Nociception and antinociception during the first week of life in mice: Sex differences and test dependence

Sternberg, Wendy F.; Smith, Lauren; Scorr, Laura

doi:10.1016/j.jpain.2004.07.002

Cited by 26 publications

(23 citation statements)

References 39 publications

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“…Sternberg et al 41. found sex differences in basal nociception and analgesic effects of morphine in neonatal CD-1 mice.…”

Section: Discussionmentioning

confidence: 98%

“…Mice were tested on two different behavioral tests of thermal nociception as described by Sternberg et al:41 the hotplate and tail withdrawal assays, which show diverse sensitivity to drugs and sex. Both the hotplate and tail withdrawal assays have been used extensively in adult rodents and have also been adapted for use in neonates previously 41…”

Section: Methodsmentioning

confidence: 99%

“…Females are generally more sensitive to pain and/or differ from males in neural circuits mediating nociception 5, 18, 30. In mice, a variety of NMDA antagonists block the acute analgesic effects of μ- or k-agonists or development of tolerance to morphine 6, 12, 33, 34, 37, 41. However, specific NMDA antagonists block the morphine analgesia only in females, whereas other NMDA antagonists block analgesia in both sexes 37.…”

Section: Introductionmentioning

confidence: 99%

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Sex Chromosome Complement Affects Nociception and Analgesia in Newborn Mice

Gioiosa

Chen

Watkins

et al. 2008

The Journal of Pain

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In animal studies of nociception, females are often more sensitive to painful stimuli, whereas males are often more sensitive to analgesia induced by μ agonists. Sex differences are found even at birth, and in adulthood are likely caused, at least in part, by differences in levels of gonadal hormones. Here we investigate nociception and analgesia in neonatal mice, and assess the contribution of the direct action of sex chromosome genes in hotplate and tail withdrawal tests. We used the four core genotypes mouse model, in which gonadal sex is independent of the complement of sex chromosomes (XX vs. XY). Mice were tested at baseline and then injected with μ-opioid agonist morphine (10mg/kg), or with the κ-opioid agonist U50,488H (U50, 12.5mg/Kg) with or without the N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801 (0.1mg/kg). On the day of birth, XX mice showed faster baseline latencies than XY in tail withdrawal, irrespective of their gonadal type. Gonadal males showed greater effects of morphine than gonadal females in the hotplate test, irrespective of their sex chromosome complement. U50 and morphine were both effective analgesics in both tests, but MK-801 did not block the U50 effect. The results suggest that sex chromosome complement and gonadal secretions both contribute to sex differences in nociception and analgesia by the day of birth. Perspective: Sex differences in pain may stem not only from the action of gonadal hormones on pain circuits, but from the sex-specific action of X and Y genes. Identification of sex chromosome genes causing sex differences could contribute to better pain therapy in females and males.

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“…Sternberg et al 41. found sex differences in basal nociception and analgesic effects of morphine in neonatal CD-1 mice.…”

Section: Discussionmentioning

confidence: 98%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Sex Chromosome Complement Affects Nociception and Analgesia in Newborn Mice

Gioiosa

Chen

Watkins

et al. 2008

The Journal of Pain

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“…A few studies suggest that sex differences in pain/analgesia develop by the early neonatal period in the rodent [37,110,192], although it is not clear whether sex differences are observed that early in humans [65,80,152]. In contrast, beginning around puberty, age-dependent sex differences occur for several types of pain in humans.…”

Section: How Does Pain Chronicity Contribute To Sex Differences In Pamentioning

confidence: 99%

Studying sex and gender differences in pain and analgesia: A consensus report

Greenspan

Craft

LeResche

et al. 2007

Pain

863

633

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In September 2006, members of the Sex, Gender and Pain Special Interest Group of the International Association for the Study of Pain met to discuss the following: (1) what is known about sex and gender differences in pain and analgesia; (2) what are the "best practice" guidelines for pain research with respect to sex and gender; and (3) what are the crucial questions to address in the near future? The resulting consensus presented herein includes input from basic science, clinical and psychosocial pain researchers, as well as from recognized experts in sexual differentiation and reproductive endocrinology. We intend this document to serve as a utilitarian and thought-provoking guide for future research on sex and gender differences in pain and analgesia, both for those currently working in this field as well as those still wondering, "Do I really need to study females?" Keywords Sex differences; Gonadal hormones; Estrogens The case for studying sex and gender differences in pain and analgesiaThe pain field has moved from debating whether sex differences in pain exist to recognizing the importance of these differences. Attention is now directed toward understanding (1) what conditions lead to the expression of sex and gender differences in pain experience and reactivity, (2) what mechanisms underlie these differences, and (3) how these differences can inform clinical management of pain.As noted in a recent review, at least 79% of animal studies published in Pain over the preceding 10 years included male subjects only, with a mere 8% of studies on females only, and another 4% explicitly designed to test for sex differences (the rest did not specify) [142]. Given the substantially greater prevalence of many clinical pain conditions in women vs. men [20,199], and growing evidence for sex differences in sensitivity to experimental pain and to analgesics [21,41,213], we recommend that all pain researchers consider testing their hypotheses in both sexes, or if restricted by practical considerations, only in females. It is invalid to assume that data obtained in male subjects will generalize to females, and the best non-human model of the modal human pain sufferer -a woman -is a female animal. If only males are examined in a given study, it is important that a rationale for exclusion of females be provided and that the potential limitation in generalizability of the findings be addressed in the discussion, particularly when examining a pain phenomenon that occurs with greater prevalence or severity in females. In both preclinical and clinical studies, a comparison of both sexes will further our understanding of individual differences in sensitivity to pain and analgesia, thus improving our ability to treat and prevent pain in all people. General considerationsTwo issues of terminology are important. First, the term "sex" refers to biologically based differences, while the term "gender" refers to socially based phenomena. Although biological sex exerts a major influence on one's gender identity, sex and gender a...

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“…Clearly, there is a connection between the HPG axis and the regulation of pain sensation, however, the underlying mechanism is not well understood and many of the published studies, both animal and human, experimental and clinical reported, at least, partly contradictory results. Gonadal hormones including estrogens and progesterone have been implicated in affecting pain sensitivity, however again results are contradictory as a clear anti or pronociceptive effect could not be demonstrated for either [143,209,63,227,34]. Our results taken together with the above mentioned data raises the possibility that kisspeptin might provide a link between the reproductive and pain modulatory systems.…”

Section: Kisspeptin and Nociceptionmentioning

confidence: 57%

Kisspeptin modulates the activity of the stress system and associated behaviours, the body temperature and nociception

Csabafi¹

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Nociception and antinociception during the first week of life in mice: Sex differences and test dependence

Cited by 26 publications

References 39 publications

Sex Chromosome Complement Affects Nociception and Analgesia in Newborn Mice

Sex Chromosome Complement Affects Nociception and Analgesia in Newborn Mice

Studying sex and gender differences in pain and analgesia: A consensus report

Kisspeptin modulates the activity of the stress system and associated behaviours, the body temperature and nociception

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