. Extrasynaptosomal concentrations of adenosine were analyzed by high-pressure liquid chromatography. Results Synaptosomal release of adenosine in the absence of morphine was similar between groups. Morphine produced a concentration-dependent adenosine release, which was less in synaptosomes from dorsal lumbar spinal cord in spinal nerve ligation compared with normal or sham animals. This reduction was removed by adding dipyridamole. Conclusion Morphine normally stimulates spinal release of adenosine, a potent antihypersensitivity compound. Because this effect of morphine is diminished in spinal nerve ligation animals, one explanation for decreased efficacy and potency of opioids in the treatment of neuropathic pain may be a dipyridamole-sensitive disruption in the opioid-adenosine link in the spinal cord.

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Lipomeningocele associated with diplomyelia in a dog

Tierärztliche Praxis Ausgabe K Kleintiere / Heimtiere ◽

10.15654/tpk-170751 ◽

2018 ◽

Vol 46 (05) ◽

pp. 323-329 ◽

Cited By ~ 2

Author(s):

Nele Ondreka ◽

Sara Malberg ◽

Emma Laws ◽

Martin Schmidt ◽

Sabine Schulze

Keyword(s):

Spinal Cord ◽

Neurological Status ◽

Split Cord Malformation ◽

Lumbar Spinal Cord ◽

Histopathological Diagnosis ◽

Type I ◽

Thoracic Spinal Cord ◽

Thoracic Spinal ◽

Subcutaneous Mass ◽

Lumbar Spinal

SummaryA 2-year-old male neutered mixed breed dog with a body weight of 30 kg was presented for evaluation of a soft subcutaneous mass on the dorsal midline at the level of the caudal thoracic spine. A further clinical sign was intermittent pain on palpation of the area of the subcutaneous mass. The owner also described a prolonged phase of urination with repeated interruption and re-initiation of voiding. The findings of the neurological examination were consistent with a lesion localization between the 3rd thoracic and 3rd lumbar spinal cord segments. Magnetic resonance imaging revealed a spina bifida with a lipomeningocele and diplomyelia (split cord malformation type I) at the level of thoracic vertebra 11 and 12 and secondary syringomyelia above the aforementioned defects in the caudal thoracic spinal cord. Surgical resection of the lipomeningocele via a hemilaminectomy was performed. After initial deterioration of the neurological status postsurgery with paraplegia and absent deep pain sensation the dog improved within 2 weeks to non-ambulatory paraparesis with voluntary urination. Six weeks postoperatively the dog was ambulatory, according to the owner. Two years after surgery the owner recorded that the dog showed a normal gait, a normal urination and no pain. Histopathological diagnosis of the biopsied material revealed a lipomeningocele which confirmed the radiological diagnosis.

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