scholarly journals ErbB4 in Spinal PV Interneurons Regulates Mechanical Allodynia in Neuropathic Pain via Modulation of Glycinergic Inhibitory Tone

2021 ◽  
Vol Volume 14 ◽  
pp. 1643-1651
Author(s):  
Yingying Yu ◽  
Guohua Wei ◽  
Qi Zhou ◽  
Huanhuan Sha
Keyword(s):  
Neuropathic Pain ◽  
Mechanical Allodynia ◽  
Inhibitory Tone

The Effect of Blocking of Antidromic Impulses by Capsaicin on Mechanical Allodynia in a Rat Model of Peripheral Neuropathic Pain

2004 ◽  
Vol 17 (1) ◽  
pp. 5 ◽  
Author(s):  
Jin Woo Shin ◽  
Kyung Don Hahm ◽  
Joong Woo Leem ◽  
Chul Hoo Park ◽  
Seung Woo Ku ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Rat Model ◽  
Mechanical Allodynia ◽  
Peripheral Neuropathic Pain

scholarly journals Static mechanical allodynia in post-surgical neuropathic pain after breast cancer treatments

2020 ◽  
Vol 20 (4) ◽  
pp. 683-691
Author(s):  
Laura Mustonen ◽  
Tommi Aho ◽  
Hanna Harno ◽  
Eija Kalso
Keyword(s):  
Breast Cancer ◽  
Neuropathic Pain ◽  
Psychological Factors ◽  
Mechanical Allodynia ◽  
Cold Pressor Test ◽  
Pain Tolerance ◽  
Cancer Surgery ◽  
Breast Cancer Surgery ◽  
Cold Pain ◽  
Static Mechanical

AbstractObjectivesStatic mechanical allodynia (SMA), i. e., pain caused by normally non-painful static pressure, is a prevalent manifestation of neuropathic pain (NP). Although SMA may significantly affect the patient’s daily life, it is less well studied in the clinical context. We aimed to characterize SMA in women with chronic post-surgical NP (CPSNP) after breast cancer surgery. Our objective was to improve understanding of the clinical picture of this prevalent pain condition. This is a substudy of a previously published larger cohort of patients with intercostobrachial nerve injury after breast cancer surgery (Mustonen et al. Pain. 2019;160:246–56).MethodsWe studied SMA in 132 patients with CPSNP after breast cancer surgery. The presence, location, and intensity of SMA were assessed at clinical sensory examination. The patients gave self-reports of pain with the Brief Pain Inventory (BPI). We studied the association of SMA to type of surgery, oncological treatments, BMI, other pains, and psychological factors. General pain sensitivity was assessed by the cold pressor test.ResultsSMA was prevalent (84%) in this cohort whereas other forms of allodynia were scarce (6%). Moderate-to-severe SMA was frequently observed even in patients who reported mild pain in BPI. Breast and the side of chest were the most common locations of SMA. SMA was associated with breast surgery type, but not with psychological factors. Severe SMA, but not self-reported pain, was associated with lower cold pain tolerance.ConclusionsSMA is prevalent in post-surgical NP after breast cancer surgery and it may represent a distinct NP phenotype. High intensities of SMA may signal the presence of central sensitization.ImplicationsSMA should be considered when examining and treating patients with post-surgical NP after breast cancer surgery.

scholarly journals Tongluo Zhitong Prescription Alleviates Allodynia, Hyperalgesia, and Dyskinesia in the Chronic Constriction Injury Model of Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Zhiyong Wang ◽  
Jianwei Wang ◽  
Lihua Qin ◽  
Weiguang Zhang
Keyword(s):  
Neuropathic Pain ◽  
Mechanical Allodynia ◽  
Chronic Constriction Injury ◽  
Catgut Suture ◽  
Cold Allodynia ◽  
Injury Model ◽  
Neuropathic Pain Model ◽  
Gait Function ◽  
Chronic Constriction Injury Model ◽  
Heat Hyperalgesia

Neuropathic pain is common in clinical practice. Exploration of new drug therapeutics has always been carried out for more satisfactory effects and fewer side-effects. In the present study, we aimed to investigate effects of Tongluo Zhitong Prescription (TZP), a compounded Chinese medicine description, on neuropathic pain model of rats with chronic constriction injury (CCI). The CCI model was established by loosely ligating sciatic nerve with catgut suture, proximal to its trifurcation. The static and dynamic allodynia, heat hyperalgesia, mechanical allodynia, cold allodynia, and gait were assessed. Our results showed that TZP alleviated CCI-induced static and dynamic allodynia, suppressed heat hyperalgesia and cold and mechanical allodynia, and improved gait function. These results suggest that TZP could alleviate neuropathic pain. Further experiments are needed to explore its mechanisms.

scholarly journals Plasticity-Related PKMζSignaling in the Insular Cortex Is Involved in the Modulation of Neuropathic Pain after Nerve Injury

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Jeongsoo Han ◽  
Minjee Kwon ◽  
Myeounghoon Cha ◽  
Motomasa Tanioka ◽  
Seong-Karp Hong ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Neuropathic Pain ◽  
Nerve Injury ◽  
Neural Plasticity ◽  
Mechanical Allodynia ◽  
Insular Cortex ◽  
Long Term Potentiation ◽  
Inhibitory Peptide ◽  
Term Potentiation ◽  
Potential Applications

The insular cortex (IC) is associated with important functions linked with pain and emotions. According to recent reports, neural plasticity in the brain including the IC can be induced by nerve injury and may contribute to chronic pain. Continuous active kinase, protein kinase Mζ(PKMζ), has been known to maintain the long-term potentiation. This study was conducted to determine the role of PKMζin the IC, which may be involved in the modulation of neuropathic pain. Mechanical allodynia test and immunohistochemistry (IHC) of zif268, an activity-dependent transcription factor required for neuronal plasticity, were performed after nerve injury. Afterζ-pseudosubstrate inhibitory peptide (ZIP, a selective inhibitor of PKMζ) injection, mechanical allodynia test and immunoblotting of PKMζ, phospho-PKMζ(p-PKMζ), and GluR1 and GluR2 were observed. IHC demonstrated that zif268 expression significantly increased in the IC after nerve injury. Mechanical allodynia was significantly decreased by ZIP microinjection into the IC. The analgesic effect lasted for 12 hours. Moreover, the levels of GluR1, GluR2, and p-PKMζwere decreased after ZIP microinjection. These results suggest that peripheral nerve injury induces neural plasticity related to PKMζand that ZIP has potential applications for relieving chronic pain.

scholarly journals Intrathecal Injection of the ς1Receptor Antagonist BD1047 Blocks Both Mechanical Allodynia and Increases in Spinal NR1 Expression during the Induction Phase of Rodent Neuropathic Pain

2008 ◽  
Vol 109 (5) ◽  
pp. 879-889 ◽  
Author(s):  
Dae-Hyun Roh ◽  
Hyun-Woo Kim ◽  
Seo-Yeon Yoon ◽  
Hyoung-Sig Seo ◽  
Young-Bae Kwon ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Dorsal Horn ◽  
Mechanical Allodynia ◽  
Maintenance Phase ◽  
Spinal Cord Dorsal Horn ◽  
Induction Phase ◽  
Receptor Subunit ◽  
Aspartate Receptor ◽  
Spinal Cord Dorsal

Background Selective blockade of spinal sigma(1) receptors (Sig-1R) suppresses nociceptive behaviors in the mouse formalin test. The current study was designed to verify whether intrathecal Sig-1R antagonists can also suppress chronic neuropathic pain. Methods Neuropathic pain was produced by chronic constriction injury (CCI) of the right sciatic nerve in rats. The Sig-1R antagonist BD1047 was administered intrathecally twice daily from postoperative days 0 to 5 (induction phase of neuropathic pain) or from days 15 to 20 (maintenance phase). Western blot and immunohistochemistry were performed to determine changes in Sig-1R expression and to examine the effect of BD1047 on N-methyl-D-aspartate receptor subunit 1 expression and phosphorylation in spinal cord dorsal horn from neuropathic rats. Results BD1047 administered on postoperative days 0-5 significantly attenuated CCI-induced mechanical allodynia, but not thermal hyperalgesia, and this suppression was blocked by intrathecal administration of the Sig-1R agonist PRE084. In contrast, BD1047 treatment during the maintenance phase of neuropathic pain had no effect on mechanical allodynia. Sig-1R expression significantly increased in the ipsilateral spinal cord dorsal horn from days 1 to 3 after CCI. Importantly, BD1047 (30 nmol) administered intrathecally during the induction, but not the maintenance phase, blocked the CCI-induced increase in N-methyl-D-aspartate receptor subunit 1 expression and phosphorylation. Conclusions These results demonstrate that spinal Sig-1Rs play a critical role in both the induction of mechanical allodynia and the activation of spinal N-methyl-d-aspartate receptors in CCI rats and suggest a potential therapeutic role for the use of Sig-1R antagonists in the clinical management of neuropathic pain.

scholarly journals Interleukin-17 is Involved in Neuropathic Pain and Spinal Synapse Plasticity on Mice

2021 ◽  
Author(s):  
Jia-Lu Sun ◽  
Wen-Jing Dai ◽  
Xin-Yuan Shen ◽  
Yu-Qiu Zhang ◽  
Ning Lü
Keyword(s):  
Neuropathic Pain ◽  
Mechanical Allodynia ◽  
Intrathecal Injection ◽  
Neutralizing Antibody ◽  
Interleukin 17 ◽  
Field Potentials ◽  
Spinal Dorsal ◽  
Synapse Plasticity ◽  
Evoked Field Potentials ◽  
C Fiber

Abstract Background: Neuropathic pain seriously affects people’s life, but its mechanism is not clear. Interleukin-17 (IL-17) is a proinflammation cytokine and involved in pain regulation. Our previous study found that IL-17 markedly enhanced the excitatory activity of spinal dorsal neurons in mice spinal slices. The present study attempts to explore if IL-17 contributes to neuropathic pain and spinal synapse plasticity.Methods：A model of spared nerve injury (SNI) was established in C57BL/6J mice and IL-17a mutant mice. The pain-like behaviors was tested, and the expression of IL-17 and its receptor, IL-17RA, was detected. C-fiber evoked field potentials were recorded in vivo. Results: In the spinal dorsal horn, IL-17 predominantly expressed in the superficial spinal astrocytes and IL-17RA expressed mostly in neurons and slightly in astrocytes. The SNI-induced static and dynamic allodynia was significantly prevented by pretreatment of neutralizing IL-17 antibody (intrathecal injection, 2 μg/10 μL) and attenuated in IL-17a mutant mice. Post-treatment of IL-17 neutralizing antibody also partially relieved the established mechanical allodynia. Moreover, spinal long-term potentiation (LTP) of C-fiber evoked field potentials, a substrate for central sensitization, was suppressed by IL-17 neutralizing antibody. Intrathecal injection of IL-17 recombinant protein (0.2 μg/10 μL) mimicked the mechanical allodynia and facilitated the spinal LTP. Conclusions: These data implied that IL-17 in the spinal cord played a crucial role in neuropathic pain and central sensitization.

Sortilins in neuropathic pain

2012 ◽  
Vol 3 (3) ◽  
pp. 183-184
Author(s):  
M. Richner ◽  
O.J. Bjerrum ◽  
Y. De Koninck ◽  
A. Nykjaer ◽  
C.B. Vaegter
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Mechanical Allodynia ◽  
Molecular Mechanisms ◽  
Intrathecal Injection ◽  
Ion Concentration ◽  
Down Regulation

AbstractBackground/aimsThe molecular mechanisms underlying neuropathic pain are incompletely understood, but recent data suggest that down-regulation of the chloride extruding co-transporter KCC2 in spinal cord sensory neurons is critical: Following peripheral nerve injury, activated microglia in the spinal cord release BDNF, which stimulates neuronal TrkB receptors and ultimately results in the reduction of KCC2 levels. Consequently, neuronal intracellular chloride ion concentration increases, impairing GABAA-receptor mediated inhibition. We have previously described how the receptor sortilin modulates neurotrophin signaling by facilitating anterograde transport of Trk receptors. Unpublished data further link SorCS2, another member of the Sortilins family of sorting receptors (sortilin, SorLA and SorCS1–3) to BDNF signaling by regulating presynaptic TrkB trafficking. The purpose of this study is to explore the involvement of Sortilins in neuropathic pain.MethodsWe subjected wild-type (wt), sortilin knockout (Sort1-/-) and SorCS2 knockout (SorCS2-/-) mice to the Spared Nerve Injury (SNI) model of peripheral nerve injury. Mechanical allodynia was measured by von Frey filaments using the up-down-up method and a 3-out-of-5 thresshold.ResultsAs previously described by several groups, wt mice developed significant mechanical allodynia following SNI. Interestingly however, mice lacking sortilin or SorCS2 were fully protected from development of allodynia and did not display KCC2 down-regulation following injury. In addition, a single intrathecal injection of antibodies against sortilin or SorCS2 could delay or rescue mechanical allodynia in wt SNI mice for 2-3 days. Finally, neither sortilin nor SorCS2 deficient mice responded to intrathecal injection of BDNF, in contrast to wt mice which developed transient mechanical allodynia.ConclusionWe hypothesize that sortilin and SorCS2 are involved in neuropathic pain development by regulating TrkB signaling. Alternatively, Sortilins may directly influence the regulation of KCC2 membrane levels following injury. Both hypotheses are currently being investigated by our group.

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