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 Electroacupuncture Alleviates Hyperalgesia by Regulating CB1 Receptor of Spinal Cord in Incisional Neck Pain Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Junying Wang ◽  
Jinling Zhang ◽  
Yonghui Gao ◽  
Yu Chen ◽  
Chenglin Duanmu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neck Pain ◽  
Analgesic Effect ◽  
Cervical Spinal Cord ◽  
Antinociceptive Effect ◽  
Neck Surgery ◽  
Superficial Layer ◽  
Cb1 Receptor ◽  
Underlying Mechanisms ◽  
Endocannabinoid Receptor

Acupuncture therapy is effective in relieving postoperative pain of neck surgery, but its underlying mechanisms remain largely unknown. This study, in the incisional neck pain rat model, was designed to explore whether the endocannabinoid receptor 1 (CB1) in the cervical spinal cord is involved in the analgesic effect of electroacupuncture (EA) or not.The incisional neck pain model was established by making a longitudinal incision and applied EA treatment of Futu (LI18), Hegu-Neiguan (LI4-PC6), or Zusanli-Yanglingquan (ST36-GB34) for pain relief. The results showed that EA LI18 and EA LI4-PC6 effectively relieve allodynia caused by neck incision, which was obviously better than EA ST34-GB34 ( P  < 0.05). After EA, the expression levels of CB1 mRNA at 4h in the EALI18 group, and 24 and 48h in both EALI18 and EALI4-PC6 groups, and those of CB1 protein at 4, 24, and 48h in the EALI18 group, and the immunoactivity of CB1 in both EALI18 and EALI4-PC6 groups at 4h were significantly upregulated in contrast to those of the model group ( P  < 0.05). EA of either acupoint group had no effect on the expression of CB2 protein ( P  > 0.05). Moreover, the antinociceptive effect of EA was reversed by AM251 (CB1 antagonist). Immunofluorescence dual staining showed that CB1 expressed in astrocytes in the superficial layer (laminae I and II) of dorsal horns of the cervical spinal cord. Therefore, the findings of this study revealed that upregulation of CB1 expression in the cervical spinal cord contributes to the analgesic effect of EA in incisional neck pain rats. The CB1 receptor expresses on astrocytes.

scholarly journals Delta Opioid Receptors Presynaptically Regulate Cutaneous Mechanosensory Neuron Input to the Spinal Cord Dorsal Horn

Neuron ◽  
2014 ◽  
Vol 81 (6) ◽  
pp. 1443 ◽  
Author(s):  
Rita Bardoni ◽  
Vivianne L. Tawfik ◽  
Dong Wang ◽  
Amaury François ◽  
Carlos Solorzano ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Opioid Receptors ◽  
Spinal Cord Dorsal Horn ◽  
Mechanosensory Neuron ◽  
Delta Opioid Receptors ◽  
Spinal Cord Dorsal

Spinal Endogenous Acetylcholine Contributes to the Analgesic Effect of Systemic Morphine in Rats

2001 ◽  
Vol 95 (2) ◽  
pp. 525-530 ◽  
Author(s):  
Shao-Rui Chen ◽  
Hui-Lin Pan
Keyword(s):  
Spinal Cord ◽  
Receptor Antagonist ◽  
Analgesic Effect ◽  
Antinociceptive Effect ◽  
Intrathecal Injection ◽  
Radiant Heat ◽  
Cholinergic Receptor ◽  
Inhibitory Effect ◽  
Withdrawal Latency ◽  
Aziridinium Ion

Background Systemic morphine is known to cause increased release of acetyicholine in the spinal cord. Intrathecal injection of the cholinergic receptor agonists or acetyicholinesterase inhibitors produces antinociception in both animals and humans. In the present study, we explored the functional importance of spinal endogenous acetylcholine in the analgesic action produced by intravenous morphine. Methods Rats were implanted with intravenous and intrathecal catheters. The antinociceptive effect of morphine was determined by the paw-withdrawal latency in response to a radiant heat stimulus after intrathecal treatment with atropine (a muscarinic receptor antagonist), mecamylamine (a nicotinic receptor antagonist), or cholinergic neurotoxins (ethylcholine mustard aziridinium ion [AF64A] and hemicholinium-3). Results Intravenous injection of 2.5 mg/kg morphine increased significantly the paw-withdrawal latency. Intrathecal pretreatment with 30 microg atropine (n = 7) or 50 microg mecamylamine (n = 6) both attenuated significantly the antinociceptive effect of morphine. The inhibitory effect of atropine on the effect of morphine was greater than that of mecamylanilne. Furthermore, the antinociceptive effect of morphine was significantly reduced in rats pretreated with intrathecal AF64A (n = 7) or hemicholinium-3 (n = 6) to inhibit the high-affinity choline transporter and acetylcholine synthesis. We found that intrathecal AF64A reduced significantly the [3H]hemicholinium-3 binding sites but did not affect its affinity in the dorsal spinal cord. Conclusions The data in the current study indicate that spinal endogenous acetylcholine plays an important role in mediating the analgesic effect of systemic morphine through both muscarinic and nicotinic receptors.

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 Inhibition of the phosphoinositide 3-kinase-AKT-cyclic GMP-c-Jun N-terminal kinase signaling pathway attenuates the development of morphine tolerance in a mouse model of neuropathic pain

2021 ◽  
Vol 17 ◽  
pp. 174480692110033
Author(s):  
Travis Okerman ◽  
Taylor Jurgenson ◽  
Madelyn Moore ◽  
Amanda H Klein
Keyword(s):  
Spinal Cord ◽  
Sciatic Nerve ◽  
Signaling Pathway ◽  
Intracellular Signaling ◽  
Morphine Tolerance ◽  
Spinal Nerve ◽  
Intracellular Signaling Pathway ◽  
Spinal Cord Dorsal ◽  
Phosphoinositide 3 Kinase ◽  
Induced Tolerance

Research presented here sought to determine if opioid induced tolerance is linked to activity changes within the PI3Kγ-AKT-cGMP-JNK intracellular signaling pathway in spinal cord or peripheral nervous systems. Morphine or saline injections were given subcutaneously twice a day for five days (15 mg/kg) to male C57Bl/6 mice. A separate cohort of mice received spinal nerve ligation (SNL) one week prior to the start of morphine tolerance. Afterwards, spinal cord, dorsal root ganglia, and sciatic nerves were isolated for quantifying total and phosphorylated- JNK levels, cGMP, and gene expression analysis of Pik3cg, Akt1, Pten, and nNos1. This pathway was downregulated in the spinal cord with increased expression in the sciatic nerve of morphine tolerant and morphine tolerant mice after SNL. We also observed a significant increase in phosphorylated- JNK levels in the sciatic nerve of morphine tolerant mice with SNL. Pharmacological inhibition of PI3K or JNK, using thalidomide, quercetin, or SP600125, attenuated the development of morphine tolerance in mice with SNL as measured by thermal paw withdrawal. Overall, the PI3K/AKT intracellular signaling pathway is a potential target for reducing the development of morphine tolerance in the peripheral nervous system. Continued research into this pathway will contribute to the development of new analgesic drug therapies.

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