roghaieh khakpay

Intra-paragigantocellularis lateralis (LPGi) injection of 17β-estradiol produces robust antinociceptive effect on the inflammatory pain in the both male and ovariectomized female rats which is possibly mediated through estrogen receptors of this nucleus. This study aimed to examine the role of estrogen receptors in the pain modulatory effect of 17β-estradiol during proestrus phase of female rats. In this study, the female Wistar rats in the range of 200-270 gr were used. For studying the influence of intra-LPGi injection of 17β-estradiol on the acute inflammatory pain modulation, cannulation into the LPGi nucleus was performed after entrance into the proestrus cycle. After entrance in the proestrus phase once again, drugs were injected and 15 minutes later, formalin was injected into the rat's hind paw. Then, formalin-induced paw jerking behavior was recorded for 60 min. This study with research ethics code IR.TBZMED.VCR.REC.1397.385 has been approved by research ethics committee at Tabriz University of Medical Sciences. The results of this study showed that intra-LPGi injection of 17β-estradiol during proestrus phase significantly attenuated paw jerking frequency both in the first (p<0.01) and in the second (p<0.001) phases of formalin test. Pretreatment of the LPGi nucleus with estrogen receptor antagonist (ICI182,780) neutralized the 17β-estradiol-induced analgesia. Our results indicated that intra-LPGi injection of 17β-estradiol induces robust analgesia on the inflammatory pain during the proestrus phase. Thus, it can be concluded that the antinociceptive effect of 17β-estradiol is probably mediated via estrogen receptors.

Background and The paragigantocellularis lateralis nucleus (LPGi) is one of the important nuclei involved in the noradrenergic descending pain modulation. 17β-Estradiol modulates nociception by binding to the estrogen receptors and also by allosteric interaction with other membrane-bound receptors like the glutamate receptors. In this study, the role of AMPA receptors of the LPGi nucleus was investigated in the 17β-estradiol-induced pain modulation in ovariectomized rats.
In this study, female Wistar rats weighing 200-270 gr were used. To investigate the role of the AMPA receptors of the LPGi nucleus, in both acute and persistent pain modulation, cannulation of the LPGi nucleus was performed. Primarily, drugs were injected and 15 minutes later 50 μl of 5% formalin was injected into the rat's hind paw. Then, the paw jerking behavior was recorded for 60 min.
The results showed that intra-LPGi injection of 17β-estradiol significantly reduced the paw jerking behavior in both phases of formalin test (P According to this study, intra-LPGi 17β-estradiol produces modest analgesia on formalin-induced pain in ovariectomized female rats, which is probably mediated via the AMPA receptors of this nucleus.

Paragigantocellularis lateralis (LPGi) nucleus plays a key role in the processing of pain information related to the descending pain modulation. Also, 17β-estradiol is involved in the pain modulation. The aim of the present study was to investigate the role of estrogen receptors of LPGi nucleus in the 17β-estradiol-induced pain modulation in the ovariectomized rats.
In this study, the female Wistar rats (180-250 gr) were used. In order to study the role of the NMDA receptors in the 17β-estradiol-induced pain modulation in the ovariectomized rats, primarily, rats were bilaterally ovariectomized and immediately cannulation of LPGi nucleus was performed. First, drugs were injected and 15 minutes later 50 μl of 5% formalin was injected into the rat's hind paw; and then, formalin-induced paw jerking behavior was recorded for 60 min.
Our results indicated that intra-LPGi injection of 17β-estradiol significantly attenuated paw jerking behavior in the both phases of formalin test. Intra-LPGi injection of estrogen receptor antagonist (ICI 182,780), had no effect on the paw jerking behavior. Pre-treatment of LPGi nucleus by ICI 182,780 counteracted the anti-nociceptive effect of 17β-estradiol both in the acute and in the chronic phases of formalin-induced paw jerking behaviour.
Based on the results of this study, it can be concluded that the intra-LPGi 17β-estradiol produces modest analgesia on the formalin-induced inflammatory pain in the ovariectomized rats, which is probably mediated via the esterogen receptors of this nucleus.

17β-Estradiol modulates nociception by binding to the estrogen receptors and also by allosteric interaction with other membrane-bound receptors like the NMDA receptors. The paragigantocellularis lateralis nucleus (LPGi) is also involved in the pain modulation. In this study, the role of NMDA receptors of the LPGi nucleus has been investigated in the 17β-estradiol-induced pain modulation in the ovariectomized rats.
In this study, the female Wistar rats in the range of 200-270 gr were used. In order to study the role of the NMDA receptors in the 17β-estradiol-induced pain modulation in the ovariectomized rats, primarily, rats were bilaterally ovariectomized and immediately cannulation of the LPGi nucleus was performed. Then, drugs were injected and 15 minutes later 50 μl of 5% formalin was injected into the rat's hind paw; and formalin-induced paw jerking behaviour was recorded for 60 min.
The results of the present study showed that the intra-LPGi injection of 17β-estradiol significantly reduced the paw jerking behavior both in the first and in the second phases of formalin test. Pretreatment of the LPGi nucleus by NMDA receptor antagonist (AP5) neutralized the antinociceptive effect of 17β-estradiol on the paw jerking frequency in the both phases of formalin test; and induced hyperalgesia in the both phases of this behavior.
These results indicated that the intra-LPGi injection of 17β-estradiol produces modest analgesia on the formalin-induced inflammatory pain. Therefore, it can be concluded that the NMDA receptors of the paragigantocellularis lateralis nucleus are probably involved in the antinociceptive effect of 17β-estradiol in the ovariectomized rats.

The 17β-estradiol acts as a neurosteroid in the brain and modulates nociception by binding to the estrogen receptors and also by allosteric interaction with other membrane-bound receptors like glutamate receptors. Paragigantocellularis lateralis nucleus (LPGi) is one of the important brain regions implicated in the pain modulation. So, this study was designed to evaluate the possible involvement of the membrane-bound AMPA receptors of LPGi nucleus in the pain modulatory effect of intra-LPGi 17β-estradiol in the male rats.
In order to study the pain modulatory effect of intra-LPGi microinjection of 17β-estradiol, cannulation into the LPGi nucleus was performed. Then, 500 nl of saline, 17β-estradiol and CNQX- the AMPA receptor antagonist- were unilaterally administered into the right LPGi by injection cannula and Hamilton syringe. In addition, for assessing the role of the AMPA receptors in the pain modulation by 17β-estradiol, 17β-estradiol was injected 15 min after the intra-LPGi administration of CNQX. Then, 50 μl of 4% formalin was subcutaneously injected into the plantar surface of contralateral hind paw and the number of paw jerking behavior was observed for 60 min.
The results showed that intra-LPGi injection of 0.8 μmol of 17β-estradiol attenuated the chronic phase (P Considering the results of this study, it can be concluded that the analgesic effect of intra-LPGi injection of 17β-estradiol might be mediated via AMPA receptors.

Beside its autonomic functions, the nucleus paragigantocellularis lateralis (LPGi) is involved in the descending pain modulation. 17β-Estradiol is a neuroactive steroid found in several brain areas such as LPGi. Intra-LPGi microinjection of 17β-estradiol can elicit the analgesic responses. 17β-Estradiol modulates nociception by binding to estrogenic receptors as well as allosteric interaction with other membrane-bound receptors like GABAA receptors. This study aimed to examine the role of GABAA receptors in the pain modulating effect of intra-LPGi injection of 17β-estradiol.
To study the antinociceptive effects of 17β-estradiol, cannulation into the LPGi nucleus of male Wistar rats was performed. About 500 nL of drug was administered 15 minutes prior to formalin injection (50 μL of 4%). Then, formalin-induced flexing and licking behaviors were recorded for 60 minutes. For evaluating the role of GABAA receptors in the estradiol-induced pain modulation, 17β-estradiol was administered into the LPGi nucleus 15 minutes after the injection of 25 ng/μL bicuculline (the GABAA receptor antagonist). Then, the formalin-induced responses were recorded.
The results of the current study showed that intra-LPGi injection of 17β-estradiol decreased the flexing duration in both phases of formalin test (P According to the results of this study, the analgesic effect of intra-LPGi 17β-estradiol on the formalin-induced inflammatory pain might be mediated via GABAA receptors.

The nucleus paragigantocellularis lateralis (LPGi) is involved in the descending pain modulation. The neurostreoid, 17β-estradiol found in the PGi nucleus and modulates nociception by binding to estrogen receptors and also by allosteric interaction with NMDA receptors. In this study, the role of NMDA receptors in the 17β-estradiol-induced pain modulation was investigated by assessing the inflammatory pain responses changes after blockade of the LPGi nucleus’ NMDA receptors.
In order to study the antinociceptive effect of intra-LPGi microinjection of 17β-estradiol, a guide cannula was implanted into the right LPGi nucleus. 500 nl of drugs were administered 15 minutes prior to formalin (50 μl of 4%) injection. Then, formalin-induced paw jerking behaviour was recorded for 60 min. For assessing the role of the NMDA receptors in the pain modulation by 17β-estradiol, it was injected 15 min after the intra-LPGi administration of 0.5 nmol of AP5 (the NMDA receptor antagonist); and paw jerking frequency was recorded for 1 h.
The results of the present study showed that intra-LPGi injection of 0.8 μmol of 17β-estradiol attenuated the chronic phase (P According to the results of this study, it can be concluded that the analgesic effect of intra-LPGi injection of 17β-estradiol on the formalin-induced inflammatory pain might be mediated via NMDA receptors.

17β-Estradiol modulates nociception by binding to the estrogenic receptors and also by allosteric interaction with other membrane-bound receptors like glutamate and GABAA receptors. In addition to its autonomic functions, paragigantocellularis lateralis (LPGi) is involved in the pain modulation, too. The aim of the current study was to investigate the involvement of the membrane-bound GABAA receptors in the pain modulatory effect of intra- LPGi injection of 17β-estradiol of male rats. This study was performed using male Wistar rats in the range of 200-270 g. In order to investigate the antinociceptive effect of intra-LPGi microinjection of 17β-estradiol, cannulation into the LPGi nucleus was performed. 500 nl of drugs were administered 15 minutes prior to formalin injection (50 μl of 4%). Then, formalin-induced paw jerking behaviour was recorded for 60 min. For assessing the role of the GABAA receptors in the estradiol induced pain modulation, 17β-estradiol was administered into the LPGi nucleus 15 min after the injection of 25 ng/μl bicuculline; and paw jerking frequency was recorded for 1 h. The results of the current study showed that intra-LPGi injection of 0.8 μmol of 17β-estradiol attenuated the chronic phase (P<0.001) of paw jerking behaviour. Bicuculine -the GABAA receptor antagonist- significantly reduced the antinociceptive effect of intra-LPGi 17β-estradiol in the chronic phase (P<0.001). It may be concluded that the analgesic effect of intra-LPGi injection of 17β-estradiol on the formalin-induced inflammatory pain might be mediated via GABAA receptors.

17β-estradiol modulates nociception by binding to estrogenic receptors and also by allosteric interaction with other membrane-bound receptors like glutamate and GABAA receptors. Beside its autonomic functions, paragigantocellularis lateralis (LPGi) nucleus is also involved in pain modulation. The aim of the current study was to investigate the role of the intracellular estrogenic receptors in the pain modulation by the LPGi nucleus of male rats. In this study, male Wistar rats in the range of 200-270 gr were used. In order to study the effect of intra- LPGi microinjection of 17β-estradiol on both acute and persistent pain modulation, cannulation of LPGi nucleus was performed. At first, drugs were injected and 15 minutes later 50 μl of 4% formalin was injected into the rat's hind paw. Then formalin-induced flexing and licking behaviours were recorded for 60 min. The results of current study showed that intra-LPGi injection of 17β-estradiol attenuated the flexing and the licking behaviours both in the first phase (P<0.01) and in the second phase (P<0.001) of formalin test. The estrogen receptor antagonist (ICI182,780) prevented 17β-estradiol-induced analgesic effect but could not reverse this effect to the control condition, and it had significant difference with the control group, yet. It may be concluded some part of the analgesic effect of 17β-estradiol in the LPGi nucleus on the formalin-induced inflammatory pain is probably mediated by estrogenic receptors.

17β-Estradiol is a neuroactive steroid and its pain modulatory role has been well studied previously. 17β-Estradiol modulates nociception by binding to its receptors and also by allosteric interaction with other membrane - bound receptors such as glutamate and GABAA receptors. Paragigantocellularis lateralis (LPGi) is also involved in pain modulation and perception, in addition to its well-known autonomic functions such as regulation of circulation. In order to study the effect of intra-LPGi injection of 17β-estradiol on both acute and persistent pain, 50 μl of 4% formalin was injected into the male rats’ hind paw, then fo rmalin-induced paw jerking behaviour was recorded for 60 min. The results of this study indicated that intra-LPGi injection of 17β-estradiol attenuated the second phase, but not the acute phase of formalin induced pain (P< 0.001). The estrogen receptor antagonist (ICI182,780) counteracted 17β-estradiol’s effect, but could not reverse the antinociceptive effect of 17β -estradiol to its basic level. It may be concluded that a part of the analgesic effect of 17β-estradiol in formalin induced inflammatory pain is mediated by intracellular estrogen receptors; the other part of this effect is possibly mediated through allosteric interactions with other membrane-bound receptors such as glutamate and GABAA receptors.

Estradiol is a neuroactive steroid, which is found in several brain areas such as locus coeruleus (LC). Estradiol modulates nociception by binding to its receptors and also by allosteric interaction with other membranebound receptors like glutamate and GABAA receptors. LC is involved in noradrenergic descending pain modulation.

In order to study the effect of 17β-estradiol on both acute and persistent pain modulation and its mechanisms, formalin was injected into the hind paw of male rats. Formalin-induced responses including licking and flexing duration and paw jerking frequency were recorded for 60 min after injection of 50 μl of 2% formalin. Also, the expression of α2 and γ1 subunits of GABAA receptor genes were examined by RT-PCR technique.

The results of the current study showed that intra-locus coeruleus injection of 17β-estradiol attenuated the second phase, but not the acute phase of formalin induced pain (P< 0.05). GABAA receptor antagonist (bicuculline) reversed the antinociceptive effect of 17β-estradiol, but the expression level of α2 and γ1 subunits of GABAA receptor genes were not significantly changed.

It may be concluded that the analgesic effect of 17β-estradiol in formalin induced inflammatory pain is possibly mediated through the interaction with membrane-bound GABAA receptors, however this effect is not exerted at the gene expression level.