Gender Differences in Opioid-mediated Analgesia

Kest, Benjamin; Sarton, Elise; Dahan, Albert; Fisher, Dennis M.

doi:10.1097/00000542-200008000-00034

Cited by 219 publications

(116 citation statements)

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“…5 Prospective human studies on the interaction of gender and the analgesic effects of opioids appear to be scarce. Gear et al have reported that postdental surgery pain relief by opioids acting at the -receptor was greater amongst females than amongst males.…”

Section: Discussionmentioning

confidence: 99%

Gender and pain upon movement are associated with the requirements for postoperative patient-controllediv analgesia: a prospective survey of 2,298 Chinese patients

Chia

Chow

Hung

et al. 2002

Can J Anesth/J Can Anesth

155

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Purpose: To investigate prospectively the influence of patient characteristics upon, and the association of postoperative measurements with, the requirements for postoperative morphine and the assessment of resting pain and pain upon movement in Chinese patients.Methods: From January 1998 to December1999, patients receiving patient-controlled iv morphine subsequent to general anesthesia and surgery at our institute (Kaohsiung Veterans General Hospital), were enrolled in the study. Demographic data (such as gender, age, weight, height and education level) and postoperative measurements, including pain scores at rest or during movement, sedation scores and morphine consumption, were recorded.Results: In total 2,298 patients were recruited. Females consumed significantly less morphine via patient-controlled analgesia (PCA) in the first three postoperative days than was the case for males (P <0.05). Gender was the strongest predictor for postoperative morphine requirements. Postoperative pain upon movement was another effective predictor for morphine requirement (P <0.05). Age, body height, body weight, education and operation sites were not associated with morphine consumption.

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Section: Discussionmentioning

confidence: 99%

Gender and pain upon movement are associated with the requirements for postoperative patient-controllediv analgesia: a prospective survey of 2,298 Chinese patients

Chia

Chow

Hung

et al. 2002

Can J Anesth/J Can Anesth

155

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“…The thin fiber afferents (i.e., group III and IV) believed to comprise the sensory arm of the exercise pressor reflex arc may also be capable of evoking the sensation of muscle pain. Estrogen has been implicated in influencing opioid-mediated analgesia (4,15,23). In addition, the activation and expression of opioid receptors have been linked to the presence of estrogen in several different areas of the central nervous system (17,22).…”

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confidence: 99%

Estrogen’s attenuating effect on the exercise pressor reflex is more opioid dependent in gonadally intact than in ovariectomized female cats

Schmitt¹,

Kaufman²

2005

Journal of Applied Physiology

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Schmitt, Petra M., and Marc P. Kaufman. Estrogen's attenuating effect on the exercise pressor reflex is more opioid dependent in gonadally intact than in ovariectomized female cats. J Appl Physiol 98: 633-639, 2005. First published September 24, 2004 doi:10.1152/ japplphysiol.00788.2004.-Using gonadally intact female cats, we showed previously that estrogen, applied topically to the spinal cord, attenuated the exercise pressor reflex. Although the mechanism by which estrogen exerted its attenuating effect is unknown, this steroid hormone has been shown to influence spinal opioid pathways, which in turn have been implicated in the regulation of the exercise pressor reflex. These findings prompted us to test the hypothesis that opioids mediate the attenuating effect of estrogen on the exercise pressor reflex in both gonadally intact female and ovariectomized cats. We therefore applied 200 l of 17␤-estradiol (0.01 g/ml) with and without the addition of 1,000 g naloxone, a -and ␦-opioid antagonist, to a spinal well covering the L 6-S1 spinal cord in decerebrated female cats that were either gonadally intact or ovariectomized. The exercise pressor reflex was evoked by electrical stimulation of the L 7 or S1 ventral root, a maneuver that caused the hindlimb muscles to contract statically. We found that, in gonadally intact cats, the attenuating effect of estrogen was more pronounced than that in ovariectomized cats. We also found that, in gonadally intact female cats, naloxone partly reversed the attenuation of the pressor response to static contraction caused by spinal estrogen application. For example, in intact cats, the pressor response to contraction before estrogen application averaged 39 Ϯ 4 mmHg (n ϭ 10), whereas the pressor response 60 min afterward averaged only 18 Ϯ 4 mmHg (P Ͻ 0.05). In contrast, the pressor response to contraction before estrogen and naloxone application averaged 33 Ϯ 5 mmHg (n ϭ 11), whereas afterward it averaged 27 Ϯ 6 mmHg (P Ͻ 0.05). In ovariectomized cats, naloxone was less effective in reversing the attenuating effect of estrogen on the exercise pressor reflex. sex hormones; static contraction; blood pressure; neural control of circulation; autonomic nervous system THE EXERCISE PRESSOR REFLEX consists of increases in mean arterial pressure, heart rate and ventilation that are evoked by static contraction of the hindlimb muscles in anesthetized or decerebrated animals (19). Recently, spinally applied estrogen was found to attenuate the arterial pressure component of the exercise pressor reflex in decerebrated cats. This attenuation was shown to be gender specific because the threshold concentration of estrogen needed to attenuate the pressor response to contraction was 1,000 times more dilute in female cats than it was in male cats (24,25).The mechanism by which spinally applied estrogen attenuated the reflex pressor response to static contraction is unknown. Nevertheless, -opioid receptors and ␦-opioid receptors have been implicated in the spinal regulation of the exercise pressor ...

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“…Because many of these neurotransmitter systems are implicated in antinociception, we tested pharmacologically diverse analgesics in GIRK2 knockout mice by using the hot plate test. Because of known sex differences in sensitivity to druginduced analgesia (14), we compared responses of male and female mice in all studies. In addition, endogenous analgesia also relies on these neuronal systems, and we studied the effects of mutation on basal antinociceptive latencies and on stressinduced analgesia.…”

mentioning

confidence: 99%

A pervasive mechanism for analgesia: Activation of GIRK2 channels

Blednov

Stoffel

Alva

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

154

116

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G protein-coupled inwardly rectifying potassium channels (GIRKs) provide a common link between numerous neurotransmitter receptors and the regulation of synaptic transmission. We asked whether GIRKs specify a single behavioral action that is produced by drugs acting on the diverse receptors coupled with GIRKs. By using GIRK2-null mutant mice, we found marked reduction or complete elimination of the antinociceptive (hot plate test) effects of ethanol, oxotremorine, nicotine, baclofen, clonidine, and the cannabinoid receptor agonist WIN 55,212. However, ketamine analgesia remained intact. For most drugs, there was a sex difference in antinociceptive action, and the impact of deletion of the GIRK2 channel was less in female mice. The deletion of the GIRK2 channel blocks the opioid-dependent component of stress-induced analgesia (SIA), whereas nonopioid SIA was not changed. We propose that opioid, ␣ adrenergic, muscarinic cholinergic, ␥-aminobutyric acid-B, and cannabinoid receptors are coupled with postsynaptic GIRK2 channels in vivo. Furthermore, this pathway accounts for essentially all of the antinociceptive effects in males, although females appear to recruit additional signal transduction mechanisms for some analgesic drugs.C hemically and pharmacologically diverse drugs reduce nociceptive responses in humans and in animal models of acute pain. Many of these drugs act through G protein coupled receptors and affect multiple pre-and postsynaptic signaling pathways (1, 2). A key question is whether there is a single G protein signal transduction pathway that is important for antinociceptive actions of many different drugs. One candidate for such a signaling system is the G protein-coupled inwardly rectifying potassium channel (GIRK). This assumption is based in part on the observation that weaver mutant mice have a mutation in GIRK2 and display reduced analgesia after either morphine or -opioid agonist (Ϫ)-U-50488 or ethanol administration (3, 4). However, the weaver mutant is not ideal for assessing the role of GIRK2 because the mutation alters the ion selectivity of GIRK2 and produces neuronal degeneration rather than a simple loss of GIRK2 function (5). Targeted mutation has produced mice lacking the GIRK2 protein; these mice lack postsynaptic responses to several neurotransmitters known to act through G protein coupled receptors, but retain normal presynaptic actions of these receptors (6-8). These mice are viable and similar to wild-type controls in many behavioral tests (9-11) and provide a unique approach to defining the role of GIRK2 in drug actions.GIRKs are activated by M 2 muscarinic, ␣ 2 adrenergic, D 2 dopaminergic, histamine, 5HT 1A , A 1 adenosine, ␥-aminobutyric acid (GABA)-B, , , and ␦ opioid, and somatostatin receptors (12, 13). Because many of these neurotransmitter systems are implicated in antinociception, we tested pharmacologically diverse analgesics in GIRK2 knockout mice by using the hot plate test. Because of known sex differences in sensitivity to druginduced analgesia (14), we compared...

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Gender Differences in Opioid-mediated Analgesia

Cited by 219 publications

References 50 publications

Gender and pain upon movement are associated with the requirements for postoperative patient-controllediv analgesia: a prospective survey of 2,298 Chinese patients

Gender and pain upon movement are associated with the requirements for postoperative patient-controllediv analgesia: a prospective survey of 2,298 Chinese patients

Estrogen’s attenuating effect on the exercise pressor reflex is more opioid dependent in gonadally intact than in ovariectomized female cats

A pervasive mechanism for analgesia: Activation of GIRK2 channels

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