The anti-inflammatory and analgesic effects of formulated full-spectrum cannabis extract in the treatment of neuropathic pain associated with multiple sclerosis

Non-steroidal anti-inflammatory drugs (NSAIDs) including both traditional non-selective NSAIDs and the selective cyclooxygenase (COX)-2 inhibitors, are widely used for their anti-inflammatory and analgesic effects. NSAIDs are a necessary choice in pain management because of the integrated role of the COX path way in the generation of inflammation and in the biochemical recognition of pain. NSAIDs are the competitive inhibitors of cyclooxygenase (COX), the enzyme which mediates the bioconversion of arachidonic acid to inflammatory prostaglandins (PGs). Their use is associated with the side effects such as gastrointestinal and renal toxicity. They are the most commonly employed first line drugs for all these conditions and many others-like musculoskeletal trauma, minor aches and pains, and dysmenorrhoea. The therapeutic anti-inflammatory action of NSAIDs is produced by the inhibition of COX-2, while the undesired side effects arise from inhibition of COX-1 activity. Thus, it was though those more selective COX-2 inhibitors would have reduced side effects. Based upon a number of selective COX-2 inhibitors (Rofecoxib, Celecoxib etc.) were developed as safer NSAIDs with improved gastric safety profile. Several newer applications like prophylaxis of stroke with aspirin are now common place. Use of these drugs for the prophylaxis of conditions like Alzheimer’s disease and colorectal cancer is being evaluated. Unfortunately, they have several toxicities ranging from minor heartburn to severe gastrointestinal haemorrhage and perforation. Therefore, newer NSAIDs have been introduced in recent years to circumvent this problem. In preliminary studies, these have shown better safety, efficacy, and tolerability but the full spectrum of adverse reactions of these drugs is yet to be fully known. This review can be used for further research as well as clinical purpose. Keywords: Non-steroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase inhibitors, prostaglandins, aspirin.

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Faculty Opinions recommendation of Botulinum toxin type A induces direct analgesic effects in chronic neuropathic pain.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1138002.595110 ◽

2008 ◽

Author(s):

Troels Jensen

Keyword(s):

Neuropathic Pain ◽

Botulinum Toxin ◽

Botulinum Toxin Type A ◽

Type A ◽

Botulinum Toxin Type ◽

Chronic Neuropathic Pain ◽

Analgesic Effects

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Assessment of biochemical determinants in Multiple Sclerosis patients following the oral administration of β-D-Mannuronic acid [M2000]

Current Drug Discovery Technologies ◽

10.2174/1570163817999200918104333 ◽

2020 ◽

Vol 17 ◽

Author(s):

Mohamad Reza Nikouei Moghaddam ◽

Monireh Movahedi ◽

Maryam Bananej ◽

Soheil Najafi ◽

Nahid Beladi Moghadam ◽

...

Keyword(s):

Multiple Sclerosis ◽

Uric Acid ◽

Vitamin D3 ◽

Chronic Inflammatory Disease ◽

Toxic Effects ◽

Control Group ◽

Therapeutic Effects ◽

Mannuronic Acid ◽

Anti Inflammatory ◽

Multiple Sclerosis Patients

Background: Multiple sclerosis is an autoimmune chronic inflammatory disease of the central nervous system that can lead to some serious disabilities. Despite using various immunomodulatory and anti-inflammatory drugs that have therapeutic effects, they cannot reduce its progression completely, and have some unwanted side effects too. The immunomodulatory and anti-inflammatory effects of the β-D-Mannuronic acid [M2000] have been proven in several surveys, and the present research was designed to determine its toxicity and therapeutic effects in MS patients. Methods: This study was performed on 15 MS patients who took 25 mg/kg/day the oral form of the β-D-Mannuronic acid for six months, and 15 healthy people as a control group. Serum levels of Urea, Creatinine, GGT, Vitamin D3, Uric acid, and Anti-Phospholipids were compared to evaluate the therapeutic and possible toxic effects of this drug after this period. Results: Non- toxic effects through the study of Urea, Creatinine, GGT, and non-significant changes in Uric acid and AntiPhospholipids levels, besides a significant rise in Vitamin, D3 levels in the M2000 treated cases were found. Conclusions: Our results suggested that β-D-Mannuronic acid is a safe drug and has no toxicity when administered orally and also has some therapeutic effects in MS patients.

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Novel Piperazinyl Derivatives with Anti-Hyperalgesic, Anti-Allodynic and Anti-Inflammatory activities Useful for the Treatment of Neuropathic Pain

Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry ◽

10.2174/187152312803305704 ◽

2012 ◽

Vol 11 (2) ◽

pp. 182-190 ◽

Cited By ~ 3

Author(s):

Monika Sharma ◽

Shraddha Suman Dash ◽

Gangadhar Matharasala ◽

Vanamala Deekshith ◽

Dharmarajan Sriram ◽

...

Keyword(s):

Neuropathic Pain ◽

Anti Inflammatory

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Anti-inflammatory and Analgesic Effects of Ketoprofen in Palm Oil Esters Nanoemulsion

Journal of Oleo Science ◽

10.5650/jos.59.667 ◽

2010 ◽

Vol 59 (12) ◽

pp. 667-671 ◽

Cited By ~ 8

Author(s):

Sakeena M. H. F. ◽

Yam M. F. ◽

Elrashid S. M. ◽

Munavvar A. S. ◽

Azmin M. N.

Keyword(s):

Palm Oil ◽

Analgesic Effects ◽

Anti Inflammatory

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New ibuprofen derivatives with thiazolidine-4-one scaffold with improved pharmaco-toxicological profile

BMC Pharmacology and Toxicology ◽

10.1186/s40360-021-00475-0 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Ioana-Mirela Vasincu ◽

Maria Apotrosoaei ◽

Sandra Constantin ◽

Maria Butnaru ◽

Liliana Vereștiuc ◽

...

Keyword(s):

Analgesic Effect ◽

Visceral Pain ◽

Biological Effects ◽

Maximum Effect ◽

Tail Flick ◽

Paw Edema ◽

Cell Viability Assay ◽

Thermal Nociception ◽

Analgesic Effects ◽

Anti Inflammatory

Abstract Background Aryl-propionic acid derivatives with ibuprofen as representative drug are very important for therapy, being recommended especially for anti-inflammatory and analgesic effects. On other hand 1,3-thiazolidine-4-one scaffold is an important heterocycle, which is associated with different biological effects such as anti-inflammatory and analgesic, antioxidant, antiviral, antiproliferative, antimicrobial etc. The present study aimed to evaluated the toxicity degree and the anti-inflammatory and analgesic effects of new 1,3-thiazolidine-4-one derivatives of ibuprofen. Methods For evaluation the toxicity degree, cell viability assay using MTT method and acute toxicity assay on rats were applied. The carrageenan-induced paw-edema in rat was used for evaluation of the anti-inflammatory effect while for analgesic effect the tail-flick test, as thermal nociception in rats and the writhing assay, as visceral pain in mice, were used. Results The toxicological screening, in terms of cytotoxicity and toxicity degree on mice, revealed that the ibuprofen derivatives (4a-n) are non-cytotoxic at 2 μg/ml. In addition, ibuprofen derivatives reduced carrageenan-induced paw edema in rats, for most of them the maximum effect was recorded at 4 h after administration which means they have medium action latency, similar to that of ibuprofen. Moreover, for compound 4d the effect was higher than that of ibuprofen, even after 24 h of administration. The analgesic effect evaluation highlighted that 4 h showed increased pain inhibition in reference to ibuprofen in thermal (tail-flick assay) and visceral (writhing assay) nociception models. Conclusions The study revealed for ibuprofen derivatives, noted as 4 m, 4 k, 4e, 4d, a good anti-inflammatory and analgesic effect and also a safer profile compared with ibuprofen. These findings could suggest the promising potential use of them in the treatment of inflammatory pain conditions.

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IL4-10 Fusion Protein Shows DMOAD Activity in a Rat Osteoarthritis Model

Cartilage ◽

10.1177/19476035211026736 ◽

2021 ◽

pp. 194760352110267

Author(s):

E.M. van Helvoort ◽

H.M. de Visser ◽

F.P.J.G. Lafeber ◽

K. Coeleveld ◽

S. Versteeg ◽

...

Keyword(s):

Fusion Protein ◽

Single Molecule ◽

Mechanical Allodynia ◽

Cartilage Damage ◽

Cartilage Degeneration ◽

Synovial Inflammation ◽

Interleukin 4 ◽

Analgesic Effects ◽

Metabolic Dysregulation ◽

Anti Inflammatory

Objective Ideally, disease-modifying osteoarthritis (OA) drugs (DMOAD) should combine chondroprotective, anti-inflammatory, and analgesic effects in a single molecule. A fusion protein of interleukin-4 (IL-4) and IL-10 (IL4-10 FP) possesses these combined effects. In this study, the DMOAD activity of rat IL4-10 FP (rIL4-10 FP) was tested in a rat model of surgically induced OA under metabolic dysregulation. Design rIL4-10 FP was produced with HEK293F cells. Bioactivity of purified rIL4-10 FP was determined in a whole blood assay. Male Wistar rats ( n = 20) were fed a high-fat diet (HFD) to induce metabolic dysregulation. After 12 weeks, OA was induced according to the Groove model. Two weeks after OA induction, rats were randomly divided into 2 groups and treated with 10 weekly, intra-articular injections of either rIL4-10 FP ( n = 10) or phosphate buffered saline (PBS; n = 10). Possible antibody formation was evaluated using ELISA, cartilage degeneration and synovial inflammation were evaluated by histology and mechanical allodynia was evaluated using the von Frey test. Results Intra-articular injections with rIL4-10 FP significantly reduced cartilage degeneration ( P = 0.042) and decreased mechanical allodynia ( P < 0.001) compared with PBS. Only mild synovial inflammation was found (nonsignificant), limiting detection of putative anti-inflammatory effects. Multiple injections of rIL4-10 FP did not induce antibodies against rIL4-10 FP. Conclusion rIL4-10 FP showed chondroprotective and analgesic activity in a rat OA model with moderate cartilage damage, mild synovial inflammation, and pain. Future studies will need to address whether less frequent intra-articular injections, for example, with formulations with increased residence time, would also lead to DMOAD activity.

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Short-chain fatty acids contribute to neuropathic pain via regulating microglia activation and polarization

Molecular Pain ◽

10.1177/1744806921996520 ◽

2021 ◽

Vol 17 ◽

pp. 174480692199652

Author(s):

Feng Zhou ◽

Xian Wang ◽

Baoyu Han ◽

Xiaohui Tang ◽

Ru Liu ◽

...

Keyword(s):

Spinal Cord ◽

Neuropathic Pain ◽

Thermal Hyperalgesia ◽

Short Chain Fatty Acids ◽

Antibiotic Administration ◽

Tnf Α ◽

Microglia Polarization ◽

Inflammatory Phenotype ◽

Phenotype Markers ◽

Anti Inflammatory

Microglia activation and subsequent pro-inflammatory responses play a key role in the development of neuropathic pain. The process of microglia polarization towards pro-inflammatory phenotype often occurs during neuroinflammation. Recent studies have demonstrated an active role for the gut microbiota in promoting microglial full maturation and inflammatory capabilities via the production of Short-Chain Fatty Acids (SCFAs). However, it remains unclear whether SCFAs is involved in pro-inflammatory/anti-inflammatory phenotypes microglia polarization in the neuropathic pain. In the present study, chronic constriction injury (CCI) was used to induce neuropathic pain in mice, the mechanical withdrawal threshold, thermal hyperalgesia were accomplished. The levels of microglia markers including ionized calcium-binding adaptor molecule 1 (Iba1), cluster of differentiation 11b (CD11b), pro-inflammatory phenotype markers including CD68, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and anti-inflammatory phenotype markers including CD206, IL-4 in the hippocampus and spinal cord were determined on day 21 after CCI. The results showed that CCI produced mechanical allodynia and thermal hyperalgesia, and also increased the expressions of microglia markers (Iba1, CD11b) and pro-inflammatory phenotype markers (CD68, IL-1β, and TNF-α), but not anti-inflammatory phenotype marker (CD206, IL-4) in the hippocampus and spinal cord, accompanied by increased SCFAs in the gut. Notably, antibiotic administration reversed these abnormalities, and its effects was also bloked by SCFAs administration. In conclusion, data from our study suggest that CCI can lead to mechanical and thermal hyperalgesia, while SCFAs play a key role in the pathogenesis of neuropathic pain by regulating microglial activation and subsequent pro-inflammatory phenotype polarization. Antibiotic administration may be a new treatment for neuropathic pain by reducing the production of SCFAs and further inhibiting the process of microglia polarization.

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Central neuropathic pain in multiple sclerosis is associated with impaired innocuous thermal pathways and neuronal hyperexcitability

Pain Medicine ◽

10.1093/pm/pnab103 ◽

2021 ◽

Author(s):

Michal Rivel ◽

Anat Achiron ◽

Mark Dolev ◽

Yael Stern ◽

Gaby Zeilig ◽

...

Keyword(s):

Multiple Sclerosis ◽

Neuropathic Pain ◽

Cross Sectional Study ◽

Healthy Controls ◽

Sectional Study ◽

Sensory Testing ◽

Cross Sectional ◽

Central Neuropathic Pain ◽

Body Regions ◽

Thermal Grill Illusion

Abstract Objective About a third of patients with multiple sclerosis (MS) suffer from chronic and excruciating central neuropathic pain (CNP). The mechanism underlying CNP in MS is not clear, since previous studies are scarce and their results are inconsistent. Our aim was to determine whether CNP in MS is associated with impairment of the spinothalamic-thalamocortical pathways (STTCs) and/or increased excitability of the pain system. Design Cross sectional study Setting General hospital Subjects 47 MS patients with CNP, 42 MS patients without CNP, and 32 healthy controls. Methods Sensory testing included the measurement of temperature, pain, and touch thresholds and the thermal grill illusion (TGI) for evaluating STTCs function, and hyperpathia and allodynia as indicators of hyperexcitability. CNP was characterized using interviews and questionnaires. Results The CNP group had higher cold and warm thresholds (p < 0.01), as well as higher TGI perception thresholds (p < 0.05), especially in painful body regions compared to controls, whereas touch and pain thresholds values were normal. The CNP group also had a significantly greater prevalence of hyperpathia and allodynia. Regression analysis revealed that whereas presence of CNP was associated with a higher cold threshold, CNP intensity, and the number of painful body regions were associated with allodynia and hyperpathia, respectively. Conclusions CNP in MS is characterized by a specific impairment of STTC function; the innocuous thermal pathways, and by pain hyperexcitability. Whereas CNP presence is associated with STTC impairment, its severity and extent are associated with pain hyperexcitability. Interventions that reduce excitability level may therefore mitigate CNP severity.

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