The activation of galanin receptor 2 plays an antinociceptive effect in nucleus accumbens of rats with neuropathic pain

AbstractOur previous research has shown that galanin plays an antinociceptive effect via binding to galanin receptors (GalRs) in nucleus accumbens (NAc). This study focused on the involvement of GalR2 in galanin-induced antinociceptive effect in NAc of neuropathic pain rats. The chronic constriction injury of sciatic nerve (CCI) was used to mimic neuropathic pain model. The hind paw withdrawal latency (HWL) to thermal stimulation and hind paw withdrawal threshold (HWT) to mechanical stimulation were measured as the indicators of pain threshold. The results showed that 14 and 28 days after CCI, the expression of GalR2 was up-regulated in bilateral NAc of rats, and intra-NAc injection of GalR2 antagonist M871 reversed galanin-induced increases in HWL and HWT of CCI rats. Furthermore, intra-NAc injection of GalR2 agonist M1145 induced increases in HWL and HWT at day 14 and day 28 after CCI, which could also be reversed by M871. Finally, we found that M1145-induced antinociceptive effect in NAc of CCI rats was stronger than that in intact rats. These results imply that the GalR2 is activated in the NAc from day 14 to day 28 after CCI and GalR2 is involved in the galanin-induced antinociceptive effect in NAc of CCI rats.

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Galanin Receptor 1 Plays an Antinociceptive Effect via Inhibiting PKA Activation in the Nucleus Accumbens of Rats With Neuropathic Pain

Physiological Research ◽

10.33549/physiolres.933941 ◽

2019 ◽

pp. 511-518 ◽

Cited By ~ 1

Author(s):

Y. ZHANG ◽

Y. GAO ◽

C.-Y. LI ◽

W. DONG ◽

Y. DONG ◽

...

Keyword(s):

Neuropathic Pain ◽

Nucleus Accumbens ◽

Sciatic Nerve ◽

Antinociceptive Effect ◽

Underlying Mechanism ◽

Galanin Receptor ◽

Nociceptive Information ◽

The Central Nervous System ◽

Galanin Receptors ◽

Galanin Receptor 1

Galanin and galanin receptors (GalRs) have been reported to be involved in the transmission and modulation of nociceptive information in the central nervous system (CNS). However, the underlying mechanism of the antinociception of GalRs in neuropathic pain remains unclear. This study investigated the antinociception induced by galanin receptor 1 (GalR1) via protein kinase A (PKA) signaling pathway in the nucleus accumbens (NAc) of rats with neuropathic pain. A mononeuropathy model was replicated by ligation of the left sciatic nerve, following which the expression of phospho-PKA (p-PKA) in the NAc were markedly up-regulated at 14th and 28th day after ligation of sciatic nerve, and p-PKA expression was down-regulated by intra-NAc injection of GalR1 agonist M617, but the GalR1 antagonist M35 did not have an effect. We also found that M35 in the NAc blocked the M617-induced increase in the hind paw withdrawal latencies (HWLs) of rats with mononeuropathy, but M35 alone had no effect on HWLs, and PKA inhibitor H-89 attenuated the M617-induced an increase in the HWLs. These results suggested that GalR1 induced an antinociception via inhibiting PKA activation, implying that GalR agonists may be potential and potent therapeutic options to treat chronic neuropathic pain.

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Evaluation of Lercanidipine in Paclitaxel-Induced Neuropathic Pain Model in Rat: A Preliminary Study

Pain Research and Treatment ◽

10.1155/2012/143579 ◽

2012 ◽

Vol 2012 ◽

pp. 1-5

Author(s):

Lekha Saha ◽

Debasish Hota ◽

Amitava Chakrabarti

Keyword(s):

Neuropathic Pain ◽

Pain Threshold ◽

Antinociceptive Effect ◽

Tail Flick ◽

Cold Allodynia ◽

Pain Model ◽

Neuropathic Pain Model ◽

Preliminary Study

Objective. To demonstrate the antinociceptive effect of lercanidipine in paclitaxel-induced neuropathy model in rat. Materials and Methods. A total of 30 rats were divided into five groups of six rats in each group as follows: Gr I: 0.9% NaCl, Gr II: paclitaxel + 0.9% NaCl, Gr III: paclitaxel + lercanidipine 0.5 μg/kg, Gr IV: paclitaxel + lercanidipine 1 μg/kg, and Gr V: paclitaxel + lercanidipine 2.5 μg/kg. Paclitaxel-induced neuropathic pain in rat was produced by single intraperitoneal (i.p.) injection of 1 mg/kg of paclitaxel on four alternate days (0, 2, 4, and 6). The tail flick and cold allodynia methods were used for assessing the pain threshold, and the assessments were done on days 0 (before first dose of paclitaxel) and on days 7, 14, 21, and 28. Results. There was a significant decrease (P<0.001) in the tail flick and cold allodynia latency in the paclitaxel-alone group from day 14 onward when compared with day 0. In the lercanidipine groups, the decrease in the tail flick and cold allodynia latency was not observed in 1.0 and 2.5 μg/kg groups and it was statistically significant (P<0.01) when compared with paclitaxel-alone group.

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PS136. Time-dependent alteration of reward-induced dopamine release in the nucleus accumbens of the neuropathic pain model rats.

The International Journal of Neuropsychopharmacology ◽

10.1093/ijnp/pyw043.136 ◽

2016 ◽

Vol 19 (Suppl_1) ◽

pp. 46-46

Keyword(s):

Neuropathic Pain ◽

Nucleus Accumbens ◽

Dopamine Release ◽

Time Dependent ◽

Pain Model ◽

Neuropathic Pain Model

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Behavioral and Morphological Evidence for the Involvement of Glial Cells in the Antinociceptive Effect of Najanalgesin in a Rat Neuropathic Pain Model

Biological and Pharmaceutical Bulletin ◽

10.1248/bpb.35.850 ◽

2012 ◽

Vol 35 (6) ◽

pp. 850-854 ◽

Cited By ~ 7

Author(s):

Yingxia Liang ◽

Weijian Jiang ◽

Zhiyu Zhang ◽

Jianfeng Yu ◽

Liang Tao ◽

...

Keyword(s):

Neuropathic Pain ◽

Glial Cells ◽

Antinociceptive Effect ◽

Morphological Evidence ◽

Pain Model ◽

Neuropathic Pain Model

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Antinociceptive effect ofButea monospermaon vincristine-induced neuropathic pain model in rats

Toxicology and Industrial Health ◽

10.1177/0748233711432573 ◽

2012 ◽

Vol 29 (1) ◽

pp. 3-13 ◽

Cited By ~ 10

Author(s):

Venkata Rathina Kumar Thiagarajan ◽

Palanichamy Shanmugam ◽

Uma Maheswari Krishnan ◽

Arunachalam Muthuraman ◽

Nirmal Singh

Keyword(s):

Neuropathic Pain ◽

Antinociceptive Effect ◽

Pain Model ◽

Neuropathic Pain Model

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Hydrogen-Rich Saline Activated Autophagy via HIF-1α Pathways in Neuropathic Pain Model

BioMed Research International ◽

10.1155/2018/4670834 ◽

2018 ◽

Vol 2018 ◽

pp. 1-13 ◽

Cited By ~ 3

Author(s):

Huixing Wang ◽

Xiaodong Huo ◽

Hongguang Chen ◽

Bo Li ◽

Jingzhi Liu ◽

...

Keyword(s):

Spinal Cord ◽

Neuropathic Pain ◽

Intractable Pain ◽

Sprague Dawley ◽

Pain Model ◽

Withdrawal Threshold ◽

Downstream Target ◽

Cord Injury ◽

Neuropathic Pain Model ◽

Regulatory Effects

Background. Neuropathic pain is a chronic and intractable pain, with very few effective analgesics. It involves an impaired cell autophagy process. Hydrogen-rich saline (HRS) reportedly reduces allodynia and hyperalgesia in a neuropathic pain model; however, it is unknown whether these effects involve autophagy induction. Methods. We investigated the relationship between HRS and cell autophagy in a neuropathic pain model generated by chronic constriction injury (CCI) in Sprague–Dawley rats. Rats received an intraperitoneal injection of HRS (10 mL/kg daily, from 1 day before until 14 days after CCI), 3MA (autophagy inhibitor), 2ME2 (HIF-1α inhibitor), or EDHB (HIF-1α agonist). The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were tested 1 day before and 1, 3, 7, 10, and 14 days after the operation. HIF-1α and cell autophagy markers in the spinal cord were evaluated by western blotting and real-time PCR assays at 14 days after CCI. Autophagosomes with double membranes were identified by transmission electron microscopy. Results. CCI caused behavioral hypersensitivity to mechanical and thermal stimulation in the hind-paw of the injured side. HRS improved MWT and TWL, activated autophagy, and increased autophagosomes and autolysosomes in CCI rats. 3-MA aggravated hyperalgesia and allodynia and suppressed autophagy, while EDHB attenuated hyperalgesia and activated the autophagy procedure and the HIF-1α downstream target gene BNIP3. HIF-1α inhibitors reversed the regulatory effects of HRS on autophagy in CCI rats at 14 days after spinal cord injury. Conclusion. HRS reduced mechanical hyperalgesia and activation of cell autophagy in neuropathic pain through a HIF1-dependent pathway.

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