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Showing 41 results for Formalin Test

Saeed Semnanian, Ghasem Attarzadeh, Mohammad Hossein Pourgholami,
Volume 1, Issue 1 (4-1997)
Abstract

Recently, vast studies have been focused on the antinociceptive and anesthetic effects of α2 adrenergic receptors, using specific drugs such as medetomidine and dexmedetomidine. In the present study, we tried to assess the peripheral and central effects of dexmedetomidine in phasic and tonic pain, on rats, using tail flick and formalin tests. Dexmedetomidine, administered intraperitoneally (25, 50 and 100 µg/kg, i.p.) or intracerebroventrically (7.5, 10 and 20 µg, i.c.v.) induced total anesthesia. This effect could be seen by 10 and 20 µg, i.c.v. doses of the drug in spinal animals, too, which was reversed by 5 µg, i.c.v. of yohimbine. Dexmedetomidine (6.5 µg, i.c.v. or 20 µg, i.p.) showed antinociceptive effects in formalin test which was reversed by yohimbine (5 µg, i.c.v.). Dexmedetomidine (5, 6.5, 7.5, 10 and 20 µg, i.c.v. or 20, 25, 50 and 100 µg/kg, i.p.) had significant antinociceptive effects in tail flick test, which could be reversed by 5 µg, i.c.v. administration of yohimbine. The results of tail flick test in the spinal animals, shows that dexmedetomidine (6 µg, i.c.v.) in these animals induces antinociception, which was reversed by yohimbine pretreatment (1 mg/kg, i.p.). These results indicate that, dexmedetomidine probably exerts, its antinociceptive effect, through spinal α2 adrenergic receptors.
Abolhassan Ahmadiani, Saeed Semnanian, Masoud Fereydouni,
Volume 1, Issue 2 (11-1997)
Abstract

  Pharmacologists believe analgesic and anti-inflammatory drugs such as non-steroidal anti-inflammatory drugs (NSAIDs) and opioid compounds, due to their side-effects and, in some cases, inadequacy, are not always useful. Therefore it seems necessary to search for newer analgesic compounds. In traditional Iranian Medicine, the leaf and rhizome of Sambucus ebulus is used as a topical medication in the treatment of pain caused by bee stings, nettle stings and joint inflammation. We therefore decided to study the analgesic effects of this plant. Two methods, the tail flick test for acute pain and the formalin test for chronic pain were employed to measure pain. Analgesic effects of 50, 100 and 200 mg/kg doses of S. ebulus rhizome extract were compared with 300 mg/kg sodium salicylate as a positive control. The plant extract relieved pain in the tail flick test and in both phases of the formalin test, while sodium salicylate only treated pain in the formalin test. In none of the two tests was naloxone effective in inhibiting the analgesic effect of S. ebulus extract. Phytochemical investigations and previous reports suggest flavinoids to be the probable analgesic compounds.


Mohammad Reza Zarrindast, Marjan Pazouki, Shadi Nassiri-Rad,
Volume 2, Issue 1 (4-1998)
Abstract

  In this study, we investigated the effect of nicotinic receptor agonists and antagonists on the analgesic response to morphine in the formalin test. In experiments conducted in mice, nicotine produced an early dose-dependent analgesic effect. At a dose of 0.5 mg/kg, mecamylamine, a nicotinic receptor inhibitor, suppressed the analgesic effect induced by 0.1 mg/kg nicotine in both stages of the formalin test, while hexamethonium had no such effect. Atropine, a muscarinic receptor antagonist, reduced the nicotine response at doses of 5 and 10 mg/kg. Mecamylamine, hexamethonium and atropine had no effect on morphine-induced analgesia. Administered separately, the antagonists had no effect on the analgesic response either. High doses of mecamylamine lead to an increase of the pain response. We conclude that cholinergic and opioid receptors play a possible role in the analgesic effect induced by nicotine.



Volume 2, Issue 1 (4-1998)
Abstract

  The paragigantocellularis (PGi) nucleus constitutes a large portion of the ventral pontomedullary reticular formation. Neurons within the PGi have been implicated in a variety of functions including cardiovascular regulation, respiratory control, pain and analgesia. Investigators have demonstrated that electrical stimulation and microinjection of L-glutamate into the PGi produce antinociception in phasic pain. In this study, we measured the analgesic effects of electrical stimulation and glutamate microinjection into the PGi using the formalin test and the tail-flick method in rats. A bipolar stimulation electrode and a guide cannula were stereotaxically inserted into the right PGi of individual rats under brief ketamine and xylazine anesthesia. One week after the implantation, a monophasic square wave (500 µs, 400 µA, 50 Hz) was delivered into the PGi for 20 seconds via the implanted electrode. Glutamate (0.5 µl, 44 nM/rat) was injected through the guide cannula. One minute after electrical stimulation or glutamate injection, the tail-flick and formalin (50 ml, 2.5%) tests were performed. The results showed that electrical stimulation and glutamate injection into the PGi caused marked antinociception in both the tail-flick and the early phase of the formalin test compared to the control rats. We conclude that electrical stimulation and glutamate injection into the PGi cause marked antinociception in phasic pain and moderate antinociception in tonic pain. These findings suggest that the PGi is also involved in alleviation of tonic pain.



Volume 2, Issue 1 (4-1998)
Abstract

  There is evidence that sweeteners such as sucrose and saccharin interact with endogenous opioid systems. Further research has shown that feeding different concentrations of sucrose and saccharin alter latency in the tail-flick test. In this study, the influence of a 12-day regimen of different sweetening agents, sucrose (32%), saccharin (0.08%) and aspartame (0.16%) on morphine-induced analgesia in the formalin test was investigated. Male albino mice (20-27 g) were used for the experiments. The animals were given 12 days to adapt to the dietary conditions. An initial subcutaneous injection of saline or morphine (1.5, 3, 6 or 9 mg/kg) was given 30 minutes before the observation period. Recording of the early phase began immediately and continued for 10 minutes. Recording of the late response began 20 minutes after injection and continued for 10 minutes. Sucrose and aspartame increased the analgesia of morphine in the early phase while saccharin had no effect. On the other hand saccharin and sucrose decreased the effect of morphine in the late phase while aspartame increased the effect of morphine-induced analgesia. In conclusion, the present data provide further evidence for an important role of dietary variables in determining the effects of exogenous opioids on pain sensitivity.



Volume 2, Issue 1 (4-1998)
Abstract

  In the present study, the effect of contralateral and bilateral electrolytic lesions of the nucleus reticularis paragigantocellularis (PGi) on tonic pain was assessed in rats. Pain-related behavior was evaluated using the formalin test 7 days after the lesion was made. PGi lesions did not produce any marked changes in the early phase of the formalin test, but significantly increased pain sensitivity in the late phase compared to the sham-operated group. Furthermore, there was no significant difference between contralateral and bilateral lesions. Since PGi lesions resulted in significant hyperalgesia, we may conclude that this region of the rostroventral medulla plays a modulatory role in the regulation of tonic pain induced by formalin as a noxious chemical stimulus.



Volume 2, Issue 2 (11-1998)
Abstract

  In this study, the effects of lead acetate on two types of pain (nociception and inflammation) induced by formalin and its interaction with the opioid system and morphine-induced analgesia were examined. Male albino mice weighing 22-27 g were used in the experiments. Morphine was administered subcutaneously 30 minutes before formalin injection. Lead acetate was intraperitoneally administered 90 minutes before any injection. Different doses of morphine induce antinociception in both phases of the formalin test. Lead acetate induced no does-dependent nociception in the early phase, but caused dose-dependent analgesia in the late phase. Pretreatment with lead acetate antagonized the effect of morphine in the early phase. On the other hand, the effect of lead acetate in the early phase was reduced by morphine and its effect was eliminated in the late phase. We conclude that lead acetate can modulate the pain response and interact with morphine-induced antinociception. Additional research is suggested to identify the mechanisms of these effects.

 



Volume 3, Issue 1 (4-1999)
Abstract

  In this study interaction of three types of calcium channel blockers nifedipine, diltiazem and verapamil on the effects of lead acetate on two types of pain (nociception and inflammation) induced by formalin in mice were examined. In order to study nociception, formalin test was selected because of greater resemblance to clinical pain. Lead acetate (50, 75, l00, 125 and 150 mg/kg) administered intraperitoneally 90 minutes before formalin injection. Nifedipine (5 mg/kg), diltiazem (10 mg/kg) and verapamil (5 mg/kg) alone or in combination with different doses of lead acetate were used. Different doses of lead acetate induced a dose-dependent anti- nociception in both phases of formalin test. When animals were administered alone by calcium channel blockers, among them diltiazem and verapamil did not induce any significant effect in both phases of formalin test but nifedipine induced anti-inflammatory effect in late phase significantly (p<0.01). Pretreatment of animals with nifedipine and verapamil potentiated lead acetate anti-nociceptive effect (early phase) in doses of 50, 75 and 50 mg/kg, respectively. Both nifedipine and diltiazem augmented lead acetate anti-inflammatory effects (late phase) in all doses used. Pretreatment of animals with verapamil did not affect lead acetate anti-nociceptive or anti-inflammatory effects. Based on these data, tile association between calcium channel blockers and lead may be explained as a synergistic action rather than a simple dose combination of both agents. It is concluded that L-type calcium channels are susceptible to lead acetate that may be blocked during lead poisoning but different L-type calcium channel subtypes have different sensitivity to lead neurotoxicity.


Alireza Parvizpour, Abolhassan Ahmadiani, Mohammad Javan, Mohammad Kamalinejad,
Volume 3, Issue 2 (11-1999)
Abstract

  There are several reports on the therapeutic effects of TFG in Iranian traditional medical literature such as antinociceptive, antipyretic, and anti-inflammatory, antidiabetic and antidiuretic effects. The anti-inflammatory and anti-pyretic effects of TFG have been confirmed in experimental models. In the present study, the antinociceptive effect of TFG extract in formalin and tail flick tests and its site of action were investigated on NMRI rats (220 ± 20 g). The TFG extract was administered by three routes, i.e. i.c.v., i.t. and i.p. at different doses. The effect of i.p. administration was also examined in tail flick test. The results showed that i.p. administration of aqueous extract of TFG leaves induced analgesia in tail flick and both phases of formalin test. The i.t. administration at doses of 0.5, 1, 2 and 3 mg/rat showed significant antinociceptive effect in formalin test, however i.c.v. administration of extract had no antinociceptive effect. The results of the present study supported the facts that: 1) TFG extract has antinociceptive effect in first and second phases of formalin and tail flick tests and 2) the site of its action in the first and second phase of formalin test might be at spinal cord and with regard to its anti-inflammatory effect, peripheral mechanisms may be involved in its analgesic effect in the second phase of formalin test.


Esmaeil Akbari, Fereshteh Motamedi, Mohamamd Reza Vaez-Mahdavi,
Volume 4, Issue 1 (4-2000)
Abstract

Amitriptyline, a tricyclic antidepressant agent is used as one of the analgesic drugs in different kinds of pain. In the present study the effect of local (subcutaneous) injection of amitriptyline (50 and 100 µg) on the acute and chronic pain using formalin test, was investigated. Our data show that local injection of amitriptyline to the paw receiving formalin, causes a decrease in pain in both phasic and tonic phases of formalin test. On the other hand, in the group that this drug was injected (100 µg) to the contralateral paw, no significant change was observed in the pain score with respect to the control group. Therefore, it seems that the observed effect is due to the local action of amitriptyline and not as a result of its systemic effect. Considering the above-mentioned results, it is concluded that: 1) Amitriptyline acts like a local anesthetic in both acute and tonic phases of formalin test. 2) The mechanism of analgesia in the acute phase is probably caused by sodium channel blockade. 3) The analgesic effect of amitriptyline in the tonic phase of formalin test might be due to its antihistaminic and anti-inflammatory effects at the peripheral level, and also is due to the changes in the CNS plasticity which occurs during the acute phase.
Mitra Mahmoudi, Mohammad Reza Zarrindast,
Volume 4, Issue 2 (10-2000)
Abstract

In the present study, the effect of GABA (γ-aminobutyric acid) receptor agonists and antagonists on morphine-induced antinociception was investigated in formalin test in rats. Intraperitoneal (i.p.) injection of different doses of morphine (1, 3, 6 and 9 mg/kg) and intracerebroventricular (i.c.v.) injection of different doses of muscimol (0.5, 1 and 2 g/rat) or baclofen (0.25, 0.5 and 1 g/rat) induced a dose-dependent antinociception in both phases of formalin test. The responses induced by muscimol or baclofen in both phases reduced by bicuculline or CGP35348 respectively. Morphine in combination with different doses of muscimol or baclofen tends to elicit higher response. The opioid receptor antagonist reduced the response induced by both GABA receptor agonists. It can be concluded that stimulation of GABAA and GABAB receptors are responsible for antinociception in formalin test. However, at least part of the antinociception is due to the opioid receptor mechanism.
Farnaz Nikbakht, Zhila Behzadi,
Volume 4, Issue 2 (10-2000)
Abstract

It has been reported that neurons in the VL PAG projecting to nucleus raphe magnus (NRM) utilize excitatory amino acids as neurotransmitter. This projection plays an important role in the descending pain modulatory system. In order to determine the role of this pathway in pain perception, male rats received unilateral injection of ibotenic acid stereotaxically. For lesioning VL PAG, unilateral injection of ibotenic acid (0.2 and 0.5 µl) (a specific neurotoxin for EAA-containing neurons) was made. After a week recovery period, the nociception was evaluated using formalin test for a period of 60 min. At the end of experiments, animals were perfused by formaldehyde 10%. Serial sections (80 µm) wee prepared using vibratome. The sections were then Nissl stained and examined to determine the lesion location. The results revealed a significant increase in the first phase of formalin test. However, in the second phase, only 0.5 µl of the neurotoxin caused a significant decrease in pain perception. It is concluded that NMDA receptors within the PAG are involved in the perception of pain as measured in the formalin test.
Mousa Sahebgharani, Mohammad Reza Zarrindast, Morteza Samini,
Volume 4, Issue 2 (10-2000)
Abstract

In this study, the effect of α-adrenoceptor agents on imipramine-induced antinociception was investigated using formalin test. Intraperitoneal (i.p.) administration of imipramine at different doses (10-80 mg/kg) induced antinociception in both phases of formalin test. In addition, intracerebroventricular (i.c.v.) injection of imipramine (1, 5, and 10 µg/rat) did not elicit any effect, although i.c.v. injection of clonidine, an α2-adrenoceptor agonist at doses of 0.05-0.8 µg/rat also elicited antinociception in both phases of the test. Furthermore, clonidine increases the antinociception induced by imipramine and yohimbine, an α2-adrenoceptor antagonist at a dose of 2 µg/rat (i.c.v.) reduced the response to imipramine at a low dose (10 mg/kg, i.p.) and clonidine (0.05 µg/rat, i.c.v.), but did not alter the response induced by higher doses of imipramine (20 and 40 mg/kg) alone or in combination with clonidine. Yohimbine by itself elicited no response. Meanwhile, phenylephrine (0.07-1.5 µg/rat, i.c.v.), an αl-adrenoceptor agonist induced antinociception in both phases of formalin test, but did not alter the imipramine-induced antinociception. The αl -adrenoceptor antagonist, prazocin neither elicited antinociception nor altered the imipramine response. Yohimbine (2 µg/rat, i.c.v.) in combination with prazocin (0.5 µg/rat, i.c.v.) further inhibited the response for imipramine alone or in combination with clonidine. Taken together, it is concluded that α2-adrenoceptor-mediated mechanism might be involved in the development of imipramine-induced antinociception.

Volume 5, Issue 2 (11-2001)
Abstract

Post-operative pain and its management remains one of the most important issues in the field of surgery and health care system. On the other hand, opioid drug abuse has a large prevalence in Iran. Formalin test has been used as a method for assessing pain and analgesia in rats. In the present study, the post-operative pain in morphine addicted rats was compared with that of non-addicted ones using formalin test. For this purpose, 26 rats were chosen and randomly divided into two groups. First group received morphine sulphate in their drinking water for 21 days. The other group received only tap water. On the day of their assessment, a longitudinal incision (1-cm) was made through skin fascia of their plantar aspect of one foot under ether anesthesia. One hour later, their pain was assessed with formalin test through intra-plantar subcutaneous injection of 0.05 ml of 2.5% formalin solution. Our results showed that acute pain (the first 5 minutes after injection) in both groups was not different significantly, but chronic pain (the next 15-45 minutes) was much intense in morphine-addicted rats.
Fereshteh Motamedi, Samira Danyali, Mohammad Reza Vaez Mahdavi,
Volume 6, Issue 1 (4-2002)
Abstract

Various physiological parameters including level of sex steroids undergo alterations following chronic administration of morphine. In this study, the effect of chronic administration of morphine on phasic and tonic pain was studied in morphine-dependent male and female rats in the presence and absence of gonads using formalin test. In addition, for evaluation of differences in dependency, withdrawal signs were observed using naloxone hydrochloride. For dependency induction, morphine sulphate was administered in drinking water for a period of 30 days. The results showed that although chronic pain is significantly greater in female rats than male ones but this pain increases in male dependent rats and decreases in female dependent animals. Thus, no gender differences were found between male and female dependent rats. Furthermore, gonadectomy led to a significant decrease in chronic pain only in male dependent rats. Meanwhile, withdrawal signs were significantly greater in female dependent rats than male ones and gonadectomy did not influence these signs. It can be concluded that following morphine addiction, pain increases in male and decreases in female rats and morphine dependency is not affected by sex hormones.
Mohammad Reza Heidari, Ali Asadipour, Mahdi Hami,
Volume 6, Issue 1 (4-2002)
Abstract

In this study, the analgesic effect of Artemisia dracunculus, which has been used in traditional medicine as an analgesic, anti-rheumatic and toothache releiver was studied. For extraction, suxhelet and percolation methods by 80% methanol was used. The extract was then concentrated and the weight of dried extract was determined and dissolved in normal saline to produce desired concentration. The analgesic effect of the extract was determined by the formalin and hot-plate tests. The results of formalin test showed that all doses of the extract have analgesic effect in comparison with control group and the extract at a dose of 800 mg/kg produces the highest analgesic effect. In this respect, there was no significant difference regarding the extracting methods. The results of hot plate showed that the extract at a dose of 800 mg/kg has a significant analgesic effect compared to control group. In addition, the analgesic effect of extract was compared with ASA and morphine by formalin and hot plate tests. The results showed that the analgesic effect of 800 mg/kg of extract was higher than ASA and lower than morphine in some trials. Furthermore, pretreatment of animals with naloxone decreased the analgesic effect of extract. Therefore, it seems that part of analgesic effect of the extract may be attributed to opioid system. At the end of the study, those rats receiving 800 and 1600 mg/kg of the extract and control ones were collected for histopathological evaluation. The results showed that there is only small congestion in liver and kidney after the extract injection. In addition, there was no sign of peptic ulcer in comparison with rats receiving indomethacin.
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Volume 8, Issue 2 (10-2004)
Abstract



Volume 9, Issue 2 (11-2005)
Abstract


Javad Sajedianfard, Faramarz Azarang, Elahe Solimannejad,
Volume 12, Issue 1 (5-2008)
Abstract

Introduction: Pain as a complex process in central nervous system (CNS) has been studied by many researchers. Pain is controlled by several CNS pathways, one of the most important of which, is the descending noradrenergic system. This system begins from locus coeruleus (LC) nucleus in pons and ends in the spinal cord. In this research, the effect of pain induced by formalin was studied. Methods: Male Sprague-Dawley rats weighing 280-320 g were categorized into two groups of control (injection of 50 μl normal saline) and test (injection of 50 μl 2.5% formalin). Rats were anesthetized by pentobarbital sodium (50 mg/kg i.p.). Microdialysis probes were inserted 24 hrs before the test was done. Rats were anesthetized by urethane and formalin test for induction of chemical and tonic pain was performed on the hind paw of the animals. Micro dialysis samples were taken in 15 minutes intervals and noradrenaline (NA) and its metabolite, 3-methoxy 4-hydroxy phenylglycol (MHPG), were measured by HPLC-ECD. Results: The NA and MHPG concentration in the first and second phases of formalin test did not change significantly in neither test nor control groups. Conclusion: LC has no role in perception of pain induced by formalin test during anesthesia.
Masoud Fereidoni, Leila Etemadi,
Volume 12, Issue 2 (8-2008)
Abstract

Introduction: Feverfew (Tanacetum parthenium) (T.p.) is widely used in folk medicine to treat many diseases. We reported the analgesic effect of T.p. flower and leaf previously. Present study is designed to find the mechanism underlying the anti-nociceptive effect of the aqueous extract of T.p. flower. Method: Based on our previous study, the dose 50 mg/kg i.p. of the T.p. aqueous extract had a potent analgesic effect on mice (NMRI) (20 ± 2 g) in formalin test which is used in the present study also. Here, we study the roles of opioidergic, sertoninergic and α - adrenergic systems on the anti-nociceptive effect of the extract. Animals had pretreated with drugs, 15 min before the extract treatments, including opioid antagonist naloxane (5mg/kg, i.p.), sertoninergic antagonist cyproheptadine (4 mg/kg, i.p.) and α-adrenergic antagonist phentolamine (20 mg/kg, i.p.) separately (each group with n≥6). Saline and extract used as controls. Results: In contrast to extract analgesic effect, pretreatment with naloxan increased the pain sensation in the neurogenic phase of formalin test (p<0.001). Pretreatment with cyproheptadine increased the sensation of pain in both early and late phases (p<0.05). Inhibition of α -adrenergic system was not be able to attenuate the anti-nociceptive effect of the extract. Discussion: The involvement of sertoninergic system in anti-nociceptive effect of the T.p. extract is proposed by the results. Also the involvement of opioidergic system has to be mentioned in this effect.

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