Trifluoro-icaritin alleviates mechanical hypersensitivity and improves motor coordination and balance in rats with spared nerve injury-induced neuropathic pain

2021 ◽  
pp. 136125
Author(s):  
Dandan Jia ◽  
Yalan Sun ◽  
Guangsen Liu ◽  
Meng Xue ◽  
Zhihua Huang ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Nerve Injury ◽  
Motor Coordination ◽  
Spared Nerve Injury ◽  
Mechanical Hypersensitivity

scholarly journals Electroacupuncture Modulates Spinal BDNF/TrκB Signaling Pathway and Ameliorates the Sensitization of Dorsal Horn WDR Neurons in Spared Nerve Injury Rats

2020 ◽  
Vol 21 (18) ◽  
pp. 6524
Author(s):  
Meng Xue ◽  
Ya-Lan Sun ◽  
Yang-Yang Xia ◽  
Zhi-Hua Huang ◽  
Cheng Huang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Signaling Pathway ◽  
Dorsal Horn ◽  
Nerve Injury ◽  
Inhibitory Effect ◽  
Spared Nerve Injury ◽  
Mechanical Hypersensitivity ◽  
C Fiber ◽  
Wdr Neurons

Neuropathic pain is more complex and severely affects the quality of patients’ life. However, the therapeutic strategy for neuropathic pain in the clinic is still limited. Previously we have reported that electroacupuncture (EA) has an attenuating effect on neuropathic pain induced by spared nerve injury (SNI), but its potential mechanisms remain to be further elucidated. In this study, we designed to determine whether BDNF/TrκB signaling cascade in the spinal cord is involved in the inhibitory effect of 2 Hz EA on neuropathic pain in SNI rats. The paw withdrawal threshold (PWT) of rats was used to detect SNI-induced mechanical hypersensitivity. The expression of BDNF/TrκB cascade in the spinal cord was evaluated by qRT-PCR and Western blot assay. The C-fiber-evoked discharges of wide dynamic range (WDR) neurons in spinal dorsal horn were applied to indicate the noxious response of WDR neurons. The results showed that 2 Hz EA significantly down-regulated the levels of BDNF and TrκB mRNA and protein expression in the spinal cord of SNI rats, along with ameliorating mechanical hypersensitivity. In addition, intrathecal injection of 100 ng BDNF, not only inhibited the analgesic effect of 2 Hz EA on pain hypersensitivity, but also reversed the decrease of BDNF and TrκB expression induced by 2 Hz EA. Moreover, 2 Hz EA obviously reduced the increase of C-fiber-evoked discharges of dorsal horn WDR neurons by SNI, but exogenous BDNF (100 ng) effectively reversed the inhibitory effect of 2 Hz EA on SNI rats, resulting in a remarkable improvement of excitability of dorsal horn WDR neurons in SNI rats. Taken together, these data suggested that 2 Hz EA alleviates mechanical hypersensitivity by blocking the spinal BDNF/TrκB signaling pathway-mediated central sensitization in SNI rats. Therefore, targeting BDNF/TrκB cascade in the spinal cord may be a potential mechanism of EA against neuropathic pain.

Intrathecal TRESK gene recombinant adenovirus attenuates spared nerve injury-induced neuropathic pain in rats

Neuroreport ◽  
2013 ◽  
Vol 24 (3) ◽  
pp. 131-136 ◽  
Author(s):  
Jun Zhou ◽  
Cheng-Xiang Yang ◽  
Ji-Ying Zhong ◽  
Han-Bing Wang
Keyword(s):  
Neuropathic Pain ◽  
Nerve Injury ◽  
Recombinant Adenovirus ◽  
Spared Nerve Injury ◽  
Gene Recombinant

Pharmacological characterisation of the spared nerve injury model of neuropathic pain

Pain ◽  
2002 ◽  
Vol 98 (1) ◽  
pp. 151-161 ◽  
Author(s):  
Helle Kirstein Erichsen ◽  
Gordon Blackburn-Munro
Keyword(s):  
Neuropathic Pain ◽  
Nerve Injury ◽  
Spared Nerve Injury ◽  
Injury Model

Co-administered gabapentin and venlafaxine in nerve injured rats: Effect on mechanical hypersensitivity, motor function and pharmacokinetics

2010 ◽  
Vol 1 (2) ◽  
pp. 91-97 ◽  
Author(s):  
Anna Folkesson ◽  
Per Hartvig Honoré ◽  
Ole J. Bjerrum
Keyword(s):  
Neuropathic Pain ◽  
Adverse Effects ◽  
Nerve Injury ◽  
Analgesic Effect ◽  
Time Course ◽  
Maximum Effect ◽  
Inhibitory System ◽  
Time Curve ◽  
Mechanical Hypersensitivity ◽  
Prolonged Duration

AbstractA high proportion of patients suffering from neuropathic pain do not receive satisfactory pain relief from their current treatment, due to incomplete efficacy and dose-limiting adverse effects. Hence, one strategy to improve treatment outcome is the use of a combination of analgesic drugs. The potential benefits of such approach include improved and prolonged duration of analgesic effect and fewer or milder adverse effects with lower doses of each drug. Gabapentin is recommended as a first-line drug in the treatment of neuropathic pain, and has recently been demonstrated to act on supraspinal structures to stimulate the descending noradrenergic pain inhibitory system. Hypothetically, the analgesic effect of gabapentin may be potentiated if combined with a drug that prolongs the action of noradrenaline.In this study, gabapentin was co-administered with the serotonin and noradrenaline reuptake inhibitor venlafaxine, and subsequently evaluated for its effect on mechanical hypersensitivity in the rat spared nerve injury model of neuropathic pain. In this model, two branches of the sciatic nerve (the tibial and common peroneal nerves) are ligated and cut, leaving the third branch (the sural nerve) intact to innervate the hind paw of the animal. Treatment-induced ataxia was tested in order to exclude biased effect measurements. Finally, the pharmacokinetics of gabapentin was investigated alone and in combination with venlafaxine to elucidate any alterations which may have consequences for the pharmacological effect and safety.The overall effect on nerve injury-induced hypersensitivity of co-administered gabapentin (60 mg/kg s.c.) and venlafaxine (60 mg/kg s.c.), measured as the area under the effect-time curve during the three hour time course of testing, was similar to the highest dose of gabapentin (200 mg/kg s.c.) tested in the study. However, this dose of gabapentin was associated with ataxia and severe somnolence, while the combination was not. Furthermore, when administered alone, an effect delay of approximately one hour was observed for gabapentin (60 mg/kg s.c.) with maximum effect occurring 1.5 to 2.5 h after dosing, while venlafaxine (60 mg/kg s.c.) was characterised by a rapid onset of action (within 30 min) which declined to baseline levels before the end of the three hour time of testing. The effect of co-administered drugs (both 60 mg/kg s.c.), in the doses used here, can be interpreted as additive with prolonged duration in comparison to each drug administered alone. An isobolographic study design, enable to accurately classify the combination effect into additive, antagonistic or synergistic, was not applied. The pharmacokinetics of gabapentin was not altered by co-administered venlafaxine, implying that a pharmacokinetic interaction does not occur. The effect of gabapentin on the pharmacokinetics of venlafaxine was not studied, since any alterations are unlikely to occur on the basis of the pharmacokinetic properties of gabapentin.In conclusion, the results from this preclinical study support the rationale for improved effect and less adverse effects through combination therapy with gabapentin and venlafaxine in the management of neuropathic pain.

scholarly journals Microglia–Astrocyte Communication via C1q Contributes to Orofacial Neuropathic Pain Associated with Infraorbital Nerve Injury

2020 ◽  
Vol 21 (18) ◽  
pp. 6834
Author(s):  
Sayaka Asano ◽  
Yoshinori Hayashi ◽  
Koichi Iwata ◽  
Akiko Okada-Ogawa ◽  
Suzuro Hitomi ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Glial Fibrillary Acidic Protein ◽  
Nerve Injury ◽  
Fluorescence Intensity ◽  
Time Window ◽  
Infraorbital Nerve ◽  
Nociceptive Neurons ◽  
Mechanical Hypersensitivity ◽  
Injury Causes ◽  
Immunohistochemical Analyses

Trigeminal nerve injury causes a distinct time window of glial activation in the trigeminal spinal subnucleus caudalis (Vc), which are involved in the initiation and maintenance phases of orofacial neuropathic pain. Microglia-derived factors enable the activation of astrocytes. The complement component C1q, which promotes the activation of astrocytes, is known to be synthesized in microglia. However, it is unclear whether microglia–astrocyte communication via C1q is involved in orofacial neuropathic pain. Here, we analyzed microglia-astrocyte communication in a rat model with infraorbital nerve injury (IONI). The orofacial mechanical hypersensitivity induced by IONI was significantly attenuated by preemptive treatment with minocycline. Immunohistochemical analyses revealed that minocycline inhibited the increase in c-Fos immune-reactive (IR) cells and the fluorescence intensity of both Iba1 and glial fibrillary acidic protein (GFAP) in the Vc following IONI. Intracisternal administration of C1q caused orofacial mechanical hypersensitivity and an increase in the number of c-Fos-IR cells and fluorescence intensity of GFAP. C1q-induced orofacial mechanical hypersensitivity was completely abrogated by intracisternal administration of fluorocitrate. The present findings suggest that the enhancement in the excitability of Vc nociceptive neurons is produced by astrocytic activation via the signaling of C1q released from activated microglia in the Vc following IONI, resulting in persistent orofacial neuropathic pain.

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