Characterization of Nociceptive Behaviors Induced by Formalin in the Glabrous and Hairy Skin of Rats

Erami, Elaheh; Azhdari-Zarmehri, Hassan; Imoto, Keiji; Furue, Hidemasa

doi:10.15412/j.bcn.03080105

Cited by 11 publications

(7 citation statements)

References 30 publications

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“…Before the initiation of formalin-induction, the mice were transferred to the formalin testing boxes and observed for 30 min. Following the induction of the formalin-induced nociception, animals were further observed for 30 min and the total time taken was 60 min as reported previously with necessary modification [23]. Mice were observed for first 10 min (early phase) and from 10 to 30 min (late phase) and total time spent in licking the injected paw was calculated for both phases.…”

Section: Methodsmentioning

confidence: 99%

RETRACTED ARTICLE: Anti-hyperalgesic properties of a flavanone derivative Poncirin in acute and chronic inflammatory pain models in mice

Afridi¹,

Khan²,

Khalid³

et al. 2019

BMC Pharmacol Toxicol

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Background Poncirin is flavanone derivative (isolated from Poncirus trifoliata) with known pharmacological activities such as anti-tumor, anti-osteoporotic, anti-inflammatory and anti-colitic. The present study aimed to explore the anti-allodynic and anti-hyperalgesic potentials of poncirin in murine models of inflammatory pain. Methods The analgesic potential of poncirin was evaluated in formalin-, acetic acid-, carrageenan- and Complete Freund’s Adjuvant (CFA)-induced inflammatory pain models in mice. Anti-allodynic and anti-hyperalgesic activities were measured using Von Frey filaments, Randall Selitto, hotplate and cold acetone tests. The serum nitrite levels were determined using Griess reagent. The Quantitative Real-time PCR (qRT-PCR) was performed to assess the effect of poncirin on mRNA expression levels of inflammatory cytokines and anti-oxidant enzymes. Results Intraperitoneal administration of poncirin (30 mg/kg) markedly reduced the pain behavior in both acetic acid-induced visceral pain and formalin-induced tonic pain models used as preliminary screening tools. The poncirin (30 mg/kg) treatment considerably inhibited the mechanical hyperalgesia and allodynia as well as thermal hyperalgesia and cold allodynia. The qRT-PCR analysis showed noticeable inhibition of pro-inflammatory cytokines (mRNA expression levels of TNF-α, IL-1β and IL-6) (p < 0.05) in poncirin treated group. Similarly, poncirin treatment also enhanced the mRNA expressions levels of anti-oxidant enzymes such as transcription factor such as nuclear factor (erythroid-derived 2)-like 2 (Nrf2) (p < 0.05), heme oxygenase (HO-1) (p < 0.05) and superoxide dismutase (SOD2) (p < 0.05). Chronic treatment of poncirin for 6 days did not confer any significant hepatic and renal toxicity. Furthermore, poncirin treatment did not altered the motor coordination and muscle strength in CFA-induced chronic inflammatory pain model. Conclusion The present study demonstrated that poncirin treatment significantly reduced pain behaviors in all experimental models of inflammatory pain, suggesting the promising analgesic potential of poncirin in inflammatory pain conditions.

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Section: Methodsmentioning

confidence: 99%

RETRACTED ARTICLE: Anti-hyperalgesic properties of a flavanone derivative Poncirin in acute and chronic inflammatory pain models in mice

Afridi¹,

Khan²,

Khalid³

et al. 2019

BMC Pharmacol Toxicol

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“…Since first reported over 40 years ago, the formalin test 1 has been widely used in pain research and is known to capture mechanisms that are likely to be relevant to many pain patients in clinic 2, 3 , including the poorly localized, burning and throbbing pain sensation 4 . The unique feature of the formalin test is that it triggers two phases of nociceptive behaviour: the first one is directly linked to the stimulation of primary sensory neurons and is followed by a second phase, which is associated with inflammation and involves central sensitisation 1, 5– 7 .…”

Section: Introductionmentioning

confidence: 99%

A refinement to the formalin test in mice

et al. 2019

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The constant refinement of tests used in animal research is crucial for the scientific community. This is particularly true for the field of pain research, where ethical standards are notably sensitive. The formalin test is widely used in pain research and some of its mechanisms resemble those underlying clinical pain in humans. Immediately upon injection, formalin triggers two waves (an early and a late phase) of strong, nociceptive behaviour, characterised by licking, biting, lifting and shaking the injected paw of the animal. Although well characterised at the behaviour level, since its proposal over four decades ago, there has not been any significant refinement to the formalin test, especially those combining minimisation of animal distress and preservation of behavioural outcomes of the test. Here, we propose a modified and improved method for the formalin test. We show that anaesthetising the animal with the inhalable anaesthetic sevoflurane at the time of the injection can produce reliable, robust and reproducible results whilst animal distress during the initial phase is reduced. Importantly, our results were validated by pharmacological suppression of the behaviour during the late phase of the test with gabapentin, the anaesthetic showing no interference with the drug. In addition, we demonstrate that this is also a useful method to screen for changes in pain behaviour in response to formalin in transgenic lines.

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“…During this phase, many mediators of inflammation, for example, histamine, prostaglandins, bradykinin, interleukin, TNF-α, and adrenergic amines, are activated, occurring with functional modifications of the spinal cord, particularly in the dorsal horn. 59,61,64 The intensity response of the nociceptive behaviors response is determined by the concentration of formalin that is administered. 62 Our study used an antinociceptive drug, morphine, as a standard reference, which was effective against pain in both phases.…”

Section: Discussionmentioning

confidence: 99%

Anti-inflammatory, Antinociceptive, and Antitumorigenesis Activities of Terminalia Bellerica (Gaertn.) Roxb. in Animal Models

Takuathung

Jaijoy

Soonthornchareonnon

et al. 2022

Natural Product Communications

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Previous pharmacological research has demonstrated that Terminalia bellerica (Gaertn.) Roxb. (TB) extract possesses several pharmacological activities. However, there is scant evidence documenting the therapeutic activities of TB extract on inflammation, pain, and cancers. Our study examined the in vivo anti-inflammation, antinociception, and antitumorigenesis effects of TB extract and investigated possible mechanisms for those effects. Anti-inflammation activities of TB extract were evaluated using ethyl phenylpropiolate (EPP)- and arachidonic acid (AA)-induced ear edema models, a cotton pellet-induced granulation formation model, and a carrageenan-induced hind paw edema model. An antinociceptive property of TB extract was assessed using a formalin-induced nociception test. An anticarcinogenesis effect was investigated using a 7,12-dimethylbenz( a) anthracene (DMBA) and 12- O-tetradecanoylphorbol-13-acetate (TPA)-induced tumorigenesis model. In the study, TB extract exhibited significant anti-inflammatory effects against EPP-induced ear edema and carrageenan-induced hind paw edema in rats. However, the TB extract showed insignificant inhibitory activity against AA-induced ear edema and cotton pellet-induced granuloma. A dose-dependent decrease in analgesic activity was observed with TB extract evidenced by decreased licking time in formalin-induced pain in mice in both the early and late phases. TB extract also significantly inhibited DMBA/TPA-induced mouse skin tumorigenesis. In conclusion, TB extract possesses anti-inflammatory, analgesic, and anticarcinogenesis properties which act, at least in part, through inhibitory effects of inflammatory mediator production.

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Characterization of Nociceptive Behaviors Induced by Formalin in the Glabrous and Hairy Skin of Rats

Cited by 11 publications

References 30 publications

RETRACTED ARTICLE: Anti-hyperalgesic properties of a flavanone derivative Poncirin in acute and chronic inflammatory pain models in mice

RETRACTED ARTICLE: Anti-hyperalgesic properties of a flavanone derivative Poncirin in acute and chronic inflammatory pain models in mice

A refinement to the formalin test in mice

Anti-inflammatory, Antinociceptive, and Antitumorigenesis Activities of Terminalia Bellerica (Gaertn.) Roxb. in Animal Models

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