Tonic pain response in mice: effects of sex, season and time of day

Perissin, L.; Facchin, Patrizia; Porro, Carlo Adolfo

doi:10.1016/s0024-3205(02)02344-5

Cited by 38 publications

(23 citation statements)

References 36 publications

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“…We observed significantly greater formalin responses during the late phase in gonadally intact females relative to males, which is consistent with previous findings in the rodent literature from a number of different groups (1,21,25,39). 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).…”

Section: Discussionsupporting

confidence: 91%

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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: 91%

“…35). By contrast, in the formalin test of chemical/inflammatory pain (16), female rats and mice have consistently been found, by a number of different investigators, to display greater sensitivity than males (1,21,25,39; see also Ref. 12) when differences were observed.…”

mentioning

confidence: 97%

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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“…However, the reliability and direction of sex differences appear to depend on multiple factors, from genes and reproductive hormones to nociceptive assays and environmental considerations. Indeed, whereas some studies reported that females are more susceptible to the development of persistent pain following tissue injury, others have shown that female and male exhibit identical sensitivity to formalin (Aloisi et al, 1994, Kim et al, 1999, Khasar et al, 2001, Gaumond et al, 2002, Perissin et al, 2003, You et al, 2006, Leo et al, 2008.…”

Section: Discussionmentioning

confidence: 99%

Altered morphine-induced analgesia in neurotensin type 1 receptor null mice

et al. 2010

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Both neurotensin (NT) and opioid agonists have been shown to induce antinociception in rodents after central administration. Besides, previous studies have revealed the existence of functional interactions between NT and opioid systems in the regulation of pain processing. We recently demonstrated that NTS1 receptors play a key role in the mediation of the analgesic effects of NT in long-lasting pain. In the present study, we therefore investigated whether NTS1 gene deletion affected the antinociceptive action of mu opioid drugs. To this end, pain behavioral responses to formalin were determined following systemic administration of morphine in both male and female NTS1 knockout mice. Acute injection of morphine (2 or 5 mg/kg) produced strong antinociceptive effects in both male and female wild-type littermates, with no significant sex differences. On the other hand, morphine analgesia was considerably reduced in NTS1-deficient mice of both sexes compared to their respective controls, indicating that the NTS1 receptor actively participates in mu opioid alleviating pain. By examining specifically the flinching, licking and biting nociceptive behaviors, we also showed that the functional crosstalk between NTS1 and mu opioid receptors influences the supraspinally-mediated behaviors. Interestingly, sexual dimorphic action of morphine-induced pain inhibition was found in NTS1 null mice in the formalin test, suggesting that the endogenous NT system interacts differently with the opioid network in male and female mice. Altogether, these results demonstrated that NTS1 receptor activation operates downstream to the opioidergic transmission and that NTS1-selective agonists combined with morphine may act synergistically to reduce persistent pain.

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“…Male mice were selected, in line with similar studies previously carried out with PSP (Ng et al, 1999;Yin, 1999;Ribeiro et al, 2000), although it is accepted that there is no difference in response to pain between female and male mice (Perissin et al, 2003). The animals were kept in a temperature-controlled room (23 T 2 -C) with 12-h light-dark cycle, with free access to food and water.…”

Section: Animalsmentioning

confidence: 99%