Persistent pain model reveals sex difference in morphine potency

Wang, Xiaoya; Traub, Richard J.; Murphy, Anne Z.

doi:10.1152/ajpregu.00022.2006

Cited by 86 publications

(78 citation statements)

References 55 publications

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“…In the Sprague-Dawley rat, sex differences in response to acute noxious electrical and chemical pain have been reported, with females exhibiting greater pain sensitivity than males. In contrast, inconsistent findings have been reported with acute noxious thermal stimuli, and no consistent sex differences in response to persistent inflammatory pain induced by intraplantar CFA have been reported (Aloisi et al, 1994;Craft et al, 2004;Craft et al 2013;Drury and Gold, 1978;Gandelman, 1983: Gaumond et al, 2002Mogil et al, 2000;Wang et al 2006).…”

Section: Animal Studiesmentioning

confidence: 99%

Estrogenic influences in pain processing

Amandusson

Blomqvist

2013

Frontiers in Neuroendocrinology

109

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Gonadal hormones not only play a pivotal role in reproductive behavior and sexual differentiation, they also contribute to thermoregulation, feeding, memory, neuronal survival, and the perception of somatosensory stimuli. Numerous studies on both animals and human subjects have also demonstrated the potential effects of gonadal hormones, such as estrogens, on pain transmission. These effects most likely involve multiple neuroanatomical circuits as well as diverse neurochemical systems and they therefore need to be evaluated specifically to determine the localization and intrinsic characteristics of the neurons engaged. The aim of this review is to summarize the morphological as well as biochemical evidence in support for gonadal hormone modulation of nociceptive processing, with particular focus on estrogens and spinal cord mechanisms.

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Section: Animal Studiesmentioning

confidence: 99%

Estrogenic influences in pain processing

Amandusson

Blomqvist

2013

Frontiers in Neuroendocrinology

109

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“…Because women are more likely than men to have a history of clinical pain experiences, and pain history influences current pain perception [170], chronicity of pain is most likely an important contributing factor to sex differences in pain/analgesia. Animal studies can be utilized to determine whether sex differences in pain/analgesia are amplified as the duration of persistent pain lengthens [39,89,210], or as subjects experience repeated episodes of pain over time. Repeated episodes of formalin testing engender adaptations in nociception that are gonadal hormone-dependent [7,31], suggesting that pain chronicity is indeed an important factor to consider in future preclinical studies of sex differences in pain/ To what extent are sex differences in pain or analgesia due to sexually dimorphic ascending (afferent) pathways vs. sexually dimorphic pain modulation?…”

Section: Future Directionsmentioning

confidence: 99%

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

Greenspan

Craft

LeResche

et al. 2007

Pain

Self Cite

861

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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“…comparison to females (Bodnar et al, 1988,Craft, 2003b,Craft, 2003a,Cook and Nickerson, 2005,Wang et al, 2006. Sex differences in morphine analgesia have been reported in studies employing orofacial (Okamoto et al, 2005), somatic (Bartok and Craft, 1997,Cicero et al, 1997,Boyer et al, 1998,Kest et al, 1999,Barrett et al, 2001 or visceral (Ji et al, 2006,Ji et al, in press) pain models.…”

mentioning

confidence: 96%

Morphine preferentially activates the periaqueductal gray–rostral ventromedial medullary pathway in the male rat: A potential mechanism for sex differences in antinociception

2007

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The midbrain periaqueductal gray (PAG), and its descending projections to the rostral ventromedial medulla (RVM), provides an essential neural circuit for opioid-produced antinociception. Recent anatomical studies have reported that the projections from the PAG to the RVM are sexually dimorphic and that systemic administration of morphine significantly suppresses pain-induced activation of the PAG in male but not female rats. Given that morphine antinociception is produced in part by disinhibition of PAG output neurons, it is hypothesized that a differential activation of PAG output neurons mediates the sexually dimorphic actions of morphine. The present study examined systemic morphine-induced activation of PAG-RVM neurons in the absence of pain. The retrograde tracer fluorogold (FG) was injected into the RVM to label PAG-RVM output neurons. Activation of PAG neurons was determined by quantifying the number of Fos-positive neurons one hour following systemic morphine administration (4.5 mg/kg). Morphine produced comparable activation of the PAG in both male and female rats, with no significant differences in either the quantitative or qualitative distribution of Fos. While microinjection of FG into the RVM labeled significantly more PAG output neurons in female rats than male rats, very few of these neurons (20%) were activated by systemic morphine administration in comparison to males (50%). The absolute number of PAG-RVM neurons activated by morphine was also greater in males. These data demonstrate widespread disinhibition of PAG neurons following morphine administration. The greater morphine-induced activation of PAG output neurons in male compared to female rats is consistent with the greater morphine-induced antinociception observed in males. Keywordspain; morphine analgesia; pain inhibition; opioid; sexual dimorphism endogenous descending pathway Morphine and other mu-opioid receptor agonists are the most effective pharmacological treatment for the alleviation of persistent pain. However, it is becoming increasingly clear that morphine does not produce the same degree of analgesia in males and females. In the majority of studies reported to date, morphine produced a greater antinociceptive response in males in Correspondence to: Anne Z. Murphy, Ph.D., Dept. Biology, Center for Behavioral Neuroscience, Georgia State University, PO Box 4010, Atlanta, amurphy@gsu.edu, Phone: 404.463.9661, Fax: 404.651.2509 Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. (Bodnar et al., 1988,Craft, 2003b,Craft, 2003a,Cook and Nickerson, 2005,Wang et al., 2006. Sex difference...

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Persistent pain model reveals sex difference in morphine potency

Abstract: . Persistent pain model reveals sex difference in morphine potency.

Cited by 86 publications

References 55 publications

Estrogenic influences in pain processing

Estrogenic influences in pain processing

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

Morphine preferentially activates the periaqueductal gray–rostral ventromedial medullary pathway in the male rat: A potential mechanism for sex differences in antinociception

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