The effect of intra-locus coeruleus injection of 17β-estradiol on inflammatory pain modulation in male rat

Azaddar

et al. 2017

BCN

Introduction: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.Methods: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.Results: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<0.001); but it only attenuated the second phase of licking behavior (P<0.001). 17β-estradiol attenuated the second phase of formalin test of both behaviors (P<0.001). Bicuculline prevented the antinociceptive effect of intra-LPGi 17β-estradiol in both first and second phases of formalin-induced responses (P<0.001).Conclusion: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.

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Analgesic Effect of 17β-Estradiol on Nucleus Paragigantocellularis Lateralis of Male Rats Mediated Via GABAA Receptors

Azaddar

et al. 2017

BCN

Estradiol‐induced antinociceptive responses on formalin‐induced nociception are independent of COX and HPA activation

Hunter

Barr

Amador

et al. 2011

Synapse

Estrogen modulates pain perception but how it does so is not fully understood. The aim of this study was to determine if estradiol reduces nociceptive responses in part via hypothalamicpituitary-adrenal (HPA) axis regulation of cyclooxygenases (COX)-1/COX-2 activity. The first study examined the effects of estradiol (20%) or vehicle with concurrent injection non-steroidal anti-inflammatory drugs (NSAIDs) on formalin-induced nociceptive responding (flinching) in ovariectomized (OVX) rats. The drugs were ibuprofen (COX-1 and COX-2 inhibitor), SC560 (COX-1 inhibitor), or NS398 (COX-2 inhibitor). In a second study, estradiol's effects on formalininduced nociception were tested in adrenalectomized (ADX), OVX, and ADX+OVX rats. Serum levels of prostaglandins (PG) PGE 2 and corticosterone were measured. Estradiol significantly decreased nociceptive responses in OVX rats with effects during both the first and the second phase of the formalin test. The non-steroidal anti-inflammatory drugs (NSAIDs) did not alter nociception at the doses used here. Adrenalectomy neither altered flinching responses in female rats nor reversed estradiol-induced antinociceptive responses. Estradiol alone had no effect on corticosterone or prostaglandin levels after the formalin test, dissociating the effects of estrogen on behavior and these serum markers. Ibuprofen and NS398 significantly reduced PGE2 levels. CORT was not decreased by OVX surgery or by estradiol below that of ADX. Only IBU significantly increased corticosterone levels. Taken together, our results suggest that estradiolinduced antinociception in female rats is independent of COX activity and HPA axis activation.

Involvement of glutamate receptors of the paragigantocellularis lateralis nucleus in the pain modulatory effect of 17β-estradiol in male rats

2018

The pain modulatory role of the paragigantocellularis lateralis nucleus (LPGi) and the 17β-estradiol has thoroughly been probed. This study investigates the contribution of ionotropic glutamate receptors in pain modulatory effect of intra-LPGi injection of 17β-estradiol. For this purpose, the LPGi nucleus cannulation was performed and drugs were injected into this nucleus, 15 min prior to the formalin test. The duration of formalin-induced flexing and licking behaviors was recorded for 60 min immediately after formalin injection. The results showed that the flexing behavior is significantly decreased by intra-LPGi injection of 0.8 µmol 17β-estradiol duringboth phases of formalin test (P < 0.001). However, 17β-estradiol attenuated the licking duration only in the second phase (P < 0.001). Interestingly, NMDA and AMPA/kainate receptor antagonists (AP5 and CNQX, respectively) significantly counteracted the analgesic effect of intra-LPGi injection of 17β-estradiol in both phases of the formalin test (P < 0.001). Consequently, the revealing results showed that the analgesic effect of intra-LPGi injection of 17β-estradiol on acute inflammatory pain might be mediated via the activation of ionotropic glutamate receptors.