Researching New Therapeutic Approaches for Abdominal Visceral Pain Treatment: Preclinical Effects of an Assembled System of Molecules of Vegetal Origin

Parisio, Carmen; Lucarini, Elena; Micheli, Laura; Toti, Alessandra; Di Cesare Mannelli, Lorenzo; Antonini, Giulia; Panizzi, Elena; Maidecchi, Anna; Giovagnoni, Emiliano; Lucci, Jacopo; Ghelardini, Carla

doi:10.3390/nu12010022

Cited by 18 publications

(14 citation statements)

References 54 publications

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“…Yet, a system of molecules of natural origin displays an intrinsic complexity capable of leading to the impossibility to define the molecular underpinnings underlying its efficacy by applying the conceptual tools typical of the study single, isolated molecules exerting pharmacological effects, such as the key-lock model. Novel epistemological tools, capable of accommodating for this intrinsic complexity at both the structural and functional level, will have to be developed [74].…”

Section: Discussionmentioning

confidence: 99%

Intra-Articular Route for the System of Molecules 14G1862 from Centella asiatica: Pain Relieving and Protective Effects in a Rat Model of Osteoarthritis

et al. 2020

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Current pharmacological therapies for the management of chronic articular diseases are far from being satisfactory, so new strategies need to be investigated. We tested the intra-articular pain relieving properties of a system of molecules from a characterized Centella asiatica extract (14G1862) in a rat model of osteoarthritis induced by monoiodoacetate (MIA). 14G1862 (0.2–2 mg mL−1) was intra-articularly (i.a.) injected 7 days after MIA, behavioural and histological evaluations were performed 14, 30 and 60 days after treatments. Moreover, the effect of 14G1862 on nitrate production and iNOS expression in RAW 264.7 macrophages stimulated with LPS was assessed. In vitro, 14G1862 treatment attenuated LPS-induced NO production and iNOS expression in a comparable manner to celecoxib. In vivo, 14G1862 significantly reduced mechanical allodynia and hyperalgesia, spontaneous pain and motor alterations starting on day 14 up to day 60. The efficacy was higher or comparable to that evoked by triamcinolone acetonide (100 μg i.a.) used as reference drug. Histological evaluation highlighted the improvement of several morphological parameters in MIA + 14G1862-treated animals with particularly benefic effects on joint space and fibrin deposition. In conclusion, i.a. treatment with Centella asiatica is a candidate to be a novel effective approach for osteoarthritis therapy.

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Section: Discussionmentioning

confidence: 99%

Intra-Articular Route for the System of Molecules 14G1862 from Centella asiatica: Pain Relieving and Protective Effects in a Rat Model of Osteoarthritis

et al. 2020

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“…The DNBS injection induces local inflammation that peaks between 3 and 7 days after the injection [36]; its intracolonic instillation sensitizes the intestinal mucosa, leading to increase epithelial permeability, haptenization of host proteins, microbial penetration, and infiltration of neutrophils, macrophages, and Th1 lymphocytes into the damaged mucosa [37]. Visceral hypersensitivity caused by the DNBS administration and subsequent intestinal damage is long lasting [37,38], and persists even after the resolution of the inflammatory acute phase [36,39,40]. For this reason, this animal model is frequently used as a postinflammatory IBS/IBDs model [39,41,42].…”

Section: Discussionmentioning

confidence: 99%

Pomegranate Mesocarp against Colitis-Induced Visceral Pain in Rats: Effects of a Decoction and Its Fractions

Parisio

Lucarini

Micheli

et al. 2020

IJMS

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The management of chronic visceral pain related to Inflammatory Bowel Diseases or Irritable Bowel Syndrome is still a clinical problem and new therapeutic strategies continue to be investigated. In the present study, the efficacy of a pomegranate decoction and of its polysaccharide and ellagitannin components in preventing the development of colitis-induced abdominal pain in rats was evaluated. After colitis induction by 2,4-dinitrobenzenesulfonic acid (DNBS), the pomegranate decoction (300 mg kg−1), polysaccharides (300 mg kg−1), and ellagitannins (45 mg kg−1) were orally administered for 14 days. Repeated treatment with decoction reduced visceral hypersensitivity in the colitic animals both at 7 and 14 days. Similar efficacy was shown by polysaccharides, but with lower potency. Ellagitannins administered at dose equivalent to decoction content showed higher efficacy in reducing the development of visceral pain. Macroscopic and microscopic evaluations performed on the colon 14 days after the damage showed that all three preparations reduced the overall amount of mast cells, the number of degranulated mast cells, and the density of collagen fibers in the mucosal stroma. Although ellagitannins seem to be responsible for most of the beneficial effects of pomegranate on DNBS-induced colitis, the polysaccharides support and enhance its effect. Therefore, pomegranate mesocarp preparations could represent a complementary approach to conventional therapies for promoting abdominal pain relief.

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“…Visceromotor response assessment was conducted in animals under light anaesthesia (2% isoflurane) 14 and 21 days after DNBS administration. The amplitude of the abdominal contraction consequent to colorectal stimulation (a balloon inflated with 0.5, 1, 2, and 3 mL referred to as distension volume) was quantified by electromyography recordings as reported by Parisio et al 64 Behavioural responses to CRD (0.5, 1, 2, and 3 mL referred to as distension volume) were assessed through abdominal withdrawal reflex (AWR) measurement in conscious animals by using a semiquantitative score (0-4) as described previously. 16 The measurements were conducted 14, 21, 28, and 35 days after DNBS administration.…”

Section: Assessment Of Visceral Sensitivity By Visceromotor Response mentioning

confidence: 99%

Acute visceral pain relief mediated by A3AR agonists in rats: involvement of N-type voltage-gated calcium channels

Lucarini¹,

Coppi²,

Micheli³

et al. 2020

Pain

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Pharmacological tools for chronic visceral pain management are still limited and inadequate. A 3 adenosine receptor (A 3 AR) agonists are effective in different models of persistent pain. Recently, their activity has been related to the block of N-type voltage-gated Ca 21 channels (Ca v 2.2) in dorsal root ganglia (DRG) neurons. The present work aimed to evaluate the efficacy of A 3 AR agonists in reducing postinflammatory visceral hypersensitivity in both male and female rats. Colitis was induced by the intracolonic instillation of 2,4dinitrobenzenesulfonic acid (DNBS; 30 mg in 0.25 mL 50% EtOH). Visceral hypersensitivity was assessed by measuring the visceromotor response and the abdominal withdrawal reflex to colorectal distension. The effects of A 3 AR agonists (MRS5980 and Cl-IB-MECA) were evaluated over time after DNBS injection and compared to that of the selective Ca v 2.2 blocker PD173212, and the clinically used drug linaclotide. A 3 AR agonists significantly reduced DNBS-evoked visceral pain both in the postinflammatory (14 and 21 days after DNBS injection) and persistence (28 and 35 days after DNBS) phases. Efficacy was comparable to effects induced by linaclotide. PD173212 fully reduced abdominal hypersensitivity to control values, highlighting the role of Ca v 2.2. The effects of MRS5980 and Cl-IB-MECA were completely abolished by the selective A 3 AR antagonist MRS1523. Furthermore, patch-clamp recordings showed that A 3 AR agonists inhibited Ca v 2.2 in dorsal root ganglia neurons isolated from either control or DNBS-treated rats. The effect on Ca 21 current was PD173212-sensitive and prevented by MRS1523. A 3 AR agonists are effective in relieving visceral hypersensitivity induced by DNBS, suggesting a potential therapeutic role against abdominal pain.

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Researching New Therapeutic Approaches for Abdominal Visceral Pain Treatment: Preclinical Effects of an Assembled System of Molecules of Vegetal Origin

Cited by 18 publications

References 54 publications

Intra-Articular Route for the System of Molecules 14G1862 from Centella asiatica: Pain Relieving and Protective Effects in a Rat Model of Osteoarthritis

Intra-Articular Route for the System of Molecules 14G1862 from Centella asiatica: Pain Relieving and Protective Effects in a Rat Model of Osteoarthritis

Pomegranate Mesocarp against Colitis-Induced Visceral Pain in Rats: Effects of a Decoction and Its Fractions

Acute visceral pain relief mediated by A3AR agonists in rats: involvement of N-type voltage-gated calcium channels

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