Gender and the behavioral manifestations of neuropathic pain

Tall, Jill M.; Stuesse, Sherry L.; Cruce, William L.R.; Crisp, Terriann

doi:10.1016/s0091-3057(00)00461-5

Cited by 61 publications

(31 citation statements)

References 28 publications

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“…Other groups have previously shown that the modality (i.e. thermal or mechanical) of the nociceptive stimuli can be modulated differentially by gonadal hormones (Tall et al, 2001). Since mechanical and thermal stimuli are reported to be mediated by primarily large Aβ afferents and C-fibers, respectively (Ossipov et al, 1999), our data supports a hypothesis that gonadal hormones can differentially modulate different subtypes of neurons that have mechanistically distinct roles in mediating diverse stimuli.…”

Section: Discussionsupporting

confidence: 84%

The organizational and activational effects of sex hormones on tactile and thermal hypersensitivity following lumbar nerve root injury in male and female rats

LaCroix-Fralish

Tawfik

DeLeo

2005

Pain

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Considerable evidence exists for sex differences in human pain sensitivity. Women typically report a higher incidence of various painful conditions and report that the conditions are more painful when compared to men. In the present study, we sought to determine whether sex differences in pain sensitivity are observed using a lumbar radiculopathy model of low back pain in the rat and whether removal or alteration of gonadal hormones at specific timepoints can modulate these sex differences. Pubertal and adult male and female Sprague-Dawley rats were castrated 2 or 6 weeks prior to L5 nerve root injury to determine the activational hormonal effects. In a separate study, neonatal male and female Sprague-Dawley rats were either castrated or injected with testosterone, respectively, on postnatal day one to determine the organizational effects of gonadal hormones on L5 nerve root injury-induced behavioral hypersensitivity. Our results demonstrate that there was a statistically significant sex difference in the magnitude of mechanical allodynia and thermal hyperalgesia following experimentally induced radiculopathy in the rat: females demonstrated decreased thresholds to tactile and thermal stimuli as compared to males. Furthermore, the enhanced female hypersensitivity was reversed in pubertal and adult animals ovariectomized 6 weeks, but not 2 weeks prior to L5 nerve root injury. Our results demonstrate that the activational effects of gonadal hormones mediate the enhanced female tactile and thermal hypersensitivity following L5 nerve root injury. These results suggest that manipulation of gonadal hormones may be a potential source for novel therapies for chronic pain in women.

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Section: Discussionsupporting

confidence: 84%

The organizational and activational effects of sex hormones on tactile and thermal hypersensitivity following lumbar nerve root injury in male and female rats

LaCroix-Fralish

Tawfik

DeLeo

2005

Pain

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“…The result is compatible with previously reported epidemiologic studies in human populations (6,8,38) and laboratory experiments in animals (1,3,7,17,34,35) showing that the female is highly sensitive to noxious stimuli and pain. On the other hand, our present results suggest the possibility that the male urethra is affected more evidently.…”

Section: Ajp-regul Integr Comp Physiolsupporting

confidence: 92%

Sex-related differences in activity of lower urinary tract in response to intravesical acid irritation in decerebrate unanesthetized mice

Yoshiyama¹,

Kobayashi²,

Araki³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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related differences in lower urinary tract (LUT) activity responding to intravesical infusion of diluted acetic acid (A/A, pH 3.0) were investigated during cystometrograms in decerebrate unanesthetized mice. A/A produced a decrease of intercontraction intervals in both female and male animals, and the extent of the decrease in male mice was much less than in female mice [19 Ϯ 5% (P ϭ 0.03) vs. 65 Ϯ 5% (P ϭ 0.03); n ϭ 6 for each], exhibiting a marked difference between the two groups in response to acid irritation of the LUT (P ϭ 0.002). A/A reduced maximal voiding pressure (MVP) (19 Ϯ 4%, P ϭ 0.03) but had no effect on pressure threshold for inducing voiding contraction (PT) (P ϭ 0.56) in females, whereas A/A did not change MVP (P ϭ 1.00) but increased PT (16 Ϯ 4%, P ϭ 0.03) in males. A/A decreased bladder compliances of female and male mice in a similar fashion (44 Ϯ 10% vs. 24 Ϯ 7%, P ϭ 0.03 for each). In male mice, A/A produced persistent dribbling of fluid after voiding contraction phase, which was virtually not seen in females. The present study demonstrates the differences between female and male mice in response to noxious stimulation in the LUT: the female bladder is more sensitive to the acid irritation, while the male urethra is more irritable to the noxious stimulus. Identification of mechanisms underlying sex-specific characteristics might be helpful for elucidating pathogenesis of painful bladder syndrome. afferent; bladder tonus; detrusor contractility; efferent; urethral resistance NUMEROUS IN VIVO PHYSIOLOGICAL and pharmacological studies examining bladder and urethral activity have been conducted exclusively in one sex of animals in each experimental design, and thus it is uncertain whether functional responses of female and male lower urinary tracts are similar. There are only a few articles detailing differences between females and males in the lower urinary tract functions. Of the available reports, for example, one previous study comparing female and male rats in cystometry revealed that volume thresholds for inducing micturition were changed in accordance with altered intravesical infusion rates in the female rat, whereas these were constant regardless of the bladder filling rates in the male (24). The study suggested the possibility that mechanosensory afferent responses to intensity of the mechanical stimulus were different between the female and male animals.Epidemiologic studies have demonstrated sex-specific differences in prevalence and incidence of certain diseases. In the urological field, it has been well documented that prevalence and incidence of interstitial cystitis, which is a syndrome consisting of severe refractory bladder symptoms such as suprapubic pain, urinary frequency, and urgency without a specific identifiable cause, for women are significantly higher than those for men (10). What pathophysiological factors are involved in these sex-related differences?Here, we proposed the possibilities that sex differences in mechanisms responsible for transmitting inflammatory pai...

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“…Very few studies have investigated sex differences in chronic pain models such as nerve injury and persistent inflammation. Notable exceptions include nerve ligation [40,113,195] and arthritis studies [4,39]. This dearth of information makes it premature to suggest which protocols or animal species are most relevant to any particular human pain condition.…”

Section: What Types Of Pain Tests Are Appropriate? Animal Studiesmentioning

confidence: 99%

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

Greenspan

Craft

LeResche

et al. 2007

Pain

846

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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Gender and the behavioral manifestations of neuropathic pain

Cited by 61 publications

References 28 publications

The organizational and activational effects of sex hormones on tactile and thermal hypersensitivity following lumbar nerve root injury in male and female rats

The organizational and activational effects of sex hormones on tactile and thermal hypersensitivity following lumbar nerve root injury in male and female rats

Sex-related differences in activity of lower urinary tract in response to intravesical acid irritation in decerebrate unanesthetized mice

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

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