Low Dose Clonidine Enhances Pregnancy Induced Analgesia to Visceral but Not Somatic Stimuli in Rats

Iwasaki, Hideki; Collins, J. G.; Saito, Yuichi; Uchida, Hideya

doi:10.1213/00000539-199002001-00171

Cited by 3 publications

(3 citation statements)

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“…Of these agents clonidine, an α 2 adrenergic receptor agonist, has been the most widely studied. Its actions are enhanced by pregnancy 50 and it appears to be particularly effective for visceral pain 51 .…”

Section: Neuraxial Adjunctsmentioning

confidence: 99%

Analgesia after Caesarean Delivery

McDonnell

Keating

Muchatuta

et al. 2009

Anaesth Intensive Care

107

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As the number of women giving birth by caesarean increases throughout most of the developed world, so too is research into postoperative pain relief for these women. Like most other post-surgical populations, the new mother needs effective pain relief so that she can mobilise early but she also has the added responsibility of needing to care for her newborn baby. There is no 'gold standard' for post-caesarean pain management; the number of options is large and the choice of method is at least partly determined by drug availability, regional and individual preferences, resource limitations and financial considerations. Most methods rely on opioids, supplemented with anti-inflammatory analgesics, nerve blocks or other adjunctive techniques. The aim of this review is to detail commonly used opioid-based methods and to review the evidence supporting non-opioid methods, when incorporated into a multimodal approach to post-caesarean pain management. Areas of promising research are also discussed.

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Section: Neuraxial Adjunctsmentioning

confidence: 99%

Analgesia after Caesarean Delivery

McDonnell

Keating

Muchatuta

et al. 2009

Anaesth Intensive Care

107

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show abstract

“…Response thresholds to somatic and visceral noxious stimuli are elevated during gestation (gestational antinociception, GSA) in rats, mice, sows (Toniolo et al, 1987;Gintzler and Bohan, 1990;Iwasaki et al, 1991), and humans (Cogan and Spinnato, 1986). Simulation of the concentration profiles of 17␤-estradiol (estrogen, E 2 ) and progesterone (P) found in the blood during pregnancy (i.e., hormone-simulated pregnancy, HSP) also increases thresholds for responsiveness to aversive stimuli (HSP analgesia, HSPA).…”

Section: Introductionmentioning

confidence: 99%

Relationship of Spinal Dynorphin Neurons to δ-Opioid Receptors and Estrogen Receptor α: Anatomical Basis for Ovarian Sex Steroid Opioid Antinociception

Gintzler

Schnell²,

Gupta

et al. 2008

J Pharmacol Exp Ther

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Pharmacological and behavioral studies suggest that spinal ␦-and -opioid antinociceptive systems are functionally associated with ovarian sex steroids. These interactions can be demonstrated specifically during pregnancy or hormone-simulated pregnancy (HSP). The analgesia associated with both conditions can be abolished by blockade of either spinal -opioid receptors or ␦-opioid receptors (DOR). Furthermore, both dynorphin (DYN) release (J Pharmacol Exp Ther 298:1213-1220) and the processing of the DYN precursor (J Neurochem 65: 1374 -1380, 1995) are significantly increased in the spinal cord during HSP. We undertook the current study to determine whether DYN, DOR, and estrogen receptor ␣ (ER␣) share anatomical relationships that permit their direct interaction. Coexpression of DOR or ER␣ by DYN neurons was assessed using fluorescence immunohistochemistry and a synaptosomal release assay. Findings show that ER␣ and DYN are coexpressed. Moreover, in the spinal cord of HSP animals, there were significant increases in the number of DYN-immunoreactive (DYN-ir) cells, ER␣-ir cells, cells double-labeled for DYN-ir and ER␣-ir and the proportion of DYN-ir cells coexpressing ER␣. Some varicose fibers in the spinal cord dorsal horn and intermediate gray matter that expressed DYN-ir also expressed DOR-ir. Activation of DORs located on DYN terminals was sufficient to inhibit K ϩ -evoked DYN release. These data define, at least in part, the anatomical substrates that may be relevant to the antinociception of gestation and its hormonal simulation. Furthermore, they provide a framework for understanding sex-based nociception and antinociception and suggest novel strategies for treating pain.Pharmacological and behavioral studies have suggested a functional association between spinal ␦-and -opioid antinociceptive systems and their modulation by ovarian sex steroids (Dawson-Basoa and Gintzler, 1998). Response thresholds to somatic and visceral noxious stimuli are elevated during gestation (gestational antinociception, GSA) in rats, mice, sows (Toniolo et al., 1987;Gintzler and Bohan, 1990;Iwasaki et al., 1991), and humans (Cogan and Spinnato, 1986). Simulation of the concentration profiles of 17␤-estradiol (estrogen, E 2 ) and progesterone (P) found in the blood during pregnancy (i.e., hormone-simulated pregnancy, HSP) also increases thresholds for responsiveness to aversive stimuli (HSP analgesia, HSPA). Moreover, the magnitude, temporal pattern of onset, and duration, and spinal opioid receptor profile of HSPA are essentially identical to those of physiological pregnancy Gintzler, 1993, 1998;Liu and Gintzler, 1999).In rats, pharmacological blockade of either spinal -opioid receptors (KOR) or ␦-opioid receptors (DOR) abolishes GSA and HSPA (Dawson-Basoa and Gintzler, 1998;Liu and Gintzler, 2000). This indicates that ovarian sex steroids can induce activation of spinal KOR and DOR analgesic systems and that both of these effects are essential for the manifestation of GSA and HSPA. Functional interactions between spinal...

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“…The predominant analgesic effects of clonidine are mediated through alpha 2 adrenergic receptors and this effect is enhanced in pregnancy. 11,12 Clonidine also provides analgesia for visceral pain and slows regression of the sensory block as reflected by the prolonged duration of analgesia in patients receiving a single dose of it. This ability of clonidine to enhance the sensory block may explain not only its postoperative analgesic effect, but also the reduced need for intraoperative analgesic supplementation when it was administered as part of the neuraxial anaesthetic technique for caesarean section.…”

Section: Discussionmentioning

confidence: 99%

The effect of clonidine with bupivacaine on perioperative hemodynamics and post-operative analgesia in cesarean section cases

Kumar

Arya

Singh

et al. 2021

Int J Reprod Contracept Obstet Gynecol

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Background: Cesarean section is the commonest procedure in Obstetric practice and postoperative pain can be a major factor for wound healing as well as mother and baby bonding. Spinal anesthesia is considered to be safest and easiest modality for cesarean section cases. Bupivacaine is the commonest drug given in spinal anesthesia, but many additive drugs have been introduced to cover post-operative analgesia. Clonidine is an alpha 2 agonist which can be used as an adjunct to heavy bupivacaine to extend analgesic effects.Methods: A randomized double-blind study was performed in 100 women undergoing elective cesarean section under spinal anaesthesia. After proper informed written consent patient undergoing cesarean section were divided by computerized method into group A (Given 10.0 mg 0.5% hyperbaric Bupivacaine) and Group B (Given 9.0 mg 0.5% hyperbaric bupivacaine and 30 μg clonidine).Results: Intraoperative hypotension is the most worrisome factor but it is transient and can be managed by ephedrine effectively. Intraoperative nausea and vomiting are slightly higher with clonidine as occurrence of hypotension is more. VAS scoring in post-operative period was better and need of first analgesic dose was much delayed in women been given clonidine with bupivacaine.Conclusions: Clonidine can be considered as adjunct in spinal anesthesia to extend post-op analgesic cover.

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Low Dose Clonidine Enhances Pregnancy Induced Analgesia to Visceral but Not Somatic Stimuli in Rats

Cited by 3 publications

References 0 publications

Analgesia after Caesarean Delivery

Analgesia after Caesarean Delivery

Relationship of Spinal Dynorphin Neurons to δ-Opioid Receptors and Estrogen Receptor α: Anatomical Basis for Ovarian Sex Steroid Opioid Antinociception

The effect of clonidine with bupivacaine on perioperative hemodynamics and post-operative analgesia in cesarean section cases

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