scholarly journals Antinociceptive effects of intrathecal cimifugin treatment: a preliminary rat study based on formalin test

2020 ◽  
Vol 15 (4) ◽  
pp. 478-485
Author(s):  
Hyun Young Lee ◽  
Young Joon Ki ◽  
Su Yeong Park ◽  
Soo Yeon Cho ◽  
Jinyoung Seo ◽  
...  
Keyword(s):  
Analgesic Effect ◽  
Formalin Test ◽  
Phase 1 ◽  
Antinociceptive Effect ◽  
Intrathecal Administration ◽  
Phase 2 ◽  
Sprague Dawley ◽  
Antinociceptive Effects ◽  
Saposhnikovia Divaricata ◽  
Rat Study

Background: Cimifugin is one of the components of the root of Saposhnikovia divaricata. The extract derived from S. divaricata is traditionally used as an analgesic. This study was conducted to evaluate the analgesic effect of intrathecal cimifugin in the formalin test.Methods: Male Sprague–Dawley rats (n = 20) were randomized into four groups for intrathecal administration of 70% dimethylsulfoxide and various doses of cimifugin (100 μg, 300 μg, and 1,000 μg). The typical flinch response after the injection of 5% formalin into the hind paw was assessed in two distinct phases: phase 1 until 10 min, and phase 2 from 10 min to 60 min. ED50 values were calculated via linear regression.Results: Intrathecal cimifugin significantly reduced the flinch response in both phases of the formalin test. Significant antinociceptive effects of cimifugin were found with the dose of 300 μg in phase 1 and the dose of 100 μg in phase 2. The ED50 value (95% confidence intervals) of intrathecal cimifugin was 696.1 (360.8–1,342.8) μg during phase 1 and 1,242.8 (42.0–48,292.5) μg during phase 2.Conclusions: Intrathecal cimifugin has an antinociceptive effect against formalin-induced pain. Cimifugin has an anti-inflammatory effect at low concentrations, and non-inflammatory analgesic effect at higher concentrations.

scholarly journals Electroacupuncture Pretreatment at GB20 Exerts Antinociceptive Effects via Peripheral and Central Serotonin Mechanism in Conscious Migraine Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Lu Liu ◽  
Pei Pei ◽  
Luo-Peng Zhao ◽  
Zheng-Yang Qu ◽  
Yu-Pu Zhu ◽  
...  
Keyword(s):  
High Performance ◽  
Antinociceptive Effect ◽  
Underlying Mechanism ◽  
Sham Acupuncture ◽  
Sprague Dawley ◽  
Grooming Behavior ◽  
Sprague Dawley Rats ◽  
Serotonin System ◽  
Antinociceptive Effects ◽  
Exploration Behavior

Background. While electroacupuncture (EA) pretreatment in migraine has been found to attenuate pain and frequencies of attacks, the underlying mechanism of its antinociceptive effect remains poorly understood. Emerging evidence suggests that the serotonin system may be involved in migraine pathophysiology.Method. Forty male Sprague-Dawley rats were randomly assigned to Control, Model, EA, and sham acupuncture (SA) groups. HomeCageScan was used to measure the effects on spontaneous nociceptive behaviors. Radioimmunoassay and high-performance liquid chromatography were used to evaluate the expression of 5-hydroxytryptamine (HT) in the plasma and three-key structure of the descending pain modulatory system.Results. Our study showed that EA pretreatment could produce a significant reduction in resting, freezing, and grooming behavior and a significant increase in exploration behavior. Furthermore, we found that the level of 5-HT in plasma was significantly increased, and it was significantly decreased in the descending pain modulatory system in Model group. The aforementioned results were significantly reversed in EA group; that is, the level of 5-HT was increased in the rostroventromedial medulla (RVM) and trigeminal nucleus caudalis (TNC) region and decreased in the plasma.Conclusion. EA pretreatment exerts antinociceptive effects in a rat model of recurrent migraine, possibly via modulation of the serotonin system.

Effects of ischemia on sarcoplasmic reticulum Ca2+ uptake and Ca2+ release in rat skeletal muscle

2001 ◽  
Vol 281 (2) ◽  
pp. E224-E232 ◽  
Author(s):  
R. Tupling ◽  
H. Green ◽  
G. Senisterra ◽  
J. Lepock ◽  
N. McKee
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Phase 1 ◽  
Tibialis Anterior Muscle ◽  
Tissue Preparation ◽  
Phase 2 ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Two Phases

In this study, we investigated the hypothesis that prolonged ischemia would impair both sarcoplasmic reticulum (SR) Ca2+ uptake and Ca2+ release in skeletal muscle. To induce total ischemia (I), a tourniquet was placed around the upper hindlimb in 30 female Sprague-Dawley rats [wt = 256 ± 6.7 (SE) g] and inflated to 350 mmHg for 4 h. The contralateral limb served as control (C). Immediately after the 4 h of ischemia, mixed gastrocnemius and tibialis anterior muscle was sampled from both limbs, and both crude muscle homogenates and SR vesicles were prepared. In another 10 control animals (CC), muscles were sampled and prepared exactly the same way, but immediately after anesthetization. Ca2+ uptake and Ca2+ release were measured in vitro with Indo-I on both homogenates and SR vesicles. As hypothesized, submaximal Ca2+ uptake was lower ( P < 0.05) in I compared with CC and C, by 25 and 45% in homogenates and SR vesicles, respectively. Silver nitrate (AgNO3)-induced Ca2+ release, which occurred in two phases ( phase 1 and phase 2), was also altered in I compared with CC and C, in both muscle homogenates and SR vesicles. With ischemia, phase 1 peak Ca2+ release was 26% lower ( P < 0.05) in SR vesicles only. For phase 2, peak Ca2+ release was 54 and 24% lower ( P < 0.05) in SR vesicles and homogenates, respectively. These results demonstrate that prolonged skeletal muscle ischemia leads to a reduced SR Ca2+uptake in both homogenates and SR vesicles. The effects of ischemia on SR Ca2+ release, however, depend on both the phase examined and the type of tissue preparation.

scholarly journals Mannitol Enhances the Antinociceptive Effects of Diphenhydramine as an Alternative Local Anesthetic

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Jo-Young Son ◽  
Jae-Seong Lim ◽  
Jae-Hyung Park ◽  
Jae-Hyeong Park ◽  
Myeong-Shin Kim ◽  
...  
Keyword(s):  
Local Anesthetic ◽  
Subcutaneous Injection ◽  
Antinociceptive Effect ◽  
Latency Time ◽  
Sprague Dawley ◽  
Hot Plate ◽  
Hot Plate Test ◽  
Plate Test ◽  
Withdrawal Latency ◽  
Antinociceptive Effects

Mannitol has recently been reported to be effective in enhancing the antinociceptive efficacy of lidocaine. No single study to date, however, has compared diphenhydramine with and without mannitol for nociceptive processing as an alternative local anesthetic. In this study, we examined the antinociceptive efficacy enhancements of diphenhydramine when combined with mannitol. Male Sprague-Dawley rats weighing 230–260 g were used in a hot plate test to evaluate the antinociceptive effects of diphenhydramine. All chemicals were dissolved in isotonic normal saline and administered subcutaneously into the plantar surface of the right hind paw at 10 min before the hot plate test. A subcutaneous injection of 0.5% or 1% diphenhydramine produced significant inhibition of the withdrawal latency time compared with the vehicle treatment. Antinociceptive effects appeared 10 min after the diphenhydramine injections and persisted for over 30 min. The antinociceptive effects of 1% diphenhydramine were not statistically different from those of 1% lidocaine. Although a subcutaneous injection of a 0.5 M mannitol solution alone did not affect the withdrawal latency time, 1% diphenhydramine with 0.5 M mannitol significantly enhanced antinociception. A subcutaneous injection of 1% diphenhydramine with epinephrine (1 : 100,000) solution did not increase the antinociceptive effect of the diphenhydramine. These results suggest that diphenhydramine with mannitol can be used as an alternative local anesthetic.

Pharmacologic Interaction between Cannabinoid and either Clonidine or Neostigmine in the Rat Formalin Test

2003 ◽  
Vol 99 (3) ◽  
pp. 701-707 ◽  
Author(s):  
Myung Ha Yoon ◽  
Jeong Il Choi
Keyword(s):  
Receptor Antagonist ◽  
Receptor Agonist ◽  
Formalin Test ◽  
Cannabinoid Receptor ◽  
Phase 1 ◽  
Antinociceptive Effect ◽  
Spinal Level ◽  
Isobolographic Analysis ◽  
Cannabinoid 1 Receptor

Background Although spinal cannabinoid receptor agonist (WIN 55,212-2) has been shown to encounter various models of pain, the role of two subtypes of cannabinoid receptor for the antinociceptive effect of cannabinoids has not been investigated at the spinal level. Spinal alpha 2 receptor agonist (clonidine) and cholinesterase inhibitor (neostigmine) are also active in the modulation of nociception. The authors examined the properties of drug interaction after coadministration of WIN 55,212-2-clonidine, and intrathecal WIN 55,212-2-neostigmine, and further clarified the role of cannabinoid 1 and 2 receptors in cannabinoid-induced antinociception at the spinal level. Methods Catheters were inserted into the intrathecal space of male Sprague-Dawley rats, and 50 microl of 5% formalin solution was injected into the hind paw to evoke the pain. Isobolographic analysis was used for evaluation of pharmacologic interaction. Results Intrathecal 55,212-2, clonidine, and neostigmine dose-dependently suppressed the flinching observed during phase 1 and 2 in the formalin test. Isobolographic analysis revealed a synergistic interaction after intrathecal delivery of WIN 55,212-2-clonidine or WIN 55,212-2-neostigmine mixture in both phases. The antinociceptive effect of WIN 55,212-2 was antagonized by cannabinoid 1 receptor antagonist (AM 251) but not by cannabinoid 2 receptor antagonist (AM 630). No antinociceptive effect was seen after intrathecal administration of cannabinoid 2 receptor agonist (JWH 133). Conclusions Intrathecal 55,212-2, clonidine, and neostigmine attenuate the facilitated state and acute pain. WIN 55,212-2 interacts synergistically with either clonidine or neostigmine. The antinociception of WIN 55,212-2 is mediated through the cannabinoid 1 receptor, but not the cannabinoid 2 receptor, at the spinal level.

Inhibition of Nociception-induced Spinal Sensitization by Anesthetic Agents 

1995 ◽  
Vol 82 (1) ◽  
pp. 259-266 ◽  
Author(s):  
Therese C. O'Connor ◽  
Stephen E. Abram
Keyword(s):  
Nitrous Oxide ◽  
Formalin Test ◽  
Phase 1 ◽  
Formalin Injection ◽  
Second Phase ◽  
Nociceptive Response ◽  
Phase 2 ◽  
Anesthetic Agents ◽  
C Fiber ◽  
Spinal Sensitization

Background Subcutaneous injection of dilute formalin in the hind paw of the rat produces a biphasic nociceptive response. Initial C-fiber activity is accompanied by flinching of the paw for about 5 min (phase 1), followed by cessation of activity and resumption of flinching beginning 15 min after injection and lasting about 40 min or more (phase 2). The second phase depends on changes in dorsal horn cell function that occur shortly after the initial C-fiber discharge. It was previously shown that isoflurane, administered during phase 1, reduced phase 2 activity, but a combination of isoflurane and nitrous oxide given throughout phase 1 did not suppress spinal sensitization. The same model was used to determine the effects of several inhalation and intravenous anesthetic agents on phase 2 of the formalin test. Methods The formalin test was carried out on male Sprague-Dawley rats. Animals anesthetized briefly with halothane to facilitate formalin injection, were compared to animals that received 1 MAC anesthesia from 5 min before to 6 min after formalin injection using halothane, enflurane, isoflurane, desflurane, or 70% N2O, or a combination of nitrous oxide plus 1 MAC halothane. Animals that were given intravenous saline immediately before injection of formalin were compared to animals given either 20 mg/kg intravenous thiopental just before formalin injection or 10 mg/kg intravenous propofol just before and 3 mg/kg immediately after formalin injection. Flinches/minute were counted at 1 and 5 min after formalin injection and thereafter at 5-min intervals for 1 h. The total of 1- and 5-min flinches were considered phase 1 activity and the total of 10-60-min flinches were considered phase 2. Total phase 2 activity was compared between groups using one-way analysis of variance. Results Animals that received halothane, enflurane, isoflurane, desflurane, or nitrous oxide during phase 1 demonstrated a significant decrease in phase 2 activity when compared to controls, while those that received a combination of nitrous oxide and halothane exhibited no difference. Animals that received intravenous thiopental anesthesia during phase 1 demonstrated no difference in phase 2 activity when compared to controls, whereas those that received propofol during phase 1 demonstrated a significant decrease of phase 2 activity. Conclusions Volatile anesthetics or nitrous oxide significantly suppress spinal sensitization, whereas the combination of nitrous oxide plus halothane causes no suppression. Thiopental does not affect spinal sensitization, whereas propofol causes significant suppression. These results may have important implications regarding the development of postoperative pain.

Peripheral Antinociceptive Action of Morphine and the Synergistic Interaction with Lamotrigine

2002 ◽  
Vol 96 (4) ◽  
pp. 921-925 ◽  
Author(s):  
Carlos F. Argüelles ◽  
Jorge E. Torres-López ◽  
Vinicio Granados-Soto
Keyword(s):  
Formalin Test ◽  
Glutamate Release ◽  
Antinociceptive Effect ◽  
Na Channels ◽  
Afferent Neurons ◽  
Functional Interaction ◽  
Functional Interactions ◽  
Antinociceptive Effects ◽  
Voltage Dependent ◽  
Female Wistar Rats

Background Lamotrigine inhibits glutamate release through the preferential blockade of voltage-dependent Na+ channels. In contrast, morphine reduces release of excitatory amino acids through the activation of opioid receptors and also inhibits tetrodotoxin-resistant Na+ channels on peripheral afferent neurons. The current study was designed to investigate the antinociceptive effects of locally administered morphine and lamotrigine. The interaction between morphine and lamotrigine at the periphery was also examined. Methods Morphine, lamotrigine, or a combination of morphine and lamotrigine was administered locally to female Wistar rats, and the antinociceptive effect was determined in the formalin test. Isobolographic analyses were used to define the nature of the functional interactions between morphine and lamotrigine. Results Peripheral administration of either morphine or lamotrigine produced a dose-related antinociceptive effect. Isobolographic analyses revealed that peripheral morphine and lamotrigine interacted synergistically in the formalin test. Conclusions The study shows a functional interaction between lamotrigine and morphine at the peripheral level.

Analgesic Effect of Electric Stimulation of Peripheral Nerves with Different Electric Frequencies Using the Formalin Test

2000 ◽  
Vol 28 (02) ◽  
pp. 291-299 ◽  
Author(s):  
Ching-Liang Hsieh ◽  
Chi-Chung Kuo ◽  
Yueh-Sheng Chen ◽  
Tsai-Chung Li ◽  
Ching-Tou Hsieh ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Analgesic Effect ◽  
Early Phase ◽  
Electric Stimulation ◽  
Formalin Test ◽  
Late Phase ◽  
Antinociceptive Effect ◽  
Neck Muscle ◽  
Nociceptive Response ◽  
Nociceptive Responses

Although electroacupuncture (EA) has been widely used to treat pain, the optimal frequency of EA therapy remains unclear. The study sought to determine the effect of different EA frequencies in a Sprague-Dawley (SD) rat model of pain. Electric stimulation (ES) at frequencies of 2 Hz, 15 Hz or 100 Hz was applied to the ipsilateral or contralateral sciatic nerve of the injected hindpaw of SD rats. Formalin (50 μl, 5%) was subcutaneously injected into the plantar surface of the left hindpaw to induce a nociceptive response. Behavior, including licking and biting, was observed to have two distinct periods, an early phase during the first 5 mins and a late phase from 21-35 mins after injection. The total biting or licking count served as an Indicator of nociceptive response. Our results indicate that ES of the ipsilateral sciatic nerve at a frequency of 2 Hz or 15 Hz reduced the nociceptive responses in both the early and the late phases of the formalin test, whereas ES at 2 Hz had greater antinociceptive effect than ES at 15 Hz in the early phase. No similar analgesic effect in the early phase was observed for ES at 100 Hz. Both pretreatment with ES at 2 Hz and naloxone (3 mg/kg, s.c.) produced a greater antinociceptive response in the late phase than when ES at 2 Hz was delivered immediately after formalin administration. In addition, ES of the neck muscle or contralateral sciatic nerve at a frequency of 2 Hz also decreased licking and biting activity in both phases. The results of this study indicate that different analgesic mechanisms are involved in the response to ES at frequencies of 2 Hz, 15 Hz and 100 Hz, and that ES at 2 Hz has a greater analgesic effect on formalin-induced nociceptive response, especially when it is delivered prior to the onset of pain. The analgesic effect of ES may be mediated via a central origin in the supraspinal level. These findings suggest that 2 Hz may be a good frequency selection for clinical EA applications in analgesia, and that pretreatment with EA at 2 Hz may be an effective method to treat post-operative pain.

scholarly journals Modulation of Morphine-induced Antinociception in Acute and Chronic Opioid Treatment by Ibudilast

2009 ◽  
Vol 111 (6) ◽  
pp. 1356-1364 ◽  
Author(s):  
Tuomas O. Lilius ◽  
Pekka V. Rauhala ◽  
Oleg Kambur ◽  
Eija A. Kalso
Keyword(s):  
Cell Activation ◽  
Antinociceptive Effect ◽  
Opioid Analgesics ◽  
Morphine Tolerance ◽  
Tail Flick ◽  
Sprague Dawley ◽  
Tail Flick Test ◽  
Glial Cell Activation ◽  
Sprague Dawley Rats ◽  
Antinociceptive Effects

Background Opioid analgesics are effective in relieving chronic pain, but they have serious adverse effects, including development of tolerance and dependence. Ibudilast, an inhibitor of glial activation and cyclic nucleotide phosphodiesterases, has shown potential in the treatment of neuropathic pain and opioid withdrawal. Because glial cell activation could also be involved in the development of opioid tolerance in rats, the authors studied the antinociceptive effects of ibudilast and morphine in different models of coadministration. Methods Antinociception was assessed using male Sprague- Dawley rats in hot plate and tail-flick tests. The effects of ibudilast on acute morphine-induced antinociception, induction of morphine tolerance, and established morphine tolerance were studied. Results Systemic ibudilast produced modest dose-related antinociception and decreased locomotor activity at the studied doses of 2.5-22.5 mg/kg. The highest tested dose of 22.5 mg/kg produced 52% of the maximum possible effect in the tail-flick test. It had an additive antinociceptive effect when combined with systemic morphine. Coadministration of ibudilast with morphine did not attenuate the development of morphine tolerance. However, in morphine-tolerant rats, ibudilast partly restored morphine-induced antinociception. Conclusions Ibudilast produces modest antinociception, and it is effective in restoring but not in preventing morphine tolerance. The mechanisms of the effects of ibudilast should be better understood before it is considered for clinical use.

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