scholarly journals Preclinical Evaluation of Polymeric Nanocomposite Containing Pregabalin for Sustained Release as Potential Therapy for Neuropathic Pain

Polymers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 3837
Author(s):  
Rafaela Figueiredo Rodrigues ◽  
Juliana Barbosa Nunes ◽  
Sandra Barbosa Neder Agostini ◽  
Paloma Freitas dos Santos ◽  
Juliana Cancino-Bernardi ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Antinociceptive Effect ◽  
Spherical Shape ◽  
Motor Deficit ◽  
Polymeric Nanocomposites ◽  
Polymeric Nanocomposite ◽  
Injury Model ◽  
Male Wistar Rats ◽  
Mechanical Nociceptive Threshold ◽  
20 Nm

This study offers a novel oral pregabalin (PG)-loaded drug delivery system based on chitosan and hypromellose phthalate-based polymeric nanocomposite in order to treat neuropathic pain (PG-PN). PG-PN has a particle size of 432 ± 20 nm, a polydispersity index of 0.238 ± 0.001, a zeta potential of +19.0 ± 0.9 mV, a pH of 5.7 ± 0.06, and a spherical shape. Thermal and infrared spectroscopy confirmed nanocomposite generation. PG-PN pharmacokinetics was studied after a single oral dose in male Wistar rats. PG-PN showed greater distribution and clearance than free PG. The antinociceptive effect of PG-PN in neuropathic pain rats was tested by using the chronic constriction injury model. The parameter investigated was the mechanical nociceptive threshold measured by the von Frey filaments test; PG-PN showed a longer antinociceptive effect than free PG. The rota-rod and barbiturate sleep induction procedures were used to determine adverse effects; the criteria included motor deficit and sedative effects. PG-PN and free PG had plenty of motors. PG-PN exhibited a less sedative effect than free PG. By prolonging the antinociceptive effect and decreasing the unfavorable effects, polymeric nanocomposites with pregabalin have shown promise in treating neuropathic pain.

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

2021 ◽  
Vol 71 (1) ◽  
Author(s):  
Yan Dong ◽  
Chong-Yang Li ◽  
Xiao-Min Zhang ◽  
Ya-Nan Liu ◽  
Shuang Yang ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Nucleus Accumbens ◽  
Pain Threshold ◽  
Antinociceptive Effect ◽  
Galanin Receptor ◽  
Pain Model ◽  
Withdrawal Threshold ◽  
Neuropathic Pain Model ◽  
Galanin Receptors ◽  
Intact Rats

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.

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 Pramipexole and tolcapone alleviate thermal and mechanical nociception in naive rats.

Folia Medica ◽  
2021 ◽  
Vol 63 (3) ◽  
pp. 377-384
Author(s):  
Anita Mihaylova ◽  
Ilia Kostadinov ◽  
Nina Doncheva ◽  
Delian Delev ◽  
Hristina Zlatanova
Keyword(s):  
Neurodegenerative Disorder ◽  
Antinociceptive Effect ◽  
Positive Control ◽  
Motor Symptoms ◽  
Dopaminergic Drugs ◽  
Thermal Nociception ◽  
Dopaminergic Neurotransmission ◽  
Latent Time ◽  
Male Wistar Rats ◽  
Non Motor Symptoms

Introduction: Parkinson&rsquo;s disease (PD) is &#1072; neurodegenerative disorder characterized mainly by its motor symptoms. The non-motor symptoms including pain are increasingly recognized in the last few decades. Existing evidence suggests that the dopaminergic neurotransmission has an essential role in pain control. Aim: The aim of the present study was to investigate the antinociceptive effect of dopaminergic drugs pramipexole and tolcapone against chemical and thermal stimuli in naive rats. Materials and methods: Male Wistar rats divided into 8 groups (n=8): saline; diclofenac 25 mg/kg body weight (bw) (positive control); pramipexole 0.5; 1 and 3 mg/kg bw; tolacapone 5; 15 and 30 mg/kg bw. Paw pressure and plantar tests were performed. Paw withdrawal pressure and latent time were measured. Statistical analysis was done by SPSS 19. Results: In the paw pressure test, pramipexole, in a dose of 1 and 3 mg/kg bw and tolcapone in a dose of 30 mg/kg bw, increased significantly the latency at 1, 2, and 3 hours compared to saline (p<0.05). In the plantar test, only the highest dose of pramipexole reached significance at 3 hours compared to the control rats (p<0.05). In contrast to pramipexole the three experimental groups with tolcapone markedly increased the latent time at 1 and 3 hours compared to saline (p<0.05). Conclusions: Pramipexole and tolcapone reduce mechanical and thermal nociception in na&iuml;ve rats by enhancing dopaminergic neurotransmission at both spinal and supraspinal levels. In addition, tolcapone stimulates noradrenergic mediation which may contribute to its antinociceptive effect.

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

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.

scholarly journals Investigation of the Combination of Pregabalin with Duloxetine or Amitriptyline on the Pharmacokinetics and Antiallodynic Effect During Neuropathic Pain in Rats

2021 ◽  
pp. E511-E520
Keyword(s):  
Neuropathic Pain ◽  
Motor Coordination ◽  
Combined Therapy ◽  
Pharmacokinetic Analysis ◽  
Test Results ◽  
Rotarod Test ◽  
Model Study ◽  
Liquid Chromatography Tandem Mass ◽  
Male Wistar Rats ◽  
Antiallodynic Effect

BACKGROUND: Amitriptyline, duloxetine, and pregabalin are among the most pharmacotherapeutic, effective treatments for neuropathic pain control. However, the evaluation of synergism by combining these treatments is still poorly investigated. OBJECTIVES: To evaluate the pharmacokinetics of the combination of pregabalin plus duloxetine and pregabalin plus amitriptyline, as well as the effect of these on neuropathic pain on rodent model. STUDY DESIGN: The experimental study. SETTING: The research took place in the research laboratories at the Federal University of Alfenas after ethics committee approval. METHODS: This study used male Wistar rats weighing between 220 and 250 g. The animals were randomly divided into the following groups: monotherapy (pregabalin, amitriptyline, duloxetine), combined therapy (pregabalin + amitriptyline, pregabalin + duloxetine), and vehicle (ultrapure water). Pharmacokinetic analysis of pregabalin or combination (pregabalin + amitriptyline or pregabalin + duloxetine) in the plasma were performed by ultraperformance liquid chromatography tandem mass spectrometry. Neuropathic pain was induced by sciatic nerve constriction (chronic constriction injury [CCI]) model, and nociceptive threshold was measured by von Frey filaments test. In addition, to evaluate the influence of the treatments on the motor coordination, the rotarod test was used. RESULTS: The pharmacokinetic disposition of pregabalin was changed in the association with amitriptyline, presenting a clearance reduction and consequently an increase in bioavailability. Furthermore, after the 14th day of CCI, pregabalin was administered orally and induced antiallodynic effect after 1, 2:15, 4, and 8 hours of its administration and showed the greatest antiallodynic effect after 4 hours of its administration. Moreover, this effect was prolonged (up to 8 hours) by combination with amitriptyline. Additionally, pregabalin and pregabalin + duloxetine showed a hypoalgesic effect in sham rats. In addition, the rotarod test results showed that drugs did not influence the motor coordination of the rats. LIMITATIONS: Potential competition mechanisms during the excretion of pregabalin, when pregabalin was combined with amitriptyline, were not investigated in this study. CONCLUSIONS: The data demonstrated that combined therapy of pregabalin plus amitriptyline improved the bioavailability of pregabalin and potentiated the efficacy of the antiallodynic effect of pregabalin alone, proving to be advantageous for the treatment of sciatic neuropathic pain. KEY WORDS: Neuropathic pain, pregabalin, duloxetine, amitriptyline, pharmacokinetic, antiallodynic effect, combined therapy, rats

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
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