Topical Loperamide-Encapsulated Liposomal Gel Increases the Severity of Inflammation and Accelerates Disease Progression in the Adjuvant-Induced Model of Experimental Rheumatoid Arthritis
Susan Hua, Thilani H. Dias, Debbie-Gai Pepperall, Yuan Yang
Abstract
This study evaluates the prophylactic effect of the peripherally-selective mu-opioid receptor agonist, loperamide, administered topically in a liposomal gel formulation on pain, inflammation, and disease progression in the adjuvant-induced model of experimental rheumatoid arthritis in female Lewis rats. In a randomized, blinded and controlled animal trial, AIA rats were divided into six groups consisting of eleven rats per group based on the following treatments: loperamide liposomal gel, free loperamide gel, empty liposomal gel, diclofenac gel (Voltaren®), no treatment, and naive control. Topical formulations were applied daily for a maximum of 17 days-starting from day 0 at the same time as immunization. The time course of the effect of the treatments on antinocieption and inflammation was assessed using a paw pressure analgesiometer and plethysmometer, respectively. Arthritis progression was scored daily using an established scoring protocol. At the end of the study, hind paws were processed for histological analysis. Administration of loperamide liposomal gel daily across the duration of the study produced significant peripheral antinociception as expected; however, increased the severity of inflammation and accelerated arthritis progression. This was indicated by an increase in paw volume, behavioral and observational scoring, and histological analysis compared to the control groups. In particular, histology results showed an increase in pannus formation and synovial inflammation, as well as an upregulation of markers of inflammation and angiogenesis. These findings may have implications for the use of loperamide and other opioids in arthritis and potentially other chronic inflammatory diseases.
Pharmacology, Toxicology and Pharmaceutical Science
7
25%
Medicine and Dentistry
5
18%
Neuroscience
1
4%
Psychology
1
4%
Unknown
14
50%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 01 April 2019.
All research outputs
#14,950,579
of 22,996,001 outputs
Outputs from Frontiers in Pharmacology
#5,274
of 16,300 outputs
Outputs of similar age
#188,386
of 317,618 outputs
Outputs of similar age from Frontiers in Pharmacology
#88
of 258 outputs
Altmetric has tracked 22,996,001 research outputs across all sources so far. This one is in the 32nd percentile – i.e., 32% of other outputs scored the same or lower than it.
So far Altmetric has tracked 16,300 research outputs from this source. They receive a mean Attention Score of 5.0. This one has gotten more attention than average, scoring higher than 60% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 317,618 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 37th percentile – i.e., 37% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 258 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 59% of its contemporaries.
