Formalin injection produces long-lasting hypersensitivity with characteristics of neuropathic pain

Salinas-Abarca, Ana Belen; Avila-Rojas, Sabino Hazael; Barragán-Iglesias, Paulino; Pineda-Farías, Jorge Baruch; Granados‐Soto, Vinicio

doi:10.1016/j.ejphar.2017.01.018

Cited by 51 publications

(43 citation statements)

References 62 publications

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“…These results are in agreement with reports that that gabapentin has an antinociceptive effect at the peripheral, spinal and systemic levels in the formalin‐induced nociceptive model [Ortega‐Varela et al, ; Carlton and Zhou, ; Granados‐Soto and Argüelles, ]. Gabapentin injected intradermally into the hindpaw can induce analgesia [Todorovic et al, ] and gabapentin is also effective in acute and chronic models of inflammatory pain [Singh et al, ; Heughan and Sawynok et al, ; Hurley et al, ] and reverses allodynia and hyperalgesia induced by 1% formalin [Salinas‐Abarca et al, ]. Gabapentin can decrease allodynia induced by nerve lesions in a neuropathic rat model [Chen et al, ; Field et al, ; Mixcoatl‐Zecuatl et al, ; Yamama et al, ; Miranda et al, ; Corona‐Ramos et al, ; Espinosa‐Juárez et al, ].…”

Section: Discussionsupporting

confidence: 90%

Synergistic Interaction of a Gabapentin‐ Mangiferin Combination in Formalin‐Induced Secondary Mechanical Allodynia and Hyperalgesia in Rats Is Mediated by Activation of NO‐Cyclic GMP‐ATP‐Sensitive K⁺ Channel Pathway

Godínez‐Chaparro

Quiñonez-Bastidas

Rojas-Hernández

et al. 2017

Drug Development Research

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Preclinical Research Gabapentin is an anticonvulsant used to treat neuropathic pain. Mangiferin is an antioxidant that has antinociceptive and antiallodynic effects in inflammatory and neuropathic pain models. The purpose of this study was to determine the interaction between mangiferin and gabapentin in the development and maintenance of formalin-induced secondary allodynia and hyperalgesia in rats. Gabapentin, mangiferin, or their fixed-dose ratio combination were administrated peripherally. Isobolographic analyses was used to define the nature of the interaction of antiallodynic and/or antihyperalgesic effects of the two compounds. Theoretical ED values for the combination were 74.31 µg/paw and 95.20 µg/paw for pre- and post-treatment, respectively. These values were higher than the experimental ED values, 29.45 µg/paw and 37.73 µg/paw respectively, indicating a synergistic interaction in formalin-induced secondary allodynia and hyperalgesia. The antiallodynic and antihyperalgesic effect induced by the gabapentin/mangiferin combination was blocked by administration of L-NAME, the soluble guanylyl cyclase inhibitor, ODQ and glibenclamide. These data suggest that the gabapentin- mangiferin combination produces a synergistic interaction at the peripheral level. Moreover, the antiallodynic and hyperalgesic effect induced by the combination is mediated via the activation of an NO-cyclic GMP-ATP-sensitive K channel pathway. Drug Dev Res 78 : 390-402, 2017. © 2017 Wiley Periodicals, Inc.

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Section: Discussionsupporting

confidence: 90%

Synergistic Interaction of a Gabapentin‐ Mangiferin Combination in Formalin‐Induced Secondary Mechanical Allodynia and Hyperalgesia in Rats Is Mediated by Activation of NO‐Cyclic GMP‐ATP‐Sensitive K⁺ Channel Pathway

Godínez‐Chaparro

Quiñonez-Bastidas

Rojas-Hernández

et al. 2017

Drug Development Research

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“…Such as the MDA values, the NOx values were significantly different compared to control for all groups that received curcumin, either conventional or liposomal ( p0.0004). No significant differences were observed between the groups treated with the same type of curcumin but at different concentrations (conventional 75, liposomal curcumin p=0.08). Significantly lower NOx values were found when the lCC2 group was compared to the CC2 group, and the lCC1 group was compared to the CC1 group ( Figure 1B).…”

Section: Resultsmentioning

confidence: 85%

“…27 A computational model developed by Fischer et al 74 supports the biphasic response, the interphase being the result of hyperpolarization and transient inactivation, followed by recovery prior to decrease in formalin concentration below threshold. However, the 1% formalin injection used in our design assured the absence of long-lasting hypersensitivity and peripheral inflammation (reported for 2% and 5% in a spinal nerve injury model) 75 and thus the comfort of animals. Despite its limitations, the formalin test is still currently used in the evaluation of both pain and inflammation in animal models.…”

Section: Study Limitationsmentioning

confidence: 99%

The effect of intravenous administration of liposomal curcumin in addition to sumatriptan treatment in an experimental migraine model in rats

Bulboacă¹,

Bolboacă²,

Stănescu³

et al. 2018

IJN

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BackgroundCurcumin has antioxidative properties that could be useful in various diseases due to its ability to act on multiple targets of various cellular pathways. We aimed to assess the efficacy of liposomal curcumin compared with curcumin solution, when in addition to sumatriptan (ST) treatment, in an experimental migraine model induced with nitroglycerin (NTG) in rats.MethodsSeven groups of 9 rats each were investigated: control group without migraine (1 mL saline solution intraperitoneal injection [ip]), control group with induced migraine, NTG+ST group (ST), NTG+ST+curcumin1 (CC1) group – 1 mg/100 g body weight (bw), NTG+ST+CC2 – 2 mg/100 g bw, NTG+ST+liposomal curcumin1 (lCC1) group – 1 mg/100 g bw, and NTG+ST+lCC2 (lCC2) group – 2 mg/100 g bw. NTG and ST were administered as 1 mL ip NTG | 1 mg/100 g bw and 1 mL ip ST | 1 mg/100 g bw, respectively. Plasma total oxidative stress (TOS), malondialdehyde (MDA), nitric oxide (NOx), thiol levels, as well as total antioxidative capacity (TAC) were assessed. The nociception process was assessed by counting the number of flinches and shakes after the formalin test.ResultsThe plasma TOS, MDA, and NOx levels, as oxidative stress parameters, were significantly decreased in the curcumin-treated groups, especially where curcumin was in liposomal form. The thiol and TAC were also improved by the curcumin treatment, with the best results obtained for the liposomal curcumin. The closest number of flinches and shakes to the control group was obtained for the group treated with liposomal curcumin at a dose of 2 mg/100 g bw.ConclusionLiposomal curcumin in a dose of 2 mg/100 g bw when in addition to ST treatment could be an optimum therapeutic strategy for migraine attacks and could represent a base for future clinical research and application.

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“…It has been reported that gabapentin and DAMGO are effective in neuropathic pain, in contrast indomethacin is no effective. Oral administration of gabapentin (10-120 mg/kg), but not indomethacin (1-10 mg/kg), reduces mechanical allodynia in spinal nerve ligation model of neuropathic pain 25,26 . Intrathecal administration of DAMGO (1 μg) inhibits mechanical hypersensitivity in the spinal nerve ligation model 27 .…”

Section: Discussionmentioning

confidence: 99%

“…2f,g). Besides theses acute effects of formalin (up to 50 min), 2% formalin has been reported to produce long-lasting mechanical allodynia and hyperalgesia for at least 2 week 26 . The formalin-induced long-lasting secondary hypersensitivity is inhibited by gabapentin, but not by indomethacin.…”

Section: Discussionmentioning

confidence: 99%

Mechanical allodynia in mice with tenascin-X deficiency associated with Ehlers-Danlos syndrome

Okuda‐Ashitaka

Kakuchi

Kakumoto

et al. 2020

Sci Rep

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tenascin-X (tnX) is a member of the extracellular matrix glycoprotein tenascin family, and tnX deficiency leads to Ehlers-Danlos syndrome, a heritable human disorder characterized mostly by skin hyperextensibility, joint hypermobility, and easy bruising. TNX-deficient patients complain of chronic joint pain, myalgia, paresthesia, and axonal polyneuropathy. However, the molecular mechanisms by which TNX deficiency complicates pain are unknown. Here, we examined the nociceptive behavioral responses of TNX-deficient mice. Compared with wild-type mice, TNX-deficient mice exhibited mechanical allodynia but not thermal hyperalgesia. TNX deficiency also increased pain sensitivity to chemical stimuli and aggravated early inflammatory pain elicited by formalin. TNX-deficient mice were significantly hypersensitive to transcutaneous sine wave stimuli at frequencies of 250 Hz (Aδ fiber responses) and 2000 Hz (Aβ fiber responses), but not to stimuli at frequency of 5 Hz (C fiber responses). in addition, the phosphorylation levels of extracellular signal-related kinase, an active neuronal marker, and the activity of nADpH-diaphorase, a neuronal nitric oxide activation marker, were enhanced in the spinal dorsal horns of TNX-deficient mice. These results suggest that TNX deficiency contributes to the development of mechanical allodynia and hypersensitivity to chemical stimuli, and it induces hypersensitization of myelinated A fibers and activation of the spinal dorsal horn.

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Formalin injection produces long-lasting hypersensitivity with characteristics of neuropathic pain

Cited by 51 publications

References 62 publications

Synergistic Interaction of a Gabapentin‐ Mangiferin Combination in Formalin‐Induced Secondary Mechanical Allodynia and Hyperalgesia in Rats Is Mediated by Activation of NO‐Cyclic GMP‐ATP‐Sensitive K⁺ Channel Pathway

Synergistic Interaction of a Gabapentin‐ Mangiferin Combination in Formalin‐Induced Secondary Mechanical Allodynia and Hyperalgesia in Rats Is Mediated by Activation of NO‐Cyclic GMP‐ATP‐Sensitive K⁺ Channel Pathway

The effect of intravenous administration of liposomal curcumin in addition to sumatriptan treatment in an experimental migraine model in rats

Mechanical allodynia in mice with tenascin-X deficiency associated with Ehlers-Danlos syndrome

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Formalin injection produces long-lasting hypersensitivity with characteristics of neuropathic pain

Cited by 51 publications

References 62 publications

Synergistic Interaction of a Gabapentin‐ Mangiferin Combination in Formalin‐Induced Secondary Mechanical Allodynia and Hyperalgesia in Rats Is Mediated by Activation of NO‐Cyclic GMP‐ATP‐Sensitive K+ Channel Pathway

Synergistic Interaction of a Gabapentin‐ Mangiferin Combination in Formalin‐Induced Secondary Mechanical Allodynia and Hyperalgesia in Rats Is Mediated by Activation of NO‐Cyclic GMP‐ATP‐Sensitive K+ Channel Pathway

The effect of intravenous administration of liposomal curcumin in addition to sumatriptan treatment in an experimental migraine model in rats

Mechanical allodynia in mice with tenascin-X deficiency associated with Ehlers-Danlos syndrome

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Synergistic Interaction of a Gabapentin‐ Mangiferin Combination in Formalin‐Induced Secondary Mechanical Allodynia and Hyperalgesia in Rats Is Mediated by Activation of NO‐Cyclic GMP‐ATP‐Sensitive K⁺ Channel Pathway

Synergistic Interaction of a Gabapentin‐ Mangiferin Combination in Formalin‐Induced Secondary Mechanical Allodynia and Hyperalgesia in Rats Is Mediated by Activation of NO‐Cyclic GMP‐ATP‐Sensitive K⁺ Channel Pathway