Oral acetaminophen-induced spinal 5-hydroxytriyptamine release produces analgesic effects in the rat formalin test

Background: Effects of vitamin B12 on pain have been demonstrated in different animal and human studies. But comparison of these effects with similar effects of ketorolac tromethamine (KT) and their combination have not been established.Objective: To assess the effects of vitamin B12 on pain and also to compare them with those of the combinations of vitamin B12 with KT in rat models.Methods: This experimental study was conducted in the Department of Physiology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, from March 2015 to February 2016. For this, 20 (twenty) Long Evans rats (215±35 gm) of both sexes were divided into control (A, with 5 ml/kg normal saline) and experimental (B1, with 15 mg/kg B12; B2, with 10 mg/kg KT; B3, with B12+KT) groups with 5 rats in each group. All the drugs and vitamin were administered intraperitoneally in a single dose just one hour before formalin test. To evaluate the treatments effect on nociceptive pain, early phase (1st- 5th minutes); on central analgesic system, interphase (6th-15th minutes); and on inflammatory pain, late phase (16th-60th minutes) of the formalin test, were observed. In all phases, total frequency of jerking and total duration of flexing and licking of the right hind paw were counted after administration of subcutaneous formalin (50 ?l, 2.5%) injection. Statistical analysis was done by ANOVA, followed by Bonferroni post hoc test. In the interpretation of results, p?0.05 was considered as significant.Results: B12 lowered only the jerking frequency and KT lowered both jerking frequency and flexinglicking duration significantly (p?0.001) in the late phase of formalin test. On the other hand, combination of B12 and KT significantly (p?0.001) lowered both the study variables in all 3 phases of formalin test.Conclusion: From this study it may be concluded that, vitamin B12 possess analgesic effects and combination of B12 with KT is more effective than those of their individual administration.Bangladesh Soc Physiol. 2016, December; 11(2): 63-69

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The Analgesic Effects of Celecoxib on the Formalin-induced Short- and Long-term Inflammatory Pain

January 2018 - Pain Physician ◽

10.36076/ppj.2017.584 ◽

2017 ◽

Vol 4 (20;4) ◽

pp. E575-584 ◽

Cited By ~ 3

Author(s):

Ya-Qun Zhao

Keyword(s):

Inflammatory Pain ◽

Formalin Test ◽

Formalin Injection ◽

Spontaneous Pain ◽

Second Phase ◽

Secondary Hyperalgesia ◽

Analgesic Effects ◽

Gastrointestinal Side Effects ◽

Short And Long Term

The non-steroidal anti-inflammatory drug celecoxib has long been used for reducing pain, in spite of moderate gastrointestinal side effects. In previous studies, it has been shown that celecoxib can inhibit formalin-induced spontaneous pain and secondary hyperalgesia. Injecting formalin into a rodent’s hind paw not only induces acute pain behaviors, but also produces long-lasting hyperalgesia. Whether celecoxib can also have long-lasting effects is still unknown. Our results show that pretreatment with an intraperitoneal injection of celecoxib at one hour before formalin injection induced inhibition on the spontaneous flinch and licking behaviors in the second phase but not the first phase. Meanwhile, FOS expressions were also reduced with celecoxib pretreatment. Consecutive administration of celecoxib also protects the hind paw from hypoalgesia and relieves formalininduced, long-lasting hyperalgesia in the ipsilateral hind paw. These analgesic effects may be related to suppression of the activation of neurons and astrocytes indicated by FOS and GFAP expressions. Based on the above findings, celecoxib demonstrated analgesic effects not only on acute spontaneous pain behavior but also on long-lasting hyperalgesia induced by formalin injection. The inhibition of neurons and astrocytes by celecoxib may be possible reasons for its analgesia. Key words: Formalin test, celecoxib, FOS, GFAP, hyperalgesia

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Preemptive Analgesic Effects of Steroid Anesthesia with Alphaxalone in the Rat Formalin Test

Anesthesiology ◽

10.1097/00000542-199603000-00013 ◽

1996 ◽

Vol 84 (3) ◽

pp. 572-579 ◽

Cited By ~ 40

Author(s):

Ian Gilron ◽

Terence J. Coderre

Keyword(s):

Central Sensitization ◽

Formalin Test ◽

Formalin Injection ◽

Receptor Subtypes ◽

Gaba A ◽

Analgesic Effects ◽

Progesterone Metabolites ◽

Behavior Of Rats

Background The role of preemptive treatment with volatile and intravenous anesthetics has been examined in previous studies using the rat formalin test. Evidence describing analgesic properties of the gamma-amino butyric acid-ergic (GABAergic) steroid anesthetics, such as alphaxalone, suggest that they may suppress the development of central sensitization to pain. This study examined the preemptive effects of phaxalone in comparison with other GABAergic anesthetics, propofol and pentobarbital. Methods The pain behavior of rats was evaluated (using the previously validated weighted scores method of behavioral rating) 15-60 min after subcutaneous hind paw injection of 50 microg 1.5% formalin. In each trial, anesthetics and their respective vehicles were administered by tail-vein injection either 0.5-10 min before or 5 min after, formalin injection. When analgesic effects were observed with any of these agents, further studies were conducted with a GABA(A) receptor antagonist in an attempt to confirm a specific receptor-mediated action of the agent. Results Alphaxalone pretreatment produced transient analgesia in the early part of phase 2, which was not observed in rats posttreated with alphaxalone. The analgesic effect of alphaxalone was antagonized by picrotoxin, as well. Neither pentobarbital nor propofol showed any analgesic effects at the doses used in our study. Conclusions Whereas alphaxalone was shown to produce preemptive analgesia through its action at the GABA(A) receptor, pentobarbital and propofol, which also are known to act at this site, showed no analgesic effects. The diversity of receptor subtypes and functional complexity of GABA(A) receptors is such that steroid anesthetics may have effects that are different from other GABAergic agents. Further research into the role of progesterone metabolites and steroid anesthetics in the prevention of central sensitization may have clinical implications for the treatment of acute or chronic pain.

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Tonic analgesic effects of Δ9-tetrahydrocannabinol as measured with the formalin test

European Journal of Pharmacology ◽

10.1016/0014-2999(80)90134-x ◽

1980 ◽

Vol 61 (3) ◽

pp. 313-315 ◽

Cited By ~ 39

Author(s):

Donald E. Moss ◽

Richard L. Johnson

Keyword(s):

Formalin Test ◽

Analgesic Effects

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Repeated administration of orexin into the thalamic paraventricular nucleus inhibits the development of morphine-induced analgesia

Protein and Peptide Letters ◽

10.2174/0929866528666211214170247 ◽

2021 ◽

Vol 28 ◽

Author(s):

Fatemeh Samani ◽

Masoumeh Kourosh Arami

Keyword(s):

Paraventricular Nucleus ◽

Formalin Test ◽

Repeated Administration ◽

Treated Group ◽

Pain Modulation ◽

Morphine Injection ◽

Chronic Morphine ◽

Analgesic Effects ◽

Male Wistar Rats ◽

The Brain

Background: Hypothalamic neuropeptides, orexins, play pivotal roles in nociception and pain modulation. Objective: In this study, we investigated the effect of the administration of orexin into the paraventricular nucleus (PVT) on the development of morphine-induced analgesia in rats. Method. Male Wistar rats weighing 250-300 g received subcutaneous (s.c.) chronic morphine (6, 16, 26, 36, 46, 56 and 66 mg/kg, 2 ml/kg) at an interval of 24 hours for 7 days. Animals were divided into two experimental groups in which the orexin (100 μM, 200 nl) and its vehicle were microinjected into the PVT nucleus for 7 days before each morphine injection. Then, the formalin test was performed for the assessment of pain-related behaviors. Results: The results demonstrated that the rats pretreated by intra-PVT orexin exhibited higher pain-related behaviors than the morphine-treated group. The analgesic effects of morphine were significantly lower in orexin plus morphine-treated rats than the vehicle plus morphine-treated ones. Conclusion: Our findings suggested that the animals receiving the prolonged intra-PVT application of orexin before morphine injection demonstrated a significant increase in the development of nociceptive behaviors in all phases. Therefore, the present study highlighted a new area of the brain involved in the effect of orexin on analgesia induced by morphine.

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Analgesic Effects of Intrathecal Curcumin in the Rat Formalin Test

The Korean Journal of Pain ◽

10.3344/kjp.2012.25.1.1 ◽

2012 ◽

Vol 25 (1) ◽

pp. 1 ◽

Cited By ~ 26

Author(s):

Yong Ku Han ◽

Seong Heon Lee ◽

Hye Jin Jeong ◽

Min Sun Kim ◽

Myung Ha Yoon ◽

...

Keyword(s):

Formalin Test ◽

Analgesic Effects

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Involvement of the L-arginine/Nitric Oxide/Cyclic GMP/KATP Channel Pathway and PPARγ Receptors in the Peripheral Antinociceptive Effect of Carbamazepine

Drug Research ◽

10.1055/a-0959-5896 ◽

2019 ◽

Vol 69 (12) ◽

pp. 650-657 ◽

Cited By ~ 3

Author(s):

Behnam Ghorbanzadeh ◽

Vahid Kheirandish ◽

Mohammad Taghi Mansouri

Keyword(s):

Nitric Oxide ◽

Methylene Blue ◽

Katp Channel ◽

Formalin Test ◽

Antinociceptive Effect ◽

Experimental Pain ◽

Analgesic Effects ◽

Pparγ Agonist ◽

Nos Inhibitor ◽

Pre Treatment

AbstractCarbamazepine has been shown to exert analgesic effects in clinical and experimental pain situation. This study was conducted to evaluate its potential peripheral antinociceptive effects and the possible involvement of L-arginine/NO/cGMP/KATP channel pathway and PPARγ receptors in an animal model of pain. The antinociceptive effect induced by intraplantar administration of carbamazepine (100–1 000 μg/paw) was assessed using the formalin test in rats. To evaluate the involvement of L-arginine/NO/cGMP/KATP channel pathway in the antinociceptive action of carbamazepine, rats were pre-treated intraplantarlly with L-arginine (a nitric oxide precursor, 100 and 200 μg/paw), L-NAME (NOS inhibitor, 50 and 100 μg/paw), methylene blue (guanylyl cyclase inhibitor, 100 and 200 μg/paw), glibenclamide (KATP channel blocker, 100 and 200 μg/paw), and diazoxide (400 μg/paw). Moreover, to investigate the possible involvement of PPARγ receptors, pioglitazone (10 μg/paw; a PPARγ agonist) alone or in combination with GW9662 (3 μg/paw; a PPARγ antagonist) were pre-treated with carbamazepine. The local ipsilateral, but not contralateral, administration of carbamazepine into the hind paw produced dose-related analgesia during both early and late phases of formalin test. Moreover, pre-treatment with L-NAME, methylene blue, and glibenclamide dose-dependently prevented carbamazepine (300 μg/paw)-induced antinociception in both phases of the test. In addition, administration of L-arginine and diazoxide before the sub-effective dose of carbamazepine (100 μg/paw) produced an antinociceptive effect. Also, antinociception induced by carbamazepine plus pioglitazone (10 μg/paw) was blocked by GW-9662 in both phases of the test. In conclusion, carbamazepine induced a peripheral antinociceptive effect through PPARγ receptors and L-arginine/NO/cGMP/KATP channel pathway, with potential for a new topical analgesic drug.

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Ameliorative Effects of Scopoletin fromCrossostephium chinensisagainst Inflammation Pain and Its Mechanisms in Mice

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/595603 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 12

Author(s):

Tien-Ning Chang ◽

Jeng-Shyan Deng ◽

Yi-Chih Chang ◽

Chao-Ying Lee ◽

Liao Jung-Chun ◽

...

Keyword(s):

Tumor Necrosis ◽

Formalin Test ◽

Late Phase ◽

No Synthase ◽

Paw Edema ◽

Analgesic Effects ◽

Anti Oxidant ◽

Cox 2 ◽

Anti Inflammatory ◽

Necrosis Factor

Scopoletin exists in nature as an anti-oxidant, hepatoprotective, and anti-inflammatory activities reagent. In this study, we have investigated the analgesic effects of the scopoletin using the models of acetic acid-induced writhing response and the formalin test, the anti-inflammatory effects of scopoletin using model ofλ-carrageenan (Carr)-induced paw edema. The treatment of ICR mice with scopoletin inhibited the numbers of writhing response and the formalin-induced pain in the late phase. This study demonstrated that the administration of scopoletin resulted in the reduction of Carr-induced mice edema, and it increased the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) after Carr injection. We also demonstrated scopoletin significantly attenuated the malondialdehyde (MDA) level in the edema paw after Carr injection. Scopoletin decreased the NO, tumor necrosis factor (TNF-α) and prostaglandin E2 (PGE2) levels on serum after Carr injection. Scopoletin decreased Carr-induced inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions in the edema paw. These anti-inflammatory mechanisms of scopoletin might be related to the decrease in the level of MDAviaincreasing the activities of SOD, CAT, and GPx in the edema paw. Also, scopoletin could affect the production of NO, TNF-α, and PGE2, and therefore affect the anti-inflammatory effects.

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