scholarly journals Antinociceptive Effects of Spinal Manipulative Therapy on Nociceptive Behavior of Adult Rats during the Formalin Test

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Stephen M. Onifer ◽  
William R. Reed ◽  
Randall S. Sozio ◽  
Cynthia R. Long
Keyword(s):  
Formalin Test ◽  
Antinociceptive Effect ◽  
Spinal Manipulative Therapy ◽  
Formalin Injection ◽  
Nociceptive Behavior ◽  
Adult Rats ◽  
Manipulative Therapy ◽  
Antinociceptive Effects ◽  
Custom Made ◽  
The Mean

Optimizing pain relief resulting from spinal manipulative therapies, including low velocity variable amplitude spinal manipulation (LVVA-SM), requires determining their mechanisms. Pain models that incorporate simulated spinal manipulative therapy treatments are needed for these studies. The antinociceptive effects of a single LVVA-SM treatment on rat nociceptive behavior during the commonly used formalin test were investigated. Dilute formalin was injected subcutaneously into a plantar hindpaw. Licking behavior was video-recorded for 5 minutes. Ten minutes of LVVA-SM at 20° flexion was administered with a custom-made device at the lumbar (L5) vertebra of isoflurane-anesthetized experimental rats (n=12) beginning 10 minutes after formalin injection. Hindpaw licking was video-recorded for 60 minutes beginning 5 minutes after LVVA-SM. Control rats (n=12) underwent the same methods except for LVVA-SM. The mean times spent licking the formalin-injected hindpaw of both groups 1–5 minutes after injection were not different. The mean licking time during the first 20 minutes post-LVVA-SM of experimental rats was significantly less than that of control rats (P<0.001). The mean licking times of both groups during the second and third 20 minutes post-LVVA-SM were not different. Administration of LVVA-SM had a short-term, remote antinociceptive effect similar to clinical findings. Therefore, mechanistic investigations using this experimental approach are warranted.

Role of the NO-cGMP-K+ channels pathway in the peripheral antinociception induced by α-bisabolol

2021 ◽  
Author(s):  
Mario I Ortiz ◽  
Raquel Cariño-Cortés ◽  
Victor Manuel Muñoz Pérez ◽  
Andres Salas Casas ◽  
Gilberto Castañeda-Hernández
Keyword(s):  
Opioid Receptors ◽  
Formalin Test ◽  
Antinociceptive Effect ◽  
Dorsal Surface ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
K Channel ◽  
Formalin Injection ◽  
K Channels ◽  
The Right

The aim of this study was to examine if the peripheral antinociception of α-bisabolol involve the participation of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) synthesis followed by K+ channel opening in the formalin test. Wistar rats were injected in the dorsal surface of the right hind paw with formalin (1%). Rats received a subcutaneous injection into the dorsal surface of the paw of vehicles or increasing doses of α-bisabolol (100-300 µg/paw). To determine whether the peripheral antinociception induced by α-bisabolol was mediated by either the opioid receptors or the NO-cGMP-K+ channels pathway, the effect of pretreatment (10 min before formalin injection) with the appropriate vehicles, naloxone, naltrexone, L-NAME, ODQ, glibenclamide, glipizide, apamin, charybdotoxin, tetraethylammonium or 4-aminopyridine on the antinociceptive effects induced by local peripheral α-bisabolol (300 µg/paw) were assessed. α-bisabolol produced antinociception during both phases of the formalin test. α-bisabolol antinociception was blocked by L-NAME, ODQ, and all the K+ channels blockers. The peripheral antinociceptive effect produced by α-bisabolol was not blocked by the opioid receptor inhibitors. α-bisabolol was able to active the NO-cGMP-K+ channels pathway in order to produce its antinoceptive effect. The participation of opioid receptors in the peripheral local antinociception induced by α-bisabolol is excluded.

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.

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 Spinal Antinociceptive Action of Amiloride and Its Interaction with Tizanidine in the Rat Formalin Test

2015 ◽  
Vol 20 (6) ◽  
pp. 321-326 ◽  
Author(s):  
Handong Ouyang ◽  
Peizong Wang ◽  
Wan Huang ◽  
Qiang Li ◽  
Bilin Nie ◽  
...  
Keyword(s):  
Side Effects ◽  
Adrenergic Receptor ◽  
Formalin Test ◽  
Antinociceptive Effect ◽  
Formalin Injection ◽  
Nociceptive Response ◽  
Sprague Dawley ◽  
Allosteric Site ◽  
Isobolographic Analysis ◽  
Antinociceptive Action

BACKGROUND: Amiloride has been reported to produce a wide variety of actions, thereby affecting several ionic channels and a multitude of receptors and enzymes. Intrathecal α2-adrenergic receptor agonists produce pronounced analgesia, and amiloride modulates α2-adrenergic receptor agonist binding and function, acting via the allosteric site on the α2A-adrenergic receptor.OBJECTIVES: To investigate the antinociceptive interaction of intrathecal amiloride and the α2-adrenoceptor agonist tizanidine using a rat formalin test.METHODS: Sprague-Dawley rats were chronically implanted with lumbar intrathecal catheters and were tested for paw flinching using formalin injection. Biphasic painful behaviour was recorded. Amiloride, tizanidine or an amiloride-tizanidine mixture was administered 10 min before formalin injection. To characterize any interactions, isobolographic analysis was performed. The effects of a pretreatment using intrathecally administered yohimbine was also tested.RESULTS: Intrathecally administered amiloride (12.5 μg to 100 μg) and tizanidine (0.5 μg to 5 μg), given separately, produced a significant dose-related suppression of the biphasic responses in the formalin test. Isobolographic analysis revealed that the combination of intrathecal amiloride and tizanidine synergistically reduced phase I and II activities. Intrathecally administered yohimbine antagonized or attenuated the antinociceptive effect of amiloride, tizanidine and the amiloride-tizanidine mixture. Intrathecally administered amiloride synergistically interacts with tizanidine to reduce the nociceptive response in the formalin test, most likely by activating α2-adrenoceptors in the spinal cord.CONCLUSIONS: Although intrathecal tizanidine produced pronounced analgesia, antinociceptive doses of intrathecal tizanidine also produced several side effects, including bradycardia and sedation. Amiloride produced antinociceptive action against the thermal nociceptive test without side effects in rats.

scholarly journals Antinociceptive Effect of Single Components Isolated from Agrimonia pilosa Ledeb. Extract

2019 ◽  
Vol 87 (3) ◽  
pp. 18
Author(s):  
Jing Hui Feng ◽  
Hee Jung Lee ◽  
Set Byeol Kim ◽  
Jeon Sub Jung ◽  
Soon Sung Lim ◽  
...  
Keyword(s):  
Antinociceptive Effect ◽  
Formalin Injection ◽  
Second Phase ◽  
Dependent Manner ◽  
Thermal Pain ◽  
Icr Mice ◽  
Chemically Induced ◽  
Pain Models ◽  
Antinociceptive Effects ◽  
Dose Dependent

Agrimonia pilosa Ledeb. produces an antinociceptive effect in ICR mice in both chemically induced and thermal pain models. In the present study, we examined the antinociceptive effects of single components isolated from Agrimonia pilosa Ledeb. (AP) extract in ICR mice. Three active compounds isolated from AP, including rutin, luteolin-7-O-glucuronide, and apigenin-7-O-glucuronide, were isolated and identified by comparing EI-MS, 1H-, 13C-NMR, and UV. We studied the antinociceptive effects of three single components administered orally at doses of 10 and 20 mg/kg in monosodium urate (MSU)-treated pain model as measured by von Frey test. Among these compounds, apigenin-7-O-glucuronide was more effective in the production of antinociceptive effects. We further characterized the antinociceptive effects and possible mechanisms of apigenin-7-O-glucuronide in writhing and formalin tests. Oral administration of Apigenin-7-O-glucuronide caused a reduction in the number of writhing and effectively reduced the pain behavior observed during the second phase of the formalin test in a dose-dependent manner. In addition, the pretreatment of yohimbine instead of naloxone or methysergide attenuated apigenin-7-O-glucuronide-induced antinociception in the writhing test. Moreover, apigenin-7-O-glucuronide caused reduction in the expression of p-P38, p-CREB, and p-mTOR induced by formalin injection. Our results indicate that apigenin-7-O-glucuronide shows an antinociceptive effect in various pain models. In addition, spinal α2-adrenergic receptors appear to be involved in the production of antinociception induced by apigenin-7-O-glucuronide. Furthermore, the antinociceptive effect of apigenin-7-O-glucuronide appears to be mediated by reduction in the expression of p-P38, p-CREB and p-mTOR levels in the spinal cord.

scholarly journals Pharmacokinetic of Diclofenac in the Presence and Absence of Glibenclamide in the Rat

2009 ◽  
Vol 12 (3) ◽  
pp. 280 ◽  
Author(s):  
María R. León-Reyes ◽  
Gilberto Castañeda-Hernández ◽  
Mario I Ortiz
Keyword(s):  
Oral Administration ◽  
Formalin Test ◽  
Antinociceptive Effect ◽  
Dorsal Surface ◽  
Pharmacokinetic Interaction ◽  
Pharmacokinetic Profile ◽  
Pharmacokinetic Parameters ◽  
Formalin Injection ◽  
Pharmacodynamic Interaction ◽  
Chromatography Method

ABSTRACT - PURPOSE. There is evidence that the sulfonylurea antidiabetic agent glibenclamide reduces the analgesic action of non-steroidal anti-inflammatory drugs (NSAIDs), opioids and neuromodulators in animal models. Therefore, in view of the vast clinical uses and interactions of NSAIDs with commonly used therapeutic agents, the interaction of the NSAID diclofenac and glibenclamide was investigated about pharmacokinetic profile and antinociceptive effect in rats. METHODS. Antinociception was assessed using the formalin test. Fifty microliters of diluted formalin was injected s.c. into the dorsal surface of the right hind paw. Nociceptive behavior was quantified as the number of flinches of the injected paw during 60 min after injection. Rats were treated with oral administration of vehicle or increasing doses of diclofenac (3-18 mg/kg) before formalin injection. To determine the pharmacodynamic interaction between diclofenac and glibenclamide, the effect of oral administration of glibenclamide (1-30 mg/kg) on the antinociceptive effect induced by diclofenac (18 mg/kg, p.o.) was assessed. To evaluate the pharmacokinetic interaction between diclofenac and glibenclamide, the effect of glibenclamide (10 mg/kg, p.o.) on the pharmacokinetic of diclofenac (18 mg/kg, p.o.) was studied in the rat. Blood samples were taken over 8 h and analyzed using a validated high-performance liquid chromatography method to generate the pharmacokinetic profile of diclofenac. Pharmacokinetic parameters were estimated using noncompartmental analysis. RESULTS. Systemic administration of diclofenac produced a dose-dependent antinociceptive effect in the formalin test. Systemic treatment with glibenclamide prevented diclofenac-induced antinociception. In pharmacokinetic interaction study, no significant (P>0.05) change in diclofenac concentration-time profiles in the presence of glibenclamide was detected. CONCLUSION. The experimental findings suggest that systemic glibenclamide is able to block the diclofenac-induced antinociception in the rat formalin test. Besides, this antagonism was not produced by diminution in the bioavailability of diclofenac. Likewise, the validated assay had sufficient accuracy and precision for pharmacokinetic determination of diclofenac in the rat.

Synergistic Antinociceptive Effect of Amitriptyline and Morphine in the Rat Orofacial Formalin Test

2004 ◽  
Vol 100 (3) ◽  
pp. 690-696 ◽  
Author(s):  
Philippe Luccarini ◽  
Laurent Perrier ◽  
Céline Dégoulange ◽  
Anne-Marie Gaydier ◽  
Radhouane Dallel
Keyword(s):  
Confidence Interval ◽  
Inflammatory Pain ◽  
Formalin Test ◽  
Antinociceptive Effect ◽  
Second Phase ◽  
Isobolographic Analysis ◽  
Antinociceptive Effects ◽  
Analgesic Agents ◽  
Rubbing Behavior ◽  
Orofacial Formalin Test

Background Combination therapy is often used to increase the clinical utility of analgesic agents. The coadministration of two compounds may achieve analgesia at doses lower than those required for either compound alone, leading to enhanced pain relief and reduction of adverse effects. Herein, the authors describe the effect of coadministration of morphine and amitriptyline on cutaneous orofacial inflammatory pain in rats. Methods Amitriptyline, morphine, or the combination of amitriptyline and morphine was administered systemically to rats, and antinociceptive effects were determined by means of the rat orofacial formalin test. Isobolographic analysis was used to define the nature of the interactions between morphine and amitriptyline. Results Amitriptyline as well as morphine produced a dose-related inhibition in the first phase and the second phase of rubbing activity. ED50 values against rubbing behavior were 14.6 mg/kg (95% confidence interval, 10.2-33.5 mg/kg) and 1.3 mg/kg (95% confidence interval, 1.0-1.7 mg/kg) for amitriptyline and morphine, respectively. Combinations of increasing fractional increments of amitriptyline and morphine ED50 doses produced a synergistic effect against rubbing behavior, as revealed by isobolographic analysis. Conclusions The current study suggests that systemic amitriptyline and morphine synergistically inhibit cutaneous orofacial inflammatory pain in rats.

Antinociceptive Effects of Heterotopic Electroacupuncture in Formalin-Induced Pain

2006 ◽  
Vol 34 (04) ◽  
pp. 565-574 ◽  
Author(s):  
Jae Hyo Kim ◽  
Young Seob Gwak ◽  
Inhyung Lee ◽  
In Churl Sohn ◽  
Min Sun Kim ◽  
...  
Keyword(s):  
Inflammatory Pain ◽  
Spinal Dorsal Horn ◽  
Late Phase ◽  
Antinociceptive Effect ◽  
Formalin Injection ◽  
Spinal Dorsal ◽  
Antinociceptive Effects ◽  
C Fiber ◽  
The Right ◽  
Lumbar Spinal

This study examined the antinociceptive effect of electroacupuncture (EA) to heterotopic acupoints on formalin-induced pain in rats. EA (2 ms, 10 Hz, and 3 mA) was delivered to heterotopic acupoints HE7 and PE7, or non-acupoints at the right fore limb, for 30 min and was immediately followed by subcutaneous formalin injection into the left hind paw, respectively. The quantified pain score, electromyogram (EMG) response of the C-fiber reflex, and cFos immunoreactivity were assessed, respectively. EA to heterotopic acupoints significantly reduced both early- and late-phase pain-like behaviors and significantly decreased the EMG responses of the C-fiber reflex after formalin injection. By contrast, EA to non-acupoints had no significant effects on pain-like behavior or the EMG response. In addition, EA to heterotopic acupoints decreased cFos immunoreactivity in the lumbar spinal dorsal horn. Therefore, EA induced pre-emptive antinociception via the extra-segmental inhibition of the formalin-induced pain, suggesting that EA to heterotopic acupoints is a useful treatment for inflammatory pain.

Antinociceptive effects of FTY720 during trauma-induced neuropathic pain are mediated by spinal S1P receptors

2015 ◽  
Vol 396 (6-7) ◽  
pp. 783-794 ◽  
Author(s):  
Dong Dong Zhang ◽  
Bona Linke ◽  
Jing Suo ◽  
Aleksandra Zivkovic ◽  
Yannick Schreiber ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Antinociceptive Effect ◽  
Intrathecal Administration ◽  
Receptor Subtypes ◽  
Nociceptive Behavior ◽  
S1p Receptors ◽  
Antinociceptive Effects ◽  
Sphingosine 1 Phosphate ◽  
S1p Receptor

Abstract FTY720 (fingolimod) is, after its phosphorylation by sphingosine kinase (SPHK) 2, a potent, non-selective sphingosine-1-phosphate (S1P) receptor agonist. FTY720 has been shown to reduce the nociceptive behavior in the paclitaxel model for chemotherapy-induced neuropathic pain through downregulation of S1P receptor 1 (S1P1) in microglia of the spinal cord. Here, we investigated the mechanisms underlying the antinociceptive effects of FTY720 in a model for trauma-induced neuropathic pain. We found that intrathecal administration of phosphorylated FTY720 (FTY720-P) decreased trauma-induced pain behavior in mice, while intraplantar administered FTY720-P had no effect. FTY720-P, but not FTY720, reduced the nociceptive behavior in SPHK2-deficient mice, suggesting the involvement of S1P receptors. Fittingly, intrathecal administration of antagonists for S1P1 or S1P3, W146 and Cay10444 respectively, abolished the antinociceptive effects of systemically administered FTY720, demonstrating that activation of both receptors in the spinal cord is necessary to induce antinociceptive effects by FTY720. Accordingly, intrathecal administration of S1P1 receptor agonists was not sufficient to evoke an antinociceptive effect. Taken together, the data show that, in contrast to its effects on chemotherapy-induced neuropathy, FTY720 reduces trauma-induced neuropathic pain by simultaneous activation of spinal S1P1 and S1P3 receptor subtypes.

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