Gestational and ovarian sex steroid antinociception: synergy between spinal κ and δ opioid systems

Dawson-Basoa, Mary E.; Gintzler, Alan R.

doi:10.1016/s0006-8993(98)00192-9

Cited by 125 publications

(74 citation statements)

References 29 publications

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“…Analgesia during pregnancy, or its hormonal simulation, is opioid-dependent in the rat as shown by the finding that it is abolished by the opiate antagonist naloxone Gintzler, 1980). It has been shown that this antinociception is mediated, at least to a large extent, by the activation of multiple spinal opioid systems involving -and -opioid receptors (Dawson-Basoa and Gintzler, 1997;Dawson-Basoa and Gintzler, 1998) even though peripheral as well as supraspinal mechanisms also contribute (Liu and Gintzler, 1999). Spinal dynorphin activity is central to the induction of pregnancy-induced analgesia and spinal dynorphin release is increased at least two-fold during hormone-simulated pregnancy (Gupta et al, 2001).…”

Section: Estrogen Receptor Neurons and The Endogenous Opioid Systemmentioning

confidence: 99%

Estrogenic influences in pain processing

Amandusson

Blomqvist

2013

Frontiers in Neuroendocrinology

104

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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: Estrogen Receptor Neurons and The Endogenous Opioid Systemmentioning

confidence: 99%

Estrogenic influences in pain processing

Amandusson

Blomqvist

2013

Frontiers in Neuroendocrinology

104

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“…For example, some chronic diseases, including migraine, temporomandibular disorders, fibromyalgia, arthritis, and interstitial cystitis, are more prevalent in females [1,2]. Women usually display stronger pain perception and request more analgesics [3,4], while in pregnancy, increasing estrogen and progestogen have an anti-nociceptive role [5,6]. Experimental studies have shown that after injection of estradiol, female ovariectomized (OVX) rats tended to have a longer latency in hot plate and tail-flick experiments [7].…”

Section: Introductionmentioning

confidence: 99%

Inhibitory effect of estrogen receptor beta on P2X3 receptors during inflammation in rats

Jiang

Sun

et al. 2016

Purinergic Signalling

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Estrogen receptor beta (ERβ) has been shown to play a therapeutic role in inflammatory bowel disease (IBD). However, the mechanism underlying how ERβ exerts therapeutic effects and its relationship with P2X3 receptors (P2X3R) in rats with inflammation is not known. In our study, animal behavior tests, visceromotor reflex recording, and Western blotting were used to determine whether the therapeutic effect of ERβ in rats with inflammation was related with P2X3R. In complete Freund adjuvant (CFA)-induced chronic inflammation in rats, paw withdrawal threshold was significantly decreased which were then reversed by systemic injection of ERβ agonists, DPN or ERB-041. In 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats, weight loss, higher DAI scores, increased visceromotor responses, and inflammatory responses were reversed by application of DPN or ERB-041. The higher expressions of P2X3R in dorsal root ganglia (DRG) of CFA-treated rats and those in rectocolon and DRG of TNBS-treated rats were all decreased by injection of DPN or ERB-041. DPN application also inhibited P2X3R-evoked inward currents in DRG neurons from TNBS rats. Mechanical hyperalgesia and increased P2X3 expression in ovariectomized (OVX) CFA-treated rats were reversed by estrogen replacements. Furthermore, the expressions of extracellular signal-regulated kinase (ERK) in DRG and spinal cord dorsal horn (SCDH) and c-fos in SCDH were significantly decreased after estrogen replacement compared with those of OVX rats. The ERK antagonist U0126 significantly reversed mechanical hyperalgesia in the OVX rats. These results suggest that estrogen may play an important therapeutic role in inflammation through downregulation of P2X3R in peripheral tissues and the nervous system, probably via ERβ, suggesting a novel therapeutic strategy for clinical treatment of inflammation.

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“…Involvement of sex steroids in the modulation of pain has been reported by previous studies that showed antinociceptive actions of physiological or experimental pregnancy in rats and women (28)(29)(30). In particular, elevated plasma levels of estrogen and progesterone have been positively correlated with the stimulation of the spinal opioid system and the increase of pain thresholds (30).…”

Section: Discussionmentioning

confidence: 67%

“…In particular, elevated plasma levels of estrogen and progesterone have been positively correlated with the stimulation of the spinal opioid system and the increase of pain thresholds (30).…”

Section: Discussionmentioning

confidence: 99%

Substance P inhibits progesterone conversion to neuroactive metabolites in spinal sensory circuit: A potential component of nociception

Patte‐Mensah

Kibaly

Mensah‐Nyagan

2005

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

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A crucial biochemical reaction in vertebrates is progesterone conversion into neuroactive metabolites such as dihydroprogesterone (5␣-DHP) and tetrahydroprogesterone (3␣,5␣-THP), which regulate several neurobiological processes, including stress, depression, neuroprotection, and analgesia. 3␣,5␣-THP is a potent stimulator of type A receptors of GABA, the main inhibitory neurotransmitter. Here, we show that in the spinal sensory circuit progesterone conversion into 5␣-DHP and 3␣,5␣-THP is inhibited dose-dependently by substance P (SP), a major mediator of painful signals. We developed a triple-labeling approach coupled with multichannel confocal microscope analysis, which revealed that, in the spinal cord (SC), SP-releasing afferents project on sensory neurons expressing simultaneously neurokinin 1 receptors (rNK1) and key enzymes catalyzing progesterone metabolism. Evidence for a potent inhibitory effect of SP on 5␣-DHP and 3␣,5␣-THP formation in the SC was provided by combining pulse-chase experiments using neurosteroid ͉ pain ͉ spinal cord ͉ steroids ͉ nervous system T he spinal cord (SC) is a pivotal structure controlling many neurophysiological activities, including somatosensory transmission, locomotion, reflexes, and neurovegetative functions. Primary sensory inputs arising from receptors in various areas of the body are integrated in multisynaptic relays in the SC that convey these inputs toward the brain (1, 2). A variety of molecules, including glutamate, substance P (SP), neurotrophins, calcitonin-gene related peptide, and adenosine triphosphate, are thought to be involved in the central transmission of sensory messages (2, 3). Among these neuromodulators, SP, the role of which is clearly established and well documented, is considered as a key neuropeptide mediating nociceptive message transmission from peripheral afferents to sensory neurons located in the SC dorsal horn (DH) (4-6). In particular, it has been shown that projection neurons in lamina I of rat DH expressing neurokinin 1 receptors (rNK1s) are selectively innervated by SP-containing afferents and respond to noxious stimulation (7). Direct structural-functional evidence for SP-mediated nociceptive transmission has also been provided in cats by multidisciplinary studies that combined various approaches, including intracellular recording from DH neurons in vivo, characterization of these neurons on the basis of their responses to peripheral noxious stimulation, cellular labeling by horseradish peroxidase, and electron microscopic identification of synaptic contacts (6-9). Moreover, intrathecal injection of SP conjugated to the cytotoxin saporin selectively destroyed DH neurons bearing rNK1 and strongly reduced hyperalgesia after capsaicin treatment, indicating that spinal rNK1 neurons are important for the development of hyperalgesia (4, 5). However, intracellular changes or neurochemical modifications that spinal rNK1 neurons undergo during nociception are poorly characterized. This situation hampers the understanding of spinal mechanisms in...

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Gestational and ovarian sex steroid antinociception: synergy between spinal κ and δ opioid systems

Cited by 125 publications

References 29 publications

Estrogenic influences in pain processing

Estrogenic influences in pain processing

Inhibitory effect of estrogen receptor beta on P2X3 receptors during inflammation in rats

Substance P inhibits progesterone conversion to neuroactive metabolites in spinal sensory circuit: A potential component of nociception

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