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Effects of microinjection of histamine into the anterior cingulate cortex on pain-related behaviors induced by formalin in rats

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Abstract

Background

The present study was aimed to investigate the effects of microinjection of histamine and its H1, H2 and H3 receptor antagonists, mepyramine, ranitidine and thioperamide, respectively, into the anterior cingulate cortex (ACC) on pain-related behaviors induced by formalin in rats.

Methods

Two stainless steel guide canulas were bilaterally implanted into the ACC of anaesthetized rats. For induction of pain, intraplantar (ipl) injection of a 2.5% formalin solution was performed. The duration of paw licking/biting and the number of paw flinching were recorded in 5 min blocks for 60 min. Locomotor activity was assessed using an open-field test.

Results

Formalin produced a marked biphasic pattern of pain. Histamine reduced the second phases of paw licking/biting and flinching. Mepyramine (2 μg/side) prevented the suppressive effect of histamine (1 μg/side) on second phase of pain, but at a dose of 8 μg/side it did not inhibit the suppressive effects of 4 μg/side of histamine. Ranitidine at doses of 2 and 8 μg/side prevented histamine (1 and 4 μg/side)-induced antinociception. Thioperamide not only suppressed the second phases of pain, but also increased the suppressive effect of histamine. Naloxone prevented suppressive effects of histamine and thioperamide on pain. Mepyramine (8 μg/side) suppressed locomotor activity.

Conclusion

The results of the present study showed pain suppressing effects for histamine. Histamine H2 and H3, and to a lesser extent, H1 receptors might be involved in histamine-induced antinociception. Opioid receptors might be involved in suppressive effects of histamine and thioperamide.

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Abbreviations

ACC:

anterior cingulate cortex

TMN:

tuberomammillary nucleus

DH:

dorsal hippocampus

DG:

dentate gyrus

PSC:

primary somatosensory cortex

PAG:

periaqueductal gray

RN:

raphe nucleus

LC:

locus coeruleus

CABA:

gama-amino butyric acid

CCK:

cholecystokinin

icv :

intracerebroventricular

sc :

subcutaneous

ip :

intraperitoneal

ipl :

intraplantar

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Authors and Affiliations

  1. Division of Physiology, Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran

    Nasrin Hamzeh-Gooshchi & Esmaeal Tamaddonfard

  2. Division of Pathology, Department of Pathobiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran

    Amir Abbas Farshid

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  1. Nasrin Hamzeh-Gooshchi
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  2. Esmaeal Tamaddonfard
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  3. Amir Abbas Farshid
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Correspondence to Nasrin Hamzeh-Gooshchi.

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Hamzeh-Gooshchi, N., Tamaddonfard, E. & Farshid, A. Effects of microinjection of histamine into the anterior cingulate cortex on pain-related behaviors induced by formalin in rats. Pharmacol. Rep 67, 593–599 (2015). https://doi.org/10.1016/j.pharep.2014.12.019

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  • DOI: https://doi.org/10.1016/j.pharep.2014.12.019

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