Sex differences in the behavioural response to persistent pain in rats

Aloisi, Anna Maria; Albonetti, Maria Emanuela; Carli, Giancarlo

doi:10.1016/0304-3940(94)90939-3

Cited by 100 publications

(47 citation statements)

References 22 publications

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“…These results are consistent with previous reports in which the onset of an arthritic state in male rats is associated with changes in paw volume, body weight, joint stiffness, and mechanical hyperalgesia (Millan et al, 1987;Nagakura et al, 2003). The increased nociceptive sensitivity in female arthritic rats is consistent with studies demonstrating that females are more sensitive than males to the nociceptive producing effects of the algogenic agents formalin and capsaicin (Aloisi et al, 1994;Gaumond et al, 2002;Barrett et al, 2003) and are in agreement with studies demonstrating that females develop a more severe arthritic state based on articular indices and gross observational measures (Wilder et al, 1982;Allen et al, 1983;Holmdahl, 1995).…”

Section: Discussionsupporting

confidence: 92%

“…Various algogenic agents, including capsaicin and formalin, can be used to produce an inflammatory condition that results in a persistent, prolonged nociceptive state. In rats injected with formalin in the hindpaw, females exhibit a significantly greater nociceptive response than males (Aloisi et al, 1994;Gaumond et al, 2002). Similarly, after intradermal tail administration of capsaicin, females exhibit a significantly greater hyperalgesic response to a water stimulus applied to the tail of the rat, and, unlike with acute tests, morphine is equally potent in reversing the hyperalgesic state in males and females .…”

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confidence: 92%

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Nociceptive Sensitivity and Opioid Antinociception and Antihyperalgesia in Freund's Adjuvant-Induced Arthritic Male and Female Rats

Cook

Nickerson²

2004

J Pharmacol Exp Ther

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The present study was designed to examine sex differences in complete Freund's adjuvant (CFA)-induced mechanical hyperalgesia and sex differences in opioid antinociception and antihyperalgesia. Female rats developed inflammation and hyperalgesia faster and exhibited greater peak hyperalgesia than male rats. In arthritic (CFA-treated) rats, lower thresholds were observed during estrus and proestrus, and in nonarthritic (vehicle-treated) rats, lower thresholds were observed during proestrus. Morphine and oxycodone were more potent in male than female arthritic rats, and butorphanol was more potent and effective in male than female arthritic rats. The potency of morphine was increased in arthritic rats, although to a greater magnitude in males. The potency of oxycodone was increased in male but not female arthritic rats. The potency of butorphanol was increased in arthritic male rats and the maximal antinociceptive effect of butorphanol was increased in arthritic female rats, but it did not result in greater than 20% antinociception. Morphine, oxycodone, and butorphanol all produced antihyperalgesic effects (returning thresholds of arthritic rats to the thresholds of nonarthritic rats) with greater potency in males than females. The peripherally acting opioid agonist loperamide produced intermediate levels of antinociception in male and female arthritic rats and no antinociception in nonarthritic rats. Loperamide was more potent in male than female arthritic rats at producing antihyperalgesia. These data demonstrate sex differences in arthritis-induced hyperalgesia and responsiveness to opioid analgesics. In arthritic rats, the antinociceptive effects of opioid agonists are most probably mediated by both central and peripheral opioid receptors, whereas their antihyperalgesic effects are mediated primarily by actions at peripheral opioid receptors.

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Section: Discussionsupporting

confidence: 92%

mentioning

confidence: 92%

Nociceptive Sensitivity and Opioid Antinociception and Antihyperalgesia in Freund's Adjuvant-Induced Arthritic Male and Female Rats

Cook

Nickerson²

2004

J Pharmacol Exp Ther

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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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“…In general, when differences are found, females of many species are more sensitive to and less tolerant of pain than are males, and also less sensitive to opioid and nonopioid analgesic manipulations pimprivate (Lipsitt and Levy, 1959;Beatty and Beatty, 1970;Bodnar et al, 1988;Feine et al, 1991;Kepler et al, 1991;Kiefel and Bodnar, 1991;Kavaliers and Innes, 1992;Aloisi et al, 1994;Menendez et al, 1994;Cicero et al, 1996; but see Gear et al, 1996).…”

Section: Sex-specific Mechanisms Of Swim Siamentioning

confidence: 99%

Identification of a Sex-Specific Quantitative Trait Locus Mediating Nonopioid Stress-Induced Analgesia in Female Mice

et al. 1997

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It is increasingly appreciated that the sexes differ in their perception of noxious stimuli and in their responsivity to exogenous and endogenous analgesic manipulations. We previously reported the existence of qualitative sex differences in the neurochemical mediation of nonopioid (i.e., naloxone-insensitive) stress-induced analgesia (SIA) produced by forced swims and suggested that female mice possess a sex-specific SIA mechanism. This femalespecific system is now known to be estrogen-dependent, to be ontogenetically organized, and to vary with reproductive status; however, its neurochemical identity remains obscure. In an attempt to identify candidate genes underlying SIA in both sexes, we performed a two-phase quantitative trait locus (QTL) mapping experiment using the BXD/Ty recombinant inbred (RI) set derived from DBA/2J (D2) and C57BL/6J (B6) inbred mouse strains and (B6xD2)F 2 hybrid mice derived from these same progenitors. All mice were subjected to 3 min forced swims in 15°C water; nociceptive sensitivity on the 54°C hot-plate assay was assessed immediately before and 2 min after cessation of the swim. We report the localization of a QTL statistically associated with SIA magnitude [p ϭ 0.00000012; logarithm of the odds (LOD) ϭ 6.1] in female mice only. This female-specific QTL, which we name Fsia1, is located on chromosome 8 at 52-84 cM from the centromere and accounts for 17-26% of the overall trait variance in this sex. The present data provide further evidence of the existence of a female-specific SIA mechanism and highlight the important role of both genetic background and gender in the inhibition of pain. Key words: sex differences; genetics; antinociception; stressinduced analgesia; gene mapping; quantitative trait locus; nonopioid; painIt is well known that the C NS contains circuitry that evolved to inhibit ascending nociceptive signals. These endogenous pain inhibition mechanisms can be activated by direct electrical stimulation or pharmacologically, but they evolved to be activated by exposure to environmental stressors, a phenomenon known as stress-induced analgesia (SIA) (Kelly, 1986). Multiple SIA systems are known to exist; in the simplest dissociation they can be divided into opioid or nonopioid forms, on the basis of their sensitivity to antagonism by the prototypic opioid receptor blockers naloxone or naltrexone (Lewis et al., 1980;Watkins and Mayer, 1982;Terman et al., 1984).It is possible to observe opioid or nonopioid SIA after the application of the same laboratory stressor by altering stress severity parameters. For instance, in Swiss-Webster mice, swims of longer duration and /or colder temperature produce increasingly nonopioid SIA, that is, SIA increasingly refractory to naloxone/naltrexone antagonism Mogil et al., 1993Mogil et al., , 1996b but see Tierney et al., 1991).Much is known regarding the neurochemical and anatomical details of endogenous opioid pain inhibition mechanisms (Basbaum and Fields, 1984). Opioid peptide neurotransmitters are released and act on opioid recep...

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Sex differences in the behavioural response to persistent pain in rats

Cited by 100 publications

References 22 publications

Nociceptive Sensitivity and Opioid Antinociception and Antihyperalgesia in Freund's Adjuvant-Induced Arthritic Male and Female Rats

Nociceptive Sensitivity and Opioid Antinociception and Antihyperalgesia in Freund's Adjuvant-Induced Arthritic Male and Female Rats

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

Identification of a Sex-Specific Quantitative Trait Locus Mediating Nonopioid Stress-Induced Analgesia in Female Mice

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