Activational action of testosterone on androgen receptors protects males preventing temporomandibular joint pain

Fanton, Letícia Esmanhoto; Macedo, Cristina Gomes de; Torres-Chávez, Karla Elena; Fischer, Luana; Tambeli, Cláudia Herrera

doi:10.1016/j.pbb.2016.07.005

Cited by 24 publications

(30 citation statements)

References 36 publications

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“…The evidence accumulated over the last decade corroborates the results obtained in the present study, suggesting a protective role of testosterone against pain, but the underlying mechanisms are still unclear [8, 22, 23, 28, 29]. The increase in the expression of voltage-dependent sodium channels, particularly NaV1.7 and NaV1.8, has already been demonstrated in previous studies using inflammatory pain models [15, 30, 31].…”

Section: Discussionsupporting

confidence: 91%

“…Flutamide is used to achieve androgenic blockade without the complications of surgical castration [27]. A recent study demonstrated that the analgesic effect of testosterone is dependent on activation of the testosterone receptor and that flutamide reversed this protective effect after formalin injection into the temporomandibular joint (TMJ) [28].…”

Section: Discussionmentioning

confidence: 99%

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Influence of androgenic blockade with flutamide on pain behaviour and expression of the genes that encode the NaV1.7 and NaV1.8 voltage-dependent sodium channels in a rat model of postoperative pain

et al. 2019

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Background Experimental studies suggest that testosterone reduces the nociceptive response after inflammatory and neuropathic stimuli, however the underlying mechanisms have not been fully elucidated. The aims of this study were to evaluate the effect of peripheral blockade of testosterone on pain behaviour and on expression levels of the genes that encode the NaV1.7 and NaV1.8 channels, in dorsal root ganglia in an acute postoperative pain model, as well as the influence of androgen blockade on the expression of these genes. Methods Postoperative pain was induced by a plantar incision and the study group received flutamide to block testosterone receptor. The animals were submitted to behavioural evaluation preoperatively, 2 h after incision, and on the 1st, 2nd, 3rd and 7th postoperative days. Von Frey test was used to evaluate paw withdrawal threshold after mechanical stimuli and the guarding pain test to assess spontaneous pain. The expression of the genes encoding the sodium channels at the dorsal root ganglia was determined by real time quantitative polymerase chain reaction. Results Animals treated with flutamide presented lower paw withdrawal threshold at the 1st, 2nd, 3rd, and 7th postoperative days. The guarding pain test showed significant decrease in the flutamide group at 2 h and on the 3rd and 7th postoperative days. No difference was detected between the study and control groups for the gene expression. Conclusions Our data suggest an antinociceptive effect of androgens following plantar incision. The expression of genes that encode voltage-gated sodium channels was not influenced by androgen blockade.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Influence of androgenic blockade with flutamide on pain behaviour and expression of the genes that encode the NaV1.7 and NaV1.8 voltage-dependent sodium channels in a rat model of postoperative pain

et al. 2019

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“…According to these studies, low levels of testosterone are related to high discomfort, anxiety, and pain in response to noxious hot stimuli (Choi et al, 2017 ). In another study, Fanton et al ( 2017 ) concluded that the protective effect of testosterone is due to the activation of androgen receptors by the hormone instead of an androgenic action of a testosterone derivative (i.e., dihydrotestosterone) during CNS development. These observations are in agreement with the testosterone effect observed in nociceptors.…”

Section: Trpv1 Trpm8 and Testosteronementioning

confidence: 99%

TRP Channels as Potential Targets for Sex-Related Differences in Migraine Pain

Artero-Morales

González-Rodríguez

Ferrer-Montiel

2018

Front. Mol. Biosci.

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Chronic pain is one of the most debilitating human diseases and represents a social and economic burden for our society. Great efforts are being made to understand the molecular and cellular mechanisms underlying the pathophysiology of pain transduction. It is particularly noteworthy that some types of chronic pain, such as migraine, display a remarkable sex dimorphism, being up to three times more prevalent in women than in men. This gender prevalence in migraine appears to be related to sex differences arising from both gonadal and genetic factors. Indeed, the functionality of the somatosensory, immune, and endothelial systems seems modulated by sex hormones, as well as by X-linked genes differentially expressed during development. Here, we review the current data on the modulation of the somatosensory system functionality by gonadal hormones. Although this is still an area that requires intense investigation, there is evidence suggesting a direct regulation of nociceptor activity by sex hormones at the transcriptional, translational, and functional levels. Data are being accumulated on the effect of sex hormones on TRP channels such as TRPV1 that make pivotal contributions to nociceptor excitability and sensitization in migraine and other chronic pain syndromes. These data suggest that modulation of TRP channels' expression and/or activity by gonadal hormones provide novel pathways for drug intervention that may be useful for targeting the sex dimorphism observed in migraine.

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“…Sexual dimorphism found in the prenatally stressed rats in pain-related indices is associated with suppression of the release of testosterone, which itself has an analgesic effect (Edinger and Frye, 2005; Da Silva et al, 2018). The sex steroid hormones estrogens and androgens modulate prenatal and postnatal development of many processes including the nociception, the HPA axis and immune system (Green and McCormick, 2016; Fanton et al, 2017). Differences in the prenatal action of the drugs on inflammatory painful behavior may also be related to the sexual differences in the development of microglia during critical periods prenatally (Nelson and Lenz, 2017).…”

Section: Discussionmentioning

confidence: 99%

Differences Between the Prenatal Effects of Fluoxetine or Buspirone Alone or in Combination on Pain and Affective Behaviors in Prenatally Stressed Male and Female Rats

Butkevich

Mikhailenko

Vershinina

et al. 2019

Front. Behav. Neurosci.

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The selective serotonin reuptake inhibitor fluoxetine and the 5-HT1A receptor agonist buspirone are used to treat depression and anxiety. Previously we demonstrated that chronic stress during pregnancy (prenatal stress) in rats, used as a model of maternal depression risk, increased inflammatory pain and depressive-like behavior in the offspring; buspirone injected to pregnant dams was protective. Clinically, the addition of buspirone to fluoxetine increases the latter’s efficacy in treating depression in patients. Here, we investigated the influence of repeated prenatal injections of fluoxetine, buspirone or their combination on pain- and depressive-like behaviors in prenatally stressed young male and female rats. Prenatal stress augmented depressive-like behavior and both thermal and inflammatory pain (formalin test), replicating our prior findings, and increased basal levels of corticosterone in the blood plasma. Both drugs and their combination reduced the effects of prenatal stress on thermal pain and depressive-like behavior independently of sex. The combination of fluoxetine and buspirone, compared with fluoxetine, was more antinociceptive in the hot plate test in both sexes, and when compared with buspirone, was more antinociceptive only in males. A detailed study of the time-course of formalin-induced pain showed a nuanced effect of these drugs that was sex-dependent. The combination of the two drugs was less effective in females than males during the initial acute phase of nociceptive behavior in flexing + shaking behaviors, whereas that combination was more effective than fluoxetine alone in the first acute phase of licking behavior in females. The antinociceptive effect of buspirone dominated that of the drug combination and of fluoxetine alone, especially during the interphase of the formalin test in both sexes for both flexing + shaking and licking, suggesting a more effective prenatal action of buspirone on the development of a descending serotonergic inhibitory system modulating pain in the spinal cord dorsal horn neurons. Our results indicate that inflammatory pain-like responses integrated at the spinal level in males were more vulnerable to prenatal stress than females. In licking, the antinociceptive effect of fluoxetine and drug combination in the interphase was more in males than females. The data underscore the importance of considering sexual dimorphism when using drug therapy.

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Activational action of testosterone on androgen receptors protects males preventing temporomandibular joint pain

Cited by 24 publications

References 36 publications

Influence of androgenic blockade with flutamide on pain behaviour and expression of the genes that encode the NaV1.7 and NaV1.8 voltage-dependent sodium channels in a rat model of postoperative pain

Influence of androgenic blockade with flutamide on pain behaviour and expression of the genes that encode the NaV1.7 and NaV1.8 voltage-dependent sodium channels in a rat model of postoperative pain

TRP Channels as Potential Targets for Sex-Related Differences in Migraine Pain

Differences Between the Prenatal Effects of Fluoxetine or Buspirone Alone or in Combination on Pain and Affective Behaviors in Prenatally Stressed Male and Female Rats

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