Ultramicronized Palmitoylethanolamide and Paracetamol, a New Association to Relieve Hyperalgesia and Pain in a Sciatic Nerve Injury Model in Rat

Inflammation is known to be an essential trigger of the pathological changes that have a critical impact on nerve repair and regeneration; moreover, damage to peripheral nerves can cause a loss of sensory function and produces persistent neuropathic pain. To date, various potential approaches for neuropathic pain have focused on controlling neuroinflammation. The aim of this study was to investigate the neuroprotective effects of a new association of ultramicronized Palmitoylethanolamide (PEAum), an Autacoid Local Injury Antagonist Amide (ALIAmide) with analgesic and anti-inflammatory properties, with Paracetamol, a common analgesic, in a rat model of sciatic nerve injury (SNI). The association of PEAum–Paracetamol, in a low dose (5 mg/kg + 30 mg/kg), was given by oral gavage daily for 14 days after SNI. PEAum–Paracetamol association was able to reduce hyperalgesia, mast cell activation, c-Fos and nerve growth factor (NGF) expression, neural histological damage, cytokine release, and apoptosis. Furthermore, the analgesic action of PEAum–Paracetamol could act in a synergistic manner through the inhibition of the NF-κB pathway, which leads to a decrease of cyclooxygenase 2-dependent prostaglandin E2 (COX-2/PGE2) release. In conclusion, we demonstrated that PEAum associated with Paracetamol was able to relieve pain and neuroinflammation after SNI in a synergistic manner, and this therapeutic approach could be relevant to decrease the demand of analgesic drugs.

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Involvement of protein isoprenylation in neuropathic pain induced by sciatic nerve injury in mice

Neuroscience Letters ◽

10.1016/j.neulet.2014.01.039 ◽

2014 ◽

Vol 564 ◽

pp. 27-31 ◽

Cited By ~ 2

Author(s):

Masahiro Ohsawa ◽

Junpei Mutoh ◽

Shohei Yamamoto ◽

Hiroaki Hisa

Keyword(s):

Neuropathic Pain ◽

Sciatic Nerve ◽

Nerve Injury ◽

Sciatic Nerve Injury ◽

Protein Isoprenylation

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Dexmedetomidine to Help Nerve Regeneration in a Rat Sciatic Nerve Injury Model

Pain Research and Management ◽

10.1155/2017/9045608 ◽

2017 ◽

Vol 2017 ◽

pp. 1-7 ◽

Cited By ~ 3

Author(s):

Wook Jeong ◽

Hsichiang Kung ◽

Chia Chi Cheng ◽

Changwoo Lim ◽

Min Jung Jung ◽

...

Keyword(s):

Sciatic Nerve ◽

Nerve Regeneration ◽

Nerve Injury ◽

Peripheral Nerve Regeneration ◽

Sciatic Nerve Injury ◽

Sprague Dawley ◽

Neuroprotective Effects ◽

Adrenoceptor Agonist ◽

Group 3 ◽

Group 2

Background. Several studies have shown that dexmedetomidine (DXM), a selective α2-adrenoceptor agonist, also has neuroprotective effects. However, its effect on impaired peripheral nerve regeneration has not been studied. Materials and Methods. Forty-five Sprague-Dawley rats were randomly assigned to three groups: group 1 (control SHAM), group 2 (sciatic nerve injury + normal saline), and group 3 (sciatic nerve injury + DXM). The rats of group 3 were subdivided into the following three groups: DXM 0.5, 6, and 20 μg·kg−1 (groups 3A, 3B, and 3C, resp.). The sciatic nerve injury was assessed for nerve regeneration at 2 and 6 weeks. Results. There were no differences between groups 2 and 3 in their sciatic functional index (SFI) values or histological findings at 2 weeks postinjury. However, SFI differences were statistically significant at 6 weeks postinjury in group 3. The gross findings with H&E staining showed that the number of axons was higher in group 3 than in group 2. There was no histological difference according to the DXM concentration. Conclusion. The coincidental functional and histological assessment results of this study suggest that DXM for 6 weeks positively affects damaged peripheral nerves.

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Ferula asafoetida Linn. is effective for early functional recovery following mechanically induced insult to the sciatic nerve of a mouse model

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v19i9.15 ◽

2020 ◽

Vol 19 (9) ◽

pp. 1903-1910

Author(s):

Syed Kashif Shahid Kamran ◽

Azhar Rasul ◽

Haseeb Anwar ◽

Shahzad Irfan ◽

Khizar Sami Ullah ◽

...

Keyword(s):

Oxidative Stress ◽

Sciatic Nerve ◽

Antioxidant Capacity ◽

Grip Strength ◽

Nerve Injury ◽

Muscle Mass ◽

Motor Function ◽

Sciatic Nerve Injury ◽

Sensory Function ◽

Ferula Asafoetida

Purpose: To evaluate the effect of Ferula asafoetida (oleo gum resin powder) on sensory and motor functions retrieval on an induced sciatic nerve injury in a mouse model.Methods: A mechanical crush was inserted in the sciatic nerve of all the experimental mice after acclimatization. The mice were allocated to four groups; one normal chow group (control, n = 7) and three Ferula asafoetida chow groups (each n = 7) of different doses (50, 100 and 200 mg/kg). Muscle grip strength, muscle mass, and sciatic functional index were measured to evaluate the motor function regain, while sensory function regain was assessed by hot plate test. Oxidative stress and glycemic levels were measured by biochemical assays.Results: The findings of this study indicate that Ferula asafoetida 200 mg/kg has a highly significant (p≤ 0.001) ameliorating effect in terms of improved grip strength (77.7 ± 5.4 % for 200 mg/kg vs. 46 ± 5.1 % for control), reversal of SFI towards normal ( -34 ± 8.1 for 200 mg/kg group vs. –61 ± 6.1 for control), decrease in paw withdrawal latency (7.10 ± 0.06 s for 200 mg/kg group vs. 15 ± 0.5 s for control) on day 12 post-injury, as well as restoration of skeletal muscle mass towards normal. Interestingly, F. asafoetida chow 50 mg/kg and 100 mg/kg groups also impacted significant (p < 0.01) improvement in the ameliorative effect. However, the differences among all treatment groups in ameliorating recovery were not significant (p > 0.05). Moreover, comparatively improved (p < 0.0001) total antioxidant capacity along with reduced total oxidant status (p = 0.01) in the Ferula asafoetida chow (200 mg/kg) group, indicate the antioxidative effect of this plant. Furthermore, the treated mice (200 mg/kg) also expressedan improved glycemic level (p = 0.0005).Conclusion: Ferula asafoetida supplementation helps to accelerate both sensory and motor function retrieval following sciatic nerve injury. This improvement is thought to be correlated with the antioxidant capacity of the plant. However, further investigations are required to identify the therapeutic principles responsible for the observed actions. Keywords: Sciatic nerve injury, Ferula asafoetida, Function recovery, Oxidative stress, Biochemical analysis

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Sophocarpine Attenuates Chronic Constriction Sciatic Nerve Injury-induced Neuropathic Pain in Mice by Inhibiting the HMGB1/TLR4/NF-κB Signaling Pathway

Iranian Red Crescent Medical Journal ◽

10.5812/ircmj.94716 ◽

2019 ◽

Vol 21 (9) ◽

Author(s):

Shaoju Jin ◽

Songtao Xu ◽

Rong Wang ◽

Tingting Wang ◽

Kunpeng Guo ◽

...

Keyword(s):

Neuropathic Pain ◽

Sciatic Nerve ◽

Signaling Pathway ◽

Nerve Injury ◽

Sciatic Nerve Injury

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The Application of Pulsed Radiofrequency to Dorsal Root Ganglion Ameliorates Neuropathic Pain by Reducing CCL2 Expression in the Early Stage After Sciatic Nerve Injury in Rats

10.21203/rs.3.rs-119934/v1 ◽

2020 ◽

Author(s):

Cheng-Fu wan ◽

Bo-Han zhang ◽

Dao-Song Dong ◽

Tao Song

Keyword(s):

Neuropathic Pain ◽

Sciatic Nerve ◽

Nerve Injury ◽

Dorsal Root ◽

Early Stage ◽

Sciatic Nerve Injury ◽

Pulsed Radiofrequency ◽

Sprague Dawley ◽

Expression Levels ◽

Ccl2 Expression

Abstract Background: Neuropathic pain (NP) can be treated effectively using pulsed radiofrequency (PRF). NP development and maintenance involves the essential neurotransmitter chemokine c-c motif ligand 2 (CCL2). The present study aimed to determine whether PRF regulated CCL2 expression in sciatic nerve injury (SNI) model rats.Methods: Sprague-Dawley rats were divided randomly into a sham group, an SNI group, and a PRF group. In the PRF group, L5 dorsal root ganglia received PRF treatment. After paw withdrawal mechanical threshold (PWMT) was examined, the expression levels of CCL2 and nuclear factor kappa B (NF-κB) in spinal dorsal horn were determined.Results: The PWMT in PRF group increased significantly compared with that of the SNI group (P < 0.05). The CCL2 and NF-κB expression levels in the PRF group were significant lower than those in the SNI group (P < 0.05).Conclusion: NP was effectively alleviated by PRF-mediated reductions in CCL2 expression via inhibition of NF-κB activation in the spinal cord of SNI model rats.

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The Effect of Prior Nerve Block on Neuropathic Pain Induced by Partial Sciatic Nerve Injury in Rats

PAIN RESEARCH ◽

10.11154/pain.12.131 ◽

1997 ◽

Vol 12 (2) ◽

pp. 131-137

Author(s):

Takumi Nagaro ◽

Kazushi Takaishi ◽

Hitoshi Kojo ◽

Elizabeth A Disbrow ◽

John H Eisele

Keyword(s):

Neuropathic Pain ◽

Sciatic Nerve ◽

Nerve Injury ◽

Nerve Block ◽

Sciatic Nerve Injury

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Gabapentin Treatment for Neuropathic Pain in a Child with Sciatic Nerve Injury

Case Reports in Medicine ◽

10.1155/2015/873157 ◽

2015 ◽

Vol 2015 ◽

pp. 1-3 ◽

Cited By ~ 5

Author(s):

Halil Ekrem Akkurt ◽

Haluk Gümüş ◽

Hamit Göksu ◽

Ömer Faruk Odabaşı ◽

Halim Yılmaz

Keyword(s):

Neuropathic Pain ◽

Sciatic Nerve ◽

Nerve Injury ◽

Pediatric Patients ◽

Muscle Power ◽

Pain Treatment ◽

Sciatic Nerve Injury ◽

Rehabilitation Programme ◽

Medical Treatments ◽

Movement Limitation

There are a restricted number of studies about usage of gabapentin for neuropathic pain treatment of pediatric patients. We shared a 12-year-old male case with severe neuropathic pain that hindered the rehabilitation programme for the loss of muscle power and movement limitation. Neuropathic pain developed after peripheral sciatic damage due to firearm traumatisation did not respond to other medical treatments but healed nearly completely after gabapentin usage.

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Spinal Ninjurin2 contributes to the neuropathic pain via NF-κB-mediated neuroinflammation in the spared sciatic nerve injury rats

International Immunopharmacology ◽

10.1016/j.intimp.2021.107918 ◽

2021 ◽

Vol 99 ◽

pp. 107918

Author(s):

Hai-Ming Guo ◽

Yu Zhang ◽

Yan Zhang ◽

Peng-Fei Jiao ◽

Xiao-Chong Fan ◽

...

Keyword(s):

Neuropathic Pain ◽

Sciatic Nerve ◽

Nerve Injury ◽

Sciatic Nerve Injury

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Gabapentin and NMDA receptor antagonists interacts synergistically to alleviate allodynia in two rat models of neuropathic pain

Scandinavian Journal of Pain ◽

10.1515/sjpain-2018-0083 ◽

2018 ◽

Vol 18 (4) ◽

pp. 687-693 ◽

Cited By ~ 4

Author(s):

Tiansheng Shi ◽

Jing-Xia Hao ◽

Zsuzsanna Wiesenfeld-Hallin ◽

Xiao-Jun Xu

Keyword(s):

Spinal Cord ◽

Neuropathic Pain ◽

Nmda Receptor ◽

Side Effects ◽

Sciatic Nerve ◽

Nerve Injury ◽

Sciatic Nerve Injury ◽

Nmda Receptor Antagonists ◽

Receptor Antagonists ◽

Mk 801

Abstract Background and aims The clinical management of neuropathic pain remains a challenge. We examined the interaction between gabapentin and NMDA receptor antagonists dextromethrophan and MK-801 in alleviating neuropathic pain-like behaviors in rats after spinal cord or sciatic nerve injury. Methods Female and male rats were produced with Ischemic spinal cord injury and sciatic nerve injury. Gabapentin, dextromethorphan, MK-801 or drug combinations were injected with increasing doses. Mechanical response thresholds were tested with von Frey hairs to graded mechanical touch/pressure, and ethyl chloride spray was applied to assess the cold sensitivity before and after injuries. Results In spinally injured rats, gabapentin and dextromethorphan did not affect allodynia-like behaviors at doses of 30 and 20 mg/kg, respectively. In contrast, combination of 15 or 30 mg/kg gabapentin with dextromethorphan at 10 mg/kg produced total alleviation of allodynia to mechanical or cold stimulation. Further reducing the dose of gapapentin to 7.5 mg/kg and dextromethorphan to 5 mg/kg still produced significant effect. MK-801, another NMDA receptor antagonist, also enhanced the effect of gabapentin in spinally injured rats. Similar synergistic anti-allodynic effect between dextromethorphan and gabapentin was also observed in a rat model of partial sciatic nerve injury. No increased side effect was seen following the combination between gabapentin and dextromethorphan. Conclusions In conclusion, the present study suggested that combining NMDA receptor antagonists with gabapentin could provide synergistic effect to alleviate neuropathic pain and reduced side effects. Implications Combining NMDA receptor antagonists with gabapentin may provide a new approach in alleviating neuropathic pain with increased efficacy and reduced side effects.

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