Testosterone affects formalin-induced responses differently in male and female rats

Aloisi, Anna Maria; Ceccarelli, Ilaria; Fiorenzani, Paolo; Padova, A.M. De; Massafra, C

doi:10.1016/j.neulet.2003.12.023

Cited by 75 publications

(49 citation statements)

References 9 publications

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“…This quantitative sex difference has been attributed to the actions of gonadal steroid hormones, in which testosterone exerts a blunting effect on formalin pain, whereas estrogen heightens sensitivity through a reduction of pain inhibition mechanisms (2,21,22). The present study revealed a strong trend toward lower pain responding during the late phase in ovariectomized females relative to their sham-operated counterparts, consistent with the notion that estrogen is responsible for the sex difference in sensitivity to formalin.…”

Section: Discussionsupporting

confidence: 86%

Sex differences in the effects of amiloride on formalin test nociception in mice

Chanda¹,

Mogil²

2006

American Journal of Physiology-Regulatory, Integrative and Comp

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Amiloride is a nonspecific blocker of acid-sensing ion channels (ASICs) that have been recently implicated in the mediation of mechanical and chemical/inflammatory nociception. Preliminary data using a transgenic model are suggestive of sex differences in the role of ASICs. We report here that systemic administration of amiloride (10–70 mg/kg ip) produces a robust, dose-dependent blockade of late/tonic phase nociceptive behavior on the mouse formalin test (5%; 20 μl) in female but not male mice, completely abolishing the known sex difference in formalin test response. Adult gonadectomy produced a “switching” of sex differences in amiloride efficacy, with castrated males displaying an amiloride blockade and ovariectomized females rendered less sensitive to amiloride. Gonadectomized mice could be switched back to their intact status using chronic estrogen benzoate or testosterone propionate replacement via osmotic minipump (6 μg/day or 250 μg/day, respectively). It is unclear whether this striking sex difference is due to sex-specific involvement of ASICs in pain processing, but the present data represent one of the first demonstrations of pain-related sex differences with no obvious opioid involvement.

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Section: Discussionsupporting

confidence: 86%

Sex differences in the effects of amiloride on formalin test nociception in mice

Chanda¹,

Mogil²

2006

American Journal of Physiology-Regulatory, Integrative and Comp

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“…The observation that testosterone has a protective role is supported by earlier demonstrations that this hormone can reduce the intensity of nociception by inhibiting its inflammationrelated component [18]. Our results also agree with the results obtained by Aloisi et al [19] and Hau et al [20] who showed a protective role of testosterone in their various studies. In our experiments, we observed a quite obvious and close relationship between the plasma testosterone concentration and the pain reaction times, which is in agreement with earlier studies [20], except that our data were collected on the same animals at different stages of sexual development.…”

Section: Discussionsupporting

confidence: 93%

Relationship between the Plasma Testosterone Level and Pain Reaction Times in Male Rats

et al. 2009

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Male prepubertal (about 4 weeks old) Wistar rats were used to estimate the pain reaction times using the tail-flick and hot-plate models; the testosterone concentration in the blood plasma was measured in all the animals before the tests. The same sets of animals were kept for the next 4 weeks under standard conditions; the experiment was repeated, and pain reaction times were also evaluated in the 8-week-old rats with blood samples collected to determine the plasma testosterone level. The results showed significant (P < 0.01) increases in the pain reaction times in both pain models in pubertal animals observed in a parallel manner with a corresponding significant (P < 0.01) increase in the plasma testosterone level. Therefore, age and sex are important factors in the choice of animals in pain experiments.

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“…Evidence for organizational versus activational effects of gonadal hormones on pain traits is mixed, with some studies showing robust effects of neonatal male castration and female testosterone-induced masculinization on pain behaviour [66][67][68][69][70] and others being strongly supportive of the primacy of circulating hormone levels in the adult [71][72][73][74][75][76][77] . The classic organizational versus activational dichotomy has recently been supplemented by the realization that direct genetic effects are possible as well: traits such as pain might be affected by genes on the Y chromosome, X-linked genes escaping inactivation, parentally imprinted genes and/or allelic mosaicism 78 .…”

Section: Nature Reviews | Neurosciencementioning

confidence: 99%

Sex differences in pain and pain inhibition: multiple explanations of a controversial phenomenon

2012

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| A clear majority of patients with chronic pain are women; however, it has been surprisingly difficult to determine whether this sex bias corresponds to actual sex differences in pain sensitivity. A survey of the currently available epidemiological and laboratory data indicates that the evidence for clinical and experimental sex differences in pain is overwhelming. Various explanations for this phenomenon have been given, ranging from experiential and sociocultural differences in pain experience between men and women to hormonally and genetically driven sex differences in brain neurochemistry. PERSPECTIVES NATURE REVIEWS | NEUROSCIENCE VOLUME 13 | DECEMBER 2012 | 859

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Testosterone affects formalin-induced responses differently in male and female rats

Cited by 75 publications

References 9 publications

Sex differences in the effects of amiloride on formalin test nociception in mice

Sex differences in the effects of amiloride on formalin test nociception in mice

Relationship between the Plasma Testosterone Level and Pain Reaction Times in Male Rats

Sex differences in pain and pain inhibition: multiple explanations of a controversial phenomenon

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