Muscle vibration measurement has long been an unique scientific study, in general, and the direct reaction of animals to feel pain (algesia), either from vascular or muscle contraction, is a complex perceptual experience. Thus this paper proposes a way to measure animal algesia quantitatively, by measuring the changes in muscle vibration due to a pinprick on the surface of the skin of a Spodoptera litura larva. Using the laser optical triangulation measurement principle, along with a CMOS image sensor, linear laser, software analysis, and other tools, we quantify the subtle object point displacement, with a precision of up to $10{\mu}m$, for our chosen Spodoptera litura larva animal model, in which it is not easy to identify the tiny changes in muscle contraction dynamics with the naked eye. We inject different concentrations of formalin reagent (empty needle, 12% formalin, and 37% formalin) to obtain a variety of different muscle vibration frequencies as the experimental results. Because of the high concentrations of reagent applied, we see a high frequency shift of muscle vibration, which can be presented as pain indices, so that the algesia can be quantified.
Spinal cord contusion injury is one of the most serious nervous system disorders, characterized by high morbidity and disability. To mimic spinal cord contusion in humans, various animal models of spinal contusion injury have been developed. These models have been developed in rats, mice, and monkeys. However, most of these models are developed using rats. Two types of animal models, i.e. bilateral contusion injury and unilateral contusion injury models, are developed using either a weight drop method or impactor method. In the weight drop method, a specific weight or a rod, having a specific weight and diameter, is dropped from a specific height on to the exposed spinal cord. Low intensity injury is produced by dropping a 5 g weight from a height of 8 cm, moderate injury by dropping 10 g weight from a height of 12.5-25 mm, and high intensity injury by dropping a 25 g weight from a height of 50 mm. In the impactor method, injury is produced through an impactor by delivering a specific force to the exposed spinal cord area. Mild injury is produced by delivering $100{\pm}5kdyn$ of force, moderate injury by delivering $200{\pm}10kdyn$ of force, and severe injury by delivering $300{\pm}10kdyn$ of force. The contusion injury produces a significant development of locomotor dysfunction, which is generally evident from the $0-14^{th}$ day of surgery and is at its peak after the $28-56^{th}$ day. The present review discusses different animal models of spinal contusion injury.
Anti-nociceptive and anti-inflammatory effects of Clematidis Radix (CR)-distillates were investigated in three different pain animal models. Highly purified distillate of CR was injected to Zusanli (ST36) acupoint, called CR herb-acupuncture in the Korean traditional medicine. In tail flick latency test, the CR herb-acupuncture treatment did not show a significant effect of relieving acute phasic pain. To investigate the anti-inflammatory effect of CR herb-acupuncture, inflammatory pain was induced by subcutaneous injection of formalin to the plantar tissue or intra-articular injection of carrageenan to the tibio-tarsal joint in the rats. And the medicinal effect of CR herb-acupuncture was evaluated by analyzing pain behavior such as licking or biting behavior, or by measuring weight distribution ratio between two foot and ankle circumference. In the rat formalin test, the analgesic effect of CR herb-acupuncture was more pronounced in the late phase (for 20 min after the early phase) than in the early phase (for the first 10 min post formalin injection). It also significantly alleviated the carrageenan-induced monoarthritis, in terms of weight distribution ratio and ankle edema. These results revealed that CR herb-acupuncture was effective to treat the inflammatory pain and could be used as an analgesic treatment with an antiinflammatory effect.
Background: Nerve ligation injury may produce mechanical allodynia, but this can be reversed after an intrathecal administration of adenosine analogues. In many animal and human studies, ATP-sensitive potassium channel blockers have been known to reverse the antinociceptive effect of various drugs. This study was performed to evaluate the mechanical antiallodynic effects of spinal R-PIA (Adenosine A1 receptor agonist) and the reversal of these effects due to pretreatment with glibenclamide (ATP-sensitive potassium channel blocker). Thus, the relationship between the antiallodynic effects of R-PIA and ATP-sensitive potassium channel were investigated in a neuropathic model. Methods: Male Sprague Dawley rats were prepared by tightly ligating the left lumbar 5th and 6th spinal nerves and implantation of a chronic lumbar intrathecal catheter for drug administration. The mechanical allodynia was measured by applying von Frey filaments ipsilateral to the lesioned hind paw. And the thresholds for paw withdrawal assessed. In study 1, either R-PIA (0.5, 1 and $2{\mu}g$) or saline were administered intrathecally for the examination of the antiallodynic effect of R-PIA. In study 2, glibenclamide (2, 5, 10 and 20 nM) was administered intrathecally 5 min prior to an R-PIA injection for investigation of the reversal of the antiallodynic effects of R-PIA. Results: The antiallodynic effect of R-PIA was produced in a dose dependent manner. In study 1, the paw withdrawal threshold was significantly increased with $2{\mu}g$ R-PIA (P < 0.05). In study 2, the paw withdrawal threshold with $2{\mu}g$ R-PIA was significantly decreased almost dose dependently by intrathecal pretreatment of 5, 10 and 20 nM glibenclamide (P < 0.05). Conclusions: These results demonstrated that an intrathecal injection of ATP-sensitive potassium channel blockers prior to an intrathecal injection of adenosine A1 receptors agonist had an antagonistic effect on R-PIA induced antiallodynia. The results suggest that the mechanism of mechanical antiallodynia, as induced by an intrathecal injection of R-PIA, may involve the ATP-sensitive potassium channel at both the spinal and supraspinal level in a rat nerve ligation injury model.
Background: Lipo-prostaglandin E1 (Lipo-$PGE_1$) has vasodilating and platelet aggregation inhibitory characteristics and it has been used as a treatment for patients with blood flow dysfunction disease. Based on the mechanisms of lumbar spinal stenosis, including veno congestion, neuro-ischemia and mechanical compression, we aimed to study whether intravenous Lipo-$PGE_1$ injection has any therapeutic effect on hyperalgesia in a rat foraminal stenosis model. Methods: In this study, twenty male Sprague-Dawley rats were divided into the control (n = 10) and Lipo-$PGE_1$ (n = 10) groups. A small stainless steel rod was inserted into the L5-6 intervertebral foramen to induce intervertebral foramen stenosis and chronic DRG compression. In the Lipo-$PGE_1$ group, $0.15{\mu}g/kg$ of Lipo-$PGE_1$ were injected intravenously via a tail vein for 10 days starting from the $3^{rd}$ day after operation. Behavioral testing for mechanical and thermal hyperalgesia was performed for 3 weeks after the injections. Results: From the $10^{th}$ day after Lipo-$PGE_1$ injection, the rats in the experimental group showed significant recovery of their mechanical threshold, and this effect was maintained for 3 weeks. No significant differences of the thermal hyperalgesia were observed between the two groups. Conclusions: These findings suggest that intravenously injected Lipo-$PGE_1$ may be effective for alleviating neuropathic pain, which isthe main symptom of spinal stenosis, by improving the blood flow dysfunction.
Oral mucositis or stomatitis produced by stomatotoxic chemotherapy and/or radiation therapy are painful, restrict oral intake and, importantly, act as sites of secondary infection and potals of entry for the endogenous oral microflora often leading to bacteremias or sepsis. A number of clinical observations and studies of animal model suggests a pathophysiological complexity in the development of mucositis. The condition appears to represent a sequential interaction of the oral mucosal cells and tissues, pro-inflammatory cytokines, and local environmental factors in the mouth. This article discussed and reviewed biological process of the mucositis and, the role of cytokines as initiators and amplifiers of the process. The recognition that the pathophysiology of mucositis is a multifactorial process has presented opportunities for intervention based upon biological attenuation.
Zhu, Yi;Sun, Mei;Liu, Peng;Shao, Weidong;Xiong, Ming;Xu, Bo
The Korean Journal of Pain
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제35권4호
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pp.423-432
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2022
Background: The decreased expression of mu-opioid receptors (MOR) in the amygdala may be a key molecular in chronic post-surgical pain (CPSP). It is known that miR-339-5p expression in the amygdala of a stressed rat model was increased. Analyzed by RNAhybrid, miR-339-5p could target opioid receptor mu 1 (oprm1) which codes MOR directly. So, the authors hypothesized that miR-339-5p could regulate the expression of MOR via targeting oprm1 and cause the effects to CPSP. Methods: To simulate perioperative short-term stress, a perioperative stress prolongs incision-induced pain hypersensitivity without changing basal pain perception rat model was built. A pmiR-RB-REPORTTM dual luciferase assay was taken to verify whether miR-339-5p could act on oprm1 as a target. The serum glucocorticoid level of rats was test. Differential expressions of MOR, GFAP, and pERK1/2 in each group of the rats' amygdala were tested, and the expressions of miR-339-5p in each group of rats' amygdalas were also measured. Results: Perioperative stress prolonged the recovery time of incision pain. The expression of MOR was down-regulated in the amygdala of rats in stress + incision (S + IN) group significantly compared with other groups (P < 0.050). miR-339-5p was up-regulated in the amygdala of rats in group S + IN significantly compared with other groups (P < 0.050). miR-339-5p acts on oprm1 3'UTR and take MOR mRNA as a target. Conclusions: Perioperative stress could increase the expression of miR-339-5p, and miR-339-5p could cause the expression of MOR to decrease via targeting oprm1. This regulatory pathway maybe an important molecular mechanism of CPSP.
Many surgeons and anesthesiologists prefer using vasoconstrictor mixed with local anesthetic agent to reduce the incidence of side effects and prolong the duration of analgesia because most local anesthetic agents, except cocaine, were believed to possess vasodilating effect. However, some investigators recently reported vasoconstricting effect of local anesthetic agents. There is still controversy on the vasoactive effect of local anesthetic agents. So this study is aimed to clarify the vasoactive effect of local anesthetics in the animal model resembling clinical settings. Rabbits were anesthesized with ketamine and haloghane, and respirations were controlled with Harvard animal ventilator. Lidocaine (0.5%, 1.0%, 1.5%) and bupivacaine (0.125%, 0.25% and 0.5%) with or without 1:100,000 epinephrine were subdermaly injected on the femoral bupivacaine of the femoral artery were measured with Doppler flow meter in vivo. The mean arterial pressure, pulse rate, arterial blood gases, pH and level of serum electrolytes were measured at every 2 minute interval for 30 minutes. Results were as follows: 1) There was no significant vasoconstriction with 0.5% lidocaine and 0.125% bupivacaine. 2) Statistically significant (p<0.05) vasodilations were observed with lidocaine (1.0~2.0%) and bupivacaine (0.25~0.5%). 3) There were no changes on the duration of vasodilation induced by local anesthetic agents of various concentrations. 4) Onset of vasodilation induced by local anesthetic agents of high concentration were faster than that of lower concentrations. 5) In the mixed injection group of epinephrine and local anesthetic agent, the vasoconstriction induced by epinephrine was completely reversed by local anesthetics, approximately 5 minutes later. In conclusion, local anesthetic agents at dose exceeding 1.0% lidocaine and 0.25% bupivacaine increase local blood flow significantly in animal study in vivo which is applicable in human clinical settings. The increase blood flow may be due to dilatation of blood vessel. Further study on the analysis of association between amount of absorbed local anesthetics in blood vessels and dilatation of blood vessels is needed.
Objectives : The purpose of this Study was to identify the effect of Dokhwalgisaeng-tang(Duhuoqisheng-tang) and Jungsongouhyul pharmacopuncture on pain control and nerve regeneration after crush injury in rat sciatic nerve. Methods : Neuropathic pain was induced by crush-induced model of right sciatic nerve. Animal groups were divided as follows; Group I: no treatment control group, Group II : experimental group treated with Dokhwalgisaeng-tang(Duhuoqisheng-tang), Group III : experimental group treated with Jungsongouhyul pharmacopuncture, and Group IV : experimental group treated with Dokhwalgisaeng-tang(Duhuoqisheng-tang) and Jungsongouhyul pharmacopuncture. To evaluate pain intensity, each group was observed paw withdrawal threshold and immunoreactivity on the c-fos before and after respective treatments in five hours, first, third, and fifth day. To evaluate nerve regeneration, those were observed SFI(Sciatic Functional Index) and GAP-43(Growth Associated Protein 43) after each treatment in seventh and thirteenth day. Results : 1. Paw withdrawal threshold to the mechanical stimuli made the significant difference between group IV and the control group after five days of the experiment. 2. Paw withdrawal threshold to the thermal stimuli made the significant difference between group I and III, I and IV, II and IV. 3. In immunohistochemical response of c-fos, as time passes, the immunoreactivity of all groups was decreased gradually. Especially, group IV was observed the lowest after three days. 4. The differences of sciatic function indexes in each group were significantly between group I and III, I and IV, II and IV after 14 days, and between group I and III, I and IV, II and IV, III and IV after 21 days. 5. In immunohistochemical response of GAP-43, all groups had higher GAP-43 immunoreactivity at the 14 days from post-injury and group IV showed highest immunoreactivity. Conclusions : Based on above the results, it is proposed that Dokhwalgisaeng-tang(Duhuoqisheng-tang) and Jungsongouhyul pharmacopuncture may be helpful as a treatment in neuropathic pain and nerve regeneration in rat model.
Anna Kang;Min-Jin Kwak;Hye Jin Choi;Seon-hui Son;Sei-hyun Lim;Ju Young Eor;Minho Song;Min Kyu Kim;Jong Nam Kim;Jungwoo Yang;Minjee Lee;Minkyoung Kang;Sangnam Oh;Younghoon Kim
한국축산식품학회지
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제44권5호
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pp.1080-1095
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2024
In contemporary society, the increasing number of pet-owning households has significantly heightened interest in companion animal health, expanding the probiotics market aimed at enhancing pet well-being. Consequently, research into the gut microbiota of companion animals has gained momentum, however, ethical and societal challenges associated with experiments on intelligent and pain-sensitive animals necessitate alternative research methodologies to reduce reliance on live animal testing. To address this need, the Fermenter for Intestinal Microbiota Model (FIMM) is being investigated as an in vitro tool designed to replicate gastrointestinal conditions of living animals, offering a means to study gut microbiota while minimizing animal experimentation. The FIMM system explored interactions between intestinal microbiota and probiotics within a simulated gut environment. Two strains of commercial probiotic bacteria, Enterococcus faecium IDCC 2102 and Bifidobacterium lactis IDCC 4301, along with a newly isolated strain from domestic dogs, Lactobacillus acidophilus SLAM AK001, were introduced into the FIMM system with gut microbiota from a beagle model. Findings highlight the system's capacity to mirror and modulate the gut environment, evidenced by an increase in beneficial bacteria like Lactobacillus and Faecalibacterium and a decrease in the pathogen Clostridium. The study also verified the system's ability to facilitate accurate interactions between probiotics and commensal bacteria, demonstrated by the production of short-chain fatty acids and bacterial metabolites, including amino acids and gamma-aminobutyric acid precursors. Thus, the results advocate for FIMM as an in vitro system that authentically simulates the intestinal environment, presenting a viable alternative for examining gut microbiota and metabolites in companion animals.
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