Prokineticin 2 Upregulation in the Peripheral Nervous System Has a Major Role in Triggering and Maintaining Neuropathic Pain in the Chronic Constriction Injury Model

The new chemokine Prokineticin 2 (PROK2) and its receptors (PKR1and PKR2) have a role in inflammatory pain and immunomodulation. Here we identified PROK2 as a critical mediator of neuropathic pain in the chronic constriction injury (CCI) of the sciatic nerve in mice and demonstrated that blocking the prokineticin receptors with two PKR1-preferring antagonists (PC1 and PC7) reduces pain and nerve damage. PROK2 mRNA expression was upregulated in the injured nerve since day 3 post injury (dpi) and in the ipsilateral DRG since 6 dpi. PROK2 protein overexpression was evident in Schwann Cells, infiltrating macrophages and axons in the peripheral nerve and in the neuronal bodies and some satellite cells in the DRG. Therapeutic treatment of neuropathic mice with the PKR-antagonist, PC1, impaired the PROK2 upregulation and signalling. This fact, besides alleviating pain, brought down the burden of proinflammatory cytokines in the damaged nerve and prompted an anti-inflammatory repair program. Such a treatment also reduced intraneural oedema and axon degeneration as demonstrated by the physiological skin innervation and thickness conserved in CCI-PC1 mice. These findings suggest that PROK2 plays a crucial role in neuropathic pain and might represent a novel target of treatment for this disease.

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Post-injury repeated administrations of minocycline improve the antinociceptive effect of morphine in chronic constriction injury model of neuropathic pain in rat

Pharmacology Biochemistry and Behavior ◽

10.1016/j.pbb.2012.07.001 ◽

2012 ◽

Vol 102 (4) ◽

pp. 520-525 ◽

Cited By ~ 14

Author(s):

Samad Nazemi ◽

Homa Manaheji ◽

Jalal Zaringhalam ◽

Mehdi Sadeghi ◽

Abbas Haghparast

Keyword(s):

Neuropathic Pain ◽

Chronic Constriction Injury ◽

Antinociceptive Effect ◽

Post Injury ◽

Injury Model ◽

Repeated Administrations ◽

Chronic Constriction Injury Model

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Chronic nanocurcumin treatment ameliorates pain-related behavior, improves spatial memory, and reduces hippocampal levels of IL-1β and TNFα in the chronic constriction injury model of neuropathic pain

Psychopharmacology ◽

10.1007/s00213-020-05739-x ◽

2021 ◽

Author(s):

Sepideh Saffarpour ◽

Atousa Janzadeh ◽

Behnaz Rahimi ◽

Fatemeh Ramezani ◽

Farinaz Nasirinezhad

Keyword(s):

Neuropathic Pain ◽

Spatial Memory ◽

Chronic Constriction Injury ◽

Injury Model ◽

Chronic Constriction Injury Model

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

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/8197281 ◽

2017 ◽

Vol 2017 ◽

pp. 1-6 ◽

Cited By ~ 1

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.

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Selective loss of spinal GABAergic or glycinergic neurons is not necessary for development of thermal hyperalgesia in the chronic constriction injury model of neuropathic pain

Pain ◽

10.1016/s0304-3959(03)00011-3 ◽

2003 ◽

Vol 104 (1) ◽

pp. 229-239 ◽

Cited By ~ 162

Author(s):

E Polgár ◽

I D. Hughes ◽

S J. Riddell ◽

J D. Maxwell ◽

Z Puskár ◽

...

Keyword(s):

Neuropathic Pain ◽

Chronic Constriction Injury ◽

Thermal Hyperalgesia ◽

Selective Loss ◽

Injury Model ◽

Chronic Constriction Injury Model

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Comparative efficacy of pregabalin and baclofen in the rodent chronic constriction injury model of neuropathic pain

International Journal of Basic & Clinical Pharmacology ◽

10.18203/2319-2003.ijbcp20185171 ◽

2018 ◽

Vol 8 (1) ◽

pp. 133

Author(s):

Saurabh Kohli ◽

Taruna Sharma ◽

Juhi Kalra ◽

Dilip C. Dhasmana

Keyword(s):

Neuropathic Pain ◽

Sciatic Nerve ◽

Chronic Constriction Injury ◽

Thermal Hyperalgesia ◽

Mechanical Hyperalgesia ◽

Comparative Efficacy ◽

First Line ◽

Injury Model ◽

Different Types ◽

Chronic Constriction Injury Model

Background: Neuropathic pain is associated with prolonged disability and is usually not responsive to conventional analgesics like NSAIDs and opioids. Even the recommended first-line drugs are effective in less than 50% patients. Thus, drugs with different mechanisms of action are needed. Baclofen, a GABA-B agonist has shown benefit in different types of neuropathic pains and is compared against pregabalin.Methods: The sciatic nerve was ligated in 2 groups of 6 rats each as per the chronic constriction injury model of neuropathic pain on day 0. After 14 days the effect of single doses of pregabalin (30mg/kg) and baclofen (5mg/kg) intraperitoneally were assessed over a 2 hours period. Thermal and mechanical hyperalgesia were assessed as measures of neuropathic pain by the hotplate and pin-prick method respectively.Results: Significant thermal and mechanical hyperalgesia was produced 14 days after sciatic nerve ligation in both the groups (p <0.05). Both pregabalin (p <0.001) and baclofen (p <0.01) were effective in decreasing thermal hyperalgesia throughout the two hours study period, but pregabalin was more effective as compared to baclofen (p <0.05) at 30, 60 and 120minutes. Both the drugs produced a significant decrease in mechanical hyperalgesia (p <0.01) throughout the study period. Again, pregabalin was the more effective drug (p <0.05) at all time points.Conclusions: Significant thermal and mechanical hyperalgesia was seen 14 days after sciatic nerve ligation. Both pregabalin and baclofen were effective in reversing the hyperalgesia, but pregabalin was the more effective of the two drugs at all time points.

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